152 research outputs found

    Dimensions of biodiversity in Chesapeake Bay demersal fishes: patterns and drivers through space and time

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    Biodiversity has typically been described in terms of species richness and composition, but theory and growing empirical evidence indicate that the diversity of functional traits, the breadth of evolutionary relationships, and the equitability with which individuals or biomass are distributed among species better characterize patterns and processes within ecosystems. Yet, the advantages of including such data come at the expense of measuring traits, sequencing genes, and counting or weighing individuals, and it remains unclear whether this greater resolution yields substantial benefits in describing diversity. We summarized a decade of high-resolution trawl data from a bimonthly trawl survey to investigate spatial and seasonal patterns of demersal fish diversity in the Chesapeake Bay, USA, with the goal of identifying areas and times of mismatch between different dimensions of diversity, and their response to environmental forcing. We found moderate to strong positive relationships among all metrics of diversity, and that functional and phylogenetic differences were well-reflected in an index derived from taxonomic (Linnaean) hierarchy. Compared with species richness and species diversity, functional, phylogenetic, and taxonomic indices peaked later in the year, which was a consequence of the distribution of biomass among functionally and evolutionarily divergent species. Generalized additive models revealed that spatial, temporal, and environmental variables explained roughly similar proportions of deviance across all aspects of diversity, suggesting that these three factors do not differentially affect the functional and phylogenetic aspects of community structure. We conclude that an index of diversity derived from taxonomic hierarchy served well as a practical surrogate for functional and phylogenetic diversity of the demersal fish community in this system. We also emphasize the importance of evenness in understanding diversity patterns, especially since most ecological communities in nature are dominated by one or few species

    Variants Within TSC2 Exons 25 and 31 Are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis

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    Inactivating mutations in TSC1 and TSC2 cause tuberous sclerosis complex (TSC). The 2012 international consensus meeting on TSC diagnosis and management agreed that the identification of a pathogenic TSC1 or TSC2 variant establishes a diagnosis of TSC, even in the absence of clinical signs. However, exons 25 and 31 of TSC2 are subject to alternative splicing. No variants causing clinically diagnosed TSC have been reported in these exons, raising the possibility that such variants would not cause TSC. We present truncating and in‐frame variants in exons 25 and 31 in three individuals unlikely to fulfil TSC diagnostic criteria and examine the importance of these exons in TSC using different approaches. Amino acid conservation analysis suggests significantly less conservation in these exons compared with the majority of TSC2 exons, and TSC2 expression data demonstrates that the majority of TSC2 transcripts lack exons 25 and/or 31 in many human adult tissues. In vitro assay of both exons shows that neither exon is essential for TSC complex function. Our evidence suggests that variants in TSC2 exons 25 or 31 are very unlikely to cause classical TSC, although a role for these exons in tissue/stage specific development cannot be excluded

    Pilot testing the feasibility of a game intervention aimed at improving help seeking and coping among sexual and gender minority youth: protocol for a randomized controlled trial

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    Background: Sexual and gender minority youth (SGMY; e.g., lesbian, gay, bisexual, and transgender youth) experience myriad substance use and mental health disparities compared with their cisgender (non-transgender) heterosexual peers. Despite much research showing these disparities are driven by experiences of bullying and cyberbullying victimization, few interventions have aimed to improve the health of bullied SGMY. One possible way to improve the health of bullied SGMY is via an online-accessible game intervention. Nevertheless, little research has examined the feasibility of using an online-accessible game intervention with SGMY. Objectives: To describe the protocol for a randomized controlled trial (RCT) pilot testing the feasibility and limited-efficacy of a game-based intervention for increasing help-seeking-related knowledge, intentions, self-efficacy, and behaviors, productive coping skills use, and coping flexibility, and reducing health risk factors and behaviors among SGMY. Methods: We enrolled 240 SGMY aged 14-18 years residing in the United States into a two-arm prospective RCT. The intervention is a theory-based, community-informed, computer-based, role playing game with three primary components: (1) encouraging help-seeking behaviors; (2) encouraging use of productive coping; and (3) raising awareness of online resources. SGMY randomized to both the intervention and control conditions will receive a list of SGMY-inclusive resources covering a variety of health-related topics. Control condition participants received only the list of resources. Notably, all study procedures are conducted online. We conveniently sampled SGMY using online website advertisements. Study assessments occur at enrollment, 1 month after enrollment, and 2 months after enrollment. The primary outcomes of this feasibility study include implementation procedures, game demand, and game acceptability. Secondary outcomes include help-seeking intentions, self-efficacy, and behaviors; productive coping strategies and coping flexibility; and knowledge and use of online resources. Tertiary outcomes include bullying and cyberbullying victimization; loneliness; mental health issues; substance use; and internalized sexual and gender minority stigma. Results: From April through July 2018, 240 participants were enrolled and randomized. Half of the enrolled participants (n=120) were randomized into the intervention condition, and half (n=120) into the control condition. At baseline, 52% of participants identified as gay or lesbian, 27% as bisexual, 24% as queer, and 12% as another non-heterosexual identity. Nearly half (47%) of participants were a gender minority, 37% were cisgender boys, and 16% were cisgender girls. There were no differences in demographic characteristics between intervention and control condition participants. Data collection is anticipated to end in November 2018. Conclusions: Online-accessible game interventions overcome common impediments of face-to-face interventions and present a unique opportunity to reach SGMY and improve their health. This trial will provide data on feasibility and limited-efficacy that can inform future online studies and a larger RCT aimed at improving health equity for SGMY. Trial Registration: ClinicalTrials.gov NCT03501264; https://clinicaltrials.gov/ct2/show/NCT03501264 (Archived by WebCite at http://www.webcitation.org/72HpafarW

    Periodic Sequence Distribution of Product Ion Abundances in Electron Capture Dissociation of Amphipathic Peptides and Proteins

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    The rules for product ion formation in electron capture dissociation (ECD) mass spectrometry of peptides and proteins remain unclear. Random backbone cleavage probability and the nonspecific nature of ECD toward amino acid sequence have been reported, contrary to preferential channels of fragmentation in slow heating-based tandem mass spectrometry. Here we demonstrate that for amphipathic peptides and proteins, modulation of ECD product ion abundance (PIA) along the sequence is pronounced. Moreover, because of the specific primary (and presumably secondary) structure of amphipathic peptides, PIA in ECD demonstrates a clear and reproducible periodic sequence distribution. On the one hand, the period of ECD PIA corresponds to periodic distribution of spatially separated hydrophobic and hydrophilic domains within the peptide primary sequence. On the other hand, the same period correlates with secondary structure units, such as a-helical turns, known for solution-phase structure. Based on a number of examples, we formulate a set of characteristic features for ECD of amphipathic peptides and proteins: (1) periodic distribution of PIA is observed and is reproducible in a wide range of ECD parameters and on different experimental platforms; (2) local maxima of PIA are not necessarily located near the charged site; (3) ion activation before ECD not only extends product ion sequence coverage but also preserves ion yield modulation; (4) the most efficient cleavage (e.g. global maximum of ECD PIA distribution) can be remote from the charged site; (5) the number and location of PIA maxima correlate with amino acid hydrophobicity maxima generally to within a single amino acid displacement; and (6) preferential cleavage sites follow a selected hydrogen spine in an a-helical peptide segment. Presently proposed novel insights into ECD behavior are important for advancing understanding of the ECD mechanism, particularly the role of peptide sequence on PIA. An improved ECD model could facilitate protein sequencing and improve identification of unknown proteins in proteomics technologies. In structural biology, the periodic/preferential product ion yield in ECD of a-helical structures potentially opens the way toward de novo site-specific secondary structure determination of peptides and proteins in the gas phase and its correlation with solution-phase structure. (J Am Soc Mass Spectrom 2009, 20, 1182-1192) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometr

    The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

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    In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD

    Computing H/D-Exchange rates of single residues from data of proteolytic fragments

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    <p>Abstract</p> <p>Background</p> <p>Protein conformation and protein/protein interaction can be elucidated by solution-phase Hydrogen/Deuterium exchange (sHDX) coupled to high-resolution mass analysis of the digested protein or protein complex. In sHDX experiments mutant proteins are compared to wild-type proteins or a ligand is added to the protein and compared to the wild-type protein (or mutant). The number of deuteriums incorporated into the polypeptides generated from the protease digest of the protein is related to the solvent accessibility of amide protons within the original protein construct.</p> <p>Results</p> <p>In this work, sHDX data was collected on a 14.5 T FT-ICR MS. An algorithm was developed based on combinatorial optimization that predicts deuterium exchange with high spatial resolution based on the sHDX data of overlapping proteolytic fragments. Often the algorithm assigns deuterium exchange with single residue resolution.</p> <p>Conclusions</p> <p>With our new method it is possible to automatically determine deuterium exchange with higher spatial resolution than the level of digested fragments.</p

    Determining and interpreting correlations in lipidomic networks found in glioblastoma cells

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    Background: Intelligent and multitiered quantitative analysis of biological systems rapidly evolves to a key technique in studying biomolecular cancer aspects. Newly emerging advances in both measurement as well as bio-inspired computational techniques have facilitated the development of lipidomics technologies and offer an excellent opportunity to understand regulation at the molecular level in many diseases. Results: We present computational approaches to study the response of glioblastoma U87 cells to gene- and chemo-therapy. To identify distinct biomarkers and differences in therapeutic outcomes, we develop a novel technique based on graph-clustering. This technique facilitates the exploration and visualization of co-regulations in glioblastoma lipid profiling data. We investigate the changes in the correlation networks for different therapies and study the success of novel gene therapies targeting aggressive glioblastoma. Conclusions: The novel computational paradigm provides unique “fingerprints” by revealing the intricate interactions at the lipidome level in glioblastoma U87 cells with induced apoptosis (programmed cell death) and thus opens a new window to biomedical frontiers. Background Glioblastoma are highly invasive brain tumors. Th
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