Search Results (5,461)

Primary ciliary dyskinesia (PCD) is a congenital motile ciliopathy causing impaired mucociliary clearance and characterized by recurrent respiratory infections affecting both the upper and lower airways. Several genes involved in taste perception pathways are expressed in extraoral tissues and have recently emerged as regulators of airway immune responses. This study aimed to (1) analyze potential correlations between PCD clinical manifestations and (2) investigate whether genetic variants within sweet signaling genes (SweetG) could be associated with PCD features. A total of 17 SNPs in nine SweetG were tested for differences in allele frequency between patients and the gnomAD European reference population using a binomial test. Regression models were used to evaluate associations between SweetG-SNPs and clinical features of patients. A cohort of 34 patients (10–69 years, 44.1% male) was included in the study. Regarding (1), a moderate/high correlation was identified among the clinical manifestations of the pathologies. Regarding (2), the minor alleles of rs5415 (SLC2A4 gene) and rs838133 (FGF21 gene) were less frequent in patients than in the reference population (p < 0.05). In addition, rs5415 and rs838133 were associated with the presence of chronic rhinosinusitis and situs inversus, respectively (p < 0.05). This study reveals associations between SweetG-SNPs and PCD as well as its specific clinical features, suggesting a potential link between sweet signaling pathways and PCD clinical variability. Although larger multicenter studies are warranted to validate these findings, they represent a promising area of research that can enhance our understanding of PCD and elucidate the genetic basis of clinical manifestations associated with the disease. Full article

Plant growth-promoting (PGP) bacteria are beneficial microbes that can help plants mitigate various biotic and abiotic stresses through different PGP functions. Flavins (FLs) are involved in flavoprotein-mediated reactions essential for plant metabolism and could act as PGP molecules. The aim of this study was to isolate and characterize potential FLs secreting bacteria from apple (Malus domestica [Suckow] Borkh) roots based on their fluorescence and to evaluate their PGP properties, including FLs secretion. A total of 26 bacteria with increased fluorescence in liquid culture were isolated from the apple roots. Based on 16S rRNA sequencing analysis, 11 genetically different strains mostly from Burkholderia and Rhizobia spp. were identified. All isolates secreted considerable amounts of riboflavin. In vitro plant assays showed that under nitrogen (N) limitation, inoculated alfalfa (Medicago sativa) plants yielded at least 25% more dry mass than non-inoculated plants, and inoculation with AK7 and FL112 enriched plant tissue N content compared to non-inoculated plants. This improved N acquisition was not linked to symbiotic N fixation. Additionally, the isolates exhibited some other PGP properties. However, no specific PGP functions were linked to improved plant N acquisition but could potentially be linked to the FLs secretion. For future investigation, the mechanisms underlying improved plant N uptake should be assessed to gain a more in-depth understanding. Full article

Cochlear implantation (CI) is a well-established intervention for improving auditory and speech development in children with severe-to-profound hearing loss. Nonetheless, postoperative rehabilitation outcomes exhibit substantial individual variability. This review synthesizes contemporary evidence on predictors of rehabilitation success following pediatric CI. A robust set of general factors is consistently linked to more favorable outcomes, including earlier age at implantation (with particular benefit within the first year of life), stronger preoperative receptive language skills and speech recognition, higher developmental quotient and nonverbal intelligence, and higher parental educational level. Regarding hearing-specific variables, later-onset deafness, a shorter duration of deafness, and identifiable etiologies (notably specific genetic mutations such as GJB2 and OTOF) exert significant influence. Furthermore, bilateral CI demonstrates superior outcomes compared to unilateral CI, with the surgical timing (simultaneous versus sequential) and factors such as electrode array selection and placement being critical determinants. Overall, postoperative outcomes arise from a complex interplay of biological, developmental, and environmental factors. Full article

Background: Developmental dysplasia of the hip (DDH) is a common orthopedic disorder characterized by abnormal development of the hip joint, which can lead to pain, instability, and early-onset osteoarthritis if left untreated. Its etiology is multifactorial, involving both genetic and environmental factors. Methods: This study investigated the association between selected single-nucleotide polymorphisms (SNPs) related to joint and bone development and the occurrence of DDH. It assessed potential copy number variations (CNVs) in key skeletal genes using MLPA. A total of 125 individuals were examined, including 43 patients with DDH and 82 healthy controls. Six SNPs were genotyped using real-time PCR with TaqMan assays: TGFB1 (rs1800470), CX3CR1 (rs3732378, rs3732379), GDF5 (rs143384), COL1A1 (rs113647555), and MMP24 (rs12479765). Allele and genotype distributions were compared between cases and controls, and CNVs in COL1A1, COL2A1, LRP5, DKK1, FZD4, and NDP genes were analyzed using Multiplex Ligation-Dependent Probe Amplification. Results: Among the examined variants, only GDF5 rs143384 showed a nominally significant association with DDH (p = 0.040), with the A allele more common in affected individuals. However, after correcting for multiple testing, this result no longer remained significant. No significant associations were detected for TGFB1, CX3CR1, COL1A1, or MMP24. Although CX3CR1 rs3732378 allele frequencies differed slightly from international reference data, no link to DDH was confirmed. Conclusions: MLPA analysis did not identify pathogenic CNVs in the analyzed loci, which indicates that the studied genes have no association with DDH in the Slovak population. Similarly, SNPs in the studied genes yielded no significant results, apart from rs143384 in GDF5, which requires further investigation to confirm our findings. Full article

Nanotechnology is becoming a key tool in plant biotechnology, enabling nanoparticles (NPs) to deliver biomolecules with high precision and to enhance plant and tissue resilience under stress. However, the literature remains fragmented across genetic delivery, in vitro regeneration, stress mitigation, and germplasm cryopreservation, and it still lacks standardized, comparable protocols and robust long-term safety assessments—particularly for NP use in cryogenic workflows. This review critically integrates recent advances in NP-enabled (i) genetic engineering and transformation, (ii) tissue culture and regeneration, (iii) nanofertilization and abiotic stress mitigation, and (iv) cryopreservation of plant germplasm. Across these areas, the most consistent findings indicate that NPs can facilitate targeted transport of DNA, RNA, proteins, and regulatory complexes; modulate oxidative and osmotic stress responses; and improve regeneration performance in recalcitrant species. In cryopreservation, selected nanomaterials act as multifunctional cryoprotective adjuvants by suppressing oxidative injury, stabilizing cellular membranes, and improving post-thaw viability and regrowth of sensitive tissues. At the same time, NP outcomes are highly context-dependent, with efficacy governed by dose, size, and surface chemistry; formulation; plant genotype; and interactions with culture media or vitrification solutions. Evidence of potential phytotoxicity, persistence, and biosafety risks highlights the need for harmonized reporting, mechanistic studies on NP–cell interfaces, and evaluation of environmental fate. Expected outcomes of this review include a consolidated framework linking NP properties to biological endpoints, identification of design principles for application-specific NP selection, and a set of research priorities to accelerate the safe and reproducible translation of nanotechnology into sustainable plant biotechnology and long-term germplasm preservation. Full article

Against the backdrop of intensifying global population aging, lower-limb exoskeleton robots serve as core devices for rehabilitation and power assistance. Their control accuracy and motion smoothness rely on precise dynamic models. However, parameter uncertainties caused by variations in human lower limbs, assembly errors, and wear pose a critical bottleneck for accurate modeling. Aiming to achieve high-precision dynamic modeling for a two-degree-of-freedom lower-limb exoskeleton, this paper proposes a parameter identification method named Tent-GA-GWO. A dynamic model incorporating joint friction and link inertia was constructed and linearized. An excitation trajectory based on Fourier series, conforming to human physiological constraints, was designed. To enhance algorithm performance, Tent chaotic mapping was employed to optimize population initialization, a nonlinear control parameter was used to balance search behavior, and genetic algorithm operators were integrated to increase population diversity. Simulation results show that, compared to the traditional GWO algorithm, Tent-GA-GWO improved convergence efficiency by 32.1% and reduced the fitness value by 0.26%, demonstrating superior identification accuracy over algorithms such as GA and LIL-GWO. Validation on a physical prototype indicated a close agreement between the computed torque based on the identified parameters and the actual output torque, confirming the method’s effectiveness and engineering feasibility. This work provides support for precise control of exoskeletons. Full article

The placenta is often described as the “window to the brain” due to its crucial role in fetal neurological development. In this study, we investigated a family where the older male offspring exhibited severe neurodevelopmental and mild motor coordination disorders. His brother displayed emotional and behavioral dysregulation along with mild motor coordination disorders. The father was asymptomatic, while the mother and daughter showed mild learning disabilities. Whole exome sequencing (WES) identified a disruptive X-linked pathogenic variant, c.1088_1089del p.Asp363GlyfsTer2, within the calpain-6 (CAPN6) gene. We have submitted this variant to the ClinVar database (RCV005234146.2). The variant was found in hemizygous condition in the affected male offspring and in heterozygous condition in both the mother and daughter. As predicted, the variant undergoes nonsense-mediated mRNA decay (NMD), preventing the translation of the CAPN6 gene into a functional protein. CAPN6 is a critical gene predominantly expressed in placental and trophoblast tissues. Although its function is not well characterized, CAPN6 is also expressed in several regions of the developing brain. Recent studies have shown that genetic variants in CAPN6 significantly influence vascular endothelial growth factor (VEGF) activity, thereby affecting angiogenesis and the blood supply essential for fetal growth and development. Although CAPN6 lacks an MIM phenotype code, we hypothesize that it might be enumerated as a novel candidate gene contributing to neurodevelopmental disorders. Functional studies are imperative to elucidate the role of CAPN6 in placental function and its potential implications for neurodevelopmental processes. This work aims to inspire further research into the role of CAPN6 in placental biology and its relevance to neurodevelopmental disorders. Full article

Vibriosis, caused by diverse Vibrio species, is among the most devastating bacterial diseases in shrimp aquaculture. Consequently, breeding shrimp for pan-vibrios resistance (PVR) presents a crucial strategy for sustainable shrimp farming. In this work, we performed a GWAS in Litopenaeus vannamei to identify genetic loci underlying resistance to pan-vibrios and validate the identified SNPs. A total of 300 shrimp from nine different regions were subjected to a comprehensive challenge. Selective genotyping of 300 resistant and susceptible individuals was conducted using a specific length amplified fragment sequencing (SLAF-seq) approach. A total of 18,184,608 high-quality SNPs were detected across the whole genome of L. vannamei. Screening identified 283 SNPs located within genes, 26 of which were associated with the PVR trait. These SNPs were subsequently validated in verification group of 80 shrimps, leading to the identification of two genotypes (GG at SNP20 and AA at SNP21) and one genotype combination (GG/AA at SNP20 and SNP21) that were significantly associated with the PVR trait. Notably, these linked SNPs were identified in the intron of LvHEATR1 gene. The highest LvHEATR1 expression was observed in immune-related tissues including hemocytes, the gills, and the hepatopancreas. Furthermore, qPCR results showed that LvHEATR1 expression was significantly higher in the vibrios-resistant (RES) group than in the vibrios-susceptible (SUS) group. This study proposed the PVR concept and provided valuable molecular markers for the genetic improvement of vibrios-resistance in L. vannamei. Full article

Leishmania guyanensis is one of 15 American human-pathogenic species, frequently linked to therapeutic failure due to its marked genetic plasticity and adaptability under drug pressure. To broaden the genomic understanding of this species, its biological traits, and potential therapeutic alternatives, we sequenced the L. guyanensis strain MHOM/BR/75/M4147. Raw reads underwent quality-filtering and assembly. Taxonomic classification utilized BLASTn and Kraken2, confirming that 99.95% of contigs matched Leishmania. The assembled genome size was 31 Mb, with an N50 of 4743 bp and 40.85× coverage. Variant calling subsequently identified 36,665 SNPs, 8210 indels, and chromosomal aneuploidies. Genomic annotation identified 3119 proteins with known molecular functions in L. guyanensis, alongside 6371 orthologous genes shared with L. major and L. panamensis. The search for pharmacological relevance yielded ten candidate genes, including one calpain and nine GSK3 family members. Phylogenetic reconstruction using the polA1 gene consistently grouped L. guyanensis, demonstrating strong discriminatory capacity, with L. martiniquensis emerging as the most divergent species. Overall, these findings expand the available genomic framework for L. guyanensis and support advances in species-specific diagnostic approaches. Full article

Graves’ disease (GD) and Thyroid Eye Disease (TED) are autoimmune disorders characterized by significant heterogeneity in treatment response. Up to 50% of GD patients relapse after antithyroid drug (ATD) withdrawal, and a substantial portion of TED patients (20–50%) are resistant to first-line glucocorticoid (GC) therapy. This review evaluates the current evidence on epigenetic modifications as predictive biomarkers to guide personalized treatment. We synthesized recent findings (up to 2025) from PubMed, focusing on DNA methylation and microRNAs (miRNAs). For GD, ATD relapse risk is linked to a persistent “epigenetic memory” in T cells, notably the hypomethylation of Th17-associated genes. Circulating miRNA signatures, including miR-346, miR-23b-5p, and miR-92a-3p, also show promise in predicting remission. For TED, GC sensitivity is strongly correlated with specific circulating miRNAs. High pre-treatment levels of miR-146a predict a positive response (100% positive predictive value), while low levels of miR-224-5p predict non-responsiveness. While DNA methylation is confirmed in TED pathogenesis, its predictive role is unstudied. Major research gaps persist, particularly the near-total absence of data on histone modifications as predictive markers and the lack of epigenetic predictors for new biologics treatments, which currently rely on genetic or pharmacokinetic markers. Epigenetic biomarkers represent a promising frontier for stratifying patients and optimizing therapeutic strategies in Graves’ autoimmunity. Full article

Interim periods between peak and off-peak operations in urban rail transit networks often suffer from mismatched headways across lines, which increases passenger transfer waiting and operating costs. This paper proposes a passenger-oriented timetable synchronization method for network-wide interim period train service. In this study, based on the AFC data, passengers are assigned to the shortest travel time paths, and passenger transfer flows are linked to connecting train pairs by consideration of the maximum acceptable waiting time. As a result, the transfer waiting time is accurately calculated by matching passengers’ platform arrival times with the departures of feasible connecting trains. A mixed integer nonlinear programming model then jointly optimizes departure headways at each line’s first station, arrival and departure times at transfer stations, subject to safety headways and time bounds. The objective minimizes total cost, combining transfer waiting time cost and train operating cost (depreciation and distance-related cost). A simulated-annealing-based genetic algorithm (SA-GA) is designed to solve the NP-hard problem. A case study on the Nanjing rail transit network from 6:30 to 7:30 reduces total cost by 6.88%, including 3.77% lower transfer waiting time cost and 14.49% lower operating cost, and shows stable results under typical transfer demand fluctuations. Full article

Listeria monocytogenes is a persistent foodborne pathogen capable of surviving in food processing environments, often in association with diverse environmental microflora. This study examines genomic determinants of persistence, specifically stress adaptation and biofilm-associated traits, in environmental Listeria species and other environmental microflora from a dairy processing facility by analyzing whole-genome sequences of 6 environmental Listeria isolates, 4 ATCC reference strains, and 22 air and floor swab cultures, annotated using the RAST platform. Subsystem analysis revealed that Listeria isolates carried a defined set of genes linked to biofilm formation, antimicrobial resistance, and stress response, though in lower abundance than environmental cultures. Listeria exhibited fewer flagellar genes but greater consistency in core stress-related genes, including those for disinfectant and osmotic stress resistance, with SigB operon and RpoN genes highlighting strong stress tolerance. In contrast, environmental cultures exhibited broader transcriptional regulators (RpoE, RpoH) and greater diversity in acid and heat shock response genes, indicating distinct survival strategies. All examined Listeria species harbor biofilm and stress-resistance genes enabling independent survival, while environmental microbiota show greater genetic diversity that may promote persistence and multispecies biofilm formation. This study underscores the complex genetic landscape that may contribute to the persistence of Listeria and environmental microbiota in dairy processing environments, providing foundational insights for environmental cross contamination control strategies. Full article

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Among the genetic risk factors linked to AD, the Apolipoprotein E4 (ApoE4) remains the strongest. It is well known that carrying the ApoE4 isoform is associated with advanced AD pathology, blood–brain barrier (BBB) disruption, and changes in lipid metabolism. In this review, we provide an overview of the role of centrally and peripherally produced ApoE in AD. After this introduction, we focus on new findings regarding ApoE4’s effects on AD pathology and BBB function. We then discuss ApoE’s role in lipid metabolism in AD, highlighting examples of lipid changes caused by carrying the ApoE4 isoform. Next, the review explores the implications of ApoE4 isoforms for current treatments—whether they involve anti-amyloid therapy or other pharmacological agents used for AD—emphasizing the importance of personalized medicine approaches for patients with this high-risk allele. This review aims to provide an updated overview of ApoE4’s effects on AD pathology and treatment. By integrating recent discoveries, it underscores the critical need to consider ApoE4 status in both research and clinical settings to enhance therapeutic strategies and outcomes for individuals with AD. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a wide range of clinical manifestations modulated by genetic factors. The aim of this study was to identify genetic determinants of severe COVID-19 affecting protein sequence to gain insight into disease pathogenesis. Variants prioritized in two patients requiring lung transplant were tested in the Milan FOGS cohort (487/869 cases/controls), highlighting an independent association between the p.F8S low-frequency variant of interferon alpha receptor 2 gene (IFNAR2) and severe disease (OR = 1.73 [1.24–2.42], p = 0.001), replicated in the COVID-19 Host Genetics Initiative cohort (26,167/2,061,934 cases/controls). In the FOGS cohort, the p.F8S variant was linked to higher circulating IL-6 levels. In keeping, bulk transcriptomic analysis in PBMCs at the peak of infection (n = 57) showed that carriers of the p.F8S variant had upregulation of immune signaling and pathogens response (p < 0.05). Functional flow cytometry experiments in healthy donors (n = 12) revealed that membrane IFNAR2 protein expression was reduced in B lymphocytes, but higher in dendritic cells (p < 0.05). Finally, by interrogating a public scRNAseq resource of PBMC of people with COVID-19, we showed that p.F8S carriers had upregulation of immune pathways specifically in dendritic cells (p < 0.05). These results suggest that the p.F8S variant may influence COVID-19 severity by enhancing adaptive immune response, thereby favoring inflammation. Full article

Gastrointestinal nematode (GIN) infections are the most prevalent parasitic diseases in grazing sheep worldwide, causing significant productivity losses, high mortality and, as a result, economic losses and emerging animal welfare concerns. Conventional control strategies, primarily relying on anthelmintic treatments, face limitations due to rising drug resistance and environmental concerns, underscoring the need for sustainable alternatives. Selective breeding for host genetic resistance has emerged as a promising strategy, while recent advances in transcriptomics and integrative omics research are providing deeper insights into the immune pathways and molecular and genetic mechanisms that underpin host–parasite interactions. This review summarizes current evidence on transcriptomic signatures associated with resistance and susceptibility to H. contortus and T. circumcincta GIN infections, highlighting candidate genes, functional genetic markers, key immune pathways, and regulatory networks. Furthermore, we discuss how other omics approaches, including genomics, proteomics, metabolomics, microbiome, and multi-omics integrations, provide perspectives that enhance the understanding of the complexity of the GIN resistance trait. Transcriptomic studies, particularly using RNA-Sequencing technology, have revealed differential gene expression, functional genetic variants, such as SNPs and INDELs, in expressed regions and splice junctions, and regulatory long non-coding RNAs that distinguish resistance from susceptible sheep, highlighting pathways related to Th2 immunity, antigen presentation, tissue repair, and stress signaling. Genomic analyses have identified SNPs, QTL, and candidate genes linked to immune regulation and parasite resistance. Proteomic and metabolomic profiling further elucidates breed- and tissue-specific alterations in protein abundance and metabolic pathways, while microbiome studies demonstrate distinct microbial signatures in resistant sheep, suggesting a role in modulating host immunity. In conclusion, emerging multi-omics approaches and their integration strategies provide a comprehensive framework for understanding the complex host–parasite interactions that govern GIN resistance, offering potential candidate biomarkers for genomic selection and breeding programs aimed at developing sustainable, parasite-resistant sheep populations. Full article