Quantitative analysis of transient and sustained transforming growth factor-β signaling dynamics

Mathematical modeling and experimental analyses reveal that TGF-β ligand depletion has an important role in converting short-term graded signaling responses to long-term switch-like responses

Child dietary patterns in Homo sapiens evolution: A systematic review

Dietary patterns spanning millennia could inform contemporary public health nutrition. Children are largely absent from evidence describing diets throughout human evolution, despite prevalent malnutrition today signaling a potential genome-environment divergence. This systematic review aimed to identify dietary patterns of children ages 6 months to 10 years consumed before the widespread adoption of agriculture. Metrics of mention frequency (counts of food types reported) and food groups (globally standardized categories) were applied to: compare diets across subsistence modes [gatherer-hunter-fisher (GHF), early agriculture (EA) groups]; examine diet quality and diversity; and characterize differences by life course phase and environmental context defined using Köppen-Geiger climate zones. The review yielded child diet information from 95 cultural groups (52 from GHF; 43 from EA/mixed subsistence groups). Animal foods (terrestrial and aquatic) were the most frequently mentioned food groups in dietary patterns across subsistence modes, though at higher frequencies in GHF than in EA. A broad range of fruits, vegetables, roots and tubers were more common in GHF, while children from EA groups consumed more cereals than GHF, associated with poor health consequences as reported in some studies. Forty-eight studies compared diets across life course phases: 28 showed differences and 20 demonstrated similarities in child versus adult diets. Climate zone was a driver of food patterns provisioned from local ecosystems. Evidence fro

Grandi Byen-supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: Study protocol for a randomized controlled trial

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. DISCUSSION: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. TRIAL REGISTRATION: NCT04785352 . Registered March 5, 2021 at https://clinicaltrials.gov/

Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines

The nonpsychoactive cannabinoid, cannabidiol (CBD), is Food and Dug Administration approved for treatment of two drug-resistant epileptic disorders and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lines using temporal multiomic profiling. FRET-based biosensor screening revealed that CBD elicits a sharp rise in cytosolic calcium, and activation of AMP-activated protein kinase in human keratinocyte and neuroblastoma cell lines. CBD treatment leads to alterations in the abundance of metabolites, mRNA transcripts, and proteins associated with activation of cholesterol biosynthesis, transport, and storage. We found that CBD rapidly incorporates into cellular membranes, alters cholesterol accessibility, and disrupts cholesterol-dependent membrane properties. Sustained treatment with high concentrations of CBD induces apoptosis in a dose-dependent manner. CBD-induced apoptosis is rescued by inhibition of cholesterol synthesis and potentiated by compounds that disrupt cholesterol trafficking and storage. Our data point to a pharmacological interaction of CBD with cholesterol homeostasis pathways, with potential implications in its therapeutic use. &nbsp;</p

The development of a novel high throughput computational tool for studying individual and collective cellular migration.

Understanding how cells migrate individually and collectively during development and cancer metastasis can be significantly aided by a computation tool to accurately measure not only cellular migration speed, but also migration direction and changes in migration direction in a temporal and spatial manner. We have developed such a tool for cell migration researchers, named Pathfinder, which is capable of simultaneously measuring the migration speed, migration direction, and changes in migration directions of thousands of cells both instantaneously and over long periods of time from fluorescence microscopy data. Additionally, we demonstrate how the Pathfinder software can be used to quantify collective cell migration. The novel capability of the Pathfinder software to measure the changes in migration direction of large populations of cells in a spatiotemporal manner will aid cellular migration research by providing a robust method for determining the mechanisms of cellular guidance during individual and collective cell migration