197 research outputs found
Antiretroviral Therapy during Tuberculosis Treatment and Marked Reduction in Death Rate of HIV-Infected Patients, Thailand1
Antiretroviral therapy is associated with a substantial reduction in deaths during TB treatment for HIV-infected TB patients
IKKβ regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways
Vascular endothelium provides a selective barrier between the blood and tissues, participates in wound healing and angiogenesis, and regulates tissue recruitment of inflammatory cells. Nuclear factor (NF)-κB transcription factors are pivotal regulators of survival and inflammation, and have been suggested as potential therapeutic targets in cancer and inflammatory diseases. Here we show that mice lacking IKKβ, the primary kinase mediating NF-κB activation, are smaller than littermates and born at less than the expected Mendelian frequency in association with hypotrophic and hypovascular placentae. IKKβ-deleted endothelium manifests increased vascular permeability and reduced migration. Surprisingly, we find that these defects result from loss of kinase-independent effects of IKKβ on activation of the serine-threonine kinase, Akt. Together, these data demonstrate essential roles for IKKβ in regulating endothelial permeability and migration, as well as an unanticipated connection between IKKβ and Akt signalling
Comparison of the microbial composition of African fermented foods using amplicon sequencing
Fermented foods play a major role in the diet of people in Africa, where a wide variety of raw materials
are fermented. Understanding the microbial populations of these products would help in the design of
specific starter cultures to produce standardized and safer foods. In this study, the bacterial diversity of
African fermented foods produced from several raw materials (cereals, milk, cassava, honey, palm sap,
and locust beans) under different conditions (household, small commercial producers or laboratory) in 8
African countries was analysed by 16S rRNA gene amplicon sequencing during the Workshop “Analysis
of the Microbiomes of Naturally Fermented Foods Training Course”. Results show that lactobacilli
were less abundant in fermentations performed under laboratory conditions compared to artisanal or
commercial fermentations. Excluding the samples produced under laboratory conditions, lactobacilli
is one of the dominant groups in all the remaining samples. Genera within the order Lactobacillales
dominated dairy, cereal and cassava fermentations. Genera within the order Lactobacillales, and genera
Zymomonas and Bacillus were predominant in alcoholic beverages, whereas Bacillus and Lactobacillus
were the dominant genera in the locust bean sample. The genus Zymomonas was reported for the first
time in dairy, cereal, cassava and locust bean fermentations
Vitronectin Increases Vascular Permeability by Promoting VE-Cadherin Internalization at Cell Junctions
Cross-talk between integrins and cadherins regulates cell function. We tested the hypothesis that vitronectin (VN), a multi-functional adhesion molecule present in the extracellular matrix and plasma, regulates vascular permeability via effects on VE-cadherin, a critical regulator of endothelial cell (EC) adhesion.Addition of multimeric VN (mult VN) significantly increased VE-cadherin internalization in human umbilical vein EC (HUVEC) monolayers. This effect was blocked by the anti-α(V)β(3) antibody, pharmacological inhibition and knockdown of Src kinase. In contrast to mult VN, monomeric VN did not trigger VE-cadherin internalization. In a modified Miles assay, VN deficiency impaired vascular endothelial growth factor-induced permeability. Furthermore, ischemia-induced enhancement of vascular permeability, expressed as the ratio of FITC-dextran leakage from the circulation into the ischemic and non-ischemic hindlimb muscle, was significantly greater in the WT mice than in the Vn(-/-) mice. Similarly, ischemia-mediated macrophage infiltration was significantly reduced in the Vn(-/-) mice vs. the WT controls. We evaluated changes in the multimerization of VN in ischemic tissue in a mouse hindlimb ischemia model. VN plays a previously unrecognized role in regulating endothelial permeability via conformational- and integrin-dependent effects on VE-cadherin trafficking.These results have important implications for the regulation of endothelial function and angiogenesis by VN under normal and pathological conditions
Eph-B4 prevents venous adaptive remodeling in the adult arterial environment
Stimulation of Eph-B4 prevents adaptive remodeling and preserves venous identity when veins are surgically placed into an arterial environment
Vascular permeability, vascular hyperpermeability and angiogenesis
The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both provide useful but complementary information. Vascular permeability by any measure is dramatically increased in acute and chronic inflammation, cancer, and wound healing. This hyperpermeability is mediated by acute or chronic exposure to vascular permeabilizing agents, particularly vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A). We demonstrate that three distinctly different types of vascular permeability can be distinguished, based on the different types of microvessels involved, the composition of the extravasate, and the anatomic pathways by which molecules of different size cross-vascular endothelium. These are the basal vascular permeability (BVP) of normal tissues, the acute vascular hyperpermeability (AVH) that occurs in response to a single, brief exposure to VEGF-A or other vascular permeabilizing agents, and the chronic vascular hyperpermeability (CVH) that characterizes pathological angiogenesis. Finally, we list the numerous (at least 25) gene products that different authors have found to affect vascular permeability in variously engineered mice and classify them with respect to their participation, as far as possible, in BVP, AVH and CVH. Further work will be required to elucidate the signaling pathways by which each of these molecules, and others likely to be discovered, mediate the different types of vascular permeability
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