Physiological relevance, localization and substrate specificity of the alternative (type II) mitochondrial NADH dehydrogenases of .

Mitochondria from harbor a branched electron-transport chain containing a proton-pumping Complex I NADH dehydrogenase and three Type II NADH dehydrogenases (NDH-2). To investigate the physiological role, localization and substrate specificity of these enzymes, the growth of various NADH dehydrogenase knockout mutants was quantitatively characterized in shake-flask and chemostat cultures, followed by oxygen-uptake experiments with isolated mitochondria. NAD(P)H:quinone oxidoreduction of the three NDH-2 were individually assessed.

Single-cell epigenetic profiling reveals an interferon response-high program associated with deficiency in kidney cancer.

Renal cell carcinoma (RCC) is characterized by recurrent somatic mutations in epigenetic regulators, which stratify patients into clinically significant subgroups with distinct prognoses and treatment responses. However, the cell type-specific epigenetic landscape of RCC-broadly and in the context of these mutations-is incompletely understood. To investigate these open questions, we integrated single nucleus ATAC sequencing data from RCC tumors across four independent cohorts.

Polymodal K channel modulation contributes to dual analgesic and anti-inflammatory actions of traditional botanical medicines.

Pain and inflammation contribute immeasurably to reduced quality of life, yet modern analgesic and anti-inflammatory therapeutics can cause dependence and side effects. Here, we screened 1444 plant extracts, prepared primarily from native species in California and the United States Virgin Islands, against two voltage-gated K channels - T-cell expressed Kv1.3 and nociceptive-neuron expressed Kv7.

Serotonin transporter knockout in rats reduces beta- and gamma-band functional connectivity between the orbitofrontal cortex and amygdala during auditory discrimination.

The orbitofrontal cortex and amygdala collaborate in outcome-guided decision-making through reciprocal projections. While serotonin transporter knockout (SERT-/-) rodents show changes in outcome-guided decision-making, and in orbitofrontal cortex and amygdala neuronal activity, it remains unclear whether SERT genotype modulates orbitofrontal cortex-amygdala synchronization. We trained SERT-/- and SERT+/+ male rats to execute a task requiring to discriminate between two auditory stimuli, one predictive of a reward (CS+) and the other not (CS-), by responding through nose pokes in opposite-side ports.

Decreased Beta Power and OFC-STN Phase Synchronization during Reactive Stopping in Freely Behaving Rats.

During natural behavior, an action often needs to be suddenly stopped in response to an unexpected sensory input-referred to as reactive stopping. Reactive stopping has been mostly investigated in humans, which led to hypotheses about the involvement of different brain structures, in particular the hyperdirect pathway. Here, we directly investigate the contribution and interaction of two key regions of the hyperdirect pathway, the orbitofrontal cortex (OFC) and subthalamic nucleus (STN), using dual-area, multielectrode recordings in male rats performing a stop-signal task.

Influence of production level, number, and stage of lactation on milk quality in compost barn systems.

This study evaluated the influence of milk production, number of lactations, and days in milk (DIM) on the quality and composition of milk from dairy cows housed in a compost barn (CB) system. The study was carried out using a six-year database, counting 31,268 observations from 2,037 cows of European breeds. Multiparous cows showed higher fat and protein production.

Proximity Labelling to Quantify Kv7.4 and Dynein Protein Interaction in Freshly Isolated Rat Vascular Smooth Muscle Cells.

Understanding protein-protein interactions is crucial for unravelling subcellular protein distribution, contributing to our understanding of cellular organisation. Moreover, interaction studies can reveal insights into the mechanisms that cover protein trafficking within cells. Although various techniques such as Förster resonance energy transfer (FRET), co-immunoprecipitation, and fluorescence microscopy are commonly employed to detect protein interactions, their limitations have led to more advanced techniques such as the in situ proximity ligation assay (PLA) for spatial co-localisation analysis.

Experience-dependent regulation of dopaminergic signaling in the somatosensory cortex.

Dopamine critically influences reward processing, sensory perception, and motor control. Yet, the modulation of dopaminergic signaling by sensory experiences is not fully delineated. Here, by manipulating sensory experience using bilateral single-row whisker deprivation, we demonstrated that gene transcription in the dopaminergic signaling pathway (DSP) undergoes experience-dependent plasticity in both granular and supragranular layers of the primary somatosensory (barrel) cortex (S1).

More than the sum of its parts: uncovering emerging effects of microbial interactions in complex communities.

Microbial communities are not only shaped by the diversity of microorganisms and their individual metabolic potential, but also by the vast amount of intra- and interspecies interactions that can occur pairwise interactions among microorganisms, we suggest that more attention should be drawn towards the effects on the entire microbiome that emerge from individual interactions between community members. The production of certain metabolites that can be tied to a specific microbe-microbe interaction might subsequently influence the physicochemical parameters of the habitat, stimulate a change in the trophic network of the community or create new micro-habitats through the formation of biofilms, similar to the production of antimicrobial substances which might negatively affect only one microorganism but cause a ripple effect on the abundance of other community members. Here, we argue that combining established as well as innovative laboratory and computational methods is needed to predict novel interactions and assess their secondary effects.

Psychological well-being in Europe after the outbreak of war in Ukraine.

The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war.

Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation.

The dynamic nature of the microtubule network is dependent in part by post-translational modifications (PTMs) - particularly through acetylation, which stabilizes the microtubule network. Whether PTMs of the microtubule network in vascular smooth muscle cells (VSMCs) contribute to the pathophysiology of hypertension is unknown. The aim of this study was to determine the acetylated state of the microtubule network in the mesenteric arteries of spontaneously hypertensive rats (SHR).

A workflow for the development of template-assisted membrane crystallization downstream processing for monoclonal antibody purification.

Monoclonal antibodies (mAbs) are commonly used biologic drugs for the treatment of diseases such as rheumatoid arthritis, multiple sclerosis, COVID-19 and various cancers. They are produced in Chinese hamster ovary cell lines and are purified via a number of complex and expensive chromatography-based steps, operated in batch mode, that rely heavily on protein A resin. The major drawback of conventional procedures is the high cost of the adsorption media and the extensive use of chemicals for the regeneration of the chromatographic columns, with an environmental cost.

Patient Preferences for Mobile Health Applications to Support Recovery.

Introduction: Smartphone apps to support individuals in recovery from substance use disorders (SUDs) are increasingly available. Although many people with SUDs express interest in recovery support apps, few try them or use them long-term. Strategies like gamification and contingency management are increasingly being considered to sustain engagement.

Complete Revascularization and Angina-Related Health Status in the ISCHEMIA Trial.

Background: The impact of complete revascularization (CR) on angina-related health status (symptoms, function, quality of life) in chronic coronary disease (CCD) has not been well studied.

Objectives: Among patients with CCD randomized to invasive (INV) vs conservative (CON) management in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), we compared the following: 1) the impact of anatomic and functional CR on health status compared with incomplete revascularization (ICR); and 2) the predicted impact of achieving CR in all INV patients compared with CON.

Methods: Multivariable regression adjusting for patient characteristics was used to compare 12-month health status after independent core laboratory-defined CR vs ICR in INV patients who underwent revascularization.

Impact of Complete Revascularization in the ISCHEMIA Trial.

Background: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported.

Objectives: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management.

MUC1 Glycopeptide Vaccine Modified with a GalNAc Glycocluster Targets the Macrophage Galactose C-type Lectin on Dendritic Cells to Elicit an Improved Humoral Response.

Mucin expression and glycosylation patterns on cancer cells differ markedly from healthy cells. Mucin 1 (MUC1) is overexpressed in several solid tumors and presents high levels of aberrant, truncated O-glycans (e.g.

Cryoprecipitate for the treatment of life-threatening hemorrhage in children.

Background: Hypofibrinogenemia is an important risk factor for poor outcomes in children with severe bleeding. There is a paucity of data on the impact of cryoprecipitate transfusion on outcomes in pediatric patients with life-threatening hemorrhage (LTH).

Study Design And Methods: This secondary analysis of a multicenter prospective observational study of children with LTH investigated subjects who were categorized by receipt of cryoprecipitate during their resuscitation and according to the etiology of their bleeding: trauma, operative, and medical.

[Non-surgical peri-implantitis treatment with or without systemic antibiotics].

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment.

Building medication for opioid use disorder prescriber capacity during the opioid epidemic: Prescriber recruitment trends and methods.

Introduction: Physicians are a critical clinical resource for patient care. Yet physician recruitment has been considerably understudied, particularly in substance use disorder (SUD) settings. This study proposes a conceptual model called the "Physician Recruitment Descriptive Factors Framework" to investigate the role of environmental, organizational, and individual factors in the use of physician recruitment strategies.

Colchicine enhances β adrenoceptor-mediated vasodilation in men with essential hypertension.

Aims: The aim of this study is to examine whether colchicine improves β adrenoceptor-mediated vasodilation in humans by conducting a double-blinded, placebo-controlled intervention study. Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries have shown that colchicine can enhance β adrenoceptor-mediated vasodilation, but this has not been determined in humans.

Machine Learning-Derived Correlations for Scale-Up and Technology Transfer of Primary Nucleation Kinetics.

Scaling up and technology transfer of crystallization processes have been and continue to be a challenge. This is often due to the stochastic nature of primary nucleation, various scale dependencies of nucleation mechanisms, and the multitude of scale-up approaches. To better understand these dependencies, a series of isothermal induction time studies were performed across a range of vessel volumes, impeller types, and impeller speeds.