Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen

Diagnosing type 2 diabetes using Haemoglobin A1c: A systematic review and meta-analysis of the diagnostic cut point based on microvascular complications

Aims: Diabetic microvascular complications of retinopathy, nephropathy and neuropathy may occur at hemoglobin A1c levels (HbA1c) below the 6.5% (48 mmol/mol) diagnostic threshold. Our objective was to assess the validity of the HbA1c diagnostic cutpoint of 6.5% based upon published evidence of the prevalence of retinopathy, nephropathy and neuropathy as markers of diabetes. Methods: Data Sources PubMed, Embase, Cochrane, Scopus and CINAHL from 1990-March 2019, grey literature sources. Study Selection All studies reported after 1990 (to ensure standardized HbA1c values) where HbA1c levels were presented in relation to prevalence of retinopathy, nephropathy or neuropathy in subjects not known to have diabetes. Data Extraction Studies were screened independently, data abstracted, and risk of bias appraised. Data Synthesis Data were synthesized using HbA1c categories of  55 (OR: 3.23; 95% CI 1.81–5.77), and African-American race (OR: 10.73; 95% CI: 4.34–26.55), to be associated with higher retinopathy prevalence. Marked heterogeneity in prevalence estimates was found across all meta-analyses (Cochran’s Q-statistic p  55 years and, most strikingly, in African-Americans, suggesting there may be excess microvascular complication prevalence (particularly nephropathy) in individuals below the diabetes diagnostic threshold

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Diagnosing type 2 diabetes using Hemoglobin A1c: a systematic review and meta-analysis of the diagnostic cutpoint based on microvascular complications

Aims Diabetic microvascular complications of retinopathy, nephropathy and neuropathy may occur at hemoglobin A1c levels (HbA1c) below the 6.5% (48 mmol/mol) diagnostic threshold. Our objective was to assess the validity of the HbA1c diagnostic cutpoint of 6.5% based upon published evidence of the prevalence of retinopathy, nephropathy and neuropathy as markers of diabetes. Methods Data Sources PubMed, Embase, Cochrane, Scopus and CINAHL from 1990-March 2019, grey literature sources. Study Selection All studies reported after 1990 (to ensure standardized HbA1c values) where HbA1c levels were presented in relation to prevalence of retinopathy, nephropathy or neuropathy in subjects not known to have diabetes. Data Extraction Studies were screened independently, data abstracted, and risk of bias appraised. Data Synthesis Data were synthesized using HbA1c categories of  Results Pooled mean prevalence was: 4.0%(95% CI: 3.2–5.0%) for retinopathy, 10.5% (95% CI: 4.0–19.5%) for nephropathy, 2.5% (95% CI: 1.1–4.3%) for neuropathy. Mean prevalence when stratified for HbA1c  55 (OR: 3.23; 95% CI 1.81–5.77), and African-American race (OR: 10.73; 95% CI: 4.34–26.55), to be associated with higher retinopathy prevalence. Marked heterogeneity in prevalence estimates was found across all meta-analyses (Cochran’s Q-statistic p  Conclusions The prevalence of nephropathy and moderate retinopathy was increased in subjects with HbA1c values ≥ 6.5% confirming the high specificity of this value for diagnosing T2DM; however, at HbA1c  55 years and, most strikingly, in African-Americans, suggesting there may be excess microvascular complication prevalence (particularly nephropathy) in individuals below the diabetes diagnostic threshold.Other Information Published in: Acta Diabetologica License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00592-020-01606-5</p

Nuclear pore-like structures in a compartmentalized bacterium

Planctomycetes are distinguished from other Bacteria by compartmentalization of cells via internal membranes, interpretation of which has been subject to recent debate regarding potential relations to Gram-negative cell structure. In our interpretation of the available data, the planctomycete Gemmata obscuriglobus contains a nuclear body compartment, and thus possesses a type of cell organization with parallels to the eukaryote nucleus. Here we show that pore-like structures occur in internal membranes of G.obscuriglobus and that they have elements structurally similar to eukaryote nuclear pores, including a basket, ringspoke structure, and eight-fold rotational symmetry. Bioinformatic analysis of proteomic data reveals that some of the G. obscuriglobus proteins associated with pore-containing membranes possess structural domains found in eukaryote nuclear pore complexes. Moreover, immunogold labelling demonstrates localization of one such protein, containing a β-propeller domain, specifically to the G. obscuriglobus pore-like structures. Finding bacterial pores within internal cell membranes and with structural similarities to eukaryote nuclear pore complexes raises the dual possibilities of either hitherto undetected homology or stunning evolutionary convergence

3-D reconstructions of the pore complex.

<p><b>(<i>A</i> and <i>B</i>)</b> Views of the 3-D reconstructions based on one spiral membrane from fraction 3 membranes (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169432#pone.0169432.g004" target="_blank">Fig 4A</a>). Pore complexes (arrows) are visible as embedded structures in the surface of the envelope, shown as viewed from the inner side of the spiral in Fig <b>5A</b> and from the outer side in Fig <b>5B</b>. Fig <b>5C</b> shows the basket structure of one of these pores projecting from the inner side of the membrane spiral. Bars, 20 nm. <b>(<i>D</i> and <i>E</i>)</b> Reconstruction of architecture of a single pore seen from two different angles. In panel <b><i>D</i></b>, a side view of the pore displays the basket structure with its distal ring (arrowhead) and a series of struts (arrow) connecting with the main pore rings. In panel <b><i>E</i></b>, a top view shows the ring-like element (arrowhead) of the main part of the pore and a central plug structure is visible within the pore connected to the ring’s inner rim via spokes.</p

Protein composition of <i>Gemmata obscuriglobus</i> pore-containing membrane.

<p><b>(<i>A</i>)</b> SDS-PAGE gel showing that <i>G</i>.<i>obscuriglobus</i> cells have three different types of membranes. Exclusively pore-containing membranes (fraction 3) display a characteristic protein profile distinct from that of membrane fractions which do not possess pore structures. <b>(<i>B</i>)</b> Venn diagram showing the number and distribution of proteins among the fractions and (in brackets) the number of proteins with the beta-propeller folds. The members of the beta-propeller cluster belong either exclusively to fraction 3 (4 proteins), or to fractions 3 and 2 (2 proteins), and to fractions 2, 3 and 6 (2 proteins). No beta-propeller containing proteins were found exclusively in fractions 2 or 6. <b>(<i>C</i>)</b> A beta-propeller family found in fraction 3 (pore-containing membranes), including some exclusive to fraction 3. Cluster analyses revealed a set of proteins with conserved C-terminal regions (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169432#pone.0169432.s017" target="_blank">S13</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169432#pone.0169432.s020" target="_blank">S16</a> Figs) that model beta-propeller folds with high (>95%) confidence. Models 3 (for protein ZP_02737072), 4 (ZP_02736670), 5 (ZP_02734776) and 6 (ZP_ZP_02734577) were deduced from proteins found exclusively in fraction 3 (pore-containing fraction); models 2 (for ZP_02737073) and 7 (for ZP_02733245) were deduced from proteins found in fractions 3 and 2 only; models 1 (for ZP_02737797) and 8 (for ZP_02731113)–for proteins found in fractions 3, 2, and 6 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169432#pone.0169432.s027" target="_blank">S4 Table</a>).</p