Diffusion-based size determination of solute particles: a method adapted for postsynaptic proteins.

The postsynaptic density (PSD) is a complex, multilayered protein network largely situated on the internal surface of the postsynaptic membrane. It is the first processing unit for incoming synaptic signals, and changes in its internal structure are associated with synaptic strength and plasticity. These structural changes are largely governed by multivalent interactions between its components.

Comprehensive SAR analysis of actomyolytics, drug candidates targeting the actomyosin complex.

There is a long-standing need for inhibitors that selectively target the actomyosin complex, the terminal effector of diverse processes that involve movement in the cells or the body. Such compounds, we term as actomyolytics, hold promise for treating numerous conditions with minimum adverse effects. In this study, we developed efficient synthesis pathways and conducted a detailed structure-activity relationship (SAR) analysis of 144 potential actomyolytics (referred to as the MPH-family) targeting the blebbistatin binding site on myosin-2.

Prehospital survival of patients with ST-elevation myocardial infarction requiring out-of-hospital cardiopulmonary resuscitation - a nationwide, real-world observational study.

Background: The mortality risk of patients presenting with ST-elevation myocardial infarction (STEMI) has been extensively researched. Even though STEMI can be diagnosed before hospital admission, prehospital mortality has been less frequently studied. We aimed to analyze the outcomes of patients with STEMI requiring out-of-hospital cardiopulmonary resuscitation (CPR).

Differential organ responses to fumonisins in rabbits: kidney, liver, and spleen membrane fatty acid composition, oxidation markers, and histopathology.

The study assessed the kidney, liver, and spleen of adult male rabbits ( = 10/group) in relation to fumonisin B series exposure (10 and 20 mg FB + FB + FB/kg feed) over a period of 65 days. The rabbit growth and feed intake remained unaffected; meanwhile, kidney and liver weights increased. The highest dose provided greater alterations in total phospholipid fatty acid profiles, particularly in the kidney (C20:5n3 and C18:0) and spleen (C18:1n7, C22:0, C20:4n6, and C20:5n3) than in the liver.

Short-Range Δ-Machine Learning: A Cost-Efficient Strategy to Transfer Chemical Accuracy to Condensed Phase Systems.

DFT-based machine-learning potentials (MLPs) are now routinely trained for condensed-phase systems, but surpassing DFT accuracy remains challenging due to the cost or unavailability of periodic reference calculations. Our previous work ( 2022, 129, 226001) demonstrated that high-accuracy periodic MLPs can be trained within the CCMD framework using extended yet finite reference calculations. Here, we introduce Δ (srΔML), a method that starts from a baseline MLP trained on low-level periodic data and adds a Δ-MLP correction based on high-level cluster calculations at the CC level.

Comparative Analysis of the Genetic Composition of Minorities in the Carpathian Basin Through Genome-Wide Autosomal Data.

Background/objectives: The Carpathian Basin is a genetically and culturally diverse region shaped by complex historical migrations and various ethnic groups. While studies based on Y-chromosomal and mitochondrial DNA have provided valuable insights into the genetic diversity of these populations, genome-wide autosomal SNP data remain underutilized in understanding the genetic structure of these groups. This study presents the first genome-wide autosomal SNP-based analysis of key Hungarian-speaking ethnic groups in the region, focusing on admixture patterns and the extent of preserved historical genetic components.

Interaction of Mycotoxins with α-Acid Glycoprotein (AGP) and Bovine Milk Proteins: Zearalenone, Zearalenols, and Sterigmatocystin Form Highly Stable Complexes with AGP.

Mycotoxins are frequent food contaminants posing health risk to humans and animals. Since these interactions have been barely studied yet, we examined the potential complex formation of mycotoxins with human α-acid glycoprotein (AGP) and with bovine milk proteins (including casein (CSN), β-lactoglobulin (LG), and α-lactalbumin (LA)) based on fluorescence spectroscopic and ultracentrifugation techniques. Only weak interactions (log = 2.

Engineering mouse chymotrypsin B1 for improved trypsinogen degradation.

The digestive protease chymotrypsin (CTR) protects the pancreas against harmful trypsin activity by promoting degradation of trypsinogen. Recently, we demonstrated that Arg236 is responsible for the higher proteolytic activity and better trypsinogen degrading capability of human CTRB2 compared to CTRB1. Introduction of Arg236 into CTRB1, which normally carries Asp236, dramatically increased degradation of human anionic trypsinogen.

Molecular and Clinical Heterogeneity in Hungarian Patients with Treacher Collins Syndrome-Identification of Two Novel Mutations by Next-Generation Sequencing.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder with variable penetrance and high genetic and phenotypic heterogeneity. It is caused by pathogenic variants in the , , and genes, and its major characteristic features are malar and mandibular hypoplasia, downward slanting of the palpebral fissures, and conductive hearing loss. In this study, five patients (two males and three females, age range from 2 to 29 years) with TCS were tested by Next-Generation Sequencing (NGS)-based sequencing and clinically characterized.

Analysis of Gyimes Csango population samples on a high-resolution genome-wide basis.

Background: The Csangos are an East-Central European ethnographic group living mainly in east of Transylvania in Romania. Traditionally, ethnography distinguishes three Csango subpopulations, the Moldavian, Gyimes and Burzenland Csangos. In our previous study we found that the Moldavian Csangos have East Asian/Siberian Turkic ancestry components that might be unique in the East-Central European region and might help to better understand the history of Hungarian speaking ethnic groups of the area.

Modeling protease-sensitive human pancreatic lipase mutations in the mouse ortholog.

Pancreatic lipase (PNLIP) is the major lipolytic enzyme secreted by the pancreas. A recent study identified human PNLIP variants P245A, I265R, F300L, S304F, and F314L in European cohorts with chronic pancreatitis. Functional analyses indicated that the variants were normally secreted but exhibited reduced stability when exposed to pancreatic proteases.

Neutralizing Autoantibodies against Interleukin-10 in Inflammatory Bowel Disease.

We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion.

Cerebrovascular dysregulation and postoperative cognitive alterations after carotid endarterectomy.

There are controversial data about the effect of carotid endarterectomy regarding postoperative cognitive function. Our aim was to analyze the effect of cerebral tissue saturation monitored by near-infrared spectroscopy (NIRS) on cognitive function. Perioperative data of 103 asymptomatic patients undergoing elective carotid surgery under general anesthesia were analyzed.

Fumonisin distorts the cellular membrane lipid profile: A mechanistic insight.

Monitoring modifications in membrane lipids in association with external stimuli/agents, including fumonisins (FUMs), is a widely employed approach to assess cellular metabolic response/status. FUMs are prevalent fusariotoxins worldwide that have diverse structures with varying toxicity across species; nevertheless, they can induce metabolic disturbances and disease, including cancer. The capacity of FUMs to disrupt membrane lipids, demonstrated across numerous species and organs/tissues, is ascribed to a multitude of factors/events, which range from direct to indirect effects.

The Impact of Frailty Components and Preoperative Mechanical Cardiac Support Changes with Time after Heart Transplantation.

Background: Frailty has been proven to be associated with mortality after orthotopic heart transplantation (OHT). The aim of our study was to determine the impact of frailty on mortality in the current era using pretransplant mechanical cardiac support (MCS).

Methods: We retrospectively calculated the frailty scores of 471 patients undergoing OHT in a single institution between January 2012 and August 2022.

Exposure to a Combination of Mycotoxins Leads to Lipid Peroxidation and Influences Antioxidant Defenses, Fatty Acid Composition of Phospholipids, and Renal Histology in Laying Hens.

The effects of combined short-term (3 days) exposure to mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB: 40 mg/kg feed) on the kidneys of laying hens were examined.

The Effect of Combined Exposure of Mycotoxins on Lipid Peroxidation, Antioxidant Defense, Fatty Acid Profile, and Histopathology in Laying Hens' Liver.

Fumonisin B1, T-2 toxin, and deoxynivalenol are frequently detected in feed materials. The mycotoxins induce free radical formation and, thereby, lipid peroxidation. The effects of mycotoxin exposure at the EU recommended limit (T-2/HT-2 toxin: 0.

Interaction of mycotoxins zearalenone, α-zearalenol, and β-zearalenol with cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, and 3A4) enzymes and organic anion transporting polypeptides (OATP1A2, OATP1B1, OATP1B3, and OATP2B1).

Zearalenone (ZEN) is a mycoestrogen produced by Fusarium fungi. ZEN is a frequent contaminant in cereal-based products, representing significant health threat. The major reduced metabolites of ZEN are α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL).

Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.

Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways.

Chemical and Physical Properties of African Catfish () Fillet Following Prolonged Feeding with Insect Meal-Based Diets.

A 25-week experiment was undertaken to explore the effect of partial replacement of dietary fishmeal (FM) with black soldier fly meal () (BS), mealworm meal () (MW), and a 1 : 1 mixture of both insect meals (BSMW) on fillet quality in African catfish (). A total of 96 fish with an average initial body weight of 248 ± 28 g were stocked into a recirculating aquaculture system and fed in four different dietary groups (control, BS, MW, and BSMW). No mortality was recorded in any of the groups.

Hormonal changes in the first 24 postoperative hours after cardiac surgical procedures.

Background: Hormone level changes after heart surgeries are a widely observed phenomenon due to neurohormonal feedback mechanisms that may affect postoperative morbidity and mortality. The current study aimed to analyze the changes in thyroid and sex hormones in the first 24 postoperative hours after heart surgery.

Methods: This prospective, observational study (registered on ClinicalTrials.

Observation of a Possible Successful Treatment of DEPDC5-Related Epilepsy with mTOR Inhibitor.

The mechanistic target of the rapamycin signaling pathway serves as a central regulator of cell metabolism, growth, proliferation, and survival. In its regulation, the GTPase-activating protein activity toward Rags1 complex has an inhibitory effect. Mutations in genes encoding this complex protein are among the most common abnormalities in focal epilepsies.