Search Results (969)

Background: Hypovitaminosis D has been associated with worse rheumatoid arthritis (RA) manifestations. Notably, different genetic studies have reported that approximately 65% of hypovitaminosis D can be partially explained using the presence of single-nucleotide variants (SNVs) in key genes involved in its metabolism. This study aimed to investigate the association and gene–gene interactions of four SNVs in vitamin D metabolism genes, rs10741657 (CYP2R1), rs10877012 (CYP27B1), rs4809959 (CYP24A1), and rs731236 TaqI (VDR), with hypovitaminosis D, RA, and its clinical disease activity in a Mexican mestizo population. Methods: This study was conducted among females: 204 RA patients and 204 control subjects (CS). Vitamin D serum levels (calcidiol) were analyzed using ELISA, SNVs through allelic discrimination with TaqMan^® probes, and were analyzed using a multifactor dimensionality reduction (MDR) method. Results: MDR analysis suggested that GG and TT genotypes of rs10877012 (CYP27B1) were linked to lower calcidiol levels, while the CT and CC genotypes of rs731236 TaqI (VDR) were associated with increased RA susceptibility and higher disease activity. Logistic regression confirmed that the GG genotype of rs10877012 (CYP27B1) was associated with hypovitaminosis D (OR = 1.8; CI: 1.1–3.0; p = 0.01), and the CT genotype of rs731236 TaqI (VDR) with RA (OR = 1.9; CI: 1.2–2.9; p < 0.01) and high DAS28-ESR (OR = 3.6; CI: 1.3–10.7; p < 0.01). Conclusions: The GG genotype of rs10877012 CYP27B1 was associated with susceptibility to hypovitaminosis D, whereas the CT genotype of rs731236 TaqI VDR confers susceptibility to RA and high clinical disease activity in the Mexican mestizo population. Full article

Ankylosing spondylitis (AS) displays wide inter-patient variability that is not accounted for by HLA-B27 alone, suggesting that additional immune and metabolic modifiers contribute to disease severity. Using a genetically matched design, we profiled peripheral blood mononuclear cells from two brother pairs discordant for AS severity and one healthy brother pair. Strand-specific RNA-seq was analyzed with a family-blocked DESeq2 model, while untargeted metabolites were quantified using gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS). Differential features were defined as follows: differentially expressed genes (DEGs) (|log₂FC| ≥ 1 and FDR < 0.05) and metabolites (VIP > 1, FC ≥ 1.2, and BH-adjusted p < 0.05). Pathway enrichment was performed with KEGG and Gene Ontology (GO). A total of 325 genes were differentially expressed. Type I interferon and neutrophil granule transcripts (e.g., IFI44L, ISG15, S100A8/A9) were markedly up-regulated, whereas mitochondrial β-oxidation genes (ACADM, CPT1A, ACOT12) were repressed. Metabolomics revealed 110 discriminant features, including 25 MS/MS-annotated metabolites. Primary bile acid intermediates were depleted, whereas oxidized fatty acid derivatives such as 12-Z-octadecadienal and palmitic amide accumulated. Spearman correlation identified two antagonistic modules (i) interferon/neutrophil genes linked to pro-oxidative lipids and (ii) lipid catabolism genes linked to bile acid species that persisted when severe and mild siblings were compared directly. Enrichment mapping associated these modules with viral defense, neutrophil degranulation, fatty acid β-oxidation, and bile acid biosynthesis pathways. This sibling-paired peripheral blood mononuclear cell (PBMC) dual-omics study delineates an interferon-driven lipid–bile acid axis that tracks AS severity, supporting composite PBMC-based biomarkers for future prospective validation and highlighting mitochondrial lipid clearance and bile acid homeostasis as potential therapeutic targets. Full article

Thiopurines are employed in inflammatory bowel diseases (IBDs; Crohn’s disease, CD; ulcerative colitis, UC) to induce remission, prevent relapse, and reduce the steroid dosage, although they can sometimes be ineffective and present side effects. Genetic variations in the TPMT and NUDT15 genes are well recognized to influence the therapeutic response, despite notable regional differences in their frequencies across various ethnic populations. Herein, the risk haplotypes TPMT*3A, *3B, *3C, and the variant NUDT15*3 were examined in a retrospective cohort of 383 Italian IBD patients who received azathioprine or 6-mercaptopurine. TPMT and NUDT15 genotyping was performed by Sanger sequencing and TaqMan allelic discrimination, respectively. Allelic and genotype frequencies and genotype–phenotype correlations in non-responder and intolerant patients were assessed in comparison to responders. In total, 17% of patients did not respond to treatment, while 20% experienced adverse events, with leukopenia found in 13% of patients. TPMT haplotypes were found in 3.1% of patients, and 1.6% had the NUDT15*3 variant. CD patients with leukopenia had a higher frequency of the TPMT risk haplotype (40% vs. 4%, p = 0.024). Although additional validation through larger prospective studies or meta-analyses is needed, our findings support the importance of TPMT gene-variant assessment for forecasting azathioprine-related leukopenia in Italian IBD patients. Full article

Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has become an intermittent yet economically significant disease of wheat in the Upper Midwest during the last decade. Because chemical and cultural controls remain ineffective, breeders rely on developing resistant varieties, yet visual ratings in inoculated nurseries are labor-intensive, subjective, and time-consuming. To accelerate this process, we combined unmanned-aerial-vehicle hyperspectral imaging (UAV-HSI) with a carefully tuned chemometric workflow that delivers rapid, objective estimates of disease severity. Principal component analysis cleanly separated BLS, leaf rust, and Fusarium head blight, with the first component explaining 97.76% of the spectral variance, demonstrating in-field pathogen discrimination. Pre-processing of the hyperspectral cubes, followed by robust Partial Least Squares (RPLS) regression, improved model reliability by managing outliers and heteroscedastic noise. Four variable-selection strategies—Variable Importance in Projection (VIP), Interval PLS (iPLS), Recursive Weighted PLS (rPLS), and Genetic Algorithm (GA)—were evaluated; rPLS provided the best balance between parsimony and accuracy, trimming the predictor set from 244 to 29 bands. Informative wavelengths clustered in the near-infrared and red-edge regions, which are linked to chlorophyll loss and canopy water stress. The best model, RPLS with optimal preprocessing and variable selection based on the rPLS method, showed high predictive accuracy, achieving a cross-validated R² of 0.823 and cross-validated RMSE of 7.452, demonstrating its effectiveness for detecting and quantifying BLS. We also explored the spectral overlap with Sentinel-2 bands, showing how UAV-derived maps can nest within satellite mosaics to link plot-level scouting to landscape-scale surveillance. Together, these results lay a practical foundation for breeders to speed the selection of resistant lines and for agronomists to monitor BLS dynamics across multiple spatial scales. Full article

Effective species identification is crucial for the conservation and management of marine mammals, particularly in regions such as the Mediterranean Sea, where several cetacean populations are endangered or vulnerable. In this study, we developed and validated a High-Resolution Melting (HRM) analysis protocol for the rapid, cost-effective, and reliable identification of the four representative marine cetacean species that occur in the Mediterranean Sea: the bottlenose dolphin (Tursiops truncatus), the striped dolphin (Stenella coeruleoalba), the sperm whale (Physeter macrocephalus), and the fin whale (Balaenoptera physalus). Species-specific primers targeting mitochondrial DNA regions (cytochrome b and D-loop) were designed to generate distinct melting profiles. The protocol was tested on both tissue and fecal samples, demonstrating high sensitivity, reproducibility, and discrimination power. The results confirmed the robustness of the method, with melting curve profiles clearly distinguishing the target species and achieving a success rate > 95% in identifying unknown samples. The use of HRM offers several advantages over traditional sequencing methods, including reduced cost, speed, portability, and suitability for degraded samples, such as those from the stranded individuals. This approach provides a valuable tool for non-invasive genetic surveys and real-time species monitoring, contributing to more effective conservation strategies for cetaceans and enforcement of regulations against illegal trade. Full article

The morphological diversity of Moroccan honey bees (Apis mellifera) was investigated using geometric morphometrics to assess wing venation patterns among three populations representing three climatic zones: desert, semiarid, and Mediterranean. A total of 193 honey bee samples were analyzed and compared to historical reference samples from the Morphometric Bee Data Bank in Oberursel, representing the three subspecies: A. m. intermissa, A. m. sahariensis, and A. m. major. Principal component analysis and linear discriminant analysis revealed significant, yet overlapping morphological differences among the climatic groups. Spatial modeling showed a significant southwest–northeast clinal gradient in wing morphology. Almost all samples were assigned to the African evolutionary lineage, except one, suggesting a dominant African genetic background. Interestingly, all three populations showed greater morphological affinity to A. m. intermissa than to A. m. sahariensis, which could indicate introgression or limitations in the current reference dataset. These discrepancies highlight the necessity of revising subspecies boundaries using updated morphometric and genomic approaches. These findings improve our understanding of honey bee biodiversity in Morocco and provide valuable information for conservation and breeding programs. Full article

Follicular lymphoma (FL) is one of the most common types of non-Hodgkin’s lymphomas. The tumor is characterized by a wide range of clinical manifestations, ranging from indolent forms to early transformation and progression with a poor prognosis. The search for clinically significant genetic changes is essential for personalized risk assessment and treatment selection. The CREBBP gene is frequently mutated in this type of lymphoma, with changes occurring at the level of the earliest tumor precursor cells. However, the prognostic and diagnostic significance of the CREBBP gene mutation status in FL has not been fully established. In this study, we analyzed sequencing data of exons 22–30 of the CREBBP gene in 86 samples from patients with different grades of FL (1–3B), including those in the 3A–3B subgroup without the t(14;18) translocation. We also investigated the prognostic significance of CREBBP gene mutations in relation to the treatment options, namely high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT/auto-HSCT) and conventional chemotherapy programs (CCT). It was found that FL patients with a single missense mutation in the KAT domain of the CREBBP gene experienced an extremely low number of early adverse events related to lymphoma and had better long-term survival rates, regardless of treatment option. In contrast, when comparing patients with FL without a missense mutation in the KAT domain or those with multiple mutations in the CREBBP gene, overall and progression free survival were worse, and early progression and histological transformation were more common. Compared to standard therapy, patients who underwent HDCT/auto-HSCT in the FL 1–3B (14;18)-positive group without a single missense mutation in the KAT domain had better survival rates and lower rates of transformation and early progression. In addition, among patients with FL 3A–3B (14;18)-negative, we found that there were no cases of a missense mutation in the KAT domain of the CREBBP gene. This suggests that a single missense mutation in the CREBBP gene may be a feature that discriminates 14;18-positive FL with a favorable prognosis from a high-risk disease. FL 3A–3B (14;18)-negative may represent a distinct variant with different biology and underlying mechanisms of development compared to classical FL. Full article

Stropharia rugosoannulata, an ecologically valuable and economically important edible mushroom, faces challenges in strain-level identification and breeding due to limited genomic resources and the lack of high-resolution molecular markers. In this study, we generated high-quality genomic data for 105 S. rugosoannulata strains and identified over 2.7 million SNPs, unveiling substantial genetic diversity within the species. Using core gene-associated multiple nucleotide polymorphism (cgMNP) markers, we developed an efficient and transferable framework for strain discrimination. The analysis revealed pronounced genetic differentiation among cultivars, clustering them into two distinct phylogenetic groups. Nucleotide diversity (π) across 83 core genes varied significantly, highlighting both highly conserved loci under purifying selection and highly variable loci potentially associated with adaptive evolution. Phylogenetic analysis of the most variable gene, Phosphatidate cytidylyltransferase mitochondrial, identified 865 SNPs, enabling precise differentiation of all 85 cultivars. Our findings underscore the utility of cgMNP markers in addressing challenges posed by horizontal gene transfer and phylogenetic noise, demonstrating their robustness in cross-species applications. By providing insights into genetic diversity, evolutionary dynamics, and marker utility, this study establishes a foundation for advancing breeding programs, conservation strategies, and functional genomics in S. rugosoannulata. Furthermore, the adaptability of cgMNP markers offers a universal tool for high-resolution strain identification across diverse fungal taxa, contributing to broader fungal phylogenomics and applied mycology. Full article

The wheat planted at the end of the rainy season in the Cerrado suffers from a strong water deficit. A selection of genetic material with drought tolerance is necessary. In improvement programs that evaluate a large number of materials, efficient, automated, and non-destructive phenotyping is essential, which requires the use of sensors. The experiment was conducted in 2016 using a phenotyping platform, where irrigation gradients ranging from 184 (WR4) to 601 mm (WR1) were created, allowing for the comparison of four genotypes. In addition to productivity, we evaluated plant height, hectoliter weight, the number of spikes per square meter, ear length, photosynthesis, and the indices calculated by the sensors. For most morphophysiological parameters, extreme stress makes it difficult to discriminate materials. WR1 (601 mm) and WR2 (501 mm) showed similar trends in almost all variables. The data validated the phenotyping platform, which creates an irrigation gradient, considering that the results obtained, in general, were proportional to the water levels. The similar trend between sensors (NDVI, PRI, and LIFT) and morphophysiological, plant growth, and crop yield evaluations validated the use of sensors as a tool in selecting drought-tolerant wheat genotypes using a non-invasive methodology. Considering that only four genotypes were used, none showed absolute and unequivocal tolerance to drought; however, each genotype exhibited some desirable characteristics related to drought tolerance mechanisms. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) represents significant health challenges, especially among patients with chronic hepatitis B (CHB). This study uses machine learning models to predict NAFLD in patients with inactive CHB. It builds on previous research by employing classification algorithms to analyze demographic, clinical, and laboratory data to identify NAFLD predictors. Methods: A single-center cross-sectional study was conducted, including 450 inactive CHB patients from Sultan Qaboos University Hospital. Five ML models were developed: Logistic Regression, Random Forest, Extreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), and Multi-Layer Perceptron (MLP). Results: The prevalence of NAFLD was 50.22%. Among the machine learning models, Random Forest achieved the highest performance with an ROC AUC of 0.983 (95% CI: 0.952–0.999), followed by XGBoost at 0.977 (95% CI: 0.938–0.999) and MLP at 0.963 (95% CI: 0.915–0.995). SVM also showed strong performance with an AUC of 0.949 (95% CI: 0.897–0.985), while Logistic Regression demonstrated comparatively lower discrimination with an AUC of 0.886 (95% CI: 0.799–0.952). Key predictive features identified included platelet count, low-density lipoprotein (LDL), hemoglobin, and alanine aminotransferase (ALT). Logistic Regression highlighted platelet count as the most significant negative predictor, while LDL and ALT were positive contributors. Conclusions: This study shows the utility of ML in improving the identification and management of NAFLD in CHB patients, enabling targeted interventions. Future research should expand on these findings, integrating genetic and lifestyle factors to enhance predictive accuracy across diverse populations. Full article

The sensory quality of black tea is intrinsically linked to cultivar genetics, yet comprehensive characterization of flavor compounds in emerging northern Guangdong black tea (NGBT) remains limited. This study employed high-performance liquid chromatography-ultraviolet (HPLC-UV) and headspace solid-phase microextraction coupled with GC-MS (HS-SPME-GC-MS) to analyze non-volatile and volatile compounds in five NGBT cultivars—Jinshahong (JSH), Danxia No.1 (DXY), Danxia No.2 (DXE), Yingde Black Tea (QTZ), and Yinghong No.9 (YHJ)—alongside sensory evaluation. Orthogonal partial least squares-discriminant analysis (OPLS-DA) identified key non-volatile discriminants (VIP > 1) ranked by contribution: total catechins > simple catechins > CG > EGCG > ester catechins > EGC. HS-SPME-GC-MS detected 97 volatiles, with eight aroma-active compounds exhibiting OAV > 1 and VIP > 1: Geraniol > Methyl salicylate > Linalool > β-Myrcene > Benzyl alcohol > (Z)-Linalool Oxide > Phenethyl alcohol > (Z)-Jasmone. These compounds drive cultivar-specific aromas in NGBTs. Findings establish a theoretical framework for evaluating cultivar-driven flavor quality and provide novel insights for targeted breeding and processing optimization of NGBTs. Full article

Background/Objectives: Wolf–Hirschhorn syndrome (WHS; OMIM #194190) is a rare neurodevelopmental disorder, caused by deletions in the distal short arm of chromosome 4. It is characterized by developmental delay, epilepsy, intellectual disability, and distinctive facial dysmorphism. Clinical presentation varies widely, complicating prognosis and individualized care. Methods: We assembled a cohort of 140 individuals with genetically confirmed WHS from Spain and Latin-America, and developed and validated a multidimensional, Clinician-Reported Outcome Assessment (ClinRO) based on the Global Functional Assessment of the Patient (GFAP), derived from standardized clinical questionnaires and weighted by HPO (Human Phenotype Ontology) term frequencies. The GFAP score quantitatively captures key functional domains in WHS, including neurodevelopment, epilepsy, comorbidities, and age-corrected developmental milestones (selected based on clinical experience and disease burden). Results: Higher GFAP scores are associated with worse clinical outcomes. GFAP showed strong correlations with deletion size, presence of additional genomic rearrangements, sex, and epilepsy severity. Ward’s clustering and discriminant analyses confirmed GFAP’s discriminative power, classifying over 90% of patients into clinically meaningful groups with different prognoses. Conclusions: Our findings support GFAP as a robust, WHS-specific ClinRO that may aid in stratification, prognosis, and clinical management. This tool may also serve future interventional studies as a standardized outcome measure. Beyond its clinical utility, GFAP also revealed substantial social implications. This underscores the broader socioeconomic burden of WHS and the potential value of GFAP in identifying high-support families that may benefit from targeted resources and services. Full article

Saccharomyces cerevisiae plays a fundamental role in winemaking, not only driving alcoholic fermentation but also producing secondary metabolites that contribute to the organoleptic properties of wine. To ensure consistent quality and process efficiency, wineries commonly employ selected starter strains. Accordingly, the ability to control strain purity and traceability is of critical importance. Currently, the inter-delta PCR method is widely used for the strain-specific genotyping of S. cerevisiae. However, its resolution diminishes when analyzing genetically similar strains, such as those isolated from related grape types or during genotyping of large yeast collections. To address this limitation, we developed a novel strategy that integrates computational and experimental approaches to identify highly specific allelic variants (single nucleotide polymorphisms, SNPs) within the S. cerevisiae genome. Comparative genomic analysis of twenty-eight different strains led to the identification of multiple strain-specific SNPs. From these, nine SNPs spanning five strains were selected and validated through targeted PCR assays. These assays confirmed the feasibility of using SNPs as reliable genetic markers for strain discrimination and traceability. Overall, our findings demonstrate that this SNP-based approach, implemented via multiplex allele-specific (AS) PCR assays, offers a rapid, cost-effective, and highly discriminatory alternative to current genotyping methods, particularly for differentiating closely related strains. Full article

Previous large-scale genetic studies identified single-nucleotide polymorphisms (SNPs) of the membrane bound O-acyltransferase domain containing 7 (MBOAT7) and patatin-like phospholipase domain containing 3 (PNPLA3) genes as risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD). However, this has not yet been investigated in Brazilian patients. In this study, we evaluated the association between the PNPLA3 variant rs738409 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis in MASLD etiology. In parallel, we also aimed to evaluate a protective SNP of the mitochondrial amidoxime-reducing component 1 (MTARC1) gene. We also evaluated TM6SF2 rs58542926, GCKR rs1260326 and rs780094, and HSD17B13 rs72613567 and they were not associated with liver fibrosis. The study was conducted at the Department of Gastroenterology and Nutrology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), and included 113 patients with liver fibrosis (F0–F1), 99 patients with significant liver fibrosis (F2–F4), and 90 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, the PNPLA3 GG genotype was more frequent in F2–F4 (23%) and F0–F1 (22%) patients than in controls (9%; p = 0.02). The MBOAT7 TT genotype was significantly associated with fibrosis, with a prevalence of 23% in F2–F4 patients versus 10% in F0–F1 and 11% in controls (p = 0.01). This association was confirmed by regression analysis (OR = 5.01 95% CI: 1.86–13.49; p = 1.41 × 10⁻³). The protective MTARC1 AA genotypes were more frequent in controls (52%) when compared to patients with fibrosis (5% p = 2.76 × 10⁻²⁰). Full article

Wine organic acids influence their overall quality. This study examines the variability of major acids (tartaric, malic, lactic, citric, acetic, and gluconic) and minor phenolic acids (gallic, protocatechuic, syringic, caftaric, caffeic, cutaric, coumaric, and 2-S-glutathionylcaftaric) in varietal red wines produced from predominantly autochthonous grape cultivars of the Canary Islands. Two hundred and five monovarietal red wine samples were analyzed to assess how the organic acid profiles differed depending on the grape cultivars employed in their production, island of provenance, denomination of origin, and aging, supporting relationships between both genetic and environmental factors. High-performance liquid chromatography and enzymatic methods were used for determining minor and major organic acids, respectively. Many significant differences between grape cultivars, geographical origin, and aging were observed, reflecting the complexity of the composition of the organic acids in red wine and its relationship with viticultural factors. Linear discriminant analysis achieved classification accuracies up to 88.3% by cultivar and 83.4% by island. Correlation and multivariate analyses helped identify compositional patterns and key discriminant acids. This study advances the comprehension of major and minor acid composition and equilibria in red wines and may support future research on quality parameters and regional typicity. Full article