5,129 research outputs found

    Characterisation of the Fusarium graminearum-Wheat Floral Interaction.

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    PublishedJournal ArticleFusarium Ear Blight is a destructive fungal disease of cereals including wheat and can contaminate the crop with various trichothecene mycotoxins. This investigation has produced a new β-glucuronidase (GUS) reporter strain that facilitates the quick and easy assessment of plant infection. The constitutively expressed gpdA:GUS strain of Fusarium graminearum was used to quantify the overall colonisation pattern. Histochemical and biochemical approaches confirmed, in susceptible wheat ear infections, the presence of a substantial phase of symptomless fungal growth. Separate analyses demonstrated that there was a reduction in the quantity of physiologically active hyphae as the wheat ear infection proceeded. A simplified linear system of rachis infection was then utilised to evaluate the expression of several TRI genes by RT-qPCR. Fungal gene expression at the advancing front of symptomless infection was compared with the origin of infection in the rachis. This revealed that TRI gene expression was maximal at the advancing front and supports the hypothesis that the mycotoxin deoxynivalenol plays a role in inhibiting plant defences in advance of the invading intercellular hyphae. This study has also demonstrated that there are transcriptional differences between the various phases of fungal infection and that these differences are maintained as the infection proceeds.Chinese governmentBritish Society for Plant Pathology (BSPP)BBSRCEU FP 6 Integrated Project BioexploitSyngent

    Separation between coherent and turbulent fluctuations. What can we learn from the Empirical Mode Decomposition?

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    The performances of a new data processing technique, namely the Empirical Mode Decomposition, are evaluated on a fully developed turbulent velocity signal perturbed by a numerical forcing which mimics a long-period flapping. First, we introduce a "resemblance" criterion to discriminate between the polluted and the unpolluted modes extracted from the perturbed velocity signal by means of the Empirical Mode Decomposition algorithm. A rejection procedure, playing, somehow, the role of a high-pass filter, is then designed in order to infer the original velocity signal from the perturbed one. The quality of this recovering procedure is extensively evaluated in the case of a "mono-component" perturbation (sine wave) by varying both the amplitude and the frequency of the perturbation. An excellent agreement between the recovered and the reference velocity signals is found, even though some discrepancies are observed when the perturbation frequency overlaps the frequency range corresponding to the energy-containing eddies as emphasized by both the energy spectrum and the structure functions. Finally, our recovering procedure is successfully performed on a time-dependent perturbation (linear chirp) covering a broad range of frequencies.Comment: 23 pages, 13 figures, submitted to Experiments in Fluid

    Partial pathogen protection by tick-bite sensitization and epitope recognition in peptide-immunized HLA DR3 transgenic mice

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    Ticks are notorious vectors of disease for humans, and many species of ticks transmit multiple pathogens, sometimes in the same tick bite. Accordingly, a broad-spectrum vaccine that targets vector ticks and pathogen transmission at the tick/host interface, rather than multiple vaccines against every possible tickborne pathogen, could become an important tool for resolving an emerging public health crisis. The concept for such a tick protective vaccine comes from observations of an acquired tick resistance (ATR) that can develop in non-natural hosts of ticks following sensitization to tick salivary components. Mice are commonly used as models to study immune responses to human pathogens but normal mice are natural hosts for many species of ticks and fail to develop ATR. We evaluated HLA DR3 transgenic (tg) “humanized” mice as a potential model of ATR and assessed the possibility of using this animal model for tick protective vaccine discovery studies. Serial tick infestations with pathogen-free Ixodes scapularis ticks were used to tick-bite sensitize HLA DR3 tg mice. Sensitization resulted in a cytokine skew favoring a Th2 bias as well as partial (57%) protection to infection with Lyme disease spirochetes (Borrelia burgdorferi) following infected tick challenge when compared to tick naïve counterparts. I. scapularis salivary gland homogenate (SGH) and a group of immunoinformatic-predicted T cell epitopes identified from the I. scapularis salivary transcriptome were used separately to vaccinate HLA DR3 tg mice, and these mice also were assessed for both pathogen protection and epitope recognition. Reduced pathogen transmission along with a Th2 skew resulted from SGH vaccination, while no significant protection and a possible T regulatory bias was seen in epitope-vaccinated mice. This study provides the first proof-of-concept for using HLA DR tg “humanized” mice for studying the potential tick protective effects of immunoinformatic- or otherwise-derived tick salivary components as tickborne disease vaccines

    HIV Protease Inhibitors Act as Competitive Inhibitors of the Cytoplasmic Glucose Binding Site of GLUTs with Differing Affinities for GLUT1 and GLUT4

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    The clinical use of several first generation HIV protease inhibitors (PIs) is associated with the development of insulin resistance. Indinavir has been shown to act as a potent reversible noncompetitive inhibitor of zero-trans glucose influx via direct interaction with the insulin responsive facilitative glucose transporter GLUT4. Newer drugs within this class have differing effects on insulin sensitivity in treated patients. GLUTs are known to contain two distinct glucose-binding sites that are located on opposite sides of the lipid bilayer. To determine whether interference with the cytoplasmic glucose binding site is responsible for differential effects of PIs on glucose transport, intact intracellular membrane vesicles containing GLUT1 and GLUT4, which have an inverted transporter orientation relative to the plasma membrane, were isolated from 3T3-L1 adipocytes. The binding of biotinylated ATB-BMPA, a membrane impermeable bis-mannose containing photolabel, was determined in the presence of indinavir, ritonavir, atazanavir, tipranavir, and cytochalasin b. Zero-trans 2-deoxyglucose transport was measured in both 3T3-L1 fibroblasts and primary rat adipocytes acutely exposed to these compounds. PI inhibition of glucose transport correlated strongly with the PI inhibition of ATB-BMPA/transporter binding. At therapeutically relevant concentrations, ritonavir was not selective for GLUT4 over GLUT1. Indinavir was found to act as a competitive inhibitor of the cytoplasmic glucose binding site of GLUT4 with a KI of 8.2 µM. These data establish biotinylated ATB-BMPA as an effective probe to quantify accessibility of the endofacial glucose-binding site in GLUTs and reveal that the ability of PIs to block this site differs among drugs within this class. This provides mechanistic insight into the basis for the clinical variation in drug-related metabolic toxicity

    A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales

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    Background People with severe asthma experience significant respiratory symptoms and suffer adverse effects of oral corticosteroids (OCS), including disturbed mood and physical symptoms. OCS impacts on health-related quality of life (HRQoL) have not been quantified. Asthma HRQoL scales are valid as outcome measures for patients requiring OCS only if they assess the deficits imposed by OCS. Aims The aim of this study was to compare the burden of disease and treatment in patients with severe asthma with items in eight asthma-specific HRQoL scales. Methods Twenty-three patients with severe asthma recruited from a severe asthma clinic were interviewed about the impact of their respiratory symptoms and the burden of their treatment. The domains from a thematic analysis of these interviews were compared with the items of eight asthma-specific HRQoL scales. Results In addition to the burden caused by symptoms, ten domains of OCS impact on HRQoL were identified: depression, irritability, sleep, hunger, weight, skin, gastric, pain, disease anxiety, and medication anxiety. Some patients experienced substantial HRQoL deficits attributed to OCS. Although all HRQoL scales include some OCS-relevant items, all eight scales fail to adequately assess the several types of burden experienced by some patients while on OCS. Conclusion The burden of OCS in severe asthma is neglected in policy and practice because it is not assessed in outcome studies. Existing asthma HRQoL scales provide an overly positive estimation of HRQoL in patients with frequent exposure to OCS and underestimate the benefit of interventions that reduce OCS exposure. Changes to existing measurement procedures are needed

    Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

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    Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

    The epidemiology of injuries across the weight-training sports

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    Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

    Breastfeeding training for health professionals and resultant changes in breastfeeding duration

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    CONTEXT: Promotion of breastfeeding in Brazilian maternity hospitals. OBJECTIVE: To quantify changes in the breastfeeding duration among mothers served by hospitals exposed to the Wellstart-SLC course, comparing them with changes among mothers attended by institutions not exposed to this course. DESIGN: Randomized Institutional Trial. SETTING: The effects of training on breastfeeding duration was assessed in eight Brazilian hospitals assigned at random to either an exposed group (staff attending the Wellstart-SLC course) or a control group. SAMPLE: For each of the eight study hospitals, two cohorts of about 50 children were visited at home at one and six months after birth. The first cohort (n = 494) was composed of babies born in the month prior to exposure to the Wellstart-SLC course, and the second cohort (n = 476) was composed of babies born six months subsequent to this exposure. MAIN MEASUREMENTS: Kaplan-Meier curves were plotted to describe the weaning process and log-rank tests were used to assess statistical differences among survival curves. Hazard ratio (HR) estimates were calculated by fitting Cox proportional hazard regression models to the data. RESULTS: The increases in estimated, adjusted rates for children born in hospitals with trained personnel were 29% (HR = 0.71) and 20% (HR = 0.80) for exclusive and full breastfeeding, respectively. No changes were identified for total breastfeeding. CONCLUSION: This randomized trial supports a growing body of evidence that training hospital health professionals in breastfeeding promotion and protection results in an increase in breastfeeding duration.CONTEXTO: Promoção do aleitamento materno em maternidades brasileiras. OBJETIVO: Quantificar mudanças na duração do aleitamento materno de mães assistidas em maternidades expostas ao curso Wellstart-SLC, comparando-as com mudanças em mães assistidas por maternidades não expostas. TIPO DE ESTUDO: Ensaio institucional randomizado. LOCAL: Os efeitos do treinamento na duração do aleitamento materno foi avaliado em oito maternidades randomicamente alocadas ao grupo exposto (equipe freqüenta o curso Wellstart-SLC) ou controle. AMOSTRA: Em cada uma das oito maternidades, duas coortes de cerca de 50 crianças foram visitadas em suas casas ao completarem um e seis meses de vida. As primeiras coortes (n = 494) foram compostas de bebês nascidos no mês anterior ao treinamento, enquanto que as segundas coortes (n = 476) foram compostas por bebês nascidos seis meses após a exposição ao curso Weelstart-SLC. VARIÁVEIS ESTUDADAS: Para descrever o processo de desmame foram traçadas curvas de Kaplan-Meier. Para avaliar as diferenças estatísticas entre as curvas de sobrevivência foi utilizado o teste log-rank. Foram calculadas estimativas das razões de risco(HR) ajustando modelos de regressão de riscos proporcionais de Cox aos dados. RESULTADOS: O aumento estimado, a partir das razões ajustadas para crianças nascidas em hospitais com pessoal treinado, foi 29% (HR = 0,71) e 20% (HR = 0,80) para aleitamento exclusivo e pleno respectivamente. Não foram identificadas mudanças para o tempo de aleitamento total. CONCLUSÕES: Esse ensaio randomizado confirma evidências crescentes de que treinar profissionais de saúde em hospitais, na promoção e proteção do aleitamento materno, resulta em aumento do tempo de aleitamento materno.Universidade Federal de São Paulo (UNIFESP) Department of PediatricsUniversidade de Santo Amaro Maternal and Child Health Graduate ProgramUniversidade Federal de São Paulo (UNIFESP) School of Public HealthState of São Paulo State Health Secretariat Health InstituteUNIFESP, Department of PediatricsUNIFESP, School of Public HealthSciEL

    Internal construct validity of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS): a Rasch analysis using data from the Scottish Health Education Population Survey

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    Background: The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) was developed to meet demand for instruments to measure mental well-being. It comprises 14 positively phrased Likert-style items and fulfils classic criteria for scale development. We report here the internal construct validity of WEMWBS from the perspective of the Rasch measurement model. Methods: The model was applied to data collected from 779 respondents in Wave 12 (Autumn 2006) of the Scottish Health Education Population Survey. Respondents were aged 16–74 (average 41.9) yrs. Results: Initial fit to model expectations was poor. The items 'I've been feeling good about myself', 'I've been interested in new things' and 'I've been feeling cheerful' all showed significant misfit to model expectations, and were deleted. This led to a marginal improvement in fit to the model. After further analysis, more items were deleted and a strict unidimensional seven item scale (the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS)) was resolved. Many items deleted because of misfit with model expectations showed considerable bias for gender. Two retained items also demonstrated bias for gender but, at the scale level, cancelled out. One further retained item 'I've been feeling optimistic about the future' showed bias for age. The correlation between the 14 item and 7 item versions was 0.954. Given fit to the Rasch model, and strict unidimensionality, SWEMWBS provides an interval scale estimate of mental well-being. Conclusion: A short 7 item version of WEMWBS was found to satisfy the strict unidimensionality expectations of the Rasch model, and be largely free of bias. This scale, SWEMWBS, provides a raw score-interval scale transformation for use in parametric procedures. In terms of face validity, SWEMWBS presents a more restricted view of mental well-being than the 14 item WEMWBS, with most items representing aspects of psychological and eudemonic well-being, and few covering hedonic well-being or affect. However, robust measurement properties combined with brevity make SWEMWBS preferable to WEMWBS at present for monitoring mental well-being in populations. Where face validity is an issue there remain arguments for continuing to collect data on the full 14 item WEMWBS
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