Genes最新文献

Background: Saline-alkali stress is a major factor limiting the growth of oats. Sugar is the primary carbon and energy source in plants which regulates plant development and growth by regulating enzyme activity and gene expression. Sucrose, glucose, and fructose are ubiquitous plant-soluble sugars that act as signalling molecules in the transcriptional regulation of various metabolic and defence-related genes.

Methods: In this study, soluble sugars, fructose, sucrose, and starch contents were measured, and transcriptomics was used to determine the differentially expressed genes (DEGs) in saline-sensitive and saline-tolerant oats after 6, 12, 24, and 48 h. DEGs annotated to carbohydrates were selected using the Kyoto Encyclopedia of Genes and Genomes.

Results: DEGs involved in carbohydrate metabolism were mainly enriched in the glycolysis/gluconeogenesis and pentose phosphate pathways, fructose and mannose metabolism, and starch and sucrose metabolism. GAPDH, SUPI, SUS2, ATP-PEK, HXK6, FBA4, TBA4, TKT, ISA3, PPDK1, and BAM2 were significantly expressed, and a quantitative reverse transcription polymerase chain reaction verified the transcriptome sequencing results.

Conclusions: In this study, oats with different salinity tolerances were used to determine sugar contents under four salinity stress durations, and transcriptome sequencing was used to explore the regulatory mechanism of sugars and provide a reference for elucidating the sugar signalling regulatory mechanism under abiotic stress.

Background: The Balkan Peninsula has served as an important migration corridor between Asia Minor and Europe throughout humankind's history and a refugium during the Last Glacial Maximum. Past migrations such as the Neolithic expansion, Bronze Age migrations, and the settlement of Slavic tribes in the Early Middle Ages, are well known for their impact on shaping the genetic pool of contemporary Balkan populations. They have contributed to the high genetic diversity of the region, especially in mitochondrial DNA (mtDNA) lineages. Serbia, located in the heart of the Balkans, reflects this complex history in a broad spectrum of mtDNA subhaplogroups. Methods: To explore genetic diversity in Serbia and the wider Balkan region, we analyzed rare mtDNA subclades-R0a, N1a, N1b, I5, W, and X2-using publicly available data. Our dataset included already published sequences from 3499 HVS-I/HVS-II and 1426 complete mitogenomes belonging to West Eurasian and African populations, containing both contemporary and archaeological samples. We assessed the parameters of genetic diversity found in different subclades across the studied regions and constructed detailed phylogeographic trees and haplotype networks to determine phylogenetic relationships. Results: Our analyses revealed the observable geographic structure and identified novel mtDNA subclades, some of which may have originated in the Balkan Peninsula (e.g., R0a1a5, I5a1, W1c2, W3b2, and X2n). Conclusions: The geographic distribution of rare subclades often reveals patterns of past population movements, routes, and gene flows. By tracing the origin and diversity of these subclades, our study provided new insights into the impact of historical migrations on the maternal gene pool of Serbia and the wider Balkan region, contributing to our understanding of the complex genetic history of this important European crossroads.

Introduction: Gene therapy has emerged as a promising frontier in the management of diabetes, offering innovative approaches to address both type 1 and type 2 diabetes. This narrative review examines the advancements in gene therapy applications, focusing on both animal and human studies, and includes a total of 11 studies in adherence to PRISMA guidelines. These studies utilize various viral vectors, such as adeno-associated virus (AAV) and lentivirus, to deliver genes that regulate insulin production and enhance angiogenesis. This review aims to synthesize recent advancements in gene therapy for both type 1 and type 2 diabetes and its complications, and to explore the evolving role of pharmacists in this emerging field. Methods: A comprehensive search was conducted to identify relevant studies on gene therapy for diabetes. Databases such as PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Google Scholar were queried using keywords such as "Diabetes", "gene therapy", "Type 1 diabetes", and "Type 2 diabetes". Both animal and human studies were included to provide a broad perspective on the advancements in this field. Results: Animal model studies have shown promising results, including sustained insulin production, improved glucose homeostasis, and enhanced wound healing. Human studies, though fewer in number, have reported significant advancements. Patients with diabetic neuropathy treated with plasmid VEGF and recombinant adeno-associated virus (rAAV) showed improvements in neuropathic symptoms and glycemic control. Other studies involving intramuscular injections of VM202 and bicistronic VEGF165/HGF plasmid have reported pain reduction, improved healing of ischemic lesions, and increased angiogenesis. Conclusions: Despite these encouraging results, limitations such as small sample sizes, short follow-up periods, and the necessity for more extensive clinical trials persist. Diabetes is a metabolic syndrome that requires the collaboration of a multidisciplinary team to assist in several aspects of implementing successful gene therapy. Several healthcare providers and policy makers may play a crucial role in patient education, counseling, and the management of gene therapy treatments.

Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient's peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient's visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient's PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control's PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient's PBMCs.

Background/Objectives: Calcium-dependent protein kinases (CDPKs) are a crucial class of calcium-signal-sensing and -response proteins that significantly regulate abiotic stress. Yinshania henryi is a member of the Brassicaceae family that primarily grows in the karst regions of southwestern China, with a notable tolerance to high-calcium soils. Currently, the function of the CDPK family of genes in Y. henryi has yet to be explored. Methods: This study employed a comprehensive approach starting with bioinformatic methods to analyze the whole-genome sequencing data of Y. henryi and identified YhCDPK genes by combining phylogenetic characteristics and protein domain analysis. Results: It then delved into the physicochemical properties, gene structure, chromosomal localization, phylogenetic tree, and promoter cis-acting elements of these YhCDPK genes. Subsequently, RNA-seq data and qRT-PCR analysis were utilized to understand the expression patterns of YhCDPK genes. Twenty-eight YhCDPK genes were found to be unevenly distributed across six chromosomes; these can be classified into four subfamilies, with many cis-acting elements in their promoter regions involved in plant growth and stress responses. Furthermore, the differential expression patterns of YhCDPK genes under different concentrations of calcium treatments were investigated using RNA-seq data and qRT-PCR analysis. Conclusions: These results are a critical first step in understanding the functions of YhCDPK genes, and they lay a foundation for further elucidating the adaptability and response mechanism of YhCDPK genes in Y. henryi to the karst environment.

Background/Objectives: The domestication of the grey wolf (Canis lupus) and subsequent creation of modern dog breeds have significantly shaped the genetic landscape of domestic canines. This study investigates the genomic effects of hybridization and breeding management practices in two hybrid wolfdog breeds: the Czechoslovakian Wolfdog (CSW) and the Saarloos Wolfdog (SAW). Methods: We analyzed the genomes of 46 CSWs and 20 SAWs, comparing them to 12 German Shepherds (GSHs) and 20 wolves (WLFs), which served as their ancestral populations approximately 70-90 years ago. Results: Our findings highlight that hybridization can increase genetic variability and mitigate the effects of inbreeding, as evidenced by the observed heterozygosity levels in both wolfdog breeds. However, the SAW genome revealed a higher coefficient of inbreeding and longer runs of homozygosity compared to the CSW, reflecting significant inbreeding during its development. Discriminant Analysis of Principal Components and fixation index analyses demonstrate that the CSW exhibits closer genetic proximity to the GSH than the SAW, likely due to differences in the numbers of GSHs used during their creation. Maximum likelihood clustering further confirmed clear genetic differentiation between these hybrid breeds and their respective ancestors, while shared ancestral polymorphism was detectable in all populations. Conclusions: These results highlight the role of controlled hybridization with captive-bred wolves and peculiar breeding strategies in shaping the genetic structure of wolfdog breeds. To ensure the long-term genetic health of these breeds, it is recommended to promote adequate and sustainable breeding practices to maintain genetic diversity, minimize inbreeding, and incorporate the careful selection of unrelated individuals from diverse lineages, while avoiding additional, uncontrolled crossings with wild wolves.

Background/objectives: Predicting the effects of protein and DNA mutations on the binding free energy of protein-DNA complexes is crucial for understanding how DNA variants impact wild-type cellular function. As many cellular interactions involve protein-DNA binding, accurately predicting changes in binding free energy (ΔΔG) is valuable for distinguishing pathogenic mutations from benign ones.

Methods: This study describes the development and optimization of the SAMPDI-3Dv2 machine learning method, which is trained on an expanded database of experimentally measured ΔΔGs. This enhanced model incorporates new features, including the 3D structure of the mutant protein, features of the mutant structure, and a position-specific scoring matrix (PSSM). Benchmarking was conducted using 5-fold cross-validation.

Results: The updated SAMPDI-3D model (SAMPDI-3Dv2) achieved Pearson correlation coefficients (PCCs) of 0.68 for protein and 0.80 for DNA mutations. These results represent significant improvements over existing tools. Additionally, the method's rapid execution time enables genome-scale predictions.

Conclusions: The improved SAMPDI-3Dv2 shows enhanced predictive performance for analyzing mutations in protein-DNA complexes. By leveraging structural information and an expanded training dataset, SAMPDI-3Dv2 provides researchers with a more accurate and efficient tool for mutation analysis, contributing to identifying pathogenic variants and improving our understanding of cellular function.

Mendelian disorders of the epigenetic machinery (MDEMs) include a large number of conditions caused by defective activity of a member of the epigenetic machinery. MDEMs are characterized by multiple congenital abnormalities, intellectual disability and abnormal growth. that can be variably up- or down-regulated. Background/Objectives: In several MDEMs, a predisposition to metabolic syndrome and obesity since childhood has been reported. Methods: To investigate the metabolic bases of this abnormal growth, we collected physical data from a heterogeneous pool of 38 patients affected by MDEMs. Thirty-five patients performed indirect calorimetry (as a measure of resting energy expenditure, REE) and blood tests to monitor plasmatic nutritional parameters. Conclusions: Although limited by a small-sized and heterogeneous sample, our study demonstrates a linear correlation between REE and physical parameters, OFC, height and weight, and observed a slight imbalance on several plasmatic spies of metabolic syndrome predisposition. Furthermore, we demonstrated a significantly higher REE in Sotos Syndrome type 1 patients compared to the controls, which resulted independent from height, suggesting that impaired metabolism in these patients may go beyond overgrowth.

Background/Objectives: DNA damage response (DDR) is a highly conserved and complex signal transduction network required for preserving genome integrity. DNA repair pathways downstream of DDR include the tyrosyl-DNA phosphodiesterase1 (TDP1) enzyme that hydrolyses the phosphodiester bond between the tyrosine residue of topoisomerase I (TopI) and 3'-phosphate end of DNA. A small TDP1 subfamily, composed of TDP1α and TDP1β, is present in plants. The aim of this work was to investigate the role of the two TDP1 genes in the DDR context. Methods: A series of Arabidopsis thaliana DDR single and double mutants defective in the sog1, e2fb, pol2A, atm, and atr genes, treated with the genotoxic agents camptothecin (CPT, inhibitor of TopI) and NSC120686 (NSC, inhibitor of TDP1), were used. These compounds were specifically used due to their known impact on the TDP1 function. The effect of the treatments was assessed via phenotypic analyses that included germination percentage, speed, and seedling growth. Subsequently, the expression of the TDP1α and TDP1β genes was monitored through qRT-PCR. Results: Overall, the gathered data indicate that the atm mutant was highly sensitive to NSC120686, both phenotypically and concerning the TDP1α gene expression profiles. Alternatively, the upregulation of TDP1β in e2fb, pol2a, and atr supports its implication in the replication stress response. Conclusions: The current study demonstrates that genotoxic stress induced by CPT and NSC has a genotype-dependent effect reflected by a differential expression of TDP1 genes and early phenotypic development.

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment. This review analyzes recent advances in CAD-related genetic markers and evaluates their diagnostic potential, focusing on their applications in diagnosis and risk stratification within precision medicine. Methods: We conducted a systematic review of CAD genomic studies from PubMed and Web of Science databases, analyzing findings from genome-wide association studies (GWASs), gene sequencing, transcriptomics, and epigenomics research. Results: GWASs and sequencing studies have identified key genetic variations associated with CAD, including JCAD/KIAA1462, GUCY1A3, PCSK9, and SORT1, which regulate inflammation, lipid metabolism, and vascular function. Transcriptomic and epigenomic analyses have revealed disease-specific gene expression patterns, DNA methylation signatures, and regulatory non-coding RNAs (miRNAs and lncRNAs), providing new approaches for early detection. Conclusions: While genetic marker research in CAD has advanced significantly, clinical implementation faces challenges including marker dynamics, a lack of standardization, and integration with conventional diagnostics. Future research should prioritize developing standardized guidelines, conducting large-scale prospective studies, and enhancing multi-omics data integration to advance genomic diagnostics in CAD, ultimately improving patient outcomes through precision medicine.