The Unique-5 and -6 Motifs of ZO-1 Regulate Tight Junction Strand Localization and Scaffolding Properties

The proper cellular location and sealing of tight junctions is assumed to depend on scaffolding properties of ZO-1, a member of the MAGUK protein family. ZO-1 contains a conserved SH3-GUK module that is separated by a variable region (unique-5), which in other MAGUKs has proven regulatory functions. To identify motifs in ZO-1 critical for its putative scaffolding functions, we focused on the SH3-GUK module including unique-5 (U5) and unique-6 (U6), a motif immediately C-terminal of the GUK domain. In vitro binding studies reveal U5 is sufficient for occludin binding; U6 reduces the affinity of this binding. In cultured cells, U5 is required for targeting ZO-1 to tight junctions and removal of U6 results in ectopically displaced junction strands containing the modified ZO-1, occludin, and claudin on the lateral cell membrane. These results provide evidence that ZO-1 can control the location of tight junction transmembrane proteins and reveals complex protein binding and targeting signals within its SH3-U5-GUK-U6 region. We review these findings in the context of regulated scaffolding functions of other MAGUK protein

Factors affecting the uptake of institutional delivery, antenatal and postnatal care in Nawalparasi district, Nepal

© 2019, Kathmandu University. All rights reserved. Background Maternal deaths and complications are highly preventable with good antenatal, postnatal and skilled care during childbirth. Inadequate information on the factors affecting these services could be barrier to a reduction of maternal deaths in low-income countries. Objective To assess the uptake of antenatal, postnatal and skilled care during childbirth. Method A cross-sectional study was conducted in eight villages of Nawalparasi district in southern Nepal. A total of 447 women who had given birth within the preceding 24 months were recruited using multistage random sampling. Data were collected using a pre-tested semi-structured questionnaire. Chi-square tests were used to assess association between variables. Result Over 70% of women had gone for at least four antenatal care check-ups while only 14.3% had at least three postnatal check-ups in their last pregnancies. The proportion of institution delivery was 54%. Women’s literacy was associated with the uptake of antenatal services (p=<0.001), postnatal care (p=0.04) and institutional delivery (p=<0.001). Knowledge of antenatal (p=<0.001) and postnatal care was also associated with uptake of respective services (p=<0.001). Conclusion The uptake and knowledge of antenatal care was much better than of postnatal care. Home delivery rates were still very high. A scaling-up of education and awareness-raising interventions in this community could help improve the uptake of maternal health services

Integronlike Structures in Campylobacter spp. of Human and Animal Origin

Resistance to antimicrobial agents used to treat severe Campylobacter spp. gastroenteritis is increasing worldwide. We assessed the antimicrobial resistance patterns of Campylobacter spp. isolates of human and animal origin. More than half (n = 32) were resistant to sulphonamide, a feature known to be associated with the presence of integrons. Analysis of these integrons will further our understanding of Campylobacter spp. epidemiology

Surface Attachment of Active Antimicrobial Coatings Onto Conventional Plastic Based Laminates and Performance Assessment of These Materials on the Storage Life of Vacuum Packaged Beef Sub-Primals

Two antimicrobial coatings, namely Sodium octanoate and Auranta FV (a commercial antimicrobial composed of bioflavonoids, citric, malic, lactic, and caprylic acids) were used. These two antimicrobials were surface coated onto the inner polyethylene layer of cold plasma treated polyamide films using beef gelatin as a carrier and coating polymer. This packaging material was then used to vacuum pack beef sub-primal cuts and stored at 4 °C. A control was prepared using the non-coated commercial laminate and the same vacuum packaged sub-primal beef cuts. During storage, microbial and quality assessments were carried out. Sodium octanoate treated packages significantly (p \u3c 0.05) reduced microbial counts for all bacteria tested with an increase of 7 and 14 days, respectively compared to control samples. No significant effect on pH was observed with any treatment. The results suggested that these food grade antimicrobials have the potential to be used in antimicrobial active packaging applications for beef products

Mental health issues in pregnant women in Nepal

Mental health of pregnant women and new mothers is a growing area of concern in both low- and high-income countries. This editorial highlights some of the key mental issues faced by women in rural Nepal and outlines an intervention based on training community health care workers by experienced UK volunteers

The timing of mandibular tooth formation in two African groups

Background: Ethnic differences in the timing of human tooth development are unclear. Aim: To describe similarities and differences in the timing of tooth formation in two groups of Sudanese children and young adults. Subjects and methods: The sample consisted of healthy individuals from Khartoum, Sudan, aged 2–23 years. The Northern group was of Arab origin (848 males, 802 females) and the Western group was of African origin (846 males, 402 females). Each mandibular left permanent tooth from first incisor to third molar was assessed from dental radiographs into one of 15 development stages. Mean ages at entry for 306 tooth stages were calculated using probit regression in males/females in each group and compared using a t-test. Results: Mean ages were not significantly different in most tooth stage comparisons between ethnic groups for both males (61/75) and females (56/76), despite a tendency of earlier mean ages in the Western group. Mean ages for most tooth stage comparisons between males and females (137/155) were not significantly different within ethnic groups suggesting low sexual dimorphism. Conclusion: The mean ages of most mandibular tooth formation stages were generally not significantly different between ethnic groups or between males and females in this study

Dopamine transporter genotype is associated with a lateralized resistance to distraction during attention selection

Although lateral asymmetries in orienting behavior are evident across species and have been linked to interhemispheric asymmetries in dopamine signaling, the relative contribution of attentional versus motoric processes remains unclear. Here we took a cognitive genetic approach to adjudicate between roles for dopamine in attentional versus response selection. A sample of nonclinical adult humans (N = 518) performed three cognitive tasks (spatial attentional competition, spatial cueing, and flanker tasks) that varied in the degree to which they required participants to resolve attentional or response competition. All participants were genotyped for two putatively functional tandem repeat polymorphisms of the dopamine transporter gene (DAT1; SLC6A3), which are argued to influence the level of available synaptic dopamine and confer risk to disorders of inattention. DAT1 genotype modulated the task-specific effects of the various task-irrelevant stimuli across both the spatial competition and spatial cueing but not flanker tasks. Specifically, compared with individuals carrying one or two copies of the 10-repeat DAT1 allele, individuals without this allele demonstrated an immunity to distraction, such that response times were unaffected by increases in the number of distractor stimuli, particularly when these were presented predominantly in the left hemifield. All three genotype groups exhibited uniform costs of resolving leftward response selection in a standard flanker task. None of these significant effects could be explained by speed–accuracy trade-offs, suggesting that participants without the 10-repeat allele of the DAT1 tandem repeat polymorphism possess an enhanced attentional ability to suppress task-irrelevant stimuli in the left hemifield

A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset

Purpose: Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset. / Design: Dataset descriptor for routinely collected eye screening data. / Participants: All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme. / Methods: The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)–led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program. / Main Outcome Measures: This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients’ diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below. / Results: At the time point of this analysis (December 31, 2019), the dataset comprised 6 202 161 images from 246 180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1 360 547 grading episodes between R0M0 and R3M1. / Conclusions: This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/

The Transforming Rho Family GTPase Wrch-1 Disrupts Epithelial Cell Tight Junctions and Epithelial Morphogenesis

Wrch-1, an atypical and transforming Rho GTPase, regulates cellular activities including proliferation and actin organization, but its functions and effectors remain poorly characterized. We show here that Wrch-1 distributes along the apical and basolateral membranes in MDCK cells and binds the cell polarity protein Par6 in a GTP-dependent manner. Activated Wrch-1 negatively regulates the kinetics of tight junction (TJ) assembly during epithelial cell polarization but has no detectable effect on overall cell polarity in confluent monolayers. It also causes a dramatic cytoskeletal reorganization and multilayering in cells grown in two-dimensional culture and disrupts cystogenesis of cells grown in three-dimensional (3D) culture. Similarly, short hairpin RNA-mediated knockdown of Wrch-1 perturbs cystogenesis in 3D culture, suggesting that tight regulation of Wrch-1 activity is necessary for normal epithelial morphogenesis. A weakly transforming effector domain mutant of activated Wrch-1 that inhibits Par6 binding abrogates the ability of Wrch-1 to disrupt TJ formation, actin organization, and epithelial morphogenesis. We hypothesize that Wrch-1-induced morphological and growth transformation may occur in part through Par6-mediated disruption of TJs and actin organization