Reduced Respiratory Sinus Arrhythmia in Infants with the Premutation.

The fragile X premutation (FXpm) is caused by a CGG repeat expansion on the gene. In adults, FXpm is linked with autonomic nervous system (ANS) dysfunction and impairment is associated with CGG repeat length. Given scant infancy research, we examined ANS functioning, via respiratory sinus arrhythmia (RSA) and interbeat interval (IBI), in 82 FXpm and neurotypical infants and their associations with CGG repeats.

Molecular Approaches to Treating Chronic Obstructive Pulmonary Disease: Current Perspectives and Future Directions.

Chronic obstructive pulmonary disease (COPD) is a clinical syndrome that presents as airflow limitation with poor reversibility accompanied by dynamic hyperinflation of the lung. It is a complex disease with chronic inflammatory airway changes caused by exposure to noxious particles or gases, such as cigarette smoke. The disease involves persistent inflammation and oxidative stress, perpetuated by frequent exacerbations.

Vagus Nerve Mediated Liver-Brain-Axis Is a Major Regulator of the Metabolic Landscape in the Liver.

The liver serves as a major energetic reservoir for other tissues and its metabolic function is controlled by humoral and neural factors. The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood.

Structure-Function Analysis of the Self-Sufficient CYP102 Family Provides New Insights into Their Biochemistry.

Cytochromes P450 are a superfamily of heme-containing monooxygenases involved in a variety of oxidative metabolic reactions, primarily catalyzing the insertion of an oxygen atom into a C-H bond. CYP102 represents the first example of a bacterial P450 that can be classified as a type II (eukaryotic-like) P450 and functions as a catalytically self-sufficient enzyme. These unique features have made CYP102 an attractive system for studying P450 structure and function.

Acid Sphingomyelinase Regulates AdipoRon-Induced Differentiation of Arterial Smooth Muscle Cells via TFEB Activation.

AdipoRon is a selective adiponectin receptor agonist that inhibits vascular remodeling by promoting the differentiation of arterial smooth muscle cells (SMCs). Our recent studies have demonstrated that activation of TFEB and its downstream autophagy-lysosomal signaling contribute to adipoRon-induced differentiation of SMCs. The present study was designed to examine whether acid sphingomyelinase (ASM; gene symbol ) is involved in mediating adipoRon-induced activation of TFEB-autophagy signaling and inhibition of proliferation/migration in arterial SMCs.

KinasePred: A Computational Tool for Small-Molecule Kinase Target Prediction.

Protein kinases are key regulators of cellular processes and critical therapeutic targets in diseases like cancer, making them a focal point for drug discovery efforts. In this context, we developed KinasePred, a robust computational workflow that combines machine learning and explainable artificial intelligence to predict the kinase activity of small molecules while providing detailed insights into the structural features driving ligand-target interactions. Our kinase-family predictive tool demonstrated significant performance, validated through virtual screening, where it successfully identified six kinase inhibitors.

The Regenerative Marriage Between High-Density Platelet-Rich Plasma and Adipose Tissue.

The use of autologous biological preparations (ABPs) and their combinations fills the void in healthcare treatment options that exists between surgical procedures, like plastic reconstructive, cosmetic, and orthopedic surgeries; non-surgical musculoskeletal biological procedures; and current pharmaceutical treatments. ABPs, including high-density platelet-rich plasma (HD-PRP), bone marrow aspirate concentrates (BMACs), and adipose tissue preparations, with their unique stromal vascular fractions (SVFs), can play important roles in tissue regeneration and repair processes. They can be easily and safely prepared at the point of care.

Systematic Characterization and Analysis of the Freeze-Thaw Tolerance Gene Set in the Budding Yeast, .

The budding yeast is a widely utilized model system with myriad applications in terms of industrial, biotechnology, and synthetic biology purposes. One such application is the biosynthesis of commercially and medically important bioactive compounds and their precursors, which oftentimes require culturing conditions at low temperatures to optimize production yield rather than cellular fitness. To lend insight into genetic modifications that may assist this goal, this work focuses on a systematic analysis of the genes that result in an increase in survival following freezing.

Shape Matters: The Utility and Analysis of Altered Yeast Mitochondrial Morphology in Health, Disease, and Biotechnology.

Mitochondria are involved in a wide array of critical cellular processes from energy production to cell death. The morphology (size and shape) of mitochondrial compartments is highly responsive to both intracellular and extracellular conditions, making these organelles highly dynamic. Nutrient levels and stressors both inside and outside the cell inform the balance of mitochondrial fission and fusion and the recycling of mitochondrial components known as mitophagy.

Trastuzumab Decreases the Expression of G1/S Regulators and Syndecan-4 Proteoglycan in Human Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, arises from skeletal muscle cells that fail to differentiate terminally. Two subgroups of RMS, fusion-positive and fusion-negative RMS (FPRMS and FNRMS, respectively), are characterized by the presence or absence of the fusion gene. RMSs frequently exhibit increased expression of human epidermal growth factor receptor-2 (HER2).

Comprehensive Analysis of High-Sensitive Flow Cytometry and Molecular Mensurable Residual Disease in Philadelphia Chromosome-Positive Acute Leukemia.

Monitoring measurable residual disease (MRD) is critical for the management of B-cell acute lymphoblastic leukemia (B-ALL). While a quantitative assessment of BCR::ABL1 transcripts is standard for Philadelphia chromosome-positive cases (Ph+ ALL), a multiparameter flow cytometry (FCM) is commonly used for MRD detection in other genetic subtypes. A total of 106 B-ALL patients underwent genetic and phenotypic analyses.

High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression.

Patients with chronic, indolent myeloproliferative neoplasms (MPNs) are at risk for transformation to highly lethal leukemia, although targetable mechanisms driving progression remain elusive. We discovered that the () gene is up-regulated with MPN progression in patients and required for evolution into myelofibrosis (MF) or acute myeloid leukemia (AML) in preclinical models. encodes the HMGA1 epigenetic regulators that modulate the chromatin state during embryogenesis and tissue regeneration.

Computational NMR Study of Alkaloids: Could the Structural Misassignment of Cryptospirolepine Have Been Avoided?

It is demonstrated that by using modern computational methods, it is possible to identify potential structural misassignments for even molecules as complex as cryptospirolepine. While methods that rely on anisotropic nuclear magnetic resonance (NMR) methods can also be used to offer a powerful orthogonal means of structure elucidation and verification, the present computational study should be feasible in most chemistry departments with access to sophisticated computational facilities. From the overall correlations calculated against experimental H and C NMR chemical shifts in the series of thirteen alkaloids, it follows that, generally, they provide a very high level of correlation.

Whole-Exome Sequencing Identifies Novel GATA5/6 Variants in Right-Sided Congenital Heart Defects.

One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important roles in embryonic development and their inactivation may result in congenital heart defects (CHDs). In this study, we performed genotypic-phenotypic analyses in two families affected by right-sided CHD diagnosed by echocardiography imaging.

SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.

The () gene encodes a neutral amino acid transporter, also referred to as alanine-serine-cysteine transporter 1, ASCT1, that helps maintain amino acid balance in the brain and periphery. In the brain, SLC1A4 plays an important role in transporting levo (L) and dopa (D) isomers of serine. L-serine is required for many cellular processes, including protein and sphingolipid synthesis, while D-serine is a co-agonist required for normal neurotransmission through -methyl-D-aspartate receptors.

Genome-Wide Association Study and Genomic Prediction of Soybean Mosaic Virus Resistance.

Soybean mosaic virus (SMV), a pathogen responsible for inducing leaf mosaic or necrosis symptoms, significantly compromises soybean seed yield and quality. According to the classification system in the United States, SMV is categorized into seven distinct strains (G1 to G7). In this study, we performed a genome-wide association study (GWAS) in GAPIT3 using four analytical models (MLM, MLMM, FarmCPU, and BLINK) on 218 soybean accessions.

Impact of Estrogen on Purinergic Signaling in Microvascular Disease.

Microvascular ischemia, especially in the heart and kidneys, is associated with inflammation and metabolic perturbation, resulting in cellular dysfunction and end-organ failure. Heightened production of adenosine from extracellular nucleotides released in response to inflammation results in protective effects, inclusive of adaptations to hypoxia, endothelial cell nitric oxide release with the regulation of vascular tone, and inhibition of platelet aggregation. Purinergic signaling is modulated by ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39, which is the dominant factor dictating vascular metabolism of extracellular ATP to adenosine throughout the cardiovascular tissues.

Proximity Effect of Optically Active h-BCN Nanoflakes Deposited on Different Substrates to Tailor Electronic, Spintronic, and Optoelectronic Properties.

Hexagonal BCN (h-BCN), an isoelectronic counterpart to graphene, exhibits chirality and offers the distinct advantage of optical activity in the vacuum ultraviolet (VUV) region, characterized by significantly higher wavelengths compared to graphene nanoflakes. h-BCN possesses a wide bandgap and demonstrates desirable semiconducting properties. In this study, we employ Density Functional Theory (DFT) calculations to investigate the proximity effects of adsorbed h-BCN flakes on two-dimensional (2D) substrates.

Citrulline Plus Arginine Induces an Angiogenic Response and Increases Permeability in Retinal Endothelial Cells via Nitric Oxide Production.

We previously observed elevated plasma levels of citrulline and arginine in diabetic retinopathy patients compared to diabetic controls. We tested our hypothesis that citrulline plus arginine induces angiogenesis and increases permeability in retinal endothelial cells. Human retinal microvascular endothelial cells (HRMECs) were treated with citrulline, arginine, or citrulline + arginine, and angiogenesis was measured with cell proliferation, migration, and tube formation assays.

Development of a Dihydrofolate Reductase Selection System for .

, the only commercially available probiotic yeast, has gained attention as a recombinant live biotherapeutic product (rLBP) empowered with the expression of heterologous therapeutic proteins for treating gastrointestinal diseases. However, the genetic modification of intended for clinical use is hindered by regulatory and technical challenges. In this study, we developed a dihydrofolate reductase (DHFR)-based selection system as an innovative alternative to traditional auxotrophic selection strategies for engineering .

Molecular Insights into Cardiovascular Disease: Unraveling Pathways for Diagnosis and Treatment.

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, with aneurysmal diseases standing out as particularly insidious threats [...

Thromboinflammatory Biomarkers in Lymphomas: Linking Inflammation to Thrombosis Risk.

Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without thrombosis using ELISA and flow cytometry according to laboratory and clinical data. Interleukin-1β was elevated across lymphomas and inversely correlated with the Khorana score for venous thromboembolism, while increased tumor necrosis factor-alpha (TNF-α) was inversely associated with the International Prognostic Index (IPI) in thrombosis-associated lymphomas.

Neurons Co-Expressing GLP-1, CCK, and PYY Receptors Particularly in Right Nodose Ganglion and Innervating Entire GI Tract in Mice.

Afferent vagal neurons convey gut-brain signals related to the mechanical and chemical sensing of nutrients, with the latter also mediated by gut hormones secreted from enteroendocrine cells. Cell bodies of these neurons are located in the nodose ganglia (NG), with the right NG playing a key role in metabolic regulation. Notably, glucagon-like peptide-1 receptor (GLP1R) neurons primarily innervate the muscle layer of the stomach, distant from glucagon-like peptide-1 (GLP-1)-secreting gut cells.

Bone Morphogenetic Protein 7 Improves Wound Healing in Diabetes by Decreasing Inflammation and Promoting M2 Macrophage Polarization.

Diabetic foot ulcers (DFUs) are a devastating complication of diabetes, presenting limited treatment success rates due to their complex pathophysiology. Bone morphogenetic protein 7 (BMP7) confers tissue protective and regenerative functions, but its potential role in diabetic wound healing is unknown. The aim of this study was to investigate the effects of topical BMP7 treatment in wound healing using a streptozotocin-induced diabetic mouse model.

Unveiling the Mechanism of Action of Palmitic Acid, a Human Topoisomerase 1B Inhibitor from the Antarctic Sponge .

Cancer remains a leading cause of death worldwide, highlighting the urgent need for novel and more effective treatments. Natural products, with their structural diversity, represent a valuable source for the discovery of anticancer compounds. In this study, we screened 750 Antarctic extracts to identify potential inhibitors of human topoisomerase 1 (hTOP1), a key enzyme in DNA replication and repair, and a target of cancer therapies.