Tissue resolved, gene structure refined equine transcriptome.

BackgroundTranscriptome interpretation relies on a good-quality reference transcriptome for accurate quantification of gene expression as well as functional analysis of genetic variants. The current annotation of the horse genome lacks the specificity and sensitivity necessary to assess gene expression especially at the isoform level, and suffers from insufficient annotation of untranslated regions (UTR) usage. We built an annotation pipeline for horse and used it to integrate 1.9 billion reads from multiple RNA-seq data sets into a new refined transcriptome.ResultsThis equine transcriptome integrates eight different tissues from 59 individuals and improves gene structure and isoform resolution, while providing considerable tissue-specific information. We utilized four levels of transcript filtration in our pipeline, aimed at producing several transcriptome versions that are suitable for different downstream analyses. Our most refined transcriptome includes 36,876 genes and 76,125 isoforms, with 6474 candidate transcriptional loci novel to the equine transcriptome.ConclusionsWe have employed a variety of descriptive statistics and figures that demonstrate the quality and content of the transcriptome. The equine transcriptomes that are provided by this pipeline show the best tissue-specific resolution of any equine transcriptome to date and are flexible for several downstream analyses. We encourage the integration of further equine transcriptomes with our annotation pipeline to continue and improve the equine transcriptome

Enterprise integration lessons learned, Journal of Telecommunications and Information Technology, 2004, nr 4

This document describes the lessons learned from a United States Navy enterprise integration initiative called Web Enabled Navy (WEN). WEN was initiated in April 2001 with the foci of integrating navy resources and providing a single-point-of-access, Web environment to all business and operational applications. The navy's applications operate within a complex network environment that spans commands afloat, ashore, and overseas. The challenges addressed are similar to those faced by large, multi-national corporations and include some unusual characteristics including islands of intermittently, bandwidth-limited, connected information consumers. Both technical and management lessons learned will be described and denoted as either prerequisite or success factors

Flip the Clinic: A Digital Health Approach to Youth Mental Health Service Delivery During the COVID-19 Pandemic and Beyond.

The demand for mental health services is projected to rapidly increase as a direct and indirect result of the COVID-19 pandemic. Given that young people are disproportionately disadvantaged by mental illness and will face further challenges related to the COVID-19 pandemic, it is crucial to deliver appropriate mental health care to young people as early as possible. Integrating digital health solutions into mental health service delivery pathways has the potential to greatly increase efficiencies, enabling the provision of "right care, first time." We propose an innovative digital health solution for demand management intended for use by primary youth mental health services, comprised of (1) a youth mental health model of care (ie, the Brain and Mind Centre Youth Model) and (2) a health information technology specifically designed to deliver this model of care (eg, the InnoWell Platform). We also propose an operational protocol of how this solution could be applied to primary youth mental health service delivery processes. By "flipping" the conventional service delivery models of majority in-clinic and minority web-delivered care to a model where web-delivered care is the default, this digital health solution offers a scalable way of delivering quality youth mental health care both in response to public health crises (such as the COVID-19 pandemic) and on an ongoing basis in the future

Current and Future Remote Sensing of Harmful Algal Blooms in the Chesapeake Bay to Support the Shellfish Industry

Harmful algal bloom (HAB) species in the Chesapeake Bay can negatively impact fish, shellfish, and human health via the production of toxins and the degradation of water quality. Due to the deleterious effects of HAB species on economically and environmentally important resources, such as oyster reef systems, Bay area resource managers are seeking ways to monitor HABs and water quality at large spatial and fine temporal scales. The use of satellite ocean color imagery has proven to be a beneficial tool for resource management in other locations around the world where high-biomass, nearly monospecific HABs occur. However, remotely monitoring HABs in the Chesapeake Bay is complicated by the presence of multiple, often co-occurring, species and optically complex waters. Here we present a summary of common marine and estuarine HAB species found in the Chesapeake Bay, Alexandrium monilatum, Karlodinium veneficum, Margalefidinium polykrikoides, and Prorocentrum minimum, that have been detected from space using multispectral data products from the Ocean and Land Colour Imager (OLCI) sensor on the Sentinel-3 satellites and identified based on in situ phytoplankton data and ecological associations. We review how future hyperspectral instruments will improve discrimination of potentially harmful species from other phytoplankton communities and present a framework in which satellite data products could aid Chesapeake Bay resource managers with monitoring water quality and protecting shellfish resources

Reproductive Trade-Offs May Moderate the Impact of Gyrodactylus salaris in Warmer Climates

Gyrodactylus salaris is a notifiable freshwater ectoparasite of salmonids. Its primary host is Atlantic salmon (Salmo salar), upon which infections can cause death, and have led to massive declines in salmon numbers in Norway, where the parasite is widespread. Different strains of S. salar vary in their susceptibility, with Atlantic strains (such as those found in Norway) exhibiting no resistance to the parasite, and Baltic strains demonstrating an innate resistance sufficient to regulate parasite numbers on the host causing it to either die out or persist at a low level. In this study, Leslie matrix and compartmental models were used to generate data that demonstrated the population growth of G. salaris on an individual host is dependent on the total number of offspring per parasite, its longevity and the timing of its births. The data demonstrated that the key factor determining the rate of G. salaris population growth is the time at which the parasite first gives birth, with rapid birth rate giving rise to large population size. Furthermore, it was shown that though the parasite can give birth up to four times, only two births are required for the population to persist as long as the first birth occurs before a parasite is three days old. As temperature is known to influence the timing of the parasite's first birth, greater impact may be predicted if introduced to countries with warmer climates than Norway, such as the UK and Ireland which are currently recognised to be free of G. salaris. However, the outputs from the models developed in this study suggest that temperature induced trade-offs between the total number of offspring the parasite gives birth to and the first birth timing may prevent increased population growth rates over those observed in Norway

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing

Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large inter-patient variability partly due to genetic variations in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: www.pharmgkb.org)

Nonlinear thermoelectric response of quantum dots: renormalized dual fermions out of equilibrium

The thermoelectric transport properties of nanostructured devices continue to attract attention from theorists and experimentalist alike as the spatial confinement allows for a controlled approach to transport properties of correlated matter. Most of the existing work, however, focuses on thermoelectric transport in the linear regime despite the fact that the nonlinear conductance of correlated quantum dots has been studied in some detail throughout the last decade. Here, we review our recent work on the effect of particle-hole asymmetry on the nonlinear transport properties in the vicinity of the strong coupling limit of Kondo-correlated quantum dots and extend the underlying method, a renormalized superperturbation theory on the Keldysh contour, to the thermal conductance in the nonlinear regime. We determine the charge, energy, and heat current through the nanostructure and study the nonlinear transport coefficients, the entropy production, and the fate of the Wiedemann-Franz law in the non-thermal steady-state. Our approach is based on a renormalized perturbation theory in terms of dual fermions around the particle-hole symmetric strong-coupling limit.Comment: chapter contributed to 'New Materials for Thermoelectric Applications: Theory and Experiment' Springer Series: NATO Science for Peace and Security Series - B: Physics and Biophysics, Veljko Zlatic (Editor), Alex Hewson (Editor). ISBN: 978-9400749863 (2012

Cognitive-Behavior Therapy (CBT) for Panic Disorder: Relationship of Anxiety and Depression Comorbidity with Treatment Outcome

Research evaluating the relationship of comorbidity to treatment outcome for panic disorder has produced mixed results. The current study examined the relationship of comorbid depression and anxiety to treatment outcome in a large-scale, multi-site clinical trial for cognitive-behavior therapy (CBT) for panic disorder. Comorbidity was associated with more severe panic disorder symptoms, although comorbid diagnoses were not associated with treatment response. Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) were not associated with differential improvement on a measure of panic disorder severity, although only rates of comorbid GAD were significantly lower at posttreatment. Treatment responders showed greater reductions on measures of anxiety and depressive symptoms. These data suggest that comorbid anxiety and depression are not an impediment to treatment response, and successful treatment of panic disorder is associated with reductions of comorbid anxiety and depressive symptoms. Implications for treatment specificity and conceptual understandings of comorbidity are discussed