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LEA (late embryogenesis abundant) proteins are intrinsically disordered proteins that contribute to stress tolerance in plants and invertebrates. Here we show that, when both plant and animal LEA proteins are co-expressed in mammalian cells with self-aggregating polyglutamine (polyQ) proteins, they reduce aggregation in a time-dependent fashion, showing more protection at early time points. A similar effect was also observed in vitro, where recombinant LEA proteins were able to slow the rate of polyQ aggregation, but not abolish it altogether. Thus, LEA proteins act as kinetic stabilisers of aggregating proteins, a novel function in protein homeostasis consistent with a proposed role as molecular shields. 相似文献
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Genome‐wide mRNA–miRNA profiling uncovers a role of the microRNA miR‐29b‐1‐5p/PHLPP1 signalling pathway in Helicobacter pylori‐driven matrix metalloproteinase production in gastric epithelial cells
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Genetica - The CRISPR/Cas (Clustered regularly interspaced short palindromic repeats/ CRISPR associated protein 9) system was discovered in bacteria and archea as an acquired immune response to... 相似文献
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Golimumab, a human anti-TNFα IgG1. monoclonal antibody, was approved in the US and Canada in April 2009 as a treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and is undergoing regulatory review in the EU for these indications. The product was developed by Centocor and Janssen Pharmaceutical KK (Johnson & Johnson subsidiaries), in collaboration with Schering-Plough and Mitsubishi Tanabe Pharma. Golimumab faces numerous protein therapeutic competitors on the market, but, as the first patient-administered, once-monthly dosed anti-TNFα drug, it will likely be an attractive option for patients.Key words: golimumab, monoclonal antibody, immunomodulator, anti-TNF, arthritis 相似文献
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Sohini Ghoshroy Manfred Binder Aurélien Tartar Deborah L Robertson 《BMC evolutionary biology》2010,10(1):198
Background
Glutamine synthetase (GS) is essential for ammonium assimilation and the biosynthesis of glutamine. The three GS gene families (GSI, GSII, and GSIII) are represented in both prokaryotic and eukaryotic organisms. In this study, we examined the evolutionary relationship of GSII from eubacterial and eukaryotic lineages and present robust phylogenetic evidence that GSII was transferred from γ-Proteobacteria (Eubacteria) to the Chloroplastida. 相似文献17.
Caterina Scoglio Walter Schumm Phillip Schumm Todd Easton Sohini Roy Chowdhury Ali Sydney Mina Youssef 《PloS one》2010,5(7)
Containing an epidemic at its origin is the most desirable mitigation. Epidemics have often originated in rural areas, with rural communities among the first affected. Disease dynamics in rural regions have received limited attention, and results of general studies cannot be directly applied since population densities and human mobility factors are very different in rural regions from those in cities. We create a network model of a rural community in Kansas, USA, by collecting data on the contact patterns and computing rates of contact among a sampled population. We model the impact of different mitigation strategies detecting closely connected groups of people and frequently visited locations. Within those groups and locations, we compare the effectiveness of random and targeted vaccinations using a Susceptible-Exposed-Infected-Recovered compartmental model on the contact network. Our simulations show that the targeted vaccinations of only 10% of the sampled population reduced the size of the epidemic by 34.5%. Additionally, if 10% of the population visiting one of the most popular locations is randomly vaccinated, the epidemic size is reduced by 19%. Our results suggest a new implementation of a highly effective strategy for targeted vaccinations through the use of popular locations in rural communities. 相似文献
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Clines, clusters, and the effect of study design on the inference of human population structure
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Previously, we observed that without using prior information about individual sampling locations, a clustering algorithm applied to multilocus genotypes from worldwide human populations produced genetic clusters largely coincident with major geographic regions. It has been argued, however, that the degree of clustering is diminished by use of samples with greater uniformity in geographic distribution, and that the clusters we identified were a consequence of uneven sampling along genetic clines. Expanding our earlier dataset from 377 to 993 markers, we systematically examine the influence of several study design variables—sample size, number of loci, number of clusters, assumptions about correlations in allele frequencies across populations, and the geographic dispersion of the sample—on the “clusteredness” of individuals. With all other variables held constant, geographic dispersion is seen to have comparatively little effect on the degree of clustering. Examination of the relationship between genetic and geographic distance supports a view in which the clusters arise not as an artifact of the sampling scheme, but from small discontinuous jumps in genetic distance for most population pairs on opposite sides of geographic barriers, in comparison with genetic distance for pairs on the same side. Thus, analysis of the 993-locus dataset corroborates our earlier results: if enough markers are used with a sufficiently large worldwide sample, individuals can be partitioned into genetic clusters that match major geographic subdivisions of the globe, with some individuals from intermediate geographic locations having mixed membership in the clusters that correspond to neighboring regions. 相似文献
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Marissa J. Stanton Samikshan Dutta Navatha Shree Polavaram Sohini Roy Michael H. Muders Kaustubh Datta 《Autophagy》2013,9(5):789-790
Understanding the molecular mechanisms promoting therapy resistance is important. Previously, we reported that VEGFC can promote cancer cell survival during stress via interaction with its receptor NRP2. While examining the molecular mechanisms involved in this survival, we performed a microarray study in which we identified two genes, WDFY1 and LAMP2, which have been suggested to function in autophagy. Our subsequent studies further confirmed the regulation of autophagy by the VEGFC-NRP2 axis in cancer during starvation- and chemotherapy-induced stress. We are currently in the process of determining the mechanism(s) through which WDFY1 and LAMP2 control autophagy; however, we did observe an increase in MTOR complex 1 (MTORC1) activity after the depletion of the VEGFC-NRP2 axis. It would therefore be interesting to study whether WDFY1 and LAMP2 can influence MTORC1 activity and regulate autophagy. Taken together, our data suggest that targeting the VEGFC-NRP2 axis in combination with chemotherapy could be an effective treatment for advanced cancers. 相似文献
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