Browse Articles

Acute mental stress-induced alpha or beta-adrenergic reactivity patterns linked to unique cardiometabolic risk profiles

Abstract Cardiometabolic risk may differ based on a stress-induced alpha(α)-adrenergic response versus a predominant beta(β)-adrenergic response. Whether these responses might serve as significant markers of distinct cardiometabolic risk profiles based on hemodynamic reactivity remain unknown. We (1) characterized predominant α-and β-adrenergic hemodynamic response patterns to acute mental stress; and (2) determined the cardiometabolic risk profile within predominant α-or β-adrenergic responders, irrespective of age, sex, or ethnicity. We included 117 South African teachers (aged 20–65 years) and administered an acute mental stress task (Color-Word-Conflict test) for one-minute. Participants’ hemodynamic response profiles were characterized as predominant α-adrenergic (decreases in cardiac output (CO) and Windkessel arterial compliance (Cwk) (lowest quartile)) (n = 48) and β-adrenergic (increases in CO, Cwk (highest quartile)) responses (n = 69) via Finometer beat-to-beat hemodynamic monitoring. Ambulatory-BP was measured and the number of 24 H-ischemic events determined by ECG. Cardiometabolic markers were analyzed using fasting blood samples, and abnormal glucose tolerance (Abnl-GT), combining prediabetes and diabetes, was defined as glycated hemoglobin (HbA1c) ≥ 5.7% and/or fasting glucose > 100 mg/dL and/or diabetes medication usage. Predominant α-adrenergic responders presented with an overall poorer cardiometabolic profile, with higher levels of HbA1c, insulin, greater insulin resistance and higher total cholesterol and lower HDL-cholesterol. Adjusted analyses indicated that a predominant α-adrenergic profile had higher odds of central obesity (P = 0.031), low HDL-cholesterol (P = 0.042), 24-H-hypertension (P < 0.001), cardiac stress (P = 0.025), ischemic events (P = 0.048) and medium-to-high 10-year stroke probability (P < 0.001), compared to β-adrenergic responders. In the β-adrenergic responders, higher odds for ischemic events, stroke probability and Abnl-GT were found (all P ≤ 0.022), compared to α-adrenergic responders. Independent of age, sex or ethnicity, the risk profile identified in predominant α-adrenergic responders mainly involved the effects of a high-pressure system, cardiac stress, and ischemia. Whereas in predominant β-adrenergic responders, the risk profile pointed to a more metabolic and hyperperfusion injury-related cardiometabolic risk.

Author Correction: Fault correcting adder design for low power applications

Physical exercise alone or combined with omega-3 modulates apical periodontitis induced in rats

Genetic data from Indigenous Greenlanders could help to narrow health-care gap

Arg209Lys and Gln508His missense variants in Rabphilin 3A cause pre- and post-synaptic dysfunctions at excitatory glutamatergic synapses

Integrated analysis and experimental validation reveal the prognostic and immunological features associated with coagulation in hepatocellular carcinoma

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted

Abstract Tissue-resident memory CD8 T (T RM ) cells provide protection from infection at barrier sites. In the small intestine, T RM cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential 1 . However, the origins of this diversity remain unknown. Here we proposed that distinct tissue niches drive the phenotypic heterogeneity of T RM cells. To test this, we leveraged spatial transcriptomics of human samples, a mouse model of acute systemic viral infection and a newly established strategy for pooled optically encoded gene perturbations to profile the locations, interactions and transcriptomes of pathogen-specific T RM cell differentiation at single-transcript resolution. We developed computational approaches to capture cellular locations along three anatomical axes of the small intestine and to visualize the spatiotemporal distribution of cell types and gene expression. Our study reveals that the regionalized signalling of the intestinal architecture supports two distinct T RM cell states: differentiated T RM cells and progenitor-like T RM cells, located in the upper villus and lower villus, respectively. This diversity is mediated by distinct ligand–receptor activities, cytokine gradients and specialized cellular contacts. Blocking TGFβ or CXCL9 and CXCL10 sensing by antigen-specific CD8 T cells revealed a model consistent with anatomically delineated, early fate specification. Ultimately, our framework for the study of tissue immune networks reveals that T cell location and functional state are fundamentally intertwined.

Homologous relationship between FabG involved in fatty acid biosynthesis and SDR on chromosome II in the multi-chromosome pathogen Vibrio anguillarum

Toward a high-throughput in vitro model for estimating vitreous humor permeability of topically applied drugs

Abstract The vitreous humor of the eye presents a crucial target for posterior segment therapy due to its proximity to the retina and relatively easy accessibility. Although intravitreous injections have long been the primary method for treating posterior segment disorders, recent successes in non-invasive topical treatments have led to the exploration of alternative administration routes. The objective of our study is to establish a platform for a Parallel Artificial Membrane Permeability Assay (PAMPA) model that mimics the posterior segment, modelling the permeation process of compounds applied topically on the eye. The study demonstrates the acceptor-phase effects of sodium hyaluronate and agar on passive permeability, while applying a previously published vitreous humor-mimetic material. Physicochemical similarities of the acceptor phase media and freshly excised porcine vitreous humor further support the applicability of the mimetic material, based on viscosity and zeta potential measurement. As a result, a new concept is introduced for measuring posterior segment permeability, with potential for future high throughput screening applications.

Genetic architecture in Greenland is shaped by demography, structure and selection

Energy potential of elephant grass broth as biomass for biogas production

Theoretical solution research on air curtain thermal insulation technology at tunnel portal in cold area

Observing formation and evolution of dislocation cells during plastic deformation

Abstract During plastic deformation of metals and alloys, dislocations self-organise in cells, which subsequently continuously decrease in size. How and when these processes take place has remained elusive, because observations of the structural dynamics in the bulk have not been feasible. We here present X-ray diffraction microscopy sequences of the structural evolution during tensile deformation of a mm-sized aluminium (111) single crystal. The formation and subsequent development of 40,000 cells are visualised. The cells form in a stochastic, isotropic and uncorrelated manner already at 1% strain. We reveal that the cell size and dislocation density distributions are log-normal and bi-modal distributions, respectively, exhibiting scaling and maintaining a fixed volume ratio between cell interior and cell boundary. This insight leads to an interpretation of the formation and evolution steps in terms of universal stochastic multiplicative processes. This work will guide dislocation dynamics modelling, as it provides unique dynamic data and understanding.

An efficient parallelization technique for the coupled problems of fluid, gas and plasma mechanics in the grid environment

A multi model deep net with an explainable AI based framework for diabetic retinopathy segmentation and classification

Transcranial direct current stimulation associated with physical exercise can help smokers to quit smoking: a randomized controlled trial

Author Correction: CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors

Unraveling carbonate fault dynamics, from friction to decarbonation, through the 1959 Mw 7.2 earthquake in Montana

Abstract Seismic rupture in carbonate rocks influences fault friction behavior through thermal evolution and mineral reactions. Focusing on the 1959 Mw 7.2 Hebgen Lake event in western Yellowstone, Montana, the largest earthquake on a normal fault in the United States, we analyze fault rock microstructures and mineralogical changes to constrain frictional heating on the fault plane. We combine thermal maturity of organic matter, magnetic fabric, and thermomagnetic methods with scanning electron microscopy to unravel variations in peak frictional temperature along the fault slip surface. The mineral changes caused by coseismic heating (e.g., nanocalcite formation or goethite to hematite reaction) occur in patches along the fault mirror, hence reflecting considerable differences in frictional heat. While coseismic thermal heterogeneities have been reported in other rock types, this is the first time they are documented and quantified specifically in carbonates. Furthermore, these results provide new mineralogical criteria to quantify coseismic frictional heat in natural faults at temperatures lower than that of decarbonation and highlight the need to consider coseismic friction processes at a scale larger than most deformation experiments. For example, we document the critical role played by fault plane attitude (dip) at the scale of a few tens of centimeters in production of frictional heat. Our results emphasize that while coseismic decarbonation dynamically weakens carbonate-hosted faults, it may generally not occur along an entire fault plane.

Global impact of the COVID-19 lockdown on biodiversity data collection

Abstract The COVID-19 pandemic triggered different governmental responses across borders, with cascading effects on people’s movements and on biodiversity data collection. We quantified changes in the number of species occurrence records collected during the first global lockdown (March 15th to May 1st 2020) relative to pre-pandemic levels using data from the Global Biodiversity Information Facility (GBIF). We modelled how such changes relate to the stringency of governmental policy responses, changes in human mobility, and countries’ population size and economic class across 129 countries. We further focused on data from the community science project eBird, which constitutes the largest dataset in GBIF, to investigate changes in participation and activity patterns of individual observers (eBirders) during the lockdown. We found that the decreases in GBIF records correlated with declines in numbers of visitors to parks and outdoor areas, and were significantly larger in developing countries compared to developed ones. While the activity ranges of eBirders shrunk across all countries analysed, the number of eBirders in developing and least developed countries declined more than in developed countries, as the lockdown disrupted the influx of international visitors. Our results suggest that community-based, local monitoring programmes are essential to reduce biases in global biodiversity monitoring.

Non-invasive vestibular nerve stimulation (VeNS) reduces visceral adipose tissue: results of a randomised controlled trial

Abstract Across multiple species, chronic vestibular stimulation activates hypothalamic regions involved in energy homeostasis and reduces body fat. This first-in-human randomised controlled trial evaluated the efficacy and safety of electrical vestibular nerve stimulation (VeNS) as a means of reducing excess body weight and fat. Overweight and obese adults were randomised 1:1 to receive 60 min of daily VeNS (n = 117) or sham stimulation (n = 124) for 6 months, together with a hypocaloric diet. The primary endpoints were weight loss based. Secondary endpoints included reduction in visceral adipose tissue (VAT). It is VAT, more than subcutaneous fat depots, which is particularly associated with the risks associated with obesity. The weight loss based primary endpoints were not met. However, mean change in VAT was significantly greater in the active (− 12.6%) versus the sham (− 4.7%) group (p = 0.03). This suggests that regular VeNS may cause a clinically meaningful reduction in VAT.