@article{kwong_mitochondrial_2018, title = {The mitochondrial calcium uniporter underlies metabolic fuel preference in skeletal muscle}, volume = {3}, issn = {2379-3708}, doi = {10.1172/jci.insight.121689}, abstract = {The mitochondrial Ca2+ uniporter (MCU) complex mediates acute mitochondrial Ca2+ influx. In skeletal muscle, MCU links Ca2+ signaling to energy production by directly enhancing the activity of key metabolic enzymes in the mitochondria. Here, we examined the role of MCU in skeletal muscle development and metabolic function by generating mouse models for the targeted deletion of Mcu in embryonic, postnatal, and adult skeletal muscle. Loss of Mcu did not affect muscle growth and maturation or otherwise cause pathology. Skeletal muscle-specific deletion of Mcu in mice also did not affect myofiber intracellular Ca2+ handling, but it did inhibit acute mitochondrial Ca2+ influx and mitochondrial respiration stimulated by Ca2+, resulting in reduced acute exercise performance in mice. However, loss of Mcu also resulted in enhanced muscle performance under conditions of fatigue, with a preferential shift toward fatty acid metabolism, resulting in reduced body fat with aging. Together, these results demonstrate that MCU-mediated mitochondrial Ca2+ regulation underlies skeletal muscle fuel selection at baseline and under enhanced physiological demands, which affects total homeostatic metabolism.}, language = {eng}, number = {22}, journal = {JCI insight}, author = {Kwong, Jennifer Q. and Huo, Jiuzhou and Bround, Michael J. and Boyer, Justin G. and Schwanekamp, Jennifer A. and Ghazal, Nasab and Maxwell, Joshua T. and Jang, Young C. and Khuchua, Zaza and Shi, Kevin and Bers, Donald M. and Davis, Jennifer and Molkentin, Jeffery D.}, year = {2018}, pmid = {30429366}, pmcid = {PMC6302934}, keywords = {Animals, Calcium, Calcium Channels, Calcium Signaling, Cardiology, Energy Metabolism, Female, Gene Targeting, Male, Mice, Mice, Transgenic, Mitochondria, Muscle Biology, Muscle, Skeletal} }
@article{grigorov_cd81_2017, title = {{CD81} large extracellular loop-containing fusion proteins with a dominant negative effect on {HCV} cell spread and replication}, volume = {98}, issn = {1465-2099}, doi = {10.1099/jgv.0.000850}, abstract = {The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species. However, with the exception of the large extracellular loop sequence, the structure-function analysis of CD81 in the HCV infectious cycle remains ill characterized. We describe here the fusion molecules between the large extracellular loops of human or mouse CD81 and lipid-raft-associated or unassociated GPI anchors. These fusion molecules have strong antiviral activity in a dominant negative fashion, independent of membrane raft association. Their expression in the hepatoma cell line Huh7.5 blocks HCV uptake, transmission and replication. These molecules will be useful to decipher the various roles of CD81 in the HCV life cycle and transmission in more detail.}, language = {eng}, number = {7}, journal = {The Journal of General Virology}, author = {Grigorov, Boyan and Molle, Jennifer and Rubinstein, Eric and Zoulim, Fabien and Bartosch, Birke}, month = jul, year = {2017}, pmid = {28721844}, keywords = {Animals, Antigens, CD81, Cell Line, Tumor, HEK293 Cells, HIV-1, HeLa Cells, Hepacivirus, Hepatitis C, Humans, Membrane Microdomains, Mice, Protein Binding, Viral Envelope Proteins, Virus Attachment, Virus Internalization, Virus Replication}, pages = {1646--1657} }
@article{szejk_comparative_2017, title = {A comparative study on the radioprotective potential of the polyphenolic glycoconjugates from medicinal plants of {Rosaceae} and {Asteraceae} families versus their aglycones}, volume = {171}, issn = {1873-2682}, doi = {10.1016/j.jphotobiol.2017.04.027}, abstract = {Radioprotective potential of the polyphenolic glycoconjugates, isolated from flowers of Sanguisorba officinalis L. (So) and Erigeron canadensis L. (Ec), and from leaves of Fragaria vesca L. (Fv) and Rubus plicatus Whe. Et N. E. (Rp) as well as their aglycones (SoA, EcA, FvA and RpA, respectively), against γ-radiation-induced lipid peroxidation in human plasma and DNA damage in lymphocytes, were investigated in vitro. These properties were assessed by measuring the concentration of thiobarbituric acid reactive substances (TBARS) and using the alkaline comet assay, and were compared to the protective effects of rutin (R) and quercetin (Q). Cytotoxicity of the glycoconjugates/aglycones towards L929 mouse fibroblasts and human lymphocytes were also measured. Plant products from S. officinalis, similar to Q, were able to reduce the most radiation-induced lipid peroxidation as well as DNA damage and extent of oxidative damage to the DNA basis. Contrary to the pure flavonoids, where Q was shown to be significantly more effective than its glycoside R, the results did not show more benefit with application of SoA/EcA over So/Ec in terms of lipid peroxidation inhibition. Moreover, glycoconjugates Ec and So showed much higher capacity in protecting lymphocytes against radiation-induced genotoxicity which may suggest that between the polyphenolic and polysaccharide parts exist some synergistic effects. There were no significant differences between Fv versus FvA or Rp versus RpA in terms of the provided radioprotection. Summarizing, plant glycoconjugates isolated by the multi-step method offered sufficient radioprotection. In addition, they possess many advantages, compared to the synthetic polyphenolic compounds or the plant extracts, such as water-solubility and minor toxicity.}, language = {eng}, journal = {Journal of Photochemistry and Photobiology. B, Biology}, author = {Szejk, Magdalena and Poplawski, Tomasz and Czubatka-Bienkowska, Anna and Olejnik, Alicja Klaudia and Pawlaczyk-Graja, Izabela and Gancarz, Roman and Zbikowska, Halina Malgorzata}, month = jun, year = {2017}, pmid = {28475935}, keywords = {Aglycone, Animals, Antioxidants, Asteraceae, Cell Line, Cell Survival, DNA, DNA Damage, Erigeron canadensis, Gamma Rays, Glycoconjugates, Humans, Lipid Peroxidation, Mice, Plants, Medicinal, Polyphenolic glycoconjugate, Polyphenols, Quercetin, Radiation-Protective Agents, Radioprotector, Rosaceae, Rutin, Sanguisorba officinalis, comet assay, γ-Irradiation}, pages = {50--57} }
@article{motenko_mousemine:_2015, title = {{MouseMine}: a new data warehouse for {MGI}}, volume = {26}, issn = {1432-1777}, shorttitle = {{MouseMine}}, doi = {10.1007/s00335-015-9573-z}, abstract = {MouseMine (www.mousemine.org) is a new data warehouse for accessing mouse data from Mouse Genome Informatics (MGI). Based on the InterMine software framework, MouseMine supports powerful query, reporting, and analysis capabilities, the ability to save and combine results from different queries, easy integration into larger workflows, and a comprehensive Web Services layer. Through MouseMine, users can access a significant portion of MGI data in new and useful ways. Importantly, MouseMine is also a member of a growing community of online data resources based on InterMine, including those established by other model organism databases. Adopting common interfaces and collaborating on data representation standards are critical to fostering cross-species data analysis. This paper presents a general introduction to MouseMine, presents examples of its use, and discusses the potential for further integration into the MGI interface.}, language = {eng}, number = {7-8}, journal = {Mammalian Genome: Official Journal of the International Mammalian Genome Society}, author = {Motenko, H. and Neuhauser, S. B. and O'Keefe, M. and Richardson, J. E.}, month = aug, year = {2015}, pmid = {26092688}, pmcid = {PMC4534495}, keywords = {Animals, Data Mining, Databases, Genetic, Genomics, Internet, Mice, Software}, pages = {325--330} }
@article{ title = {Subnetwork-Specific Homeostatic Plasticity in Mouse Visual Cortex In Vivo.}, type = {article}, year = {2015}, identifiers = {[object Object]}, keywords = {Animals,Female,Homeostasis,Homeostasis: physiology,Male,Mice,Mice, Inbred C57BL,Nerve Net,Nerve Net: physiology,Neuronal Plasticity,Neuronal Plasticity: physiology,Photic Stimulation,Photic Stimulation: methods,Sensory Deprivation,Sensory Deprivation: physiology,Visual Cortex,Visual Cortex: physiology,Visual Pathways,Visual Pathways: physiology}, pages = {1290-303}, volume = {86}, websites = {http://www.sciencedirect.com/science/article/pii/S0896627315004171}, month = {6}, day = {3}, id = {570f4aa4-00d6-3d2c-a463-f0f56e9e2820}, created = {2016-10-18T09:31:38.000Z}, accessed = {2016-06-06}, file_attached = {false}, profile_id = {a284bdcb-0ee1-3dea-9317-7f47c0e9b4ec}, group_id = {9e2da818-7db2-32de-9369-b0c1c4c7aea1}, last_modified = {2016-10-18T09:31:39.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Barnes2015}, abstract = {Homeostatic regulation has been shown to restore cortical activity in vivo following sensory deprivation, but it is unclear whether this recovery is uniform across all cells or specific to a subset of the network. To address this issue, we used chronic calcium imaging in behaving adult mice to examine the activity of individual excitatory and inhibitory neurons in the same region of the layer 2/3 monocular visual cortex following enucleation. We found that only a fraction of excitatory neurons homeostatically recover activity after deprivation and inhibitory neurons show no recovery. Prior to deprivation, excitatory cells that did recover were more likely to have significantly correlated activity with other recovering excitatory neurons, thus forming a subnetwork of recovering neurons. These network level changes are accompanied by a reduction in synaptic inhibition onto all excitatory neurons, suggesting that both synaptic mechanisms and subnetwork activity are important for homeostatic recovery of activity after deprivation.}, bibtype = {article}, author = {Barnes, Samuel J and Sammons, Rosanna P and Jacobsen, R Irene and Mackie, Jennifer and Keller, Georg B and Keck, Tara}, journal = {Neuron}, number = {5} }
@article{calderone_virusmentha:_2015, title = {{VirusMentha}: a new resource for virus-host protein interactions}, volume = {43}, issn = {1362-4962}, shorttitle = {{VirusMentha}}, doi = {10.1093/nar/gku830}, abstract = {Viral infections often cause diseases by perturbing several cellular processes in the infected host. Viral proteins target host proteins and either form new complexes or modulate the formation of functional host complexes. Describing and understanding the perturbation of the host interactome following viral infection is essential for basic virology and for the development of antiviral therapies. In order to provide a general overview of such interactions, a few years ago we developed VirusMINT. We have now extended the scope and coverage of VirusMINT and established VirusMentha, a new virus-virus and virus-host interaction resource build on the detailed curation protocols of the IMEx consortium and on the integration strategies developed for mentha. VirusMentha is regularly and automatically updated every week by capturing, via the PSICQUIC protocol, interactions curated by five different databases that are part of the IMEx consortium. VirusMentha can be freely browsed at http://virusmentha.uniroma2.it/ and its complete data set is available for download.}, language = {eng}, number = {Database issue}, journal = {Nucleic Acids Research}, author = {Calderone, Alberto and Licata, Luana and Cesareni, Gianni}, month = jan, year = {2015}, pmid = {25217587}, pmcid = {PMC4384001}, keywords = {Animals, Databases, Protein, Humans, Internet, Mice, Protein Interaction Mapping, Viral Proteins, Viruses}, pages = {D588--592} }
@article{kalderimis_intermine:_2014, title = {{InterMine}: extensive web services for modern biology}, volume = {42}, issn = {1362-4962}, shorttitle = {{InterMine}}, doi = {10.1093/nar/gku301}, abstract = {InterMine (www.intermine.org) is a biological data warehousing system providing extensive automatically generated and configurable RESTful web services that underpin the web interface and can be re-used in many other applications: to find and filter data; export it in a flexible and structured way; to upload, use, manipulate and analyze lists; to provide services for flexible retrieval of sequence segments, and for other statistical and analysis tools. Here we describe these features and discuss how they can be used separately or in combinations to support integrative and comparative analysis.}, language = {eng}, number = {Web Server issue}, journal = {Nucleic Acids Research}, author = {Kalderimis, Alex and Lyne, Rachel and Butano, Daniela and Contrino, Sergio and Lyne, Mike and Heimbach, Joshua and Hu, Fengyuan and Smith, Richard and Stěpán, Radek and Sullivan, Julie and Micklem, Gos}, month = jul, year = {2014}, pmid = {24753429}, pmcid = {PMC4086141}, keywords = {Animals, Chromosomes, Databases, Factual, Humans, Internet, Mice, Sequence Analysis, DNA, Software, User-Computer Interface}, pages = {W468--472} }
@article{sanino_polymeric_2014, title = {Polymeric vesicles loaded with gadoteridol as reversible and concentration-independent magnetic resonance imaging thermometers}, volume = {10}, issn = {1550-7033}, abstract = {The use of temperature sensitive liposomes (TSLs) loaded with paramagnetic Gd(III) complexes have been explored to develop MRI agents able to provide a imaging guide to heating-based therapies. Though the performance of such probes has been already demonstrated in vivo at preclinical level, further improvements (e.g., concentration independent image response, reversibility of the sensor) are necessary to increase the accuracy of the temperature readout. This work reports for the first time, the potential of Gd-loaded polymersomes (bilayered vesicles made of amphiphilic di-block copolymers) as improved thermosensitive MRI probes. Differently from conventional TSLs, such probes do not display a defined gel-to-liquid temperature transition and, therefore, they did not release their content in a wide temperature range, thereby allowing reversible temperature readouts. Moreover, a ratiometric approach based on the measurement of the ratio between transverse and longitudinal water protons relaxation rates (R2/R1) allows a temperature readout independent of the probe concentration. The imaging performance of temperature sensitive polymersomes prepared in this work was tested both in vitro and in vivo after subcutaneous injection in healthy mice.}, language = {eng}, number = {8}, journal = {Journal of Biomedical Nanotechnology}, author = {Sanino, Alberto and Dastrú, Walter and Mainini, Francesco and Delli Castelli, Daniela and Aime, Silvio and Terreno, Enzo}, month = aug, year = {2014}, pmid = {25016661}, keywords = {Animals, Female, Gadolinium, Heterocyclic Compounds, Liposomes, Magnetic Resonance Imaging, Mice, Mice, Inbred BALB C, Organometallic Compounds, Polymers, Temperature, Thermometry}, pages = {1620--1626} }
@article{nagakura_characterization_2013-1, title = {Characterization of cognitive deficits in a transgenic mouse model of {Alzheimer}'s disease and effects of donepezil and memantine}, volume = {703}, issn = {1879-0712}, doi = {10.1016/j.ejphar.2012.12.023}, abstract = {Alzheimer's disease is characterized by a progressive decline in cognitive function and involves β-amyloid (Aβ) in its pathogenesis. To characterize cognitive deficits associated with Aβ accumulation, we analyzed PS1/APP mice overexpressing mutant presenilin-1 (PS1, M146L; line 6.2) and amyloid precursor protein (APP, K670N/M671L; line Tg2576), a mouse model of Alzheimer's disease with accelerated Aβ production. Age-dependent changes in working and spatial memory behaviors were investigated using Y-maze and Morris water maze tasks, respectively, in female PS1/APP mice at ages of 2, 4, 6, and 12 months. Significant deficits in working and spatial memory were observed from 4 and 6 months of age, respectively. Acute single-dose administrations of memantine, a low-to-moderate-affinity N-methyl-d-aspartate (NMDA) antagonist, showed improvements in working memory deficits at 4 months of age, whereas donepezil, an acetylcholinesterase (AChE) inhibitor, did not. However, both drugs improved spatial memory dysfunction at 6 months of age at therapeutically relevant doses. No age-related dramatic changes were observed in expression levels of several proteins relating to memory dysfunction and also the mechanisms of donepezil and memantine in the cerebral cortex of PS1/APP mice until 6 months of age. Taken together, these results suggest dysfunctions in cholinergic and/or glutamatergic transmissions may be involved in the cognitive deficits associated with Aβ toxicity. Since donepezil and memantine have been widely used for treating patients of Alzheimer's disease, these results also suggest that cognitive deficits in PS1/APP mice assessed in the Y-maze and Morris water maze tasks are a useful animal model for evaluating novel Alzheimer's disease therapeutics.}, language = {eng}, number = {1-3}, journal = {European Journal of Pharmacology}, author = {Nagakura, Akira and Shitaka, Yoshitsugu and Yarimizu, Junko and Matsuoka, Nobuya}, month = mar, year = {2013}, pmid = {23276665}, keywords = {Alzheimer Disease, Animals, Brain, Cholinesterase Inhibitors, Cyclic AMP Response Element-Binding Protein, Disease Models, Animal, Female, Indans, Maze Learning, Memantine, Memory, Memory Disorders, Mice, Mice, Transgenic, Nootropic Agents, Piperidines, Receptors, AMPA}, pages = {53--61} }
@article{ torres_myd88_2013, title = {{MyD}88 is crucial for the development of a protective {CNS} immune response to Toxoplasma gondii infection}, volume = {10}, issn = {1742-2094}, doi = {10.1186/1742-2094-10-19}, abstract = {{BACKGROUND}: Toxoplasmosis is one of the most common parasitic infections in humans. It can establish chronic infection and is characterized by the formation of tissue cysts in the brain. The cysts remain largely quiescent for the life of the host, but can reactivate and cause life-threatening toxoplasmic encephalitis in immunocompromised patients, such as those with {AIDS}, neoplastic diseases and organ transplants. Toll-like receptor ({TLR}) adaptor {MyD}88 activation is required for the innate sensing of Toxoplasma gondii. Mice deficient in {MyD}88 have defective {IL}-12 and Th1 effector responses, and are highly susceptible to the acute phase of T. gondii infection. However, the role of this signaling pathway during cerebral infection is poorly understood and requires examination. {METHOD}: {MyD}88-deficient mice and control mice were orally infected with T. gondii cysts. Cellular and parasite infiltration in the peripheral organs and in the brain were determined by histology and immunohistochemistry. Cytokine levels were determined by {ELISA} and chemokine {mRNA} levels were quantified by real-time {PCR} ({qPCR}). {RESULTS}: Thirteen days after infection, a higher parasite burden was observed but there was no histological change in the liver, heart, lungs and small intestine of {MyD}88⁻/⁻ and {MyD}88⁺/⁺ mice. However, {MyD}88⁻/⁻ mice compared to {MyD}88⁺/⁺ mice were highly susceptible to cerebral infection, displayed high parasite migration to the brain, severe neuropathological signs of encephalitis and succumbed within 2 weeks of oral infection. Susceptibility was primarily associated with lower expression of Th1 cytokines, especially {IL}-12, {IFN}-γ and {TNF}-α, significant decrease in the expression of {CCL}3, {CCL}5, {CCL}7 and {CCL}19 chemokines, marked defect of {CD}8⁺ T cells, and infiltration of {CD}11b⁺ and F4/80⁺ cells in the brain. {CONCLUSION}: {MyD}88 is essential for the protection of mice during the cerebral installation of T. gondii infection. These results establish a role for {MyD}88 in T cell-mediated control of T. gondii in the central nervous system ({CNS}).}, language = {eng}, journal = {Journal of Neuroinflammation}, author = {Torres, Marbel and Guiton, Rachel and Lacroix-Lamandé, Sonia and Ryffel, Bernhard and Leman, Samuel and Dimier-Poisson, Isabelle}, year = {2013}, pmid = {23374751}, pmcid = {PMC3566937}, keywords = {Animals, Brain, Female, Immunity, Cellular, Mice, Mice, Inbred {BALB} C, Mice, Knockout, Myeloid Differentiation Factor 88, Toxoplasma, Toxoplasmosis, Animal, Toxoplasmosis, Cerebral}, pages = {19} }
@article{xu_keap1_2013, title = {{KEAP}1 is a redox sensitive target that arbitrates the opposing radiosensitive effects of parthenolide in normal and cancer cells}, volume = {73}, issn = {1538-7445}, doi = {10.1158/0008-5472.CAN-12-4297}, abstract = {Elevated oxidative stress is observed more frequently in cancer cells than in normal cells. It is therefore expected that additional exposure to a low level of reactive oxygen species (ROS) will push cancer cells toward death, whereas normal cells might maintain redox homeostasis through adaptive antioxidant responses. We previously showed that parthenolide enhances ROS production in prostate cancer cells through activation of NADPH oxidase. The present study identifies KEAP1 as the downstream redox target that contributes to parthenolide's radiosensitization effect in prostate cancer cells. In vivo, parthenolide increases radiosensitivity of mouse xenograft tumors but protects normal prostate and bladder tissues against radiation-induced injury. Mechanistically, parthenolide increases the level of cellular ROS and causes oxidation of thioredoxin (TrX) in prostate cancer cells, leading to a TrX-dependent increase in a reduced state of KEAP1, which in turn leads to KEAP1-mediated PGAM5 and Bcl-xL (BCL2L1) degradation. In contrast, parthenolide increases oxidation of KEAP1 in normal prostate epithelial cells, leading to increased Nrf2 (NFE2L2) levels and subsequent Nrf2-dependent expression of antioxidant enzymes. These results reveal a novel redox-mediated modification of KEAP1 in controlling the differential effect of parthenolide on tumor and normal cell radiosensitivity. Furthermore, they show it is possible to develop a tumor-specific radiosensitizing agent with radioprotective properties in normal cells.}, number = {14}, journal = {Cancer research}, author = {Xu, Yong and Fang, Fang and Miriyala, Sumitra and Crooks, Peter A and Oberley, Terry D and Chaiswing, Luksana and Noel, Teresa and Holley, Aaron K and Zhao, Yanming and Kiningham, Kelley K and Clair, Daret K St and Clair, William H St}, month = jul, year = {2013}, pmid = {23674500}, keywords = {Animals, Antioxidants, Carrier Proteins, Cell Line, Cell Line, Tumor, Epithelial Cells, Humans, Intracellular Signaling Peptides and Proteins, Kelch-Like ECH-Associated Protein 1, Male, Mice, Mice, Nude, Mitochondrial Proteins, NF-E2-Related Factor 2, Oxidation-Reduction, Oxidative Stress, Phosphoprotein Phosphatases, Prostatic Neoplasms, Radiation Tolerance, Radiation-Sensitizing Agents, Random Allocation, Reactive Oxygen Species, Sesquiterpenes, Thioredoxins, Ubiquitin, Xenograft Model Antitumor Assays, bcl-X Protein}, pages = {4406--4417} }
@article{ title = {Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells.}, type = {article}, year = {2012}, identifiers = {[object Object]}, keywords = {Animals,Cells, Cultured,Cultured,Endothelium,Endothelium: pathology,Flow Cytometry,Gene Silencing,Humans,Immunoprecipitation,Mice,Multiple Myeloma,Multiple Myeloma: blood supply,Multiple Myeloma: pathology,Neovascularization, Pathologic,Pathologic,Real-Time Polymerase Chain Reaction,Signal Transduction,Syndecan-1,Syndecan-1: genetics,Syndecan-1: physiology,Tumor Cells, Cultured,Vascular Endothelial Growth Factor A,Vascular Endothelial Growth Factor A: metabolism,Vascular Endothelial Growth Factor Receptor-2,Vascular Endothelial Growth Factor Receptor-2: met}, pages = {1081-90}, volume = {26}, websites = {http://dx.doi.org/10.1038/leu.2011.290}, month = {5}, publisher = {Macmillan Publishers Limited}, id = {0dc3a323-ae53-325a-9f8b-74d28f5e217a}, created = {2016-06-24T20:50:03.000Z}, accessed = {2014-12-01}, file_attached = {false}, profile_id = {954a987f-819f-3985-95a4-2991e0cf0552}, group_id = {8440dcff-74cc-3783-aef7-fe2749cfc7ef}, last_modified = {2016-06-24T20:50:03.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Lamorte2012}, short_title = {Leukemia}, abstract = {Angiogenesis is considered a hallmark of multiple myeloma (MM) progression. In the present study, we evaluated the morphological and functional features of endothelial cells (ECs) derived from bone marrow (BM) of patients affected by MM (MMECs). We found that MMECs compared with normal BM ECs (BMECs) showed increased expression of syndecan-1. Silencing of syndecan-1 expression by RNA interference technique decreased in vitro EC survival, proliferation and organization in capillary-like structures. In vivo, in severe combined immunodeficient mice, syndecan-1 silencing inhibited MMEC organization into patent vessels. When overexpressed in human umbilical vein ECs and BMECs, syndecan-1 induced in vitro and in vivo angiogenic effects. Flow-cytometric analysis of MMECs silenced for syndecan-1 expression indicated a decreased membrane expression of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2). Immunoprecipitation and confocal analysis showed colocalization of VEGFR-2 with syndecan-1. Absence of nuclear translocation of VEGFR-2 in syndecan-1-knockdown cells together with the shift from perinuclear localization to recycling compartments suggest a role of syndecan-1 in modulation of VEGFR-2 localization. This correlated with an in vitro decreased VEGF-induced invasion and motility. These results suggest that syndecan-1 may contribute to the highly angiogenic phenotype of MMECs by promoting EC proliferation, survival and modulating VEGF-VEGFR-2 signalling.}, bibtype = {article}, author = {Lamorte, S and Ferrero, S and Aschero, S and Monitillo, L and Bussolati, B and Omedè, P and Ladetto, M and Camussi, G}, journal = {Leukemia}, number = {5} }
@article{ ISI:000302388100020, Author = {Ning, Kang and Fermin, Damian and Nesvizhskii, Alexey I.}, Title = {{Comparative Analysis of Different Label-Free Mass Spectrometry Based Protein Abundance Estimates and Their Correlation with RNA-Seq Gene Expression Data}}, Journal = {{JOURNAL OF PROTEOME RESEARCH}}, Year = {{2012}}, Volume = {{11}}, Number = {{4}}, Pages = {{2261-2271}}, Month = {{APR}}, Abstract = {{An increasing number of studies involve integrative analysis of gene and protein expression data taking advantage of new technologies such as next-generation transcriptome sequencing (RNA-Seq) and highly sensitive mass spectrometry (MS) instrumentation. Thus, it becomes interesting to revisit the correlative analysis of gene and protein expression data using more recently generated data sets. Furthermore, within the proteomics community there is a substantial interest in comparing the performance of different label-free quantitative proteomic strategies. Gene expression data can be used as an indirect benchmark for such protein-level comparisons. In this work we use publicly available mouse data to perform a joint analysis of genomic and proteomic data obtained on the same organism. First, we perform a comparative analysis of different label-free protein quantification methods (intensity based and spectral count based and using various associated data normalization steps) using several software tools on the proteomic side. Similarly, we perform correlative analysis of gene expression data derived using microarray and RNA-Seq methods on the genomic side. We also investigate the correlation between gene and protein expression data, and various factors affecting the accuracy of quantitation at both levels. It is observed that spectral count based protein abundance metrics, which are easy to extract from any published data, are comparable to intensity based measures with respect to correlation with gene expression data. The results of this work should be useful for designing robust computational pipelines for extraction and joint analysis of gene and protein expression data in the context of integrative studies.}}, DOI = {{10.1021/pr201052x}}, ISSN = {{1535-3893}}, ResearcherID-Numbers = {{Nesvizhskii, Alexey/A-5410-2012}}, Unique-ID = {{ISI:000302388100020}}, }
@article{ tanti_differential_2012, title = {Differential environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus}, volume = {63}, issn = {1873-7064}, doi = {10.1016/j.neuropharm.2012.04.022}, abstract = {The hippocampus is involved in both cognitive and emotional processing; these different functions are topographically distributed along its septo-temporal axis, the dorsal (septal) hippocampus being preferentially involved in cognitive processes such as learning and memory while the ventral (temporal) hippocampus participates in emotional regulation and anxiety-related behaviors. Newborn hippocampal neurons become functionally integrated into hippocampal networks and are likely to contribute to hippocampal functions, but whether their regulation and function are homogenous throughout this axis is not clear. Here we investigate changes in cell proliferation and neurogenesis along the septo-temporal axis of the hippocampus induced by the Unpredictable Chronic Mild Stress model of depression (UCMS), chronic fluoxetine treatment and enriched environment. Mice were either subjected to UCMS, standard housing or enriched environment. Stress-exposed mice were treated daily with fluoxetine (10 mg/kg) or vehicle. Effects of UCMS regimen, fluoxetine treatment and enrichment were assessed by physical measures and behavioral testing. Quantitative changes in cell proliferation and neurogenesis were assessed by immunohistochemistry using BrdU labeling. Results indicate that UCMS decreased cell proliferation and neurogenesis preferentially in the ventral hippocampus, an effect that was reversed by fluoxetine treatment. Environmental enrichment on the other hand increased cell proliferation in both divisions but promoted neurogenesis only in the dorsal hippocampus. These results indicate that environmental factors can differentially regulate neurogenesis in a region-specific manner. This may possibly underlie heterogeneous function of newborn neurons along the septo-temporal axis of the hippocampus and have functional significance as to their implication in stress related disorders and memory processes.}, language = {eng}, number = {3}, journal = {Neuropharmacology}, author = {Tanti, Arnaud and Rainer, Quentin and Minier, Frederic and Surget, Alexandre and Belzung, Catherine}, month = {September}, year = {2012}, pmid = {22561281}, keywords = {Animals, Animals, Newborn, Antidepressive Agents, Second-Generation, Antimetabolites, Anxiety, Bromodeoxyuridine, Cell Proliferation, Depression, Dose-Response Relationship, Drug, Eating, Environment, Fluoxetine, Grooming, Hair, Hippocampus, Male, Memory, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Motor Activity, Neurogenesis, Recognition (Psychology), Stress, Psychological}, pages = {374--384} }
@article{behbehani_single-cell_2012, title = {Single-cell mass cytometry adapted to measurements of the cell cycle.}, volume = {81}, issn = {1552-4930}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22693166}, doi = {10.1002/cyto.a.22075}, abstract = {Mass cytometry is a recently introduced technology that utilizes transition element isotope-tagged antibodies for protein detection on a single-cell basis. By circumventing the limitations of emission spectral overlap associated with fluorochromes utilized in traditional flow cytometry, mass cytometry currently allows measurement of up to 40 parameters per cell. Recently, a comprehensive mass cytometry analysis was described for the hematopoietic differentiation program in human bone marrow from a healthy donor. The current study describes approaches to delineate cell cycle stages utilizing 5-iodo-2-deoxyuridine (IdU) to mark cells in S phase, simultaneously with antibodies against cyclin B1, cyclin A, and phosphorylated histone H3 (S28) that characterize the other cell cycle phases. Protocols were developed in which an antibody against phosphorylated retinoblastoma protein (Rb) at serines 807 and 811 was used to separate cells in G0 and G1 phases of the cell cycle. This mass cytometry method yielded cell cycle distributions of both normal and cancer cell populations that were equivalent to those obtained by traditional fluorescence cytometry techniques. We applied this to map the cell cycle phases of cells spanning the hematopoietic hierarchy in healthy human bone marrow as a prelude to later studies with cancers and other disorders of this lineage.}, number = {7}, journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology}, author = {Behbehani, Gregory K and Bendall, Sean C and Clutter, Matthew R and Fantl, Wendy J and Nolan, Garry P}, month = jul, year = {2012}, keywords = {Animals, Antibodies, Antibodies: chemistry, Bone Marrow Cells, Bone Marrow Cells: metabolism, Bone Marrow Cells: physiology, Cell Cycle Checkpoints, Cell Differentiation, Cell Line, Cell Proliferation, Cell Separation, Cyclin A, Cyclin A: metabolism, Cyclin B1, Cyclin B1: metabolism, DNA Replication, flow cytometry, Hematopoiesis, Histones, Histones: metabolism, Humans, Immunophenotyping, Membrane Proteins, Membrane Proteins: metabolism, Mice, Retinoblastoma Protein, Retinoblastoma Protein: metabolism, Single-Cell Analysis, Single-Cell Analysis: methods, Staining and Labeling, T-Lymphocytes, T-Lymphocytes: metabolism, T-Lymphocytes: physiology, Transition Elements, Transition Elements: chemistry}, pages = {552--66} }
@article{ title = {Surface modifications by gas plasma control osteogenic differentiation of MC3T3-E1 cells.}, type = {article}, year = {2012}, identifiers = {[object Object]}, keywords = {Adsorption,Adsorption: drug effects,Animals,Atmospheric Pressure,Atomic Force,Biocompatible Materials,Biocompatible Materials: pharmacology,Bovine,Bovine: metabolism,Cell Adhesion,Cell Adhesion: drug effects,Cell Differentiation,Cell Differentiation: drug effects,Cell Line,Cell Proliferation,Cell Proliferation: drug effects,Gene Expression Regulation,Gene Expression Regulation: drug effects,Hydrophobic and Hydrophilic Interactions,Hydrophobic and Hydrophilic Interactions: drug eff,Lactic Acid,Lactic Acid: pharmacology,Mice,Microscopy,Osteoblasts,Osteoblasts: cytology,Osteoblasts: drug effects,Osteoblasts: metabolism,Osteogenesis,Osteogenesis: drug effects,Plasma Gases,Plasma Gases: pharmacology,Polymers,Polymers: pharmacology,Serum Albumin,Surface Properties,Surface Properties: drug effects}, pages = {2969-77}, volume = {8}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/22522130}, month = {8}, id = {9d5183f9-1415-385b-a3aa-26e528b01ce9}, created = {2012-10-12T15:06:59.000Z}, accessed = {2013-01-30}, file_attached = {true}, profile_id = {78b6d3f1-1bc3-3383-82b0-f5d02daa98a6}, last_modified = {2017-03-10T15:48:51.694Z}, tags = {bio,helium,helium ion microscopy,him}, read = {true}, starred = {false}, authored = {true}, confirmed = {true}, hidden = {false}, citation_key = {Barradas2012}, source_type = {citeulike:JOUR}, user_context = {Journal article}, folder_uuids = {5c13111f-15fa-46f1-8ccb-f62f3e385126}, abstract = {Numerous studies have shown that the physicochemical properties of biomaterials can control cell activity. Cell adhesion, proliferation, differentiation as well as tissue formation in vivo can be tuned by properties such as the porosity, surface micro- and nanoscale topography and chemical composition of biomaterials. This concept is very appealing for tissue engineering since instructive properties in bioactive materials can be more economical and time efficient than traditional strategies of cell pre-differentiation in vitro prior to implantation. The biomaterial surface, which is easy to modify due to its accessibility, may provide the necessary signals to elicit a certain cellular behavior. Here, we used gas plasma technology at atmospheric pressure to modify the physicochemical properties of polylactic acid and analyzed how this influenced pre-osteoblast proliferation and differentiation. Tetramethylsilane and 3-aminopropyl-trimethoxysilane with helium as a carrier gas or a mixture of nitrogen and hydrogen were discharged to polylactic acid discs to create different surface chemical compositions, hydrophobicity and microscale topographies. Such modifications influenced protein adsorption and pre-osteoblast cell adhesion, proliferation and osteogenic differentiation. Furthermore polylactic acid treated with tetramethylsilane enhanced osteogenic differentiation compared to the other surfaces. This promising surface modification could be further explored for potential development of bone graft substitutes.}, bibtype = {article}, author = {Barradas Cravo, Ana Margarida and Lachmann, Kristina and Hlawacek, Gregor and Frielink, Cathelijne and Truckenmoller, Roman and Boerman, Otto C. and van Gastel, Raoul and Garritsen, Henk and Thomas, Michael and Moroni, Lorenzo and van Blitterswijk, Clemens and de Boer, Jan}, journal = {Acta biomaterialia}, number = {8} }
@article{bearr_species_2012, title = {Species specific differences in the in vitro metabolism of the flame retardant mixture, {Firemaster}® {BZ}-54.}, volume = {124-125}, issn = {1879-1514}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22889877}, doi = {10.1016/j.aquatox.2012.06.006}, abstract = {Firemaster(®) BZ-54 is a flame retardant additive and consists of a brominated benzoate (2-ethylhexyl 2,3,4,5-tetrabromobenzoate; TBB) and a brominated phthalate (bis (2-ethylhexyl) 2,3,4,5-tetrabromophthalate; TBPH). Previous research has shown that fathead minnows exposed in vivo to Firemaster(®) BZ-54 accumulate TBB and TBPH. This study examined the in vitro biotransformation potential of TBB and TBPH in hepatic subcellular fractions (i.e., S9, microsomes and cytosol) in the fathead minnow, common carp, mouse and snapping turtle. Metabolism was evaluated by measuring the loss of the parent TBB or TBPH and identifying potential metabolites in the sample extracts. Metabolic loss of TBPH was measured for all species, while TBB loss was observed for all species except for the snapping turtle. Several metabolites were observed in all of the incubations except for snapping turtle. Metabolites observed appeared to be derived from TBB, given their structures and lack of appearance in the snapping turtle incubations. One of these metabolites, 2,3,4,5-tetrabromomethylbenzoate has been identified for the first time in a biological system. When metabolized, TBB and TBPH loss was found in each subcellular fraction suggesting that the enzyme(s) involved are present in both soluble and membrane-bound forms. It can be concluded that a broad range of species are capable of metabolizing TBB and TBPH to various metabolites and further research should be carried out to ascertain the specific products formed from metabolism of TBB and TBPH.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, author = {Bearr, Jonathan S and Mitchelmore, Carys L and Roberts, Simon C and Stapleton, Heather M}, month = nov, year = {2012}, pmid = {22889877}, keywords = {Animals, Benzoates, Benzoates: metabolism, Carps, Carps: metabolism, Cyprinidae, Cyprinidae: metabolism, Flame Retardants: metabolism, Flame retardants, Liver, Liver: metabolism, Mice, Phthalic Acids, Phthalic Acids: metabolism, Species Specificity, Turtles, Turtles: metabolism}, pages = {41--7} }
@article{ isingrini_fluoxetine_2012, title = {Fluoxetine effect on aortic nitric oxide-dependent vasorelaxation in the unpredictable chronic mild stress model of depression in mice}, volume = {74}, issn = {1534-7796}, doi = {10.1097/PSY.0b013e31823a43e0}, abstract = {{OBJECTIVE}: Major depression is an independent risk factor for the development of cardiovascular diseases. However, the exact mechanism by which depression may induce cardiovascular events is unclear. Endothelial dysfunction has been reported as a possible link between depression and subsequent cardiovascular events as described in depressed subjects. The purpose of this study was to investigate endothelial dysfunction and atherosclerosis formation in the aorta of mice exposed to the unpredictable chronic mild stress ({UCMS}) procedure. {METHODS}: {BALB}/c mice were exposed to two 7-week {UCMS} procedures separated by 6 weeks. Treatments (fluoxetine 10 mg/kg; {NaCl} 0.9%) started at the third week until the end of the seventh week of each procedure. Endothelial function was evaluated by in vitro assessment of acetylcholine-induced vasorelaxation in aortic rings. By using specific inhibitors for nitric oxide ({NO})- and prostacyclin-dependent relaxation, we assessed the part played by {NO}, prostacyclin, and endothelium-derived hyperpolarizing factor ({EDHF})-like mediators in endothelium-dependent relaxation. Atherosclerosis was evaluated by histological examination. {RESULTS}: Depression-like behavior was increased in the {UCMS} versus unstressed group and was reversed by chronic fluoxetine treatment. Vascular reactivity study indicated that {UCMS} induced a decrease in the {NO}-dependent relaxation that was partially compensated by an {EDHF}-like dependent relaxation. Because fluoxetine per se increased the {NO}-dependent relaxation, fluoxetine was able to reverse {UCMS} effect on the {NO} component and abolished the {EDHF}-like component. Atherosclerotic lesion was found in aorta of {UCMS} and nonstressed animals. {CONCLUSIONS}: As an independent risk factor, {UCMS} reproduced the endothelial alterations observed in depression but was not sufficient to provoke morphological alterations.}, language = {eng}, number = {1}, journal = {Psychosomatic Medicine}, author = {Isingrini, Elsa and Belzung, Catherine and Freslon, Jean-Louis and Machet, Marie-Christine and Camus, Vincent}, month = {January}, year = {2012}, pmid = {22210237}, keywords = {Acetylcholine, Animals, Aorta, Atherosclerosis, Biological Factors, Depressive Disorder, Major, Disease Models, Animal, Dose-Response Relationship, Drug, Endothelium, Vascular, Endothelium-Dependent Relaxing Factors, Epoprostenol, Fluoxetine, Logistic Models, Mice, Mice, Inbred {BALB} C, Nitric Oxide, Random Allocation, Serotonin Uptake Inhibitors, Stress, Psychological, Vasodilation}, pages = {63--72} }
@article{haddadin_thrombospondin-1_2012, title = {Thrombospondin-1 ({TSP}1)-null and {TSP}2-null mice exhibit lower intraocular pressures}, volume = {53}, issn = {1552-5783}, url = {http://ezproxynco.flo.org/login?url=https://doi.org/10.1167/iovs.11-9013}, doi = {10.1167/iovs.11-9013}, abstract = {PURPOSE: Thrombospondin-1 (TSP1) and TSP2 are matricellular proteins that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling. Both TSP1 and TSP2 are found in the trabecular meshwork (TM). In cadaver eyes with primary open-angle glaucoma (POAG), TSP1 is increased in one third of patients. We hypothesized that TSP1 and TSP2 participate in the regulation of intraocular pressure (IOP). Methods. IOPs of TSP1-null, TSP2-null mice, and their corresponding wild-type (WT) mice were measured using a commercial rebound tonometer. Fluorophotometric measurements assessed aqueous turnover. Central corneal thickness (CCT) was measured by optical coherence tomography. Iridocorneal angles were examined using light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM). RESULTS: Average IOPs of TSP1-null and TSP2-null mice were 10\% and 7\% less than that of the corresponding WT mice, respectively. CCTs were 6.5\% less in TSP1-null mice (P {\textless} 0.05) and 1.1\% less in TSP2-null mice (P {\textgreater} 0.05). Fluorophotometric measurements suggest that aqueous turnover rates in TSP1-null and TSP2-null mice are greater than those of WT mice. LM of the TSP1-null and TSP2-null iridocorneal angles reveals morphology, which is indistinguishable from that of their corresponding WTs. IF revealed possible concurrent underexpression of TSP2 in TSP1-null mice and of TSP1 in TSP2-null mice. TEM revealed larger collagen fibril diameters in TSP1-null and TSP2-null mice compared with WTs. CONCLUSIONS: TSP1-null and TSP2-null mice have lower IOPs than their WT counterparts. The rate of aqueous turnover suggests that the mechanism is enhanced outflow facility. An alteration in the extracellular matrix may contribute to this finding.}, number = {10}, journal = {Investigative Ophthalmology \& Visual Science}, author = {Haddadin, Ramez I. and Oh, Dong-Jin and Kang, Min Hyung and Villarreal, Guadalupe and Kang, Ja-Heon and Jin, Rui and Gong, Haiyan and Rhee, Douglas J.}, month = sep, year = {2012}, pmid = {22930728}, pmcid = {PMC3462480}, keywords = {Animals, Aqueous Humor, Cell Adhesion, Cell Adhesion Molecules, Disease Models, Animal, Endothelium, Corneal, Extracellular Matrix, Fluorophotometry, Gene Expression Regulation, Glaucoma, Open-Angle, Immunoblotting, Intraocular Pressure, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, RNA, Reverse Transcriptase Polymerase Chain Reaction, Thrombospondin 1, Thrombospondins, Tomography, Optical Coherence, Trabecular Meshwork}, pages = {6708--6717} }
@article{ title = {In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids.}, type = {article}, year = {2012}, identifiers = {[object Object]}, keywords = {Alginates,Alginates: chemistry,Animals,Cell Survival,Cell Survival: physiology,Cells, Cultured,Collagen,Collagen: chemistry,Glucuronic Acid,Glucuronic Acid: chemistry,Hexuronic Acids,Hexuronic Acids: chemistry,Immunohistochemistry,Islets of Langerhans,Islets of Langerhans: cytology,Male,Mice,Mice, Inbred BALB C,Microscopy, Atomic Force,Oxygen Consumption,Oxygen Consumption: physiology,Rats,Rats, Sprague-Dawley,Spheroids, Cellular,Spheroids, Cellular: cytology,Spheroids, Cellular: metabolism}, pages = {837-45}, volume = {33}, websites = {http://www.sciencedirect.com/science/article/pii/S0142961211012178}, month = {1}, id = {cd3077ec-1796-3882-bf3c-6abfde361e86}, created = {2016-06-24T20:49:47.000Z}, accessed = {2015-04-02}, file_attached = {false}, profile_id = {954a987f-819f-3985-95a4-2991e0cf0552}, group_id = {8440dcff-74cc-3783-aef7-fe2749cfc7ef}, last_modified = {2016-06-24T20:49:47.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Lee2012}, abstract = {In this study, we suggest in situ islet spheroid formation and encapsulation on a single platform without replating as a method for producing mono-disperse spheroids and minimizing damage to spheroids during encapsulation. Using this approach, the size of spheroid can be controlled by modulating the size of the concave well. Here, we used 300 μm concave wells to reduce spheroid size and thereby eliminating the central necrosis caused by large volume. As the encapsulation material, we used alginate and collagen-alginate composite (CAC), and evaluated their suitability through diverse in vitro tests, including measurements of viability, oxygen consumption rate (OCR), hypoxic damage to encapsulated spheroids, and insulin secretion. For in situ encapsulation, alginate or CAC was spread over a concave microwell array containing spheroids, and CaCl(2) solution was diffused through a nano-porous dialysis membrane to achieve uniform polymerization, forming convex structures. By this process, the formation of uniform-size islet spheroids and their encapsulation without an intervening replating step was successfully performed. As a control, intact islets were evaluated concurrently. The in vitro test demonstrated excellent performance of CAC-encapsulated spheroids, and on the basis of these results, we transplanted the islet spheroids-encapsulated with CAC into the intraperitoneal cavity of mice with induced diabetes for 4 weeks, and evaluated subsequent glucose control. Intact islets were also transplanted as control to investigate the effect of encapsulation. Transplanted CAC-encapsulated islet spheroids maintained glucose levels below 200 mg/dL for 4 weeks, at which they were still active. At the end of the implantation experiment, we carried out intraperitoneal glucose tolerance test (IPGTT) in mice to investigate whether the implanted islets remained responsive to glucose. The glucose level in mice with CAC-encapsulated islet spheroids dropped below 200 mg/dL 60 min after glucose injection and was stably maintained. In conclusion, the proposed encapsulation method enhances the viability and function of islet spheroids, and protects these spheroids from immune attack.}, bibtype = {article}, author = {Lee, Bo Ram and Hwang, Jin Wook and Choi, Yoon Young and Wong, Sau Fung and Hwang, Yong Hwa and Lee, Dong Yun and Lee, Sang-Hoon}, journal = {Biomaterials}, number = {3} }
@article{ title = {Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation.}, type = {article}, year = {2012}, identifiers = {[object Object]}, keywords = {Activating Transcription Factor 4,Activating Transcription Factor 4: metabolism,Animals,Cell Line, Tumor,Cell Proliferation,Glycolysis,Humans,Kinetics,Mice,Models, Biological,Multiprotein Complexes,Protein-Serine-Threonine Kinases,Protein-Serine-Threonine Kinases: metabolism,Proteins,Proteins: metabolism,Pyruvate Kinase,Pyruvate Kinase: antagonists & inhibitors,Pyruvate Kinase: genetics,Pyruvate Kinase: metabolism,RNA, Small Interfering,RNA, Small Interfering: genetics,Serine,Serine: biosynthesis,Signal Transduction,TOR Serine-Threonine Kinases}, pages = {6904-9}, volume = {109}, websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3345000&tool=pmcentrez&rendertype=abstract}, month = {5}, day = {1}, id = {f80d7600-f8d5-3649-aa61-a938ab6d3eed}, created = {2016-04-27T01:24:33.000Z}, accessed = {2016-04-11}, file_attached = {false}, profile_id = {95ad1c8a-ddc5-3572-ab20-1b5660ace0c4}, group_id = {409b6953-b59c-338c-b6e7-a89d45a37162}, last_modified = {2016-04-27T01:24:33.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, abstract = {Despite the fact that most cancer cells display high glycolytic activity, cancer cells selectively express the less active M2 isoform of pyruvate kinase (PKM2). Here we demonstrate that PKM2 expression makes a critical regulatory contribution to the serine synthetic pathway. In the absence of serine, an allosteric activator of PKM2, glycolytic efflux to lactate is significantly reduced in PKM2-expressing cells. This inhibition of PKM2 results in the accumulation of glycolytic intermediates that feed into serine synthesis. As a consequence, PKM2-expressing cells can maintain mammalian target of rapamycin complex 1 activity and proliferate in serine-depleted medium, but PKM1-expressing cells cannot. Cellular detection of serine depletion depends on general control nonderepressible 2 kinase-activating transcription factor 4 (GCN2-ATF4) pathway activation and results in increased expression of enzymes required for serine synthesis from the accumulating glycolytic precursors. These findings suggest that tumor cells use serine-dependent regulation of PKM2 and GCN2 to modulate the flux of glycolytic intermediates in support of cell proliferation.}, bibtype = {article}, author = {Ye, Jiangbin and Mancuso, Anthony and Tong, Xuemei and Ward, Patrick S and Fan, Jing and Rabinowitz, Joshua D and Thompson, Craig B}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {18} }
@article{ slupianek_bcr/abl_2011, title = {{}/{ABL} stimulates {WRN} to promote survival and genomic instability}, volume = {71}, issn = {1538-7445}, doi = {10.1158/0008-5472.CAN-10-1066}, abstract = {BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSB) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), nonhomologous end-joining (NHEJ), and single-strand annealing (SSA). Here, we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTK), such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC-mediated activation of transcription and Bcl-xL-dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability.}, language = {eng}, number = {3}, journal = {Cancer Research}, author = {Slupianek, Artur and Poplawski, Tomasz and Jozwiakowski, Stanislaw K. and Cramer, Kimberly and Pytel, Dariusz and Stoczynska, Ewelina and Nowicki, Michal O. and Blasiak, Janusz and Skorski, Tomasz}, month = {February}, year = {2011}, pmid = {21123451}, pmcid = {PMC3032814}, keywords = {Animals, Cell Line, Tumor, Chromosome Aberrations, DNA Breaks, Double-Stranded, DNA Repair, DNA, Neoplasm, Disease Progression, Exodeoxyribonucleases, Fusion Proteins, bcr-abl, Genomic Instability, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Mice, Oxidative Stress, Phosphorylation, Protein-Tyrosine Kinases, RecQ Helicases, Recombinant Fusion Proteins}, pages = {842--851} }
@article{yim_suppressive_2011, title = {Suppressive {Effects} of {Amarouciaxanthin} {A} on {3T3}-{L1} {Adipocyte} {Differentiation} through {Down}-regulation of {PPARγ} and {C}/{EBPα} {mRNA} {Expression}}, volume = {59}, issn = {0021-8561}, url = {https://doi.org/10.1021/jf103290f}, doi = {10.1021/jf103290f}, abstract = {Fucoxanthin is converted to fucoxanthinol and amarouciaxanthin A in mice. It was previously reported that fucoxanthinol attenuated the adipogenesis of 3T3-L1 cells. However, the effects of amarouciaxanthin A on adipocyte differentiation have not been clarified. This study examined the effects of amarouciaxanthin A on 3T3-L1 adipogenesis by comparing the effects of fucoxanthinol, isofucoxanthinol, and amarouciaxanthin B. Amarouciaxanthin A significantly decreased glycerol-3-phosphate dehydrogenase (GPDH) activity, which was measured as an indicator of adipocyte differentiation. The suppressive effect of amarouciaxanthin A was stronger than that of fucoxanthinol, amarouciaxanthin B, and isofucoxanthinol. The mRNA expressions of adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and glucose-transporter 4 (Glut4) in 3T3-L1 cells were markedly down-regulated by amarouciaxanthin A compared to fucoxanthinol. Furthermore, the expression levels of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (C/EBPα),, which are the key adipogenic transcriptional factors, were also decreased by amarouciaxanthin A during adipocyte differentiation. These results show that amarouciaxanthin A, which is a dominant metabolite of fucoxanthin in white adipose tissue, suppressed 3T3-L1 adipocyte differentiation.}, number = {5}, urldate = {2020-02-19}, journal = {Journal of Agricultural and Food Chemistry}, author = {Yim, Mi-Jin and Hosokawa, Masashi and Mizushina, Yoshiyuki and Yoshida, Hiromi and Saito, Yasunori and Miyashita, Kazuo}, month = mar, year = {2011}, keywords = {Saito Y}, pages = {1646--1652} }
@article{dingemans_neurotoxicity_2011, title = {Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system.}, volume = {119}, issn = {1552-9924}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3223008&tool=pmcentrez&rendertype=abstract}, doi = {10.1289/ehp.1003035}, abstract = {Polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-) or methoxylated forms have been detected in humans. Because this raises concern about adverse effects on the developing brain, we reviewed the scientific literature on these mechanisms.}, number = {7}, journal = {Environmental health perspectives}, author = {Dingemans, Milou M L and van den Berg, Martin and Westerink, Remco H S}, month = jul, year = {2011}, pmid = {21245014}, keywords = {Animal, Animal: drug effects, Animals, Behavior, Brain, Brain: drug effects, Brain: embryology, Embryo, Environmental Pollutants, Environmental Pollutants: pharmacokinetics, Environmental Pollutants: toxicity, Female, Flame Retardants: pharmacokinetics, Flame Retardants: toxicity, Flame retardants, Halogenated Diphenyl Ethers, Halogenated Diphenyl Ethers: toxicity, Humans, Hydroxylation, Mammalian, Mammalian: drug effects, Mice, Nervous System, Nervous System: drug effects, Nervous System: embryology, Nervous System: metabolism, Oxidative Stress, Oxidative Stress: drug effects, Polychlorinated Biphenyls, Polychlorinated Biphenyls: chemistry, Polychlorinated Biphenyls: poisoning, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Risk Assessment}, pages = {900--7} }
@article{navarro_phosphoproteomic_2011, title = {Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic {T} lymphocytes}, volume = {12}, issn = {1529-2916}, doi = {10.1038/ni.2008}, abstract = {Here we report an unbiased analysis of the cytotoxic T lymphocyte (CTL) serine-threonine phosphoproteome by high-resolution mass spectrometry. We identified approximately 2,000 phosphorylations in CTLs, of which approximately 450 were controlled by T cell antigen receptor (TCR) signaling. A significantly overrepresented group of molecules identified included transcription activators, corepressors and chromatin regulators. A focus on chromatin regulators showed that CTLs had high expression of the histone deacetylase HDAC7 but continually phosphorylated and exported this transcriptional repressor from the nucleus. Dephosphorylation of HDAC7 resulted in its accumulation in the nucleus and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. Screening of the CTL phosphoproteome has thus identified intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators and determine the CTL functional program.}, language = {eng}, number = {4}, journal = {Nature Immunology}, author = {Navarro, Maria N. and Goebel, Jurgen and Feijoo-Carnero, Carmen and Morrice, Nick and Cantrell, Doreen A.}, month = apr, year = {2011}, pmid = {21399638}, pmcid = {PMC3110993}, keywords = {Amino Acid Sequence, Animals, Antigen, Cell Nucleus, Cells, Chromatography, Confocal, Cultured, Cytosol, Cytotoxic, DAG, Female, Gene Expression Profiling, Green Fluorescent Proteins, Histone Deacetylases, Inbred C57BL, Liquid, Male, Mass Spectrometry, Mice, Microscopy, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Phosphoproteins, Phosphorylation, Proteomics, Receptors, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Cell, T-Lymphocytes, Transgenic}, pages = {352--361} }
@article{ mutlu_effects_2011, title = {Effects of nitric oxide synthase inhibitors 1-(2-trifluoromethylphenyl)--imidazole ({TRIM}) and 7-nitroindazole (7-{NI}) on learning and memory in mice}, volume = {25}, issn = {1472-8206}, doi = {10.1111/j.1472-8206.2010.00851.x}, abstract = {Nitric oxide ({NO}) plays an important role in hippocampal long-term potentiation ({LTP}), which is involved in memory processes. This led to the hypothesis that nitric oxide synthase ({NOS}) inhibitors will have disturbing effects on learning and memory. The aim of our study was to investigate the effects of the new selective neuronal and inducible {NOS} inhibitor 1- (2-trifluoromethylphenyl) imidazole ({TRIM}) (10-50 mg/kg) on learning and memory and compare it to the nonselective {NOS} inhibitor 7-{NI} (15-45 mg/kg) using different behavioral tests in Swiss mice, thus clarifying the role of neuronal {NOS} ({nNOS}) and endothelial {NOS} ({eNOS}) in cognitive processes. {TRIM} had no specific effect on either learning or memory parameters, while 7-{NI} (30 mg/kg) disturbed spatial memory in the probe trial of the Morris water maze test, which was performed on the last day of the test. No differences between {TRIM} and the control groups were observed, while 7-{NI} (30 and 45 mg/kg) significantly disturbed memory in the novel object recognition test. In the social transmission of food preference test, both {TRIM} (50 mg/kg) and 7-{NI} (45 mg/kg) impaired hippocampal olfactory memory, but the total food consumption was also significantly decreased at these doses. In the passive avoidance test, {TRIM} did not disturb the performance, while memory impairment was observed, even with lower doses of 7-{NI}. All of these results suggest that {TRIM} has no clear effect on cognitive impairment compared to 7-{NI} and that inhibition of both {nNOS} and {eNOS} are necessary for the deterioration of memory processes.}, language = {eng}, number = {3}, journal = {Fundamental \& Clinical Pharmacology}, author = {Mutlu, Oguz and Ulak, Güner and Belzung, Catherine}, month = {June}, year = {2011}, pmid = {20608991}, keywords = {Animals, Enzyme Inhibitors, Food Preferences, Hippocampus, Imidazoles, Indazoles, Learning, Locomotion, Long-Term Potentiation, Male, Maze Learning, Memory, Mice, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type {III}}, pages = {368--377} }
@inproceedings{nguyen_search_2011, title = {In search of a cost effective way to develop autonomous floor mapping robots}, doi = {10.1109/ROSE.2011.6058510}, abstract = {Simulation can be used to reduce the time and cost to develop a new technology. This paper describes the development of an autonomous floor mapping robot. In order to reduce the cost of building prototypes to test the program, we used the Simbad 3D simulator. To test in a more realistic environment, we established a way to control objects in a virtual world Second Life. Then, for the hardware part, we built a low cost robot with cheap but accurate Sharp IR sensors with a regular optical mouse.}, booktitle = {2011 {IEEE} {International} {Symposium} on {Robotic} and {Sensors} {Environments} ({ROSE})}, author = {Nguyen, Hung and Eguchi, A. and Hooten, D.}, year = {2011}, keywords = {Floor mapping, Floors, Mice, Navigation, Robot kinematics, Robot sensing systems, Simbad 3D simulator, Simulation, autonomous floor mapping robots, infrared detectors, mobile robots, mouse controllers (computers), path planning, realistic environment, regular optical mouse, sharp IR sensors, virtual reality, virtual world second life}, pages = {107--112} }
@article{vagula_effects_2011, title = {Effects of {BDE}-85 on the oxidative status and nerve conduction in rodents.}, volume = {30}, issn = {1092-874X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21772022}, doi = {10.1177/1091581811411109}, abstract = {BDE-85 is a congener of a class of flame-retardant compounds called polybrominated diphenyl ethers (PBDEs). Although there are some studies on other congeners of PBDEs, there are none on the toxicity potential of this penta-BDE member. This study, therefore, reports the oxidative status and sciatic nerve conduction properties following BDE-85 treatment in rodents. The oxidative stress markers, lipid hydroperoxides, and the activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and catalase, in the exposed mice liver and brain tissues showed tissue-specific alterations following intraperitoneal injection of 0.25 mg/kg body weight of BDE-85 for 4 days. The results indicate a significant disruption in the oxidant/antioxidant equilibrium and setting in of oxidative stress. Isolated sciatic nerves of rats exposed to 5 µg/mL or 20 µg/mL of BDE-85 showed a significant reduction in nerve conduction velocity and compound action potential amplitudes, indicating physiological damage to the sciatic nerves.}, number = {4}, journal = {International journal of toxicology}, author = {Vagula, Mary C and Kubeldis, Nathan and Nelatury, Charles F}, month = aug, year = {2011}, pmid = {21772022}, keywords = {Animals, Antioxidants, Antioxidants: metabolism, Biological Markers, Brain, Brain: drug effects, Catalase, Catalase: metabolism, Flame Retardants: toxicity, Flame retardants, Glutathione Peroxidase, Glutathione Peroxidase: metabolism, Glutathione Transferase, Glutathione Transferase: metabolism, Halogenated Diphenyl Ethers, Halogenated Diphenyl Ethers: toxicity, Lipid Peroxides, Lipid Peroxides: metabolism, Liver, Liver: drug effects, Male, Mice, Neural Conduction, Neural Conduction: drug effects, Oxidative Stress, Oxidative Stress: drug effects, Rats, Reactive Oxygen Species, Reactive Oxygen Species: metabolism, Sprague-Dawley, Superoxide Dismutase, Superoxide Dismutase: metabolism}, pages = {428--34} }
@article{ title = {3-Dimensional cell culture for on-chip differentiation of stem cells in embryoid body.}, type = {article}, year = {2011}, identifiers = {[object Object]}, keywords = {Animals,Cell Count,Cell Culture Techniques,Cell Culture Techniques: instrumentation,Cell Differentiation,Cell Differentiation: drug effects,Cell Line,Cells,Embryoid Bodies,Embryoid Bodies: cytology,Embryoid Bodies: drug effects,Feasibility Studies,Immobilized,Immobilized: cytology,Kinetics,Mice,Microfluidic Analytical Techniques,Microfluidic Analytical Techniques: methods,Neurons,Neurons: cytology,Tretinoin,Tretinoin: pharmacology,Tumor}, pages = {874-82}, volume = {11}, websites = {http://pubs.rsc.org/en/content/articlehtml/2011/lc/c0lc00516a}, month = {3}, publisher = {The Royal Society of Chemistry}, day = {7}, id = {ae111aeb-3d11-392e-b6d2-34f5dea4aa49}, created = {2016-06-24T20:49:48.000Z}, accessed = {2015-02-23}, file_attached = {false}, profile_id = {954a987f-819f-3985-95a4-2991e0cf0552}, group_id = {8440dcff-74cc-3783-aef7-fe2749cfc7ef}, last_modified = {2016-06-24T20:49:48.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Kim2011}, language = {en}, abstract = {This paper proposes a microfluidic device for the on-chip differentiation of an embryoid body (EB) formed in a microwell via 3-dimensional cultures of mouse embryonic carcinoma (EC) cells. The device adjusted the size of the EB by fluid volume, differentiated the EB by chemical treatment, and evaluated its effects in EC cells by on-chip immunostaining. A microfluidic resistance network was designed to control the size of the embryoid body. The duration time and flow rate into each microwell regulated the initial number of trapped cells in order to adjust the size of the EB. The docked cells were aggregated and formed a spherical EB on the non-adherent surface of the culture chip for 3 days. The EC cells in the EB were then differentiated into diverse cell lineages without attachment for an additional 4 days; meanwhile, retinoic acid (RA) was applied without serum to direct the cells into early neuronal lineage. On-chip immunostaining of the EB in the microwell with a neuronal marker was conducted to assess the differentiation-inducing ability of RA. The effect of RA on neuronal differentiation was analyzed with confocal microscopic images of the TuJ1 marker. The RA-treated cells expressed more neuronal markers and appeared as mature neuronal cells with long neurites. The fluorescence intensity of the TuJ1 in the RA-treated EB was twice that observed in the non-treated EB on day 5. It was demonstrated that the pre-screening of inducing chemicals on the early neuronal differentiation of EC cells in a single microfluidic chip was indeed feasible. This chip is expected to constitute a useful tool for assessing the early differentiation of ES cells without attachment, and is also expected to prove useful as an anti-cancer drug test platform for the cytotoxicity assay with cellular spheroids.}, bibtype = {article}, author = {Kim, Choong and Lee, Kang Sun and Bang, Jae Hoon and Kim, Young Eyn and Kim, Min-Cheol and Oh, Kwang Wook and Lee, Soo Hyun and Kang, Ji Yoon}, journal = {Lab on a chip}, number = {5} }
@article{ isingrini_altered_2011, title = {Altered aortic vascular reactivity in the unpredictable chronic mild stress model of depression in mice: {UCMS} causes relaxation impairment to {ACh}}, volume = {103}, issn = {1873-507X}, shorttitle = {Altered aortic vascular reactivity in the unpredictable chronic mild stress model of depression in mice}, doi = {10.1016/j.physbeh.2011.04.002}, abstract = {Major depression is an independent risk factor for the development of cardiovascular disease. This impact of depression on vascular function seems to be mediated by the endothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation, which represents a reliable predictor of atherosclerosis and has been regularly found to be associated with depression. This study aimed at investigating aortic vascular reactivity in mice submitted to the unpredictable chronic mild stress (UCMS) procedure, a reliable model of depression. The results confirm the effectiveness of the UCMS procedure to induce neuroendocrine, physical and behavioral depression-like alterations as well as a significant decrease of acetylcholine-induced vasorelaxation without any effect on phenylephrine-induced vasoconstriction. In this study, we reveal an altered vascular reactivity in an animal model of depression, demonstrating an endothelial dysfunction reminiscent to the one found in depressed patients.}, language = {eng}, number = {5}, journal = {Physiology \& Behavior}, author = {Isingrini, Elsa and Surget, Alexandre and Belzung, Catherine and Freslon, Jean-Louis and Frisbee, Jefferson and O'Donnell, James and Camus, Vincent and d'Audiffret, Alexandre}, month = {July}, year = {2011}, pmid = {21504753}, keywords = {Acetylcholine, Animals, Aorta, Behavior, Animal, Corticosterone, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Mice, Mice, Inbred BALB C, Phenylephrine, Stress, Psychological, Vasoconstriction, Vasodilation}, pages = {540--546} }
@article{ tye_amygdala_2011, title = {Amygdala circuitry mediating reversible and bidirectional control of anxiety}, volume = {471}, issn = {1476-4687}, doi = {10.1038/nature09820}, abstract = {Anxiety--a sustained state of heightened apprehension in the absence of immediate threat--becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala ({BLA}) terminals in the central nucleus of the amygdala ({CeA})--achieved by viral transduction of the {BLA} with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream {CeA}--exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin ({eNpHR}3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of {BLA} somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific {BLA}-{CeA} projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.}, language = {eng}, number = {7338}, journal = {Nature}, author = {Tye, Kay M and Prakash, Rohit and Kim, Sung-Yon and Fenno, Lief E and Grosenick, Logan and Zarabi, Hosniya and Thompson, Kimberly R and Gradinaru, Viviana and Ramakrishnan, Charu and Deisseroth, Karl}, month = {March}, year = {2011}, pmid = {21389985}, keywords = {Animals, Anxiety, Anxiety Disorders, Halorhodopsins, Light, Mice, Models, Neurological, Neural Pathways, Neurons, Stress, Physiological, Synapses, amygdala}, pages = {358--362} }
@article{ title = {A critical role for Neurofascin in regulating action potential initiation through maintenance of the axon initial segment.}, type = {article}, year = {2011}, identifiers = {[object Object]}, keywords = {Action Potentials,Action Potentials: physiology,Animals,Axons,Axons: physiology,Cell Adhesion Molecules,Cell Adhesion Molecules: genetics,Cell Adhesion Molecules: metabolism,Electrophysiology,Mice,Nerve Growth Factors,Nerve Growth Factors: genetics,Nerve Growth Factors: metabolism,Neurons,Neurons: physiology,Ranvier's Nodes,Ranvier's Nodes: physiology,Sodium Channels,Sodium Channels: physiology,Transgenic}, pages = {945-56}, volume = {69}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/21382554,http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3057015&tool=pmcentrez&rendertype=abstract}, month = {3}, publisher = {Elsevier Inc.}, day = {10}, id = {cafbe02e-82e7-3786-baf2-1250383a4757}, created = {2011-03-10T21:56:38.000Z}, accessed = {2014-06-17}, file_attached = {true}, profile_id = {b662c5f6-8d1c-39ee-8a62-3ff04dae55cf}, last_modified = {2017-03-09T18:36:24.602Z}, read = {true}, starred = {false}, authored = {true}, confirmed = {true}, hidden = {false}, private_publication = {false}, abstract = {The axon initial segment (AIS) is critical for the initiation and propagation of action potentials. Assembly of the AIS requires interactions between scaffolding molecules and voltage-gated sodium channels, but the molecular mechanisms that stabilize the AIS are poorly understood. The neuronal isoform of Neurofascin, Nfasc186, clusters voltage-gated sodium channels at nodes of Ranvier in myelinated nerves: here, we investigate its role in AIS assembly and stabilization. Inactivation of the Nfasc gene in cerebellar Purkinje cells of adult mice causes rapid loss of Nfasc186 from the AIS but not from nodes of Ranvier. This causes AIS disintegration, impairment of motor learning and the abolition of the spontaneous tonic discharge typical of Purkinje cells. Nevertheless, action potentials with a modified waveform can still be evoked and basic motor abilities remain intact. We propose that Nfasc186 optimizes communication between mature neurons by anchoring the key elements of the adult AIS complex.}, bibtype = {article}, author = {Zonta, Barbara and Desmazieres, Anne and Rinaldi, Arianna and Tait, Steven and Sherman, Diane L and Nolan, Matthew F and Brophy, Peter J}, journal = {Neuron}, number = {5} }
@article{casals-casas_endocrine_2011, title = {Endocrine disruptors: from endocrine to metabolic disruption.}, volume = {73}, issn = {1545-1585}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21054169}, doi = {10.1146/annurev-physiol-012110-142200}, abstract = {Synthetic chemicals currently used in a variety of industrial and agricultural applications are leading to widespread contamination of the environment. Even though the intended uses of pesticides, plasticizers, antimicrobials, and flame retardants are beneficial, effects on human health are a global concern. These so-called endocrine-disrupting chemicals (EDCs) can disrupt hormonal balance and result in developmental and reproductive abnormalities. New in vitro, in vivo, and epidemiological studies link human EDC exposure with obesity, metabolic syndrome, and type 2 diabetes. Here we review the main chemical compounds that may contribute to metabolic disruption. We then present their demonstrated or suggested mechanisms of action with respect to nuclear receptor signaling. Finally, we discuss the difficulties of fairly assessing the risks linked to EDC exposure, including developmental exposure, problems of high- and low-dose exposure, and the complexity of current chemical environments.}, journal = {Annual review of physiology}, author = {Casals-Casas, Cristina and Desvergne, Béatrice}, month = jan, year = {2011}, pmid = {21054169}, keywords = {Animals, Cytoplasmic and Nuclear, Cytoplasmic and Nuclear: drug effects, Cytoplasmic and Nuclear: metabolism, Diabetes Mellitus, Endocrine Disruptors, Endocrine Disruptors: analysis, Endocrine Disruptors: chemistry, Endocrine Disruptors: toxicity, Environmental Exposure, Environmental Pollutants, Environmental Pollutants: analysis, Environmental Pollutants: chemistry, Environmental Pollutants: toxicity, Female, Flame retardants, Humans, Male, Metabolic Syndrome X, Metabolic Syndrome X: chemically induced, Mice, Obesity, Obesity: chemically induced, Rats, Receptors, Signal Transduction, Signal Transduction: drug effects, Type 2, Type 2: chemically induced}, pages = {135--62} }
@article{ title = {Predicting a human gut microbiota's response to diet in gnotobiotic mice.}, type = {article}, year = {2011}, identifiers = {[object Object]}, keywords = {Animals,Bacteroides,Bacteroides: genetics,Bacteroides: physiology,Biomass,Caseins,Caseins: administration & dosage,Desulfovibrio,Desulfovibrio: genetics,Desulfovibrio: physiology,Diet,Dietary Carbohydrates,Dietary Carbohydrates: administration & dosage,Dietary Fats, Unsaturated,Dietary Fats, Unsaturated: administration & dosage,Dietary Proteins,Dietary Proteins: administration & dosage,Dietary Sucrose,Dietary Sucrose: administration & dosage,Escherichia coli,Escherichia coli: genetics,Escherichia coli: physiology,Feces,Feces: microbiology,Gastrointestinal Tract,Gastrointestinal Tract: microbiology,Gene Expression Profiling,Gene Expression Regulation, Bacterial,Germ-Free Life,Gram-Negative Bacteria,Gram-Negative Bacteria: physiology,Gram-Positive Bacteria,Gram-Positive Bacteria: genetics,Gram-Positive Bacteria: physiology,Humans,Infant,Infant Food,Linear Models,Male,Metagenome,Mice,Mice, Inbred C57BL,Models, Animal}, pages = {101-4}, volume = {333}, websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3303606&tool=pmcentrez&rendertype=abstract}, month = {7}, day = {1}, id = {af1e4fc6-0a0c-3a10-9f98-a61be2064c2e}, created = {2016-06-24T20:50:03.000Z}, accessed = {2014-10-10}, file_attached = {false}, profile_id = {954a987f-819f-3985-95a4-2991e0cf0552}, group_id = {8440dcff-74cc-3783-aef7-fe2749cfc7ef}, last_modified = {2016-06-24T20:50:03.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Faith2011}, abstract = {The interrelationships between our diets and the structure and operations of our gut microbial communities are poorly understood. A model community of 10 sequenced human gut bacteria was introduced into gnotobiotic mice, and changes in species abundance and microbial gene expression were measured in response to randomized perturbations of four defined ingredients in the host diet. From the responses, we developed a statistical model that predicted over 60% of the variation in species abundance evoked by diet perturbations, and we were able to identify which factors in the diet best explained changes seen for each community member. The approach is generally applicable, as shown by a follow-up study involving diets containing various mixtures of pureed human baby foods.}, bibtype = {article}, author = {Faith, Jeremiah J and McNulty, Nathan P and Rey, Federico E and Gordon, Jeffrey I}, journal = {Science (New York, N.Y.)}, number = {6038} }
@article{ slupianek_bcr/abl_2011, title = {{BCR}/{ABL} stimulates {WRN} to promote survival and genomic instability}, volume = {71}, issn = {1538-7445}, doi = {10.1158/0008-5472.CAN-10-1066}, abstract = {BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSB) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), nonhomologous end-joining (NHEJ), and single-strand annealing (SSA). Here, we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTK), such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC-mediated activation of transcription and Bcl-xL-dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability.}, language = {eng}, number = {3}, journal = {Cancer Research}, author = {Slupianek, Artur and Poplawski, Tomasz and Jozwiakowski, Stanislaw K. and Cramer, Kimberly and Pytel, Dariusz and Stoczynska, Ewelina and Nowicki, Michal O. and Blasiak, Janusz and Skorski, Tomasz}, month = {February}, year = {2011}, pmid = {21123451}, pmcid = {PMC3032814}, keywords = {Animals, Cell Line, Tumor, Chromosome Aberrations, DNA Breaks, Double-Stranded, DNA Repair, DNA, Neoplasm, Disease Progression, Exodeoxyribonucleases, Fusion Proteins, bcr-abl, Genomic Instability, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Mice, Oxidative Stress, Phosphorylation, Protein-Tyrosine Kinases, RecQ Helicases, Recombinant Fusion Proteins}, pages = {842--851} }
@article{Delalande2010, abstract = {Our study aimed at evaluating the use of ultrasound-assisted microbubbles gene transfer in mice Achilles tendons. Using a plasmid encoding luciferase gene, it was found that an efficient and stable gene expression for more than two weeks was obtained when tendons were injected with 10 microg of plasmid in the presence of 5x10(5) BR14 microbubbles with the following acoustic parameters: 1 MHz, 200 kPa, 40\% duty cycle and 10 min of exposure time. The rate of gene expression was 100-fold higher than that obtained with naked plasmid injected alone without ultrasound or with ultrasound in absence of microbubbles. The long term expression of transgene makes ultrasound-assisted microbubble a suitable method for gene therapy in tendons.}, author = {Delalande, Anthony and Bureau, Michel-Francis and Midoux, Patrick and Bouakaz, Ayache and Pichon, Chantal}, doi = {10.1016/j.ultras.2009.09.035}, file = {:C$\backslash$:/Users/emnicolas/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Delalande et al. - 2010 - Ultrasound-assisted microbubbles gene transfer in tendons for gene therapy.pdf:pdf}, issn = {1874-9968}, journal = {Ultrasonics}, keywords = {Achilles Tendon,Animals,Contrast Media,Contrast Media: chemistry,Equipment Design,Fluorocarbons,Fluorocarbons: chemistry,Gene Expression,Gene Transfer Techniques,Genetic Therapy,Genetic Therapy: methods,Luciferases, Firefly,Luciferases, Firefly: genetics,Mice,Microbubbles,Phospholipids,Phospholipids: chemistry,Plasmids,Plasmids: administration \& dosage,Statistics, Nonparametric,Transfection,Ultrasonics}, month = feb, number = {2}, pages = {269--72}, pmid = {19857885}, publisher = {Elsevier B.V.}, title = {{Ultrasound-assisted microbubbles gene transfer in tendons for gene therapy.}}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19857885}, volume = {50}, year = {2010} }
@article{delli_castelli_vivo_2010, title = {In vivo {MRI} multicontrast kinetic analysis of the uptake and intracellular trafficking of paramagnetically labeled liposomes}, volume = {144}, issn = {1873-4995}, doi = {10.1016/j.jconrel.2010.03.005}, abstract = {This work aims at developing a MRI method that allows to get more insight into the understanding of the in vivo fate of liposomes and their payload. The method relies on the temporal assessment of the contrast changes induced by the presence of a classical relaxation agent versus the effect induced by a CEST (chemical exchange saturation transfer) agent. Liposomes were loaded with the paramagnetic complexes, Gd-HPDO3A and [Tm-DOTMA](-) [Na](+), in order to endow the nanovesicles with the characteristic properties of T(1)/T(2) and CEST/T(2) MRI agents, respectively. The paramagnetically loaded liposomes were injected directly into the tumor (B16 melanoma xenograft in mice) where they generate T(1), T(2), and CEST MR contrasts that were quantitatively monitored over time (0-48h). The kinetic of each contrast enhancement reports about peculiar properties relative to the fate of the liposomes in the tumor environment. A kinetic model has been set-up to fit the experimental multicontrast data in order to extract the relevant information about the cellular uptake of the liposomes and the release of their payload. Upon comparing conventional stealth liposomes with pH-sensitive ones, it has been shown that the latter ones differ essentially in the step associated with the release of the drug that is likely occurring in the endosomal acidic vesicles.}, language = {eng}, number = {3}, journal = {Journal of Controlled Release: Official Journal of the Controlled Release Society}, author = {Delli Castelli, Daniela and Dastrù, Walter and Terreno, Enzo and Cittadino, Evelina and Mainini, Francesco and Torres, Elena and Spadaro, Michela and Aime, Silvio}, month = jun, year = {2010}, pmid = {20230865}, keywords = {Animals, Cell Line, Tumor, Contrast Media, Female, Gadolinium, Heterocyclic Compounds, Liposomes, Magnetic Resonance Imaging, Magnetics, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Nanoparticles, Neoplasm Transplantation, Organometallic Compounds, Staining and Labeling}, pages = {271--279} }
@article{Esposito2009, abstract = {Fluorescence microscopy is a non-invasive technique that allows high resolution imaging of cytoskeletal structures. Advances in the field of fluorescent labelling (e.g., fluorescent proteins, quantum dots, tetracystein domains) and optics (e.g., super-resolution techniques and quantitative methods) not only provide better images of the cytoskeleton, but also offer an opportunity to quantify the complex of molecular events that populate this highly organised, yet dynamic, structure.For instance, fluorescence lifetime imaging microscopy and Forster resonance energy transfer imaging allow mapping of protein-protein interactions; furthermore, techniques based on the measurement of photobleaching kinetics (e.g., fluorescence recovery after photobleaching, fluorescence loss in photobleaching, and fluorescence localisation after photobleaching) permit the characterisation of axonal transport and, more generally, diffusion of relevant biomolecules.Quantitative fluorescence microscopy techniques offer powerful tools for understanding the physiological and pathological roles of molecular machineries in the living cell.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Esposito, A. and Schlachter, S. and Schierle, G. S. and Elder, A. D. and Diaspro, A. and Wouters, F. S. and Kaminski, C. F. and Iliev, A. I.}, biburl = {http://www.bibsonomy.org/bibtex/2e233c6531b3b38c0e14016d30b887410/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {f0c57923ba9d698668d19dcc5a81ab70}, intrahash = {e233c6531b3b38c0e14016d30b887410}, issn = {1940-6029 (Electronic) 1940-6029 (Linking)}, journal = {Methods Mol Biol}, keywords = {imported}, note = {Esposito, Alessandro Schlachter, Simon Schierle, Gabriele S Kaminski Elder, Alan D Diaspro, Alberto Wouters, Fred S Kaminski, Clemens F Iliev, Asparouh I Biotechnology and Biological Sciences Research Council/United Kingdom Research Support, Non-U.S. Gov't United States Methods in molecular biology (Clifton, N.J.) Methods Mol Biol. 2009;586:117-42.}, pages = {117-42}, shorttitle = {Quantitative fluorescence microscopy techniques}, timestamp = {2010-12-14T18:12:10.000+0100}, title = {Quantitative fluorescence microscopy techniques}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19768427}, volume = 586, year = 2009 }
@article{ title = {Retinoic acid promotes limb induction through effects on body axis extension but is unnecessary for limb patterning.}, type = {article}, year = {2009}, identifiers = {[object Object]}, keywords = {Aldehyde Oxidoreductases,Aldehyde Oxidoreductases: genetics,Aldehyde Oxidoreductases: metabolism,Animals,Body Patterning,Body Patterning: physiology,Embryo, Mammalian,Embryo, Mammalian: anatomy & histology,Embryo, Mammalian: drug effects,Embryo, Mammalian: physiology,Embryonic Induction,Extremities,Extremities: anatomy & histology,Extremities: embryology,Fibroblast Growth Factor 8,Fibroblast Growth Factor 8: genetics,Fibroblast Growth Factor 8: metabolism,Limb Buds,Limb Buds: physiology,Mice,Mice, Knockout,Retinal Dehydrogenase,Signal Transduction,Signal Transduction: physiology,Tretinoin,Tretinoin: pharmacology}, pages = {1050-7}, volume = {19}, websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2701469&tool=pmcentrez&rendertype=abstract}, month = {7}, publisher = {Elsevier Ltd}, day = {23}, id = {515e0bca-299c-394e-b95d-ed7a2b842bc8}, created = {2016-04-08T12:19:45.000Z}, accessed = {2014-03-31}, file_attached = {true}, profile_id = {994bc413-6766-31df-917a-32165aa30f6c}, group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e}, last_modified = {2017-03-14T10:42:46.538Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Zhao2009}, folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748}, private_publication = {false}, abstract = {Retinoic acid (RA) is thought to be a key signaling molecule involved in limb bud patterning along the proximodistal or anteroposterior axes functioning through induction of Meis2 and Shh, respectively. Here, we utilize Raldh2-/- and Raldh3-/- mouse embryos lacking RA synthesis to demonstrate that RA signaling is not required for limb expression of Shh and Meis2. We demonstrate that RA action is required outside of the limb field in the body axis during forelimb induction but that RA is unnecessary at later stages when hindlimb budding and patterning occur. We provide evidence for a model of trunk mesodermal RA action in which forelimb induction requires RA repression of Fgf8 in the developing trunk similar to how RA controls somitogenesis and heart development. We demonstrate that pectoral fin development in RA-deficient zebrafish embryos can be rescued by an FGF receptor antagonist SU5402. In addition, embryo ChIP assays demonstrate that RA receptors bind the Fgf8 promoter in vivo. Our findings suggest that RA signaling is not required for limb proximodistal or anteroposterior patterning but that RA inhibition of FGF8 signaling during the early stages of body axis extension provides an environment permissive for induction of forelimb buds.}, bibtype = {article}, author = {Zhao, Xianling and Sirbu, Ioan Ovidiu and Mic, Felix a and Molotkova, Natalia and Molotkov, Andrei and Kumar, Sandeep and Duester, Gregg}, journal = {Current biology : CB}, number = {12} }
@article{talsness_components_2009, title = {Components of plastic: experimental studies in animals and relevance for human health.}, volume = {364}, issn = {1471-2970}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2873015&tool=pmcentrez&rendertype=abstract}, doi = {10.1098/rstb.2008.0281}, abstract = {Components used in plastics, such as phthalates, bisphenol A (BPA), polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA), are detected in humans. In addition to their utility in plastics, an inadvertent characteristic of these chemicals is the ability to alter the endocrine system. Phthalates function as anti-androgens while the main action attributed to BPA is oestrogen-like activity. PBDE and TBBPA have been shown to disrupt thyroid hormone homeostasis while PBDEs also exhibit anti-androgen action. Experimental investigations in animals indicate a wide variety of effects associated with exposure to these compounds, causing concern regarding potential risk to human health. For example, the spectrum of effects following perinatal exposure of male rats to phthalates has remarkable similarities to the testicular dysgenesis syndrome in humans. Concentrations of BPA in the foetal mouse within the range of unconjugated BPA levels observed in human foetal blood have produced effects in animal experiments. Finally, thyroid hormones are essential for normal neurological development and reproductive function. Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds.}, number = {1526}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, author = {Talsness, Chris E and Andrade, Anderson J M and Kuriyama, Sergio N and Taylor, Julia A and vom Saal, Frederick S}, month = jul, year = {2009}, pmid = {19528057}, keywords = {Animals, Body Burden, Endocrine System, Endocrine System: drug effects, Environmental Exposure, Environmental Exposure: analysis, Flame retardants, Growth and Development, Growth and Development: drug effects, Halogenated Diphenyl Ethers, Halogenated Diphenyl Ethers: analysis, Halogenated Diphenyl Ethers: toxicity, Humans, Mice, Nervous System, Nervous System: drug effects, Phenols, Phenols: analysis, Phenols: toxicity, Phthalic Acids, Phthalic Acids: analysis, Phthalic Acids: toxicity, Plastics, Plastics: chemistry, Polybrominated Biphenyls, Polybrominated Biphenyls: analysis, Polybrominated Biphenyls: toxicity, Rats, Reproduction, Reproduction: drug effects, ffr, frelec, tox}, pages = {2079--96} }
@article{ title = {Spike inference from calcium imaging using sequential Monte Carlo methods.}, type = {article}, year = {2009}, identifiers = {[object Object]}, keywords = {animals,biological,calcium,calcium metabolism,cytology/metabolism,fluorescence,inbred c57bl,intracellular space,intracellular space metabolism,metabolism,mice,models,monte carlo method,neurons,neurons cytology,neurons metabolism,probability,time factors}, pages = {636-655}, volume = {97}, websites = {http://dx.doi.org/10.1016/j.bpj.2008.08.005}, month = {7}, institution = {Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA. joshuav@jhu.edu}, id = {ea71e181-8857-33ea-b063-d3d46eb47138}, created = {2015-06-19T07:45:09.000Z}, file_attached = {false}, profile_id = {182bbbf9-24a3-3af3-9ed6-563e8f89259b}, group_id = {8d229673-0aec-3014-b0f6-eda47f83e147}, last_modified = {2015-06-19T07:45:23.000Z}, read = {false}, starred = {false}, authored = {true}, confirmed = {true}, hidden = {false}, citation_key = {smc-oopsi}, source_type = {article}, abstract = {As recent advances in calcium sensing technologies facilitate simultaneously imaging action potentials in neuronal populations, complementary analytical tools must also be developed to maximize the utility of this experimental paradigm. Although the observations here are fluorescence movies, the signals of interest--spike trains and/or time varying intracellular calcium concentrations--are hidden. Inferring these hidden signals is often problematic due to noise, nonlinearities, slow imaging rate, and unknown biophysical parameters. We overcome these difficulties by developing sequential Monte Carlo methods (particle filters) based on biophysical models of spiking, calcium dynamics, and fluorescence. We show that even in simple cases, the particle filters outperform the optimal linear (i.e., Wiener) filter, both by obtaining better estimates and by providing error bars. We then relax a number of our model assumptions to incorporate nonlinear saturation of the fluorescence signal, as well external stimulus and spike history dependence (e.g., refractoriness) of the spike trains. Using both simulations and in vitro fluorescence observations, we demonstrate temporal superresolution by inferring when within a frame each spike occurs. Furthermore, the model parameters may be estimated using expectation maximization with only a very limited amount of data (e.g., approximately 5-10 s or 5-40 spikes), without the requirement of any simultaneous electrophysiology or imaging experiments.}, bibtype = {article}, author = {Vogelstein, Joshua T. and Watson, Brendon O and Packer, Adam M and Yuste, Rafael and Jedynak, Bruno M and Paninski, Liam}, journal = {Biophysical Journal}, number = {2} }
@article{ ISI:000264790600042, Author = {Ho, Lena and Ronan, Jehnna L. and Wu, Jiang and Staahl, Brett T. and Chen, Lei and Kuo, Ann and Lessard, Julie and Nesvizhskii, Alexey I. and Ranish, Jeff and Crabtree, Gerald R.}, Title = {{An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency}}, Journal = {{PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}}, Year = {{2009}}, Volume = {{106}}, Number = {{13}}, Pages = {{5181-5186}}, Month = {{MAR 31}}, Abstract = {{Mammalian SWI/SNF {[}also called BAF (Brg/Brahma-associated factors)] ATP-dependent chromatin remodeling complexes are essential for formation of the totipotent and pluripotent cells of the early embryo. In addition, subunits of this complex have been recovered in screens for genes required for nuclear reprogramming in Xenopus and mouse embryonic stem cell (ES) morphology. However, the mechanism underlying the roles of these complexes is unclear. Here, we show that BAF complexes are required for the self-renewal and pluripotency of mouse ES cells but not for the proliferation of fibroblasts or other cells. Proteomic studies reveal that ES cells express distinctive complexes (esBAF) defined by the presence of Brg (Brahma-related gene), BAF155, and BAF60A, and the absence of Brill (Brahma), BAF170, and BAF60C. We show that this specialized subunit composition is required for ES cell maintenance and pluripotency. Our proteomic analysis also reveals that esBAF complexes interact directly with key regulators of pluripotency, suggesting that esBAF complexes are specialized to interact with ES cell-specific regulators, providing a potential explanation for the requirement of BAF complexes in pluripotency.}}, DOI = {{10.1073/pnas.0812889106}}, ISSN = {{0027-8424}}, ResearcherID-Numbers = {{Nesvizhskii, Alexey/A-5410-2012}}, Unique-ID = {{ISI:000264790600042}}, }
@article{ title = {Ectopic Meis1 expression in the mouse limb bud alters P-D patterning in a Pbx1-independent manner.}, type = {article}, year = {2009}, identifiers = {[object Object]}, keywords = {Animals,Body Patterning,Body Patterning: genetics,Body Patterning: physiology,Embryo, Mammalian,Embryo, Mammalian: embryology,Embryo, Mammalian: metabolism,Gene Expression Regulation, Developmental,Homeodomain Proteins,Homeodomain Proteins: genetics,Homeodomain Proteins: metabolism,Homeodomain Proteins: physiology,Immunohistochemistry,In Situ Hybridization,Limb Buds,Limb Buds: embryology,Limb Buds: metabolism,Mice,Mice, Inbred C57BL,Mice, Transgenic,Neoplasm Proteins,Neoplasm Proteins: genetics,Neoplasm Proteins: metabolism,Neoplasm Proteins: physiology,Time Factors,Transcription Factors,Transcription Factors: genetics,Transcription Factors: metabolism,Transcription Factors: physiology}, pages = {1483-94}, volume = {53}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/19247936}, month = {1}, id = {126d963a-2456-3fa6-94ca-b4f994d865d7}, created = {2016-04-08T12:19:35.000Z}, accessed = {2014-01-20}, file_attached = {true}, profile_id = {994bc413-6766-31df-917a-32165aa30f6c}, group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e}, last_modified = {2017-03-14T10:42:46.538Z}, read = {true}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Mercader2009}, folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748}, private_publication = {false}, abstract = {During limb development, expression of the TALE homeobox transcription factor Meis1 is activated by retinoic acid in the proximal-most limb bud regions, which give rise to the upper forelimb and hindlimb. Early subdivision of the limb bud into proximal Meis-positive and distal Meis-negative domains is necessary for correct proximo-distal (P-D) limb development in the chick, since ectopic Meis1 overexpression abolishes distal limb structures, produces a proximal shift of limb identities along the P-D axis, and proximalizes distal limb cell affinity properties. To determine whether Meis activity is also required for P-D limb specification in mammals, we generated transgenic mice ectopically expressing Meis1 in the distal limb mesenchyme under the control of the Msx2 promoter. Msx2:Meis1 transgenic mice display altered P-D patterning and shifted P-D Hox gene expression domains, similar to those previously described for the chicken. Meis proteins function in cooperation with PBX factors, another TALE homeodomain subfamily. Meis-Pbx interaction is required for nuclear localization of both proteins in cell culture, and is important for their DNA-binding and transactivation efficiency. During limb development, Pbx1 nuclear expression correlates with the Meis expression domain, and Pbx1 has been proposed as the main Meis partner in this context; however, we found that Pbx1 deficiency did not modify the limb phenotype of Msx2:Meis1 mice. Our results indicate a conserved role of Meis activity in P-D specification of the tetrapod limb and suggest that Pbx function in this context is either not required or is provided by partners other than Pbx1.}, bibtype = {article}, author = {Mercader, Nadia and Selleri, Licia and Criado, Luis Miguel and Pallares, Pilar and Parras, Carlos and Cleary, Michael L and Torres, Miguel}, journal = {The International journal of developmental biology}, number = {8-10} }
@article{ title = {Spike inference from calcium imaging using sequential Monte Carlo methods.}, type = {article}, year = {2009}, identifiers = {[object Object]}, keywords = {animals,biological,calcium,calcium metabolism,cytology/metabolism,fluorescence,inbred c57bl,intracellular space,intracellular space metabolism,metabolism,mice,models,monte carlo method,neurons,neurons cytology,neurons metabolism,probability,time factors}, pages = {636-655}, volume = {97}, websites = {http://dx.doi.org/10.1016/j.bpj.2008.08.005}, month = {7}, institution = {Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA. joshuav@jhu.edu}, id = {5729a160-7320-3bff-9495-5d3a14595c1e}, created = {2015-06-19T08:32:45.000Z}, file_attached = {false}, profile_id = {182bbbf9-24a3-3af3-9ed6-563e8f89259b}, group_id = {8d229673-0aec-3014-b0f6-eda47f83e147}, last_modified = {2015-06-19T08:33:08.000Z}, read = {false}, starred = {true}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Vogelstein2009c}, source_type = {article}, abstract = {As recent advances in calcium sensing technologies facilitate simultaneously imaging action potentials in neuronal populations, complementary analytical tools must also be developed to maximize the utility of this experimental paradigm. Although the observations here are fluorescence movies, the signals of interest - spike trains and/or time varying intracellular calcium concentrations - are hidden. Inferring these hidden signals is often problematic due to noise, nonlinearities, slow imaging rate, and unknown biophysical parameters. We overcome these difficulties by developing sequential Monte Carlo methods (particle filters) based on biophysical models of spiking, calcium dynamics, and fluorescence. We show that even in simple cases, the particle filters outperform the optimal linear (i.e., Wiener) filter, both by obtaining better estimates and by providing error bars. We then relax a number of our model assumptions to incorporate nonlinear saturation of the fluorescence signal, as well external stimulus and spike history dependence (e.g., refractoriness) of the spike trains. Using both simulations and in vitro fluorescence observations, we demonstrate temporal superresolution by inferring when within a frame each spike occurs. Furthermore, the model parameters may be estimated using expectation maximization with only a very limited amount of data (e.g., ???5-10 s or 5-40 spikes), without the requirement of any simultaneous electrophysiology or imaging experiments. ?? 2009 by the Biophysical Society.}, bibtype = {article}, author = {Vogelstein, Joshua T. and Watson, Brendon O. and Packer, Adam M. and Yuste, Rafael and Jedynak, Bruno M and Paninski, Liam and Paninskik, Liam}, journal = {Biophysical Journal}, number = {2} }
@article{ title = {Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids.}, type = {article}, year = {2009}, identifiers = {[object Object]}, keywords = {3T3 Cells,Animals,Bone Neoplasms,Bone Neoplasms: secondary,Cell Line, Tumor,Cell Proliferation,Cell Survival,Coculture Techniques,Endothelial Cells,Endothelial Cells: cytology,Endothelium, Vascular,Endothelium, Vascular: cytology,Humans,Male,Mice,Microfluidics,Microfluidics: methods,Microscopy, Fluorescence,Microscopy, Video,Neoplasm Metastasis,Prostatic Neoplasms,Prostatic Neoplasms: pathology,Spheroids, Cellular,Umbilical Veins,Umbilical Veins: cytology}, pages = {3020-7}, volume = {30}, websites = {http://www.sciencedirect.com/science/article/pii/S0142961209002294}, month = {6}, id = {1bfa0742-54c5-3c66-8092-67f12e26f4fa}, created = {2016-06-24T20:49:25.000Z}, accessed = {2015-02-19}, file_attached = {false}, profile_id = {954a987f-819f-3985-95a4-2991e0cf0552}, group_id = {8440dcff-74cc-3783-aef7-fe2749cfc7ef}, last_modified = {2016-06-24T20:49:26.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Hsiao2009}, abstract = {The niche microenvironment in which cancer cells reside plays a prominent role in the growth of cancer. It is therefore imperative to mimic the in vivo tumor niche in vitro to better understand cancer and enhance development of therapeutics. Here, we engineer a 3D metastatic prostate cancer model that includes the types of surrounding cells in the bone microenvironment that the metastatic prostate cancer cells reside in. Specifically, we used a two-layer microfluidic system to culture 3D multi-cell type spheroids of fluorescently labeled metastatic prostate cancer cells (PC-3 cell line), osteoblasts and endothelial cells. This method ensures uniform incorporation of all co-culture cell types into each spheroid and keeps the spheroids stationary for easy tracking of individual spheroids and the PC-3's residing inside them over the course of at least a week. This culture system greatly decreased the proliferation rate of PC-3 cells without reducing viability and may more faithfully recapitulate the in vivo growth behavior of malignant cancer cells within the bone metastatic prostate cancer microenvironment.}, bibtype = {article}, author = {Hsiao, Amy Y and Torisawa, Yu-suke and Tung, Yi-Chung and Sud, Sudha and Taichman, Russell S and Pienta, Kenneth J and Takayama, Shuichi}, journal = {Biomaterials}, number = {16} }
@article{zhang_estrogen-induced_2009, title = {Estrogen-induced uterine abnormalities in {TIMP}-1 deficient mice are associated with elevated plasmin activity and reduced expression of the novel uterine plasmin protease inhibitor serpinb7}, volume = {76}, issn = {1098-2795}, doi = {10.1002/mrd.20938}, abstract = {Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein capable of regulating a variety of biological processes in a wide array of tissue and cell types. We have previously demonstrated that TIMP-1 deficient mice exhibit alterations in normal uterine morphology and physiology. Most notably, absence of TIMP-1 is associated with an altered uterine phenotype characterized by profound branching of the uterine lumen and altered adenogenesis. To begin to assess the mechanism by which TIMP-1 may control these uterine events, we utilized steroid-treated ovariectomized wild-type and TIMP-1 null mice exposed to estrogen for 72 hr. Administration of estrogen to TIMP-1 deficient mice resulted in development of an abnormal uterine histo-architecture characterized by increased endometrial gland density, luminal epithelial cell height, and abnormal lumen structure. To determine the mediators which may contribute to the abnormal uterine morphology in the TIMP-1 deficient mice, cDNA microarray analysis was performed. Analysis revealed that expression of two plasmin inhibitors (serpbinb2 and serbinb7) was significantly reduced in the TIMP-1 null mice. Associated with the reduction in expression of these inhibitors was a significant increase in plasmin activity. Localization of the novel uterine serpinb7 revealed that expression was confined to the luminal and glandular epithelial cells. Further, expression of uterine serpinb7 was decreased by estrogen and showed an inverse relationship with plasmin activity. We conclude from these studies that in addition to controlling MMP activity, TIMP-1 may also control activity of serine proteases through modulation of serine protease inhibitors such as serpinb7.}, language = {eng}, number = {2}, journal = {Molecular Reproduction and Development}, author = {Zhang, Xuan and Hoang, Etter and Nothnick, Warren B.}, month = feb, year = {2009}, pmid = {18537133}, pmcid = {PMC2614461}, keywords = {Analysis of Variance, Animals, Blotting, Western, DNA Primers, Estrogens, Female, Fibrinolysin, In Situ Hybridization, Mice, Microarray Analysis, Reverse Transcriptase Polymerase Chain Reaction, Serpins, Tissue Inhibitor of Metalloproteinase-1, Urogenital Abnormalities, Uterus}, pages = {160--172} }
@article{herath_isolation_2009, title = {Isolation, structure and biological activity of phomafungin, a cyclic lipodepsipeptide from a widespread tropical {Phoma} sp}, volume = {17}, issn = {1464-3391}, doi = {10.1016/j.bmc.2008.12.009}, abstract = {We isolated a cyclic lipodepsipeptide, phomafungin, from a Phoma sp. The distinct antifungal activity of phomafungin in the crude extract was initially discovered by mechanistic profiling in the Candida albicans fitness test. The purified compound contains a 28 member ring consisting of eight amino acids and a beta-hydroxy-gamma-methyl-hexadecanoic acid, and displays a broad spectrum of antifungal activity against Candida spp., Aspergillus fumigatus and Trichophyton mentagrophytes with MIC of 2-8 microg/ml, and toxicity to mice at 25 mg/kg. The linear peptide derived from opening of the lactone ring was devoid of antifungal activity as well as toxicity. Phomafungin has been identified in a number of Phoma spp. collected from Africa and the Indian and Pacific Ocean islands.}, language = {eng}, number = {3}, journal = {Bioorganic \& medicinal chemistry}, author = {Herath, Kithsiri and Harris, Guy and Jayasuriya, Hiranthi and Zink, Deborah and Smith, Scott and Vicente, Francisca and Bills, Gerald and Collado, Javier and González, Antonio and Jiang, Bo and Kahn, Jennifer Nielsen and Galuska, Stefan and Giacobbe, Robert and Abruzzo, George and Hickey, Emily and Liberator, Paul and Xu, Deming and Roemer, Terry and Singh, Sheo B}, month = feb, year = {2009}, keywords = {Amino Acid Sequence, Animals, Antifungal Agents, Ascomycota, Aspergillus fumigatus, Depsipeptides, Lipopeptides, Mice, Trichophyton}, pages = {1361--1369} }
@article{ clement_pharmacological_2009, title = {Pharmacological alterations of anxious behaviour in mice depending on both strain and the behavioural situation}, volume = {4}, issn = {1932-6203}, doi = {10.1371/journal.pone.0007745}, abstract = {A previous study comparing non-emotive mice from the strain C57BL/6/{ByJ} with {ABP}/Le mice showed {ABP}/Le to be more anxious in an open-field situation. In the present study, several compounds affecting anxiety were assayed on {ABP}/Le and C57BL/6/{ByJ} mice using three behavioural models of anxiety: the elevated plus-maze, the light-dark discrimination test and the free exploratory paradigm. The compounds used were the full benzodiazepine receptor agonist, chlordiazepoxide, and the antagonist, flumazenil, the {GABA}(A) antagonist, bicuculline, the full 5-{HT}(1A) agonist 8-{OH}-{DPAT}, and the mixed 5-{HT}(1A)/5-{HT}(1B) agonist, {RU} 24969. Results showed the effect of the compounds to be dependent on both the strain and the behavioural task. Several compounds found to be anxiolytic in {ABP}/Le mice had an anxiogenic effect on C57BL/6/{ByJ} mice. More behavioural changes were observed for {ABP}/Le in the elevated plus-maze, but the clearest findings for C57BL/6/{ByJ} mice were observed in the light-dark discrimination apparatus. These data demonstrate that anxious behaviour is a complex phenomenon which cannot be described by a single behavioural task nor by the action of a single compound.}, language = {eng}, number = {11}, journal = {{PloS} One}, author = {Clément, Yan and Le Guisquet, Anne-Marie and Venault, Patrice and Chapouthier, Georges and Belzung, Catherine}, year = {2009}, pmid = {19907641}, pmcid = {PMC2770638}, keywords = {8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Anxiety, Behavior, Animal, Benzodiazepines, Bicuculline, Chlordiazepoxide, Female, Indoles, Light, Male, Maze Learning, Mice, Mice, Inbred C57BL, Phosphorylation}, pages = {e7745} }
@article{ title = {Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance.}, type = {article}, year = {2008}, identifiers = {[object Object]}, keywords = {Animals,Antigens,Antineoplastic Agents,Antineoplastic Agents: pharmacology,B-Lymphocytes,B-Lymphocytes: pathology,Boronic Acids,Boronic Acids: pharmacology,CD20,CD20: analysis,CD27,CD27: analysis,Clone Cells,Clone Cells: drug effects,Clone Cells: pathology,Cyclophosphamide,Cyclophosphamide: analogs & derivatives,Cyclophosphamide: pharmacology,Dexamethasone,Dexamethasone: pharmacology,Drug Resistance,Humans,Inbred Strains,Mice,Multiple Myeloma,Multiple Myeloma: pathology,Neoplasm,Neoplastic Stem Cells,Neoplastic Stem Cells: drug effects,Neoplastic Stem Cells: pathology,Plasma Cells,Plasma Cells: drug effects,Plasma Cells: pathology,Pyrazines,Pyrazines: pharmacology,Syndecan-1,Syndecan-1: analysis,Thalidomide,Thalidomide: analogs & derivatives,Thalidomide: pharmacology,Tumor Stem Cell Assay}, pages = {190-7}, volume = {68}, websites = {http://cancerres.aacrjournals.org/content/68/1/190.full}, month = {1}, day = {1}, id = {494ed8c9-5c08-3403-8b42-0d004f92312a}, created = {2016-06-24T20:49:19.000Z}, accessed = {2014-11-18}, file_attached = {false}, profile_id = {954a987f-819f-3985-95a4-2991e0cf0552}, group_id = {8440dcff-74cc-3783-aef7-fe2749cfc7ef}, last_modified = {2016-06-24T20:49:19.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Matsui2008}, abstract = {Many agents are active in multiple myeloma, but the majority of patients relapse. This clinical pattern suggests most cancer cells are eliminated, but cells with the clonogenic potential to mediate tumor regrowth are relatively chemoresistant. Our previous data suggested that CD138(+) multiple myeloma plasma cells cannot undergo long-term proliferation but rather arise from clonogenic CD138(neg) B cells. We compared the relative sensitivity of these distinct cell types to clinical antimyeloma agents and found that dexamethasone, lenadilomide, bortezomib, and 4-hydroxycyclophosphamide inhibited CD138(+) multiple myeloma plasma cells but had little effect on CD138(neg) precursors in vitro. We further characterized clonogenic multiple myeloma cells and stained cell lines using the Hoechst side population and Aldefluor assays. Each assay identified CD138(neg) cells suggesting that they possess high drug efflux capacity and intracellular drug detoxification activity. We also found that multiple myeloma cells expressing the memory B-cell markers CD20 and CD27 could give rise to clonogenic multiple myeloma growth in vitro and engraft immunodeficient nonobese diabetes/severe combined immunodeficient mice during both primary and secondary transplantation. Furthermore, both the side population and Aldefluor assays were capable of identifying circulating clonotypic memory B-cell populations within the peripheral blood of multiple myeloma patients. Our results suggest that circulating clonotypic B-cell populations represent multiple myeloma stem cells, and the relative drug resistance of these cells is mediated by processes that protect normal stem cells from toxic injury.}, bibtype = {article}, author = {Matsui, William and Wang, Qiuju and Barber, James P and Brennan, Sarah and Smith, B Douglas and Borrello, Ivan and McNiece, Ian and Lin, Lan and Ambinder, Richard F and Peacock, Craig and Watkins, D Neil and Huff, Carol Ann and Jones, Richard J}, journal = {Cancer research}, number = {1} }
@article{ title = {Visualizing cold spots: TRPM8-expressing sensory neurons and their projections.}, type = {article}, year = {2008}, identifiers = {[object Object]}, keywords = {Afferent Pathways,Afferent Pathways: metabolism,Animals,Antipruritics,Antipruritics: pharmacology,Blood Vessels,Blood Vessels: innervation,Blood Vessels: metabolism,Calcitonin Gene-Related Peptide,Calcitonin Gene-Related Peptide: metabolism,Capsaicin,Capsaicin: pharmacology,Cells, Cultured,Cold Temperature,Ganglia, Spinal,Ganglia, Spinal: cytology,Gene Expression Regulation,Gene Expression Regulation: drug effects,Gene Expression Regulation: physiology,Green Fluorescent Proteins,Green Fluorescent Proteins: genetics,Green Fluorescent Proteins: metabolism,Menthol,Menthol: pharmacology,Mice,Mice, Inbred C57BL,Mice, Transgenic,Neurons, Afferent,Neurons, Afferent: cytology,Neurons, Afferent: drug effects,Neurons, Afferent: physiology,Spinal Cord,Spinal Cord: cytology,Spinal Cord: physiology,TRPM Cation Channels,TRPM Cation Channels: deficiency,TRPM Cation Channels: metabolism,TRPV Cation Channels,TRPV Cation Channels: metabolism}, pages = {566-75}, volume = {28}, websites = {http://www.jneurosci.org/content/28/3/566.long}, month = {1}, day = {16}, id = {4d21c71d-9f99-3b94-b72a-2b06dbb03877}, created = {2016-02-10T11:58:54.000Z}, accessed = {2016-02-10}, file_attached = {false}, profile_id = {3e449d8a-90c5-35f9-aaa3-cdbb3ca120e9}, group_id = {2ad31c26-29a3-3f9c-b495-1b90dc1c4bb6}, last_modified = {2016-02-10T11:58:54.000Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, abstract = {Environmental stimuli such as temperature and pressure are sensed by dorsal root ganglion (DRG) neurons. DRG neurons are heterogeneous, but molecular markers that identify unique functional subpopulations are mainly lacking. ThermoTRPs are members of the transient receptor potential family of ion channels and are gated by shifts in temperature. TRPM8 is activated by cooling, and TRPM8-deficient mice have severe deficits in cool thermosensation. The anatomical and functional properties of TRPM8-expressing fibers have not been not comprehensively investigated. We use mice engineered to express the farnesylated enhanced green fluorescent protein (EGFPf) from the TRPM8 locus (TRPM8(EGFPf)) to explore this issue. Virtually all EGFPf-positive cultured DRG neurons from hemizygous mice (TRPM8(EGFPf/+)) responded to cold and menthol. In contrast, EGFPf-positive DRGs from homozygous mice (TRPM8(EGFPf/EGFPf)) had drastically reduced cold responses and no menthol responses. In vivo, EGFPf-positive neurons marked a unique population of DRG neurons, a majority of which do not coexpress nociceptive markers. The fraction of DRG neurons expressing EGFPf was not altered under an inflammatory condition, although an increase in TRPV1-coexpressing neurons was observed. TRPM8(EGFPf) neurons project to the superficial layer I of the spinal cord, making distinct contacts when compared with peptidergic projections. At the periphery, TRPM8(EGFPf) projections mark unique endings in the most superficial layers of epidermis, including bush/cluster endings of the mystacial pads. We show that TRPM8 expression functionally associates with cold sensitivity in cultured DRGs, and provide the first glimpses of the unique anatomical architecture of cold fibers in vivo.}, bibtype = {article}, author = {Dhaka, Ajay and Earley, Taryn J and Watson, James and Patapoutian, Ardem}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, number = {3} }
@article{weiler_top-down_2008, title = {Top-down laminar organization of the excitatory network in motor cortex}, volume = {11}, issn = {1097-6256}, doi = {10.1038/nn2049}, abstract = {Cortical layering is a hallmark of the mammalian neocortex and a major determinant of local synaptic circuit organization in sensory systems. In motor cortex, the laminar organization of cortical circuits has not been resolved, although their input-output operations are crucial for motor control. Here, we developed a general approach for estimating layer-specific connectivity in cortical circuits and applied it to mouse motor cortex. From these data we computed a laminar presynaptic --{\textgreater} postsynaptic connectivity matrix, W(post,pre), revealing a complement of stereotypic pathways dominated by layer 2 outflow to deeper layers. Network modeling predicted, and experiments with disinhibited slices confirmed, that stimuli targeting upper, but not lower, cortical layers effectively evoked network-wide events. Thus, in motor cortex, descending excitation from a preamplifier-like network of upper-layer neurons drives output neurons in lower layers. Our analysis provides a quantitative wiring-diagram framework for further investigation of the excitatory networks mediating cortical mechanisms of motor control.}, language = {eng}, number = {3}, journal = {Nature neuroscience}, author = {Weiler, Nicholas and Wood, Lydia and Yu, Jianing and Solla, Sara A and Shepherd, Gordon M G}, month = mar, year = {2008}, pmid = {18246064}, keywords = {Action Potentials, Animals, Brain Mapping, Excitatory Postsynaptic Potentials, Glutamic Acid, Mice, Motor Cortex, Nerve Net, Neural Networks (Computer), Neural Pathways, Neurons, Organ Culture Techniques, Photic Stimulation, Photochemistry, Synaptic Transmission}, pages = {360--366} }
@article{ sibille_large-scale_2008, title = {Large-scale estimates of cellular origins of {mRNAs}: enhancing the yield of transcriptome analyses}, volume = {167}, issn = {0165-0270}, shorttitle = {Large-scale estimates of cellular origins of {mRNAs}}, doi = {10.1016/j.jneumeth.2007.08.009}, abstract = {Gene expression profiling holds great promise for identifying molecular pathologies of central nervous system disorders. However, the analysis of brain tissue poses unique analytical challenges, as typical microarray signals represent averaged transcript levels across neuronal and glial cell populations. Here we have generated ratios of gene transcript levels between gray and adjacent white matter samples to estimate the relative cellular origins of expression. We show that incorporating these ratios into transcriptome analysis (i) provides new analytical perspectives, (ii) increases the potential for biological insight obtained from postmortem transcriptome studies, (iii) expands knowledge about glial and neuronal cellular programs and (iv) facilitates the generation of cell-type specific hypotheses. This approach represents a robust and cost-effective "add-on" to transcriptome analyses of the mammalian brain. As this approach can be applied post hoc, we provide tables of ratios for analysis of existing mouse and human brain datasets.}, language = {eng}, number = {2}, journal = {Journal of Neuroscience Methods}, author = {Sibille, Etienne and Arango, Victoria and Joeyen-Waldorf, Jennifer and Wang, Yingjie and Leman, Samuel and Surget, Alexandre and Belzung, Catherine and Mann, J. John and Lewis, David A.}, month = {January}, year = {2008}, pmid = {17889939}, pmcid = {PMC2262176}, keywords = {Animals, Brain, Cluster Analysis, Cohort Studies, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Humans, Mice, Microarray Analysis, Nerve Tissue Proteins, Neuroglia, Neurons, Postmortem Changes, {RNA}, Messenger, Transcription, Genetic}, pages = {198--206} }
@article{ cachard-chastel_prucalopride_2008, title = {Prucalopride and donepezil act synergistically to reverse scopolamine-induced memory deficit in C57Bl/6j mice}, volume = {187}, issn = {0166-4328}, doi = {10.1016/j.bbr.2007.10.008}, abstract = {It is known that 5-{HT}(4) receptor agonists increase {sAPPalpha} levels in the cortex and hippocampus of mice as well as in a model of Alzheimer's disease ({AD}). As {sAPPalpha} is thought to have pro-mnesic properties, we assessed whether its increase induces cognitive improvement in a spatial memory task and whether it reverses a scopolamine-induced memory deficit. Mice treated or not treated with scopolamine were trained in the Morris water maze for 3 days. Before the probe test, they received an injection of either a 5-{HT}(4) receptor agonist (prucalopride or {RS} 67333), or an acetylcholinesterase inhibitor (donepezil), or both drugs. As expected, scopolamine decreased performance, an effect that was not reversed by the drugs tested when injected alone. However, prucalopride (5 mg kg(-1), s.c.) acted synergistically with donepezil (0.75 mg kg(-1), s.c.) to counteract completely scopolamine-induced amnesia. Western blot analysis of tissue homogenates in the cortex and hippocampus shows that {sAPPalpha} levels did not differ between saline- and scopolamine-treated mice. Furthermore, a region-dependent drug action was observed since the scopolamine-treated mice display a tendency to increase {sAPPalpha} levels in the hippocampus after donepezil or in the cortex after prucalopride. Our results suggest that a combined treatment with a 5-{HT}(4) receptor agonist with an acetylcholinesterase inhibitor has beneficial effects on memory in mice. Moreover, it seems to enhance {sAPPalpha} levels in two brain regions highly affected in {AD}. Thus, a drug polytherapy could be interesting not only to enhance cognitive performance and decrease drawbacks but also to get the best action in each brain region.}, language = {eng}, number = {2}, journal = {Behavioural Brain Research}, author = {Cachard-Chastel, M. and Devers, S. and Sicsic, S. and Langlois, M. and Lezoualc'h, F. and Gardier, A. M. and Belzung, C.}, month = {March}, year = {2008}, pmid = {18061284}, keywords = {Amyloid beta-Protein Precursor, Analysis of Variance, Aniline Compounds, Animals, Benzofurans, Cerebral Cortex, Cholinesterase Inhibitors, Drug Synergism, Hippocampus, Indans, Male, Maze Learning, Memory Disorders, Mice, Mice, Inbred C57BL, Motor Activity, Nootropic Agents, Piperidines, Scopolamine Hydrobromide, Serotonin 5-{HT}4 Receptor Agonists, Statistics, Nonparametric}, pages = {455--461} }
@article{ yalcin_mouse_2008, title = {Mouse strain differences in the unpredictable chronic mild stress: a four-antidepressant survey}, volume = {193}, issn = {0166-4328}, shorttitle = {Mouse strain differences in the unpredictable chronic mild stress}, doi = {10.1016/j.bbr.2008.04.021}, abstract = {There have been few comparisons of strains and antidepressants in the unpredictable chronic mild stress ({UCMS}) paradigm in mice. This study was undertaken to determine the influence of such factors using four antidepressants drugs including the tricyclics imipramine (20 mg/(kgday)) and desipramine (10 mg/(kgday)), the tetracyclic maprotiline (20 mg/(kgday)) and the selective serotonin reuptake inhibitor ({SSRI}) fluoxetine (10mg/(kgday)) in both Swiss and {BALB}/c mice. A 6-week {UCMS} regimen induced deterioration of the coat state and decreased grooming behaviours in the splash test in {BALB}/c mice but not Swiss mice. The four antidepressants reversed the {UCMS}-induced effects in {BALB}/c mice in both measures. However, imipramine and fluoxetine reached significance in the splash test while desipramine and maprotiline displayed only a trend. In conclusion, these results emphasize that {BALB}/c mice are more sensitive than Swiss mice for studying the effects of the {UCMS} model as well as for testing antidepressant-like properties.}, language = {eng}, number = {1}, journal = {Behavioural Brain Research}, author = {Yalcin, Ipek and Belzung, Catherine and Surget, Alexandre}, month = {November}, year = {2008}, pmid = {18565601}, keywords = {Animals, Animals, Outbred Strains, Antidepressive Agents, Antidepressive Agents, Second-Generation, Antidepressive Agents, Tricyclic, Anxiety, Behavior, Animal, Chronic Disease, Depression, Desipramine, Fluoxetine, Grooming, Imipramine, Injections, Intraperitoneal, Male, Maprotiline, Mice, Mice, Inbred {BALB} C, Mice, Inbred {DBA}, Serotonin Uptake Inhibitors, Species Specificity, Stress, Psychological, Time Factors}, pages = {140--143} }
@article{ title = {The apical ectodermal ridge is a timer for generating distal limb progenitors.}, type = {article}, year = {2008}, identifiers = {[object Object]}, keywords = {Animals,Apoptosis,Body Patterning,Cell Proliferation,DNA-Binding Proteins,DNA-Binding Proteins: genetics,DNA-Binding Proteins: metabolism,Ectoderm,Ectoderm: cytology,Ectoderm: embryology,Ectoderm: metabolism,Embryonic Stem Cells,Embryonic Stem Cells: cytology,Embryonic Stem Cells: metabolism,Extremities,Extremities: embryology,Female,Gene Expression Regulation, Developmental,Homeodomain Proteins,Homeodomain Proteins: genetics,Homeodomain Proteins: metabolism,Mice,Mice, Knockout,Mice, Transgenic,Models, Biological,Mutation,Pregnancy,Receptor, Fibroblast Growth Factor, Type 2,Receptor, Fibroblast Growth Factor, Type 2: defici,Receptor, Fibroblast Growth Factor, Type 2: geneti,Signal Transduction,Wnt Proteins,Wnt Proteins: metabolism,beta Catenin,beta Catenin: metabolism}, pages = {1395-405}, volume = {135}, websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2574509&tool=pmcentrez&rendertype=abstract}, month = {4}, id = {ec40b96a-2b83-3505-aebf-900ef60c88b4}, created = {2016-04-08T12:19:26.000Z}, accessed = {2015-03-24}, file_attached = {true}, profile_id = {994bc413-6766-31df-917a-32165aa30f6c}, group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e}, last_modified = {2017-03-14T10:42:46.538Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Lu2008}, folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748}, private_publication = {false}, abstract = {The apical ectodermal ridge (AER) is a transient embryonic structure essential for the induction, patterning and outgrowth of the vertebrate limb. However, the mechanism of AER function in limb skeletal patterning has remained unclear. In this study, we genetically ablated the AER by conditionally removing FGFR2 function and found that distal limb development failed in mutant mice. We showed that FGFR2 promotes survival of AER cells and interacts with Wnt/beta-catenin signaling during AER maintenance. Interestingly, cell proliferation and survival were not significantly reduced in the distal mesenchyme of mutant limb buds. We established Hoxa13 expression as an early marker of distal limb progenitors and discovered a dynamic morphogenetic process of distal limb development. We found that premature AER loss in mutant limb buds delayed generation of autopod progenitors, which in turn failed to reach a threshold number required to form a normal autopod. Taken together, we have uncovered a novel mechanism, whereby the AER regulates the number of autopod progenitors by determining the onset of their generation.}, bibtype = {article}, author = {Lu, Pengfei and Yu, Ying and Perdue, Yasmine and Werb, Zena}, journal = {Development (Cambridge, England)}, number = {8} }
@article{ bourin_animal_2007, title = {Animal models of anxiety in mice}, volume = {21}, issn = {1472-8206}, url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1472-8206.2007.00526.x/abstract}, doi = {10.1111/j.1472-8206.2007.00526.x}, abstract = {Among the multiple possibilities to study human pathologies, animal models remain one of the most used pathways. They allow to access to unavailable answers in human patients and to learn about mechanisms of action of drugs. Primarily developed with rats, animal models in anxiety have been adapted with a mixed success for mice, an easy-to-use mammal with better genetic possibilities than rats. In this review, we have focused on the most used animal models in anxiety in mice. Both conditioned and unconditioned models are described, to represent all types of animal models of anxiety. Behavioural studies require strong care for variable parameters, linked to environment, handling or paradigm; we have discussed about this topic. Finally, we focused on the consequences of re-exposure to the apparatus. Test–retest procedures can bring in new answers, but should be deeply studied, to revalidate the whole paradigm as an animal model of anxiety.}, language = {en}, number = {6}, urldate = {2013-09-23TZ}, journal = {Fundamental \& Clinical Pharmacology}, author = {Bourin, Michel and Petit-Demoulière, Benoit and Nic Dhonnchadha, Brid and Hascöet, Martine}, year = {2007}, keywords = {Anxiety, Mice, animal model, behavioural studies, test–retest}, pages = {567--574} }
@article{ sibille_lack_2007, title = {Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity}, volume = {12}, issn = {1359-4184}, doi = {10.1038/sj.mp.4001990}, abstract = {Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-{HT}) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-{HT} system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-{HT}(1B) receptor (5-{HT}(1B)R), a candidate gene for 5-{HT}-mediated age-related functions. We show that the lack of 5-{HT}(1B)R (Htr1b({KO}) mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1b({KO}) mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1b({KO}) mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1b({KO}) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems ({IGF}-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-{HT} function, thus identifying 5-{HT} as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-{HT}.}, language = {eng}, number = {11}, journal = {Molecular Psychiatry}, author = {Sibille, E. and Su, J. and Leman, S. and Le Guisquet, A. M. and Ibarguen-Vargas, Y. and Joeyen-Waldorf, J. and Glorioso, C. and Tseng, G. C. and Pezzone, M. and Hen, R. and Belzung, C.}, month = {November}, year = {2007}, pmid = {17420766}, pmcid = {PMC2515886}, keywords = {Age Factors, Aging, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Dopamine Plasma Membrane Transport Proteins, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Hand Strength, In Situ Hybridization, Maze Learning, Mice, Mice, Knockout, Microarray Analysis, Motor Activity, Reaction Time, Receptor, Serotonin, 5-{HT}1B, Survival Analysis}, pages = {1042--1056, 975} }
@Article{VonWegner_2007_5301, author = {Von Wegner, F. and Both, M. and Fink, R. H. and Friedrich, O.}, journal = {IEEE Transactions on Medical Imaging}, number = {7}, pages = {925-34}, title = {Fast XYT imaging of elementary calcium release events in muscle with multifocal multiphoton microscopy and wavelet denoising and detection}, volume = {26}, year = {2007}, keywords = {Algorithms, Animals, Calcium/*metabolism, Calcium, Signaling/physiology, Cells, Cultured, Image, Enhancement/methods, Image, Interpretation, Computer-Assisted/*methods, Imaging, Three-Dimensional/methods, Metabolic, Clearance, Rate, Mice, Microscopy, Fluorescence, Multiphoton/*methods, Muscle, Fibers/*cytology/*metabolism, Muscle, Skeletal/*cytology/*metabolism, Reproducibility, of, Results, Sensitivity, and, Specificity}, title_with_no_special_chars = {Fast XYT imaging of elementary calcium release events in muscle with multifocal multiphoton microscopy and wavelet denoising and detection} }
@article{ title = {Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme.}, type = {article}, year = {2007}, identifiers = {[object Object]}, keywords = {Animals,Body Patterning,Cell Lineage,Embryo, Mammalian,Embryo, Mammalian: anatomy & histology,Embryo, Mammalian: physiology,Female,Homeodomain Proteins,Homeodomain Proteins: genetics,Homeodomain Proteins: metabolism,LIM-Homeodomain Proteins,Limb Buds,Limb Buds: anatomy & histology,Limb Buds: embryology,Male,Mesoderm,Mesoderm: cytology,Mesoderm: embryology,Mice,Mice, Transgenic,Pregnancy,Transcription Factors,Transcription Factors: genetics,Transcription Factors: metabolism}, pages = {3713-22}, volume = {134}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/17715176}, month = {10}, id = {86d2cb50-c634-33d1-9773-d2b82c86031d}, created = {2016-04-08T12:19:26.000Z}, accessed = {2014-06-03}, file_attached = {true}, profile_id = {994bc413-6766-31df-917a-32165aa30f6c}, group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e}, last_modified = {2017-03-14T10:42:46.538Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Arques2007}, folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748}, private_publication = {false}, abstract = {Regionalization of embryonic fields into independent units of growth and patterning is a widespread strategy during metazoan development. Compartments represent a particular instance of this regionalization, in which unit coherence is maintained by cell lineage restriction between adjacent regions. Lineage compartments have been described during insect and vertebrate development. Two common characteristics of the compartments described so far are their occurrence in epithelial structures and the presence of signaling regions at compartment borders. Whereas Drosophila compartmental organization represents a background subdivision of embryonic fields that is not necessarily related to anatomical structures, vertebrate compartment borders described thus far coincide with, or anticipate, anatomical or cell-type discontinuities. Here, we describe a general method for clonal analysis in the mouse and use it to determine the topology of clone distribution along the three limb axes. We identify a lineage restriction boundary at the limb mesenchyme dorsoventral border that is unrelated to any anatomical discontinuity, and whose lineage restriction border is not obviously associated with any signaling center. This restriction is the first example in vertebrates of a mechanism of primordium subdivision unrelated to anatomical boundaries. Furthermore, this is the first lineage compartment described within a mesenchymal structure in any organism, suggesting that lineage restrictions are fundamental not only for epithelial structures, but also for mesenchymal field patterning. No lineage compartmentalization was found along the proximodistal or anteroposterior axes, indicating that patterning along these axes does not involve restriction of cell dispersion at specific axial positions.}, bibtype = {article}, author = {Arques, Carlos G and Doohan, Roisin and Sharpe, James and Torres, Miguel}, journal = {Development (Cambridge, England)}, number = {20} }
@article{lundgren_viral_2007, title = {Viral infection and {PBDE} exposure interact on {CYP} gene expression and enzyme activities in the mouse liver.}, volume = {242}, issn = {0300-483X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17964055}, doi = {10.1016/j.tox.2007.09.014}, abstract = {In the present study coxsackievirus B3 (CVB3) adapted to Balb/c mice was used to examine whether infection affects xenobiotic-metabolising CYP1A1 and CYP2B gene expression (measured by RT-PCR) and the corresponding enzyme activities of ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-depentylase (PROD), as observed on day 3 of infection. To study the simultaneous effects of xenobiotic exposure, mice were administered the polybrominated diphenyl ether (PBDE) compounds BDE-99 (single congener) and Bromkal 70-5 DE (commercial mixture). Serum thyroxine levels were also measured. High numbers of CVB3 were found in the livers of infected mice but no significant effects of PBDE on virus replication were observed. In infected mice gene expression and CYP activities were decreased in comparison with non-infected mice, especially for CYP2B. PBDE exposure in the non-infected mice was characterised by an increase in both CYP2B and PROD levels/activities, whereas CYP1A levels increased and EROD activity decreased. In general, PBDE exposure in the infected mice did not increase EROD and PROD activities to the same extent as in the non-infected exposed mice. Infected mice exposed to BDE-99 showed significantly higher CYP2B and PROD levels than both the infected non-exposed and Bromkal-exposed groups. T(4) levels were greatly decreased by infection and a tendency of reduced T(4) levels after PBDE exposure could be observed in non-infected mice. In conclusion, infection reduced the detoxifying capacity of the liver and the serum T(4) levels. PBDE exposure can modify these effects. Notably, in the infected mice differences between BDE-99 and Bromkal were observed on CYP2B gene expression and PROD activity.}, number = {1-3}, journal = {Toxicology}, author = {Lundgren, Magnus and Darnerud, Per Ola and Molin, Ylva and Lilienthal, Hellmuth and Blomberg, Jonas and Ilbäck, Nils-Gunnar}, month = dec, year = {2007}, pmid = {17964055}, keywords = {Animal, Animals, Brominated, Brominated: toxicity, Coxsackievirus Infections, Coxsackievirus Infections: enzymology, Coxsackievirus Infections: genetics, Coxsackievirus Infections: virology, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A1: genetics, Cytochrome P-450 CYP1A1: metabolism, Cytochrome P-450 CYP2B1, Cytochrome P-450 CYP2B1: genetics, Cytochrome P-450 CYP2B1: metabolism, Cytochrome P-450 Enzyme System, Cytochrome P-450 Enzyme System: genetics, Cytochrome P-450 Enzyme System: metabolism, Disease Models, Enterovirus B, Enzymologic, Enzymologic: drug effe, Female, Flame retardants, Gene Expression Regulation, Halogenated Diphenyl Ethers, Human, Human: drug effects, Human: pathogenicity, Hydrocarbons, Inbred BALB C, Liver, Liver: drug effects, Liver: enzymology, Liver: virology, Mice, Oxazines, Oxazines: metabolism, Phenyl Ethers, Phenyl Ethers: toxicity, Reverse Transcriptase Polymerase Chain Reaction, Thyroxine, Thyroxine: blood, Time Factors, Virus Replication, Virus Replication: drug effects, ffr, tox}, pages = {100--8} }
@article{zhang_regulation_2007, title = {Regulation of {MMP}-9 expression and activity in the mouse uterus by estrogen}, volume = {74}, issn = {1040-452X}, doi = {10.1002/mrd.20582}, abstract = {Matrix metalloproteinases (MMPs) are spatiotemporally expressed in the uterus across normal estrous and menstrual cycles and are known to participate in the extensive endometrial tissue remodeling. MMP-9/gelatinase B is one of the major MMPs found in the uterus that modulates uterine biology during various reproductive processes. Although it seems that uterine MMP-9 is under ovarian steroid hormonal control, there are conflicting reports regarding steroidal hormonal regulation of MMP-9 expression, and there is little information on the effects of estrogen in vivo in this respect. We therefore examined the steroidal regulation of MMP-9 within the mouse uterus. Female mice (2-3 months old) were ovariectomized and treated with estradiol-l7beta (E(2)) or E(2) + progesterone (P(4)) and uterine gelatinase activity and expression were determined. Gelatin zymography revealed that E(2) alone or in combination with P(4) increased MMP-9 activation, whereas Northern analysis showed that E(2) decreased MMP-9 steady state mRNA expression and an estrogen receptor antagonist ICI-182, 780 blocked this effect. In contrast, uterine MMP-2 expression and activity were not affected by steroidal treatments. Pretreatment with a transcription inhibitor actinomycin D or translation inhibitor cycloheximide indicates that E(2) regulates uterine MMP-9 at multiple points, involving transcriptional and posttranscriptional control as well as modulation of inhibitor activities. Collectively, these data suggest that E(2) regulates uterine MMP-9 expression and activity in vivo via a complex mechanism. This estrogen regulation of MMP-9 activity may play an important role in uterine tissue remodeling.}, language = {eng}, number = {3}, journal = {Molecular Reproduction and Development}, author = {Zhang, Xuan and Christenson, Lane K. and Nothnick, Warren B.}, month = mar, year = {2007}, pmid = {16967517}, keywords = {Animals, Cycloheximide, Dactinomycin, Drug Interactions, Estrogens, Female, Gelatinases, Gene Expression Regulation, Matrix Metalloproteinase 9, Mice, Nucleic Acid Synthesis Inhibitors, Ovariectomy, Progesterone, Protein Synthesis Inhibitors, RNA, Messenger, Time Factors, Uterus}, pages = {321--331} }
@article{viberg_neonatal_2006, title = {Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or nonabromodiphenyl ether, impairs spontaneous behavior and learning and memory functions of adult mice.}, volume = {92}, issn = {1096-6080}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16611620}, doi = {10.1093/toxsci/kfj196}, abstract = {Polybrominated diphenyl ethers (PBDEs), used as flame retardants, have been shown to be increasing in the environment and in human mother's milk. We have earlier reported that lower brominated PBDEs, such as tetra-, penta-, and hexa-brominated diphenyl ethers, can cause developmental neurotoxic effects in mice. Recently, this was also observed with the full-brominated PBDE, deca-brominated diphenyl ether (PBDE 209), although it was suggested that the effects were caused by a (possibly debrominated) metabolite thereof. The present study revealed that 2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether (PBDE 206), 2,2',3,4,4',5,5',6-octabromodiphenyl ether (PBDE 203), and to a minor extent also 2,2',3,4,4',5',6'-heptabromodiphenyl ether (PBDE 183) can induce developmental neurotoxic effects. Neonatal Naval Medical Research Institute male mice were exposed on postnatal day 3 or 10 to PBDE 206, PBDE 203, or PBDE 183, given as a single oral dose of 21 mumol/kg body weight. At the adult age of 2-3 months, the mice were observed for performance in a spontaneous behavior test and the Morris water maze test. PBDE 203 and PBDE 206, when administered on neonatal day 10, caused disturbances in spontaneous behavior, leading to disrupted habituation and a hyperactive condition in adults at the age of 2 months. These behavioral changes were also seen in 2-month-old mice exposed to PBDE 203 on neonatal day 3. Furthermore, exposure to PBDE 203 on neonatal day 10 affected learning and memory functions in adult mice. The developmental neurotoxic effects were most pronounced in mice exposed to PBDE 203. These developmental neurobehavioral defects were in agreement with those we observed previously with lower brominated PBDEs and with PBDE 209. It is important to consider the fact that different PBDE congeners can have differing degrees of potency, when comparing levels of PBDEs in the environment and in mother's milk.}, number = {1}, journal = {Toxicological sciences}, author = {Viberg, Henrik and Johansson, Niclas and Fredriksson, Anders and Eriksson, Johan and Marsh, Göran and Eriksson, Per}, month = jul, year = {2006}, pmid = {16611620}, keywords = {Animal, Animal: drug effects, Animals, Behavior, Ethers, Flame retardants, Learning, Learning: drug effects, Male, Memory, Memory: drug effects, Mice, Newborn, Polybrominated Biphenyls, Polybrominated Biphenyls: toxicity, frelec, tox}, pages = {211--8} }
@article{el_messaoudi_coactivator-associated_2006, title = {Coactivator-associated arginine methyltransferase 1 ({CARM}1) is a positive regulator of the {Cyclin} {E}1 gene.}, volume = {103}, issn = {0027-8424}, doi = {10.1073/pnas.0605692103}, abstract = {The Cyclin E1 gene (CCNE1) is an ideal model to explore the mechanisms that control the transcription of cell cycle-regulated genes whose expression rises transiently before entry into S phase. E2F-dependent regulation of the CCNE1 promoter was shown to correlate with changes in the level of H3-K9 acetylation/methylation of nucleosomal histones positioned at the transcriptional start site region. Here we show that, upon growth stimulation, the same region is subject to variations of H3-R17 and H3-R26 methylation that correlate with the recruitment of coactivator-associated arginine methyltransferase 1 (CARM1) onto the CCNE1 and DHFR promoters. Accordingly, CARM1-deficient cells lack these modifications and present lowered levels and altered kinetics of CCNE1 and DHFR mRNA expression. Consistently, reporter gene assays demonstrate that CARM1 functions as a transcriptional coactivator for their E2F1/DP1-stimulated expression. CARM1 recruitment at the CCNE1 gene requires activator E2Fs and ACTR, a member of the p160 coactivator family that is frequently overexpressed in human breast cancer. Finally, we show that grade-3 breast tumors present coelevated mRNA levels of ACTR and CARM1, along with their transcriptional target CCNE1. All together, our results indicate that CARM1 is an important regulator of the CCNE1 gene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, author = {El Messaoudi, Selma and Fabbrizio, Eric and Rodriguez, Carmen and Chuchana, Paul and Fauquier, Lucas and Cheng, Donghang and Theillet, Charles and Vandel, Laurence and Bedford, Mark T and Sardet, Claude and Messaoudi, Selma El and Fabbrizio, Eric and Rodriguez, Carmen and Chuchana, Paul and Fauquier, Lucas and Cheng, Donghang and Theillet, Charles and Vandel, Laurence and Bedford, Mark T and Sardet, Claude}, year = {2006}, pmid = {16938873}, keywords = {Activin Receptors- Type I, Animals, Cell Culture Techniques, Cell Proliferation, Cells- Cultured, E2F Transcription Factors, Fibroblasts, Gene Expression Regulation, Genes- Reporter, Genes- cdc, Histones, Kinetics, Luciferases, Methylation, Mice, MicroRNAs, NIH 3T3 Cells, Nucleosomes, Promoter Regions- Genetic, Protein-Arginine N-Methyltransferases, RNA- Messenger, RNA- Small Interfering, Swiss 3T3 Cells, Trans-Activators, Transcription Factor DP1}, pages = {13351--13356} }
@article{yaghmaie_age-dependent_2006, title = {Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice.}, volume = {24}, issn = {0736-5748}, url = {http://www.sciencedirect.com/science/article/pii/S0736574806000943}, doi = {10.1016/j.ijdevneu.2006.08.008}, abstract = {Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF-1R), the cells of the supraoptic nucleus (SON) display some of the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22 months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each section of supraoptic hypothalamus. Results show that while the total number of cells in the SON of ad-libitum fed mice does not change significantly with aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad-libitum fed mice with aging. In contrast to this, calorie restricted mice show both a decline in the total number of cells and IGF-1R immunoreactive cells in the SON with age, but with the decrease in the latter being notably attenuated when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR induces greater loss in the total number of cells in the SON with age, it reduces the degree of age-dependent loss seen in IGF-1R expressing cells. As a result, when compared to Old-AL mice, the SON of Old-CR mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging.}, number = {7}, journal = {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience}, author = {Yaghmaie, F and Saeed, O and Garan, S A and Voelker, M A and Gouw, A M and Freitag, W and Sternberg, H and Timiras, P S}, month = nov, year = {2006}, pmid = {17034982}, keywords = {Age Factors, Aging, Aging: physiology, Animals, Anterior, Anterior: cytology, Caloric Restriction, Caloric Restriction: methods, Cell Count, Cell Count: methods, Hypothalamus, Immunohistochemistry, Immunohistochemistry: methods, Insulin-Like Growth Factor I, Insulin-Like Growth Factor I: metabolism, Mice, Neurons, Neurons: metabolism}, pages = {431--6} }
@article{kazmierczak_analysis_2006, title = {Analysis of {FimX}, a phosphodiesterase that governs twitching motility in {Pseudomonas} aeruginosa}, volume = {60}, issn = {0950-382X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/16677312}, doi = {10.1111/j.1365-2958.2006.05156.x}, abstract = {Type IV pili (Tfp) are polar surface structures of Pseudomonas aeruginosa required for twitching motility, biofilm formation and adherence. One protein required for the assembly of tfp is FimX, which possesses both GGDEF and EAL domains characteristic of diguanylate cyclases and phosphodiesterases respectively. In this work we demonstrate that FimX has phosphodiesterase activity towards bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), but does not show diguanylate cyclase activity. Instead, the imperfect GGDEF domain of FimX likely serves to activate phosphodiesterase activity when bound to GTP, as has recently been described for the Caulobacter crescentus composite GGDEF-EAL protein, CC3396. Bacteria expressing FimX in which either the GGDEF or EAL domain is deleted or mutated have phenotypes indistinguishable from a DeltafimX strain, demonstrating the importance of both domains to function. Previous work has shown that FimX localizes to the bacterial pole. In this work we show that restriction of FimX to a single pole requires intact GGDEF and EAL domains. Deletion of the amino-terminal REC domain of FimX, which contains a putative polar localization signal, results in a protein that still supports intermediate levels of pilus assembly and function. RFP-FimXDeltaREC, unlike RFP-FimX, is no longer localized to the bacterial pole, while transmission electron microscopy shows that surface pili can originate from non-polar sites in this mutant. Although DeltafimX mutants show limited in vitro cytotoxicity, they are as virulent as the wild-type strain in a murine model of acute pneumonia.}, number = {4}, urldate = {2009-10-09TZ}, journal = {Molecular Microbiology}, author = {Kazmierczak, Barbara I and Lebron, Maria B and Murray, Thomas S}, month = may, year = {2006}, pmid = {16677312}, keywords = {Animals, Bacterial Proteins, Cell Movement, Cyclic GMP, Female, Fimbriae, Bacterial, Hela Cells, Humans, Mice, Mice, Inbred C57BL, Phosphoric Diester Hydrolases, Phosphorus-Oxygen Lyases, Pneumonia, Bacterial, Point Mutation, Protein Structure, Tertiary, Pseudomonas aeruginosa, Sequence Deletion, Virulence}, pages = {1026--1043} }
@article{ title = {Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes.}, type = {article}, year = {2006}, identifiers = {[object Object]}, keywords = {Adoptive Transfer,Animals,Cell Communication,Cell Communication: immunology,Chemotaxis, Leukocyte,Chemotaxis, Leukocyte: immunology,Diagnostic Imaging,Immunohistochemistry,Lymph Nodes,Lymph Nodes: immunology,Lymph Nodes: metabolism,Lymph Nodes: ultrastructure,Lymphocytes,Lymphocytes: cytology,Lymphocytes: immunology,Lymphocytes: metabolism,Mice,Mice, Inbred C57BL,Microscopy, Confocal,Microscopy, Electron, Scanning,Microscopy, Electron, Transmission,Stromal Cells,Stromal Cells: immunology,Stromal Cells: ultrastructure}, pages = {989-1001}, volume = {25}, websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2692293&tool=pmcentrez&rendertype=abstract}, month = {12}, id = {ab0488e6-a7c2-3c42-9061-9806d5b10076}, created = {2014-11-06T10:54:42.000Z}, accessed = {2014-04-01}, file_attached = {true}, profile_id = {397d75f1-832d-36e0-bbe6-b6878f88c402}, group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e}, last_modified = {2017-03-14T10:42:46.538Z}, read = {true}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Bajenoff2006}, folder_uuids = {012ffa25-2a44-4a25-bcea-c88915e4c046}, private_publication = {false}, abstract = {After entry into lymph nodes (LNs), B cells migrate to follicles, whereas T cells remain in the paracortex, with each lymphocyte type showing apparently random migration within these distinct areas. Other than chemokines, the factors contributing to this spatial segregation and to the observed patterns of lymphocyte movement are poorly characterized. By combining confocal, electron, and intravital microscopy, we showed that the fibroblastic reticular cell network regulated naive T cell access to the paracortex and also supported and defined the limits of T cell movement within this domain, whereas a distinct follicular dendritic cell network similarly served as the substratum for movement of follicular B cells. These results highlight the central role of stromal microanatomy in orchestrating cell migration within the LN.}, bibtype = {article}, author = {Bajénoff, Marc and Egen, Jackson G and Koo, Lily Y and Laugier, Jean Pierre and Brau, Frédéric and Glaichenhaus, Nicolas and Germain, Ronald N}, journal = {Immunity}, number = {6} }
@article{jansen_stem_2006, title = {Stem cell profiling by nuclear magnetic resonance spectroscopy}, volume = {56}, copyright = {CC0 1.0 Universal Public Domain Dedication}, issn = {0740-3194}, doi = {10.1002/mrm.20968}, abstract = {The classification of embryonic and adult stem cells, including their derivatives, is still limited, and often these cells are best defined by their functional properties. Recent gene array studies have yielded contradictory results. Also, very little is known about the metabolic properties of these exciting cells. In this study, proton (1H) NMR spectroscopy was used to identify the major low-molecular-weight metabolites in murine embryonic stem cells (ESC) and their neural stem cell (NSC) derivatives. ESC are characterized by an unusually low number of NMR-detectable metabolites, high phosphocholine (PC) content, and nondetectable glycerophosphocholine (GPC). The metabolic profiles of NSC resemble glial cells and oligodendrocyte progenitors, but with considerably higher PC, GPC, and myo-inositol content. The results suggest that NMR spectroscopy in vitro can provide markers to study the effects of differentiation on cell metabolism, and potentially to assess stem cell preparations for differentiation status.}, language = {eng}, number = {3}, journal = {Magnetic Resonance in Medicine}, author = {Jansen, Jacobus F. A. and Shamblott, Michael J. and van Zijl, Peter C. M. and Lehtimäki, Kimmo K. and Bulte, Jeff W. M. and Gearhart, John D. and Hakumäki, Juhana M.}, month = sep, year = {2006}, pmid = {16858672}, keywords = {Magnetic Resonance Spectroscopy, Animals, Mice, Neurons, Stem Cells, Cell Line, Phosphorylcholine}, pages = {666--670} }
@article{moo06usi, title = {Using the Outcome for Imputation of Missing Predictor Values Was Preferred}, volume = {59}, journal = {J Clin Epi}, doi = {10.1016/j.jclinepi.2006.01.009}, author = {Moons, Karel G. M. and Donders, Rogier A. R. T. and Stijnen, Theo and Harrell, Frank E.}, year = {2006}, keywords = {teaching-mds,missing-data,graphics,imputation,response,aregimpute,mice}, pages = {1092-1101}, citeulike-article-id = {13265492}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jclinepi.2006.01.009}, posted-at = {2014-07-14 14:09:58}, priority = {0}, annote = {use of outcome variable; excellent graphical summaries of simulations} }
@article{ title = {In situ characterization of CD4+ T cell behavior in mucosal and systemic lymphoid tissues during the induction of oral priming and tolerance}, type = {article}, year = {2005}, identifiers = {[object Object]}, keywords = {*Immunity, Mucosal,Administration, Oral,Animals,Antigens/administration & dosage,CD4-Positive T-Lymphocytes/cytology/*immunology,Cell Movement/*immunology,Immunologic Memory,Lymph Nodes/cytology/immunology,Lymphocyte Activation/immunology,Mice,Mice, Inbred BALB C,Mice, Transgenic,Mucous Membrane/cytology/immunology,Ovalbumin}, pages = {1815-1823}, volume = {201}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/15928201}, id = {dffec1ba-2aa0-37df-b367-0f51c60881dc}, created = {2018-03-05T02:58:05.695Z}, file_attached = {true}, profile_id = {fc9ef84f-888b-33fd-b1d3-fbf022f2f0c8}, group_id = {21bf6821-cbba-3be9-9d50-072f76d57584}, last_modified = {2018-03-05T02:58:05.807Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Zinselmeyer2005}, private_publication = {false}, abstract = {The behavior of antigen-specific CD4+ T lymphocytes during initial exposure to antigen probably influences their decision to become primed or tolerized, but this has not been examined directly in vivo. We have therefore tracked such cells in real time, in situ during the induction of oral priming versus oral tolerance. There were marked contrasts with respect to rate and type of movement and clustering between naive T cells and those exposed to antigen in immunogenic or tolerogenic forms. However, the major difference when comparing tolerized and primed T cells was that the latter formed larger and longer-lived clusters within mucosal and peripheral lymph nodes. This is the first comparison of the behavior of antigen-specific CD4+ T cells in situ in mucosal and systemic lymphoid tissues during the induction of priming versus tolerance in a physiologically relevant model in vivo.}, bibtype = {article}, author = {Zinselmeyer, B H and Dempster, J and Gurney, A M and Wokosin, D and Miller, M and Ho, H and Millington, O R and Smith, K M and Rush, C M and Parker, I and Cahalan, M and Brewer, J M and Garside, P}, journal = {J Exp Med}, number = {11} }
@article{den_brok_situ_2004, title = {In situ tumor ablation creates an antigen source for the generation of antitumor immunity}, volume = {64}, issn = {0008-5472}, doi = {10.1158/0008-5472.CAN-03-3949}, abstract = {Tumor-destructing techniques, like radiofrequency ablation (RFA), allow eradication of large tumors. Potentially, in situ tumor destruction also can provide the immune system with an antigen source for the induction of antitumor immunity. Antigen-presenting cells could take up antigens in the periphery after which they induce specific immune responses. Recent data show that especially antigen-presenting dendritic cells are crucial for the induction of potent immune responses. However, virtually nothing is known regarding the induction of immune responses after in situ tumor destruction in mice or humans. We used the well-defined murine B16-OVA melanoma cell line to develop a novel tumor model to explore: (a). the immunologic consequences of in situ tumor destruction; and (b). the efficacy of a combination approach of tumor destruction and immunostimulation. Applying this model system we demonstrate that following RFA, a weak but detectable immune response develops, directed against OVA, but also against a broader range of B16 antigens. Adoptive transfer experiments further indicate that antitumor reactivity can be transferred to naïve mice by splenocytes. To augment the response observed, we administered a blocking monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 at the time of tumor destruction. Interestingly, this strongly enhanced antitumor immunity, resulting in long-lasting tumor protection. These results illustrate that in situ tumor destruction can provide a useful antigen source for the induction of antitumor immunity, provided that additional immunostimulatory signals are coadministered.}, language = {eng}, number = {11}, journal = {Cancer Research}, author = {den Brok, Martijn H. M. G. M. and Sutmuller, Roger P. M. and van der Voort, Robbert and Bennink, Erik J. and Figdor, Carl G. and Ruers, Theo J. M. and Adema, Gosse J.}, month = jun, year = {2004}, pmid = {15173017}, keywords = {Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, Differentiation, Antigens, Neoplasm, CTLA-4 Antigen, Catheter Ablation, Cricetinae, Female, Immunotherapy, Adoptive, Interferon-gamma, Lymphocyte Activation, Male, Melanoma, Experimental, Mice, Mice, Inbred C57BL, T-Lymphocytes}, pages = {4024--4029}, }
@article{ title = {Structures of new sesquiterpenes and hepatoprotective constituents from the Egyptian herbal medicine Cyperus longus.}, type = {article}, year = {2004}, identifiers = {[object Object]}, keywords = {Animals,Cells,Cultured,Cyperus,Cyperus: chemistry,Egypt,Galactosamine,Galactosamine: pharmacology,Hepatocytes,Hepatocytes: drug effects,Herbal Medicine,Medicinal,Medicinal: chemistry,Mice,Molecular Structure,Monoterpenes,Monoterpenes: chemistry,Monoterpenes: isolation & purification,Monoterpenes: pharmacology,Oxidation-Reduction,Plants,Sesquiterpenes,Sesquiterpenes: chemistry,Sesquiterpenes: isolation & purification,Sesquiterpenes: pharmacology,Stereoisomerism}, pages = {569-76}, volume = {67}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/15104485}, month = {4}, id = {ac4b00f0-dcaf-3d36-8606-94e3a456bd0b}, created = {2014-11-13T17:56:03.000Z}, file_attached = {true}, profile_id = {5a758209-74fb-3a9c-b322-2ae7f22f7b6c}, group_id = {63e349d6-2c70-3938-9e67-2f6483f6cbab}, last_modified = {2014-11-18T21:16:50.000Z}, read = {true}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, notes = { <m:linebreak></m:linebreak> <m:bold>From Duplicate 1 ( </m:bold> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:bold> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> </m:bold> <m:linebreak></m:linebreak> <m:bold> <m:linebreak></m:linebreak> <m:italic>Structures of new sesquiterpenes and hepatoprotective constituents from the Egyptian herbal medicine Cyperus longus.</m:italic> <m:linebreak></m:linebreak> </m:bold> <m:linebreak></m:linebreak> <m:bold> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> </m:bold> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:bold> - Xu, Fengming; Morikawa, Toshio; Matsuda, Hisashi; Ninomiya, Kiyofumi; Yoshikawa, Masayuki )<m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> </m:bold> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> <m:linebreak></m:linebreak> }, abstract = {Six new sesquiterpenes, cyperusols A(1) (1), A(2) (2), B(1) (3), B(2) (4), C (5), and D (6), together with two monoterpenes and 13 sesquiterpenes were isolated from an Egyptian herbal medicine, the whole plants of Cyperus longus. The stereostructures of the new sesquiterpenes were determined on the basis of chemical and physicochemical evidence. In addition, the principal constituents were found to exhibit inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.}, bibtype = {article}, author = {Xu, Fengming and Morikawa, Toshio and Matsuda, Hisashi and Ninomiya, Kiyofumi and Yoshikawa, Masayuki}, journal = {Journal of natural products}, number = {4} }
@article{ title = {T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node.}, type = {article}, year = {2004}, identifiers = {[object Object]}, keywords = {Animals,Cell Separation,Dendritic Cells,Dendritic Cells: immunology,Flow Cytometry,Lymph Nodes,Lymph Nodes: immunology,Mice,T-Lymphocyte Subsets,Transgenic}, pages = {998-1003}, volume = {101}, websites = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=327133&tool=pmcentrez&rendertype=abstract%5Cnhttp://www.ncbi.nlm.nih.gov/pubmed/14722354%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC327133}, id = {945373a1-10e0-3282-b9aa-ce7ce90313a1}, created = {2018-03-05T02:58:05.329Z}, file_attached = {true}, profile_id = {fc9ef84f-888b-33fd-b1d3-fbf022f2f0c8}, group_id = {21bf6821-cbba-3be9-9d50-072f76d57584}, last_modified = {2018-03-05T02:58:05.483Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Miller2004a}, private_publication = {false}, abstract = {Dendritic cells (DCs) ingest antigens in peripheral tissues and migrate to lymph nodes where they present MHC class II-bound antigen to CD4(+) T cells. We used two-photon microscopy to image the single-cell dynamics of interactions between DCs and T cells within intact lymph nodes in the absence of relevant antigen. DCs were fluorescently labeled in vivo by cutaneous injection of alum adjuvant including carboxyfluorescein diacetate succinimidyl ester (CFSE). CFSE-positive DCs (CD11c(+), CD11b(+), and low-to-intermediate CD8(+)) were observed in draining lymph nodes 24-72 h later. Labeled DCs meandered slowly (2-3 microm x min(-1)) in the T cell zone near B cell follicles but vigorously extended long agile dendrites. Encounters between T cells and DCs arose as T cells moved autonomously along random paths. Moreover, T cells did not accumulate around DCs, and their relative velocities approaching and departing DCs were equivalent, implying that T cells are not attracted toward DCs by chemotactic gradients but rather encounter them by chance. T cell/DC contacts occurred primarily on dendrites at arm's length from the DC soma and typically lasted approximately 3 min, enabling an individual DC to interact with up to 5000 T cells per hour. We conclude that dynamic DC gesticulation and random T cell motility together enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid initiation of the immune response.}, bibtype = {article}, author = {Miller, Mark J and Hejazi, Arsalan S and Wei, Sindy H and Cahalan, Michael D and Parker, Ian}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {4} }
@Article{Li_2004_1137, author = {Li, L. and Wartchow, C. A. and Danthi, S. N. and Shen, Z. and Dechene, N. and Pease, J. and Choi, H. S. and Doede, T. and Chu, P. and Ning, S. and Lee, D. Y. and Bednarski, M. D. and Knox, S. J.}, journal = {Int J Radiat Oncol Biol Phys}, note = {Journal Article United States}, number = {4}, pages = {1215-27}, title = {A novel antiangiogenesis therapy using an integrin antagonist or anti-flk-1 antibody coated 90y-labeled nanoparticles}, volume = {58}, year = {2004}, keywords = {Angiogenesis, Inhibitors/*therapeutic, use, Animals, Antibodies, Monoclonal/*therapeutic, use, Apoptosis, Cell, Line, Tumor, Drug, Screening, Assays, Antitumor, Female, In, Situ, Nick-End, Labeling, Integrins/*antagonists, &, inhibitors, Liposomes, Melanoma, Experimental/blood, supply/drug, therapy, Mice, Mice, Inbred, BALB, C, Mice, Inbred, C3H, Mice, Nude, Models, Animal, *Nanotechnology, Neoplasms/*blood, supply/*drug, therapy, Neovascularization, Pathologic/*drug, therapy, Pentetic, Acid/therapeutic, use, Receptors, Vitronectin/*antagonists, &, inhibitors, Vascular, Endothelial, Growth, Factor, Receptor-2/*antagonists, &, inhibitors}, title_with_no_special_chars = {A novel antiangiogenesis therapy using an integrin antagonist or antiFlk1 antibody coated 90Ylabeled nanoparticles} }
@Article{Guccione_2004_1116, author = {Guccione, S. and Li, K. C. and Bednarski, M. D.}, journal = {IEEE Eng Med Biol Mag}, note = {Journal Article Review United States the quarterly magazine of the Engineering in Medicine \& Biology Society}, number = {5}, pages = {50-6}, title = {Molecular imaging and therapy directed at the neovasculature in pathologies. how imaging can be incorporated into vascular-targeted delivery systems to generate active therapeutic agents}, volume = {23}, year = {2004}, keywords = {Angiogenesis, Inhibitors/*administration, &, dosage, Animals, Antibodies/administration, &, dosage/immunology, Contrast, Media/administration, &, dosage, Disease, Models, Animal, *Drug, Delivery, Systems, Gadolinium/administration, &, dosage, Integrin, alphaVbeta3/antagonists, &, inhibitors/immunology, Magnetic, Resonance, Angiography/*methods, Mice, Microspheres, Nanotechnology, Neoplasms/*blood, supply/*drug, therapy/pathology, Neovascularization, Pathologic/*diagnosis/*drug, therapy, Particle, Size, Rabbits}, title_with_no_special_chars = {Molecular imaging and therapy directed at the neovasculature in pathologies How imaging can be incorporated into vasculartargeted delivery systems to generate active therapeutic agents} }
@article{ santarelli_requirement_2003, title = {Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants}, volume = {301}, issn = {1095-9203}, doi = {10.1126/science.1083328}, abstract = {Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.}, language = {eng}, number = {5634}, journal = {Science (New York, N.Y.)}, author = {Santarelli, Luca and Saxe, Michael and Gross, Cornelius and Surget, Alexandre and Battaglia, Fortunato and Dulawa, Stephanie and Weisstaub, Noelia and Lee, James and Duman, Ronald and Arancio, Ottavio and Belzung, Catherine and Hen, René}, month = {August}, year = {2003}, pmid = {12907793}, keywords = {8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Antidepressive Agents, Antidepressive Agents, Second-Generation, Antidepressive Agents, Tricyclic, Behavior, Animal, Cell Division, Conditioning (Psychology), Dentate Gyrus, Fear, Feeding Behavior, Fluoxetine, Grooming, Hippocampus, Long-Term Potentiation, Male, Mice, Mice, Knockout, Neurons, Receptors, Serotonin, Receptors, Serotonin, 5-{HT}1, Stress, Physiological, Synaptic Transmission}, pages = {805--809} }
@article{viberg_neonatal_2003, title = {Neonatal exposure to polybrominated diphenyl ether ({PBDE} 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice.}, volume = {192}, issn = {0041-008X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/14550744}, abstract = {Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Flame retardants are used to suppress or inhibit combustion processes in an effort to reduce the risk of fire. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), are present and increasing in the environment and in human milk. The present study shows that neonatal exposure to 2,2',4,4',5,5'-hexaBDE (PBDE 153), a PBDE persistent both in environment and in human milk, can induce developmental neurotoxic effects, such as changes in spontaneous behaviour (hyperactivity), impairments in learning and memory, and reduced amounts of nicotinic receptors, effects that get worse with age. Neonatal NMRI male mice were orally exposed on day 10 to 0.45, 0.9, or 9.0 mg of PBDE 153/kg of body weight. Spontaneous behaviour (locomotion, rearing, and total activity) was observed in 2-, 4-, and 6-month-old mice, Morris water maze at an age of 6 months. The behaviour tests showed that the effects were dose-response and time-response related. Animals showing defects in learning and memory also showed significantly reduced amounts of nicotinic receptors in hippocampus, using alpha-bungarotoxin binding assay. The observed developmental neurotoxic effects seen for PBDE 153 are similar to those seen for PBDE 99 and for certain PCBs. Furthermore, PBDEs appear to as potent as the PCBs.}, number = {2}, journal = {Toxicology and applied pharmacology}, author = {Viberg, Henrik and Fredriksson, Anders and Eriksson, Per}, month = oct, year = {2003}, pmid = {14550744}, keywords = {Administration, Age Factors, Animals, Binding Sites, Dose-Response Relationship, Drug, Female, Flame Retardants: toxicity, Flame retardants, Halogenated Diphenyl Ethers, Hippocampus, Hippocampus: growth \& development, Hippocampus: metabolism, Inbred Strains, Male, Maze Learning, Maze Learning: drug effects, Memory, Memory: drug effects, Mice, Motor Activity, Motor Activity: drug effects, Newborn, Nicotinic, Nicotinic: biosynthesis, Oral, Phenyl Ethers, Polybrominated Biphenyls, Polybrominated Biphenyls: toxicity, Receptors, Swimming, ffr, tox}, pages = {95--106} }
@article{ ducottet_effects_2003, title = {Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice}, volume = {27}, issn = {0278-5846}, doi = {10.1016/S0278-5846(03)00051-4}, abstract = {Several recent studies on corticotropin-releasing factor ({CRF}) have suggested that this neuropeptide may play a role in depression. Consequently, {CRF} receptor antagonists have been proposed as potential new agents for the treatment of this condition. This study investigated the effects of a 4-week treatment with the well-known {CRF}(1) receptor antagonist, antalarmin, and the prototypical selective serotonin reuptake inhibitor ({SSRI}), fluoxetine, in the chronic mild stress ({CMS}) model in {BALB}/c mice. Animals were exposed to 9 weeks of {CMS} which rapidly (within 2 weeks) produced decrease of physical state ({PS}), body weight gain and blunted emotional response in the light/dark test. Chronic treatment with antalarmin (10 mg/kg ip) and fluoxetine (10 mg/kg ip) led to an improvement of {CMS}-induced modifications. These results suggest that {CRF}(1) receptor antagonists may represent potential antidepressants.}, language = {eng}, number = {4}, journal = {Progress in Neuro-Psychopharmacology \& Biological Psychiatry}, author = {Ducottet, Cecile and Griebel, Guy and Belzung, Catherine}, month = {June}, year = {2003}, pmid = {12787849}, keywords = {Animals, Depression, Disease Models, Animal, Drug Therapy, Combination, Fluoxetine, Male, Mice, Mice, Inbred {BALB} C, Pyrimidines, Pyrroles, Receptors, Corticotropin-Releasing Hormone, Serotonin Uptake Inhibitors, Stress, Psychological}, pages = {625--631} }
@Article{Lowe_2003_1248, author = {Lowe, H. C. and Jang, I. K. and Khachigian, L. M.}, journal = {Thromb.Haemost.}, note = {DA - 20031104 NOT IN FILE}, number = {5}, pages = {774-780}, title = {Animal models of vulnerable plaque. clinical context and current status}, volume = {90}, year = {2003}, keywords = {Animals, Arteriosclerosis, Disease, Models, Animal, etiology, Lipid, Metabolism, Mice, pathology, Syndrome, therapy, Thrombosis}, title_with_no_special_chars = {Animal models of vulnerable plaque Clinical context and current status} }
@article{schapiro_inhibition_2003, title = {Inhibition of bacterial {DNA} replication by zinc mobilization during nitrosative stress}, volume = {100}, issn = {0027-8424}, url = {http://www.ncbi.nlm.nih.gov/pubmed/12829799}, doi = {10.1073/pnas.1033133100}, abstract = {Phagocytic cells inhibit the growth of intracellular pathogens by producing nitric oxide (NO). NO causes cell filamentation, induction of the SOS response, and DNA replication arrest in the Gram-negative bacterium Salmonella enterica. NO also induces double-stranded chromosomal breaks in replication-arrested Salmonella lacking a functional RecBCD exonuclease. This DNA damage depends on actions of additional DNA repair proteins, the RecG helicase, and RuvC endonuclease. Introduction of a recG mutation restores both resistance to NO and the ability of an attenuated recBC mutant Salmonella strain to cause lethal infection in mice, demonstrating that bacterial DNA replication is inhibited during host-pathogen interactions. Inhibition of DNA replication during nitrosative stress is invariably accompanied by zinc mobilization, implicating DNA-binding zinc metalloproteins as critical targets of NO-related antimicrobial activity.}, number = {14}, urldate = {2009-11-13TZ}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, author = {Schapiro, Jeffrey M and Libby, Stephen J and Fang, Ferric C}, month = jul, year = {2003}, pmid = {12829799}, keywords = {Animals, Bacterial Proteins, Chromosome Breakage, Chromosomes, Bacterial, DNA Damage, DNA Helicases, DNA Repair, DNA Replication, DNA, Bacterial, Endodeoxyribonucleases, Escherichia coli Proteins, Exodeoxyribonuclease V, Exodeoxyribonucleases, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, NADPH Oxidase, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Phagocytosis, S-Nitrosothiols, Salmonella enterica, Zinc}, pages = {8496--8501} }
@article{pullen_flame_2003, title = {The flame retardants tetrabromobisphenol {A} and tetrabromobisphenol {A}-bisallylether suppress the induction of interleukin-2 receptor alpha chain ({CD}25) in murine splenocytes.}, volume = {184}, issn = {0300-483X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/12505372}, abstract = {Polybrominated flame retardants (PBF) are frequently used additives in electronical equipment. They are ubiquitous environmental contaminants which bioaccumulate with several health effects for humans and the environment. This study investigated immunotoxic effects of the PBF tetrabromobisphenol A (TBBP A), tetrabromobisphenol A-bisallylether (TBBP A-AE), tetrabromobisphenol A-bis-(2,3-dibromopropyl-ether) (TBBP A-PE), decabromodiphenylether (DBDE), and 2,4,6-tribromophenol (TBP) in vitro. The structurally related polychlorinated aromatic hydrocarbon 3,4,3',4'-tetrachlorobiphenyl (PCB77) and dioxins mediate their immunotoxicity via the Ah-receptor gene complex. A highly relevant function of the Ah receptor, the induction of CYP 1A1 in hepatocytes of C57BL/6 mice by the established inducers 3-methylcholanthrene (MC) and PCB77 was compared to the effect of PBF by measurement of ethoxyresorufin-o-deethylase (EROD) activity. The PBF did not show any induction of CYP 1A1, while EROD activity of hepatocytes exposed to MC and PCB77 was induced 10.8- and 8.7-fold, respectively. To investigate immunotoxic effects of the flame retardants, splenocytes of C57BL/6 mice were incubated with subtoxic doses of the flame retardants and PCB77 and activated by concanavalin A (Con A). The flame retardants TBBP A and TBBP A-AE significantly inhibited the expression of interleukin-2 receptor alpha chain (CD25) in contrast to TBBP A-PE, DBDE, TBP, and PCB77 as shown by immunohistochemistry and quantitative analysis by laser scanning cytometry. None of the substances had any effect on the Con A-induced production of cytokines. Hence, TBBP A and TBBP A-AE may act as immunotoxic compounds by specifically inhibiting the expression of CD25.}, number = {1}, journal = {Toxicology}, author = {Pullen, Sabine and Boecker, Ronald and Tiegs, Gisa}, month = feb, year = {2003}, pmid = {12505372}, keywords = {Animals, Cell Separation, Cell Survival, Cell Survival: drug effects, Confocal, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A1: biosynthesis, Cytokines, Cytokines: metabolism, Enzyme Induction, Enzyme Induction: drug effects, Enzyme-Linked Immunosorbent Assay, Female, Flame Retardants: toxicity, Flame retardants, Hepatocytes, Hepatocytes: drug effects, Immunohistochemistry, Inbred C57BL, Indicators and Reagents, Interleukin-2, Interleukin-2: biosynthesis, Mice, Microscopy, Polybrominated Biphenyls, Polybrominated Biphenyls: toxicity, Receptors, Solutions, Spleen, Spleen: cytology, Spleen: drug effects, Spleen: metabolism, Tetrazolium Salts, Thiazoles, frelec, tox}, pages = {11--22} }
@Article{Ivan_2002_1345, author = {Ivan, Eugen and Khatri, Jaikirshan J. and Johnson, Chad and Magid, Richard and Godin, Denis and Nandi, Sudeshna and Lessner, Susan and Galis, Zorina S.}, journal = {Circulation}, note = {10.1161/01.CIR.0000016825.17448.11 NOT IN FILE}, number = {22}, pages = {2686-2691}, title = {Expansive arterial remodeling is associated with increased neointimal macrophage foam cell content: {T}he murine model of macrophage-rich carotid artery lesions}, volume = {105}, year = {2002}, keywords = {Arteries, Carotid, Arteries, Macrophages, Matrix, Metalloproteinases, methods, Mice}, title_with_no_special_chars = {Expansive Arterial Remodeling Is Associated With Increased Neointimal Macrophage Foam Cell Content The Murine Model of MacrophageRich Carotid Artery Lesions} }
@article{ clement_genetic_2002, title = {Genetic basis of anxiety-like behaviour: a critical review}, volume = {57}, issn = {0361-9230}, shorttitle = {Genetic basis of anxiety-like behaviour}, abstract = {The way genetic and/or environmental factors influence psychiatric disorders is an enduring question in the field of human psychiatric diseases. Anxiety-related disorders provide a relevant example of how such an interaction is involved in the aetiology of a psychiatric disease. In this paper we review the literature on that subject, reporting data derived from human and rodent studies. We present in a critical way the animal models used in the studies aimed at investigating the genetic basis of anxiety, including inbred mice, selected lines, multiple marker strains, or knockout mice and review data reporting environmental components influencing anxiety-related behaviours. We conclude that anxiety is a complex behaviour, underlined not only by genetic or environmental factors but also by multiple interactions between these two factors.}, language = {eng}, number = {1}, journal = {Brain Research Bulletin}, author = {Clément, Yan and Calatayud, François and Belzung, Catherine}, month = {January}, year = {2002}, pmid = {11827738}, keywords = {Animals, Anxiety, Chromosome Mapping, Disease Models, Animal, Environment, Gene Targeting, Genetic Predisposition to Disease, Humans, Mice, Mice, Inbred Strains, Neurotransmitter Agents, Rats}, pages = {57--71} }
@Article{Hood_2002_1342, author = {Hood, J. D. and Bednarski, M. and Frausto, R. and Guccione, S. and Reisfeld, R. A. and Xiang, R. and Cheresh, D. A.}, journal = {Science}, note = {Ca50286/ca/nci P41 rr09784/rr/ncrr T32 ca09696/ca/nci Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States}, number = {5577}, pages = {2404-7}, title = {Tumor regression by targeted gene delivery to the neovasculature}, volume = {296}, year = {2002}, keywords = {Adenosine, Triphosphate/metabolism, Animals, Apoptosis, Cations, Endothelium, Vascular/cytology/metabolism/pathology, Gene, Targeting, Gene, Therapy/*methods, Gene, Transfer, Techniques, Genetic, Vectors, Humans, In, Situ, Nick-End, Labeling, Ligands, Lipids, Melanoma, Experimental/blood, supply/pathology/therapy, Mice, Mice, Inbred, BALB, C, Mutation, *Nanotechnology, Neoplasm, Metastasis, Neoplasm, Transplantation, Neoplasms, Experimental/blood, supply/pathology/*therapy, Neovascularization, Pathologic/pathology/*therapy, Proto-Oncogene, Proteins, c-raf/*genetics/metabolism, Random, Allocation, Receptors, Vitronectin/*metabolism, Tumor, Cells, Cultured}, title_with_no_special_chars = {Tumor regression by targeted gene delivery to the neovasculature} }
@Article{Lutgens_2002_1366, author = {Lutgens, E. and Gijbels, M. and Smook, M. and Heeringa, P. and Gotwals, P. and Koteliansky, V. E. and Daemen, M. J.}, journal = {Arterioscler.Thromb.Vasc.Biol.}, note = {DA - 20020617 NOT IN FILE}, number = {6}, pages = {975-982}, title = {Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression}, volume = {22}, year = {2002}, keywords = {administration, &, dosage, Animals, antagonists, &, inhibitors, Apolipoproteins, Apolipoproteins, E, Arteriosclerosis, Atherosclerosis, Carotid, Stenosis, Comparative, Study, deficiency, Disease, Progression, Drug, Administration, Schedule, drug, effects, Fibrin, Fibrosis, genetics, Hemorrhage, Immunoglobulin, Fc, Fragments, Immunoglobulin, G, Inflammation, Male, metabolism, Mice, Mice, Inbred, C57BL, Mice, Mutant, Strains, pathology, pharmacology, Phenotype, physiology, Receptors, Transforming, Growth, Factor, beta, Recombinant, Fusion, Proteins, Research, Support, Non-U.S.Gov't, Signal, Transduction, Solubility, Transforming, Growth, Factor, beta}, title_with_no_special_chars = {Transforming growth factorbeta mediates balance between inflammation and fibrosis during plaque progression} }
@article{ title = {Understanding human disease mutations through the use of interspecific genetic variation}, type = {article}, year = {2001}, identifiers = {[object Object]}, keywords = {*Evolution, Molecular,Amino Acids/genetics,Animals,Cattle,Cricetinae,Cystic Fibrosis Transmembrane Conductance Regulato,Databases, Nucleic Acid,Eye Proteins/genetics,Gene Frequency,Genetic Predisposition to Disease/*genetics,Glucosephosphate Dehydrogenase/genetics,Homeodomain Proteins/genetics,Humans,Leukocyte L1 Antigen Complex,Membrane Glycoproteins/genetics,Mice,Mutation,Neural Cell Adhesion Molecules/genetics,Paired Box Transcription Factors,Phenylalanine Hydroxylase/genetics,Phylogeny,Polymorphism, Single Nucleotide,Rats,Repressor Proteins/genetics,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, Non-P.H.S.,Research Support, U.S. Gov't, P.H.S.,Species Specificity,Tumor Suppressor Proteins,Variation (Genetics)}, pages = {2319-2328}, volume = {10}, websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689479}, id = {615db8bf-ae06-347d-a726-890771c0ab9a}, created = {2017-06-19T13:46:04.109Z}, file_attached = {true}, profile_id = {de68dde1-2ff3-3a4e-a214-ef424d0c7646}, group_id = {b2078731-0913-33b9-8902-a53629a24e83}, last_modified = {2017-06-19T13:46:04.233Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, source_type = {Journal Article}, notes = {<m:note>0964-6906 (Print)<m:linebreak/>Journal Article</m:note>}, abstract = {Data on replacement mutations in genes of disease patients exist in a variety of online resources. In addition, genome sequencing projects and individual gene sequencing efforts have led to the identification of disease gene homologs in diverse metazoan species. The availability of these two types of information provides unique opportunities to investigate factors that are important in the development of genetically based disease by contrasting long and short-term molecular evolutionary patterns. Therefore, we conducted an analysis of disease-associated human genetic variation for seven disease genes: the cystic fibrosis transmembrane conductance regulator, glucose-6-phosphate dehydrogenase, the neural cell adhesion molecule L1, phenylalanine hydroxylase, paired box 6, the X-linked retinoschisis gene and TSC2/tuberin. Our analyses indicate that disease mutations show definite patterns when examined from an evolutionary perspective. Human replacement mutations resulting in disease are overabundant at amino acid positions most conserved throughout the long-term history of metazoans. In contrast, human polymorphic replacement mutations and silent mutations are randomly distributed across sites with respect to the level of conservation of amino acid sites within genes. Furthermore, disease-causing amino acid changes are of types usually not observed among species. Using Grantham's chemical difference matrix, we find that amino acid changes observed in disease patients are far more radical than the variation found among species and in non-diseased humans. Overall, our results demonstrate the usefulness of evolutionary analyses for understanding patterns of human disease mutations and underscore the biomedical significance of sequence data currently being generated from various model organism genome sequencing projects.}, bibtype = {article}, author = {Miller, M P and Kumar, S}, journal = {Hum Mol Genet}, number = {21} }
@article{zhang_estrogen_2001, title = {Estrogen inhibits lipopolysaccharide-induced tumor necrosis factor-alpha release from murine macrophages}, volume = {23}, issn = {0379-0355}, abstract = {During their reproductive years, female have a lower risk for atherosclerosis as compared with age-matched males, although the mechanisms behind this are not clearly understood. Cytokines, including TNF-alpha play an important role in the pathogenesis of atherosclerosis. We therefore evaluated whether or not there was any difference between 17 beta-estradiol and testosterone in modulating TNF-alpha release from murine bone marrow-derived macrophages (BMM) in vitro. Cells were incubated with or without physiological concentrations (10(-10)-10(-8) M) of 17 beta-estradiol or testosterone for 48 h, followed by an additional 6 h in the absence or presence of lipopolysaccharide (LPS; 10 micrograms/ml). The amount of TNF-alpha released into the culture medium was determined with radioimmunoassay. We found that 17 beta-estradiol or testosterone alone did not affect TNF-alpha release from BMM as compared to untreated controls. Preincubation with 17 beta-estradiol significantly inhibited LPS-induced TNF-alpha release by 18.15\% (p {\textless} 0.05). 25.28\% (p {\textless} 0.05) and 40.83\% (p {\textless} 0.01) for 10(-10), 10(-9) and 10(-8) M of 17 beta-estradiol, respectively, as compared to LPS alone. In contrast, testosterone tested for 3 concentrations did not significantly effect TNF-alpha release induced by LPS. The results indicate that 17 beta-estradiol, but not testosterone, inhibits TNF-alpha release from LPS-stimulated macrophages, which may be one of the mechanisms by which estrogen protects against atherosclerosis.}, language = {eng}, number = {4}, journal = {Methods and Findings in Experimental and Clinical Pharmacology}, author = {Zhang, X. and Wang, L. and Zhang, H. and Guo, D. and Qiao, Z. and Qiao, J.}, month = may, year = {2001}, pmid = {11676224}, keywords = {Animals, Bone Marrow Cells, Cells, Cultured, Estradiol, Female, Lipopolysaccharides, Macrophages, Male, Mice, Testosterone, Tumor Necrosis Factor-alpha}, pages = {169--173} }
@article{ title = {Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development.}, type = {article}, year = {2000}, identifiers = {[object Object]}, keywords = {Animals,DNA-Binding Proteins,DNA-Binding Proteins: genetics,Ectoderm,Ectoderm: metabolism,Ectoderm: physiology,Egg Proteins,Egg Proteins: genetics,Feedback,Feedback: physiology,Fibroblast Growth Factor 4,Fibroblast Growth Factors,Fibroblast Growth Factors: genetics,Fibroblast Growth Factors: metabolism,Gene Expression Regulation, Developmental,Genes, Lethal,Hedgehog Proteins,Homeodomain Proteins,Integrases,Integrases: genetics,Limb Buds,Limb Buds: embryology,Membrane Glycoproteins,Membrane Glycoproteins: genetics,Mice,Mice, Inbred C57BL,Mice, Knockout,Mice, Transgenic,Proteins,Proteins: genetics,Proto-Oncogene Proteins,Proto-Oncogene Proteins: genetics,Proto-Oncogene Proteins: metabolism,Receptors, Cell Surface,Signal Transduction,Signal Transduction: genetics,Trans-Activators,Viral Proteins,Zona Pellucida,Zona Pellucida: physiology}, pages = {83-6}, volume = {25}, websites = {http://www.ncbi.nlm.nih.gov/pubmed/10802662}, month = {5}, id = {80cc23bf-01ef-371f-aca0-1552efb115d3}, created = {2016-04-08T12:19:42.000Z}, file_attached = {true}, profile_id = {994bc413-6766-31df-917a-32165aa30f6c}, group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e}, last_modified = {2017-03-14T10:42:46.538Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, citation_key = {Sun2000}, folder_uuids = {37786225-e8d4-483b-be04-dfc97f200748}, private_publication = {false}, abstract = {Development of the vertebrate limb bud depends on reciprocal interactions between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Sonic hedgehog (SHH) and fibroblast growth factors (FGFs) are key signalling molecules produced in the ZPA and AER, respectively. Experiments in chicks suggested that SHH expression in the ZPA is maintained by FGF4 expression in the AER, and vice versa, providing a molecular mechanism for coordinating the activities of these two signalling centres. This SHH/FGF4 feedback loop model is supported by genetic evidence showing that Fgf4 expression is not maintained in Shh-/- mouse limbs. We report here that Shh expression is maintained and limb formation is normal when Fgf4 is inactivated in mouse limbs, thus contradicting the model. We also found that maintenance of Fgf9 and Fgf17 expression is dependent on Shh, whereas Fgf8 expression is not. We discuss a model in which no individual Fgf expressed in the AER (AER-Fgf) is solely necessary to maintain Shh expression, but, instead, the combined activities of two or more AER-Fgfs function in a positive feedback loop with Shh to control limb development.}, bibtype = {article}, author = {Sun, X and Lewandoski, M and Meyers, E N and Liu, Y H and Maxson, R E and Martin, G R}, journal = {Nature genetics}, number = {1} }
@article{ belzung_flumazenil_2000, title = {Flumazenil induces benzodiazepine partial agonist-like effects in {BALB}/c but not C57BL/6 mice}, volume = {148}, issn = {0033-3158}, abstract = {{RATIONALE}: Some anxiety disorders may be treated in a different way than normal anxiety. {OBJECTIVE}: This study was aimed at investigating the action of the benzodiazepine receptor antagonist flumazenil, compared to that of the benzodiazepine receptor full agonist chlordiazepoxide, in an animal model of generalised anxiety disorder (the {BALB}/c mouse). {METHODS}: Flumazenil (0.0001, 0.001, 0. 01, 0.1 and 1 mg/kg) or chlordiazepoxide (5 mg/kg) were administered to {BALB}/c or C57BL/6 mice subjected to the light/dark test, the elevated plus maze or a passive avoidance step-through paradigm. {RESULTS}: Chlordiazepoxide and flumazenil (at all doses tested in the elevated plus maze and at the doses of 0.001 and 0.01 mg/kg in the light/dark test) induced a strong anxiolytic effect in {BALB}/c mice. Flumazenil did not induce anxiolysis in C57BL/6 mice, whatever the behavioral test or the dose used. However, chlordiazepoxide elicited anxiolysis in this strain in both procedures. In the passive avoidance test, chlordiazepoxide was amnesic in both strains but flumazenil had no effect. {CONCLUSION}: Flumazenil induces partial agonist-like effects in {BALB}/c and not in C57BL/6 mice, suggesting a possible benzodiazepine receptor set point shift toward the agonistic direction in some pathological anxiety states such as generalised anxiety disorder.}, language = {eng}, number = {1}, journal = {Psychopharmacology}, author = {Belzung, C. and Le Guisquet, A. M. and Crestani, F.}, month = {January}, year = {2000}, pmid = {10663414}, keywords = {Animals, Anxiety, Avoidance Learning, Behavior, Animal, Chlordiazepoxide, Darkness, Dose-Response Relationship, Drug, Flumazenil, {GABA} Modulators, {GABA}-A Receptor Agonists, Light, Male, Maze Learning, Mice, Mice, Inbred {BALB} C, Mice, Inbred C57BL, Species Specificity, Time Factors}, pages = {24--32} }
@article{carter_nesting_2000, title = {Nesting behavior of house mice ({Mus} domesticus) selected for increased wheel-running activity}, volume = {30}, issn = {0001-8244}, abstract = {Nest building was measured in "active" (housed with access to running wheels) and "sedentary" (without wheel access) mice (Mus domesticus) from four replicate lines selected for 10 generations for high voluntary wheel-running behavior, and from four randombred control lines. Based on previous studies of mice bidirectionally selected for thermoregulatory nest building, it was hypothesized that nest building would show a negative correlated response to selection on wheel-running. Such a response could constrain the evolution of high voluntary activity because nesting has also been shown to be positively genetically correlated with successful production of weaned pups. With wheel access, selected mice of both sexes built significantly smaller nests than did control mice. Without wheel access, selected females also built significantly smaller nests than did control females, but only when body mass was excluded from the statistical model, suggesting that body mass mediated this correlated response to selection. Total distance run and mean running speed on wheels was significantly higher in selected mice than in controls, but no differences in amount of time spent running were measured, indicating a complex cause of the response of nesting to selection for voluntary wheel running.}, language = {eng}, number = {2}, journal = {Behavior Genetics}, author = {Carter, P. A. and Swallow, J. G. and Davis, S. J. and Garland, T.}, month = mar, year = {2000}, pmid = {10979598}, keywords = {Animals, Body Weight, Female, Genotype, Male, Mice, Motor Activity, Nesting behavior, Selection, Genetic}, pages = {85--94} }
@Article{Reddick_1998_1616, author = {Reddick, R. L. and Zhang, S. H. and Maeda, N.}, journal = {Atherosclerosis}, note = {DA - 19990304 NOT IN FILE}, number = {2}, pages = {297-305}, title = {Aortic atherosclerotic plaque injury in apolipoprotein E deficient mice}, volume = {140}, year = {1998}, keywords = {Animals, Aorta, Aorta, Abdominal, Aortic, Diseases, Apolipoproteins, E, Arteriosclerosis, blood, Blood, Platelets, Cell, Division, Comparative, Study, complications, deficiency, Disease, Models, Animal, Endothelium, Vascular, etiology, Female, Fibrin, Foam, Cells, genetics, Genotype, Hyperlipidemia, injuries, Male, metabolism, Mice, Mice, Inbred, C57BL, Muscle, Smooth, Vascular, pathology, Research, Support, Non-U.S.Gov't, Research, Support, U.S.Gov't, P.H.S., Thrombosis}, title_with_no_special_chars = {Aortic atherosclerotic plaque injury in apolipoprotein E deficient mice} }
@Article{Springer_1998_1624, author = {Springer, M. L. and Chen, A. S. and Kraft, P. E. and Bednarski, M. and Blau, H. M.}, journal = {Mol Cell}, note = {Ag 09521/ag/nia F32 hl08991/hl/nhlbi Hd 18179/hd/nichd etc. Journal Article Research Support, U.S. Gov't, P.H.S. United states}, number = {5}, pages = {549-58}, title = {VEGF gene delivery to muscle: {P}otential role for vasculogenesis in adults}, volume = {2}, year = {1998}, keywords = {Acetyltransferases, Animals, Blotting, Western, Cell, Movement, Cells, Cultured, Endothelial, Growth, Factors/adverse, effects/blood/*genetics/*physiology, Endothelium, Vascular/cytology, Enzyme-Linked, Immunosorbent, Assay, Extremities/*blood, supply, Fluorescent, Antibody, Technique, Gene, Expression, *Gene, Transfer, Techniques, Genetic, Vectors, Hemangioma/blood, supply, Histone, Acetyltransferases, Lymphokines/adverse, effects/blood/*genetics/*physiology, Macrophages/cytology, Magnetic, Resonance, Imaging, Mice, Muscle, Skeletal/*blood, supply/cytology/metabolism, *Neovascularization, Physiologic, Retroviridae/genetics, *Saccharomyces, cerevisiae, Proteins, Vascular, Endothelial, Growth, Factor, A, Vascular, Endothelial, Growth, Factors}, title_with_no_special_chars = {VEGF gene delivery to muscle Potential role for vasculogenesis in adults} }
@Article{Ara_1998_1636, author = {Ara, J. and Przedborski, S. and Naini, A. B. and Jackson-Lewis, V. and Trifiletti, R. R. and Horwitz, J. and Ischiropoulos, H.}, journal = {Proc Natl Acad Sci U S A}, note = {1-k01-ns01724/ns/ninds 1-ro1-ag13966/ag/nia Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states}, number = {13}, pages = {7659-63}, title = {Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)}, volume = {95}, year = {1998}, keywords = {1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/*pharmacology, Animals, Electrophoresis, Gel, Two-Dimensional, Mice, Nitrates/*pharmacology, PC12, Cells, Rats, Superoxide, Dismutase/metabolism, Tyrosine, 3-Monooxygenase/*antagonists, &, inhibitors}, title_with_no_special_chars = {Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1methyl4phenyl1236tetrahydropyridine MPTP} }
@article{ beuzen_link_1995, title = {Link between emotional memory and anxiety states: a study by principal component analysis}, volume = {58}, issn = {0031-9384}, shorttitle = {Link between emotional memory and anxiety states}, abstract = {Numerous theoretical as well as pharmacological arguments lead to the assumption that anxiety and memory are two closely linked concepts. Nevertheless, the study of this relationship is full of complexities because neither memory nor anxiety are unitary phenomena. Indeed, the term memory covers a large number of concepts, and anxiety has been divided in two main classes, "state" and "trait" anxiety. Recently the neophobic responses exhibited by Balb/c mice confronted to the free exploratory paradigm have been proposed as a "trait anxiety" model while response exhibited in the light/dark choice procedure as a "state anxiety" one. The aim of this study was to further clarify the link between these two anxiety types and memory of emotional events assessed in the passive avoidance test. The relationship between the variables measured in these three tests were assessed by a principal component analysis that confirmed that the behavior recorded in the two anxiety tests does not reflect the same psychological state, and showed that emotional memory is linked to "state" but not "trait" anxiety.}, language = {eng}, number = {1}, journal = {Physiology \& Behavior}, author = {Beuzen, A. and Belzung, C.}, month = {July}, year = {1995}, pmid = {7667407}, keywords = {Animals, Anxiety, Arousal, Avoidance Learning, Choice Behavior, Emotions, Exploratory Behavior, Fear, Female, Male, Mental Recall, Mice, Mice, Inbred Strains, Reaction Time, Social Environment}, pages = {111--118} }
@Article{Nakashima_1994_1801, author = {Nakashima, Y. and Plump, A. S. and Raines, E. W. and Breslow, J. L. and Ross, R.}, journal = {Arterioscler.Thromb.}, note = {DA - 19940204 NOT IN FILE}, number = {1}, pages = {133-140}, title = {Apoe-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree}, volume = {14}, year = {1994}, keywords = {Animals, Aorta, Aorta, Thoracic, Apolipoproteins, E, Arteries, Arteriosclerosis, Atherosclerosis, Carotid, Arteries, Connective, Tissue, Coronary, Vessels, deficiency, Diet, Endothelium, Vascular, etiology, Humans, Hypercholesterolemia, Leukocytes, Mononuclear, Macrophages, Mice, Mice, Inbred, BALB, C, Mice, Inbred, C57BL, Mice, Transgenic, Microscopy, Electron, pathology, Pulmonary, Artery, Research, Support, Non-U.S.Gov't, Research, Support, U.S.Gov't, P.H.S., therapy}, title_with_no_special_chars = {ApoEdeficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree} }
@Article{Zhang_1994_1781, author = {Zhang, S. H. and Reddick, R. L. and Burkey, B. and Maeda, N.}, journal = {J.Clin.Invest}, note = {DA - 19941013 NOT IN FILE}, number = {3}, pages = {937-945}, title = {Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption}, volume = {94}, year = {1994}, keywords = {Animals, Aorta, Apolipoproteins, E, Arteries, Arteriosclerosis, Atherosclerosis, blood, Cholesterol, Comparative, Study, Diet, Diet, Atherogenic, Female, genetics, Heterozygote, Homozygote, Humans, Lipoproteins, Lipoproteins, HDL, Cholesterol, Liver, Macrophages, Male, metabolism, Mice, Mice, Inbred, C57BL, Mice, Inbred, Strains, Mice, Mutant, Strains, Muscle, Smooth, Vascular, pathology, Reference, Values, Research, Support, Non-U.S.Gov't, Research, Support, U.S.Gov't, P.H.S., Triglycerides, ultrastructure}, title_with_no_special_chars = {Dietinduced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption} }
@article{ belzung_hippocampal_1992, title = {Hippocampal mossy fibres: implication in novelty reactions or in anxiety behaviours?}, volume = {51}, issn = {0166-4328}, shorttitle = {Hippocampal mossy fibres}, abstract = {Hippocampal mossy fibre distribution is known to correlate with various processes including responses to novelty. Unfortunately, these correlations have been calculated using behavioural variables recorded in situations including anxiogenic components and so it is not clear whether the hippocampal trait is related to novelty reactions or to anxiety. In order to better elucidate the functional role of the supra- ({SP}-{MF}), intra-infra-({IIP}-{MF}) and dentate gyrus ({CA}4) mossy fibres synaptic area, we investigated their covariations with behavioural measures recorded in situations related to novelty (free exploration test, confrontation with a novel object) or to anxiety (light/dark choice test). The hippocampus-behaviour correlation matrix reveals that {IIP}-{MF} and {SP}-{MF} correlate with variables linked to novelty reactions while {CA}4 correlates with measures related to anxiety.}, language = {eng}, number = {2}, journal = {Behavioural Brain Research}, author = {Belzung, C.}, month = {November}, year = {1992}, pmid = {1466781}, keywords = {Animals, Anxiety, Arousal, Brain Mapping, Choice Behavior, Dark Adaptation, Exploratory Behavior, Hippocampus, Interneurons, Male, Mice, Mice, Inbred Strains, Motor Activity, Nerve Fibers, Reaction Time, Social Environment, Species Specificity, Synapses}, pages = {149--155} }
@article{mcgregor_responses_1991, title = {Responses of the {L}5178Y mouse {Lymphoma} cell forward mutation assay. {V}: 27 coded chemicals.}, volume = {17}, issn = {0893-6692}, url = {http://www.ncbi.nlm.nih.gov/pubmed/1902415}, abstract = {Twenty-seven chemicals were tested for their mutagenic potential in the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay using procedures based upon those described by McGregor et al. (McGregor DB, Martin R, Cattanach P, Edwards I, McBride D, Caspary WJ (1987): Environ Mol Mutagen 9:143-160). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Statistically significant responses were obtained with acid orange 10, aniline, benzaldehyde, o-chloroaniline, chlorodibromomethane, cytembena, 1,2-dibromo-4-(1,2-dibromomethyl) cyclohexane, dieldrin, lithocholic acid, oxytetracycline, phenazopyridine HCl, 1-phenyl-3-methyl-5-pyrazolone, sodium diethyldithiocarbamate, solvent yellow 14, tetraethylthiuram disulfide (disulfiram), 2,4-toluene diisocyanate, and 2,6-toluene diisocyanate. Apart from phenazopyridine HCl, acid orange 10, and solvent yellow 14, rat liver S9 mix was not a requirement for the mutagenic activity of these compounds. Chemical not identified as mutagens were N-4-acetylaminofluorene, chlorpheniramine maleate, chloropropamide, 1,4-dioxane, endrin, ethylene glycol, iron dextran, methapyrilene, sodium(2-ethylhexyl)alcohol}, number = {3}, journal = {Environmental and molecular mutagenesis}, author = {McGregor, D B and Brown, A G and Howgate, S and McBride, D and Riach, C and Caspary, W J}, month = jan, year = {1991}, pmid = {1902415}, keywords = {Animals, Cultured, Data Interpretation, Evaluation Studies as Topic, Flame retardants, Inbred F344, Male, Mice, Molecular Structure, Mutagenicity Tests, Mutagens, Mutagens: toxicity, Quality Control, Rats, Statistical, Thymidine Kinase, Thymidine Kinase: genetics, Trifluridine, Tumor Cells}, pages = {196--219} }
@article{ title = {DNA binding study of isophorone in rats and mice}, type = {article}, year = {1990}, identifiers = {[object Object]}, keywords = {Animals,Cyclohexanones/*metabolism,DNA/*metabolism,Female,Male,Mice,Rats,Rats, Inbred F344}, pages = {684-685}, volume = {64}, websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2090039}, edition = {1990/01/01}, id = {be1a97a7-cc9c-3bef-a0c9-625b8898ee26}, created = {2017-06-19T13:43:15.318Z}, file_attached = {false}, profile_id = {de68dde1-2ff3-3a4e-a214-ef424d0c7646}, group_id = {b2078731-0913-33b9-8902-a53629a24e83}, last_modified = {2017-06-19T13:43:15.427Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, source_type = {Journal Article}, language = {eng}, notes = {<m:note>Thier, R<m:linebreak/>Peter, H<m:linebreak/>Wiegand, H J<m:linebreak/>Bolt, H M<m:linebreak/>Letter<m:linebreak/>Germany<m:linebreak/>Archives of toxicology<m:linebreak/>Arch Toxicol. 1990;64(8):684-5.</m:note>}, bibtype = {article}, author = {Thier, R and Peter, H and Wiegand, H J and Bolt, H M}, journal = {Arch Toxicol}, number = {8} }
@article{ title = {Inhalation pharmacokinetics of isoprene in rats and mice}, type = {article}, year = {1990}, identifiers = {[object Object]}, keywords = {*Hemiterpenes,*Pentanes,Administration, Inhalation,Animals,Butadienes/administration & dosage/metabolism/*pha,Male,Mice,Rats,Rats, Inbred Strains,Respiration,Species Specificity}, pages = {89-92}, volume = {86}, websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2401276}, edition = {1990/06/01}, id = {f47847e8-c1c1-3582-8bc5-759bce22ad1c}, created = {2017-06-19T13:44:56.401Z}, file_attached = {false}, profile_id = {de68dde1-2ff3-3a4e-a214-ef424d0c7646}, group_id = {b2078731-0913-33b9-8902-a53629a24e83}, last_modified = {2017-06-19T13:44:56.548Z}, read = {false}, starred = {false}, authored = {false}, confirmed = {true}, hidden = {false}, source_type = {Journal Article}, language = {eng}, notes = {<m:note>Peter, H<m:linebreak/>Wiegand, H J<m:linebreak/>Filser, J G<m:linebreak/>Bolt, H M<m:linebreak/>Laib, R J<m:linebreak/>Comparative Study<m:linebreak/>United states<m:linebreak/>Environmental health perspectives<m:linebreak/>Environ Health Perspect. 1990 Jun;86:89-92.</m:note>}, abstract = {Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 mumole/hr/kg for rats and 400 mumole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 mumole/hr/kg for rats and 0.4 mumole/hr/kg for mice. Our data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound.}, bibtype = {article}, author = {Peter, H and Wiegand, H J and Filser, J G and Bolt, H M and Laib, R J}, journal = {Environ Health Perspect} }
@article{ belzung_benzodiazepine_1988-1, title = {Benzodiazepine antagonist {RO} 15-1788 partly reverses some anxiolytic effects of ethanol in the mouse}, volume = {95}, issn = {0033-3158}, abstract = {The effects of the benzodiazepine ({BZD}) receptor antagonist {RO} 15-1788 (3 mg/kg) on the anxiolytic properties of ethanol in mice confronted with a light/dark choice procedure and with the staircase test were investigated. {RO} 15-1788 reversed the effects of ethanol on some of the behavioural parameters without eliciting intrinsic effects when given alone. These data closely resemble those we previously obtained with several {BZD} receptor inverse agonists such as {RO} 15-3505, {RO} 15-4513 or beta-{CCM}. Since anxiogenic-like properties of low doses of {RO} 15-1788 have been identified by other authors, it is suggested that the antagonistic action of this drug against some of the behavioural effects of ethanol could be due to its being a partial {BZD} inverse agonist.}, language = {eng}, number = {4}, journal = {Psychopharmacology}, author = {Belzung, C. and Vogel, E. and Misslin, R.}, year = {1988}, pmid = {2905501}, keywords = {Animals, Anti-Anxiety Agents, Behavior, Animal, Ethanol, Flumazenil, Male, Mice}, pages = {516--519} }