The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1 Cells.

Inhibition of the prolyl-4-hydroxylase domain (PHD) enzymes, leading to the stabilization of hypoxia-inducible factor (HIF) α as well as to the stimulation of erythropoietin (Epo) synthesis, is the functional mechanism of the new anti-anemia drug roxadustat. Little is known about the effects of roxadustat on the Epo-producing cell pool. To gain further insights into the function of PHD inhibitors, we characterized the abundance of mesenchymal stem cell (MSC)-like cells after roxadustat treatment of mice.

Repeat radiofrequency catheter ablation of atrial tachycardias in patients with congenital heart disease.

Introduction: Atrial tachycardias (AT) in patients with congenital heart disease (CHD) are significantly contributing to morbidity and mortality. Aim of this study was to evaluate the long-term course of CHD patients requiring repeat ablation procedures (RAP) of AT.

Patients And Methods: All 144 patients with CHD who had undergone ablation of AT at our center between January 2003 and October 2018 were enrolled.

Estimating the effect of practicing nursing professionals density on cumulative carbapenem-resistance prevalence in gram-negative invasive Isolates: a 30 European country observational modeling study.

Background: The burden of antimicrobial-resistance, specifically carbapenem-resistance in gram-negative bacteria (CRGN), presents a serious public health threat worldwide. In Europe, Southern and Eastern countries (SEC) display a higher CRGN-prevalence as compared to Northern and Western countries (NWC). Since SEC also display lower nurse-density on average, we hypothesized that the occurrence of CRGN might correlate with nurse understaffing and therefore aimed at quantifying a potential independent effect of nurse-density on total CRGN in Europe.

Effects of Atrial Fibrillation on the Human Ventricle.

Rationale: Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction.

Objective: This study investigates the effects and molecular mechanisms of AF on the human LV.

Chimpanzees consider freedom of choice in their evaluation of social action.

Judgements of wrongdoing in humans often hinge upon an assessment of whether a perpetrator acted out of free choice: whether they had more than one option. The classic inhibitors of free choice are constraint (e.g.

Development of high-affinity fluorinated ligands for cannabinoid subtype 2 receptor, and in vitro evaluation of a radioactive tracer for imaging.

The development of neurodegenerative diseases is associated with cerebral inflammation, which activates resident immune cells of the central nervous system (CNS), namely microglial cells that show an up-regulation of the cannabinoid subtype 2 receptor (CBR) expression. Therefore our work aimed to design and synthesize a radiotracer for the detection of CBR expression by positron emission tomography (PET) allowing an early diagnosis of neurodegenerative diseases. For the development of such a PET tracer, N-alkyl-substituted indole-3-yl-tetramethylcyclopropylketones served as lead structures due to their high CBR potency and selectivity, allowing radiolabeling on the N-alkyl chain.

Impact of COVID-19 on the Neurosurgical Resident Training Program: An Early Experience.

Background:  The present study evaluates the impact of COVID-19 pandemic restrictions during the first lockdown period in spring 2020 on the neurosurgical resident training program, and provides constructive approaches to deal with such situations.

Methods:  A concurrent embedded mixed methods design was used. Qualitative data were collected through in-depth interviews from all neurosurgical residents at three university hospitals in Germany.

Nonswelling and Hydrolytically Stable Hydrogels Uncover Cellular Mechanosensing in 3D.

While matrix stiffness regulates cell behavior on 2D substrates, recent studies using synthetic hydrogels have suggested that in 3D environments, cell behavior is primarily impacted by matrix degradability, independent of stiffness. However, these studies did not consider the potential impact of other confounding matrix parameters that typically covary with changes in stiffness, particularly, hydrogel swelling and hydrolytic stability, which may explain the previously observed distinctions in cell response in 2D versus 3D settings. To investigate how cells sense matrix stiffness in 3D environments, a nonswelling, hydrolytically stable, linearly elastic synthetic hydrogel model is developed in which matrix stiffness and degradability can be tuned independently.

Brown adipose tissue activation is not related to hypermetabolism in emphysematous chronic obstructive pulmonary disease patients.

Background: Brown adipose tissue (BAT) has been primarily researched as a potential target for mitigating obesity. However, the physiological significance of BAT in relation to cachexia remains poorly understood. The objective of this study was to investigate the putative contribution of BAT on different components of energy metabolism in emphysematous chronic obstructive pulmonary disease (COPD) patients.

Widespread occurrence of covalent lysine-cysteine redox switches in proteins.

We recently reported the discovery of a lysine-cysteine redox switch in proteins with a covalent nitrogen-oxygen-sulfur (NOS) bridge. Here, a systematic survey of the whole protein structure database discloses that NOS bridges are ubiquitous redox switches in proteins of all domains of life and are found in diverse structural motifs and chemical variants. In several instances, lysines are observed in simultaneous linkage with two cysteines, forming a sulfur-oxygen-nitrogen-oxygen-sulfur (SONOS) bridge with a trivalent nitrogen, which constitutes an unusual native branching cross-link.

Spatial and temporal control of mitochondrial H O release in intact human cells.

Hydrogen peroxide (H O ) has key signaling roles at physiological levels, while causing molecular damage at elevated concentrations. H O production by mitochondria is implicated in regulating processes inside and outside these organelles. However, it remains unclear whether and how mitochondria in intact cells release H O .

Drivers of gut microbiome variation within and between groups of a wild Malagasy primate.

Background: Various aspects of sociality can benefit individuals' health. The host social environment and its relative contributions to the host-microbiome relationship have emerged as key topics in microbial research. Yet, understanding the mechanisms that lead to structural variation in the social microbiome, the collective microbial metacommunity of an animal's social network, remains difficult since multiple processes operate simultaneously within and among animal social networks.

Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk.

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry.

Bacterial Spectrum and Infective Foci in Patients Operated for Infective Endocarditis: Time to Rethink Strategies?

Objective: The rising incidence of infective endocarditis (IE) accompanied by the de-escalation of antibiotic prophylaxis and the complexity of surgical treatment makes IE a daunting foe. We reviewed all patients who underwent cardiac surgery for IE at our institution with a focus on causative organisms and infective foci.

Methods: A review of 3,952 consecutive patients who underwent cardiac surgery at our institution between January 2013 and December 2017 revealed 160 patients (4%) who were operated for IE.

Sustained Control of Pyruvate Carboxylase by the Essential Second Messenger Cyclic di-AMP in Bacillus subtilis.

In Bacillus subtilis and other Gram-positive bacteria, cyclic di-AMP is an essential second messenger that signals potassium availability by binding to a variety of proteins. In some bacteria, c-di-AMP also binds to the pyruvate carboxylase to inhibit its activity. We have discovered that in B.

Fungal fruit body assemblages are tougher in harsh microclimates.

Forest species are affected by macroclimate, however, the microclimatic variability can be more extreme and change through climate change. Fungal fruiting community composition was affected by microclimatic differences. Here we ask whether differences in the fruiting community can be explained by morphological traits of the fruit body, which may help endure harsh conditions.

Gene-gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer.

Background: Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility.

Time experience in patients with schizophrenia and affective disorders.

Background: The experience of time, or the temporal order of external and internal events, is essential for humans. In psychiatric disorders such as depression and schizophrenia, impairment of time processing has been discussed for a long time.

Aims: In this explorative pilot study, therefore, the subjective time feeling as well as objective time perception were determined in patients with depression and schizophrenia, along with possible neurobiological correlates.

Generation of homozygous Na1.8 knock-out iPSC lines by CRISPR Cas9 genome editing to investigate a potential new antiarrhythmic strategy.

The sodium channel Na1.8, encoded by SCN10A, is reported to contribute to arrhythmogenesis by inducing the late I and thereby enhanced persistent Na current. However, its exact electrophysiological role in cardiomyocytes remains unclear.

Fibril Structure Demonstrates the Role of Iodine Labelling on a Pentapeptide Self-Assembly.

Iodination has long been employed as a successful labelling strategy to gain structural insights into proteins and other biomolecules via several techniques, including Small Angle X-ray Scattering, Inductively Coupled Plasma Mass Spectrometer (ICP-MS), and single-crystal crystallography. However, when dealing with smaller biomolecular systems, interactions driven by iodine may significantly alter their self-assembly behaviour. The engineering of amyloidogenic peptides for the development of ordered nanomaterials has greatly benefitted from this possibility.

Methods for Assessment of Viability and Germination of Resting Spores.

Clubroot caused by the obligate biotrophic parasite is a destructive soil borne disease of cruciferous crops. Resting spores of can survive in the soil for a long period without hosts or external stimulants. The viability and germination rate of resting spores are crucial factors of the inoculum potential in the field.

Development and Evaluation of Peptidomimetic Compounds against SARS-CoV-2 Spike Protein: An in silico and in vitro Study.

Background: Coronavirus disease 2019 (COVID-19) as global pandemic disease has been adversely affecting public health and social life with considerable loss of human life worldwide. Therefore, there is an urgent need for developing novel therapeutics to combat COVID-19. The causative agent of COVID-19 is SARS-CoV-2 which targets human angiotensin converting enzyme 2 (ACE2) as cellular receptor via its spike (S) protein.

Ultrafast population coding and axo-somatic compartmentalization.

Populations of cortical neurons respond to common input within a millisecond. Morphological features and active ion channel properties were suggested to contribute to this astonishing processing speed. Here we report an exhaustive study of ultrafast population coding for varying axon initial segment (AIS) location, soma size, and axonal current properties.