Bioorthogonal Functionalization of Material Surfaces with Bioactive Molecules.

The functionalization of material surfaces with biologically active molecules is crucial for enabling technologies in life sciences, biotechnology, and medicine. However, achieving biocompatibility and bioorthogonality with current synthetic methods remains a challenge. We report herein a novel surface functionalization method that proceeds chemoselectively and without a free transition metal catalyst.

Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome.

Metabolic Syndrome (MetS) raises cardiovascular disease risk. Extracellular vesicles (EVs) have emerged as important mediators of insulin sensitivity, although few studies on vascular function exist in humans. We determined the effect of insulin on EVs in relation to vascular function.

High-throughput screening of toxicants that modulate extravillous trophoblast migration.

Migration and subsequent invasion of extravillous trophoblasts into the uterus is essential for proper formation of the placenta. Disruption of these processes may result in poor pregnancy outcomes including preeclampsia, placenta accreta, fetal growth restriction, or fetal death. Currently, there are several methods for quantifying cell migration and invasion in vitro, each with limitations.

Leveraging Nutrient-Rich Traditional Foods to Improve Diets among Indigenous Populations in India: Value Chain Analysis of Finger Millet and Kionaar Leaves.

Many indigenous foods are nutrient-rich but are often underutilized even among populations at high risk of malnutrition. The aims of this study were to conduct value chain analysis of one cultivated crop (finger millet among the Munda tribe) and one wild green leafy vegetable (Koinaar leaves among the Sauria Paharia tribe) of two Indigenous communities in Jharkhand state, India and to identify entry points for interventions aimed at supporting production and consumption. Semi-structured interviews were conducted with stakeholders among each tribal group and transcripts were open coded and organized based on key themes across the steps of the value chain for each food independently.

Phosphatidic Acid Mediates the Nem1-Spo7/Pah1 Phosphatase Cascade in Yeast Lipid Synthesis.

In the yeast Saccharomyces cerevisiae, the PAH1-encoded Mg-dependent phosphatidate (PA) phosphatase Pah1 regulates the bifurcation of PA to diacylglycerol (DAG) for triacylglycerol (TAG) synthesis and to CDP-DAG for phospholipid synthesis. Pah1 function is mainly regulated via control of its cellular location by phosphorylation and dephosphorylation. Pah1 phosphorylated by multiple protein kinases is sequestered in the cytosol apart from its substrate PA in the membrane.

Aortic waveform responses to insulin in late versus early chronotype with metabolic syndrome.

Late chronotype (LC) correlates with reduced metabolic insulin sensitivity and cardiovascular disease. It is unclear if insulin action on aortic waveforms and inflammation is altered in LC versus early chronotype (EC). Adults with metabolic syndrome (n = 39, MetS) were classified as either EC (Morning-Eveningness Questionnaire [MEQ] = 63.

Brain insulin resistance and cognitive function: influence of exercise.

Exercise has systemic health benefits in people, in part, through improving whole body insulin sensitivity. The brain is an insulin-sensitive organ that is often underdiscussed relative to skeletal muscle, liver, and adipose tissue. Although brain insulin action may have only subtle impacts on peripheral regulation of systemic glucose homeostasis, it is important for weight regulation as well as mental health.

Childhood Stunting and Wasting Following Independence in South Sudan.

Background: South Sudan has experienced ongoing civil and environmental problems since gaining independence in 2011 that may influence childhood nutritional status.

Objective: To estimate the prevalence of undernutrition among children in South Sudan in 2018 and 2019 compared to the prevalence in 2010.

Methods: Data on height and weight were collected using a 2-stage stratified sample framework in which households were randomly selected at the county level and nutritional status was calculated for all children under 5 years of age to determine height-for-age, weight-for-height, and weight-for-age Z-scores (HAZ, WHZ, and WAZ) and the prevalence of stunting, wasting, and underweight.

Early chronotype with metabolic syndrome favours resting and exercise fat oxidation in relation to insulin-stimulated non-oxidative glucose disposal.

New Findings: What is the central question of this study? Chronotype reflects differences in circadian-mediated metabolic and hormonal profiles. But, does resting and/or exercise fuel use differ in early versus late chronotype as it relates to insulin sensitivity? What are the main finding and its importance? Early chronotypes with metabolic syndrome utilized more fat during rest and exercise independent of aerobic fitness when compared with late chronotypes. Early chronotypes were also more physically active throughout the day.

Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction.

Dietary interventions such as sulfur amino acid restriction (SAAR) target multiple drivers of aging, and show promise for preventing or delaying the onset of chronic diseases. SAAR promotes metabolic health and longevity in laboratory animals. The effects of SAAR on proteostasis remain relatively unexplored.

Metabolic protection by the dietary flavonoid 7,8-dihydroxyflavone requires an intact gut microbiome.

Background: 7,8-dihydroxyflavone (DHF) is a naturally occurring flavonoid found in , , and species that confers protection against high-fat diet (HFD) induced metabolic pathologies selectively in female mice. We have previously reported that this metabolic protection is associated with early and stable remodeling of the intestinal microbiome, evident in female but not male DHF-supplemented mice. Early changes in the gut microbiome in female DHF-fed mice were highly predictive of subsequent metabolic protection, suggesting a causative association between the gut microbiome and the metabolic effects of DHF.

The Anticancer Drug Bleomycin Shows Potent Antifungal Activity by Altering Phospholipid Biosynthesis.

Invasive fungal infections are difficult to treat with limited drug options, mainly because fungi are eukaryotes and share many cellular mechanisms with the human host. Most current antifungal drugs are either fungistatic or highly toxic. Therefore, there is a critical need to identify important fungal specific drug targets for novel antifungal development.

Microsomal triglyceride transfer protein-mediated transfer of β-carotene from donor to acceptor vesicles in vitro.

Dietary β-carotene is the most abundant vitamin A precursor. Once absorbed by the enterocytes, the provitamin A carotenoid can either be cleaved into retinoids (vitamin A and its derivatives) or incorporated in its intact form within chylomicrons to be distributed throughout the body for utilization and/or storage by other tissues. From the liver, together with endogenous lipids, intact β-carotene can also be incorporated within very low-density lipoprotein/low-density lipoprotein (VLDL/LDL) for transport to other tissues and organs.

Microbial Analysis of Umbilical Cord Blood Reveals Novel Pathogens Associated with Stillbirth and Early Preterm Birth.

Stillbirths account for half of all perinatal mortality, but the underlying cause of a significant portion of the cases remains unknown. We set out to test the potential role and extent of microbial infection in stillbirth through a case-control analysis of fetal cord blood collected from the multisite Stillbirth Collaborative Research Network. Cases ( = 60) were defined as stillbirths at >20 weeks of gestation, and controls ( = 176) were live births.

The Influence of Food Environments on Food Security Resilience during the COVID-19 Pandemic: An Examination of Urban and Rural Difference in Kenya.

Hunger and food insecurity has worsened due to the COVID-19 pandemic. The types of food environments (e.g.

Insulin infusion decreases medium-sized extracellular vesicles in adults with metabolic syndrome.

Elevated extracellular vesicles (EVs) are associated with glucose dysmetabolism. However, the effects of insulin on EVs and subsequent relationships with insulin sensitivity, substrate oxidation, and inflammation are unknown. We tested the hypothesis that insulin would lower EVs and relate to insulin action.

Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling.

Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization.

Glycogen synthase kinase homolog Rim11 regulates lipid synthesis through the phosphorylation of Pah1 phosphatidate phosphatase in yeast.

Pah1 phosphatidate (PA) phosphatase plays a major role in triacylglycerol synthesis in Saccharomyces cerevisiae by producing its precursor diacylglycerol and concurrently regulates de novo phospholipid synthesis by consuming its precursor PA. The function of Pah1 requires its membrane localization, which is controlled by its phosphorylation state. Pah1 is dephosphorylated by the Nem1-Spo7 protein phosphatase, whereas its phosphorylation occurs by multiple known and unknown protein kinases.

MicroRNA detection in biologically relevant media using a split aptamer platform.

MicroRNA (miRNA)-based intercellular communication has been implicated in many functional and dysfunctional biological processes. This has raised interest in the potential use of miRNAs as biomarkers for diagnosis and prognosis. Though the list of clinically significant miRNA biomarkers is expanding, it remains challenging to adapt current chemical tools to investigate miRNAs in complex environments native to cells and tissues.

Introducing a New Bond-Forming Activity in an Archaeal DNA Polymerase by Structure-Guided Enzyme Redesign.

DNA polymerases have evolved to feature a highly conserved activity across the tree of life: formation of, without exception, internucleotidyl O-P linkages. Can this linkage selectivity be overcome by design to produce xenonucleic acids? Here, we report that the structure-guided redesign of an archaeal DNA polymerase, 9°N, exhibits a new activity undetectable in the wild-type enzyme: catalyzing the formation of internucleotidyl N-P linkages using 3'-NH-ddNTPs. Replacing a metal-binding aspartate in the 9°N active site with asparagine was key to the emergence of this unnatural enzyme activity.

SCD1 is nutritionally and spatially regulated in the intestine and influences systemic postprandial lipid homeostasis and gut-liver crosstalk.

Stearoyl-CoA desaturase-1 is an endoplasmic reticulum (ER)-membrane resident protein that inserts a double bond into saturated fatty acids, converting them into their monounsaturated counterparts. Previous studies have demonstrated an important role for SCD1 in modulating tissue and systemic health. Specifically, lack of hepatic or cutaneous SCD1 results in significant reductions in tissue esterified lipids.