Anillin tunes contractility and regulates barrier function during Rho flare-mediated tight junction remodeling.

To preserve barrier function, cell-cell junctions must dynamically remodel during cell shape changes. We have previously described a rapid tight junction repair pathway characterized by local, transient activation of RhoA, termed 'Rho flares,' which repair leaks in tight junctions via promoting local actomyosin-mediated junction remodeling. In this pathway, junction elongation is a mechanical trigger that initiates RhoA activation through an influx of intracellular calcium and recruitment of p115RhoGEF.

The Heterotaxy Gene CCDC11 Is Important for Cytokinesis via RhoA Regulation.

Mutations in CCDC11 (cfap53) have been identified in multiple patients with heterotaxy (Htx), a disorder of left-right (LR) patterning of the internal organs. In Xenopus, depletion of Ccdc11 causes defects in LR patterning, recapitulating the patient phenotype. Upon Ccdc11 depletion, monociliated cells of the Left-Right Organizer (LRO) exhibit multiple cilia per cell.

Mechanosensitive recruitment of Vinculin maintains junction integrity and barrier function at epithelial tricellular junctions.

Apical cell-cell junctions, including adherens junctions and tight junctions, adhere epithelial cells to one another and regulate selective permeability at both bicellular junctions and tricellular junctions (TCJs). Although several specialized proteins are known to localize at TCJs, it remains unclear how actomyosin-mediated tension transmission at TCJs contributes to the maintenance of junction integrity and barrier function at these sites. Here, utilizing the embryonic epithelium of gastrula-stage Xenopus laevis embryos, we define a mechanism by which the mechanosensitive protein Vinculin helps anchor the actomyosin network at TCJs, thus maintaining TCJ integrity and barrier function.

Proof of concept of the Universal Baby video innovation for early child development in Lima, Peru.

Objective: Community-based video interventions offer an effective and potentially scalable early interaction coaching tool for caregivers living in low resource settings. We tested the Universal Baby (UB) video innovation; an early interaction coaching tool using video sourced and produced locally with early child development (ECD) expert supervision.

Methods: This proof-of-concept study enrolled 40 caregivers of children ages 10-18 months assigned to intervention and control groups by health establishments in Carabayllo, Lima, Peru.

Methodology for adapting a co-created early childhood development intervention and implementation strategies for use by frontline workers in India and Guatemala: a systematic application of the FRAME-IS framework.

There is little evidence on optimizing the effectiveness and implementation of evidence-based early childhood development (ECD) interventions when task-shifted to frontline workers. In this Methods Forum paper, we describe our adaptation of the International Guide for Monitoring Child Development (GMCD) for task-shifting to frontline workers in Guatemala and India. In 2021-2022, implementers, trainers, frontline workers, caregivers, and international GMCD experts collaborated to adapt the GMCD for a task shifted implementation by frontline workers.

Evaluation of a novel approach to community health care delivery in Ifanadiana District, Madagascar.

Despite widespread adoption of community health (CH) systems, there are evidence gaps to support global best practice in remote settings where access to health care is limited and community health workers (CHWs) may be the only available providers. The nongovernmental health organization Pivot partnered with the Ministry of Public Health (MoPH) to pilot a new enhanced community health (ECH) model in rural Madagascar, where one CHW provided care at a stationary CH site while additional CHWs provided care via proactive household visits. The program included professionalization of the CHW workforce (i.

Patterning of the cell cortex by Rho GTPases.

The Rho GTPases - RHOA, RAC1 and CDC42 - are small GTP binding proteins that regulate basic biological processes such as cell locomotion, cell division and morphogenesis by promoting cytoskeleton-based changes in the cell cortex. This regulation results from active (GTP-bound) Rho GTPases stimulating target proteins that, in turn, promote actin assembly and myosin 2-based contraction to organize the cortex. This basic regulatory scheme, well supported by in vitro studies, led to the natural assumption that Rho GTPases function in vivo in an essentially linear matter, with a given process being initiated by GTPase activation and terminated by GTPase inactivation.

Assessing child development scores among minority and Indigenous language versus dominant language speakers: a cross-sectional analysis of national Multiple Indicator Cluster Surveys.

Background: Multiple studies have highlighted the inequities minority and Indigenous children face when accessing health care. Health and wellbeing are positively impacted when Indigenous children are educated and receive care in their maternal language. However, less is known about the association between minority or Indigenous language use and child development risks and outcomes.

Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study.

Introduction: Three years into the pandemic, there remains significant uncertainty about the true infection and mortality burden of COVID-19 in the World Health Organization Africa region. High quality, population-representative studies in Africa are rare and tend to be conducted in national capitals or large cities, leaving a substantial gap in our understanding of the impact of COVID-19 in rural, low-resource settings. Here, we estimated the spatio-temporal morbidity and mortality burden associated with COVID-19 in a rural health district of Madagascar until the first half of 2021.

ZnUMBA - a live imaging method to detect local barrier breaches.

Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods measure changes in global barrier function, they lack the sensitivity needed to detect local or transient barrier breaches, and they do not reveal the location of barrier leaks. Therefore, we previously developed a method that we named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction leaks with high spatiotemporal resolution.

Factors associated with recovery from stunting at 24 months of age among infants and young children enrolled in the Pediatric Development Clinic (PDC): A retrospective cohort study in rural Rwanda.

Introduction: Stunting (low height/length-for-age) in early life is associated with poor long-term health and developmental outcomes. Nutrition interventions provided during the first 1,000 days of life can result in improved catch-up growth and development outcomes. We assessed factors associated with stunting recovery at 24 months of age among infants and young Children enrolled in Pediatric Development Clinics (PDC) who were stunted at 11 months of age.

Fusing safety and efficacy: A maternal bivalent RSV prefusion F vaccine.

In this phase 3 trial, Kampmann et al. demonstrated safety and efficacy of a maternal bivalent RSV prefusion F vaccine. Vaccine efficacy was achieved in reducing severe RSV-associated lower respiratory tract infections in infants at 90 and 180 days following birth.

Neighbor cells restrain furrowing during epithelial cytokinesis.

Cytokinesis challenges epithelial tissue homeostasis by generating forces that pull on neighboring cells cell-cell junctions. Previous work has shown that junction reinforcement at the furrow in epithelia regulates the speed of furrowing. This suggests the cytokinetic array that drives cell division is subject to resistive forces from epithelial neighbor cells.

Assessment of aflatoxin exposure, growth faltering and the gut microbiome among children in rural Guatemala: protocol for an observational prospective cohort and bioreactor simulations.

Introduction: Aflatoxin B1 (AFB1) is a carcinogen produced by and which grow on maize. Given the high prevalence of child stunting (ie, impaired growth) and other nutritional disorders in low-income and middle-income countries, where maize is consumed, the role of aflatoxin exposure may be significant. Observational reports have demonstrated associations between aflatoxin exposure and impaired child growth; however, most have been cross-sectional and have not assessed seasonal variations in aflatoxin, food preparation and dynamic changes in growth.

Geographic barriers to care persist at the community healthcare level: Evidence from rural Madagascar.

Geographic distance is a critical barrier to healthcare access, particularly for rural communities with poor transportation infrastructure who rely on non-motorized transportation. There is broad consensus on the importance of community health workers (CHWs) to reduce the effects of geographic isolation on healthcare access. Due to a lack of fine-scale spatial data and individual patient records, little is known about the precise effects of CHWs on removing geographic barriers at this level of the healthcare system.

Readability of publicly available mental health information: A systematic review.

Objective: Relatively little research has examined the health literacy demand of public communication (e.g. websites, pamphlets, and posters) about mental disorders.

Prevalence of Hypertension, Diabetes, and Other Cardiovascular Disease Risk Factors in Two Indigenous Municipalities in Rural Guatemala: A Population-Representative Survey.

Background: Nearly 50% of Guatemalans are Indigenous Maya, yet few studies have examined the prevalence of modifiable cardiovascular disease (CVD) risk factors in Indigenous Maya populations. Therefore, we sought to estimate the prevalence of modifiable CVD risk factors in two Indigenous Maya areas in Guatemala.

Methods: We conducted, between June 2018 and October 2019, a population-representative survey of adults aged 18 years and older in two rural Indigenous Maya municipalities in Guatemala.

Readability and Suitability of Information Presented on a University Health Center Website.

This study evaluated the readability and suitability of a university health center public website. Readability formulas estimated the reading grade and age required for comprehension of health information. The Suitability Assessment of Materials (SAM) instrument determined adequacy of the webpages for the intended audience.

p115RhoGEF activates RhoA to support tight junction maintenance and remodeling.

In vertebrates, epithelial cell-cell junctions must rapidly remodel to maintain barrier function as cells undergo dynamic shape-change events. Consequently, localized leaks sometimes arise within the tight junction (TJ) barrier, which are repaired by short-lived activations of RhoA, called "Rho flares." However, how RhoA is activated at leak sites remains unknown.

Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy.

Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues.

SNAP- and Halo-tagging and dye introduction protocol for live microscopy in embryos.

Traditional fluorescent proteins exhibit limitations in brightness and photostability that hinder optimal characterization of the dynamic cellular behavior of proteins of interest. SNAP- and Halo-tagging are alternatives to traditional fluorescent protein tagging utilizing bright, stable chemical dyes, which may improve signal-to-noise ratio. However, there has been limited use of this approach in developing organisms.