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  • 1
    Publication Date: 2011-10-05
    Description: Increasing evidence suggests that regulatory T cell (Treg) function is impaired in chronic inflammatory diseases such as rheumatoid arthritis (RA). Here we demonstrate that Tregs are unable to modulate the spontaneous production of TNF-α from RA synovial cells cultured from the diseased synovium site. Cytokine (IL-2, IL-6, TNF-α) activated T cells (Tck), cells we previously demonstrated to mimic the effector function of pathogenic RA synovial T cells, contained Tregs that survived and divided in this cytokine environment; however, the up-regulation of key molecules associated with Treg function (CTLA-4 and LFA-1) was impaired. Furthermore, Tregs were unable to suppress the function of Tcks, including contact-dependent induction of TNF-α from macrophages, supporting the concept that impaired Treg function/responsiveness contributes to chronicity of RA. However, ectopic foxp3 expression in both Tcks and pathogenic RA synovial T cells attenuated their cytokine production and function, including contact-dependent activation of macrophages. This diminished response to cytokine activation after ectopic foxp3 expression involved inhibited NF-κB activity and differed mechanistically from that displayed endogenously in conventional Tregs. These results suggest that diseases such as RA may perpetuate owing to the inability of Tregs to control cytokine-activated T-cell function. Understanding the mechanism whereby foxp3 attenuates the pathogenic function of synovial T cells may provide insight into the mechanisms of chronicity in inflammatory disease and potentially reveal new therapeutic candidates.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2014-09-12
    Description: The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects. Scientific Reports 4 doi: 10.1038/srep06328
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 3
    Publication Date: 1999-03-05
    Description: Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elchebly, M -- Payette, P -- Michaliszyn, E -- Cromlish, W -- Collins, S -- Loy, A L -- Normandin, D -- Cheng, A -- Himms-Hagen, J -- Chan, C C -- Ramachandran, C -- Gresser, M J -- Tremblay, M L -- Kennedy, B P -- New York, N.Y. -- Science. 1999 Mar 5;283(5407):1544-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada, H3G 1Y6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10066179" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/therapy ; Dietary Fats/administration & dosage ; Gene Targeting ; Glucose Tolerance Test ; Insulin/blood/*metabolism/pharmacology ; Insulin Receptor Substrate Proteins ; Insulin Resistance ; Liver/metabolism ; Male ; Mice ; Mice, Knockout ; Muscle, Skeletal/metabolism ; Obesity/*metabolism/therapy ; Phosphoproteins/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatases/*genetics/*metabolism ; Receptor, Insulin/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-08-30
    Description: Complex gene-environment interactions are considered important in the development of obesity. The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial populations. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches, which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes, but the analyses were carried out mainly in non-intervention settings. To investigate the temporal relationships between food intake, gut microbiota and metabolic and inflammatory phenotypes, we conducted diet-induced weight-loss and weight-stabilization interventions in a study sample of 38 obese and 11 overweight individuals. Here we report that individuals with reduced microbial gene richness (40%) present more pronounced dys-metabolism and low-grade inflammation, as observed concomitantly in the accompanying paper. Dietary intervention improves low gene richness and clinical phenotypes, but seems to be less efficient for inflammation variables in individuals with lower gene richness. Low gene richness may therefore have predictive potential for the efficacy of intervention.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cotillard, Aurelie -- Kennedy, Sean P -- Kong, Ling Chun -- Prifti, Edi -- Pons, Nicolas -- Le Chatelier, Emmanuelle -- Almeida, Mathieu -- Quinquis, Benoit -- Levenez, Florence -- Galleron, Nathalie -- Gougis, Sophie -- Rizkalla, Salwa -- Batto, Jean-Michel -- Renault, Pierre -- ANR MicroObes consortium -- Dore, Joel -- Zucker, Jean-Daniel -- Clement, Karine -- Ehrlich, Stanislav Dusko -- England -- Nature. 2013 Aug 29;500(7464):585-8. doi: 10.1038/nature12480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Sante et de la Recherche Medicale, U872, Nutriomique, Equipe 7, Centre de Recherches des Cordeliers, Paris 75006, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23985875" target="_blank"〉PubMed〈/a〉
    Keywords: Basal Metabolism ; Body Weight/drug effects ; *Diet ; Diet, Carbohydrate-Restricted ; Dietary Fiber/pharmacology/therapeutic use ; Dietary Proteins/pharmacology ; Eating ; Energy Intake ; Female ; Fruit ; Gastrointestinal Tract/drug effects/*microbiology ; Gene-Environment Interaction ; Genes, Bacterial/genetics ; Humans ; Inflammation/microbiology ; Male ; Metagenome/drug effects/*genetics ; Obesity/diet therapy/microbiology ; Overweight/diet therapy/microbiology ; Vegetables ; Weight Loss/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-06-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kennedy, Daniel P -- Adolphs, Ralph -- R01 MH080721/MH/NIMH NIH HHS/ -- England -- Nature. 2011 Jun 22;474(7352):452-3. doi: 10.1038/474452a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21697937" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*physiology ; *Cities/epidemiology/statistics & numerical data ; Gyrus Cinguli/*physiology ; Humans ; Hydrocortisone/analysis ; Life Style ; Mental Disorders/epidemiology ; Mental Health/statistics & numerical data ; Rural Health/statistics & numerical data ; Stress, Psychological/blood/epidemiology/*physiopathology ; Time Factors ; Urban Health/statistics & numerical data
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-11-11
    Description: beta-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice beta-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis--as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin from nucleus accumbens in the context of chronic stress reveals beta-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish beta-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257892/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dias, Caroline -- Feng, Jian -- Sun, Haosheng -- Shao, Ning Yi -- Mazei-Robison, Michelle S -- Damez-Werno, Diane -- Scobie, Kimberly -- Bagot, Rosemary -- LaBonte, Benoit -- Ribeiro, Efrain -- Liu, XiaoChuan -- Kennedy, Pamela -- Vialou, Vincent -- Ferguson, Deveroux -- Pena, Catherine -- Calipari, Erin S -- Koo, Ja Wook -- Mouzon, Ezekiell -- Ghose, Subroto -- Tamminga, Carol -- Neve, Rachael -- Shen, Li -- Nestler, Eric J -- P50 MH096890/MH/NIMH NIH HHS/ -- R00 MH094405/MH/NIMH NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):51-5. doi: 10.1038/nature13976. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Department of Psychiatry, University of Texas Southwestern, Dallas, Texas 75390, USA. ; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383518" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics ; Animals ; DEAD-box RNA Helicases/*genetics/metabolism ; Depression/physiopathology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/*genetics/metabolism ; Neurons/metabolism ; *Resilience, Psychological ; Ribonuclease III/*genetics/metabolism ; Signal Transduction ; Stress, Physiological/*genetics ; beta Catenin/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-08-01
    Description: Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate 〈 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qin, Nan -- Yang, Fengling -- Li, Ang -- Prifti, Edi -- Chen, Yanfei -- Shao, Li -- Guo, Jing -- Le Chatelier, Emmanuelle -- Yao, Jian -- Wu, Lingjiao -- Zhou, Jiawei -- Ni, Shujun -- Liu, Lin -- Pons, Nicolas -- Batto, Jean Michel -- Kennedy, Sean P -- Leonard, Pierre -- Yuan, Chunhui -- Ding, Wenchao -- Chen, Yuanting -- Hu, Xinjun -- Zheng, Beiwen -- Qian, Guirong -- Xu, Wei -- Ehrlich, S Dusko -- Zheng, Shusen -- Li, Lanjuan -- England -- Nature. 2014 Sep 4;513(7516):59-64. doi: 10.1038/nature13568. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China [3]. ; 1] State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China [2]. ; 1] Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France [2]. ; State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China. ; Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France. ; 1] State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China. ; 1] Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France [2] King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London Bridge, London SE1 9RT, UK. ; 1] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China [2] Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University, 310003 Hangzhou, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079328" target="_blank"〉PubMed〈/a〉
    Keywords: Case-Control Studies ; Chronic Disease ; Diabetes Mellitus, Type 2/microbiology ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Genetic Markers/genetics ; Health ; Humans ; Inflammatory Bowel Diseases/microbiology ; Liver Cirrhosis/*diagnosis/*microbiology ; *Metagenomics ; Microbiota/*genetics/*physiology ; Mouth/microbiology ; Phylogeny ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2012-08-04
    Description: A large-scale geographical study of the ice pack in the seasonal ice zone of the Weddell Sea, Antarctica, took place from September to October 2006. Sea ice brines with a salinity greater than 58 and temperature lower than −3.6°C were sampled from 22 ice stations. The brines had large deficits in total alkalinity and in the concentrations of the major dissolved macronutrients (total dissolved inorganic carbon, nitrate, and soluble reactive phosphorus) relative to their concentrations in the surface oceanic water and conservative behavior during seawater freezing. The concentration deficits were related to the dissolved inorganic carbon-consuming processes of photosynthesis, CaCO3 precipitation, and CO2 degassing. The largest concentration deficits in total dissolved inorganic carbon were found to be associated with CaCO3 precipitation and CO2 degassing, because the magnitude of the photosynthesis-induced concentration deficit in total dissolved inorganic carbon is controlled by the size of the inorganic nutrient pool, which can be limited in sea ice by its openness to exchange with the surrounding oceanic water.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 9
    Publication Date: 2013-10-30
    Description: A set S of nodes in a graph G = ( V , E ) is independent if no two nodes in S are adjacent. We present two types of self-stabilizing algorithms for finding disjoint independent sets R and B . In one type, R is maximal independent in G and B is maximal independent in the induced subgraph G [ V – R ]. In the second type, R is maximal independent in G [ V – B ] and B is maximal independent in G [ V – R ]. Both the central and distributed schedulers are considered.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
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  • 10
    Publication Date: 2014-01-29
    Description: High spectral resolution (~80 000) and signal-to-noise observations from the Ultraviolet and Visual Echelle Spectrograph Paranal Observatory Project (UVES-POP) are used to study the interstellar molecular lines CN (3874 Å), CH + (3957, 4232 Å) and CH (3886, 4300 Å) towards 74 O- and B-type stellar sightlines. Additionally, archive data are presented for 140 ELODIE early-type stellar sightlines at R  = 42 000, plus 25 FEROS at R  = 48 000 and 3 UVES at R  〉 50 000, mainly in the CH + (4232 Å) and CH (3886, 4300 Å) transitions. Detection rates are ~45 per cent for CN and ~67 per cent for the other lines in the POP sample, and ~10–15 per cent for CH + and CH lines in the additional sample. CH and CH + are well correlated between log[ N (CH) cm –2 ]~12–14, implying that these clouds are CH + -like CH and not CN-like CH. CH is also very well correlated with Na i D in the range log[ N (Na i cm –2 ]) ~12.2–14.2. A few sightlines show tentative velocity shifts of ~2 km s –1 between CH and CH + , which appear to be caused by differences in component strength in blends, and hence do not provide firm evidence for shocks. Finally, we describe a search for 13 CH + in a sightline towards HD 76341. No 13 CH + is detected, placing a limit on the 13 CH + to 12 CH + ratio of ~0.01. If a formal fit is attempted, the equivalent width ratio in the two isotopes is a factor ~90 but with large errors.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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