Multidimentional proteomics for cell biology

The proteome is a dynamic system in which each protein has interconnected properties — dimensions — that together contribute to the phenotype of a cell. Measuring these properties has proved challenging owing to their diversity and dynamic nature. Advances in mass spectrometry-based proteomics now enable the measurement of multiple properties for thousands of proteins, including their abundance, isoform expression, turnover rate, subcellular localization, post-translational modifications and interactions. Complementing these experimental developments are new data analysis, integration and visualization tools as well as data-sharing resources. Together, these advances in the multidimensional analysis of the proteome are transforming our understanding of various cellular and physiological processes

Emerging role of the calcium-activated, small conductance, SK3 K ⁺ channel in distal tubule function: Regulation by TRPV4

The Ca2+-activated, maxi-K (BK) K+ channel, with low Ca2+-binding affinity, is expressed in the distal tubule of the nephron and contributes to flow-dependent K+ secretion. In the present study we demonstrate that the Ca2+-activated, SK3 (KCa2.3) K + channel, with high Ca2+-binding affinity, is also expressed in the mouse kidney (RT-PCR, immunoblots). Immunohistochemical evaluations using tubule specific markers demonstrate significant expression of SK3 in the distal tubule and the entire collecting duct system, including the connecting tubule (CNT) and cortical collecting duct (CCD). In CNT and CCD, main sites for K+ secretion, the highest levels of expression were along the apical (luminal) cell membranes, including for both principal cells (PCs) and intercalated cells (ICs), posturing the channel for Ca2+- dependent K+ secretion. Fluorescent assessment of cell membrane potential in native, split-opened CCD, demonstrated that selective activation of the Ca2+-permeable TRPV4 channel, thereby inducing Ca2+ influx and elevating intracellular Ca2+ levels, activated both the SK3 channel and the BK channel leading to hyperpolarization of the cell membrane. The hyperpolarization response was decreased to a similar extent by either inhibition of SK3 channel with the selective SK antagonist, apamin, or by inhibition of the BK channel with the selective antagonist, iberiotoxin (IbTX). Addition of both inhibitors produced a further depolarization, indicating cooperative effects of the two channels on Vm. It is concluded that SK3 is functionally expressed in the distal nephron and collecting ducts where induction of TRPV4-mediated Ca2+ influx, leading to elevated intracellular Ca2+ levels, activates this high Ca2+- affinity K+ channel. Further, with sites of expression localized to the apical cell membrane, especially in the CNT and CCD, SK3 is poised to be a key pathway for Ca2+-dependent regulation of membrane potential and K+ secretion. © 2014 Berrout et al

Psychodynamic Guided Self-help for Adult Deperssion through the Internet: A Randomised Controlled Trial.

Abstract Background and aims: Psychodynamic psychotherapy (PDT) is an effective treatment for major depressive disorder (MDD), but not all clients with MDD can receive psychotherapy. Using the Internet to provide psychodynamic treatments is one way of improving access to psychological treatments for MDD. The aim of this randomised controlled trial was to investigate the efficacy of an Internet-based psychodynamic guided self-help treatment for MDD. Methods: Ninety-two participants who were diagnosed with MDD according to the Mini-International Neuropsychiatric Interview were randomised to treatment or an active control. The treatment consisted of nine treatment modules based on psychodynamic principles with online therapist contact. The active control condition was a structured support intervention and contained psychoeducation and scheduled weekly contacts online. Both interventions lasted for 10 weeks. The primary outcome measure was the Beck Depression Inventory-II (BDI-II). Results: Mixed-effects model analyses of all randomised participants showed that participants receiving Internet-based PDT made large and superior improvements compared with the active control group on the BDI-II (between-group Cohen’s d = 1.11). Treatment effects were maintained at a 10-month follow-up. Conclusions: Internet-based psychodynamic guided self-help is an efficacious treatment for MDD that has the potential to increase accessibility and availability of PDT for MDD

The effects of integrated care: a systematic review of UK and international evidence

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

jMOTU and Taxonerator: Turning DNA Barcode Sequences into Annotated Operational Taxonomic Units

BACKGROUND: DNA barcoding and other DNA sequence-based techniques for investigating and estimating biodiversity require explicit methods for associating individual sequences with taxa, as it is at the taxon level that biodiversity is assessed. For many projects, the bioinformatic analyses required pose problems for laboratories whose prime expertise is not in bioinformatics. User-friendly tools are required for both clustering sequences into molecular operational taxonomic units (MOTU) and for associating these MOTU with known organismal taxonomies. RESULTS: Here we present jMOTU, a Java program for the analysis of DNA barcode datasets that uses an explicit, determinate algorithm to define MOTU. We demonstrate its usefulness for both individual specimen-based Sanger sequencing surveys and bulk-environment metagenetic surveys using long-read next-generation sequencing data. jMOTU is driven through a graphical user interface, and can analyse tens of thousands of sequences in a short time on a desktop computer. A companion program, Taxonerator, that adds traditional taxonomic annotation to MOTU, is also presented. Clustering and taxonomic annotation data are stored in a relational database, and are thus amenable to subsequent data mining and web presentation. CONCLUSIONS: jMOTU efficiently and robustly identifies the molecular taxa present in survey datasets, and Taxonerator decorates the MOTU with putative identifications. jMOTU and Taxonerator are freely available from http://www.nematodes.org/

Self- and peer assessment may not be an accurate measure of PBL tutorial process

<p>Abstract</p> <p>Background</p> <p>Universidade Cidade de São Paulo adopted a problem-based learning (PBL) strategy as the predominant method for teaching and learning medicine. Self-, peer- and tutor marks of the educational process are taken into account as part of the final grade, which also includes assessment of content. This study compared the different perspectives (and grades) of evaluators during tutorials with first year medical students, from 2004 to 2007 (n = 349), from seven semesters.</p> <p>Methods</p> <p>The tutorial evaluation method was comprised of the students' self assessment (SA) (10%), tutor assessment (TA) (80%) and peer assessment (PA) (10%) to calculate a final educational process grade for each tutorial. We compared these three grades from each tutorial for seven semesters using ANOVA and a post hoc test.</p> <p>Results</p> <p>A total of 349 students participated with 199 (57%) women and 150 (42%) men. The SA and PA scores were consistently greater than the TA scores. Moreover, the SA and PA groups did not show statistical difference in any semester evaluated, while both differed from tutor assessment in all semesters (Kruskal-Wallis, Dunn's test). The Spearman rank order showed significant (p < 0.0001) and positive correlation for the SA and PA groups (r = 0.806); this was not observed when we compared TA with PA (r = 0.456) or TA with SA (r = 0.376).</p> <p>Conclusion</p> <p>Peer- and self-assessment marks might be reliable but not valid for PBL tutorial process, especially if these assessments are used for summative assessment, composing the final grade. This article suggests reconsideration of the use of summative assessment for self-evaluation in PBL tutorials.</p

Declining extra-pair paternity with laying order associated with initial incubation behavior, but independent of final clutch size in the blue tit

Although functional explanations for female engagement in extra-pair copulation have been studied extensively in birds, little is known about how extra-pair paternity is linked to other fundamental aspects of avian reproduction. However, recent studies indicate that the occurrence of extra-pair offspring may generally decline with laying order, possibly because stimulation by eggs induces incubation, which may suppress female motivation to acquire extra-pair paternity. Here we tested whether experimental inhibition of incubation during the laying phase, induced by the temporary removal of eggs, resulted in increased extra-pair paternity, in concert with a later cessation of laying, in blue tits (Cyanistes caeruleus). As expected, experimental females showed a more gradual increase in nocturnal incubation duration over the laying phase and produced larger clutches than controls. Moreover, incubation duration on the night after the first egg was laid predicted how extra-pair paternity declined with laying order, with less incubation being associated with more extra-pair offspring among the earliest eggs in the clutch. However, incubation duration on this first night was unrelated to our experimental treatment and independent of final clutch size. Consequently, the observed decline in extra-pair paternity with laying order was unaffected by our manipulation and larger clutches included proportionally fewer extra-pair offspring. We suggest that female physiological state prior to laying, associated with incubation at the onset of laying, determines motivation to acquire extra-pair paternity independent of final clutch size. This decline in proportion of extra-pair offspring with clutch size may be a general pattern within bird species

Cognitive function, social integration and mortality in a U.S. national cohort study of older adults

<p>Abstract</p> <p>Background</p> <p>Prior research suggests an interaction between social networks and Alzheimer's disease pathology and cognitive function, all predictors of survival in the elderly. We test the hypotheses that both social integration and cognitive function are independently associated with subsequent mortality and there is an interaction between social integration and cognitive function as related to mortality in a national cohort of older persons.</p> <p>Methods</p> <p>Data were analyzed from a longitudinal follow-up study of 5,908 American men and women aged 60 years and over examined in 1988–1994 followed an average 8.5 yr. Measurements at baseline included self-reported social integration, socio-demographics, health, body mass index, C-reactive protein and a short index of cognitive function (SICF).</p> <p>Results</p> <p>Death during follow-up occurred in 2,431. In bivariate analyses indicators of greater social integration were associated with higher cognitive function. Among persons with SICF score of 17, 22% died compared to 54% of those with SICF score of 0–11 (p < 0.0001). After adjusting for confounding by baseline socio-demographics and health status, the hazards ratio (HR) (95% confidence limits) for low SICF score was 1.43 (1.13–1.80, p < 0.001). After controlling for health behaviors, blood pressure and body mass, C-reactive protein and social integration, the HR was 1.36 (1.06–1.76, p = 0.02). Further low compared to high social integration was also independently associated with increased risk of mortality: HR 1.24 (1.02–1.52, p = 0.02).</p> <p>Conclusion</p> <p>In a cohort of older Americans, analyses demonstrated a higher risk of death independent of confounders among those with low cognitive function and low social integration with no significant interaction between them.</p

Molecular Approach to the Identification of Fish in the South China Sea

BACKGROUND: DNA barcoding is one means of establishing a rapid, accurate, and cost-effective system for the identification of species. It involves the use of short, standard gene targets to create sequence profiles of known species against sequences of unknowns that can be matched and subsequently identified. The Fish Barcode of Life (FISH-BOL) campaign has the primary goal of gathering DNA barcode records for all the world's fish species. As a contribution to FISH-BOL, we examined the degree to which DNA barcoding can discriminate marine fishes from the South China Sea. METHODOLOGY/PRINCIPAL FINDINGS: DNA barcodes of cytochrome oxidase subunit I (COI) were characterized using 1336 specimens that belong to 242 species fishes from the South China Sea. All specimen provenance data (including digital specimen images and geospatial coordinates of collection localities) and collateral sequence information were assembled using Barcode of Life Data System (BOLD; www.barcodinglife.org). Small intraspecific and large interspecific differences create distinct genetic boundaries among most species. In addition, the efficiency of two mitochondrial genes, 16S rRNA (16S) and cytochrome b (cytb), and one nuclear ribosomal gene, 18S rRNA (18S), was also evaluated for a few select groups of species. CONCLUSIONS/SIGNIFICANCE: The present study provides evidence for the effectiveness of DNA barcoding as a tool for monitoring marine biodiversity. Open access data of fishes from the South China Sea can benefit relative applications in ecology and taxonomy