Valine Restriction Extends Survival in a Drosophila Model of Short-Chain Enoyl-CoA Hydratase 1 (ECHS1) Deficiency.

Short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare genetic disorder caused by biallelic pathogenic variants in the ECHS1 gene. ECHS1D is characterised by severe neurological and physical impairment that often leads to childhood mortality. Therapies such as protein and single nutrient-restricted diets show poor efficacy, whereas the development of new treatments is hindered by the low prevalence of the disorder and a lack of model systems for treatment testing.

Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten.

Testicular tumors are the most common malignancy of young men and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to nestin expressing cells.

Vitamin D Receptor Regulates the Expression of the Grainyhead-Like 1 Gene.

Vitamin D plays an important pleiotropic role in maintaining global homeostasis of the human body. Its functions go far beyond skeletal health, playing a crucial role in a plethora of cellular functions, as well as in extraskeletal health, ensuring the proper functioning of multiple human organs, including the skin. Genes from the Grainyhead-like () family code for transcription factors necessary for the development and maintenance of various epithelia.

Molecular variations to the proteome of zebrafish larvae induced by environmentally relevant copper concentrations.

Contaminants are increasingly accumulating in aquatic environments and biota, with potential adverse effects on individual organisms, communities and ecosystems. However, studies that explore the molecular changes in fish caused by environmentally relevant concentrations of metals, such as copper (Cu), are limited. This study uses embryos of the model organism zebrafish (Danio rerio) to investigate effect of Cu on the proteome and amino acid (AA) composition of fish.

An agricultural livelihood intervention is associated with reduced HIV stigma among people with HIV.

Objective: HIV stigma undermines antiretroviral treatment (ART) adherence and viral suppression. Livelihood interventions may target drivers of negative attitudes towards people with HIV (PWH) by improving their health and strengthening their economic contributions. We examined the effects of a multisectoral agricultural livelihood intervention on HIV stigma among PWH in western Kenya.

Grainyhead-like 2 interacts with noggin to regulate tissue fusion in mouse.

Defective tissue fusion during mammalian embryogenesis results in congenital anomalies, such as exencephaly, spina bifida and cleft lip and/or palate. The highly conserved transcription factor grainyhead-like 2 (Grhl2) is a crucial regulator of tissue fusion, with mouse models lacking GRHL2 function presenting with a fully penetrant open cranial neural tube, facial and abdominal clefting (abdominoschisis), and an open posterior neuropore. Here, we show that GRHL2 interacts with the soluble morphogen protein and bone morphogenetic protein (BMP) inhibitor noggin (NOG) to impact tissue fusion during development.

The Role of PLAG1 in Mouse Brain Development and Neurogenesis.

The pleomorphic adenoma gene 1 (Plag1) is a transcription factor involved in the regulation of growth and cellular proliferation. Here, we report the spatial distribution and functional implications of PLAG1 expression in the adult mouse brain. We identified Plag1 promoter-dependent β-galactosidase expression in various brain structures, including the hippocampus, cortex, choroid plexus, subcommisural organ, ependymal cells lining the third ventricle, medial and lateral habenulae and amygdala.

Cryosectioning and Immunohistochemistry Using Frozen Adult Murine Brain Neural Tissue.

Cryopreservation and immunohistochemistry offer a comprehensive, robust, and simple methodology to investigate neural patterning and cellular function. Rapid freezing of the whole brain allows excellent preservation of neural ultrastructure and tissue architecture without destroying sensitive protein epitopes that are often compromised following standard paraffin embedding histological techniques. Here, we present a rapid and simple protocol for employing cryosectioning and subsequent immunohistochemistry in the study of adult murine brain neural tissue.

Neural Stem/Progenitor Cell (NSPC) Extraction and Culture.

Neural stem-progenitor cells (NSPCs) are multipotent, self-renewing cells that generate radial glial cells (RGC). RGCs then give rise to neurons and glia during neural development. Here, we describe the process of NSPC isolation and culturing to form clonal aggregates termed neurospheres.

In Situ Hybridization to Characterize Neurulation and Midbrain-Hindbrain Boundary Formation in Zebrafish.

Whole-mount in situ hybridization is cable to harness the inherent advantages of zebrafish as a model organism for developmental biology, particularly when visualizing the formation of the neural tube, specifically at the level of the midbrain-hindbrain boundary. The size and transparency of developing zebrafish embryos allow for the visualization of neural markers in vivo along the length of the developing zebrafish central nervous system. In practice, this technique is useful for examining defects in neurulation and midbrain-hindbrain boundary formation that may arise following gene manipulation, for example, CRISPR mutagenesis.

Understanding lifetime and dispersion of cough-emitted droplets in air.

To understand the exact transmission routes of SARS-CoV-2 and to explore effects of time, space and indoor environment on the dynamics of droplets and aerosols, rigorous testing and observation must be conducted. In the current work, the spatial and temporal dispersions of aerosol droplets from a simulated cough were comprehensively examined over a long duration (70 min). An artificial cough generator was constructed to generate reliably repeatable respiratory ejecta.

Transforming masculine norms to improve men's contraceptive acceptance: results from a pilot intervention with men in western Kenya.

Men's adherence to constraining male gender norms can lead them to resist contraceptive use. Very few interventions have attempted to transform masculine norms to encourage greater contraceptive acceptance and gender equality. We designed and evaluated a small-scale community-based intervention targeting the masculine norms tied to contraceptive resistance among partnered men ( = 150) in two western Kenya communities (intervention vs.

Protocol for the pilot quasi-experimental controlled trial of a gender-responsive implementation strategy with providers to improve HIV outcomes in Uganda.

Background: Antiretroviral treatment (ART) is the most effective clinical intervention for reducing morbidity and mortality among persons living with HIV. However, in Uganda, there are disparities between men and women in viral load suppression and related HIV care engagement outcomes, which suggests problems with the implementation of ART. Gender norms are a known driver of HIV disparities in sub-Saharan Africa, and patient-provider relationships are a key factor in HIV care engagement; therefore, the role of gender norms is important to consider in interventions to achieve the equitable provision of treatment and the quality of ART counseling.

Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish.

Organophosphate (OP) insecticides are used to eliminate agricultural threats posed by insects, through inhibition of the neurotransmitter acetylcholinesterase (AChE). These potent neurotoxins are extremely efficacious in insect elimination, and as such, are the preferred agricultural insecticides worldwide. Despite their efficacy, however, estimates indicate that only 0.

Application of machine learning for the low-cost prediction of soot concentration in a turbulent flame.

The second most potent forcer of climate change, soot, has severe harmful effects on both human health and the environment. Accurate numerical modeling of soot formation is extremely complex and has a high computational cost due to its dependence on many physical and chemical interactions, specifically in turbulent flames. The high computational cost of coupling chemistry, fluid dynamics, thermodynamics, and heat transfer raise the need for a novel, precise, and computationally cost-effective numerical technique for predicting soot concentrations.

Relationship Power, Antiretroviral Adherence, and Physical and Mental Health Among Women Living with HIV in Rural Kenya.

Little is known about the association of gender-based power imbalances and health and health behaviors among women with HIV (WWH). We examined cross-sectional baseline data among WWH in a cluster-randomized control trial (NCT02815579) in rural Kenya. We assessed associations between the Sexual Relationship Power Scale (SRPS) and ART adherence, physical and mental health, adjusting for sociodemographic and social factors.

The Impact of Land Tenure Security on a Livelihood Intervention for People Living with HIV in Western Kenya.

Few studies have explored land access, a structural driver of health, and women's participation in livelihood interventions to improve food security and HIV outcomes. This qualitative study, embedded within Shamba Maisha (NCT02815579)-a randomized controlled trial (RCT) examining the impact of a multisectoral intervention among farmers living with HIV in western Kenya-sought to explore the influence of perceived access to and control of land on agricultural productivity, investments, and benefits. Thirty in-depth interviews (IDIs) were conducted with purposively sampled men and women, 3 to 6 months after receiving intervention inputs; data were deductively and inductively coded and analyzed.

Crucial Convolution: Genetic and Molecular Mechanisms of Coiling during Epididymis Formation and Development in Embryogenesis.

As embryonic development proceeds, numerous organs need to coil, bend or fold in order to establish their final shape. Generally, this occurs so as to maximise the surface area for absorption or secretory functions (e.g.

Transcription Factors in Cancer.

This Special Issue comprises three original studies and five review articles [...

Grainyhead-like (Grhl) Target Genes in Development and Cancer.

Grainyhead-like (GRHL) factors are essential, highly conserved transcription factors (TFs) that regulate processes common to both natural cellular behaviours during embryogenesis, and de-regulation of growth and survival pathways in cancer. Serving to drive the transcription, and therefore activation of multiple co-ordinating pathways, the three GRHL family members (GRHL1-3) are a critical conduit for modulating the molecular landscape that guides cellular decision-making processes during proliferation, epithelial-mesenchymal transition (EMT) and migration. Animal models and in vitro approaches harbouring GRHL loss or gain-of-function are key research tools to understanding gene function, which gives confidence that resultant phenotypes and cellular behaviours may be translatable to humans.