347 research outputs found

    Identifying multiple coral reef regimes and their drivers across the Hawaiian archipelago

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    Loss of coral reef resilience can lead to dramatic changes in benthic structure, often called regime shifts, which significantly alter ecosystem processes and functioning. In the face of global change and increasing direct human impacts, there is an urgent need to anticipate and prevent undesirable regime shifts and, conversely, to reverse shifts in already degraded reef systems. Such challenges require a better understanding of the human and natural drivers that support or undermine different reef regimes. The Hawaiian archipelago extends across a wide gradient of natural and anthropogenic conditions and provides us a unique opportunity to investigate the relationships between multiple reef regimes, their dynamics and potential drivers. We applied a combination of exploratory ordination methods and inferential statistics to one of the most comprehensive coral reef datasets available in order to detect, visualize and define potential multiple ecosystem regimes. This study demonstrates the existence of three distinct reef regimes dominated by hard corals, turf algae or macroalgae. Results from boosted regression trees show nonlinear patterns among predictors that help to explain the occurrence of these regimes, and highlight herbivore biomass as the key driver in addition to effluent, latitude and depth

    Molecular signatures of neurodegeneration in the cortex of PS1/PS2 double knockout mice

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    <p>Abstract</p> <p>Background</p> <p>Familial Alzheimer's disease-linked variants of presenilin (PSEN1 and PSEN2) contribute to the pathophysiology of disease by both gain-of-function and loss-of-function mechanisms. Deletions of <it>PSEN1 </it>and <it>PSEN2 </it>in the mouse forebrain result in a strong and progressive neurodegenerative phenotype which is characterized by both anatomical and behavioral changes.</p> <p>Results</p> <p>To better understand the molecular changes associated with these morphological and behavioral phenotypes, we performed a DNA microarray transcriptome profiling of the hippocampus and the frontal cortex of the <it>PSEN1/PSEN2 </it>double knock-out mice and littermate controls at five different ages ranging from 2–8 months. Our data suggest that combined deficiencies of <it>PSEN1 </it>and <it>PSEN2 </it>results in a progressive, age-dependent transcriptome signature related to neurodegeneration and neuroinflammation. While these events may progress differently in the hippocampus and frontal cortex, the most critical expression signatures are common across the two brain regions, and involve a strong upregulation of <it>cathepsin </it>and <it>complement </it>system transcripts.</p> <p>Conclusion</p> <p>The observed neuroinflammatory expression changes are likely to be causally linked to the neurodegenerative phenotype observed in mice with compound deletions of <it>PSEN1 </it>and <it>PSEN2</it>. Furthermore, our results suggest that the evaluation of inhibitors of PS/γ-secretase activity for treatment of Alzheimer's Disease must include close monitoring for signs of calpain-cathepsin system activation.</p

    Plug-Based Microfluidics with Defined Surface Chemistry to Miniaturize and Control Aggregation of Amyloidogenic Peptides

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    Small with control: For miniaturization of protein aggregation experiments the interfacial chemistry must be controlled to avoid protein aggregation caused by interfacial adsorption. Plug-based microfluidics with defined surface chemistry (see schematic picture) can then be used to perform hundreds of aggregation experiments with volume-limited samples, such as cerebrospinal fluid from mice

    Characterization of HIV-Specific CD4+T Cell Responses against Peptides Selected with Broad Population and Pathogen Coverage

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    CD4+ T cells orchestrate immunity against viral infections, but their importance in HIV infection remains controversial. Nevertheless, comprehensive studies have associated increase in breadth and functional characteristics of HIV-specific CD4+ T cells with decreased viral load. A major challenge for the identification of HIV-specific CD4+ T cells targeting broadly reactive epitopes in populations with diverse ethnic background stems from the vast genomic variation of HIV and the diversity of the host cellular immune system. Here, we describe a novel epitope selection strategy, PopCover, that aims to resolve this challenge, and identify a set of potential HLA class II-restricted HIV epitopes that in concert will provide optimal viral and host coverage. Using this selection strategy, we identified 64 putative epitopes (peptides) located in the Gag, Nef, Env, Pol and Tat protein regions of HIV. In total, 73% of the predicted peptides were found to induce HIV-specific CD4+ T cell responses. The Gag and Nef peptides induced most responses. The vast majority of the peptides (93%) had predicted restriction to the patient’s HLA alleles. Interestingly, the viral load in viremic patients was inversely correlated to the number of targeted Gag peptides. In addition, the predicted Gag peptides were found to induce broader polyfunctional CD4+ T cell responses compared to the commonly used Gag-p55 peptide pool. These results demonstrate the power of the PopCover method for the identification of broadly recognized HLA class II-restricted epitopes. All together, selection strategies, such as PopCover, might with success be used for the evaluation of antigen-specific CD4+ T cell responses and design of future vaccines

    Active Tension Network model suggests an exotic mechanical state realized in epithelial tissues.

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    Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal - "isogonal" - deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit y embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena

    Hydrocarbon Biogeochemical Setting of the Baffin Island Oil Spill Experimental Sites. III. Biota

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    A baseline for petroleum residues in the Cape Hatt region of Baffin Island in arctic Canada was obtained in anticipation of controlled oil releases of the Baffin Island Oil Spill (BIOS) Project. Tissue hydrocarbons in a variety of arctic marine species were dominated by biogenic hydrocarbons. UV/F analysis of tissues indicated an upper limit of petroleum residues in the low to sub micro g/g concentration range. PAHs were detected in samples in the low ng/g concentration range and revealed a distribution of the combustion type. The hydrocarbon baseline in the BIOS study area was found to be as low as might be found anywhere on earth and therefore ideally suited to the BIOS study.Key words: BIOS, arctic marine Canada, hydrocarbon baseline, organismsMots cl&eacute;s: BIOS, Arctique marin canadien, niveau de r&eacute;f&eacute;rence d&rsquo;hydrocarbures, organisme

    Parsing human and biophysical drivers of coral reef regimes

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    Coral reefs worldwide face unprecedented cumulative anthropogenic effects of interacting local human pressures, global climate change and distal social processes. Reefs are also bound by the natural biophysical environment within which they exist. In this context, a key challenge for effective management is understanding how anthropogenic and biophysical conditions interact to drive distinct coral reef configurations. Here, we use machine learning to conduct explanatory predictions on reef ecosystems defined by both fish and benthic communities. Drawing on the most spatially extensive dataset available across the Hawaiian archipelago-20 anthropogenic and biophysical predictors over 620 survey sites-we model the occurrence of four distinct reef regimes and provide a novel approach to quantify the relative influence of human and environmental variables in shaping reef ecosystems. Our findings highlight the nuances of what underpins different coral reef regimes, the overwhelming importance of biophysical predictors and how a reef's natural setting may either expand or narrow the opportunity space for management interventions. The methods developed through this study can help inform reef practitioners and hold promises for replication across a broad range of ecosystems. © 2019 The Author(s

    Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

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    Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc
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