58 research outputs found

    Proteolysis of Human Thrombin Generates Novel Host Defense Peptides

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    The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P. aeruginosa sepsis, as well as lipopolysaccharide-induced shock. Moreover, the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes, features typical of “classical” helical antimicrobial peptides. These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion

    Morphology of the first instar larva of obligatory traumatic myiasis agents (Diptera: Calliphoridae, Sarcophagidae)

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    There are only three fly species that are obligate agents of traumatic myiasis of humans and livestock: a single species of flesh fly, Wohlfahrtia magnifica (Sarcophagidae), and two species of blow flies, Chrysomya bezziana and Cochliomyia hominivorax (Calliphoridae). The morphology of their first instar larvae is thoroughly and consistently documented here with light microscopy photographs and scanning electron microscopy micrographs. The following morphological structures are documented: pseudocephalon, antennal complex, maxillary palpus, oral ridges, thoracic and abdominal spinulation, spiracular field, posterior spiracles and cephaloskeleton. New diagnostic features drawn from the cephaloskeleton and the spinulation of abdominal segments, including the anal pad, are discovered and extensively described. Earlier descriptions in the literature are revisited, and major discrepancies between these and the results of the current study are discussed. The present results allow clarification, correction and, especially, complementation of information provided by earlier authors. The relatively distant taxonomic position of all three species is evidence that obligatory myiasis has arisen independently, and the extensively similar morphology in the first instar larvae of Chrysomya bezziana, Cochliomyia hominivorax and W. magnifica in comparison to necrophagous species, especially the enhancement of the anterior part of the cephaloskeleton and the segmental spinulation, is therefore best interpreted as homoplasic adaptations to a life strategy as obligate vertebrate parasites. An identification key for first instar larvae of all obligatory traumatic myiasis agents of mammals is provided.Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited

    Functional characterization of the human myosin-7a motor domain

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    Myosin-7a participates in auditory and visual processes. Defects in MYO7A, the gene encoding the myosin-7a heavy chain, are causative for Usher syndrome 1B, the most frequent cause of deaf-blindness in humans. In the present study, we performed a detailed kinetic and functional characterization of the isolated human myosin-7a motor domain to elucidate the details of chemomechanical coupling and the regulation of motor function. A rate-limiting, slow ADP release step causes long lifetimes of strong actin-binding intermediates and results in a high duty ratio. Moreover, our results reveal a Mg2+-sensitive regulatory mechanism tuning the kinetic and mechanical properties of the myosin-7a motor domain. We obtained direct evidence that changes in the concentration of free Mg2+ ions affect the motor properties of human myosin-7a using an in vitro motility assay system. Our results suggest that in a cellular environment, compartment-specific fluctuations in free Mg2+ ions can mediate the conditional switching of myosin-7a between cargo moving and tension bearing modes

    The dimensions of prosociality: a cross-cultural lexical analysis

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    The West is usually portrayed as relatively individualistic. It is further argued that this tendency has influenced academia, leading to an underappreciation of the importance of prosociality. In the interest of exploring this topic, an enquiry was conducted into conceptualisations of prosociality across the world’s cultures. This enquiry focused on so-called untranslatable words, i.e., which lack an exact translation into another language (in this case, English). Through a quasi-systematic search of academic and grey literature, together with additional data collection, over 200 relevant terms were located. An adapted form of grounded theory identified five dimensions: socialising/congregating; morals/ethics; compassion/kindness; interaction/communication; and communality. The analysis sheds light on the dynamics of prosociality, as understood by cultures across the globe. Moreover, the roster of terms featured have the potential to enrich the nomological network in psychology, allowing for a richer conceptualisation of the social dimensions of human functioning

    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    Myosin cleft movement and its coupling to actomyosin dissociation

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    It has long been known that binding of actin and nucleotides to myosin are antagonistic, an observation that led to the biochemical basis for the crossbridge cycle of muscle contraction. Thus ATP binding to actomyosin causes actin dissociation, while actin binding to the myosin accelerates ADP and phosphate release. Structural studies have indicated that communication between the actin and nucleotide binding sites involves the opening and closing of the cleft between the upper and lower 50K domains of the myosin he ad. Here we test the proposal that the cleft responds to actin and nucleotide binding in a reciprocal manner and show that cleft movement is coupled to actin binding and dissociation. We monitored cleft movement using pyrene excimer fluorescence from probes engineered across the cleft
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