The bacterial flagellum is a macromolecular protein complex that harvests energy from ion-flow across the inner membrane to power bacterial swimming in viscous fluids via rotation of the flagellar filament. Bacteria such as are capable of bi-directional flagellar rotation even though ion flow is uni-directional. How uni-directional ion-movement through the inner membrane is utilized by this macromolecular machine to drive bi-directional flagellar rotation is not understood, but a chemotactic response regulator in the cytoplasm is known to reverse the direction of rotation.
View Article and Find Full Text PDFThe bacterial flagellum is a macromolecular protein complex that harvests energy from uni-directional ion flow across the inner membrane to power bacterial swimming via rotation of the flagellar filament. Rotation is bi-directional, with binding of a cytoplasmic chemotactic response regulator controlling reversal, though the structural and mechanistic bases for rotational switching are not well understood. Here we present cryoelectron microscopy structures of intact Salmonella flagellar basal bodies (3.
View Article and Find Full Text PDFThe bacterial flagellum is a macromolecular protein complex that enables motility in many species. Bacterial flagella self-assemble a strong, multicomponent drive shaft that couples rotation in the inner membrane to the micrometre-long flagellar filament that powers bacterial swimming in viscous fluids. Here, we present structures of the intact Salmonella flagellar basal body, encompassing the inner membrane rotor, drive shaft and outer-membrane bushing, solved using cryo-electron microscopy to resolutions of 2.
View Article and Find Full Text PDFWe here introduce the third major release of the SIMPLE (Single-particle IMage Processing Linux Engine) open-source software package for analysis of cryogenic transmission electron microscopy (cryo-EM) movies of single-particles (Single-Particle Analysis, SPA). Development of SIMPLE 3.0 has been focused on real-time data processing using minimal CPU computing resources to allow easy and cost-efficient scaling of processing as data rates escalate.
View Article and Find Full Text PDFThis study's aim was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) might lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134; also known as TNFRSF4) and CD14+ monocytes expressing OX40L (CD252; also known as TNFSF4) by flow cytometric analysis. A significant difference was observed between the groups for CD14+ OX40L+ (UC: n=11, 85.
View Article and Find Full Text PDFConnective tissue growth factor (CTGF) or cellular communication network 2 (CCN2) is a matricellular protein essential for normal embryonic development and tissue repair. CTGF exhibits cell- and context-dependent activities, but CTGF function in vascular development and barrier function is unknown. We show that endothelial cells (ECs) are one of the major cellular sources of CTGF in the developing and adult retinal vasculature.
View Article and Find Full Text PDFProtein secretion through type-three secretion systems (T3SS) is critical for motility and virulence of many bacteria. Proteins are transported through an export gate containing three proteins (FliPQR in flagella, SctRST in virulence systems). A fourth essential T3SS protein (FlhB/SctU) functions to "switch" secretion substrate specificity once the growing hook/needle reach their determined length.
View Article and Find Full Text PDFBackground: To date, responsiveness to tumor necrosis factor alpha inhibitors in ulcerative colitis (UC) patients is not predictable. This is partially due to a lack of understanding of the underlying inflammatory processes. The aim of this study was to identify immunological subgroups of patients with UC and to test responsiveness to adalimumab in these subgroups in the mouse model of ulcerative colitis (UC), which is based on NOD/scid IL-2Rγ null (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMCs; NSG-UC).
View Article and Find Full Text PDFCellular communication network factor 1 (CCN1) is a dynamically expressed, matricellular protein required for vascular development and tissue repair. The gene is a presumed target of Yes-associated protein (YAP), a transcriptional coactivator that regulates cell growth and organ size. Herein, we demonstrate that the promoter is indeed a direct genomic target of YAP in endothelial cells (ECs) of new blood vessel sprouts and that deficiency in mice downregulates and alters cytoskeletal and mitogenic gene expression.
View Article and Find Full Text PDFGlucose is the preferred source of energy in activated inflammatory cells. Glucose uptake into the cell is ensured by a family of glucose uptake transporters (GLUTs), which have been identified as off-target molecules of the HIV protease inhibitor ritonavir. In this study, we examined the effect of ritonavir on inflammation and Peripheral blood mononuclear cells (PBMCs) were activated with anti-CD3 in the presence or absence of ritonavir and analyzed by flow cytometric analysis.
View Article and Find Full Text PDFIn the version of this article initially published, the PDB code associated with the study was given as 6F2E but should have been 6F2D in Table 1 and the data availability statement. The error has been corrected in the HTML and PDF versions of the article.
View Article and Find Full Text PDFExport of proteins through type III secretion systems is critical for motility and virulence of many major bacterial pathogens. Three putative integral membrane proteins (FliP, FliQ, FliR) are suggested to form the core of an export gate in the inner membrane, but their structure, assembly and location within the final nanomachine remain unclear. Here, we present the cryoelectron microscopy structure of the Salmonella Typhimurium FliP-FliQ-FliR complex at 4.
View Article and Find Full Text PDFWe projected changes in weather extremes, hydrological impacts and vulnerability to food insecurity at global warming of 1.5°C and 2°C relative to pre-industrial, using a new global atmospheric general circulation model HadGEM3A-GA3.0 driven by patterns of sea-surface temperatures and sea ice from selected members of the 5th Coupled Model Intercomparison Project (CMIP5) ensemble, forced with the RCP8.
View Article and Find Full Text PDFBiological soil crusts (biocrusts) cover about 12% of the Earth's land masses, thereby providing ecosystem services and affecting biogeochemical fluxes on a global scale. They comprise photoautotrophic cyanobacteria, algae, lichens and mosses, which grow together with heterotrophic microorganisms, forming a model system to study facilitative interactions and assembly principles in natural communities. Biocrusts can be classified into cyanobacteria-, lichen-, and bryophyte-dominated types, which reflect stages of ecological succession.
View Article and Find Full Text PDFFactor H-related protein (FHR) 1 is one of the five human FHRs that share sequence and structural homology with the alternative pathway complement inhibitor FH. Genetic studies on disease associations and functional analyses indicate that FHR-1 enhances complement activation by competitive inhibition of FH binding to some surfaces and immune proteins. We have recently shown that FHR-1 binds to pentraxin 3.
View Article and Find Full Text PDFDryland vegetation developed morphological and physiological strategies to cope with drought. However, as aridity increases, vascular plant coverage gets sparse and microbially-dominated surface communities (MSC), comprising cyanobacteria, algae, lichens and bryophytes together with heterotropic bacteria, archaea and fungi, gain relevance. Nevertheless, the relevance of MSC net primary productivity has only rarely been considered in ecosystem scale studies, and detailed information on their contribution to the total photosynthetic biomass reservoir is largely missing.
View Article and Find Full Text PDFAcute coronary syndrome is a common condition with a major global impact on healthcare resources and expenditure. International guidelines are clear in specifying that patients with acute ST-elevation myocardial infarction (STEMI) should receive urgent coronary reperfusion with either primary percutaneous coronary intervention (PCI) or thrombolysis. Although PCI is the gold standard in the treatment of STEMI, this is not always achievable in a rural hospital with no cardiac catheterization service.
View Article and Find Full Text PDFPrior studies indicate a substantial link between maternal depression and early child health but give limited consideration to the direction of this relationship or the context in which it occurs. We sought to create a contextually informed conceptual framework of this relationship through semi-structured interviews with women that had lived experience of caring for an HIV-infected child while coping with depression and anxiety symptoms. Caregivers explained their role in raising healthy children as complex and complicated by poverty, stigma, and isolation.
View Article and Find Full Text PDFRespir Med Case Rep
November 2016
Eosinophilic cholecystitis (EC) is a rare inflammatory condition of the gallbladder, confirmed by a cellular infiltrate comprised of more than 90% eosinophils in the gallbladder wall on histological examination. Although the etiology of EC is largely unknown, local autoimmune reactions within the gallbladder wall to inflammatory mediators from distal sites of inflammation have been hypothesized. Talc pleurodesis (TP) is a common clinical procedure used within respiratory medicine.
View Article and Find Full Text PDFMammalian butyrophilins have various important functions, one for lipid binding but others as ligands for co-inhibition of αβ T cells or for stimulation of γδ T cells in the immune system. The chicken BG homologues are dimers, with extracellular immunoglobulin variable (V) domains joined by cysteines in the loop equivalent to complementarity-determining region 1 (CDR1). BG genes are found in three genomic locations: BG0 on chromosome 2, BG1 in the classical MHC (the BF-BL region) and many BG genes in the BG region just outside the MHC.
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