Search Results (1,451)

Common bunt (CB), caused by Tilletia caries and Tilletia laevis, poses a significant threat to wheat grain quality and yield. In organic farming, the development of resistant genotypes is the most effective way to combat the pathogen. This study aimed to identify new resistance sources against CB in international nurseries: Winter Wheat Nursery from Central Asia (WWN-CA) and International Common Bunt Resistance Nursery (CBUNT-RN), for strengthening winter breeding programs in Kazakhstan. Germplasm panels were evaluated against CB under artificial infection conditions in southeastern Kazakhstan and genotyped with KASP markers associated with QTLs (QBt.ifa-1AL, QBt.ifa-1BS, QBt.ifa-7AL and QBt.ifa-7DS) conferring bunt resistance. Results of immunological experiments and genotyping revealed 7 and 11 genotypes in WWN-CA and CBUNT-RN, respectively, and resistance to CB. CB incidence negatively correlated with SL (r = −0.23), NSS (r = −0.31), NKS (r = −0.41), and GWS (r = −0.44) (all p ≤ 0.01), in WWN-CA. ANOVA confirmed these findings, in which a pronounced reduction in these yield components was observed between inoculated and control HS groups (p ≤ 0.05). The QTL QBt.ifa-1AL on chromosome 1A shows promise for MAS against CB. The novel genetic knowledge and resistant resources identified here represent a valuable tool to enrich Central Asian germplasm with new alleles of resistance genes to advance organic farming in Kazakhstan. Full article

Lupinus is recognized as a nutrient-dense legume rich in protein, raw fiber, antioxidants, and unsaturated fatty acids, contributing significantly to human nutrition and health. In Ecuador, the Andean Crops and Plant Genetic Resources program of INIAP maintains a germplasm bank comprising 257 uncharacterized accessions. This study aimed to evaluate the nutritional and phytochemical composition of ten promising sweet Lupin genotypes (L. mutabilis) exhibiting good agronomic characteristics, resistance and/or tolerance to biotic and abiotic stresses, superior grain quality and significantly reduced seed alkaloid content in experimental trails. These genotypes were compared with two accessions of L. albus and L. angustifolius used as control genotypes. Except for carbohydrate content, L. mutabilis genotypes exhibited similar or superior nutritional profiles compared to genotype controls with high protein (44.7%), fat (19.91%), and ash (4.16%) contents and reduced alkaloid concentrations, notably, two genotypes LmAnds16 and LmFRs43 with 0.04%. However, it exhibited the highest polyphenol (8.84 mg·g⁻¹) and flavonoid (0.67 mg·g⁻¹) concentrations and antioxidant activity for ABTS (19.94 µmol TE·g⁻¹) and FRAP (300.30 µmol TE·g⁻¹) on a dry weight basis (DW). These results are important for the generation of new varieties of Lupinus focused on its nutritional quality and to produce nutraceutical and functional foods. Full article

Background: High body mass index (BMI) is a causal risk factor for endometrial cancer, but the tumor molecular mechanisms affected by adiposity remain poorly understood. Here, we characterize the tumor multi-omic landscape of endometrial cancers that have developed on a background of lifelong germline genetic liability to elevated BMI. Methods: We built a polygenic score (PGS) for BMI in women using data on independent, genome-wide significant variants associated with adult BMI in 434,794 women. We performed germline (blood) genotype quality control and imputation on data from 354 endometrial cancer cases from The Cancer Genome Atlas (TCGA). We assigned each case in this TCGA cohort their genetically predicted BMI based on the BMI PGS. Multivariable generalized linear models adjusted for age, stage, microsatellite status and genetic principal components were used to test for associations between the BMI germline PGS and endometrial cancer tumor genome-wide genomic, transcriptomic, proteomic, epigenomic and immune traits in TCGA. Results: High BMI germline PGS was associated with (i) upregulated tumor gene expression in IL6-JAK-STAT3 signaling (FDR = 4.2 × 10⁻⁷) and in other immune/inflammatory pathways; (ii) increased estimated intra-tumor activated mast cell infiltration (FDR = 0.008); and (iii) increased single base substitution (SBS) mutational signature 1 (FDR = 0.03), implicating age-related mutagenesis. In contrast, BMI at diagnosis associated with elevated progesterone receptor expression and alterations in estrogen and androgen signaling. Conclusions: Thus, we integrated germline, somatic and clinical data to identify associations between genetically predicted lifelong liability to higher BMI and endometrial cancer tumor molecular features. These associations inform our understanding of how high BMI may influence the development of this cancer, shaping endometrial tumor biology differentially over the long term. Full article

The Arunachali mithun (Bos frontalis) is a semi-domesticated bovine of profound cultural and economic significance to the indigenous Arunachali tribal communities of Northeastern India, yet it remains among the least genomically characterised large ruminants, leaving its conservation status without an empirical genetic foundation. We performed whole-genome re-sequencing (~10× coverage) of 11 individuals and analysed 4,943,593 high-quality biallelic single nucleotide polymorphisms (SNPs) after stringent quality control. Genome-wide mean observed heterozygosity (H_o = 0.2854), expected heterozygosity (H_e = 0.3347), and nucleotide diversity (π = 7.16 × 10⁻⁴) revealed moderate genetic diversity, substantially lower than that of related commercial bovine species. A consistent heterozygosity deficit (H_o − H_e = −0.0493) and the convergence of four independent inbreeding coefficients around 0.143–0.147 indicated moderate inbreeding of predominantly reflecting an ancient origin, corroborated by runs of homozygosity (ROH) analysis in which 93.2% of 24,937 detected segments fell in the short length class (100–250 kb). Linkage disequilibrium decayed from r² ≈ 0.57 at <100 kb to a plateau of r² ≈ 0.33 beyond 4–5 Mb, consistent with a small effective population size (N_e) declining from approximately 101,850 (~2228 generations ago) to approximately 160 (~5 generations ago), with ab Ne of approximately 3865 at ~100 generations ago and 423 at ~10 generations ago. These findings establish a whole-genome-based genetic diversity baseline for the Arunachali mithun and provide actionable genomic evidence for conservation and managed breeding interventions. Full article

Cadmium (Cd) pollution adversely affects crop productivity and grain quality. Durum wheat (Triticum turgidum L. subsp. durum (Desf.) Husn.), a widely consumed cereal crop, can accumulate substantial levels of Cd in edible tissues, threatening human health. Therefore, advances in understanding Cd toxicity in plants and the molecular mechanisms underlying Cd accumulation and detoxification are needed to develop resistant cultivars and ensure safe food production. Although Cd homeostasis has been previously studied in bread wheat, its accumulation varies among species and cultivars owing to differences in their physiological and genetic makeup. However, the molecular mechanisms underlying Cd homeostasis in durum wheat have not been comprehensively reviewed. Here, we synthesize current knowledge on the molecular basis of Cd uptake, transport, and detoxification in durum wheat. Specialized transporter families, including MRPs/ABCCs, HMAs, and members of the YSL, ZIFL, and IREG families, play critical roles in mediating Cd compartmentalization and limiting its cytosolic toxicity. Genes such as HMT1, TdHMA3-B1a, and members of the NAS gene family significantly reduced Cd accumulation in grains. Future studies should focus on the integration of physiological, molecular genetics, and multi-omics approaches to uncover the regulatory networks controlling Cd homeostasis in durum wheat. Full article

Circadian clocks are endogenous timing systems that coordinate plant physiology, metabolism, development, and stress responses with daily and seasonal environmental cycles. In crops, circadian and photoperiodic pathways influence agronomically important traits including photosynthesis, carbon allocation, flowering time, growth, stress resilience, and nutritional quality. Although flowering time and photoperiod response pathways have long been indirectly exploited during domestication and breeding, the broader potential of circadian regulation for crop improvement and time-sensitive management remains only partially developed. This review examines the role of plant circadian clocks in crop productivity, with emphasis on molecular mechanisms, crop-specific clock-associated loci, breeding strategies, and chrono-agricultural applications. We summarize conserved and divergent features of the plant clock, including transcriptional repression and activation modules, environmental entrainment, and post-transcriptional regulatory layers. We then discuss how circadian regulation shapes productivity traits and highlight examples from rice, wheat, barley, maize, soybean, sorghum, tomato, and other crops. These examples show that agricultural adaptation often involves fine-tuning or rewiring circadian and photoperiodic outputs rather than maintaining a universal optimal clock state. Finally, we evaluate chrono-agriculture as an emerging framework for aligning management practices with biological timing. While controlled-environment agriculture and high-value horticultural systems are currently the most practical settings for testing chrono-agricultural strategies, open-field applications require careful consideration of environmental variability, sensor limitations, labour, machinery logistics, economic feasibility, and multi-environment validation. Integrating circadian biology with crop genetics, phenotyping, modelling, and agronomy may provide new opportunities to improve productivity, resilience, resource-use efficiency, and quality traits in sustainable agricultural systems. Full article

Ring finger protein 126 (RNF126) is a RING-type E3 ubiquitin ligase that has recently emerged as a multifaceted regulator of cellular homeostasis, stress adaptation, and disease progression. Through its structurally distinct zinc-finger and catalytic RING domains, RNF126 orchestrates substrate recognition and ubiquitin transfer, generating diverse ubiquitin linkages with both proteolytic and nonproteolytic functions. Initially characterized as a component of the protein quality control (PQC) machinery, RNF126 cooperates with chaperones such as BAG6 and UBQLN1 to eliminate mislocalized and misfolded proteins, thereby maintaining proteostasis. Beyond PQC, RNF126 plays pivotal roles in DNA damage response pathways by regulating homologous recombination, non-homologous end joining, checkpoint signaling, and genome stability through substrates, including MRE11, Ku80, RNF168, and 14-3-3σ. Genetic studies have further demonstrated its importance in embryogenesis and male fertility, and accumulating evidence has identified RNF126 as a critical driver of malignancy in multiple cancers. RNF126 promotes tumor progression by degrading or modulating key regulators, such as p21, PTEN, p53, PDKs, and LKB1, thereby enhancing proliferation, metabolic reprogramming, anoikis resistance, metastasis, and chemo/radioresistance. Intriguingly, RNF126 exhibits context-dependent functions, acting as an oncogene or tumor suppressor depending on the tissue type and substrate selection. In addition to cancer, RNF126 has been implicated in neurodegeneration, cardiac pathology, antiviral immunity and adaptive immune regulation. This review summarizes the current knowledge of RNF126 structure, ubiquitin signaling mechanisms, physiological functions, and pathological roles, while discussing emerging therapeutic strategies and future challenges for targeting RNF126 in precision medicine. Full article

Background/Objectives: Adenomyosis is a common estrogen-dependent gynecological condition with a largely undefined genetic architecture. Ciliary dysfunction has been implicated in its pathogenesis, positioning genes governing ciliary structure and motility as biologically plausible candidates for investigation. The DNAH5 gene encodes a critical component of the outer dynein arms within the ciliary axoneme, and pathogenic variants are among the most common causes of primary ciliary dyskinesia. This study aimed to systematically determine the frequency of a novel synonymous DNAH5 variant, NM_001369.3:c.9258C>T, p.(Leu3086=), in a large, histopathologically confirmed sporadic adenomyosis cohort from Turkiye, and to evaluate its occurrence relative to population-level reference data. Methods: A total of 121 women with histopathologically confirmed adenomyosis following hysterectomy were enrolled. Sanger sequencing was performed under stringent quality control conditions, including primer specificity verification by NCBI BLAST and UCSC In Silico PCR. Variant frequency was compared against gnomAD v4.0 and an in-house Turkish exome database (NGS Cloud; ~30,000 sequences) using Fisher’s exact test. In silico splice site analysis was performed using SpliceAI, and variant classification followed ACMG/AMP guidelines. Results: The variant was detected in 63 of 121 patients (52.1%; 95% CI: 43.1–61.0%), exclusively in the heterozygous state; no homozygous carriers were identified. The variant was absent from both gnomAD v4.0 across all populations and the NGS Cloud Turkish exome database (MAF: 0.0000), yielding a frequency difference (p < 2.2 × 10⁻¹⁶). SpliceAI analysis predicted no significant splice site impact (all delta scores < 0.1). The variant was classified as a variant of uncertain significance (VUS; BP7, PM2_supporting). Conclusions: This study identifies a difference in the frequency of a novel synonymous DNAH5 variant between a histopathologically confirmed adenomyosis cohort from Turkiye and population-level reference datasets, in which the variant was absent. Given the unphenotyped nature of the reference dataset, these findings are hypothesis-generating and do not establish a causal genetic association. Replication in independent cohorts and functional studies are warranted to elucidate the biological significance of this variant in adenomyosis susceptibility. Full article

This paper proposes a genetic algorithm (GA) for the Dual-Resource Flexible Job Shop Scheduling Problem with Partial Resource Allocation (DRFJSSP-PRA), a particular variant of a dual-resource constrained scheduling problem that has not been fully explored due to its intricate nature. The DRFJSSP-PRA poses a challenging scheduling problem, having several applications in many industries, including food, chemistry and pharmaceutics. The proposed algorithm is applied to real-world scheduling instances in pharmaceutical quality control. The objective function considered is the total completion time. The GA is compared with three state-of-the-art algorithms. For small- and medium-size instances, the proposed algorithm achieves optimal or near optimal results for the majority of the instances tested. For large-sized instances, the proposed GA outperforms all the other algorithms, in all of the tested instances. Thus, the experimental results show that the proposed GA achieves competitive results for any type of instance. The proposed algorithm also has the ability to optimize production processes through scheduling, leading to potential cost savings, increased efficiency, and improved competitiveness. Full article

Background/Objectives: Immune checkpoints are critical regulatory pathways that maintain peripheral tolerance and prevent autoimmunity. Among these, the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis serves as a major inhibitory pathway that terminates T cell responses. While protein-based checkpoint blockade (ICB) targeting this axis has revolutionized clinical cancer therapy, its clinical efficacy is frequently limited by low response rates, immune-related adverse events (irAEs), and the emergence of adaptive resistance. To break through these bottlenecks, genetic interruption has emerged as a high-precision alternative to modulate the PD-1/PD-L1 pathway at the nucleotide level. Methods: A comprehensive systematic review of literature was performed across major databases (PubMed, Web of Science), with a focus on high quality studies published up to 2026. Results: Direct genomic disruption via CRISPR/Cas9 and post-transcriptional silencing through RNA interference can effectively neutralize inhibitory signaling at its source. Recent advances demonstrate that targeting upstream regulatory nodes—including metabolic checkpoints (e.g., lactate metabolism) and biophysical mechanisms (e.g., liquid–liquid phase separation)—provides superior transcriptional control over PD-L1. Furthermore, engineering CAR-T cells with multiplex gene editing (e.g., TCR/B2M/PD-1 knockout) or localized scFv secretion significantly enhances antitumor potency while reducing systemic toxicity. Innovations in organ-targeted lipid nanoparticles and stimuli-responsive biomimetic carriers further address the delivery barriers in solid tumors. Conclusions: Gene therapy provides a high-precision platform for PD-1/PD-L1 modulation, offering a viable strategy to overcome adaptive resistance. Future clinical application depends on the refinement of safer editing tools, such as base editing, and the standardization of intelligent delivery systems to ensure controllable and scalable cancer immunotherapy. Full article

This study was conducted to investigate the effects of dietary supplementation with graded levels of SPTM on growth performance, slaughter performance, physiological parameters, and jejunal morphology of Wenchang chickens. A total of 400 female Wenchang chickens at 81 days of age with the same genetic background and similar body weight (1190.80 ± 5.54 g) were randomly allocated into four treatment groups with five replicates per group and 20 chickens per replicate. Birds were fed diets supplemented with 0%, 3%, 9%, and 12% SPTM, respectively. The experimental period lasted 40 days. The results showed that dietary SPTM supplementation had no significant effects on growth performance, slaughter performance, organ indices, or serum biochemical parameters (p > 0.05). However, significant effects were observed on serum enzyme activities, immune parameters, jejunal morphology, meat quality, and nutrient composition. Specifically, serum alanine aminotransferase (ALT) activity in the 9% SPTM group was significantly lower than that in all other groups (p < 0.05). Aspartate aminotransferase (AST) activity in the 3% SPTM group was significantly lower than that in the 12% SPTM group (p < 0.05). Breast muscle moisture content in the 12% SPTM group was significantly lower than that in the control group (p < 0.05). Total amino acid and threonine contents in the breast muscle of the 12% SPTM group were significantly lower than those in the 0% and 3% SPTM groups (p < 0.05). Lauric acid (C12:0) and myristic acid (C14:0) contents in the breast muscle of the 9% and 12% SPTM groups were significantly higher than those in the 0%, and 3% SPTM groups (p < 0.05). These selective effects on meat quality traits suggest that SPTM has potential as a partial corn replacer, but further studies are needed to optimize inclusion levels and validate sensory outcomes. This systematic investigation of the effects of SPTM on physiological parameters and meat quality in Wenchang chickens provides a theoretical basis for the rational and efficient utilization of SPTM in Wenchang chicken production. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and osteoporosis (OP) are epidemiologically linked, but shared cell-type-specific molecular features remain unclear. We integrated public single-cell/single-nucleus transcriptomic datasets for OP (GSE147287) and MASLD (GSE289173) with two-sample Mendelian randomization (MR), colocalization, network annotation, macrophage-focused in silico perturbation, and exploratory serum assessment. After quality control, 13,753 OP cells and 42,438 MASLD cells/nuclei were analyzed. Macrophages were consistently identified in both datasets and showed disease-associated expansion. Directionally concordant macrophage differentially expressed genes yielded 147 shared candidate genes, with enrichment mainly involving lipid/sterol metabolism, extracellular matrix and adhesion processes, immune presentation, lysosomal processing, and phagocytic pathways. MR prioritized MUC20 as the only candidate with concordant odds ratios greater than 1 for both OP (OR = 1.044, 95% CI 1.003–1.086) and MASLD (OR = 1.111, 95% CI 1.038–1.189). Colocalization supported shared genetic signals for MUC20 in OP (PP.H4 = 0.855) and MASLD (PP.H4 = 0.816). In silico perturbation suggested a limited but pathway-enriched predicted transcriptional footprint. Serum MUC20 was higher in patients with OP+MASLD than in healthy controls. This integrative analysis identified shared macrophage-associated transcriptional themes and prioritized MUC20 as a candidate molecule for future liver–bone crosstalk studies. Full article

Indigenous goat populations are valuable genetic resources for livestock production in arid and semi-arid environments, yet many remain insufficiently characterized at the phenotypic and genomic levels. This study investigated phenotypic variation and genome-wide associations in two local Ardi goat lines in Bahrain: Ardi Bahraini and Ardi Mu’atar, the latter being distinguished by a characteristic facial marking pattern. A total of 280 goats were phenotypically characterized for qualitative traits and body measurements, and 76 animals were genotyped using the Illumina Caprine 60K single nucleotide polymorphism (SNP) BeadChip. After quality control, 49,716 autosomal SNPs were retained for genome-wide association analysis. Phenotypic analysis showed that the two lines differed significantly in body weight, body length, hip height, face width, tail length, ear width, and tail circumference, while discriminant analysis identified tail length, ear width, tail circumference, and facial patterns differentiating the lines. Principal component analysis (PCA) showed partial genomic clustering of the two lines, and genome-wide significant and suggestive SNPs based on Bonferroni and false discovery rate (FDR) thresholds on chromosomes 6, 13, 14, and 29. The strongest association was observed for rs268277393 on chromosome 13, located near DOK5 (Docking Protein 5) and TRNAC-GCA (transfer RNA cysteine, anticodon GCA), and was associated with the Ardi Mu’atar facial pattern. Additional candidate regions were located near genes with possible roles in pigmentation, development, or morphological variation. These findings provide preliminary genomic evidence supporting the phenotypic distinctiveness of Ardi Mu’atar goats and identify candidate markers that may contribute to future conservation and breeding programs. Further validation in larger populations and functional studies will be required to confirm the biological role of these candidate regions. Full article

Cadmium (Cd) contamination in agricultural soil poses a severe threat to rice growth and food safety worldwide. Seedling-stage Cd tolerance directly determines rice establishment and subsequent yield under Cd stress, but its genetic basis remains largely unclear. In this study, a genome-wide association study (GWAS) was conducted using 490 diverse accessions from the 3000 Rice Genome Project (3K RGP). Three biomass-related traits, shoot height (SH), shoot dry weight (SDW), and root dry weight (RDW), were measured under control and Cd stress conditions, along with their relative values. A total of 3,196,134 high-quality SNPs were used for genetic analysis, and population structure was corrected by principal component analysis (PCA) and kinship matrix. In total, 39 stable QTLs were detected, including 19 for RDW, 18 for SDW, and 2 for SH, most of which were specifically identified under Cd stress. Three major QTLs (qSDW1.1, qRDW3.2, qRDW5.2) were prioritized for candidate gene mining. Combining LD block analysis, gene annotation, Cd-responsive transcriptome data, and haplotype analysis, OsAKR2 (LOC_Os01g62870), OsAS1 (LOC_Os03g18130), and LOC_Os05g11320 were identified as key candidate genes regulating seedling Cd tolerance, and superior haplotypes of these genes were identified. This study reveals the genetic architecture of rice seedling Cd tolerance and provides elite QTLs, genes, and haplotypes for molecular breeding of Cd-resilient rice varieties. Full article

Host genetic susceptibility to urogenital Chlamydia trachomatis (Ct) reinfection remains poorly understood. Coding variants identified in prior genome-wide association studies (GWAS) explained only a small fraction of the risk of reinfection. Our goal in this study was to characterize whether more risk would be captured by sequence variation that traditional GWAS insufficiently captures. Specifically, we evaluated the risk attributable to SNPs present in regulatory, non-coding regions; post-transcriptional regulation by microRNAs (miRNAs) that may depend on sequence variation in either the miRNA or the target mRNA; and copy number variants (CNVs). We analyzed GWAS data from African American women with or without documented urogenital Ct reinfection. Fine mapping and independent association analyses identified 30 unique index single-nucleotide polymorphisms (iSNPs), which were expanded to variants in linkage disequilibrium. Regulatory annotation was performed using HaploReg, RegulomeDB, FORGEdb, rSNPBase, and GTEx. We examined whether genes identified in the Ct reinfection GWAS are targeted by known Ct infection–associated microRNAs using curated databases. Genome-wide CNV calling was conducted using SNP intensity data, followed by stringent quality control and gene-level association testing. Functional annotation prioritized 7 SNPs with strong regulatory evidence, with stringent criteria for regulatory relevance, using HaploReg, RegulomeDB, FORGEdb, and rSNPBase. The strongest signals were observed at the CHIT1 locus, where multiple intronic variants (including rs2486963 and rs2244385) overlapped regulatory chromatin, altered transcription factor binding motifs, and acted as cis-expression quantitative trait loci for CHIT1 in whole blood. Additional regulatory variants were identified near TDRP, ERICH1, and DLGAP1, showing tissue-specific regulatory effects. MicroRNA analysis revealed extensive post-transcriptional targeting of SOCS6 and SULF1, while CHIT1 showed no curated Ct-associated miRNA interactions. CNV analysis identified 5775 high-confidence events, with nominal gene-level associations observed for ATAD3A, CARD14, TMEM240, and ZNF140. These results indicate that a greater fraction of the susceptibility to urogenital Ct reinfection may be driven by genetic variation affecting immune and epithelial pathways rather than protein-coding changes. Full article