224 research outputs found

    A systematic review and meta-analysis of longitudinal studies of the antecedents and consequences of wellbeing among university students

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    Background and objectives: Wellbeing among university students is associated with better academic outcomes and diminished harm from mental illness. This study systematically reviews and meta-analyses longitudinal studies of the antecedents and consequences of wellbeing within this population, providing an overview which establishes a ‘natural history’ of wellbeing to form a background for intervention and policy. Method: This study was a systematic review and meta-analysis of the peer-reviewed literature, based on a broad range of search terms across four journal databases in psychology, medicine and education. Studies were organised by the domain of their study variables (i.e., Self, Relationships, or Institutional Context) and variables relating to wellbeing were extracted. The incremental effect of study variables measured at baseline upon prospective wellbeing was calculated with semipartial correlation coefficients which controlled for baseline wellbeing. Meta-regressions were used to examine the effect of follow-up interval on effect sizes. Results: Sixty-two longitudinal studies of university student cohorts were identified. In 57 studies, wellbeing was an outcome variable. Meta-analyses showed that effects were moderated by measurement interval between baseline and follow-up, becoming weaker with longer intervals, and that this was not an artifact of the measurement instrument. The study factors with the strongest positive effect sizes after controlling for baseline wellbeing were authenticity, self-esteem, self-support for autonomy, emotional repair, and ability to regulate distress and despondency; relationship commitment and group memberships; self-identification with the university and time pressure. Study factors with the strongest negative effect sizes were uncertainty regarding university, materialism, a belief in social complexity, depression, and stress. In five studies, wellbeing was an antecedent, showing positive associations with educational outcomes. Conclusion: This review identified several antecedents of student wellbeing which could be targeted for interventions. These included self-relationship, emotion regulation, and interventions to decrease mental illness. Universities might also make it easier to establish and maintain groups (e.g., study cohorts, interest groups). Many variables which affect wellbeing are not amenable to study with experimental methods, but their study and use in wellbeing interventions should not be neglected. Because the antecedents of wellbeing are numerous and diverse, further research in the area should take advantage of research methods which maximise the variety of data collected and minimise respondent burden, such as passively collected and linked data

    A logic-based diagram of signalling pathways central to macrophage activation.

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    BACKGROUND: The complex yet flexible cellular response to pathogens is orchestrated by the interaction of multiple signalling and metabolic pathways. The molecular regulation of this response has been studied in great detail but comprehensive and unambiguous diagrams describing these events are generally unavailable. Four key signalling cascades triggered early-on in the innate immune response are the toll-like receptor, interferon, NF-kappaB and apoptotic pathways, which co-operate to defend cells against a given pathogen. However, these pathways are commonly viewed as separate entities rather than an integrated network of molecular interactions. RESULTS: Here we describe the construction of a logically represented pathway diagram which attempts to integrate these four pathways central to innate immunity using a modified version of the Edinburgh Pathway Notation. The pathway map is available in a number of electronic formats and editing is supported by yEd graph editor software. CONCLUSION: The map presents a powerful visual aid for interpreting the available pathway interaction knowledge and underscores the valuable contribution well constructed pathway diagrams make to communicating large amounts of molecular interaction data. Furthermore, we discuss issues with the limitations and scalability of pathways presented in this fashion, explore options for automated layout of large pathway networks and demonstrate how such maps can aid the interpretation of functional studies

    The Alzheimer's-related amyloid beta peptide is internalised by R28 neuroretinal cells and disrupts the microtubule associated protein 2 (MAP-2)

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    Age-related Macular Degeneration (AMD) is a common, irreversible blinding condition that leads to the loss of central vision. AMD has a complex aetiology with both genetic as well as environmental risks factors, and share many similarities with Alzheimer's disease. Recent findings have contributed significantly to unravelling its genetic architecture that is yet to be matched by molecular insights. Studies are made more challenging by observations that aged and AMD retinas accumulate the highly pathogenic Alzheimer's-related Amyloid beta (A?) group of peptides, for which there appears to be no clear genetic basis. Analyses of human donor and animal eyes have identified retinal A? aggregates in retinal ganglion cells (RGC), the inner nuclear layer, photoreceptors as well as the retinal pigment epithelium. A? is also a major drusen constituent; found correlated with elevated drusen-load and age, with a propensity to aggregate in retinas of advanced AMD. Despite this evidence, how such a potent driver of neurodegeneration might impair the neuroretina remains incompletely understood, and studies into this important aspect of retinopathy remains limited. In order to address this we exploited R28 rat retinal cells which due to its heterogeneous nature, offers diverse neuroretinal cell-types in which to study the molecular pathology of A?. R28 cells are also unaffected by problems associated with the commonly used RGC-5 immortalised cell-line, thus providing a well-established model in which to study dynamic A? effects at single-cell resolution. Our findings show that R28 cells express key neuronal markers calbindin, protein kinase C and the microtubule associated protein-2 (MAP-2) by confocal immunofluorescence which has not been shown before, but also calretinin which has not been reported previously. For the first time, we reveal that retinal neurons rapidly internalised A?1-42, the most cytotoxic and aggregate-prone amongst the A? family. Furthermore, exposure to physiological amounts of A?1-42 for 24 h correlated with impairment to neuronal MAP-2, a cytoskeletal protein which regulates microtubule dynamics in axons and dendrites. Disruption to MAP-2 was transient, and had recovered by 48 h, although internalised A? persisted as discrete puncta for as long as 72 h. To assess whether A? could realistically localise to living retinas to mediate such effects, we subretinally injected nanomolar levels of oligomeric A?1-42 into wildtype mice. Confocal microscopy revealed the presence of focal A? deposits in RGC, the inner nuclear and the outer plexiform layers 8 days later, recapitulating naturally-occurring patterns of A? aggregation in aged retinas. Our novel findings describe how retinal neurons internalise A? to transiently impair MAP-2 in a hitherto unreported manner. MAP-2 dysfunction is reported in AMD retinas, and is thought to be involved in remodelling and plasticity of post-mitotic neurons. Our insights suggest a molecular pathway by which this could occur in the senescent eye leading to complex diseases such as AMD

    People are essential to linking biodiversity data

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    People are one of the best known and most stable entities in the biodiversity knowledge graph. The wealth of public information associated with people and the ability to identify them uniquely open up the possibility to make more use of these data in biodiversity science. Person data are almost always associated with entities such as specimens, molecular sequences, taxonomic names, observations, images, traits and publications. For example, the digitization and the aggregation of specimen data from museums and herbaria allow us to view a scientist’s specimen collecting in conjunction with the whole corpus of their works. However, the metadata of these entities are also useful in validating data, integrating data across collections and institutional databases and can be the basis of future research into biodiversity and science. In addition, the ability to reliably credit collectors for their work has the potential to change the incentive structure to promote improved curation and maintenance of natural history collections

    Post-bronchoscopy fatal endobronchial hemorrhage in a woman with bronchopulmonary mucormycosis: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>During infection, Mucorales fungi invade major blood vessels, leading to extensive necrosis, and in cases of extensive pulmonary disease, bleeding into the lungs may occur.</p> <p>Case presentation</p> <p>We report an unexpected event of post-bronchoscopy fatal endobronchial hemorrhage in a 62-year-old HIV-negative Italian woman with well controlled diabetes mellitus who presented with diffuse cavitated pulmonary lesions. Fiberoptic bronchoscopy revealed bilateral obstruction of the segmental bronchi. Fatal massive bleeding occurred after standard biopsy procedures. Histologic examination showed that the hyphae were more deeply colored by hematoxylin-eosin (H&E) than by other stains for fungi. Culture and autopsy confirmed bronchopulmonary mucormycosis.</p> <p>Conclusion</p> <p>Infection by Mucorales fungi should be considered in the diabetes population regardless of the degree of metabolic control. In these patients, particular caution should be taken during bronchoscopic procedures because of the greater friability of the fungal lesions.</p

    New Abundant Microbial Groups in Aquatic Hypersaline Environments

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    We describe the microbiota of two hypersaline saltern ponds, one of intermediate salinity (19%) and a NaCl saturated crystallizer pond (37%) using pyrosequencing. The analyses of these metagenomes (nearly 784 Mb) reaffirmed the vast dominance of Haloquadratum walsbyi but also revealed novel, abundant and previously unsuspected microbial groups. We describe for the first time, a group of low GC Actinobacteria, related to freshwater Actinobacteria, abundant in low and intermediate salinities. Metagenomic assembly revealed three new abundant microbes: a low-GC euryarchaeon with the lowest GC content described for any euryarchaeon, a high-GC euryarchaeon and a gammaproteobacterium related to Alkalilimnicola and Nitrococcus. Multiple displacement amplification and sequencing of the genome from a single archaeal cell of the new low GC euryarchaeon suggest a photoheterotrophic and polysaccharide-degrading lifestyle and its relatedness to the recently described lineage of Nanohaloarchaea. These discoveries reveal the combined power of an unbiased metagenomic and single cell genomic approach

    A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background

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    Nephrotic syndrome is characterised by severe proteinuria, hypoalbuminaemia, oedema and hyperlipidaemia. Genetic studies of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signalling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is essential for embryonic development and, in association with laminin β2 and laminin γ1, it is a major component of the glomerular basement membrane. Mutations in LAMA5 were recently identified in children with nephrotic syndrome. We have identified a novel missense mutation (E884G) in the uncharacterised L4a domain of LAMA5 where homozygous mice develop nephrotic syndrome with severe proteinuria with histological and ultrastructural changes in the glomerulus. The levels of LAMA5 are reduced in vivo and the assembly of the laminin 521 heterotrimer significantly reduced in vitro. Proteomic analysis of the glomerular extracellular fraction revealed changes in the matrix composition. Importantly, the genetic background had a significant effect on aspects of disease progression from proteinuria to changes in podocyte morphology. This novel model will provide insights into patho-mechanisms of nephrotic syndrome and pathways that influence the response to a dysfunctional glomerular basement membrane

    The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

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    Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

    A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

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    We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

    Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

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    Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it
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