CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles of in microglia endocytosis and synaptic pruning.

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations into how ASD-risk genes alter development. Most functional genomics studies have focused on the role of these genes in neurons and neural progenitor cells.

Impact of Multidirectional Pacing on Activation and Repolarization Parameters to Localize Ischemic Ventricular Tachycardia Circuits.

Background: In ventricular tachycardia (VT), optimal substrate mapping strategies identifying arrhythmogenic sites are not established.

Objectives: This study sought to evaluate multidirectional pacing on the distribution of specific conduction and repolarization metrics to localize re-entrant VT sites in a porcine infarct model.

Methods: Substrate maps were created in 13 pigs with chronic myocardial infarction using the Advisor HD Grid (Abbott) during right ventricular (RV), left ventricular, biventricular pacing (BIV), and sinus rhythm (SR).

Small Extracellular Vesicles in the Pericardium Modulate Macrophage Immunophenotype in Coronary Artery Disease.

Coronary artery disease (CAD) is a major health issue. This study focused on pericardial macrophages and small extracellular vesicles (sEVs) in CAD. The macrophages in CAD patients showed reduced expression of protective markers and unchanged levels of proinflammatory receptors.

Impaired Brown midrib12 function orchestrates sorghum resistance to aphids via an auxin conjugate indole-3-acetic acid-aspartic acid.

Lignin, a complex heterogenous polymer present in virtually all plant cell walls, plays a critical role in protecting plants from various stresses. However, little is known about how lignin modifications in sorghum will impact plant defense against sugarcane aphids (SCA), a key pest of sorghum. We utilized the sorghum brown midrib (bmr) mutants, which are impaired in monolignol synthesis, to understand sorghum defense mechanisms against SCA.

AI assistance in aesthetic medicine-A consensus on objective medical standards.

Background: Aesthetic medicine has traditionally relied on clinical scales for the objective assessment of baseline appearance and treatment outcomes. However, the scales focus on limited aesthetic areas mostly and subjective interpretation inherent in these scales can lead to variability, which undermines standardization efforts.

Objective: The consensus meeting aimed to establish guidelines for AI application in aesthetic medicine.

Validation and clinical application of implantable loop recorders for diagnosis of atrial fibrillation in horses.

Background: Paroxysmal atrial fibrillation (pAF) occurs sporadically and can impair athletic performance. Gold standard for diagnosis is surface electrocardiography (ECG), however, this requires AF to be sustained. Implantable loop recorders (ILRs) are routinely used for AF detection in human medicine.

Structural and Interactional Analysis of the Flavonoid Pathway Proteins: Chalcone Synthase, Chalcone Isomerase and Chalcone Isomerase-like Protein.

Chalcone synthase (CHS) and chalcone isomerase (CHI) catalyze the first two committed steps of the flavonoid pathway that plays a pivotal role in the growth and reproduction of land plants, including UV protection, pigmentation, symbiotic nitrogen fixation, and pathogen resistance. Based on the obtained X-ray crystal structures of CHS, CHI, and chalcone isomerase-like protein (CHIL) from the same monocotyledon, , along with the results of the steady-state kinetics, spectroscopic/thermodynamic analyses, intermolecular interactions, and their effect on each catalytic step are proposed. In addition, PvCHI's unique activity for both naringenin chalcone and isoliquiritigenin was analyzed, and the observed hierarchical activity for those type-I and -II substrates was explained with the intrinsic characteristics of the enzyme and two substrates.

Responses of Wheat () Constitutively Expressing Four Different Monolignol Biosynthetic Genes to Fusarium Head Blight Caused by .

The Fusarium head blight (FHB) pathogen produces the trichothecene mycotoxin deoxynivalenol and reduces wheat yield and grain quality. Spring wheat () genotype CB037 was transformed with constitutive expression (CE) constructs containing sorghum () genes encoding monolignol biosynthetic enzymes caffeoyl coenzyme A (CoA) 3--methyltransferase (), 4-coumarate-CoA ligase (), or coumaroyl shikimate 3-hydroxylase () or monolignol pathway transcriptional activator . Spring wheats were screened for type I (resistance to initial infection, using spray inoculations) and type II (resistance to spread within the spike, using single-floret inoculations) resistances in the field (spray) and greenhouse (spray and single floret).

Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear.

Methods And Results: We employed a large animal model, the female landrace pig, and used multiple in vivo and ex vivo approaches including pharmacological challenges, electrophysiology, and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate.

Catheter-based pulmonary vein isolation fails to prevent transient atrial arrhythmogenic changes related to acute obstructive respiratory events in a porcine model.

Aims: Pulmonary vein isolation (PVI) is the corner stone of modern rhythm control strategies in patients with atrial fibrillation (AF). Sleep-disordered breathing (SDB) is prevalent in more than 50% of patients undergoing AF ablation, and studies have indicated a greater recurrence rate after PVI in patients with SDB. Herein, we study the effect of catheter-based PVI on AF in a pig model for SDB.

A new dawn for the study of cell type evolution.

Animal evolution is influenced by the emergence of new cell types, yet our understanding of this process remains elusive. This prompts the need for a broader exploration across diverse research organisms, facilitated by recent breakthroughs, such as gene editing tools and single-cell genomics. Essential to our understanding of cell type evolution is the accurate identification of homologous cells.

Lower Recurrence Rates of Atrial Fibrillation and MACE Events After Early Compared to Late Ablation: A Danish Nationwide Register Study.

Background: Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events.

A situational test of the health belief model: How perceived susceptibility mediates the effects of the environment on behavioral intentions.

Objective: Existing evidence regarding the role of perceived susceptibility in shaping preventative health behavior is mixed for the Health Belief Model (HBM). To clarify whether and under which conditions perceived susceptibility affects preventative behavior, this study aims to better understand how situational environmental factors affect perceived susceptibility, thereby shaping health decisions, and whether this mediation relationship is conditioned by other HBM cognitions, namely perceived benefits and severity.

Methods: Therefore, we employed a scenario-based experiment in a large, representative sample of the German population (N = 4,802) in April 2022.

Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy.

Myocarditis has emerged as an immune-related adverse event of immune checkpoint inhibitor (ICI) cancer therapy associated with significant mortality. To ensure patients continue to safely benefit from life-saving cancer therapy, an understanding of fundamental immunological phenomena underlying ICI myocarditis is essential. We recently developed the NOD-cMHCI/II-/-.

Systematic review of the patient burden of generalised myasthenia gravis in Europe, the Middle East, and Africa.

Background: Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG.

Methods: Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa.

Structural and electro-anatomical characterization of the equine pulmonary veins: implications for atrial fibrillation.

Introduction/objectives: Spontaneous pulmonary vein (PV) activity triggers atrial fibrillation (AF) in humans. Although AF frequently occurs in horses, the origin remains unknown. This study investigated the structural and electro-anatomical properties of equine PVs to determine the potential presence of an arrhythmogenic substrate.

Examining double standards in layoff preferences and expectations for gender, age, and ethnicity when violating the social norm of vaccination.

Whether vaccination refusal is perceived as a social norm violation that affects layoff decisions has not been tested. Also unknown is whether ascribed low-status groups are subject to double standards when they violate norms, experiencing stronger sanctions in layoff preferences and expectations, and whether work performance attenuates such sanctioning. Therefore, we study layoff preferences and expectations using a discrete choice experiment within a large representative online survey in Germany (N = 12,136).

A brief measure of complete subjective well-being in Germany: A population-based validation of a German version of the Flourish Index (FI) and the Secure Flourish Index (SFI).

Measuring subjective well-being in a multidimensional, valid, reliable, and parsimonious way is important for both social science research and social policy. Here, we present an efficient measure of distinct domains of subjective well-being and overall flourishing. The Flourishing Index (FI) consists of five sub-domains: 1.