Enter exitrons

Staiger D, Simpson GG. Enter exitrons. Genome Biology. 2015;16(1): 136.Exitrons are exon-like introns located within protein-coding exons. Removal or retention of exitrons through alternative splicing increases proteome complexity and thus adds to phenotypic diversity

Scale adaptive simulation of unsteady cavitation flow around a plane convex hydrofoil with a semi-cylindrical obstacle

The present study focuses on the numerical simulation of unsteady cavitating flow around a plane-convex hydrofoil with a semi-cylindrical obstacle, which is based on the cavitationerosion experiment perform at LMH-EPFL using the vortex cavitation generator tunnel. The turbulence model k-¿ SST SAS method, which presents advantages in terms of computational consumption and reproduction of the phenomenon, has been applied in OpenFOAM version 4 to reproduce the unsteady behavior of cavitating flow. Additionally, the Zwart-Gerber-Belamri (ZGB) cavitation model has been applied, based on a previous work where this model was implemented in OpenFOAM. The model is based on Rayleigh Plesset equation, which considers small cavities with changes of void fraction for condensation and vaporization and using empirical calibration numbers based on previous research. Regarding the mesh development, the present work explores two configurations of grid mesh containing hexahedra (hex) and split-hexahedra (split-hex) automatically generated from triangulated surface geometries based on previous numerical studies. The aforementioned method aims to optimize computational demand and phenomenon reproducibility. Results show that the unsteady cavitating flows behavior has been reproduced with good accuracy and shows special details which are important for erosion studies in futures works.Peer ReviewedPostprint (published version

Association of self-reported physical activity with obstructive sleep apnea: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

We examined associations of mild and moderate to severe obstructive sleep apnea (OSA; apnea-hypopnea index ≥5 and ≥15, respectively) with recommended amounts of moderate-vigorous physical activity (MVPA) or vigorous physical activity (VPA) and by type of activity (i.e., recreational, transportation, and work activity). The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter population-based study, enrolled individuals from 2008 to 2011 from four U.S. metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California). Participants in this study included 14,206 self-identified Hispanic/Latino ages 18 to 74 years from theHCHS/SOL. Survey logistic regression analysis was used to compute odds ratios [OR] and 95% confidence intervals [CI], adjusting for sociodemographics, smoking status, and body mass index (BMI). Relative to being inactive, performing some MVPA (>0 to <150 minutes/week) or meeting the recommended MVPA (≥150 minutes/week) were associated with lower odds of mild OSA (ORs and 95% CIs 0.70 [0.61-0.82] and 0.76 [0.63-0.91], respectively), as well as moderate to severe OSA (ORs and 95% CIs 0.76 [0.62-0.93] and 0.76 [0.59-0.98], respectively). Associations of VPA with OSA were not significant. Engaging in medium or high levels of transportation activity was associated with lower odds of mild OSA (OR: 0.84, 95% CI: 0.74-0.96; OR: 0.64, 95% CI: 0.43-0.95, respectively). Performing some recreational MVPA was associated with lower likelihood of mild and moderate to severe OSA (OR: 0.82, 95% CI: 0.71-0.93; OR: 0.79, 95% CI: 0.64-0.97, respectively). Health promotion and OSA prevention efforts should encourage individuals to engage in at least some MVPA

Probability distributed time delays: integrating spatial effects into temporal models

Background: In order to provide insights into the complex biochemical processes inside a cell, modelling approaches must find a balance between achieving an adequate representation of the physical phenomena and keeping the associated computational cost within reasonable limits. This issue is particularly stressed when spatial inhomogeneities have a significant effect on system's behaviour. In such cases, a spatially-resolved stochastic method can better portray the biological reality, but the corresponding computer simulations can in turn be prohibitively expensive.Results: We present a method that incorporates spatial information by means of tailored, probability distributed time-delays. These distributions can be directly obtained by single in silico or a suitable set of in vitro experiments and are subsequently fed into a delay stochastic simulation algorithm (DSSA), achieving a good compromise between computational costs and a much more accurate representation of spatial processes such as molecular diffusion and translocation between cell compartments. Additionally, we present a novel alternative approach based on delay differential equations (DDE) that can be used in scenarios of high molecular concentrations and low noise propagation.Conclusions: Our proposed methodologies accurately capture and incorporate certain spatial processes into temporal stochastic and deterministic simulations, increasing their accuracy at low computational costs. This is of particular importance given that time spans of cellular processes are generally larger (possibly by several orders of magnitude) than those achievable by current spatially-resolved stochastic simulators. Hence, our methodology allows users to explore cellular scenarios under the effects of diffusion and stochasticity in time spans that were, until now, simply unfeasible. Our methodologies are supported by theoretical considerations on the different modelling regimes, i.e. spatial vs. delay-temporal, as indicated by the corresponding Master Equations and presented elsewhere

Conservative route to genome compaction in a miniature annelid

The causes and consequences of genome reduction in animals are unclear because our understanding of this process mostly relies on lineages with often exceptionally high rates of evolution. Here, we decode the compact 73.8-megabase genome of Dimorphilus gyrociliatus, a meiobenthic segmented worm. The D. gyrociliatus genome retains traits classically associated with larger and slower-evolving genomes, such as an ordered, intact Hox cluster, a generally conserved developmental toolkit and traces of ancestral bilaterian linkage. Unlike some other animals with small genomes, the analysis of the D. gyrociliatus epigenome revealed canonical features of genome regulation, excluding the presence of operons and trans-splicing. Instead, the gene-dense D. gyrociliatus genome presents a divergent Myc pathway, a key physiological regulator of growth, proliferation and genome stability in animals. Altogether, our results uncover a conservative route to genome compaction in annelids, reminiscent of that observed in the vertebrate Takifugu rubripes

District Health Managers' Perceptions of Supervision in Malawi and Tanzania.

Mid-level cadres are being used to address human resource shortages in many African contexts, but insufficient and ineffective human resource management is compromising their performance. Supervision plays a key role in performance and motivation, but is frequently characterised by periodic inspection and control, rather than support and feedback to improve performance. This paper explores the perceptions of district health management teams in Tanzania and Malawi on their role as supervisors and on the challenges to effective supervision at the district level. This qualitative study took place as part of a broader project, "Health Systems Strengthening for Equity: The Power and Potential of Mid-Level Providers". Semi-structured interviews were conducted with 20 district health management team personnel in Malawi and 37 council health team members in Tanzania. The interviews covered a range of human resource management issues, including supervision and performance assessment, staff job descriptions and roles, motivation and working conditions. Participants displayed varying attitudes to the nature and purpose of the supervision process. Much of the discourse in Malawi centred on inspection and control, while interviewees in Tanzania were more likely to articulate a paradigm characterised by support and improvement. In both countries, facility level performance metrics dominated. The lack of competency-based indicators or clear standards to assess individual health worker performance were considered problematic. Shortages of staff, at both district and facility level, were described as a major impediment to carrying out regular supervisory visits. Other challenges included conflicting and multiple responsibilities of district health team staff and financial constraints. Supervision is a central component of effective human resource management. Policy level attention is crucial to ensure a systematic, structured process that is based on common understandings of the role and purpose of supervision. This is particularly important in a context where the majority of staff are mid-level cadres for whom regulation and guidelines may not be as formalised or well-developed as for traditional cadres, such as registered nurses and medical doctors. Supervision needs to be adequately resourced and supported in order to improve performance and retention at the district level

Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies

The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R. These residues are predicted to undergo substantial movement during the transition of the receptor ion channel from the closed to the open state, predictions which are made based on structural homology models generated from the crystal structures of the zebrafish P2X4R. Our results provide evidence that among the six pairs of cysteine mutants, D48C/I133C and K81C/V304C formed disulphide bonds that impaired the channel gating to support the notion that such conformational changes, particularly those in the outer ends of the transmembrane domains, are critical for human P2X7R activation