Explore the vast range of titles available.

The textbook description of mitochondrial respiratory complexes (RCs) views them as free-moving entities linked by the mobile carriers coenzyme Q (CoQ) and cytochrome c (cyt c). This model (known as the fluid model) is challenged by the proposal that all RCs except complex II can associate in supercomplexes (SCs). The proposed SCs are the respirasome (complexes I, III, and IV), complexes I and III, and complexes III and IV. The role of SCs is unclear, and their existence is debated. By genetic modulation of interactions between complexes I and III and III and IV, we show that these associations define dedicated CoQ and cyt c pools and that SC assembly is dynamic and organizes electron flux to optimize the use of available substrates.

Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell–cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress.

Potassium (K+) is a key monovalent cation necessary for multiple aspects of cell growth and survival. In plants, this cation also plays a key role in the control of stomatal movement. KAT1 and its homolog KAT2 are the main inward rectifying channels present in guard cells, mediating K+ influx into these cells, resulting in stomatal opening. To gain further insight into the regulation of these channels, we performed a split-ubiquitin protein-protein interaction screen searching for KAT1 interactors in Arabidopsis (Arabidopsis thaliana). We characterized one of these candidates, BCL2-ASSOCIATED ATHANOGENE4 (BAG4), in detail using biochemical and genetic approaches to confirm this interaction and its effect on KAT1 activity. We show that BAG4 improves KAT1-mediated K+ transport in two heterologous systems and provide evidence that in plants, BAG4 interacts with KAT1 and favors the arrival of KAT1 at the plasma membrane. Importantly, lines lacking or overexpressing the BAG4 gene show altered KAT1 plasma membrane accumulation and alterations in stomatal movement. Our data allowed us to identify a KAT1 regulator and define a potential target for the plant BAG family. The identification of physiologically relevant regulators of K+ channels will aid in the design of approaches that may impact drought tolerance and pathogen susceptibility.

Abstract Environmental pollution is one of the main challenges faced by humanity. By their ubiquity and vast range of metabolic capabilities, microorganisms are affected by pollution with consequences on their host organisms and on the functioning of their environment. They also play key roles in the fate of pollutants through the degradation, transformation, and transfer of organic or inorganic compounds. Thus, they are crucial for the development of nature-based solutions to reduce pollution and of bio-based solutions for environmental risk assessment of chemicals. At the intersection between microbial ecology, toxicology, and biogeochemistry, microbial ecotoxicology is a fast-expanding research area aiming to decipher the interactions between pollutants and microorganisms. This perspective paper gives an overview of the main research challenges identified by the Ecotoxicomic network within the emerging One Health framework and in the light of ongoing interest in biological approaches to environmental remediation and of the current state of the art in microbial ecology. We highlight prevailing knowledge gaps and pitfalls in exploring complex interactions among microorganisms and their environment in the context of chemical pollution and pinpoint areas of research where future efforts are needed. Overview of the main research challenges at different scales for microbial ecotoxicology as identified by the Ecotoxicomic network in the light of the current state of the art.

Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell–cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress.

BackgroundStudies have shown that cannabis impairs driving and it associated with an increase in the risk of traffic road accidents involvement. Spain has implemented roadside drug testing, with later laboratory confirmation on positive cases.ObjectiveTo assess the presence and concentration of cannabis, as well as their combined use with other drugs (laboratory confirmation after the on-road screening) in Spanish drivers between 2011–2016.MethodsSpanish roadside mandatory alcohol and drug testing using saliva are carried out by our Traffic Police using Dräger Alcotest® 6810 device, and Dräger DrugTest® 5000, DrugWipe®, or Alere™ DDS®2 Mobile Test System. Confirmation analysis and quantification of cannabis using chromatographic techniques were performed for all positive cases (n=65 244 of 1 79 645 testing carried out). Statistical analysis was carried out using SPSS version 23.0.FindingsDelta-9-tetrahydrocannabinol (THC) was confirmed in 79.5% of all positive cases (n=51869). Combined use with other substances was observed in the 50.8%, mainly with cocaine (43.7%) and amphetamine-like substances (15.5%). Concentration values were important across the covered period (median 113.0 ng/mL). THC positive cases were mainly males (96.3%) and aged 20–40 years old.ConclusionsCannabis is frequently detected substance among Spanish drivers.Policy implicationsThe figures found evidence the need for intervention in this area. The continuity of roadside drug testing is considered important factor for deterring driving under the influence of substances.This work was supported by the Instituto de Salud Carlos III, Redes Temáticas de Investigación Cooperativa, Red de Trastornos Adictivos [grant number RD16/0017/0006], co-funded by FEDER funds of the European Union: a way to build Europe.

BackgroundSome drugs impair tasks related to driving, and roadside drug testing remains an important tool for deterring driving under the influence of them.ObjectiveTo assess the presence and concentration of methadone, and their combined use with other drugs (laboratory confirmation after the on-road screening) in Spanish drivers between 2011–2016.MethodsIn Spain, roadside mandatory drug testing using saliva are carried out by the Traffic Police using Dräger DrugTest® 5000, DrugWipe®, or Alere™ DDS®2 Mobile Test System. For positive cases in the period covered, 65244, confirmation analysis and quantification of methadone using chromatographic techniques were performed. Statistical analysis was carried out with R programming language (3.4.1) and SPSS version 23.0.FindingsMethadone was confirmed in 4.1% of positive cases: these tested also positive to 6-acetylmorphine (heroin metabolite, 81.9%) and other illicit drugs, such as cocaine (80%) and cannabis (45%). Only in a minority of methadone positives (0.4%) cases no other substances were detected. Concentration values reached important levels (median 201.4 ng/mL) and there was a relationship with age (R-squared=0.1475, p<0.005).ConclusionsPoly drug use (heroin, cocaine, cannabis) was the rule in drivers with methadone positive confirmation analyses.Policy implicationsAs methadone is a physician prescribed medication, improving opioid prescription, promoting the use of less driving-impairing medications, and giving more clear information to patients (risk communication) is a need.This work was supported by the Instituto de Salud Carlos III, Redes Temáticas de Investigación Cooperativa, Red de Trastornos Adictivos [grant RD16/0017/0006], co-funded by FEDER funds of the European Union: a way to build Europe.

Abnormalities in the origin of vertebral arteries are relatively uncommon, but extremely rare when this abnormality happens on both sides. We present an anatomic variation in which both vertebral arteries came from the proximal descending thoracic aorta beyond the left subclavian artery with no other supra-aortic vessels accompanying the abnormality. The right vertebral artery took a retro-oesophageal course (lusoria artery), while the right and the left vertebral arteries enter the transverse foramina at the 7th cervical vertebra. From an embryological point of view, and overall controversial, this anomaly can be explained by the bilateral persistence of the 8th intersegmental artery as the origin of vertebral artery, instead of the dorsal segment of the 7th intersegmental artery being the origin, which is normally the case. The adequate identification of vertebral artery anomalies in complementary explorations is very important to avoid misdiagnosed vertebral occlusions or unexpected vertebral artery injuries during supra-aortic trunks, thyroid, and oesophagus open surgeries, among others, or even over the course of endovascular procedures.

Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is to analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Prospective design study with concurrent data retrieval from automated medical records of all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64.6 ± 18.2 years. One hundred eighty-one (34.7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR 6–11). In-hospital mortality was 23.8% (124/521). The modeling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0.85 (0.82–0.88). The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients.

Potassium (K+) is a key monovalent cation necessary for multiple aspects of cell growth and survival. In plants, this cation also plays a key role in the control of stomatal movement. KAT1 and its homolog KAT2 are the main inward rectifying channels present in guard cells, mediating K+ influx into these cells, resulting in stomatal opening. To gain further insight into the regulation of these channels, we performed a split-ubiquitin protein-protein interaction screen searching for KAT1 interactors in Arabidopsis (Arabidopsis thaliana). We characterized one of these candidates, BCL2-ASSOCIATED ATHANOGENE4 (BAG4), in detail using biochemical and genetic approaches to confirm this interaction and its effect on KAT1 activity. We show that BAG4 improves KAT1-mediated K+ transport in two heterologous systems and provide evidence that in plants, BAG4 interacts with KAT1 and favors the arrival of KAT1 at the plasma membrane. Importantly, lines lacking or overexpressing the BAG4 gene show altered KAT1 plasma membrane accumulation and alterations in stomatal movement. Our data allowed us to identify a KAT1 regulator and define a potential target for the plant BAG family. The identification of physiologically relevant regulators of K+ channels will aid in the design of approaches that may impact drought tolerance and pathogen susceptibility.