192 research outputs found

    The Fisk-Vanderbilt Master’s-to-Ph.D. Bridge Program: Recognizing, Enlisting, and Cultivating Unrealized or Unrecognized Potential in Underrepresented Minority Students

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    The Fisk-Vanderbilt Masters-to-Ph.D. Bridge Program is a model for substantially increasing the number of underrepresented minority students earning doctoral degrees in the physical sciences. The program presently leads the nation in master’s degrees in physics for African-Americans, and is one of the top ten producers of physics master’s degrees among all U.S. citizens. The program is on pace to become the nation’s top producer of underrepresented minority Ph.Ds. in physics, astronomy, and materials science. We summarize the main features of the program, including two of its core strategies: Partnering a minority-serving institution and a major research university through collaborative research, and using the master’s degree as a pathway to the Ph.D. We discuss our methods for recognizing and selecting for unrealized potential in students during the admissions process, and for cultivating this potential to develop successful scientists and leaders

    Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics

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    Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)–induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin–GIT1 binding and promoting the localization of a GIT1–PIX–PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20–30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1–PIX–PAK module near the leading edge

    'Relieved to be seen'-patient and carer experiences of psychosocial assessment in the emergency department following self-harm: qualitative analysis of 102 free-text survey responses.

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    From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-23Publication status: PublishedObjectivesWe sought to explore patient and carer experiences of psychosocial assessments following presentations to hospital after self-harm.DesignThematic analysis of free-text responses to an open-ended online survey.SettingBetween March and November 2019, we recruited 88 patients (82% women) and 14 carers aged ≥18 years from 16 English mental health trusts, community organisations, and via social media.ResultsPsychosocial assessments were experienced as helpful on some occasions but harmful on others. Participants felt better, less suicidal and less likely to repeat self-harm after good-quality compassionate and supportive assessments. However, negative experiences during the assessment pathway were common and, in some cases, contributed to greater distress, less engagement and further self-harm. Participants reported receiving negative and stigmatising comments about their injuries. Others reported that they were refused medical care or an anaesthetic. Stigmatising attitudes among some mental health staff centred on preconceived ideas over self-harm as a 'behavioural issue', inappropriate use of services and psychiatric diagnosis.ConclusionOur findings highlight important patient experiences that can inform service provision and they demonstrate the value of involving patients/carers throughout the research process. Psychosocial assessments can be beneficial when empathetic and collaborative but less helpful when overly standardised, lacking in compassion and waiting times are unduly long. Patient views are essential to inform practice, particularly given the rapidly changing service context during and after the COVID-19 emergency

    Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor

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    The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier

    Large-Scale Variation in Wave Attenuation of Oyster Reef Living Shorelines and the Influence of Inundation Duration

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    One of the paramount goals of oyster reef living shorelines is to achieve sustained and adaptive coastal protection, which requires meeting ecological (i.e., develop a self-sustaining oyster population) and engineering (i.e., provide coastal defense) targets. In a large-scale comparison along the Atlantic and Gulf coasts of the United States, the efficacy of various designs of oyster reef living shorelines at providing wave attenuation was evaluated accounting for the ecological limitations of oysters with regards to inundation duration. A critical threshold for intertidal oyster reef establishment is 50% inundation duration. Living shorelines that spent less than half of the time (\u3c 50%) inundated were not considered suitable habitat for oysters, however, were effective at wave attenuation (68% reduction in wave height). Reefs that experienced \u3e 50% inundation were considered suitable habitat for oysters, but wave attenuation was similar to controls (no reef; ~5% reduction in wave height). Many of the oyster reef living shoreline approaches therefore failed to optimize the ecological and engineering goals. In both inundation regimes, wave transmission decreased with an increasing freeboard (difference between reef crest elevation and water level), supporting its importance in the wave attenuation capacity of oyster reef living shorelines. However, given that the reef crest elevation (and thus freeboard) should be determined by the inundation duration requirements of oysters, research needs to be re-focused on understanding the implications of other reef parameters (e.g. width) for optimising wave attenuation. A broader understanding of the reef characteristics and seascape contexts that result in effective coastal defense by oyster reefs is needed to inform appropriate design and implementation of oyster-based living shorelines globally

    The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

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    Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.National Human Genome Research Institute (U.S.) (Grant number 1U54HG004555-01)Wellcome Trust (London, England) (Grant number WT062023)Wellcome Trust (London, England) (Grant number WT077198

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

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    We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases
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