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Kenneth W. Bayles - One of the best experts on this subject based on the ideXlab platform.
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the Biological Role of death and lysis in biofilm development
Nature Reviews Microbiology, 2007Co-Authors: Kenneth W. BaylesAbstract:Microorganisms communicate and cooperate to perform a wide range of multicellular behaviours including biofilm formation. In this Opinion, Kenneth Bayles discusses the Role of regulated bacterial cell death and lysis in biofilm development, and how this process is functionally analogous to apoptosis in eukaryotic development.
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The Biological Role of death and lysis in biofilm development.
Nature reviews. Microbiology, 2007Co-Authors: Kenneth W. BaylesAbstract:Recent studies have revealed that the regulated death of bacterial cells is important for biofilm development. Following cell death, a sub-population of the dead bacteria lyse and release genomic DNA, which then has an essential Role in intercellular adhesion and biofilm stability. This Opinion focuses on the Role of regulated cell death and lysis in biofilm development and provides a functional comparison between bacterial programmed cell death and apoptosis. The hypothesis that the differential regulation of these processes during biofilm development contributes to the antibiotic tolerance of biofilm cells is also explored.
Farhad Hormozdiari - One of the best experts on this subject based on the ideXlab platform.
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functional disease architectures reveal unique Biological Role of transposable elements
Nature Communications, 2019Co-Authors: Farhad Hormozdiari, Bryce Van De Geijn, Joseph Nasser, Omer Weissbrod, Steven Gazal, Luke J OconnorAbstract:Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze data from 41 independent diseases and complex traits to draw three conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39 ± 2% of heritability), TE explain substantially more heritability than expected based on their depletion for known functional annotations. This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring Biological function. Third, Short Interspersed Nuclear Elements (SINE) are far more enriched for blood traits than for other traits. Our results can help elucidate the Biological Roles that TE play in the genetic architecture of diseases. Transposable elements (TE) make up a large component of the human genome and have been shown to contribute to human diseases. Here, Hormozdiari et al. estimate the contribution of TEs to the heritability of 41 complex traits and diseases and find enrichment of SINEs in blood traits.
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functional disease architectures reveal unique Biological Role of transposable elements
bioRxiv, 2018Co-Authors: Farhad Hormozdiari, Bryce Van De Geijn, Joseph Nasser, Omer Weissbrod, Steven Gazal, Luke J OconnorAbstract:Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as ''junk DNA'', they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases and complex traits remains unknown. Here, we analyze data from 41 independent diseases and complex traits (average N=320K) to draw three main conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39{+/-}2% of heritability; enrichment of 0.72{+/-}0.03; 0.38-1.23 enrichment across four main TE classes), TE explain substantially more heritability than expected based on their depletion for known functional annotations (expected enrichment of 0.35{+/-}0.03; 2.11x ratio of true vs. expected enrichment). This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring Biological function; SNPs inside the oldest 20% of TE explain 2.45x more heritability than SNPs inside the youngest 20% of TE. Third, Short Interspersed Nuclear Elements (SINE; one of the four main TE classes) are far more enriched for blood traits (2.05{+/-}0.30) than for other traits (0.96{+/-}0.09); this difference is far greater than expected based on the weaker depletion of SINEs for regulatory annotations in blood compared to other tissues. Our results elucidate the Biological Roles that TE play in the genetic architecture of diseases and complex traits.
Elena Garciafruitos - One of the best experts on this subject based on the ideXlab platform.
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Biological Role of bacterial inclusion bodies a model for amyloid aggregation
FEBS Journal, 2011Co-Authors: Antonio Villaverde, Natalia Sanchez De Groot, Elena Garciafruitos, Raimon Sabate, Salvador VenturaAbstract:Inclusion bodies are insoluble protein aggregates usually found in recombinant bacteria when they are forced to produce heterologous protein species. These particles are formed by polypeptides that cross-interact through sterospecific contacts and that are steadily deposited in either the cell's cytoplasm or the periplasm. An important fraction of eukaryotic proteins form inclusion bodies in bacteria, which has posed major problems in the development of the biotechnology industry. Over the last decade, the fine dissection of the quality control system in bacteria and the recognition of the amyloid-like architecture of inclusion bodies have provided dramatic insights on the dynamic biology of these aggregates. We discuss here the relevant aspects, in the interface between cell physiology and structural biology, which make inclusion bodies unique models for the study of protein aggregation, amyloid formation and prion biology in a physiologically relevant background.
Paul G Furtmuller - One of the best experts on this subject based on the ideXlab platform.
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secreted heme peroxidase from dictyostelium discoideum insights into catalysis structure and Biological Role
Journal of Biological Chemistry, 2017Co-Authors: Andrea Nicolussi, Joe Dan Dunn, Georg Mlynek, Marzia Bellei, Marcel Zamocky, Gianantonio Battistuzzi, Kristina Djinoviccarugo, Paul G FurtmullerAbstract:Oxidation of halides and thiocyanate by heme peroxidases to antimicrobial oxidants is an important cornerstone in the innate immune system of mammals. Interestingly, phylogenetic and physiological studies suggest that homologous peroxidases are already present in mycetozoan eukaryotes such as Dictyostelium discoideum. This social amoeba kills bacteria via phagocytosis for nutrient acquisition at its single-cell stage and for antibacterial defense at its multicellular stages. Here, we demonstrate that peroxidase A from D. discoideum (DdPoxA) is a stable, monomeric, glycosylated, and secreted heme peroxidase with homology to mammalian peroxidases. The first crystal structure (2.5 A resolution) of a mycetozoan peroxidase of this superfamily shows the presence of a post-translationally-modified heme with one single covalent ester bond between the 1-methyl heme substituent and Glu-236. The metalloprotein follows the halogenation cycle, whereby compound I oxidizes iodide and thiocyanate at high rates (>108 m −1 s−1) and bromide at very low rates. It is demonstrated that DdPoxA is up-regulated and likely secreted at late multicellular development stages of D. discoideum when migrating slugs differentiate into fruiting bodies that contain persistent spores on top of a cellular stalk. Expression of DdPoxA is shown to restrict bacterial contamination of fruiting bodies. Structure and function of DdPoxA are compared with evolutionary-related mammalian peroxidases in the context of non-specific immune defense.
Volker F Wendisch - One of the best experts on this subject based on the ideXlab platform.
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transaldolase in bacillus methanolicus biochemical characterization and Biological Role in ribulose monophosphate cycle
BMC Microbiology, 2020Co-Authors: Johannes Pfeifenschneider, Benno Markert, Jessica Stolzenberger, Trygve Brautaset, Volker F WendischAbstract:The Gram-positive facultative methylotrophic bacterium Bacillus methanolicus uses the sedoheptulose-1,7-bisphosphatase (SBPase) variant of the ribulose monophosphate (RuMP) cycle for growth on the C1 carbon source methanol. Previous genome sequencing of the physiologically different B. methanolicus wild-type strains MGA3 and PB1 has unraveled all putative RuMP cycle genes and later, several of the RuMP cycle enzymes of MGA3 have been biochemically characterized. In this study, the focus was on the characterization of the transaldolase (Ta) and its possible Role in the RuMP cycle in B. methanolicus. The Ta genes of B. methanolicus MGA3 and PB1 were recombinantly expressed in Escherichia coli, and the gene products were purified and characterized. The PB1 Ta protein was found to be active as a homodimer with a molecular weight of 54 kDa and displayed KM of 0.74 mM and Vmax of 16.3 U/mg using Fructose-6 phosphate as the substrate. In contrast, the MGA3 Ta gene, which encodes a truncated Ta protein lacking 80 amino acids at the N-terminus, showed no Ta activity. Seven different mutant genes expressing various full-length MGA3 Ta proteins were constructed and all gene products displayed Ta activities. Moreover, MGA3 cells displayed Ta activities similar as PB1 cells in crude extracts. While it is well established that B. methanolicus can use the SBPase variant of the RuMP cycle this study indicates that B. methanolicus possesses Ta activity and may also operate the Ta variant of the RuMP.