Search Results (1,212)

Hereditary ataxias are a highly heterogenous group of diseases characterized by loss of coordination. In this study, we investigated a family of random-bred dogs, in which two siblings were affected by a slowly progressive ataxia. They presented with clinical signs of progressive cerebellar ataxia, hypermetria, and absent menace response. The MRI revealed generalized brain atrophy, reduced cortical demarcation, hypoplastic corpus callosum, and cerebellar folia thinning, highly suggestive of a neurodegenerative disorder. We sequenced the genomes of the two affected dogs and their unaffected parents. Filtering for protein-changing variants that had homozygous alternate genotypes in the affected dogs, heterozygous genotypes in the parents, and homozygous reference genotypes in 1576 control genomes yielded a single missense variant in the RAB24 gene, XM_038534663.1:c.239G>T or XP_038390591.1:p.(Gly80Val). Genotypes at this variant showed the expected co-segregation with the ataxia phenotype in the investigated family. The predicted amino acid affects the conserved RabF4 motif. Glycine-80 resides at the protein surface and the introduction of a hydrophobic isopropyl side chain of the mutant valine might impede solvent accessibility. Another missense variant in RAB24, p.Glu38Pro, was previously reported to cause a clinically similar form of cerebellar ataxia in Gordon Setters and Old English Sheepdogs. Taken together, the available data suggest that RAB24:p.Gly80Val represents the causal variant in the studied dogs. To the best of our knowledge, this is only the second report of a potentially pathogenic RAB24 variant in any species and further supports that RAB24 should be considered a candidate gene in human ataxia patients with unclear molecular etiology. Full article

Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original human clinical and animal research studies were included; titles and abstracts were manually scanned for relevance to the effect of parental smoking on offspring reproductive outcomes (Date of search:18/03/2025). Results: This systematic review incorporates 30 studies identified from three databases (PubMed, Web of Science, and Scopus). The results indicate that male offspring exhibit reduced spermatogenic capacity, characterized by decreased testicular size, lower sperm count, and impaired hormonal biosynthesis, with reductions of 30–40% in sperm production. Dual-parental smoking exacerbates these effects, with sperm counts averaging 85 million per ml in human male offspring from dual-smoking households, compared to 111 million per ml in single-smoking households. Animal studies provide mechanistic insights, revealing reduced testis weight in nicotine-exposed male rats and increased oxidative stress in offspring. Conclusions: This review highlights the dose-dependent and sex-specific effects of smoking on the fertility of offspring and underscores the need for standardized protocols to enhance the consistency and comparability of future research in both human and animal studies. Full article

Conventional methods for generating knock-out or knock-in mammalian cell models using CRISPR-Cas9 genome editing often require tedious single-cell clone selection and expansion. In this study, we develop and optimise rapid and robust strategies to engineer homozygous fluorescent reporter knock-in cell pools with precise genome editing, circumventing clonal variability inherent to traditional approaches. To reduce false-positive cells associated with random integration, we optimise the design of donor DNA by removing the start codon of the fluorescent reporter and incorporating a self-cleaving T2A peptide system. Using fluorescence-assisted cell sorting (FACS), we efficiently identify and isolate the desired homozygous fluorescent knock-in clones, establishing stable cell pools that preserve parental cell line heterogeneity and faithfully reflect endogenous transcriptional regulation of the target gene. We evaluate the knock-in efficiency and rate of undesired random integration in the electroporation method with either a dual-plasmid system (sgRNA and donor DNA in two separate vectors) or a single-plasmid system (sgRNA and donor DNA combined in one vector). We further demonstrate that coupling our single-plasmid construct with an integrase-deficient lentivirus vector (IDLV) packaging system efficiently generates fluorescent knock-in reporter cell pools, offering flexibility between electroporation and lentivirus transduction methods. Notably, compared to the electroporation methods, the IDLV system significantly minimises random integration. Moreover, the resulting reporter cell lines are compatible with most of the available genome-wide sgRNA libraries, enabling unbiased CRISPR screens to identify key transcriptional regulators of a gene of interest. Overall, our methodologies provide a powerful genetic tool for rapid and robust generation of fluorescent reporter knock-in cell pools with precise genome editing by CRISPR-Cas9 for various research purposes. Full article

Exosomes are nanoscale extracellular vesicles (EVs) that carry biomolecular signatures reflective of their parent cells, making them powerful tools for non-invasive diagnostics and therapeutic monitoring. Despite their potential, clinical application is hindered by challenges such as low abundance, heterogeneity, and the complexity of biological samples. To address these limitations, plasmonic biosensing technologies—particularly propagating surface plasmon resonance (PSPR), localized surface plasmon resonance (LSPR), and surface-enhanced Raman scattering (SERS)—have been developed to enable label-free, highly sensitive, and multiplexed detection at the single-vesicle level. This review outlines recent advancements in nanoplasmonic platforms for exosome detection and profiling, emphasizing innovations in nanostructure engineering, microfluidic integration, and signal enhancement. Representative applications in oncology, neurology, and immunology are discussed, along with the increasingly critical role of artificial intelligence (AI) in spectral interpretation and diagnostic classification. Key technical and translational challenges—such as assay standardization, substrate reproducibility, and clinical validation—are also addressed. Overall, this review highlights the synergy between exosome biology and plasmonic nanotechnology, offering a path toward real-time, precision diagnostics via sub-femtomolar detection of exosomal miRNAs through next-generation biosensing strategies. Full article

This paper examines the importance of ‘education outside the classroom’ (EOtC) in an Australian secondary school. The primary aim was to develop a sense of belonging, build resilience, and enhance wellbeing in female students. This study investigated two cohorts of Year 9 students (aged 14–15 yrs) who participated in a four-week residential EOtC pilot program. The first cohort (Wave 1; N = 58) undertook the program alongside (N = 39) boys. The second cohort was single-sex girls (Wave 2; N = 28). A mixed-methods research design was implemented to inform experiences of students, parents, and staff and to triangulate inferences drawn from the data. Quantitative data was gained from pre- and post-program surveys with students and parents, whilst qualitative data was gathered from student focus groups, staff, and parents through semi-structured interviews to assess more nuanced impacts. School belonging was measured using the PISA six-item scale. Academic buoyancy was quantified using the four-item Academic Buoyancy Scale. Self-efficacy, peer relations, and resilience were evaluated by employing the 34-item Adolescent Girls’ Resilience Scale. The findings revealed significant improvements in students’ sense of belonging, including higher levels of school belonging than reported Australia-wide averages for 15-year-olds. Despite students’ mean academic buoyancy scores being more than a point lower than reported baseline scores for Australian high school students, it was promising to see a modest increase following the EOtC program. In conclusion, EOtC is a potent vehicle for developing a sense of belonging, enhancing resilience, and equipping students to deal with academic challenges. Full article

This study examines how U.S. immigration policies enact legal violence and multigenerational punishment through the spousal reunification process, particularly in mixed-status, transnational families. Building on the concept of “deportability,” we introduce “importability” to describe a beneficiary’s potential to secure permanent residency, which varies according to social markers such as race, gender, and region of origin. Drawing from a content analysis of threads on the Immigration Pathways (IP) web forum, we analyze discussions among U.S. citizen petitioners navigating marriage-based green card applications, with a focus on experiences involving administrative processing (AP) (i.e., marriage fraud investigations). Our findings show that couples who do not align with the state’s conception of “proper” family—particularly U.S. citizen women petitioning for Black African partners—face intensified scrutiny, long delays, and burdensome requirements, including DNA tests and surveillance. These bureaucratic obstacles produce prolonged family separation, financial strain, and diminished sense of belonging, especially for children in single-parent households. Through the lens of “importability,” we reveal how legal violence and multigenerational punishment of immigration policies on mixed-status families beyond deportation threats, functioning as a gatekeeping mechanism that disproportionately affects marginalized families. This research highlights the understudied consequences of immigration policies on citizen petitioners and contributes to a broader understanding of inequality in U.S. immigration enforcement. Full article

This study investigates the complex relationship between levels of religiosity and attitudes toward secularization among individuals receiving higher religious education in Türkiye. Secularization is defined as the diminishing influence of religion in public life and the rise of critical attitudes toward religious norms, a process that accelerated particularly during the modernization period following the establishment of the Republic. The primary aim of the research is to analyze whether there is a significant relationship between secular attitudes and the perceived influence of Islam among theology faculty students. The study employs a quantitative, descriptive survey design and includes a sample of 380 undergraduate, graduate, and doctoral students from the faculties of theology at Kocaeli, Sakarya, Marmara, and Istanbul universities. Data were collected using the “Perceived Influence of Religion Scale” and the “Secular Attitude Scale,” both of which demonstrated acceptable reliability (Cronbach’s Alpha = 0.70). Demographic variables such as age, gender, marital status, parental education level, type of education (formal or distance), and economic status were also incorporated into the analysis. The findings revealed statistically significant differences based on marital status, parental education level, type of education program, and previous educational background. For instance, single students reported perceiving a higher influence of religion compared to their married counterparts, while students with fathers who held university degrees perceived a lower influence of religion. These results offer valuable insights into how modern social transformations influence religious attitudes and practices. Full article

Juvenile substance use continues to be well researched. Prior research suggests that youth substance use can have far-reaching impacts. While several causes of substance use have been explored, including parental supervision and family structure, it is unclear if caregiver type can impact a juvenile’s substance-using behavior. The current study uses school-level data to examine self-reported substance use among youth who reside with both biological parents, a single parent, custodial grandparent(s), or other caregiver types. The results identify significant differences in self-reported substance use across primary caregiver types. These findings have implications for specific substance use prevention programs to target youth who reside in custodial grandparent-headed households. Full article

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental condition typically requiring information from multiple informants for accurate diagnosis. However, the consistency and diagnostic value of reports from teachers, parents, primary care providers (PCPs), and other professionals remain debated. This study aimed to examine the role and diagnostic accuracy of different informants in the referral and diagnostic process for ADHD in children aged 3–11. Methods: This retrospective study analyzed data from 120 children referred for suspected ADHD. Initial reports were obtained from teachers, parents, PCPs, and other professionals, and final diagnoses were determined through comprehensive neuropsychiatric evaluations. Diagnostic concordance and informant-specific contributions were assessed. Results: Of the 120 children, 64 (53.3%) received an ADHD diagnosis. Teachers were the most frequent informants, followed by parents, with fewer referrals from PCPs and other professionals. No significant differences in diagnostic accuracy were found among informants, aligning with previous studies suggesting that no single informant is superior in identifying ADHD. Notably, over 93% of referred children were diagnosed with a neuropsychiatric disorder, though not necessarily ADHD. Conclusions: The findings underscore the importance of combining reports from parents and teachers to capture symptom expression across different environments, which is essential for accurate ADHD diagnosis. Enhanced training for informants and a multidisciplinary approach is recommended to improve diagnostic accuracy and support early identification and intervention efforts. These results support nuanced evaluation strategies that account for informant variability and help mitigate potential misinterpretations of ADHD symptoms. Full article

The reaction of either the L (2S3R) or D (2R3S) enantiomers of H₂N-C*H(R)CO₂⁻ (R = -C*H(OH)CH₃ or -C*H(OH)CH(CH₃)₂) and the L (2S) or D (2R) enantiomers of H₂N-C*H(C(CH3)₂OH)CO₂⁻ with imidazole-4-carboxaldehyde and nickel(II) acetate in methanol yields a single stereoisomer of an oxazolidine. There is retention of chirality on ring positions 4 and 5 (if C_β is chiral) of the oxazolidine, C_α and C_β of the parent amino acid, and transfer of chirality to the newly generated stereogenic centers, ring positions 3, the amino acid nitrogen atom, N_AA, and 2, the aldehyde carbon atom, C_ald. Specifically, when C_α has an S configuration, both N_AA and C_ald are formed as R. Likewise, a C_α which is R results in both N_AA and C_ald being formed as S. For example, the reaction of L threonine (C_α is S and C_β is R) with 4-imidazolecarboxaldehyde in the presence of nickel(II) gives the facial Λ NiL₂, where L is (2R, 3R, 4S, 5R) 4-carboxylato-5-methyl-2-(4-imidazolyl)-1,3-oxazolidine. The same reaction with D threonine produces the enantiomeric Δ complex of (2S, 3S, 4R, 5S) 4-carboxylato-5-methyl-2-(4-imidazoyl)-1,3-oxazolidine. The high stereospecificity is thought to be based on the fused three-ring structure of the characterized nickel complexes in which the hydrogen atoms of C_α, N_AA, and C_ald must be cis to one another. Identical reactions occur with 2-pyridine carboxaldehyde and LT or DT. In contrast, the reactions of L allo threonine (2S3S) and the primary alcohols, L or D serine, give the conventional meridionally coordinated aldimine product. Full article

Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major threat to global rice productivity. Although hybrid rice breeding has significantly enhanced yields, persistent genetic vulnerabilities within restorer lines continue to compromise BB resistance. This study addresses this challenge by implementing functional marker-assisted selection (FMAS) to pyramid two broad-spectrum resistance (R) genes, Xa21 and Xa23, into the elite, yet BB-susceptible, restorer line K608R. To enable precise Xa23 genotyping, we developed a novel three-primer functional marker (FM) system (IB23/CB23/IR23). This system complements the established U1/I2 markers used for Xa21. This recombination-independent FMAS platform facilitates simultaneous, high-precision tracking of both homozygous and heterozygous alleles, thereby effectively circumventing the linkage drag limitations typical of conventional markers. Through six generations of marker-assisted backcrossing followed by intercrossing, we generated K608R2123 pyramided lines harboring both R genes in homozygous states, achieving a recurrent parent genome recovery rate of 96.93%, as determined by single nucleotide polymorphism (SNP) chip analysis. The pyramided lines exhibited enhanced resistance against six virulent Xoo pathogenic races while retaining parental yield performance across key agronomic traits. Our FMAS strategy overcomes the historical trade-off between broad-spectrum resistance and the preservation of elite phenotypes, with the developed lines exhibiting resistance coverage complementary to that of both introgressed R genes. This integrated approach provides breeders with a reliable molecular tool to accelerate the development of high-yielding, disease-resistant varieties, demonstrating significant potential for practical deployment in rice improvement programs. The K608R2123 germplasm represents a dual-purpose resource suitable for both commercial hybrid seed production and marker-assisted breeding programs, and it confers synergistic resistance against diverse Xoo races, thereby providing a pivotal breeding resource for sustainable BB control in epidemic regions. Full article

Background: Youth tobacco use remains a significant public health concern, particularly in urban communities disproportionately burdened by health disparities. In Baltimore City, where tobacco-related harms are elevated, understanding the relationship between tobacco use—including e-cigarettes—and mental health among high school students is essential for guiding equitable prevention and cessation strategies. The CEASE (Communities Engaged and Advocating for a Smoke-free Environment) program, in collaboration with the American Lung Association’s Not On Tobacco (N-O-T) initiative, developed an online school-based survey to inform community-responsive interventions. Aims: This study aimed to examine the associations between cigarette use, including conventional cigarette use, and self-rated mental health among high school students in Baltimore City. Methods: High school students in Baltimore City completed an anonymous online survey that assessed demographic characteristics, tobacco knowledge and use, mental health, and related behaviors. Self-rated mental health was dichotomized as poor versus fair/good. Tobacco use categories included current use of e-cigarettes and conventional cigarettes. Logistic regression models were used to examine associations between tobacco use and self-rated mental health, adjusting for age, gender, race, and parental education. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results: No statistically significant associations were found between self-rated mental health and e-cigarette use and conventional tobacco use after adjusting for covariates. Conclusions: The absence of a significant association may reflect unique aspects of the social context in Baltimore City, where youth may not use tobacco products as a coping mechanism for mental health challenges. Alternatively, it may be due to limitations in measurement, particularly the use of a single-item mental health assessment. These findings should be considered preliminary. Future research using more comprehensive mental health measures and larger samples is warranted to further explore these complex relationships. Full article

Non-Native Tree Species (NNTs) play crucial roles in global and European forests. However, in the Czech Republic, NNTs represent a tiny fraction of the forested areas due to limited research on their potential use. The country is actively afforesting abandoned agricultural lands; NNTs which are already tested and certified could enhance the country’s forestry system. This study aimed to evaluate the initial growth of Castanea sativa, Platanus acerifolia, and Corylus colurna under three soil treatments on abandoned agricultural soil, evaluate the survival and mortality of the tree species, and further compare the soil dynamics among the three ecosystems to describe the initial state and short-term changes in the soil environment. The research plot was set in the Doubek area, 20 km East of Prague. Moreover, soil-improving materials, Humac (1.0 t·ha⁻¹) and Alginite (1.5 t·ha⁻¹), were established on the side of the control plot at the afforested part. The heights of plantations of tree species were measured from 2020 to 2024. Furthermore, 47 soil samples were collected at varying depths from three ecosystems (afforested soil, arable land, and old forest) in 2022. A single-factor ANOVA was run, followed by a post hoc test. The result shows that the Control-C plot (Castanea Sativa + Platanus acerifolia + Corylus colurna + agricultural soil without amendment) had the highest total growth (mean annual increment in the year 2024) for Castanea sativa (KS = 40.90 ± a21.61) and Corylus colurna (LS = 55.62 ± 59.68); Alginite-A (Castanea Sativa + Platanus acerifolia + Corylus colurna + Alginite) did best for Platanus acerifolia (PT = 39.85 ± 31.52); and Humac-B (Castanea Sativa + Platanus acerifolia + Corylus colurna + Humac) had the lowest growth. Soil dynamics among the three ecosystems showed that the old forest (plot two) significantly differs from arable soil (plot one), Humac and Platanus on afforested land (plot three), Platanus and Alginite on afforested land (plot four), and Platanus without amendment (plot five) in horizon three (the subsoil or horizon B) and in horizon four (the parent material horizon or horizon C). Results document the minor response of plantations to soil-improving matters at relatively rich sites, good growth of plantations, and initial changes in the soil characteristics in the control C plot. We recommend both sparing old forests and the afforestation of abandoned agricultural soils using a control treatment for improved tree growth and sustained soil quality. Further studies on the species’ invasiveness are needed to understand them better. Full article

Background/Objective: Cerivastatin (Cer), a cholesterol-lowering statin, was withdrawn from the market due to fatal cases of rhabdomyolysis, particularly when co-administered with gemfibrozil (Gem), a strong CYP2C8 inhibitor. However, the pharmacokinetic (PK) mechanisms underlying these adverse events remain unclear. This study investigates the impact of drug–drug interactions (DDIs) involving Gem and itraconazole (Itr), a potent CYP3A4 inhibitor, on plasma concentrations of Cer and its major metabolites—M23, M1, and cerivastatin lactone (Cer-L)—with a focus on the risk of excessive Cer-L accumulation. Methods: We applied a newly developed Metabolite-Linked Model that simultaneously characterizes parent drug and metabolite kinetics by estimating metabolite formation fractions (f_M) and elimination rate constants (K_eM). The model was calibrated using observed DDI data from Cer + Gem and Cer + Itr scenarios and then used to predict outcomes in an untested Cer + Gem + Itr combination. Results: The model accurately reproduced observed metabolite profiles in single-inhibitor DDIs. Predicted AUCR values for Cer-L were 4.2 (Cer + Gem) and 2.1 (Cer + Itr), with reduced K_eM indicating CYP2C8 and CYP3A4 as primary elimination pathways. In the dual-inhibitor scenario, Cer-L AUCR reached ~70—far exceeding that of the parent drug—suggesting severe clearance impairment and toxic accumulation. Conclusions: Dual inhibition of CYP2C8 and CYP3A4 may cause dangerously elevated Cer-L levels, contributing to Cer-associated rhabdomyolysis. This modeling approach offers a powerful framework for evaluating DDI risks involving active or toxic metabolites, supporting safer drug development and regulatory assessment. Full article

This study investigates the factors affecting the choice of school travel mode among students in Mersin, Türkiye, focusing on walking, private car, public transit and school bus. A two-step modeling approach was adopted. First, a latent class cluster analysis (LCCA) was applied to identify subgroups of students with similar characteristics. Then, separate multinomial logit (MNL) models were estimated for each cluster. The data come from the 2022 Urban Transport Master Plan household survey and include 2798 students from 2092 households. The results show that trip distance is the most consistent and significant factor across all clusters, as increasing distance makes students more likely to use motorized modes instead of walking. Gender also demonstrates a consistent influence in specific clusters, where male students are less likely to travel by private car. Similarly, residing in a single-family house consistently increases the likelihood of car use in multiple clusters. Conversely, the influence of household structure, parental education, income, and household size differs significantly between clusters, underlining the importance of considering group-level differences in school travel behavior. These findings suggest that policies aiming to promote sustainable school travel should be sensitive to the needs of different student groups. Integrating land use and transportation planning may help to support active and shared modes of travel. Full article