Search Results (1,155)

Background/Objectives: Inflammatory and oxidative-stress-related processes contribute to post-myocardial infarction (MI) remodeling and may influence long-term cardiovascular outcomes. Recent findings have highlighted the potential role of non-coding RNAs in regulating these processes. LncRNA MALAT1 acts as a ceRNA that “sponges” miR-146a, reducing its ability to repress downstream targets such as COX-2. The aim of this study was to assess MALAT1 and miR-146a expression in PBMCs and plasma COX-2 in controls and patients six months post-MI. In addition, we investigated whether MALAT1 rs3200401 and miR-146a rs2910164 variants were associated with MI susceptibility, MALAT1 and miR-146a expression, plasma COX-2 levels, and left ventricle (LV) echocardiographic parameters. Methods: The study included 534 patients and 381 controls for genetic analyses, while expression analyses were performed in a subset of 89 patients and 39 controls. TaqMan™ assays were used for genotyping and for quantification of MALAT1 and miR-146a expression. Plasma COX-2 levels were measured using ELISA. Results: Compared to controls, patients had higher MALAT1 expression, whereas lower miR-146a expression was observed only in unadjusted analyses. Plasma COX-2 levels were higher in patients with advanced heart failure (NYHA III–IV) compared with NYHA I-II. The rs3200401 TT genotype was more frequent in patients, whereas rs2910164 genotype distributions were similar between groups. The rs3200401-rs2910164 TG allele combination was associated with increased MI risk. Conclusions: MALAT1 may serve as a potential long-term biomarker of post-MI molecular alterations, whereas the role of miR-146a requires further investigation in larger cohorts. The rs3200401 variant may represent a genetic marker associated with MI susceptibility and adverse LV remodeling. Further studies are needed for confirmation. Full article

Necrotizing enterocolitis (NEC) is a multifactorial disease associated with prematurity, intestinal hypoperfusion, dysbiosis, and oxidative stress. Interindividual variability in disease occurrence suggests a role for genetic susceptibility. Null genotypes of the GSTM1 and GSTT1 genes result in absent glutathione S-transferase activity and may impair antioxidant defenses. This study investigated whether GSTM1 and GSTT1 null genotypes are associated with NEC development and severity in preterm newborns. This single-center case–control pilot study included 100 preterm newborns (50 NEC and 50 controls). Genotyping was performed by multiplex polymerase chain reaction. Baseline characteristics were comparable between groups (p > 0.05). Stages II-A and II-B accounted for 82% of NEC cases. A significant inverse correlation was observed between gestational age and postnatal age at NEC diagnosis (r = −0.5994; p < 0.0001). The GSTM1-null genotype was more frequent in the NEC group (60% vs. 36%) and was associated with increased disease risk in both unadjusted (OR = 2.667; 95%CI: 1.188–5.986; p = 0.027) and adjusted analyses (aOR = 3.09; 95%CI: 1.29–7.40; p = 0.011). No significant associations were observed for GSTT1, combined genotypes, or disease severity. These findings provide preliminary evidence of an association between the GSTM1-null genotype and NEC susceptibility. Given the exploratory pilot design, these results should be considered hypothesis-generating and require confirmation in larger prospective studies. Full article

Even before the discovery of DNA, Claude Shannon developed a mathematical model of Mendelian inheritance. Unlike the widely recognized Hardy–Weinberg equilibrium, Shannon’s genetic algebra has received little scholarly attention. Here, we revisit Shannon’s algebra and develop two complementary extensions for modern population genetics. First, we formulate a finite population version of Shannon’s framework, moving beyond the idealized infinite population setting to propagate allelic and genotypic frequencies under realistic sampling conditions. Second, we combine Shannon’s algebra with an analytical genotype–phenotype mapping framework to characterize genotypic configurations compatible with observed phenotypic frequencies, using auxiliary variables to express the inherent degeneracy of the genotype–phenotype relationship. Together, these extensions provide a unified framework in which phenotypic observations constrain the underlying genetic structure, and these constraints are propagated through inheritance via Shannon’s algebra. The resulting analytical expressions for offspring phenotypic distributions apply to both complete and incomplete penetrance and extend naturally to multilocus systems. This work highlights Shannon’s algebra as a flexible analytical tool for two complementary problems: (i) forward propagation of genetic information in finite populations, and (ii) analytical description of phenotypic inheritance from inferred genotypic information. Full article

The floodplains of the Paraná and Paraguay rivers form the Chaco wetland, one of the most species-rich plant ecosystems in Argentina. Because wild grasses can serve as reservoirs of fungal species that cause disease and mycotoxin contamination of cereal crops, we examined asymptomatic, wild grasses from the Chaco wetlands for the presence of the genus Fusarium, which includes multiple species that cause agriculturally important diseases and/or mycotoxin contamination of crops. We focused our efforts on the identification and characterization of the multispecies lineage known as the Fusarium fujikuroi species complex (FFSC). Using morphological traits and partial DNA sequences of the TEF1 gene, we determined that 58 isolates recovered from the grasses were members of FFSC. Fifty of the isolates were identified as one of six FFSC species, including the economically important plant pathogenic species F. proliferatum, F. subglutinans, and F. verticillioides. To our knowledge, two of the species, F. anthophilum and F. pseudocircinatum, have not been reported previously in Argentina. Our analyses also indicated that eight of the FFSC isolates were a novel species, herein described as Fusarium varsavskyanum. A polymerase chain reaction (PCR) assay and genome sequence data indicate that each isolate of F. varsavskyanum isolate had only one mating type idiomorph (MAT1-1 or MAT1-2), which suggests that the fungus is heterothallic. Genome sequence analysis indicated that F. varsavskyanum has the genetic potential to produce, (i) the emerging mycotoxins fusaric acid and beauvericin (or enniatins); (ii) the pigments bikaverin, carotenoids, and fusarubin; and (iii) the plant hormones auxins, cytokinins, and gibberellins. Thus, asymptomatic grasses from the Chaco wetland can harbor Fusarium species that in some agroecosystems can cause economically important diseases and/or mycotoxin contamination of crops. It remains to be determined whether the genotypes of Fusarium species that occur on the wetland grasses, including F. varsavskyanum genotypes, can negatively impact agriculture. Full article

African swine fever (ASF) is a highly fatal, febrile infectious disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV). Recently, highly virulent recombinant ASFVs with chimeric genomes derived from p72 genotype I and II viruses have emerged in China, Vietnam, and Russia. These genotype I/II recombinants can evade immunity induced by genotype II–based vaccines, thereby complicating disease control efforts. To address this challenge, a novel duplex quantitative PCR (qPCR) assay was developed to simultaneously detect and differentiate genotypes I, II, and I/II recombinants in a single reaction. The assay exhibited high sensitivity and specificity, with a reliable detection limit of 10 copies/reaction for genotype I and II ASFV DNA. Validation using clinical samples collected in northern Vietnam in 2025 confirmed a robust performance in accurately distinguishing circulating genotype II viruses from recombinant genotype I/II viruses, including the detection of potential co-infection. Whole-genome sequencing of selected positive samples further corroborated these findings. Overall, this qPCR assay provides a precise and efficient tool for identifying currently circulating ASFV genotypes, thereby facilitating improved disease surveillance and supporting a comprehensive understanding of the evolving epidemiological landscape of ASF in regions with increasing viral genetic diversity. Full article

Objectives: Patients with thalassemia major are at high risk of developing blood-borne infections, including toxoplasmosis, due to their dependence on frequent blood transfusions and underlying immune system disorders. This study was designed to investigate this hidden risk and provide data for policymaking in blood transfusion services in a region with a high endemicity. Methods: A total of 300 blood samples from thalassemia patients in northern Iran were collected. Serological testing was conducted to detect IgG and IgM antibodies. DNA extraction followed, with molecular screening performed via PCR. Finally, genotyping of T. gondii was carried out using nested PCR focused on the GRA6 gene. Results: The serological analysis revealed 59.7% of patients exhibited IgG against T. gondii, while only 0.6% tested positive for IgM. The results of the molecular screening revealed 2.7% of patients had DNA of T. gondii. The results of genetic analysis showed 75% had type II, 12.5% had type I, and 12.5% belonged to type III. Conclusions: This study provides serological and molecular evidence of a high chronic Toxoplasma gondii burden in thalassemia patients from northern Iran, an endemic region. A significant association between blood transfusion history and seropositivity, along with parasite DNA detection, suggests elevated exposure risk, though direct transfusion transmission remains unproven. Finding’s support integrating nested PCR with routine serology for diagnosing infection in this population. Full article

Enlarged vestibular aqueduct (EVA) is a common inner ear malformation that causes sensorineural hearing loss. It is frequently associated with pathogenic variants in the SLC26A4 gene. This study aimed to investigate the genetic basis of hearing loss in Mongolian patients with EVA. Whole-exome sequencing was performed in 19 Mongolian patients from 15 unrelated families diagnosed with EVA with or without cochlear incomplete partition type II. All patients underwent high-resolution computed tomography of the temporal bone to confirm the diagnosis. Biallelic SLC26A4 pathogenic variants were identified in all 15 families, achieving a 100% diagnostic yield. The most frequent variant was c.919-2A>G (40%), followed by c.2027T>A (23.3%) and c.1318A>T (16.7%). The spectrum of variants includes population-specific variants found in East Asians (c.919-2A>G), North Asians (c.2027T>A), and Southwest Asians (c.716T>A), suggesting a unique mutation spectrum in this Mongolian cohort characterized by variants prevalent across various Eurasian populations, which remains to be confirmed in larger studies. Furthermore, correlation analyses on multi-ethnic allele frequencies of biallelic SLC26A4 genotypes demonstrated positive correlations with deaf cohorts of East Asian, North Asian, Northeast Asian, and Western Asian groups. Digenic inheritance (with pathogenic variants in FOXI1, KCNJ10, or EPHA2) was not observed, and there was no clear genotype–phenotype correlation between specific SLC26A4 genotypes and hearing levels or inner ear malformations. This study provides a comprehensive overview of the genetic landscape of EVA in the Mongolian population. The identification of biallelic SLC26A4 pathogenic variants in all families underscores the clinical role of this gene in EVA pathogenesis. The observed pan-ethnic mutation spectrum likely reflects the genetic diversity resulting from historical migrations of Mongolians. Full article

The molecular management of elite-relevant lines in clonally exploited crops requires more than broad genetic structure alone. In Stevia rebaudiana, breeding materials derived from cv. ‘Morita II’ may retain useful variation while also concentrating molecularly similar lines, increasing redundancy within selection pipelines. This study assessed whether a reduced five-locus SSR dataset could provide an operational molecular-affinity framework for redundancy screening and breeding-context interpretation of previously identified elite-relevant lines in a ‘Morita II’-derived breeding collection. A curated five-locus SSR dataset comprising 85 genotypes from a tropical breeding programme was analysed using the Wang relatedness estimator, operational molecular-affinity classes, UPGMA clustering based on Wang-derived dissimilarity and permutation-based assessment of mean Wang relatedness. The collection combined a broad fraction of comparisons showing no detectable positive molecular affinity with a relevant high-affinity component, and this pattern differed between the two reference molecular strata. One subset showed a compact high-affinity profile and higher mean Wang relatedness than expected under random reassignment, whereas the other was dominated by comparisons with no detectable positive molecular affinity. Importantly, the five-locus SSR framework is interpreted here as an operational, locally validated decision-support tool rather than as genome-wide or pedigree-level relatedness inference. These findings suggest that reduced SSR-derived molecular-affinity information can complement phenotypic, physiological and clonal evaluations by providing redundancy context for line retention, clonal advancement, and parental-diversification decisions in tropical stevia breeding. Full article

Sudden cardiac death (SCD) in athletes often represents the first manifestation of an underlying inherited cardiovascular disorder exposed by adrenergic stress, altered calcium cycling, mechanical loading, and metabolic demand during intense exercise. This review focuses on the molecular architecture that links genotype to arrhythmogenic phenotype in athletes, emphasizing sarcomeric force generation and energetic inefficiency in hypertrophic cardiomyopathy, desmosomal failure and Hippo/Wnt/transforming growth factor-beta (TGF-β) signaling in arrhythmogenic cardiomyopathy, and ion-channel and calcium/calmodulin-dependent protein kinase II (CaMKII)calcium handling abnormalities in inherited channelopathies. This review further examines how exercise-induced physiological remodeling intersects with these pathways through insulin-like growth factor-1 (IGF-1)/phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling, mitochondrial biogenesis, oxidative stress, inflammatory signaling, and epigenetic regulation. Attention is given to the molecular basis of genotype-positive/phenotype-negative states, variable penetrance, and exercise-mediated disease expression. Finally, the integration of molecular biology with genomic data, polygenic risk, and emerging digital phenotyping is discussed to refine mechanism-based risk stratification and identify future therapeutic targets for prevention of SCD in athletes. Full article

African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating swine disease. To date, no commercial ASF vaccine has been authorized for global marketing except in Vietnam, and emerging genotype I/II recombinant ASFV strains pose severe new challenges to ASF control. Live-attenuated vaccines (LAVs) are widely recognized as the most promising strategy for ASF control. This review systematically summarizes three conventional development strategies for ASF LAVs, dissects the molecular mechanisms of two core bottlenecks—intergenotypic ASFV recombination and vaccine strain reversion to virulence—and elaborates rational design strategies for next-generation LAVs based on cutting-edge technologies. These strategies can fundamentally mitigate the aforementioned risks, offering promising solutions for addressing the major limitations of conventional ASF LAVs. Full article

Background/objectives: Obesity is a multifactorial condition influenced by interactions between genetic susceptibility and environmental factors. The fat mass and obesity-associated (FTO) gene has been widely linked to obesity risk, particularly the rs9939609 polymorphism, which is associated with higher body mass index (BMI) and adiposity. However, evidence in adolescents remains inconsistent, and lifestyle factors such as physical activity and diet may modify genetic risk. The objectives of this study were: (i) to examine the influence of environmental, genetic, physical activity, and dietary factors on the BMI and overweight-related variables of adolescents, and (ii) to assess the impact of the rs9939609 polymorphism in the FTO gene on these variables. Methods: A cross-sectional study was conducted involving 206 adolescents aged 12 to 16 years. Body mass index (BMI), physical fitness, physical activity levels, adherence to the Mediterranean diet, mobile phone usage, and FTO rs9939609 genotyping from buccal swabs were collected. Results: No significant associations were found between the FTO genotype and BMI, or with physical activity, mobile phone usage and dietary habits. Boys showed higher physical fitness and physical activity levels than girls (p < 0.05). The only factor significantly associated with BMI was regular breakfast consumption: adolescents who habitually ate breakfast had a lower prevalence of overweight (χ² = 7.98, p = 0.005). Conclusions: The rs9939609 polymorphism in the FTO gene was not associated with overweight in this adolescent cohort. The findings underscore the relevance of healthy behaviours, particularly regular breakfast consumption and physical activity, especially among boys, as factors potentially associated with lower prevalence of overweight during adolescence. Full article

Human leukocyte antigen (HLA) loci are highly polymorphic genome regions, with allele frequencies varying significantly across different populations. Population HLA frequency databases may contain biases and make cross-study comparison complicated due to varying data curation protocols, genotyping methodologies, resolution, and inconsistencies in the selection criteria for population samples. This study presents HLA allele frequencies of class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQB1, -DQA1), as well as their combined haplotypes obtained from over 18,000 whole genome sequencing samples of the Russian population. The cohort was stratified based on PCA and admixture components, providing frequencies for 14 different ethnic groups. For 12 groups cohort size allowed us to reach average saturation of 96% of allele frequencies in groups. Moreover, we demonstrated the utility of composed statistics for disease population study using type 1 diabetes (T1D) as an example. Genetically defined population clusters with similar aggregated genetic risk for T1D demonstrated substantial differences in frequencies of risk and protective HLA alleles. Obtained frequency data were made publicly available through the Allele Frequency Net Database improving previously sparse coverage in HLA frequencies data for the East Europe and North Asia regions. Full article

Witches’ broom disease (WBD), caused by the fungus Moniliophthora perniciosa, poses a major threat to cocoa production and little is yet known about how the fungus adapts at the molecular level, particularly in the apoplastic environment during early infection. Here, we investigated how apoplastic washing fluid (AWF) from two cocoa genotypes with contrasting resistance to WBD modulates the mycelial protein profile of two M. perniciosa isolates: (i) Mp553—low infection level; and (ii) Mp565—high infection level. A total of 1272 proteins were identified. Mp565, showed increased accumulation of proteins associated with oxidative stress response, energy metabolism, and virulence when exposed to AWF from the resistant variety TSH1188. Key proteins such as phosphoglycerate kinase, enolase, and heat shock were significantly modulated. Interestingly, AWF from the resistant variety promoted the suppression of metabolic proteins, suggesting an effective defense response in the resistant genotype. Furthermore, interaction network analysis revealed the central role of the MPER_11800 protein, a potential regulator of fungal adaptation. The findings underscore the importance of the T. cacao apoplast in both plant defense and fungal adaptation. The study also reveals key molecular targets, such as MPER_11800, for potential strategies to control WBD. These insights enhance our understanding of M. perniciosa pathogenicity and offer valuable directions for developing novel interventions to mitigate the impact of this devastating disease. Full article

Recombinant genotype I–II African swine fever virus (ASFV) strains with high virulence have been increasingly reported in China and Vietnam since 2023, raising significant concerns for disease control. In this study, we characterized the hematological, virological, pathological, and immunological dynamics in ASFV-inoculated pigs, with particular emphasis on temporal changes associated with mortality following the onset of viremia. Specific-pathogen-free pigs were intramuscularly inoculated with 1 × 10³ or 1 × 10⁵ HAD₅₀/mL of ASFV LS100 virus strain and developed acute disease characterized by high fever and severe hemorrhagic manifestations. The incubation period ranged from 3 to 5 days, with mortality occurring between 6 and 10 days post-inoculation (dpi). Viral genomic DNA was detected in blood, oral swabs, and rectal swabs as early as 2–4 dpi. Pathological examination revealed prominent necrotic skin lesions and joint swelling. Although hematological parameters and serum biochemical profiles were comparable between high- and low-dose groups, differences in viral load distribution were observed. Notably, cytokine profiling in whole blood revealed a strong and persistent upregulation of pro-inflammatory mediators, including IL-1β, IL-6, IL-12p40, TNF-α, IFN-γ, CCL2, CCL3, CCL14, CXCL9, and CXCL10, which correlated with persistent fever from 2 to 7 dpi. Collectively, these findings confirm that naturally occurring recombinant genotype I–II ASFV strains are highly virulent and capable of inducing severe systemic inflammation. Their continued circulation poses substantial challenges for ASF control and prevention in Vietnam and threatens the global swine industry. Full article

Three species of suid herpesviruses (SuHVs) have been reported in pigs, specifically pseudorabies virus (PRV), porcine cytomegalovirus (PoCMV), and porcine lymphotropic herpesvirus (PLHV). However, their genetic diversity and epidemic circulating status in China remain largely unclear. In this study, 7200 nasal swabs and 2571 serum samples were collected from pigs across 17 provincial regions in China in 2017. All samples were pooled into 22 libraries based on sample type and geographic origin for high-throughput next-generation sequencing. Metaviromic analysis identified all three SuHV species, revealing marked variations in their detection rates and viral abundance. Notably, PoCMV and PRV were detected in all 17 sampled provinces, accompanied by high viral genome sequence abundance (RPM > 1 × 10²), while PLHV was only found in nasal swabs from 10 provinces, with extremely low sequence abundance (RPM < 2). Further phylogenetic and genetic diversity analyses revealed notable molecular characteristics of the three circulating SuHVs: PoCMV exhibited substantial genetic diversity with at least two major evolutionary clades identified in Chinese pig populations; variant genotype II PRV strains were confirmed as the predominant circulating lineage; and potential PLHV variants with partial sequence divergence from the reference strain were also found to circulate in China. These findings enrich the molecular epidemiological data of SuHVs in Chinese pig populations and highlight the previously overlooked, highly widespread circulation of PoCMV, warranting attention to its potential impacts on swine health and production performance. Full article