Search Results (21,646)

Oncomodulin (OCM) is the most abundant Ca²⁺ buffering protein found in mature outer hair cells (OHCs). Cadherin 23 (CDH23) is a crucial component of the tip-links in hair cell stereocilia. The absence or dysfunction of these two proteins contributes to the early onset of age-related hearing loss (AHL). In this study, we investigated the effects of the Cdh23^753G→A mutation on OHC function using new Ocm-knockout (KO) mouse models (Ocm^tm1a/tm1a) with or without the Cdh23^753G→A mutation. Despite having the same genetic background, Ocm-KO mice carrying the Cdh23^753G→A mutation displayed a notable decline in OHC function across all measured frequencies as early as three months of age. In contrast, Ocm-KO mice without the Cdh23^753G→A mutation did not exhibit comparable hearing loss until they reached twelve months of age. Additionally, we examined the role of OCM in preserving OHC function under ototoxic stress induced by HPβCD (2-hydroxypropyl-β-cyclodextrin). The distortion product otoacoustic emission data show that the administration of HPβCD resulted in a more pronounced decline in OHC function in Ocm-KO mice compared to wild-type (WT) mice. Time-lapse recording also shows that HPβCD treatment led to greater structural deterioration and more rapid rupture events in OHCs from Ocm-KO mice than in those from WT mice. These findings suggest that the Cdh23^753G→A mutation, rather than other potential strain-specific genetic factors associated with AHL, significantly exacerbates the early onset of AHL phenotypes in Ocm-KO mice. Furthermore, our data indicates that the OCM protein in OHCs enhances their ability to withstand ototoxic stimuli. Full article

Sensorineural hearing loss (SNHL) can result from genetic mutations, excessive noise exposure, ototoxic drugs, and aging. Glutamate excitotoxicity is one of the underlying mechanisms of SNHL. However, the specific roles of different glutamate receptor subtypes in normal signaling and excitotoxic damage remain unclear. Addressing these questions requires relevant experimental models. This review compares existing protocols for the isolation and cultivation of primary spiral ganglion cells. It also evaluates the utility of this model for studying glutamatergic transmission and glutamate-induced excitotoxicity. A literature search was conducted in PubMed, Scopus, Google Scholar, and Web of Science. We identified 16 relevant English-language articles published since 1990, when the model was first used to study glutamatergic signaling. Our analysis reveals significant heterogeneity in spiral ganglion cell isolation protocols and culture conditions. We highlight major differences in glutamate concentrations and exposure times used to model excitotoxicity. The most significant limitation of this model is the loss of the native microenvironment of auditory neurons, including their dendritic and axonal contacts. Nevertheless, primary spiral ganglion cells serve as a suitable in vitro model for investigating auditory neuron function and pathology. The number of neurons and neurite length serve as reliable indicators of otoprotective effects under conditions of glutamate excitotoxicity. Based on an analysis of the key stages of primary SGC culture establishment, this study proposes approaches to overcome limitations and improve the practice of using this model. A better understanding of the function of glutamate receptors of SGNs and the mechanisms behind glutamate excitotoxicity could help us to develop new treatments for SNHL. This review serves as a practical guide for researchers implementing or optimizing primary SGC cultures. Full article

Tomato landraces possess distinct flavors, colors, textures and aromas, making them suitable for traditional cuisine. Tomato landraces contain a wide range of genes, including those involved in fruit quality, that can be isolated and used in local breeding programs. In regions recognized as centers of origin, domestication and diversification, traditional farmers play an important role in the preservation of tomato landraces adapted to local conditions and agricultural practices, on the whole maintaining high genetic diversity. This work aimed to evaluate the effects of the crop cycle (C), genotype (G) and C × G interactions on the contents of soluble solids, reducing sugars, lycopene, total polyphenols, flavonoids, and vitamin C, as well as the pH and antioxidant activity, in fifteen tomato landraces (genotypes) undergoing phenotypic selection and a commercial tomato variety (control). All the varieties were grown in two crop cycles under uniform greenhouse management using a randomized block design with four repetitions. Fruit composition was analyzed with AOAC and spectrophotometric methods. Significant differences (p ≤ 0.01) were detected in the soluble solid content, pH, flavor and maturity indices, polyphenol and flavonoid contents, and antioxidant activity between C, G and C × G interactions. In contrast, titratable acidity, reducing sugars, lycopene and vitamin C did not differ between cycles. Coefficients of phenotypic and genotypic variation and broad-sense heritability (H²) ranged from 4.3 to 33.7, 2.0 to 19.0, and 3.2 to 63.5%, respectively. H² for bioactive compounds ranged from moderate to slightly high (16.3–38.8%). These findings, supported by laboratory analyses, suggest that genotypes under agronomic selection have potential as parents to enhance fruit quality in current and future breeding programs. Full article

Pharmaceutical care provides the conceptual foundation for integrating pharmacogenetics into everyday pharmacy practice. Defined by Hepler and Strand as “the responsible provision of drug therapy for the purpose of achieving specific outcomes that improve a patient’s quality of life”, pharmaceutical care emphasizes a patient-centered approach in which the pharmacist collaborates with the patient, physician, and other healthcare professionals to design, implement, and monitor individualized therapeutic plans. In this context, pharmacogenetics can be regarded as an extension of pharmaceutical care: while the traditional model relies on monitoring patient outcomes and adherence, PGx adds a genetic dimension that allows treatment to be optimized from the very beginning. The pharmacist’s role therefore evolves from not only ensuring safe and effective use of medicines, but also interpreting genetic test results, supporting adherence to genetically guided therapy, and educating patients about the implications of their personal genetic profile. The introduction of pharmacogenetics testing as one of the potential services offered by community pharmacies is a promising proposition that may revolutionize the approach to drug therapy. Pharmacogenetics, a subset of pharmacogenomics, focuses on the study of DNA sequence variations that influence response to drugs. Thanks to advances in the field of genomics, it has become possible to study the genetic basis of variability in drug response. The identification of alleles responsible for the rapid or slow metabolism of xenobiotics has ushered in a new era in pharmacology. The aim of this interdisciplinary field, combining genetics and pharmacology, is to adapt treatment to a specific patient based on the analysis of their genome and gene polymorphism. Throughout the world, pharmacogenetics is gaining importance as a tool for personalizing medicine. In countries such as the United States, Canada, and the United Kingdom, programs integrating pharmacogenetics with healthcare are being developed. Clinical trials and the implementation of genetic tests into medical practice allow for better matching of medications and reducing the risk of side effects. Pharmacists will play a key role in integrating pharmacogenetics into healthcare. As specialists in the field of pharmacotherapy, they will support physicians in interpreting the results of genetic tests and adapting drug therapy to the individual needs of the patient. Additionally, pharmacists can educate patients and healthcare professionals about the benefits of pharmacogenetics and monitor the effects and safety of medications. Their involvement in the process of personalization of treatment may contribute to improving the effectiveness and safety of pharmacological therapies. Full article

Background: Gestation is a period of significant biological plasticity where the intrauterine environment influences fetal development via “fetal programming”. This study systematically reviews and meta-analyzes the association between genetic determinants—specifically the NR3C1, FKBP5, and CRHR1 genes, chosen for their pivotal role in the functional regulation and feedback sensitivity of the hypothalamic–pituitary–adrenal (HPA) axis—and stress reactivity during pregnancy. Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and Web of Science, yielding an initial total of 1430 records. After removing duplicates and screening 669 studies, a total of 34 primary observational studies were included in the systematic review and qualitative synthesis. For the quantitative synthesis, 27 articles provided sufficient data, resulting in k = 39 independent effect sizes analyzed via a mixed-effects model to account for tissue-specific and cohort-specific outcomes. Results: Systematic analysis reveals that maternal psychosocial stress significantly correlates with NR3C1 hypermethylation, acting as a biological mediator for neonatal cortisol dysregulation and hippocampal volume reduction. The FKBP5 rs1360780 polymorphism emerged as a key moderator of structural vulnerability, showing a “double-hit” effect when combined with epigenetic alterations. Furthermore, the study identifies sex-specific susceptibility, with divergent placental trajectories for male and female fetuses. Meta-analytic estimates confirmed the robustness of these associations (Rosenthal Fail-Safe N = 431,000), despite a general trend toward statistical significance (p = 0.079) in heterogeneous cohorts. Conclusions: The findings underscore a stable link between genetic determinants and prenatal stress reactivity. The interaction between molecular predisposition and environmental factors defines the health of the mother–infant dyad. These results advocate for a transition toward Precision Prenatal Medicine, integrating polygenic risk scores and epigenetic monitoring to implement early, targeted preventive interventions. Full article

Azo dyes demonstrate dose-dependent carcinogenic and mutagenic effects in exposed cells. Among remediation approaches, microbial adsorption is the most sustainable and environmentally friendly method for eliminating azo dyes. A novel Aspergillus terreus silica composite was developed as a sustainable adsorbent for crystal violet dye (CVD) removal. The fungal strain was isolated from dye wastewater and was genetically identified by 18S rRNA gene sequencing. Dried mycelia of A. terreus (PX920301) were combined with SiO₂ (1:1 w/w) through iterative hydration-drying cycles, yielding a composite characterized by FTIR analyses. Removal CVD %, adsorption capacity, and CVD residual were calculated, and the adsorption process was optimized using Box–Behnken design (four factors, 25 runs). The biosafety of the composite was assessed for phytotoxicity and microbial toxicity. The composite was also applied to real dyes wastewater collected from the bacteriological laboratory. Aspergillus terreus-silica composite showed the highest CVD removal percentage by 85.4%, adsorption capacity (qe) 121.1 mg/L, and lowest CVD residual by 7.26 mg/L, followed by the dried active mycelia (DA-mycelia) with CVD removal 40.23%, adsorption capacity (qe) 57.05 mg/L, and CVD residual by 29.73 mg/L. Optimization data cleared that the maximum experimental values of CVD removal (%) was 99.59% (predicted value 100%) obtained in run number (4) using initial CVD concentration (200 mg/L), pH (8), adsorbent composite weight (0.1 g), and contact time (48 h). Biosafety evaluation demonstrated negligible phytotoxicity against Triticum aestivum seedlings post-treatment, with restored germination and growth comparable to controls. Microbial toxicity assays via well-diffusion to seven microbial isolates confirmed no toxic activities against the tested bacteria, yeast, and fungi, underscoring the composite’s environmental safety. The composite could decolorize the real dye wastewater of laboratories by 95.37%. In conclusion, A. terreus mycelial-silica composite offers a cost-effective, sustainable, and eco-friendly alternative solution for dye bioremediation. Full article

White clover (Trifolium repens L.) is a major legume in Mediterranean agroecosystems. This study systematically evaluates 15 autochthonous white clover populations from the Trikala region of Greece, focusing on chemical composition and derived nutritional indices relevant for germplasm characterization and breeding. Fifteen local populations were evaluated under controlled pot cultivation over two consecutive years. Clonal plants were harvested at the early flowering stage. Key traits—crude protein (CP), Ash, Fat, crude fibre (FIBRE), acid detergent fibre (ADF), neutral detergent fibre (NDF), digestible dry matter (DDM), dry matter intake (DMI), and relative feed value (RFV)—were measured. Combined ANOVA revealed significant differences among populations for all traits (p ≤ 0.001), while genotype × year interactions were present but generally minor compared to genotypic effects. Broad-sense heritability was high across most traits (H² = 90.8–99.4%), demonstrating strong genetic control. CP showed positive correlations with DDM, DMI, and RFV, whereas ADF and NDF were negatively correlated with intake and digestibility. Canonical and discriminant analyses showed that a reduced set of traits (CP, Ash, FIBRE, RFV) contributed strongly to differentiation among populations. Hierarchical clustering (heatmap) confirmed these groupings based on fibre and digestibility-related traits. Populations such as Dendrochori and Gorgogyri consistently showed favorable chemical and nutritional profiles, while Fiki and Dendrochori showed the highest stability across years. The present study highlights substantial genetic variability among local white clover populations and identifies trait structures of relevance for germplasm characterization. These findings enhance the characterization of genetic diversity in Trifolium repens and support its potential use in future breeding research under Mediterranean environments. Full article

Background/Objectives: Adults with intellectual disability are known to experience complex health needs, including an elevated presence of chronic conditions. Cardiovascular risk factors are a concern, yet the evidence base is fragmented, and the scope and focus of current research are not well understood. Methods: We conducted a scoping review to map the existing evidence on cardiovascular risk factors among adults with intellectual disability. The review included studies reporting on risk factor prevalence as well as participant characteristics (ethnicity, living arrangements, age, sex, and type of disability). Cardiovascular-related outcomes were extracted to clarify the health disparities documented in this population. Results: Searches of seven databases for studies published from 2013 onward yielded 15,598records, of which 85 met the inclusion criteria. Evidence was dominated by cross-sectional studies, with a few randomized controlled trials. Hypertension, Type 2 diabetes and obesity were commonly reported. Patterns appeared to reflect lifestyle, medication effects, genetic syndromes—particularly Down syndrome and Prader–Willi syndrome—and the severity of the disability. A notable share of the studies originated from the United Kingdom and the United States. Findings reveal a complex cardiovascular risk profile, emphasizing the need for tailored prevention and management. Conclusions: Adults with intellectual disability face a substantial burden of cardiovascular risk factors. Evidence on effective interventions remains limited, highlighting a need for targeted, evidence-informed approaches to improve cardiovascular health and long-term outcomes. Full article

Background/Objectives: Malaria remains a major global health burden, particularly in sub-Saharan Africa, where the recent invasion and urban expansion of Anopheles stephensi are increasing transmission risk in densely populated areas. Conventional vector control strategies, including widespread insecticide application, are progressively losing efficacy due to the rapid spread of resistance. These limitations have accelerated the development of genetic control approaches aimed at either suppressing vector populations or replacing them with genetically modified mosquitoes incapable of transmitting pathogens, with the shared objective of reducing disease transmission. For population suppression strategies, an essential component is a conditional regulatory system that enables precise control of toxic or otherwise deleterious effector proteins. The most widely used platform, the tetracycline-dependent (Tet) system, modulates gene expression in response to tetracycline. However, this system can exhibit leaky expression and variable regulation, which may compromise its reliability and limit its application in certain contexts. The dihydrofolate reductase (DHFR) destabilization domain (DD) system, developed in Drosophila, offers an alternative strategy for post-translational control of protein stability. In this system, proteins fused to a destabilization domain are rapidly degraded unless stabilized by the small molecule trimethoprim (TMP), enabling tight and reversible control. In Drosophila and prior reports, this system has been associated with relatively low fitness costs, although such effects have not been systematically evaluated in mosquitoes. Before adapting this system for mosquito genetic control, it is therefore essential to assess the impact of TMP exposure on key life-history traits. Methods: Here, we assessed the effects of varying TMP concentrations on mosquito development, survival, and reproductive output. Results: Our results demonstrate that low concentrations of TMP exposure had no detectable effects on immature development, adult survival, or reproductive output under the conditions tested, supporting the implementation of the DHFR-DD system in mosquitoes. Importantly, these effects were dose-dependent, with moderate to high TMP concentrations producing measurable impacts on mosquito fitness. Conclusions: These findings provide a foundational step toward the development of more precise and reliable conditional expression systems for genetic vector control, advancing innovative strategies to mitigate malaria transmission in high-risk regions. Full article

The intensive use of agricultural inputs and the increasing incorporation of nano-materials into crop management practices raise concerns about their ecotoxicological interactions in plant systems. This study evaluated phytotoxicity, cytotoxicity, and genotoxicity in Allium cepa L. under experimental nano-agrochemical exposure scenarios combining two conventional nitrogen fertilizers—ammonium sulfate (AS) and urea—with silver nanoparticles (AgNPs). Biological responses were assessed across fertilizer concentrations (0.03–0.5 g/L), applied individually, simultaneously, and sequentially, to identify modulatory effects of AgNPs on plant proliferative activity and genomic stability. Results showed the relative stability of morphophysiological indicators associated with root growth, whereas cytogenetic biomarkers exhibited selective alterations under specific conditions. Significant increases in genetic damage markers were detected at intermediate ammonium sulfate concentrations, suggesting sublethal phytotoxicity windows not reflected by macroscopic growth parameters. In addition, modulation of the mitotic index and absence of generalized genotoxic effects in most combined or sequential treatments indicate that AgNPs primarily acted as modulators of proliferative responses rather than direct cytotoxic agents. Overall, these findings highlight the dynamic and non-linear nature of nano-agrochemical interactions in plant systems and underscore the importance of multibiomarker approaches for the early detection of genomic instability. The results provide experimental evidence relevant to the environmental risk assessment of nano-enabled fertilization strategies under realistic mixed-exposure scenarios. This study contributes to advancing the ecotoxicological understanding of emerging agricultural technologies and supports the need for further mechanistic research and field-based evaluations to guide the safe and sustainable use of nanomaterials in crop production. Full article

Background: Quantitative genetic analysis of image- or video-derived phenotypes is increasingly being performed for a wide range of traits. Pig body weight values estimated by a conventional approach or a computer vision system can be considered two different measurements of the same trait but with different sources of phenotyping error. Previous studies have shown that trait measurement error, defined as the difference between manually collected phenotypes and image-derived phenotypes, can be influenced by genetics, suggesting that the error is systematic rather than random and is more likely to lead to misleading quantitative genetic analysis results. Therefore, we investigated the effect of trait measurement error on the genetic analysis of pig body weight (BW). Results: Calibrated scale-based and image-based BW showed high coefficients of determination and goodness of fit. Genomic heritability estimates for scale-based and image-based BW were mostly identical across growth periods. Genomic heritability estimates for trait measurement error were consistently negligible, regardless of the choice of computer vision algorithm. In addition, genome-wide association analysis revealed no overlap between the top markers identified for scale-based BW and those associated with trait measurement error. Overall, the deep learning-based regressions outperformed the adaptive thresholding segmentation methods. Conclusion: This study showed that manually measured scale-based and image-based BW phenotypes yielded the same quantitative genetic results. We found no evidence that BW trait measurement error could be influenced, at least in part, by genetic factors. This suggests that trait measurement error in pig BW does not contain systematic errors that could bias downstream genetic analysis. Full article

Mosquito-borne infectious diseases remain a major challenge to public health, highlighting the need for efficient and accessible gene editing approaches. Receptor-mediated ovary transduction of cargo (ReMOT) offers an alternative to embryonic microinjection, in which P2C, an ovary-targeting peptide, enables ovarian delivery of the editing components. However, key design parameters and operational boundaries of the P2C-based ReMOT system have not been clearly defined. Here, we performed a methodological evaluation of the P2C-mediated ReMOT CRISPR/Cas9 system in Aedes aegypti. Cas9-P2C fusion proteins with different configurations were constructed and assessed through ovarian targeting assays, in vitro cleavage analyses, and in vivo gene editing experiments. Our results show that full-length Cas9-P2C fusion proteins exhibit nuclease activity and enable effective ovarian delivery. In contrast, linear truncation of the P2C peptide markedly reduced ovarian targeting, indicating a dependence on structural integrity. Using this delivery strategy, we generated kynurenine monooxygenase (KMO) edited mosquitoes, demonstrating feasibility under the conditions tested. In addition, protein injection was also associated with reduced reproductive performance, providing physiological reference for ReMOT applications. Overall, this study defines the key design parameters and operational boundaries of the P2C-based ReMOT system, providing methodological guidance for its application and optimization in future mosquito genetic studies. Full article

Background: Most patients with hepatocellular carcinoma (HCC) present with advanced disease and have limited systemic treatment options. Oxaliplatin shows clinical activity in HCC but its effectiveness is frequently curtailed by intrinsic and acquired resistance. We sought to systematically identify genetic vulnerabilities that increase oxaliplatin sensitivity in HCC. Methods: Genome-scale negative-selection CRISPR–Cas9 screens were conducted in two genetically distinct HCC cell lines (Hep3B and MHCC-97H) under low-dose oxaliplatin to discover conserved determinants of sensitivity. Selected DNA damage response (DDR) hits were validated. An oxaliplatin-resistant MHCC-97H subline was generated for transcriptomic profiling to characterize resistance-associated programs. Screen results were integrated with TCGA-LIHC expression and survival data to evaluate clinical relevance. Additionally, we analyzed bulk RNA-seq data from biopsy specimens collected from 36 HCC patients prior to initiation of hepatic arterial infusion chemotherapy (HAIC), comparing expression levels of the DDR genes between patients with objective response and non-responders. Results: Screens in both cell lines converged on DDR pathways, particularly nucleotide excision repair (NER) and the Fanconi anemia/interstrand crosslink repair network; shared sensitizers included ERCC4 (XPF), FANCE and SLX4. Validation experiments showed that disruption of representative DDR factors (POLH and XPA) synergistically increased oxaliplatin efficacy at concentrations as low as 0.5 μM. Transcriptomic analysis of the resistant MHCC-97H subline revealed coordinated upregulation of DNA repair programs, G2/M checkpoint and E2F target signatures, and epithelial–mesenchymal transition features. Integration with TCGA-LIHC data demonstrated frequent overexpression of many screen-identified DDR genes in primary HCC and an association between higher expression of selected factors and poorer patient survival. In the HAIC cohort, several DDR genes, including ATR, BRCA2, CDK7, MUS81, MUTYH, PARG, POLH, POLK and XPA, were significantly lower in the objective response group. Conclusions: DDR components represent candidate biomarkers and therapeutic targets whose inhibition may enhance oxaliplatin efficacy in HCC. Full article

This article is an in-depth analysis of the performance and efficiency of various control systems used in quadrotor unmanned aerial vehicles (UAVs). The study is focused on the comparison of three main control approaches, including Sliding Mode Control (SMC), Fuzzy Logic Control (FLC), and an extended version of Sliding Mode Control with the use of the Gray Wolf Optimizer (SMC-GWO), as well as a supportive validation model the Genetic Algorithm (SMC-GA). Based on the Newton–Euler formulation, the mathematical model of a quadrotor has been developed to provide a true picture of the dynamic behavior of the quadrotor. The model was then implemented in MATLAB/Simulink 2025b to test the performance of the system in its nominal and perturbed conditions. The findings have shown that the hybrid SMC-GWO controller has significant improvement in response speed, accuracy, and stability compared to the other controllers. Precisely, the SMC-GWO demonstrated 78.46 percent decrease in rise time and 23.40 percent decrease in settling time compared to the traditional SMC, as well as a nearly negligible steady-state error (SSE = 0.0008) in the roll channel. The proposed controller in the pitch channel reduced the rise time by 93.65 percent and the settling time by 20.22 percent, with a much smoother and more stable tracking and an effectively negligible steady-state error (SSE = 0.0001). The hybrid controller in the yaw channel had a 77.94 percent better rise time and 23.16 percent better settling time, resulting in a steady-state error of 0.0022. In relation to altitude control, SMC -GWO decreased the rise time by 91.87 percent and settling time by 25.04 percent over classical SMC, yet the steady-state error was almost zero. Under constant, time-varying actuator disturbances, the SMC-GWO controller also demonstrated better system stabilization and trajectory-tracking behavior than both SMC and FLC, as well as slightly better behavior than SMC-GA in the presence of faults and disturbances. These results verify that a UAV control framework based on the combination of the Gray Wolf Optimizer and Sliding Mode Control is more resilient, quick, and significantly more precise. Full article

Sunflower downy mildew, caused by Plasmopara halstedii, remains one of the most destructive diseases worldwide. The genetic diversity of P. halstedii populations continues to challenge resistance breeding efforts. This study evaluates the effectiveness of key resistance genes against P. halstedii isolates collected in Hungary. Eight isolates were tested using the sunflower differential lines HA-335, RHA-419, and RHA-340, with the resistance genes Pl6, Pl_Arg, and Pl8, respectively. Disease development was assessed by observing sporulation and symptoms including stunting, chlorosis, damping-off, and abnormal development at three time points after inoculation. Plant height was also measured to evaluate growth responses. The Pl6 resistance gene (HA-335) did not provide effective protection against any of the tested isolates, indicating that Pl6 does not confer reliable resistance against the Hungarian isolates examined in this study. The resistance conferred by Pl8 was not uniformly effective against the Hungarian isolates tested. This study provides the first report of Pl8-virulent P. halstedii isolates identified in both Hungary and Central Europe. The resistance gene Pl_Arg (RHA-419) conferred resistance to all tested P. halstedii isolates. These findings highlight the changing virulence profiles of P. halstedii populations in Hungary, emphasizing the need for ongoing pathogen monitoring and strategic use of resistance genes. Full article