Novel Variants Lead to Aberrant Splicing in a Patient with Chediak-Higashi Syndrome.

The advent of next-generation sequencing (NGS) has revolutionized the analysis of genetic data, enabling rapid identification of pathogenic variants in patients with inborn errors of immunity (IEI). Sometimes, the use of NGS-based technologies is associated with challenges in the evaluation of the clinical significance of novel genetic variants. In silico prediction tools, such as SpliceAI neural network, are often used as a first-tier approach for the primary examination of genetic variants of uncertain clinical significance.

Model Organisms in Aging Research: Evolution of Database Annotation and Ortholog Discovery.

Background: This study aims to analyze the exploration degree of popular model organisms by utilizing annotations from the UniProtKB (Swiss-Prot) knowledge base. The research focuses on understanding the genomic and post-genomic data of various organisms, particularly in relation to aging as an integral model for studying the molecular mechanisms underlying pathological processes and physiological states.

Methods: Having characterized the organisms by selected parameters (numbers of gene splice variants, post-translational modifications, etc.

Construction of Promoter Elements for Strong, Moderate, and Weak Gene Expression in .

Background/objectives: Transcriptional promoters play an essential role in regulating protein expression. Promoters with weak activity generally lead to low levels of expression, resulting in fewer proteins being produced. At the same time, strong promoters are commonly used in studies using transgenic organisms as model systems.

Pseudotyped Viruses: A Useful Platform for Pre-Clinical Studies Conducted in a BSL-2 Laboratory Setting.

The study of pathogenic viruses has always posed significant biosafety challenges. In particular, the study of highly pathogenic viruses requires methods with low biological risk but relatively high sensitivity and convenience in detection. In recent years, pseudoviruses, which consist of a backbone of one virus and envelope proteins of another virus, have become one of the most widely used tools for exploring the mechanisms of viruses binding to cells, membrane fusion and viral entry, as well as for screening the libraries of antiviral substances, evaluating the potential of neutralizing monoclonal antibodies, developing neutralization tests, and therapeutic platforms.

Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.

Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges.

The Construction of Heterothallic Strains of Using the I-SceI Meganuclease.

The methylotrophic yeast belongs to the group of homothallic fungi that are able to spontaneously change their mating type by inversion of chromosomal DNA in the MAT locus region. As a result, natural and genetically engineered cultures of these yeasts typically contain a mixture of sexually dimorphic cells that are prone to self-diploidisation and spore formation accompanied by genetic rearrangements. These characteristics pose a significant challenge to the development of genetically stable producers for industrial use.

Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model.

In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, N/N, O/O, and C/C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds N-H⋯O=C due to heavy isotope substitution decreases in the row H/D >> N/N > O/O > C/C.

Unveiling the Mechanisms of a Remission in Major Depressive Disorder (MDD)-like Syndrome: The Role of Hippocampal Palmitoyltransferase Expression and Stress Susceptibility.

Post-translational modifications of proteins via palmitoylation, a thioester linkage of a 16-carbon fatty acid to a cysteine residue, reversibly increases their affinity for cholesterol-rich lipid rafts in membranes, changing their function. Little is known about how altered palmitoylation affects function at the systemic level and contributes to CNS pathology. However, recent studies suggested a role for the downregulation of palmitoyl acetyltransferase (DHHC) 21 gene expression in the development of Major Depressive Disorder (MDD)-like syndrome.

Lipid Coating Modulates Effects of Nanoceria on Oxidative Metabolism in Human Embryonic Lung Fibroblasts: A Case of Cardiolipin.

The unique redox properties of nanoscale cerium dioxide determine its diverse application in biology and medicine as a regulator of oxidative metabolism. Lipid modifiers of the nanoparticle surface change their biochemical properties and bioavailability. Complexes with lipids can be formed upon contact of the nanoparticles with the membrane.

Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial.

Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2-3% of the world's population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity.

Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives.

Glucocorticoids (GCs) are routinely used to treat hematological malignancies; however, long-term treatment with GCs can lead to atrophic and metabolic adverse effects. Selective glucocorticoid receptor agonists (SEGRAs) with reduced side effects may act as a superior alternative to GCs. More than 30 SEGRAs have been described so far, yet none of them reached clinical trials for anti-cancer treatment.

Antimicrobial Potential of Secalonic Acids from Arctic-Derived INA 01369.

In this study, two compounds have been isolated from the Arctic-derived fungus INA 13460. Structural elucidation, performed using 2D NMR and HR-ESIMS data, has identified the compounds as stereoisomers of secalonic acids, dimeric tetrahydroxanthones. The absolute configurations of these stereoisomers have been determined through conformational NMR analysis and circular dichroism spectroscopy.

Immunomodulatory Effect of Phage Depolymerase Dep_kpv74 with Therapeutic Potential Against K2-Hypervirulent .

The emergence of multidrug-resistant hypervirulent (hvKp) has made it difficult to treat and control infections caused by this bacterium. Previously, the therapeutic effectiveness of phage-encoded depolymerase Dep_kpv74 in a mouse model of -induced thigh soft tissue infection was reported. In this study, the effect of Dep_kpv74 on blood parameters in mice, the proliferation and subpopulation composition of spleen lymphocytes, and the activity and stability of the enzyme at different pH and temperatures were further explored.

Green Silver Nanoparticles: An Antibacterial Mechanism.

Silver nanoparticles (AgNPs) are a promising tool in the fight against pathogenic microorganisms. "Green" nanoparticles are especially valuable due to their environmental friendliness and lower energy consumption during production, as well as their ability to minimize the number of toxic by-products. This review focuses on the features of AgNP synthesis using living organisms (bacteria, fungi, plants) and the involvement of various biological compounds in this process.

Molecular Genetic Assessment Aids in Clarifying Phylogenetic Status of Iranian Kerman Wild Sheep.

Two species of wild sheep inhabit Iran: Asiatic mouflon () and urial (). Phylogenetic relationships between populations distributed in this country are complex and still remain unclear. This study aimed to clarify, by genetic assessment, the phylogenetic status of Kerman wild sheep, considered to be a hybrid of the two species.

Farming of Indigenous Crayfish in Russia: A Mini-Review of Recent Studies.

Natural populations of crayfish in Europe have experienced significant declines due to the spread of crayfish plague, overfishing, competition with invasive crayfish species, and habitat degradation. Consequently, crayfish farming has gained importance in meeting the increasing demand for crayfish products. Although Russia boasts abundant water resources, the development of crayfish aquaculture remains nascent.

Blood Morphology and Hematology of Adult Baikal Seals ( Gmelin, 1788) Under Professional Care.

Studying the blood cell morphology of marine mammals provides an opportunity to elucidate the physiological mechanisms of adaptive changes associated with the aquatic habitat that occur at the cellular level, as well as adaptations to changing environmental conditions and under various physiological and pathological processes. The Baikal seal [ (family Phocidae)] is endemic to the freshwater Lake Baikal, but comprehensive hematology data are not available. We studied the morphological features of blood cells of twelve clinically normal, adult Baikal seals ( = 6 males, = 6 females) from two oceanariums under professional care for eight years.

Identification of Candidate Genes Associated with Meat Production of Aberdeen Angus Cattle.

The use of GWASs in agriculture allows associations between SNPs and quantitative or qualitative traits in cattle to be estimated. This study investigated the relationships among a number of economically useful carcass traits (slaughter weight, meat yield, and meat marbling) with a group of SNPs that can act as DNA markers. Blood samples from Aberdeen Angus bulls (n = 260) were used as material for SNP genotyping.

The Role of the Tumor Microenvironment in T-Cell Redirecting Therapies of Large B-Cell Lymphoma: Lessons Learned from CAR-T to Bispecific Antibodies.

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster.

Systemic Mechanisms of Ionic Regulation in Carcinogenesis.

Cancer is a complex disease characterized by uncontrolled cell proliferation at various levels, leading to tumor growth and spread. This review focuses on the role of ion homeostasis in cancer progression. It describes a model of ion-mediated regulation in both normal and cancerous cell proliferation.

Childhood-Onset Takayasu Arteritis: Clinical Features of Disease and Relapse Risk Factors.

Takayasu's arteritis (TA) is a systemic vasculitis that primarily affects the aorta and major arteries. Despite aggressive treatment with glucocorticoids (GCs) and non-biological disease-modifying antirheumatic drugs (nbDMARDs), about 30% of patients experience resistance to therapy or relapse. This study aimed to identify risk factors associated with refractory and relapse TA in pediatric patients.

Urinary Microbiota of Healthy Prepubescent Girls and Boys-A Pilot Study.

Background: The urinary microbiota of healthy children has rarely been studied, and potential differences between boys and girls have not been addressed. Thus, this study aimed to compare the urinary microbiota of healthy prepubescent girls and boys.

Methods: We included healthy children aged between 4 and 10 years who were free of functional or organic urinary tract diseases and had no history of urinary tract infection.

Bacterial Diversity in Native Heart Valves in Infective Endocarditis.

Infective endocarditis (IE) is an infectious disease caused by the hematogenous dissemination of bacteria into heart valves. Improving the identification of pathogens that cause IE is important to increase the effectiveness of its therapy and reduce the mortality caused by this pathology. Ten native heart valves obtained from IE patients undergoing heart valve replacements were analyzed.

Intra- and Interspecies Conjugal Transfer of Plasmids in Gram-Negative Bacteria.

Plasmid-mediated resistance is a significant mechanism that contributes to the gradual decrease in the efficacy of antibiotics from various classes, including carbapenems. The aim of this study is to investigate the frequency of transfer of carbapenemase-encoding plasmids from to and . Matings were performed on agar with subsequent isolation of transconjugant, recipient, and donor colonies.

Olivetol's Effects on Metabolic State and Gut Microbiota Functionality in Mouse Models of Alimentary Obesity, Diabetes Mellitus Type 1 and 2, and Hypercholesterolemia.

Background: Disorders of glucose and lipid metabolism, such as obesity, diabetes mellitus, or hypercholesterolemia, can cause serious complications, reduce quality of life, and lead to increased premature mortality. Olivetol, a natural compound, could be proposed as a promising therapeutic agent for preventing, treating, or alleviating metabolic complications of such pathological conditions.

Methods: In this study, the researchers conducted a broad parallel investigation of olivetol's effects on metabolic state and gut microbiota functionality in mouse models of alimentary obesity, diabetes mellitus type 1 and 2, and hypercholesterolemia.