404 research outputs found

    α6ß4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of α3ß1 integrin

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    Growth factor-induced cell migration and proliferation are essential for epithelial wound repair. Cell migration during wound repair also depends upon expression of laminin-5, a ligand for α6ß4 integrin. We investigated the role of α6ß4 integrin in laminin-5-dependent keratinocyte migration by re-expressing normal or attachment-defective ß4 integrin in ß4 integrin null keratinocytes. We found that expression of ß4 integrin in either a ligand bound or ligand unbound state was necessary and sufficient for EGF-induced cell migration. In a ligand bound state, ß4 integrin supported EGF-induced cell migration though sustained activation of Rac1. In the absence of α6ß4 integrin ligation, Rac1 activation became tempered and EGF chemotaxis proceeded through an alternate mechanism that depended upon α3ß1 integrin and was characterized by cell scattering. α3ß1 integrin also relocalated from cell-cell contacts to sites of basal clustering where it displayed increased conformational activation. The aberrant distribution and activation of α3ß1 integrin in attachment-defective ß4 cells could be reversed by the activation of Rac1. Conversely, in WT ß4 cells the normal cell-cell localization of α3ß1 integrin became aberrant after the inhibition of Rac1. These studies indicate that the extracellular domain of ß4 integrin, through its ability to bind ligand, functions to integrate the divergent effects of growth factors on the cytoskeleton and adhesion receptors so that coordinated keratinocyte migration can be achieved

    Parasite-stress promotes in-group assortative sociality: the cases of strong family ties and heightened religiosity

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    Throughout the world people differ in the magnitude with which they value strong family ties or heightened religiosity. We propose that this cross-cultural variation is a result of a contingent psychological adaptation that facilitates in-group assortative sociality in the face of high levels of parasite-stress while devaluing in-group assortative sociality in areas with low levels of parasite-stress. This is because in-group assortative sociality is more important for the avoidance of infection from novel parasites and for the management of infection in regions with high levels of parasite-stress compared with regions of low infectious disease stress. We examined this hypothesis by testing the predictions that there would be a positive association between parasite-stress and strength of family ties or religiosity. We conducted this study by comparing among nations and among states in the United States of America. We found for both the international and the interstate analyses that in-group assortative sociality was positively associated with parasite-stress. This was true when controlling for potentially confounding factors such as human freedom and economic development. The findings support the parasite-stress theory of sociality, that is, the proposal that parasite-stress is central to the evolution of social life in humans and other animals

    Targeted mutation of barley (1,3;1,4)-β-glucan synthases reveals complex relationships between the storage and cell wall polysaccharide content

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    Barley (Hordeum vulgare L) grain is comparatively rich in (1,3;1,4)-β-glucan, a source of fermentable dietary fibre that protects against various human health conditions. However, low grain (1,3;1,4)-β-glucan content is preferred for brewing and distilling. We took a reverse genetics approach, using CRISPR/Cas9 to generate mutations in members of the Cellulose synthase-like (Csl) gene superfamily that encode known (HvCslF6 and HvCslH1) and putative (HvCslF3 and HvCslF9) (1,3;1,4)-β-glucan synthases. Resultant mutations ranged from single amino acid (aa) substitutions to frameshift mutations causing premature stop codons, and led to specific differences in grain morphology, composition and (1,3;1,4)-β-glucan content. (1,3;1,4)-β-Glucan was absent in the grain of cslf6 knockout lines, whereas cslf9 knockout lines had similar (1,3;1,4)-β-glucan content to wild-type (WT). However, cslf9 mutants showed changes in the abundance of other cell-wall-related monosaccharides compared with WT. Thousand grain weight (TGW), grain length, width and surface area were altered in cslf6 knockouts, and to a lesser extent TGW in cslf9 knockouts. cslf3 and cslh1 mutants had no effect on grain (1,3;1,4)-β-glucan content. Our data indicate that multiple members of the CslF/H family fulfil important functions during grain development but, with the exception of HvCslF6, do not impact the abundance of (1,3;1,4)-β-glucan in mature grain.</p

    Is In-Vivo laparoscopic simulation learning a step forward in the Undergraduate Surgical Education?

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    BACKGROUND: Essentials Skills in the Management of Surgical Cases - ESMSC is an International Combined Applied Surgical Science and Wet Lab course addressed at the Undergraduate level. Laparoscopic Skills is a fundamental element of Surgical Education and various Simulation-Based Learning (SBL) models have been endorsed. This study aims to explore if there is any significant difference in delegates' performance depending on whether they completed In Vivo module prior to the equivalent in the laparoscopic simulator. MATERIALS AND METHODS: 37 Medical Students from various EU countries were divided in 2 groups, and both completed the "Fundamentals in Laparoscopic Surgery" module in the Dry-lab Laparoscopic Simulator as well as the same module "In Vivo" on a swine model. Group A (18 students, 48.6%) completed the "Fundamentals in Laparoscopic Surgery - FLS" module prior to the "In Vivo", whereas group B completed the "In Vivo" module first. Direct Observation of Procedural Skills (DOPS) were used to assess delegates' performance. RESULTS: The mean DOPS scores for the "FLS" and "In Vivo" models were 2.27 ± 0.902 and 2.03 ± 0.833, respectively, and the delegates' performance was not statistically significantly different between them (p = 0.128). There was no statistically significant difference in the scores among different gender, year of study, school and handedness groups. The alteration in the sequence between Dry-lab "FLS" and "In Vivo" modules did not affect the performance in neither the "FLS" nor the "In Vivo" models. CONCLUSIONS: The inexpensive, but low-fidelity "FLS" model could serve an equal alternative Simulation-Based Learning model for the early undergraduate training. Our study demonstrated that high fidelity In Vivo simulation for laparoscopic skills does not affect significantly the improvement in the delegates' performance at the undergraduate level. Further studies should be conducted to identify at which stage of training should high fidelity simulation be introduced

    Anatomical Society core regional anatomy syllabus for undergraduate medicine: the Delphi process

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    A modified Delphi method was employed to seek consensus when revising the UK and Ireland's core syllabus for regional anatomy in undergraduate medicine. A Delphi panel was constructed involving ‘expert’ (individuals with at least 5 years’ experience in teaching medical students anatomy at the level required for graduation). The panel (n = 39) was selected and nominated by members of Council and/or the Education Committee of the Anatomical Society and included a range of specialists including surgeons, radiologists and anatomists. The experts were asked in two stages to ‘accept’, ‘reject’ or ‘modify’ (first stage only) each learning outcome. A third stage, which was not part of the Delphi method, then allowed the original authors of the syllabus to make changes either to correct any anatomical errors or to make minor syntax changes. From the original syllabus of 182 learning outcomes, removing the neuroanatomy component (163), 23 learning outcomes (15%) remained unchanged, seven learning outcomes were removed and two new learning outcomes added. The remaining 133 learning outcomes were modified. All learning outcomes on the new core syllabus achieved over 90% acceptance by the panel

    The application of an ecosystem services framework to estimate the economic value of dung beetles to the U.K. cattle industry

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    Agrobiodiversity is declining across global farm production systems. These declines transcend both farm animal genetic resources (FAnGR) and plant genetic resources (PGR). Both can sustain greater adaptability and resilience in commercial production through so called ‘option value’. In addition, PGR and FAnGR embody cultural and heritage attributes that are often absent in global agriculture, but remain valued by society. Conservation is therefore important and economic incentives represent a potential supply-side mechanism to improve the status of rare breeds, cultivars and crop wild relatives. Yet, the exploration of incentive instruments for their conservation remains underexplored but may improve conservation outcomes. Using different survey instruments and modelling approaches (including choice modelling, linear programming and multi criteria decision analysis) I investigate how rationalising incentive support, through more targeted interventions, could result in better conservation outcomes. The findings suggest optimising subsidy support relies on three key factors. First, conservation contracts offered to farmers for conservation should reflect local farm business preferences and circumstances. This includes addressing barriers-to-entry in conservation programmes and the design of contractual schemes, that when improved will likely increase participation in conservation contracts. Second, identifying least cost suppliers of conservation services may enable more diversity to be conserved at comparable cost. Third, optimising what species, varieties and breeds are supported may improve conservation outcomes through more rational investments in diversity. Policy responses to address declining agrobiodiversity should consider the use of tender instruments (i.e. reverse auctions) to identify least cost suppliers for conservation services. Optimisation modelling and decision analysis techniques can be used to measure trade-offs inherent in different conservation goals, including social equity and diversity. Ultimately there is a need to balance the supply of use and non-use values of diversity that span the total economic value framework. While the drive for sustainable intensification of production may improve productivity, we need to be clear how breed and cultivar diversity can be encompassed into future policy priorities that reflect the need for greater food security plus cultural and heritage value attributes. The implications of deploying new and potentially disruptive technologies (i.e. gene editing) in the context of farm diversity are discussed

    Enzymatic Cross-Linking of Alkali Extracted Arabinoxylans: Gel Rheological and Structural Characteristics

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    Ferulated arabinoxylans were alkali-extracted from wheat bran at different incubation times (0.0, 0.5, 1.0, 1.5 and 2.0 h). Wheat bran ferulated arabinoxylans (WBAX) arabinose-to-xylose ratio, ferulic acid content, intrinsic viscosity and viscosimetric molecular weight values decreased as the incubation time of extraction increased. WBAX enzymatic cross-linking capability was affected by incubation time while an increase in WBAX concentration from 5 to 6% (w/v) favored gelation. The WBAX gels formed presented a macroporous structure with mesh size ranging from 40 to 119 nm and hardness values varying from 1.7 to 5 N

    Iminosugar inhibitors of carbohydrate-active enzymes that underpin cereal grain germination and endosperm metabolism

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    Starch is a major energy store in plants. It provides most of the calories in the human diet and, as a bulk commodity, it is used across broad industry sectors. Starch synthesis and degradation are not fully understood, owing to challenging biochemistry at the liquid/solid interface and relatively limited knowledge about the nature and control of starch degradation in plants. Increased societal and commercial demand for enhanced yield and quality in starch crops requires a better understanding of starch metabolism as a whole. Here we review recent advances in understanding the roles of carbohydrate-active enzymes in starch degradation in cereal grains through complementary chemical and molecular genetics. These approaches have allowed us to start dissecting aspects of starch degradation and the interplay with cell-wall polysaccharide hydrolysis during germination. With a view to improving and diversifying the properties and uses of cereal grains, it is possible that starch degradation may be amenable to manipulation through genetic or chemical intervention at the level of cell wall metabolism, rather than simply in the starch degradation pathway per se

    Preparing the family and children for surgery

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    The focus of this literature analysis is the concept of preparing the family and children for surgery. As posited in the literature, surgery causes stress and anxiety that have a negative impact on both parents and their children. Therefore, the need for health care professionals to facilitate positive preparation for surgery to minimize anxiety and enhance postoperative recovery is important. Preparing the family and children for surgery is discussed in depth under the following themes: Preoperative Anxiety in Children, the Impact of Preoperative Anxiety on the Pediatric Patients and Parents, Preoperative Psychological Preparation for Children and Parents, and the Role of Nurse Practitioners in Preoperative Preparation. Through reviewing the literature, it would appear that some areas of preparation for parents are not as sufficient as they could be, particularly with regard to adequate preoperative education programs. The majority of studies reported that therapeutic play and clown interventions used for psychological preparation of parents and their children have been effective in minimizing and decreasing anxiety levels

    Predicting residents' performance: A prospective study

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    BACKGROUND: Objective criteria for predicting residents' performance do not exist. The purpose of this study was to test the hypothesis that global assessment by an intern selection committee (ISC) would correlate with the future performance of residents. METHODS: A prospective study of 277 residents between 1992 and 1999. Global assessment at the time of interview was compared to subsequent clinical (assessed by chief residents) and cognitive performance (assessed by the American Board of Pediatrics in-service training examination). RESULTS: ISC ratings correlated significantly with clinical performance at 24 and 36 months of training (r = 0.58, P < .001; and r = 0.60, P < .001 respectively). ISC ratings also correlated significantly with in-service exam scores in the 1(st), 2(nd), and 3(rd) years of training (r = 0.35, P = .0016; r = 0.39, P = 0.0003; r = 0.50, P = 0.005 respectively). CONCLUSIONS: Global assessment by an ISC predicted residents' clinical and cognitive performances
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