Regulation of Intracellular Calcium Concentration by Nanosecond Pulsed Electric Fields

Changes in [Ca2+]i response of individual Jurkat cells to nanosecond pulsed electric fields (nsPEFs) of 60 ns and field strengths of 25, 50, and 100 kV/cm were investigated. The magnitude of the nsPEF-induced rise in [Ca2+]i was dependent on the electric field strength. With 25 and 50 kV/cm, the [Ca2+]i response was due to the release of Ca2+ from intracellular stores and occurred in less than 18 ms. With 100 kV/cm, the increase in [Ca2+]i was due to both internal release and to influx across the plasma membrane. Spontaneous changes in [Ca2+]i exhibited a more gradual increase over several seconds. The initial, pulse-induced [Ca2+]i response initiates at the poles of the cell with respect to electrode placement and co-localizes with the endoplasmic reticulum. The results suggest that nsPEFs target both the plasma membrane and subcellular membranes and that one of the mechanisms for Ca2+ release may be due to nanopore formation in the endoplasmic reticulum

Changes in authoritarianism before and during the COVID-19 pandemic: Comparisons of latent means across East and West Germany, gender, age, and education

Modern theories of authoritarianism have stressed the importance of threat to the expression of authoritarian attitudes and intolerance. Arguably, authoritarian tendencies may have increased during COVID-19 pandemic, a major threat to life and security. One issue arising when comparing mean scores is that of measurement invariance. Meaningful comparisons are only possible, if latent constructs are similar between groups and/or across time. This prerequisite is rarely ever tested in research on authoritarianism. In this study, we aim to analyze the short scale for authoritarianism KSA-3 by investigating its measurement invariance on two levels (three first-order and one second-order factors) and latent mean changes using two German representative samples (N = 4,905). Specifically, we look at differences before and during the pandemic (2017 vs. 2020). While measurement invariance holds across both levels in all conditions, we find a decrease in latent means in 2020, contrary to expectations and established theories. Moreover, latent means differ with regard to gender, education, and east-west Germany. We conclude that analyses of latent means and measurement invariance instead of mean comparisons with composites should become the standard. Future studies should focus on threat as a moderator between authoritarianism and intolerance, and on possible interactions with context variables

Lung Ultrasound for the Exclusion of Pneumothorax after Interventional Bronchoscopies—A Retrospective Study

A chest X-ray (CXR) is recommended after bronchoscopies with an increased risk of pneumothorax (PTX). However, concerns regarding radiation exposure, expenses and staff requirements exist. A lung ultrasound (LUS) is a promising alternative for the detection of PTX, though data are scarce. This study aims to investigate the diagnostic yield of LUS compared to CXR, to exclude PTX after bronchoscopies with increased risk. This retrospective single-centre study included transbronchial forceps biopsies, transbronchial lung cryobiopsies and endobronchial valve treatments. Post-interventional PTX screening consisted of immediate LUS and CXR within two hours. In total, 271 patients were included. Early PTX incidence was 3.3%. Sensitivity, specificity, and the positive and negative predictive values of LUS were 67.7% (95% CI 29.93–92.51%), 99.2% (95% CI 97.27–99.91%), 75.0% (95% CI 41.16–92.79%) and 98.9% (95% CI 97.18–99.54%), respectively. PTX detection by LUS enabled the immediate placement of two pleural drains along with the bronchoscopy. With CXR, three false-positives and one false-negative were observed; the latter evolved into a tension-PTX. LUS correctly diagnosed these cases. Despite low sensitivity, LUS enables early diagnosis of PTX, thus preventing treatment delays. We recommend immediate LUS, in addition to LUS or CXR after two to four hours and monitoring for signs and symptoms. Prospective studies with higher sample sizes are needed

Ancient segmentally duplicated LCORL retrocopies in equids.

LINE-1 is an active transposable element encoding proteins capable of inserting host gene retrocopies, resulting in retro-copy number variants (retroCNVs) between individuals. Here, we performed retroCNV discovery using 86 equids and identified 437 retrocopy insertions. Only 5 retroCNVs were shared between horses and other equids, indicating that the majority of retroCNVs inserted after the species diverged. A large number (17-35 copies) of segmentally duplicated Ligand Dependent Nuclear Receptor Corepressor Like (LCORL) retrocopies were present in all equids but absent from other extant perissodactyls. The majority of LCORL transcripts in horses and donkeys originate from the retrocopies. The initial LCORL retrotransposition occurred 18 million years ago (17-19 95% CI), which is coincident with the increase in body size, reduction in digit number, and changes in dentition that characterized equid evolution. Evolutionary conservation of the LCORL retrocopy segmental amplification in the Equidae family, high expression levels and the ancient timeline for LCORL retrotransposition support a functional role for this structural variant

Discrete wetland groundwater discharges revealed with a three-dimensional temperature model and botanical indicators (Boxford, UK)

Wetlands provide unique goods and services, as habitats of high biodiversity. Hydrology is the principal control on wetland functioning; hence, understanding the water source is fundamental. However, groundwater inflows may be discrete and easily missed. Research techniques are required with low cost and minimal impact in sensitive settings. In this study, the effectiveness of using a three-dimensional (3D) temperature model and botanical indicators to characterise groundwater discharge is explored at the CEH (Centre for Ecology and Hydrology) River Lambourn Observatory, Boxford, UK. This comprises a 10 ha lowland riparian wetland, designated for its scientific interest and conservation value. Temperature data were collected in winter at multiple depths down to 0.9 m over approximately 3.6 ha and transformed into a 3D model via ordinary kriging. Anomalous warm zones indicated distinct areas of groundwater upwelling which were concurrent with relic channel structures. Lateral heat propagation from the channels was minimal and restricted to within 5–10 m. Vertical temperature sections within the channels suggest varying degrees of groundwater discharge along their length. Hydrochemical analysis showed that warmer peat waters were akin to deeper aquifer waters, confirming the temperature anomalies as areas of groundwater discharge. Subsequently, a targeted vegetation survey identified Carex paniculata as an indicator of groundwater discharge. The upwelling groundwater contains high concentrations of nitrate which is considered to support the spatially restricted growth of Carex paniculata against a background of poor fen communities located in reducing higher-phosphate waters

Do agri-environment schemes result in improved water quality?

Welsh Government. Grant Number: 183/2007/0

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

LANDWISE NFM: How soil management and land use affects soil properties and flood risk: Results from the broad-scale and detailed field surveys

Summary of findings so far • Management of near surface soil properties and preferential flow pathways is important so that deeper soil water storage is available and accessible. • Land use and management practices can significantly enhance soil physical and hydrological/hydraulic properties and flood mitigation potential • Increasing organic matter content increases soil porosity, creating more soil water storage and potential to mitigate flooding. • Fields with ‘low’ starting organic matter content can greatly improve soil porosity therefore soil water storage with relatively modest organic matter increases. • Organic additions are not the only way to improve soil structure, innovative management practices (e.g. controlled traffic and min till) also improve soil structure, saturated hydraulic conductivity and therefore NFM potential. • Mature woodland has the highest organic matter content, soil porosity, saturated hydraulic conductivity and NFM potential relative to arable and grass land use. • Effects of arable rotations and inclusion of grass in rotations are being investigated