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991.
Indroneal Banerjee Jianlin Zhang Thomas Moore-Morris Emily Pfeiffer Kyle S. Buchholz Ao Liu Kunfu Ouyang Matthew J. Stroud Larry Gerace Sylvia M. Evans Andrew McCulloch Ju Chen 《PLoS genetics》2014,10(2)
Recent interest has focused on the importance of the nucleus and associated nucleoskeleton in regulating changes in cardiac gene expression in response to biomechanical load. Mutations in genes encoding proteins of the inner nuclear membrane and nucleoskeleton, which cause cardiomyopathy, also disrupt expression of a biomechanically responsive gene program. Furthermore, mutations in the outer nuclear membrane protein Nesprin 1 and 2 have been implicated in cardiomyopathy. Here, we identify for the first time a role for the outer nuclear membrane proteins, Nesprin 1 and Nesprin 2, in regulating gene expression in response to biomechanical load. Ablation of both Nesprin 1 and 2 in cardiomyocytes, but neither alone, resulted in early onset cardiomyopathy. Mutant cardiomyocytes exhibited altered nuclear positioning, shape, and chromatin positioning. Loss of Nesprin 1 or 2, or both, led to impairment of gene expression changes in response to biomechanical stimuli. These data suggest a model whereby biomechanical signals are communicated from proteins of the outer nuclear membrane, to the inner nuclear membrane and nucleoskeleton, to result in changes in gene expression required for adaptation of the cardiomyocyte to changes in biomechanical load, and give insights into etiologies underlying cardiomyopathy consequent to mutations in Nesprin 1 and 2. 相似文献
992.
Matthew R. First Steven A. Policastro Matthew J. Strom Scott C. Riley Stephanie H. Robbins-Wamsley Lisa A. Drake 《Biofouling》2014,30(6):685-693
A volumetric approach for determining the fouling burden on surfaces is presented, consisting of a 3D camera imaging system with fine (5?μm) resolution. Panels immersed in an estuary on the southwest coast of Florida, USA were imaged and the data were used to quantify seasonal changes in the biofouling community. Test panels, which were submerged in seawater for up to one?year, were analyzed before and after gentle scrubbing to quantify the biovolume of the total fouling community (ie soft and hard organisms) and the hard fouling community. Total biofouling ranged from 0.01 to 1.16?cm3 cm?2 throughout the immersion period; soft fouling constituted 22–87% of the total biovolume. In the future, this approach may be used to inform numerical models of fluid–surface interfaces and to evaluate, with high resolution, the morphology of fouling organisms in response to antifouling technologies. 相似文献
993.
Corinna Richter Ron L. Dy Rebecca E. McKenzie Bridget N.J. Watson Corinda Taylor James T. Chang Matthew B. McNeil Raymond H.J. Staals Peter C. Fineran 《Nucleic acids research》2014,42(13):8516-8526
Clustered regularly interspaced short palindromic repeats (CRISPR), in combination with CRISPR associated (cas) genes, constitute CRISPR-Cas bacterial adaptive immune systems. To generate immunity, these systems acquire short sequences of nucleic acids from foreign invaders and incorporate these into their CRISPR arrays as spacers. This adaptation process is the least characterized step in CRISPR-Cas immunity. Here, we used Pectobacterium atrosepticum to investigate adaptation in Type I-F CRISPR-Cas systems. Pre-existing spacers that matched plasmids stimulated hyperactive primed acquisition and resulted in the incorporation of up to nine new spacers across all three native CRISPR arrays. Endogenous expression of the cas genes was sufficient, yet required, for priming. The new spacers inhibited conjugation and transformation, and interference was enhanced with increasing numbers of new spacers. We analyzed ∼350 new spacers acquired in priming events and identified a 5′-protospacer-GG-3′ protospacer adjacent motif. In contrast to priming in Type I-E systems, new spacers matched either plasmid strand and a biased distribution, including clustering near the primed protospacer, suggested a bi-directional translocation model for the Cas1:Cas2–3 adaptation machinery. Taken together these results indicate priming adaptation occurs in different CRISPR-Cas systems, that it can be highly active in wild-type strains and that the underlying mechanisms vary. 相似文献
994.
Laurence Rohmer Michael A Jacobs Mitchell J Brittnacher Christine Fong Hillary S Hayden Didier Hocquet Eli J Weiss Matthew Radey Yves Germani Kaisar Ali Talukder Anthony J Hager John M Kemner Elizabeth H Sims-Day Susana Matamouros Kyle R Hager Samuel I Miller 《BMC genomics》2014,15(1)
Background
Shigella dysenteriae type 1 (Sd1) causes recurrent epidemics of dysentery associated with high mortality in many regions of the world. Sd1 infects humans at very low infectious doses (10 CFU), and treatment is complicated by the rapid emergence of antibiotic resistant Sd1 strains. Sd1 is only detected in the context of human infections, and the circumstances under which epidemics emerge and regress remain unknown.Results
Phylogenomic analyses of 56 isolates collected worldwide over the past 60 years indicate that the Sd1 clone responsible for the recent pandemics emerged at the turn of the 20th century, and that the two world wars likely played a pivotal role for its dissemination. Several lineages remain ubiquitous and their phylogeny indicates several recent intercontinental transfers. Our comparative genomics analysis reveals that isolates responsible for separate outbreaks, though closely related to one another, have independently accumulated antibiotic resistance genes, suggesting that there is little or no selection to retain these genes in-between outbreaks. The genomes appear to be subjected to genetic drift that affects a number of functions currently used by diagnostic tools to identify Sd1, which could lead to the potential failure of such tools.Conclusions
Taken together, the Sd1 population structure and pattern of evolution suggest a recent emergence and a possible human carrier state that could play an important role in the epidemic pattern of infections of this human-specific pathogen. This analysis highlights the important role of whole-genome sequencing in studying pathogens for which epidemiological or laboratory investigations are particularly challenging.Electronic supplementary material
The online version of this article (doi: 10.1186/1471-2164-15-355) contains supplementary material, which is available to authorized users. 相似文献995.
Carrie M. Gower Matthew E. K. Chang 《Critical reviews in biochemistry and molecular biology》2014,49(2):102-115
AbstractProtein kinases are key players in a large number of cellular signaling pathways. Dysregulated kinase activity has been implicated in a number of diseases, and members of this enzyme family are of therapeutic interest. However, due to the fact that most inhibitors interact with the highly conserved ATP-binding sites of kinases, it is a significant challenge to develop pharmacological agents that target only one of the greater than 500 kinases present in humans. A potential solution to this problem is the development of bisubstrate and bivalent kinase inhibitors, in which an active site-directed moiety is tethered to another ligand that targets a location outside of the ATP-binding cleft. Because kinase signaling specificity is modulated by regions outside of the ATP-binding site, strategies that exploit these interactions have the potential to provide reagents with high target selectivity. This review highlights examples of kinase interaction sites that can potentially be exploited by bisubstrate and bivalent inhibitors. Furthermore, an overview of efforts to target these interactions with bisubstrate and bivalent inhibitors is provided. Finally, several examples of the successful application of these reagents in a cellular setting are described. 相似文献
996.
997.
Linda M. McAllister-Lucas Xiaohong Jin Shufang Gu Katy Siu Scott McDonnell Jürgen Ruland Phillip C. Delekta Matthew Van Beek Peter C. Lucas 《The Journal of biological chemistry》2010,285(34):25880-25884
The CARMA1, Bcl10, and MALT1 proteins together constitute a signaling complex (CBM signalosome) that mediates antigen-dependent activation of NF-κB in lymphocytes, thereby representing a cornerstone of the adaptive immune response. Although CARMA1 is restricted to cells of the immune system, the analogous CARMA3 protein has a much wider expression pattern. Emerging evidence suggests that CARMA3 can substitute for CARMA1 in non-immune cells to assemble a CARMA3-Bcl10-MALT1 signalosome and mediate G protein-coupled receptor activation of NF-κB. Here we show that one G protein-coupled receptor, the type 1 receptor for angiotensin II, utilizes this mechanism for activation of NF-κB in endothelial and vascular smooth muscle cells, thereby inducing pro-inflammatory signals within the vasculature, a key factor in atherogenesis. Further, we demonstrate that Bcl10-deficient mice are protected from developing angiotensin-dependent atherosclerosis and aortic aneurysms. By uncovering a novel vascular role for the CBM signalosome, these findings illustrate that CBM-dependent signaling has functions outside the realm of adaptive immunity and impacts pathobiology more broadly than previously known. 相似文献
998.
Jerzy K. Kulski Silvana Gaudieri Matthew Bellgard Lois Balmer Keith Giles Hidetoshi Inoko Roger L. Dawkins 《Journal of molecular evolution》1997,45(6):599-609
Sequence analysis of a 237 kb genomic fragment from the central region of the MHC has revealed that the HLA-B and HLA-C genes
are contained within duplicated segments peri-B (53 kb) and peri-C (48 kb), respectively, and separated by an intervening
sequence (IF) of 30 kb. The peri-B and peri-C segments share at least 90% sequence homology except when interrupted by insertions/deletions
including Alu, L1, an endogenous retrovirus, and pseudogenes. The sequences of peri-B, IF, and peri-C were searched for the
presence of Alu elements to use as markers of evolution, chromosomal rearrangements, and polymorphism. Of 29 Alu elements,
14 were identified in peri-B, 11 in peri-C, and 4 in IF. The Alu elements in peri-B and peri-C clustered phylogenetically
into two clades which were classified as ``preduplication' and ``postduplication' clades. Four Alu J elements that are shared
by peri-B and peri-C and are flanked by homologous sequences in their paralogous locations, respectively, clustered into a
``preduplication' clade. By contrast, the majority of Alu elements, which are unique to either peri-B or peri-C, clustered
into a postduplication clade together with the Alu consensus subfamily members ranging from platyrrhine-specific (Spqxcg)
to catarrhine-specific Alu sequences (Y). The insertion of platyrrhine-specific Alu elements in postduplication locations
of peri-B and peri-C implies that these two segments are the products of a duplication which occurred in primates prior to
the divergence of the New World primate from the human lineage (35–44 mya). Examination of the paralogous Alu integration
sites revealed that 9 of 14 postduplication Alu sequences have produced microsatellites of different length and sequence within
the Alu 3′-poly A tail. The present analysis supports the hypothesis that HLA-B and HLA-C genes are products of an extended
segmental duplication between 44 and 81 million years ago (mya), and that subsequent diversification of both genomic segments
occurred because of the mobility and mutation of retroelements such as Alu repeats.
Received: 21 May 1997 / Accepted: 9 July 1997 相似文献
999.
1000.
Advancing ecological research with ontologies 总被引:1,自引:0,他引:1