Search results for "Tos"
showing 10 items of 12217 documents
Molecular Mechanism of Inhibition of DNA Methylation by Zebularine
2017
In this work, we have analyzed the molecular mechanism of inhibition of a C5-DNA methyltransferase by zebularine using classical and QM/MM simulations. We found that the reaction proceeds with the addition of an unprotonated cysteine to the C6 position of the ring followed by methyl transfer to the C5 position. However, while the first step is reversible and presents a moderate free-energy barrier, the second step presents a large free-energy barrier, preventing the formation of the methylated complex. This mechanistic proposal agrees with recent experimental observations that point to the formation of a reversible covalent complex between DNA containing zebularine and methyltransferases. T…
IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice
2019
Background In people with SLE and in the MRL- Fas lpr lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ. Methods To investigate whether IL-34–dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL- Fas lpr mice expressing IL-34 and IL-34 knockout (KO) MRL- Fas lpr mice. We also assessed expression of IL-34 and the cFMS and PTPRZ receptors in patients with lupus nephritis. Results Intrarenal IL-3…
Fermentation of Nocellara Etnea table olives by functional starter cultures at different low salt concentrations
2018
Nocellara Etnea is one of the main Sicilian cultivars traditionally used to produce both olive oil and naturally fermented table olives. In the present study, the effect of different salt concentrations on physico-chemical, microbiological, sensorial, and volatile organic compounds (VOCs) formation was evaluated in order to obtain functional Nocellara Etnea table olives. The experimental design consisted of 8 treatments as follow: fermentations at 4, 5, 6, and 8% of salt with (E1-E4 samples) and without (C1-C4 samples) the addition of starters. All the trials were carried out at room temperature (18 +/- 2 degrees C) and monitored for an overall period of 120 d. In addition, the persistence …
Ethanol Production by Selected Intestinal Microorganisms and Lactic Acid Bacteria Growing under Different Nutritional Conditions
2016
To gain some specific insight into the roles microorganisms might play in non-alcoholic fatty liver disease (NAFLD), some intestinal and lactic acid bacteria and one yeast (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) were characterized by high performance liquid chromatography for production of ethanol when grown on different carbohydrates: hexoses (glucose and fructose), pentoses (arabinose and ribose), disaccharides (lactose and lactulose), and inulin. Highest amounts of ethanol were produced by S. …
The Anti-apoptotic Murine Cytomegalovirus Protein vMIA-m38.5 Induces Mast Cell Degranulation.
2020
Mast cells (MC) represent "inbetweeners" of the immune system in that they are part of innate immunity by acting as first-line sentinels for environmental antigens but also provide a link to adaptive immunity by secretion of chemokines that recruit CD8 T cells to organ sites of infection. An interrelationship between MC and cytomegalovirus (CMV) has been a blank area in science until recently when the murine model revealed a role for MC in the resolution of pulmonary infection by murine CMV (mCMV). As to the mechanism, MC were identified as a target cell type of mCMV. Infected MC degranulate and synthesize the CC-chemokine ligand-5 (CCL-5), which is released to attract protective virus-spec…
The macroecology of cancer incidences in humans is associated with large-scale assemblages of endemic infections.
2018
8 pages; International audience; It is now well supported that 20% of human cancers have an infectious causation (i.e., oncogenic agents). Accumulating evidence suggests that aside from this direct role, other infectious agents may also indirectly affect cancer epidemiology through interactions with the oncogenic agents within the wider infection community. Here, we address this hypothesis via analysis of large-scale global data to identify associations between human cancer incidence and assemblages of neglected infectious agents. We focus on a gradient of three widely-distributed cancers with an infectious cause: bladder (~2% of recorded cancer cases are due to Shistosoma haematobium), liv…
High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and…
2016
Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thic…
Population Genetics of Latvians in the Context of Admixture between North-Eastern European Ethnic Groups
2018
Abstract This article presents a review on population genetics of Latvians, which alongside Lithuanians are the two extant Baltic speaking populations. The article provides a description of genome-wide single nucleotide polymorphism (SNP) data and contains a comparative analysis of the results of studies performed on classical autosomal genetic markers, mitochondrial DNA (mtDNA) and the non-recombining part of the Y chromosome (NRY), with data on neighbouring populations. The study also covers data of recently performed ancient DNA (aDNA) studies carried out on samples from the territory of today’s Latvia. The results of population genetic studies have shown a mixture of eastern and western…
Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor
2017
Bacteria use membrane-integral sensor histidine kinases (HK) to perceive stimuli and transduce signals from the environment to the cytosol. Information on how the signal is transmitted across the membrane by HKs is still scarce. Combining both liquid- and solid-state NMR, we demonstrate that structural rearrangements in the extracytoplasmic, citrate-sensing Per-Arnt-Sim (PAS) domain of HK CitA are identical for the isolated domain in solution and in a longer construct containing the membrane-embedded HK and lacking only the kinase core. We show that upon citrate binding, the PAS domain contracts, resulting in a shortening of the C-terminal β-strand. We demonstrate that this contraction of t…
The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism.
2018
Hydrolysis reaction marks the basis of life yet the mechanism of this crucial biochemical reaction is not completely understood. We recently reported the mechanisms of hydrolysis of nucleoside triphosphate and phosphate monoester. These two reactions hydrolyze P-O-P and P-O-C linkages, respectively. Here, we present the mechanism of hydrolysis of δ-6-phosphogluconolactone, which is an important precursor in the second step of the pentose phosphate pathway. Its hydrolysis requires the cleavage of C-O-C linkage and its mechanism is hitherto unknown. We report three mechanisms of hydrolysis of δ-6-phosphogluconolactone based on density functional computations. In the energetically most favorab…