Caveolae are cell-surface membrane invaginations that play critical roles in cellular processes including signaling and membrane homeostasis. The cavin proteins, in cooperation with caveolins, are essential for caveola formation. Here we show that a minimal N-terminal domain of the cavins, termed HR1, is required and sufficient for their homo- and hetero-oligomerization. Crystal structures of the mouse cavin1 and zebrafish cavin4a HR1 domains reveal highly conserved trimeric coiled-coil architectures, with intersubunit interactions that determine the specificity of cavin-cavin interactions. The HR1 domain contains a basic surface patch that interacts with polyphosphoinositides and coordinates with additional membrane-binding sites within the cavin C terminus to facilitate membrane association and remodeling. Electron microscopy of purified cavins reveals the existence of large assemblies, composed of a repeating rod-like structural element, and we propose that these structures polymerize through membrane-coupled interactions to form the unique striations observed on the surface of caveolae in vivo.

Caveolar proteins and caveolae negatively regulate a second clathrin-independent endocytic CLIC/GEEC pathway; caveolin-1 affects membrane diffusion properties of raft-associated CLIC cargo, and the scaffolding domain of caveolin-1 is required and sufficient for endocytic inhibition.

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Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.

Background Anemia remains a major public health challenge with high prevalence among women in South and Southeast Asian countries. Reductions in anemia rates have been stalled, despite the implementation of different maternal health and nutrition programs. This study aimed to assess the prevalence and factors associated with anemia among women of reproductive age in seven selected South and Southeast Asian countries. Methods This cross-sectional analysis utilized data from the most recent demographic and health surveys from seven selected South and Southeast Asian countries

BackgroundAnemia during pregnancy is a major public health problem globally with multiple causes including inadequate dietary intakes. The aim of the study was to assess the effect of nutrition education on nutritional knowledge, hemoglobin level and dietary intake of anemic pregnant women.Materials and methodsA quasi-experimental study was conducted among 115 mild to moderately anemic pregnant women attending ante natal clinics. Pregnant women were consecutively enrolled and assigned to receive nutrition education and diet plan in intervention group (n = 58) and general education only in control group (n = 57). The nutrition education was given to pregnant women on individual basis at the time of enrollment and follow-ups were done through biweekly phone calls and every 4 weeks during ANC visits. Baseline data were collected using semi-structure questionnaire for interview and hemoglobin level was also measured. Data were collected after 10 weeks of nutrition education intervention. Independent sample t-test was used to compare differences between the two groups.ResultsOut of 115 pregnant women enrolled, 107 completed the study (Intervention: 53; Control: 54). At the end of the nutrition education intervention and iron rich food based diet plan, the change in hemoglobin level was significantly high in the intervention over control group [0.56±0.40gm/dl vs. 0.16±0.82gm/dl, p = 0.002]. The change in the maternal nutritional knowledge score on anemia and iron rich foods was significantly high in the intervention over control group [8.26±4.57 vs. 1.05±6.59, p<0.001].Consumption of iron rich food was significantly high in the intervention group (P<0.05).ConclusionProvision of nutrition education and iron rich food based diet plan was significantly associated with improved hemoglobin levels, improved dietary intake and nutritional knowledge on anemia and iron rich foods.

Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly in high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling and resistance to cytotoxic and targeted therapies1–4. To uncover therapeutic targets for tumours with CCNE1 amplification, we undertook genome-scale CRISPR–Cas9-based synthetic lethality screens in cellular models of CCNE1 amplification. Here we report that increasing CCNE1 dosage engenders a vulnerability to the inhibition of the PKMYT1 kinase, a negative regulator of CDK1. To inhibit PKMYT1, we developed RP-6306, an orally bioavailable and selective inhibitor that shows single-agent activity and durable tumour regressions when combined with gemcitabine in models of CCNE1 amplification. RP-6306 treatment causes unscheduled activation of CDK1 selectively in CCNE1-overexpressing cells, promoting early mitosis in cells undergoing DNA synthesis. CCNE1 overexpression disrupts CDK1 homeostasis at least in part through an early activation of the MMB–FOXM1 mitotic transcriptional program. We conclude that PKMYT1 inhibition is a promising therapeutic strategy for CCNE1-amplified cancers.

Sec16A is known to be required for COPII vesicle formation from the ER. Here, Bruno et al. show that, independent of its role at the ER, Sec16A is a RAB10 effector involved in the insulin-stimulated formation of specialized transport vesicles that ferry the GLUT4 glucose transporter to the plasma membrane of adipocytes.