1,529 research outputs found

    Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

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    The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

    The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder

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    Using data from a prospective population based study, the prevalence and psychopathological correlates of sibling bullying in children with and without autism spectrum disorder (ASD) were estimated. There were 475 children with ASD and 13,702 children without ASD aged 11 years. Children with ASD were more likely to be bullied by their siblings compared to those without ASD. They were also more likely than those without ASD to both bully and be bullied by their siblings, which was associated with lower prosocial skills as well as more internalizing and externalizing problems compared to those not involved in any sibling bullying. Interventions to improve social and emotional outcomes in children with ASD should focus on both the affected and the unaffected sibling

    Surface and Temporal Biosignatures

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    Recent discoveries of potentially habitable exoplanets have ignited the prospect of spectroscopic investigations of exoplanet surfaces and atmospheres for signs of life. This chapter provides an overview of potential surface and temporal exoplanet biosignatures, reviewing Earth analogues and proposed applications based on observations and models. The vegetation red-edge (VRE) remains the most well-studied surface biosignature. Extensions of the VRE, spectral "edges" produced in part by photosynthetic or nonphotosynthetic pigments, may likewise present potential evidence of life. Polarization signatures have the capacity to discriminate between biotic and abiotic "edge" features in the face of false positives from band-gap generating material. Temporal biosignatures -- modulations in measurable quantities such as gas abundances (e.g., CO2), surface features, or emission of light (e.g., fluorescence, bioluminescence) that can be directly linked to the actions of a biosphere -- are in general less well studied than surface or gaseous biosignatures. However, remote observations of Earth's biosphere nonetheless provide proofs of concept for these techniques and are reviewed here. Surface and temporal biosignatures provide complementary information to gaseous biosignatures, and while likely more challenging to observe, would contribute information inaccessible from study of the time-averaged atmospheric composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets. Fixed figure conversion error

    Quantitative metric profiles capture three-dimensional temporospatial architecture to discriminate cellular functional states

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    <p>Abstract</p> <p>Background</p> <p>Computational analysis of tissue structure reveals sub-visual differences in tissue functional states by extracting quantitative signature features that establish a diagnostic profile. Incomplete and/or inaccurate profiles contribute to misdiagnosis.</p> <p>Methods</p> <p>In order to create more complete tissue structure profiles, we adapted our cell-graph method for extracting quantitative features from histopathology images to now capture temporospatial traits of three-dimensional collagen hydrogel cell cultures. Cell-graphs were proposed to characterize the spatial organization between the cells in tissues by exploiting graph theory wherein the nuclei of the cells constitute the <it>nodes </it>and the approximate adjacency of cells are represented with <it>edges</it>. We chose 11 different cell types representing non-tumorigenic, pre-cancerous, and malignant states from multiple tissue origins.</p> <p>Results</p> <p>We built cell-graphs from the cellular hydrogel images and computed a large set of features describing the structural characteristics captured by the graphs over time. Using three-mode tensor analysis, we identified the five most significant features (metrics) that capture the compactness, clustering, and spatial uniformity of the 3D architectural changes for each cell type throughout the time course. Importantly, four of these metrics are also the discriminative features for our histopathology data from our previous studies.</p> <p>Conclusions</p> <p>Together, these descriptive metrics provide rigorous quantitative representations of image information that other image analysis methods do not. Examining the changes in these five metrics allowed us to easily discriminate between all 11 cell types, whereas differences from visual examination of the images are not as apparent. These results demonstrate that application of the cell-graph technique to 3D image data yields discriminative metrics that have the potential to improve the accuracy of image-based tissue profiles, and thus improve the detection and diagnosis of disease.</p

    A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson’s disease

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    Background: The aim of this study was to evaluate the efficacy of a group Cognitive Behavioural Therapy (CBT) treatment for depression and anxiety in Parkinson’s disease (PD). Methods: A waitlist-controlled trial design was used. Eighteen adults with PD and a comorbid DSM-IV-TR diagnosis of depression and/or anxiety were randomised to either Intervention (8-week group CBT treatment) or Waitlist (8-week clinical monitoring preceding treatment). The Depression, Anxiety, Stress Scale-21 (DASS-21) was the primary outcome. Assessments were completed at Time 1 (pretreatment), Time 2 (posttreatment/post-waitlist) and 1-month and 6-month follow-ups. Results: At Time 2, participants who received CBT reported greater reductions in depression (Mchange = -2.45) than Waitlist participants (Mchange = .29) and this effect was large, d = 1.12, p = .011. Large secondary effects on anxiety were also observed for CBT participants, d = .89, p = .025. All treatment gains were maintained and continued to improve during the follow-up period. At 6-month follow-up, significant and large effects were observed for both depression (d = 2.07) and anxiety (d = 2.26). Conclusions: Group CBT appears to be an efficacious treatment approach for depression and anxiety in PD however further controlled trials with larger numbers of participants are required

    Identification and characterization of secreted and pathogenesis-related proteins in Ustilago maydis

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    Interactions between plants and fungal pathogens require a complex interplay at the plant–fungus interface. Extracellular effector proteins are thought to play a crucial role in establishing a successful infection. To identify pathogenesis-related proteins in Ustilago maydis we combined the isolation of secreted proteins using a signal sequence trap approach with bioinformatic analyses and the subsequent characterization of knock-out mutants. We identified 29 secreted proteins including hydrophobins and proteins with a repetitive structure similar to the repellent protein Rep1. Hum3, a protein containing both, a hydrophobin domain and a repetitive Rep1-like region, is shown to be processed during passage through the secretory pathway. While single knock-outs of hydrophobin or repellent-like genes did not affect pathogenicity, we found a strong effect of a double knock-out of hum3 and the repetitive rsp1. Yeast-like growth, mating, aerial hyphae formation and surface hydrophobicity were unaffected in this double mutant. However, pathogenic development in planta stops early after penetration leading to a complete loss of pathogenicity. This indicates that Hum3 and Rsp1 are pathogenicity proteins that share an essential function in early stages of the infection. Our results demonstrate that focusing on secreted proteins is a promising way to discover novel pathogenicity proteins that might be broadly applied to a variety of fungal pathogens

    Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study

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    <p>Abstract</p> <p>Background</p> <p>The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1) improve nutrition, (2) increase health literacy and, (3) increase physical activity. This study is a response to this call to action.</p> <p>Methods</p> <p>After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1). Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2).</p> <p>Results</p> <p>There were no significant differences between the two groups in baseline bone mineral density (BMD) or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass). In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition.</p> <p>Both groups experienced a significant positive mean annualized percent change (MAPC) in BMD compared to expectation [AlgaeCal 1: 1.15%, <it>p </it>= 0.001; AlgaeCal 2: 2.79%, <it>p </it>= 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, <it>p </it>= 0.14; AlgaeCal 2: 2.18%, <it>p </it>< 0.001]. The MAPC in AlgaeCal 2 was significantly greater than that in AlgaeCal 1 (<it>p </it>= 0.005). The MAPC contrast between compliant and partially compliant subjects was significant for both plans (<it>p </it>= 0.001 and <it>p </it>= 0.003 respectively). No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group.</p> <p>Conclusions</p> <p>Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from baseline was significantly greater than the increase from baseline in AlgaeCal 1. Increased compliance was associated with greater increases in BMD in both groups. No adverse effects were reported in either group.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01114685">NCT01114685</a></p
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