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91.
Experimental structure determination continues to be challenging for membrane proteins. Computational prediction methods are therefore needed and widely used to supplement experimental data. Here, we re‐examined the state of the art in transmembrane helix prediction based on a nonredundant dataset with 190 high‐resolution structures. Analyzing 12 widely‐used and well‐known methods using a stringent performance measure, we largely confirmed the expected high level of performance. On the other hand, all methods performed worse for proteins that could not have been used for development. A few results stood out: First, all methods predicted proteins in eukaryotes better than those in bacteria. Second, methods worked less well for proteins with many transmembrane helices. Third, most methods correctly discriminated between soluble and transmembrane proteins. However, several older methods often mistook signal peptides for transmembrane helices. Some newer methods have overcome this shortcoming. In our hands, PolyPhobius and MEMSAT‐SVM outperformed other methods. Proteins 2015; 83:473–484. © 2014 Wiley Periodicals, Inc. 相似文献
92.
Adalid-Peralta L Fragoso G Fleury A Sciutto E 《International journal of biological sciences》2011,7(9):1412-1426
To fulfill its function, the immune system must detect and interpret a wide variety of signals and adjust the magnitude, duration, and specific traits of each response during the complex host-parasite relationships in parasitic infections. Inflammation must be tightly regulated since uncontrolled inflammation may be as destructive as the triggering stimulus and leads to immune-mediated tissue injury. During recent years, increasing evidence points to regulatory T cells (Tregs) as key anti-inflammatory cells, critically involved in limiting the inflammatory response. Herein, we review the published information on the induction of Tregs and summarize the most recent findings on Treg generation in parasitic diseases. 相似文献
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Marvin Schulz Falko Krause Nicolas Le Novère Edda Klipp Wolfram Liebermeister 《Molecular systems biology》2011,7(1)
The exploding number of computational models produced by Systems Biologists over the last years is an invitation to structure and exploit this new wealth of information. Researchers would like to trace models relevant to specific scientific questions, to explore their biological content, to align and combine them, and to match them with experimental data. To automate these processes, it is essential to consider semantic annotations, which describe their biological meaning. As a prerequisite for a wide range of computational methods, we propose general and flexible similarity measures for Systems Biology models computed from semantic annotations. By using these measures and a large extensible ontology, we implement a platform that can retrieve, cluster, and align Systems Biology models and experimental data sets. At present, its major application is the search for relevant models in the BioModels Database, starting from initial models, data sets, or lists of biological concepts. Beyond similarity searches, the representation of models by semantic feature vectors may pave the way for visualisation, exploration, and statistical analysis of large collections of models and corresponding data. 相似文献
96.
Background & Aims
CCL25/CCR9 is a non-promiscuous chemokine/receptor pair and a key regulator of leukocyte migration to the small intestine. We investigated here whether CCL25/CCR9 interactions also play a role in the regulation of inflammatory responses in the large intestine.Methods
Acute inflammation and recovery in wild-type (WT) and CCR9−/− mice was studied in a model of dextran sulfate sodium (DSS)-induced colitis. Distribution studies and phenotypic characterization of dendritic cell subsets and macrophage were performed by flow cytometry. Inflammatory bowel disease (IBD) scores were assessed and expression of inflammatory cytokines was studied at the mRNA and the protein level.Results
CCL25 and CCR9 are both expressed in the large intestine and are upregulated during DSS colitis. CCR9−/− mice are more susceptible to DSS colitis than WT littermate controls as shown by higher mortality, increased IBD score and delayed recovery. During recovery, the CCR9−/− colonic mucosa is characterized by the accumulation of activated macrophages and elevated levels of Th1/Th17 inflammatory cytokines. Activated plasmacytoid dendritic cells (DCs) accumulate in mesenteric lymph nodes (MLNs) of CCR9−/− animals, altering the local ratio of DC subsets. Upon re-stimulation, T cells isolated from these MLNs secrete significantly higher levels of TNFα, IFNγ, IL2, IL-6 and IL-17A while down modulating IL-10 production.Conclusions
Our results demonstrate that CCL25/CCR9 interactions regulate inflammatory immune responses in the large intestinal mucosa by balancing different subsets of dendritic cells. These findings have important implications for the use of CCR9-inhibitors in therapy of human IBD as they indicate a potential risk for patients with large intestinal inflammation. 相似文献97.
Joke Vandewalle Marijke Bauters Hilde Van Esch Stefanie Belet Jelle Verbeeck Nathalie Fieremans Maureen Holvoet Jodie Vento Ana Spreiz Dieter Kotzot Edda Haberlandt Jill Rosenfeld Joris Andrieux Bruno Delobel Marie-Bertille Dehouck Koen Devriendt Jean-Pierre Fryns Peter Marynen Amy Goldstein Guy Froyen 《Human genetics》2013,132(10):1177-1185
Loss-of-function mutations in several different neuronal pathways have been related to intellectual disability (ID). Such mutations often are found on the X chromosome in males since they result in functional null alleles. So far, microdeletions at Xq24 reported in males always have been associated with a syndromic form of ID due to the loss of UBE2A. Here, we report on overlapping microdeletions at Xq24 that do not include UBE2A or affect its expression, in patients with non-syndromic ID plus some additional features from three unrelated families. The smallest region of overlap, confirmed by junction sequencing, harbors two members of the mitochondrial solute carrier family 25, SLC25A5 and SLC25A43. However, identification of an intragenic microdeletion including SLC25A43 but not SLC25A5 in a healthy boy excluded a role for SLC25A43 in cognition. Therefore, our findings point to SLC25A5 as a novel gene for non-syndromic ID. This highly conserved gene is expressed ubiquitously with high levels in cortex and hippocampus, and a presumed role in mitochondrial exchange of ADP/ATP. Our data indicate that SLC25A5 is involved in memory formation or establishment, which could add mitochondrial processes to the wide array of pathways that regulate normal cognitive functions. 相似文献
98.
Kari E. Ellingsen Nigel G. Yoccoz Torkild Tveraa Kenneth T. Frank Edda Johannesen Marti J. Anderson Andrey V. Dolgov Nancy L. Shackell 《Global Change Biology》2020,26(5):2897-2907
Determining the importance of physical and biological drivers in shaping biodiversity in diverse ecosystems remains a global challenge. Advancements have been made towards this end in large marine ecosystems with several studies suggesting environmental forcing as the primary driver. However, both empirical and theoretical studies point to additional drivers of changes in diversity involving trophic interactions and, in particular, predation. Moreover, a more integrated but less common approach to the assessment of biodiversity changes involves analyses of spatial β diversity, whereas most studies to date assess only changes in species richness (α diversity). Recent research has established that when cod, a dominant generalist predator, was overfished and collapsed in a northwest Atlantic food web, spatial β diversity increased; that is, the spatial structure of the fish assemblage became increasingly heterogeneous. If cod were to recover, would this situation be reversible, given the inherent complexity and non‐linear dynamics that typify such systems? A dramatic increase of cod in an ecologically similar large marine ecosystem may provide an answer. Here we show that spatial β diversity of fish assemblages in the Barents Sea decreased with increasing cod abundance, while decadal scale changes in temperature did not play a significant role. These findings indicate a reversibility of the fish assemblage structure in response to changing levels of an apex predator and highlight the frequently overlooked importance of trophic interactions in determining large‐scale biodiversity patterns. As increased cod abundance was largely driven by changes in fisheries management, our study also shows that management policies and practices, particularly those involving apex predators, can have a strong effect in shaping spatial diversity patterns, and one should not restrict the focus to effects of climate change alone. 相似文献
99.
Junliang Hao Veronique Dehlinger Adam M. Fivush Helene C.E. Rudyk Thomas C. Britton Sean P. Hollinshead Benjamin P. Vokits Barry P. Clark Steven S. Henry Steven M. Massey Langu Peng Bruce A. Dressman Beverly A. Heinz Edda F. Roberts Mallorie R. Bracey-Walker Steven Swanson John T. Catlow Patrick L. Love James A. Monn 《Bioorganic & medicinal chemistry letters》2013,23(5):1249-1252
A novel series of selective negative allosteric modulators (NAMs) for metabotropic glutamate receptor 5 (mGlu5) was discovered from an isothiazole scaffold. One compound of this series, (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide (24), demonstrated satisfactory pharmacokinetic properties and, following oral dosing in rats, produced dose-dependent and long-lasting mGlu5 receptor occupancy. Consistent with the hypothesis that blockade of mGlu5 receptors will produce analgesic effects in mammals, compound 24 produced a dose-dependent reduction in paw licking responses in the formalin model of persistent pain. 相似文献