Crystal structure of yeast V1‐ATPase in the autoinhibited state

Vacuolar ATPases (V‐ATPases) are essential proton pumps that acidify the lumen of subcellular organelles in all eukaryotic cells and the extracellular space in some tissues. V‐ATPase activity is regulated by a unique mechanism referred to as reversible disassembly, wherein the soluble catalytic sector, V₁, is released from the membrane and its MgATPase activity silenced. The crystal structure of yeast V₁ presented here shows that activity silencing involves a large conformational change of subunit H, with its C‐terminal domain rotating ~150° from a position near the membrane in holo V‐ATPase to a position at the bottom of V₁ near an open catalytic site. Together with biochemical data, the structure supports a mechanistic model wherein subunit H inhibits ATPase activity by stabilizing an open catalytic site that results in tight binding of inhibitory ADP at another site.     

Morphological variation associated with dispersal capacity in a tree‐killing bark beetle Dendroctonus ponderosae Hopkins

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Predicting the success of an invader: Niche shift versus niche conservatism

Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype–environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat‐shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental‐induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe.     

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

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A comparison of genetic stability in tea [Camellia sinensis (L.) Kuntze] plantlets derived from callus with plantlets from long-term in vitro propagation

Plant Cell, Tissue and Organ Culture (PCTOC) - The development of tissue-specific or inducible promoters is important for plant genetic engineering. In this study, we isolated two novel promoters...     

Hypertension awareness,treatment, and control and their association with healthcare access in the middle-aged and older Indian population: A nationwide cohort study

BackgroundHypertension is the most important cardiovascular risk factor in India, and representative studies of middle-aged and older Indian adults have been lacking. Our objectives were to estimate the proportions of hypertensive adults who had been diagnosed, took antihypertensive medication, and achieved control in the middle-aged and older Indian population and to investigate the association between access to healthcare and hypertension management.Methods and findingsWe designed a nationally representative cohort study of the middle-aged and older Indian population, the Longitudinal Aging Study in India (LASI), and analyzed data from the 2017–2019 baseline wave (N = 72,262) and the 2010 pilot wave (N = 1,683). Hypertension was defined as self-reported physician diagnosis or elevated blood pressure (BP) on measurement, defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg. Among hypertensive individuals, awareness, treatment, and control were defined based on self-reports of having been diagnosed, taking antihypertensive medication, and not having elevated BP, respectively. The estimated prevalence of hypertension for the Indian population aged 45 years and older was 45.9% (95% CI 45.4%–46.5%). Among hypertensive individuals, 55.7% (95% CI 54.9%–56.5%) had been diagnosed, 38.9% (95% CI 38.1%–39.6%) took antihypertensive medication, and 31.7% (95% CI 31.0%–32.4%) achieved BP control. In multivariable logistic regression models, access to public healthcare was a key predictor of hypertension treatment (odds ratio [OR] = 1.35, 95% CI 1.14–1.60, p = 0.001), especially in the most economically disadvantaged group (OR of the interaction for middle economic status = 0.76, 95% CI 0.61–0.94, p = 0.013; OR of the interaction for high economic status = 0.84, 95% CI 0.68–1.05, p = 0.124). Having health insurance was not associated with improved hypertension awareness among those with low economic status (OR = 0.96, 95% CI 0.86–1.07, p = 0.437) and those with middle economic status (OR of the interaction = 1.15, 95% CI 1.00–1.33, p = 0.051), but it was among those with high economic status (OR of the interaction = 1.28, 95% CI 1.10–1.48, p = 0.001). Comparing hypertension awareness, treatment, and control rates in the 4 pilot states, we found statistically significant (p < 0.001) improvement in hypertension management from 2010 to 2017–2019. The limitations of this study include the pilot sample being relatively small and that it recruited from only 4 states.ConclusionsAlthough considerable variations in hypertension diagnosis, treatment, and control exist across different sociodemographic groups and geographic areas, reducing uncontrolled hypertension remains a public health priority in India. Access to healthcare is closely tied to both hypertension diagnosis and treatment.

Jinkook Lee and colleagues investigate hypertension management and its association with healthcare access in middle-aged and older adults in India.     

Yeast pyruvate kinase: essential lysine residues in the active site

1. Yeast pyruvate kinase was purified to near homogeneity and subjected to chemical modification by trinitrobenzenesulfonate and by P1, P2-bis (5' pyridoxal) diphosphate. 2. Labeled peptides were isolated and their amino acid composition was determined. 3. The results suggest that yeast pyruvate kinase has an essential lysine residue, and that this residue is in a location equivalent to an essential lysine described in the muscle enzyme. 4. Protection experiments indicate that this lysine is located at the nucleotide binding site.     

Human cerebral organoids reveal progenitor pathology in EML1‐linked cortical malformation

Malformations of human cortical development (MCD) can cause severe disabilities. The lack of human‐specific models hampers our understanding of the molecular underpinnings of the intricate processes leading to MCD. Here, we use cerebral organoids derived from patients and genome edited‐induced pluripotent stem cells to address pathophysiological changes associated with a complex MCD caused by mutations in the echinoderm microtubule‐associated protein‐like 1 (EML1) gene. EML1‐deficient organoids display ectopic neural rosettes at the basal side of the ventricular zone areas and clusters of heterotopic neurons. Single‐cell RNA sequencing shows an upregulation of basal radial glial (RG) markers and human‐specific extracellular matrix components in the ectopic cell population. Gene ontology and molecular analyses suggest that ectopic progenitor cells originate from perturbed apical RG cell behavior and yes‐associated protein 1 (YAP1)‐triggered expansion. Our data highlight a progenitor origin of EML1 mutation‐induced MCD and provide new mechanistic insight into the human disease pathology.