Search Results (1,175)

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Disparities in the functional classification of secretory genes among aphid taxa may be attributed to variations in coding sequences and gene expression profiles. However, the driving factors that regulate sequence evolution remain unclear. This study aimed to investigate the differences in coding sequences and expression patterns of secretory genes between the rose grain aphid (Metopolophium dirhodum) and the pea aphid (Acrythosiphon pisum), with a particular focus on their roles in evolutionary adaptations and functional diversity. The study involved the rearing of aphids, RNA extraction, de novo transcriptome assembly, functional annotation, secretory protein prediction, and comparative analysis of coding sequences and expression patterns across various functional categories using bioinformatics tools. The results revealed that metabolic genes exhibited greater coding sequence divergence, indicating the influence of positive selection. Moreover, significant expression divergence was noted among functional categories, particularly in metabolic and genetic information processing genes, which exhibited higher variability. This study enhances our understanding of the molecular mechanisms that contribute to phenotypic and genetic diversity among aphid species. This study elucidates the relationship between variations in coding sequences and differences in gene expression among functional categories, thereby establishing a foundation for future studies on gene evolution in response to environmental pressures. Full article

Antimicrobial resistance is an escalating global threat that undermines the efficacy of modern antibiotics and places a substantial economic burden on healthcare systems—costing Europe alone over EUR 11.7 billion each year due to rising medical expenses and productivity losses. While genomics and transcriptomics have significantly advanced our understanding of the genetic foundations of resistance, they often fail to capture the dynamic, real-time adaptations that enable bacterial survival. Proteomics, particularly mass spectrometry-based strategies, bridges this gap by uncovering the functional protein-level changes that drive resistance, persistence, and tolerance under antibiotic pressure. In this review, we examine how proteomic approaches provide new insights into resistance mechanisms across various antibiotic classes, with a particular focus on β-lactams, aminoglycosides, and fluoroquinolones, highlighting clinically relevant pathogens, especially members of the ESKAPE group. Finally, we examine future directions, including the integration of proteomics with other omic technologies and the growing role of artificial intelligence in resistance prediction, paving the way for more predictive, personalized, and effective solutions to combat antimicrobial resistance. Full article

Alzheimer’s disease (AD) and ischemic stroke (IS) are prevalent neurological disorders that frequently co-occur in the same individuals. Recent studies have demonstrated that AD and IS share several common risk factors and pathogenic elements, including an overlapping genomic architecture. However, the relationship between IS risk gene polymorphisms and AD has been less extensively studied. We aimed at determining whether IS risk gene polymorphisms were associated with the risk of AD and the severity of AD in AD patients. We utilized data of AD patients and normal controls (NCs) sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. IS risk single nucleotide polymorphisms (SNPs) were identified through the most recent and largest IS genome-wide association study (GWAS) meta-analysis. Subsequently, we conducted SNP-based association analysis of IS-risk SNPs with the risk of AD, along with amyloid, tau, and neuroimaging for AD. The generalized multifactor dimensionality reduction (GMDR) model was used to assess the interactions among IS-risk SNPs and apolipoprotein E (ApoE) ε4. Protein–protein interactions (PPIs) of the IS-risk genes product and APOE were explored using the STRING database. Seven IS-risk SNPs were involved in the study. Five SNPs were found to be associated with at least one measurement of cerebrospinal fluid (CSF) levels of amyloid-beta 1–42 (Aβ₄₂), total tau (t-tau), and phosphorylated tau 181 (p-tau₁₈₁), as well as the volumes of the hippocampus, whole brain, entorhinal cortex, and mid-temporal regions. After multiple testing corrections, we found that T allele of rs1487504 contributed to an increased risk of AD in non-ApoE ε4 carriers. The combination of rs1487504 and ApoE ε4 emerged as the optimal two-factor model, and its interaction was significantly related to the risk of AD. Additionally, C allele of rs880315 was significantly associated with elevated levels of CSF Aβ₄₂ in AD patients, and A allele of rs10774625 was significantly related to a reduction in the volume of the entorhinal cortex in AD patients. This study found that IS risk SNPs were associated with both the risk of AD and AD major indicators in the ADNI cohort. These findings elucidated the role of IS in AD from a genetic perspective and provided an innovative approach to predict AD through IS-risk SNPs. Full article

Peanut (Arachis hypogaea L.) is a globally important oilseed cash crop, yet its limited genetic diversity and unique reproductive biology present persistent challenges for conventional crossbreeding. Traditional breeding approaches are often time-consuming and inadequate, mitigating the pace of cultivar development. Essential for double fertilization and programmed cell death (PCD), DUF679 membrane proteins (DMPs) represent a membrane protein family unique to plants. In the present study, a comprehensive analysis of the DMP gene family in peanuts was conducted, which included the identification of 21 family members. Based on phylogenetic analysis, these genes were segregated into five distinct clades (I–V), with AhDMP8A, AhDMP8B, AhDMP9A, and AhDMP9B in clade IV exhibiting high homology with known haploid induction genes. These four candidates also displayed significantly elevated expression in floral tissues compared to other organs, supporting their candidacy for haploid induction in peanuts. Subcellular localization prediction, confirmed through co-localization assays, demonstrated that AhDMPs primarily localize to the plasma membrane, consistent with their proposed roles in the reproductive signaling process. Furthermore, chromosomal mapping and synteny analyses revealed that the expansion of the AhDMP gene family is largely driven by whole-genome duplication (WGD) and segmental duplication events, reflecting the evolutionary dynamics of the tetraploid peanut genome. Collectively, these findings establish a foundational understanding of the AhDMP gene family and highlight promising targets for future applications in haploid induction-based breeding strategies in peanuts. Full article

Enhancing quality traits is a primary objective in silage maize breeding programs. The use of genome-wide association studies (GWAS) for quality traits, in combination with the integration of genetic resources, presents an opportunity to identify crucial genomic regions and candidate genes influencing silage maize quality. In this study, a GWAS was conducted on 580 inbred lines of silage maize, and a meta-analysis was performed on 477 quantitative trait loci (QTLs) from 34 studies. The analysis identified 27 significant single nucleotide polymorphisms (SNPs) and 87 consensus QTLs (cQTLs), with 7 cQTLs associated with multiple quality traits. By integrating the SNPs identified through association mapping, one SNP was found to overlap with the cQTL interval related to crude protein, neutral detergent fiber, and starch content. Furthermore, enrichment analysis predicted 300 and 5669 candidate genes through GWAS and meta-analysis, respectively, highlighting pathways such as cellular metabolism, the biosynthesis of secondary metabolites, ribosome function, carbon metabolism, protein processing in the endoplasmic reticulum, and amino acid biosynthesis. The examination of 13 candidate genes from three co-located regions revealed Zm00001d050977 as a cytochrome P450 family gene, while the other 2 genes primarily encode proteins involved in stress responses and other biological pathways. In conclusion, this research presents a methodology combining GWAS and meta-analysis to identify genomic regions and potential genes influencing quality traits in silage maize. These findings serve as a foundation for the identification of significant QTLs and candidate genes crucial for improving silage maize quality. Full article

Potassium is the most abundant macronutrient in plants, participating in essential physiological processes such as turgor maintenance. A reduction in cell turgor is a hallmark of the ripening process associated with fruit softening. The dynamic of K⁺ fluxes in fleshy fruits is largely unknown; however, the reallocation of K⁺ into the apoplast has been proposed as a contributing factor to the decrease in fruit turgor, contributing to fruit softening. High-affinity K⁺ transporters belonging to the KUP/HT/HAK transporter family have been implicated in this process in some fruits. In this study, a comprehensive genome-wide analysis of the KUP/KT/HAK family of high-affinity K⁺ transporters in strawberry (Fragaria × ananassa Duch.) was conducted, identifying 60 putative transporter genes. The chromosomal distribution of the FaKUP gene family and phylogenetic relationship and structure of predicted proteins were thoroughly examined. Transcriptomic profiling revealed the expression of 19 FaKUP genes within the fruit receptacle, with a predominant downregulation observed during ripening, particularly in FaKUP14, 24 and 47. This pattern suggests their functional relevance in early fruit development and turgor maintenance. Mineral composition analyses confirmed that K⁺ is the most abundant macronutrient in strawberry fruits, exhibiting a slight decrease as ripening progressed. Membrane potential (E_m) and diffusion potentials (E_D) at increasing external K⁺ concentrations were measured by electrophysiology in parenchymal cells of green and white fruits. The results obtained suggest a significant diminution in cytosolic K⁺ levels in white compared to green fruits. Furthermore, the slope of change in E_D at increasing external K⁺ concentration indicated a lower K⁺ permeability of the plasma membrane in white fruits, aligning with transcriptomic data. This study provides critical insights into the regulatory mechanisms of K⁺ transport during strawberry ripening and identifies potential targets for genetic modifications aimed at enhancing fruit firmness and shelf life. Full article

As a pivotal model organism in Lepidoptera research, the silkworm (Bombyx mori) holds significant importance in life science due to its economic value and biotechnological applications. Advancements in proteomics and bioinformatics have enabled substantial progress in characterizing the B. mori proteome. Systematic screening and identification of protein–protein interactions (PPIs) have progressively elucidated the molecular mechanisms governing key biological processes, including viral infection, immune regulation, and growth development. This review comprehensively summarizes traditional PPI detection techniques, such as yeast two-hybrid (Y2H) and immunoprecipitation (IP), alongside emerging methodologies such as mass spectrometry-based interactomics and artificial intelligence (AI)-driven PPI prediction. We critically analyze the strengths, limitations, and technological integration strategies for each approach, highlighting current field challenges. Furthermore, we elaborate on the molecular regulatory networks of Bombyx mori nucleopolyhedrovirus (BmNPV) from multiple perspectives: apoptosis and cell cycle regulation; viral protein invasion and trafficking; non-coding RNA-mediated modulation; metabolic reprogramming; and host immune evasion. These insights reveal the dynamic interplay between viral replication and host defense mechanisms. Collectively, this synthesis aims to provide a robust theoretical foundation and technical guidance for silkworm genetic improvement, infectious disease management, and the advancement of related biotechnological applications. Full article

As an auxin-responsive gene, Gretchen Hagen 3 (GH3) maintains hormonal homeostasis by conjugating excess auxin with amino acids in plant stress-related signaling pathways. GH3 genes have been characterized in many plant species, but the characteristics of pepper (Capsicum annuum L.) GH3 (CaGH3) gene family members in response to multiple stimulants are largely unknown. In this study, we systematically identified the CaGH3 gene family at the genome level and identified eight members on four chromosomes in pepper. CaGH3s were divided into two groups (I and III) and shared conserved motifs, domains, and gene structures. Moreover, CaGH3s had close evolutionary relationships with tomato (Solanum lycopersicum L.), and the promoters of most CaGH3 genes contained hormone and abiotic stress response elements. A protein interaction prediction analysis demonstrated that the CaGH3-3/3-6/3-7/3-8 proteins were possibly core members of the CaGH3 family interaction. In addition, qRT-PCR results showed that CaGH3 genes were differentially expressed in pepper tissues and could be induced by phytohormones (IAA, ABA, and MeJA) and abiotic stresses (salt, low temperature, and drought) with different patterns. In addition, CaGH3-5 and CaGH3-7 were cloned, and the sequences showed a high degree of conservation. Moreover, the results of subcellular localization indicated that they were located in the membrane and chloroplast. Notably, after overexpressing CaGH3-7 in tomato, RNA-seq was performed on wild-type and transgenic lines, and the differentially expressed genes were mainly enriched in response to external stimuli. This study not only lays the foundation for a comprehensive understanding of the function of the CaGH3 gene family during plant growth and stress responses but also provides potential genetic resources for pepper resistance breeding. Full article

Background: The mammalian mitochondrial genome has long been considered to encode only 13 proteins. However, a recent study identified a nested alternative open reading frame (nAltORF) within the primate mitochondrial cytb gene, which we designate ncytb, that is reportedly translated in the cytosol using the standard genetic code. This discovery challenges conventional understanding and raises questions about the prevalence, conservation, and translational adaptation of such ORFs. Methods: This study conducted a comprehensive bioinformatic analysis of nested ncytb genes in 289 primate and 380 rodent mitochondrial cytb sequences. Results: Nested ncytb genes meeting the criteria (>150 codons, standard genetic code) were identified in only 10.73% of primate and 20.53% of rodent species, suggesting a patchy phylogenetic distribution. While their encoded proteins showed homology to the previously reported protein encoded by the Homo sapiens nested ncytb gene, overall amino acid conservation was low, and characteristic protein domains or signal peptides were generally not predicted. Crucially, the Kozak consensus sequences surrounding the putative start codons of these ncytb genes were exclusively “weak” or “adequate”, with none classified as “strong” or “optimal”. Codon Adaptation Index (CAI) and Relative Codon Deoptimization Index (RCDI) analyses of the nested ncytb genes revealed neither significant adaptation nor deoptimization to the codon usage of nuclear and mitochondrial genes. Furthermore, cosine similarity analysis indicated that ncytb genes exhibit significantly lower codon usage similarity to both nuclear and mitochondrial gene sets compared to their host cytb genes. Conclusions: These findings collectively suggest that while ncytb genes exist in some mammals, their inconsistent presence, weak translational initiation signals, and lack of adaptation to cytosolic codon usage characterize them as dispensable genetic elements rather than core functional genes. Full article

Aeromonas spp. are opportunistic pathogens that are widely distributed in water sources, with several species being associated with fish and human diseases. We have previously identified an Aeromonas AB005 isolate from diseased Acipencer baerii. This isolate was identified as A. hydrophila based on the 16S rRNA and gyrB gene sequences. However, this novel strain does not produce indole and tested negative for ornithine decarboxylase and d-xylose fermentation—differences that set it apart from typical A. hydrophila strains. In the present study, this strain was subjected to whole-genome sequencing and compared with the genomes of the type strain (Aeromonas hydrophila ATCC 7966^T) and other Aeromonas spp. Comprehensive genome analysis suggests that AB005 represents a distinct species within the genus. The draft genome of the AB005 strain comprises 4,780,815 base pairs with a GC content of 61.2% and contains 6104 predicted protein-coding sequences along with numerous genes implicated in antibiotic resistance. The core/pan-genome analysis reveals extensive genetic diversity, indicative of a dynamic genomic structure. These findings collectively underscore the taxonomic distinction of the AB005 strain as a novel species and highlight its potential pathogenic implications in aquaculture and public health settings. Full article

Background/Objectives: The treatment of multiple myeloma (MM) remains a challenge, as almost all patients will eventually relapse. Proteasome inhibitors are a cornerstone in the management of MM. Unfortunately, validated biomarkers predicting drug response are largely missing. Therefore, we aimed to identify genes associated with drug resistance or sensitization to proteasome inhibitors. Methods: We performed genome-wide CRISPR-Cas9 knockout (KO) screens in human KMS-28-BM myeloma cells to identify genetic determinants associated with resistance or sensitization to proteasome inhibitors. Results: We show that KO of KLF13 and PSMC4 induces drug resistance, while NUDCD2, OSER1 and HERC1 KO cause drug sensitization. Subsequently, we focused on top sensitization hit, NUDCD2, which acts as a co-chaperone of Hsp90 to regulate the LIS1/dynein complex. RNA sequencing showed downregulation of genes involved in the ERAD pathway and in ER-associated ubiquitin-dependent protein catabolic processes in both untreated and carfilzomib-treated NUDCD2 KO cells, suggesting that NUDCD2 depletion alters protein degradation. Furthermore, bortezomib-treated NUDCD2 KO cells showed a decreased expression of genes that have a function in oxidative phosphorylation and the mitochondrial membrane, such as Carnitine Palmitoyltransferase 1A (CPT1A). CPT1A catalyzes the uptake of long chain fatty acids into mitochondria. Mitochondrial lipid metabolism has recently been reported as a possible therapeutic target for MM drug sensitivity. Conclusions: These results contribute to the search for therapeutic targets that can sensitize MM patients to proteasome inhibitors. Full article

This paper conducts a literature review on the role of natural killer cells in haploidentical hematopoietic stem cell transplantation. Theoretical concepts related to KIR genes are introduced regarding their structure, nomenclature, genetic organization, polymorphism, and inheritance pattern, types of KIR proteins and receptors, HLA ligands for KIR receptors, and the definition of different NK alloreactivity prediction models for the donor of haploidentical hematopoietic stem cell transplantation and the recipient. These models include the following and consider incompatibility: ligand–ligand, receptor–ligand, gene–gene, and KIR haplotype models or the KIR-B donor group. These models consider the presence or absence of specific ligands or receptors and/or KIR genes in the donor and recipient to predict alloreactivity. Determining the best model for predicting KIR alloreactivity and its significance in donor selection algorithms for haploidentical transplantation is still under investigation. Full article

Predominantly antibody deficiencies (PADs) are the most prevalent types of inherited errors of immunity (IEI) and are characterized by a broad range of clinical manifestations, such as recurrent infections, autoimmunity, lymphoproliferation, atopy and malignancy. The aim of this study was to identify genetic defects associated with PADs in order to improve diagnosis and personalized care. Twenty patients (male/female: 12/8, median age of disease onset: 16.5 years, range: 1–50) were analyzed by next-generation sequencing (NGS) using a custom panel of 30 genes associated with PADs and their possible disease phenotype. The detected variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and inheritance, and the penetrance patterns were evaluated by PCR–Sanger sequencing. Novel and rare mutations associated with the phenotype of common variable immunodeficiency (CVID) in genes encoding the transcription factors NFKB1, NFKB2 and IKZF1/IKAROS were identified. Alphafold3 protein structure prediction was utilized to perform a comprehensive visualization strategy and further delineate the mutation-bearing domains and elucidate their potential impact on protein function. This study highlights the value of genetic testing in PADs and will guide further research and improvement in diagnosis and treatment. Full article

The combination of Chinsurah Boro II (BT)-type cytoplasmic male sterility (CMS) and Rf1, the main fertility restorer gene (Rf) for CMS-BT, has been extensively utilized for the production of three-line commercial japonica hybrid seeds. The identification of new Rf genes holds significance for the breeding of BT-type restorer lines, aiming to enhance the heterosis level of BT-type japonica hybrids. In the present study, ‘02428’, a wide-compatibility japonica variety, was observed to partially restore fertility to BT-type CMS lines. Genetic analysis revealed that ‘02428’ carries a dominant Rf gene, Rf21(t), responsible for the fertility restoration of BT-type CMS lines. Leveraging bulked segregant analysis (BSA) resequencing technology and molecular markers, the Rf21(t) locus was identified, and mapped within a candidate interval of 6–12.5 Mb on chromosome 2. Using the iso-cytoplasmic restorer populations, Rf21(t) was ultimately mapped to an interval of approximately 77 kb, encompassing 12 predicted genes, including LOC_Os02g17360, encoding a PPR-domain-containing protein and LOC_Os02g17380 (Rf2), a cloned Rf for Lead-rice-type CMS. A comparative sequence analysis, gene expression profiling and gene knockout experiments confirmed that LOC_Os02g17360 and LOC_Os02g17380 are the most likely candidates of Rf21(t). Furthermore, Rf21(t) showed the dosage effect on the fertility restoration of BT-type CMS lines. This newly identified Rf21(t) represents a valuable genetic resource for the breeding of BT-type japonica restorer lines. Our findings offer practical insights for breeders interested in advancing BT-type japonica hybrid development. Full article