3,072 research outputs found

    Peroxisomal APX knockdown triggers antioxidant mechanisms favourable for coping with high photorespiratory H2O2 induced by CAT deficiency in rice

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    The physiological role of peroxisomal ascorbate peroxidases (pAPX) is unknown; therefore, we utilized pAPX4 knockdown rice and catalase (CAT) inhibition to assess its role in CAT compensation under high photorespiration. pAPX4 knockdown induced co-suppression in the expression of pAPX3. The rice mutants exhibited metabolic changes such as lower CAT and glycolate oxidase (GO) activities and reduced glyoxylate content; however, APX activity was not altered. CAT inhibition triggered different changes in the expression of CAT, APX and glutathione peroxidase (GPX) isoforms between non-transformed (NT) and silenced plants. These responses were associated with alterations in APX, GPX and GO activities, suggesting redox homeostasis differences. The glutathione oxidation-reduction states were modulated differently in mutants, and the ascorbate redox state was greatly affected in both genotypes. The pAPX suffered less oxidative stress and photosystem II (PSII) damage and displayed higher photosynthesis than the NT plants. The improved acclimation exhibited by the pAPX plants was indicated by lower H2O2 accumulation, which was associated with lower GO activity and glyoxylate content. The suppression of both pAPXs and/or its downstream metabolic and molecular effects may trigger favourable antioxidant and compensatory mechanisms to cope with CAT deficiency. This physiological acclimation may involve signalling by peroxisomal H2O2, which minimized the photorespiration.</p

    Juvenile Batten disease (CLN3): Detailed Ocular Phenotype, Novel Observations, Delayed Diagnosis, Masquerades, and Prospects for Therapy

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    PURPOSE To characterize the retinal phenotype of juvenile neuronal ceroid lipofuscinosis (JNCL), highlight delayed and mistaken diagnosis, and propose an algorithm for early identification. DESIGN Retrospective case series. SUBJECTS Eight children (5 females) with JNCL. METHODS Review of clinical notes, retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), electroretinography (ERG), and both microscopy and molecular genetic testing. MAIN OUTCOME MEASUREMENTS Demographic data, signs and symptoms, visual acuity, FAF and OCT findings, ERG phenotype, and microscopy/molecular genetics. RESULTS Subjects presented with rapid bilateral vision loss over one to eighteen months, with mean visual acuity deteriorating from 0.44 LogMAR (range: 0.20 - 1.78 LogMAR) at baseline, to 1.34 LogMAR (0.30 LogMAR - light perception) at last follow-up. Age of onset ranged from 3 to 7 years (mean 5.3 years). The age at diagnosis of JNCL ranged from 7 to 10 years (mean 8.3 years). Six children displayed eccentric fixation, and six had cognitive or neurological signs at time of diagnosis (75%). Seven patients had bilateral bull’s-eye maculopathy at presentation. Coats-like exudative vasculopathy, not previously reported in JNCL, was observed in one patient. OCT imaging revealed near complete loss of outer retinal layers, and marked atrophy of the nerve fibre and ganglion cell layers, at the central macula. An ‘electronegative’ ERG was present in four patients (50%), but with additional a-wave reduction; there was an undetectable ERG in the remaining four. Blood film microscopy revealed vacuolated lymphocytes and electron microscopy showed lysosomal (fingerprint) inclusions, in all eight patients. CONCLUSIONS In a young child with bilateral rapidly progressive vision loss and macular disturbance, blood film microscopy to detect vacuolated lymphocytes is a rapid, readily accessible, and sensitive screening test for JNCL. Early suspicion of JNCL can be aided by detailed directed history and high-resolution retinal imaging, with subsequent targeted microscopy/genetic testing. Early diagnosis is critical to ensure appropriate management, counselling, support and social care for children and their families. Furthermore, although potential therapies for this group of disorders are in early phase clinical trial, realistic expectations are that successful intervention will be most effective when initiated at the earliest stage of disease

    Violence against women: The perspective of academic women

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    <p>Abstract</p> <p>Background</p> <p>Opinion surveys about potential causes of violence against women (VAW) are uncommon. This study explores academic women's opinions about VAW and the ways of reducing violence.</p> <p>Methods</p> <p>Quantitative and qualitative methods were used in this descriptive study. One hundred-and-fifteen academicians participated in the study from two universities. A questionnaire was used regarding the definition and the causes of VAW, the risk groups and opinions about the solutions. Additionally, two authors interviewed 8 academicians from universities other than that of the interviewing author.</p> <p>Results</p> <p>Academicians discussed the problem from the perspective of "gender-based violence" rather than "family violence". The majority of the participants stated that nonworking women of low socioeconomic status are most at risk for VAW. They indicated that psychological violence is more prevalent against educated women, whilst physical violence is more likely to occur against uneducated and nonworking women. Perpetrator related factors were the most frequently stated causes of VAW. Thirty-five percent of the academicians defined themselves as at risk of some act of VAW. Recommendations for actions against violence were empowerment of women, increasing the educational levels in the society, and legal measures.</p> <p>Conclusions</p> <p>Academic women introduced an ecological approach for the explanation of VAW by stressing the importance of taking into account the global context of the occurrence of VAW. Similar studies with various community members -including men- will help to define targeted interventions.</p

    Outcomes of TB Treatment by HIV Status in National Recording Systems in Brazil, 2003–2008

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    BACKGROUND: Although the Brazilian national reporting system for tuberculosis cases (SINAN) has enormous potential to generate data for policy makers, formal assessments of treatment outcomes and other aspects of TB morbidity and mortality are not produced with enough depth and rigor. In particular, the effect of HIV status on these outcomes has not been fully explored, partly due to incomplete recording in the national database. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we assessed TB treatment outcomes, including rates of cure, default, mortality, transfer and multidrug resistant TB (MDR-TB) among a purposively chosen sample of 161,481 new cases reported in SINAN between 2003 and 2008. The study population included all new cases reported in the six States with the highest level of completeness of the HIV status field in the system. These cases were mostly male (67%), white (62%), had pulmonary TB (79%) and a suspect chest X ray (83%). Treatment outcomes were best for those HIV negative cases and worst for those known HIV positive patients (cure rate of 85.7% and 55.7% respectively). In multivariate modeling, the risk of having an unfavorable outcome (all outcomes except cure) was 3.09 times higher for those HIV positive compared with those HIV negative (95% CI 3.02-3.16). The risk of death and default also increased with HIV positivity. The group without a known HIV status showed intermediate outcomes between the groups above, suggesting that this group includes some with HIV infection. CONCLUSIONS: HIV status played an important role in TB treatment outcomes in the study period. The outcomes observed in those with known HIV were poor and need to be improved. Those in the group with unknown HIV status indicate the need for wider HIV testing among new TB cases

    Resistance and differential susceptibility of Bidens pilosa and B-subalternans biotypes to ALS-inhibiting herbicides

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    The frequent application of herbicides in agricultural areas may select resistant biotypes in weed populations, whose biological characteristics influence the speed and patterns of resistance. This research aims to charactere, simultaneously, resistance patterns and differential susceptibility of Bidens pilosa and B. subalternans biotypes to ALS-inhibiting herbicides of the imidazolinone and sulfonylurea chemical groups. Six hairy beggarticks biotypes, four suspected resistant and two known susceptible, were treated with eight rates of chlorimuron-ethyl or imazethapyr, in greenhouse conditions. Percent control and percent fresh weight of the plants were evaluated at 28 days after the application. B. subalternans is less susceptible to ALS-inhibiting herbicides than B. pilosa; B. subalternans biotypes were more resistant than B. pilosa biotypes; there are B. pilosa and B. subalternans biotypes with cross resistance to the ALS-inhibiting herbicides of the sulfonylurea and imidazolinone groups; there are different patterns of cross resistance to the diverse groups of ALS-inhibiting herbicides.63213914

    An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

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    Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays
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