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Trotta, A.

Publications and source records attributed to Trotta, A..

4 recordsLinked to original sources

The Maudsley Environmental Risk Score for Psychosis

Risk prediction algorithms have long been used in health research and practice (e.g., in prediction of cardiovascular disease, diabetes, etc.) However, similar tools have not been developed for mental health problems, despite extensive research on risk factors. For example, for psychotic disorders, attempts to sum environmental risk are rare, usually unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the total environmental risk for psychotic disorders, which can be used in research and clinical practice.\n\nWe first reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis and, then, used the largest available meta-analyses to derive current best estimates of risk. We devised a method of scoring individuals based on the level of exposure to each risk factor, using odds ratios from the meta-analyses, to produce an Environmental Risk Score (ERS).\n\nSix risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use, and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on permuted data showed that most of population would be at low/moderate risk with a small minority at increased environmental risk for psychosis.\n\nThis is the first systematic approach to develop an aggregate measure of environmental risk for psychoses. This can be used as a continuous measure of liability to disease or transformed to a relative risk. Its predictive ability will improve with the collection of additional, population specific data.

epidemiology

Methyl viologen can affect mitochondrial function in Arabidopsis.

Reactive oxygen species (ROS) are key signalling intermediates in plant metabolism, defence, and stress adaptation. The chloroplast and mitochondria are centres of metabolic control and ROS production, which coordinate stress responses in other cell compartments. The herbicide and experimental tool, methyl viologen (MV) induces ROS generation in the chloroplast under illumination, but is also toxic in non-photosynthetic organisms. We used MV to probe plant ROS signalling in compartments other than the chloroplast. Taking a genetic approach in Arabidopsis thaliana, we used natural variation, QTL mapping, and mutant studies with MV in the light, but also under dark conditions, when the chloroplast electron transport is inactive. These studies revealed a light-independent MV-induced ROS-signalling pathway, suggesting mitochondrial involvement. Mitochondrial Mn SUPEROXIDE DISMUTASE was required for ROS-tolerance and the effect of MV was enhanced by exogenous sugar, providing further evidence for the role of mitochondria. Mutant and hormone feeding assays revealed roles for stress hormones in organellar ROS-responses. The radical-induced cell death1 mutant, which is tolerant to MV-induced ROS and exhibits altered mitochondrial signalling, was used to probe interactions between organelles. Our studies implicate mitochondria in the response to ROS induced by MV.

plant biology

Regulation of chloroplast NADH dehydrogenase-like complex by NADPH-dependent thioredoxin system

Linear electron transport in the thylakoid membrane drives both photosynthetic NADPH and ATP production, while cyclic electron flow (CEF) around photosystem I only promotes the translocation of protons from stroma to thylakoid lumen. The chloroplast NADH-dehydrogenase-like complex (NDH) participates in one CEF route transferring electrons from ferredoxin back to the plastoquinone pool with concomitant proton pumping to the lumen. CEF has been proposed to balance the ratio of ATP/NADPH production and to control the redox poise particularly in fluctuating light conditions, but the mechanisms regulating the NDH complex remain unknown. We have investigated potential regulation of the CEF pathways by the chloroplast NADPH-thioredoxin reductase (NTRC) in vivo by using an Arabidopsis knockout line of NTRC as well as lines overexpressing NTRC. Here we present biochemical and biophysical evidence showing that NTRC activates the NDH-dependent CEF and regulates the generation of proton motive force, thylakoid conductivity to protons and redox balance between the thylakoid electron transfer chain and the stroma during changes in light conditions. Further, protein-protein interaction assays suggest a putative thioredoxin-target site in close proximity to the ferredoxin binding domain of NDH, thus providing a plausible mechanism for regulation of the NDH ferredoxin:plastoquinone oxidoreductase activity by NTRC.\n\nOne sentence summaryChloroplast thioredoxins regulate photosynthetic cyclic electron flow that balances the activities of light and carbon fixation reactions and improves plant fitness under fluctuating light conditions.

plant biology

Aging Of Antiviral CD8+ Memory T Cells Fosters Increased Survival, Metabolic Adaptations And Lymphoid Tissue Homing

Aging of established antiviral T cell memory fosters a series of progressive adaptations that paradoxically improve rather than compromise protective CD8+T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8+ memory T cell (CD8+TM) homeostasis. Over time, CD8+TM become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8+TM quiescence and fitness but also impart the re-acquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8+TM from blood and nonlymphoid tissues to lymphatic organs results in CD8+TM accumulations in bone marrow, splenic white pulp and particularly lymph nodes. Altogether, these data demonstrate how temporal alterations of fundamental homeostatic determinants converge to render aged CD8+TM poised for greater recall responses.\n\nABBREVIATIONST cell subsets

immunology