Influence of Pacing Mode and Rate on Peripheral Levels of Atrial Natriuretic Peptide (ANP)

The effect of acute modifications of pacing mode and rate on plasma ANP levels was evaluated. ANP was determined in ten resting patients with ODD pacemokers due to binodal disease or intermittent second- and third-degree AV block. At 82/minute pacing rate the ANP plasma levels (normal range 2 to 30 fmol/mL) corresponded to those under AAI (4.05 ± 2.10 fmol/mL) and DDD (4.18 ± 2.02 fmol/mL) pacing, but increased significantly (P < 0.05) during VVI pacing (6.96 ± 3.70 fmol/mL). Acceleration of DDD stimulation frequency from 82 to 113/minutes led to significant increases of ANP levels by the factor of three in all chosen AV delays. The lowest ANP plasma levels were measured of 175 msec AV delay under 82/minute pacing rate in DDD mode. Under 113/minutes the differences of ANP concentration after variations of AV delays were less pronounced. The influences of altered atrial pressure and tension on ANP release are discussed to account for changes in ANP plasma levels following different modes and rates of pacemaker stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75366/1/j.1540-8159.1989.tb01862.x.pd

Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP.

We aimed to develop an efficient, flexible and scalable approach to diagnostic genome-wide sequence analysis of genetically heterogeneous clinical presentations. Here we present G2P ( www.ebi.ac.uk/gene2phenotype ) as an online system to establish, curate and distribute datasets for diagnostic variant filtering via association of allelic requirement and mutational consequence at a defined locus with phenotypic terms, confidence level and evidence links. An extension to Ensembl Variant Effect Predictor (VEP), VEP-G2P was used to filter both disease-associated and control whole exome sequence (WES) with Developmental Disorders G2P (G2PDD; 2044 entries). VEP-G2PDD shows a sensitivity/precision of 97.3%/33% for de novo and 81.6%/22.7% for inherited pathogenic genotypes respectively. Many of the missing genotypes are likely false-positive pathogenic assignments. The expected number and discriminative features of background genotypes are defined using control WES. Using only human genetic data VEP-G2P performs well compared to other freely-available diagnostic systems and future phenotypic matching capabilities should further enhance performance

EyeG2P: an automated variant filtering approach improves efficiency of diagnostic genomic testing for inherited ophthalmic disorders

BACKGROUND: Genomic variant prioritisation is one of the most significant bottlenecks to mainstream genomic testing in healthcare. Tools to improve precision while ensuring high recall are critical to successful mainstream clinical genomic testing, in particular for whole genome sequencing where millions of variants must be considered for each patient. METHODS: We developed EyeG2P, a publicly available database and web application using the Ensembl Variant Effect Predictor. EyeG2P is tailored for efficient variant prioritisation for individuals with inherited ophthalmic conditions. We assessed the sensitivity of EyeG2P in 1234 individuals with a broad range of eye conditions who had previously received a confirmed molecular diagnosis through routine genomic diagnostic approaches. For a prospective cohort of 83 individuals, we assessed the precision of EyeG2P in comparison with routine diagnostic approaches. For 10 additional individuals, we assessed the utility of EyeG2P for whole genome analysis. RESULTS: EyeG2P had 99.5% sensitivity for genomic variants previously identified as clinically relevant through routine diagnostic analysis (n=1234 individuals). Prospectively, EyeG2P enabled a significant increase in precision (35% on average) in comparison with routine testing strategies (p<0.001). We demonstrate that incorporation of EyeG2P into whole genome sequencing analysis strategies can reduce the number of variants for analysis to six variants, on average, while maintaining high diagnostic yield. CONCLUSION: Automated filtering of genomic variants through EyeG2P can increase the efficiency of diagnostic testing for individuals with a broad range of inherited ophthalmic disorders

Knowledge Sharing on Best Practices for Managing Crop Genebanks

The Crop Genebank Knowledge Base (CGKB) is an initiative of the Consultative Group of International Agriculture Research (CGIAR) System-wide Genetic Resources Programme (SGRP). The CGKB was created for sharing knowledge about best practices for managing plant genetic resources (PGR), and making effective decisions about genebank management. Genebank practices from CGIAR Centers and national genebanks were gathered for nine crops (banana, barley, cassava, chickpea, forage grasses and legumes, maize, rice and wheat). This information will help PGR professionals to participate in a global crop conservation effort. An interactive approach with many partners and stakeholders was used to gather published and unpublished information about genebank management. Information on crop-specific best practices was initially collected from crop experts using pre-defined forms. In parallel, a web portal was developed using the open-source content management system (CMS) Joomla!. The CMS allows several editors to maintain pages and update them. Other participatory tools such as wiki pages, a blog, a discussion forum and online forms have been set up to gather future contributions, including information on other crops. The site provides a one-stop platform for information on conservation, characterization, regeneration and safety duplication of each of the nine crops. It also provides information on general (non-crop-specific) genebank management procedures, as well as a comprehensive bibliography of online publications, a glossary, links to relevant external websites, video and photo materials, and training modules. This paper discusses a process of collective action to develop a multi-institutional web platform, highlights important criteria for success, challenges and major lessons learned, and proposes options for the way forward

Ensembl 2014

Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate genomic analysis in chordate species with an emphasis on human, major vertebrate model organisms and farm animals. Over the past year we have increased the number of species that we support to 77 and expanded our genome browser with a new scrollable overview and improved variation and phenotype views. We also report updates to our core datasets and improvements to our gene homology relationships from the addition of new species. Our REST service has been extended with additional support for comparative genomics and ontology information. Finally, we provide updated information about our methods for data access and resources for user training

Moth assemblages in Costa Rica rain forest mirror small-scale topographic heterogeneity

In many tropical lowland rain forests, topographic variation increases environmental heterogeneity, thus contributing to the extraordinary biodiversity of tropical lowland forests. While a growing number of studies have addressed effects of topographic differences on tropical insect communities at regional scales (e.g., along extensive elevational gradients), surprisingly little is known about topographic effects at smaller spatial scales. The present study investigates moth assemblages in a topographically heterogeneous lowland rain forest landscape, at distances of less than a few hundred meters, in the Golfo Dulce region (SW Costa Rica). Three moth lineages—Erebidae–Arctiinae (tiger and lichen moths), the bombycoid complex, and Geometridae (inchworm moths)—were examined by means of automatic light traps in three different forest types: creek forest, slope forest, and ridge forest. Altogether, 6,543 individuals of 419 species were observed. Moth assemblages differed significantly between the three forest types regarding species richness, total abundance, and species composition. Moth richness and abundance increased more than fourfold and eightfold from creek over slope to ridge forest sites. All three taxonomic units showed identical biodiversity patterns, notwithstanding their strong differences in multiple eco‐morphological traits. An indicator species analysis revealed that most species identified as characteristic were associated either with the ridge forest alone or with ridge plus slope forests, but very few with the creek forest. Despite their mobility, local moth assemblages are highly differentially filtered from the same regional species pool. Hence, variation in environmental factors significantly affects assemblages of tropical moth species at small spatial scales

agr-Mediated Dispersal of Staphylococcus aureus Biofilms

The agr quorum-sensing system of Staphylococcus aureus modulates the expression of virulence factors in response to autoinducing peptides (AIPs). Recent studies have suggested a role for the agr system in S. aureus biofilm development, as agr mutants exhibit a high propensity to form biofilms, and cells dispersing from a biofilm have been observed displaying an active agr system. Here, we report that repression of agr is necessary to form a biofilm and that reactivation of agr in established biofilms through AIP addition or glucose depletion triggers detachment. Inhibitory AIP molecules did not induce detachment and an agr mutant was non-responsive, indicating a dependence on a functional, active agr system for dispersal. Biofilm detachment occurred in multiple S. aureus strains possessing divergent agr systems, suggesting it is a general S. aureus phenomenon. Importantly, detachment also restored sensitivity of the dispersed cells to the antibiotic rifampicin. Proteinase K inhibited biofilm formation and dispersed established biofilms, suggesting agr-mediated detachment occurred in an ica-independent manner. Consistent with a protease-mediated mechanism, increased levels of serine proteases were detected in detaching biofilm effluents, and the serine protease inhibitor PMSF reduced the degree of agr-mediated detachment. Through genetic analysis, a double mutant in the agr-regulated Aur metalloprotease and the SplABCDEF serine proteases displayed minimal extracellular protease activity, improved biofilm formation, and a strongly attenuated detachment phenotype. These findings indicate that induction of the agr system in established S. aureus biofilms detaches cells and demonstrate that the dispersal mechanism requires extracellular protease activity

Meta-analysis of heterogeneous Down Syndrome data reveals consistent genome-wide dosage effects related to neurological processes

<p>Abstract</p> <p>Background</p> <p>Down syndrome (DS; trisomy 21) is the most common genetic cause of mental retardation in the human population and key molecular networks dysregulated in DS are still unknown. Many different experimental techniques have been applied to analyse the effects of dosage imbalance at the molecular and phenotypical level, however, currently no integrative approach exists that attempts to extract the common information.</p> <p>Results</p> <p>We have performed a statistical meta-analysis from 45 heterogeneous publicly available DS data sets in order to identify consistent dosage effects from these studies. We identified 324 genes with significant genome-wide dosage effects, including well investigated genes like <it>SOD1</it>, <it>APP</it>, <it>RUNX1 </it>and <it>DYRK1A </it>as well as a large proportion of novel genes (N = 62). Furthermore, we characterized these genes using gene ontology, molecular interactions and promoter sequence analysis. In order to judge relevance of the 324 genes for more general cerebral pathologies we used independent publicly available microarry data from brain studies not related with DS and identified a subset of 79 genes with potential impact for neurocognitive processes. All results have been made available through a web server under <url>http://ds-geneminer.molgen.mpg.de/</url>.</p> <p>Conclusions</p> <p>Our study represents a comprehensive integrative analysis of heterogeneous data including genome-wide transcript levels in the domain of trisomy 21. The detected dosage effects build a resource for further studies of DS pathology and the development of new therapies.</p

The combined effects of obesity, abdominal obesity and major depression/anxiety on health-related quality of life: The lifelines cohort study

Copyrigh