Search Results (290)

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Background/Objectives: Global warming and rising CO₂ concentrations pose significant challenges to plant systems. Amid these pressures, this study contributes to understanding how tropical species respond by simultaneously evaluating reproductive and genetic traits. It specifically investigates the effects of maternal exposure to warming and elevated CO₂ on progeny physiology, genetic diversity, and population structure in Stylosanthes capitata, a resilient forage legume native to Brazil. Methods: Maternal plants were cultivated under controlled treatments, including ambient conditions (control), elevated CO₂ at 600 ppm (eCO₂), elevated temperature at +2 °C (eTE), and their combined exposure (eTEeCO₂), within a Trop-T-FACE field facility (Temperature Free-Air Controlled Enhancement and Free-Air Carbon Dioxide Enrichment). Seed traits (seeds per inflorescence, hundred-seed mass, abortion, non-viable seeds, coat color, germination at 32, 40, 71 weeks) and abnormal seedling rates were quantified. Genetic diversity metrics included the average (A) and effective (Ae) number of alleles, observed (Ho) and expected (He) heterozygosity, and inbreeding coefficient (Fis). Population structure was assessed using Principal Coordinates Analysis (PCoA), Analysis of Molecular Variance (AMOVA), number of migrants per generation (Nm), and genetic differentiation index (Fst). Two- and three-way Analysis of Variance (ANOVA) were used to evaluate factor effects. Results: Compared to control conditions, warming increased seeds per inflorescence (+46%), reduced abortion (−42.9%), non-viable seeds (−57%), and altered coat color. The germination speed index (GSI +23.5%) and germination rate (Gr +11%) improved with warming; combined treatments decreased germination time (GT −9.6%). Storage preserved germination traits, with warming enhancing performance over time and reducing abnormal seedlings (−54.5%). Conversely, elevated CO₂ shortened GSI in late stages, impairing germination efficiency. Warming reduced Ae (−35%), He (−20%), and raised Fis (maternal 0.50, progeny 0.58), consistent with the species’ mixed mating system; A and Ho were unaffected. Allele frequency shifts suggested selective pressure under eTE. Warming induced slight structure in PCoA, and AMOVA detected 1% (maternal) and 9% (progeny) variation. Fst = 0.06 and Nm = 3.8 imply environmental influence without isolation. Conclusions: Warming significantly shapes seed quality, reproductive success, and genetic diversity in S. capitata. Improved reproduction and germination suggest adaptive advantages, but higher inbreeding and reduced diversity may constrain long-term resilience. The findings underscore the need for genetic monitoring and broader genetic bases in cultivars confronting environmental stressors. Full article

Background/Objectives: Maternal exposures are known to influence the risk of isolated cleft lip with or without cleft palate (CL/P)—a common and highly heritable birth defect with a multifactorial etiology. Methods: To identify new risk loci, we conducted a genome-wide gene–environment interaction (GEI) analysis of CL/P with maternal smoking and vitamin use in Filipinos (N_cases = 540, N_controls = 260). Since GEI analyses are typically low in power and the results can be difficult to interpret, we applied multiple testing frameworks to evaluate potential GEI effects: a one degree-of-freedom (1df) GxE test, the 3df joint test, and the two-step EDGE approach. Results: While no genome-wide significant interactions were detected, we identified 11 suggestive GEIs with smoking and 24 with vitamin use. Several implicated loci contain biologically plausible genes. Notable interactions with smoking include loci near FEZF1, TWIST2, and NET1. While FEZF1 is involved in early neuronal development, TWIST2 and NET1 regulate epithelial–mesenchymal transition, which is required for proper lip and palate fusion. Interactions with vitamins encompass CECR2—a chromatin remodeling protein required for neural tube closure—and FURIN, a critical protease during early embryogenesis that activates various growth factors and extracellular matrix proteins. The activity of both proteins is influenced by folic acid. Conclusions: Our findings highlight the critical role of maternal exposures in identifying genes associated with structural birth defects such as CL/P and provide new paths to explore for CL/P genetics. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

The cryopreservation of rabbit semen is a valuable strategy for genetic resource preservation and efficient artificial insemination, but outcomes remain inconsistent, partly due to variations in sperm concentration per dose. This study aimed to evaluate the in vivo effects of different sperm concentrations (15, 25, 35, 55, and 75 million per straw) on fertility, prolificacy, and offspring growth in nulliparous and multiparous does. A total of 384 rabbit females were inseminated using frozen–thawed semen, and their reproductive performance was compared with fresh semen. Fertility and kindling rates varied with sperm concentration and parity: nulliparous does showed the highest fertility at 15 million sperm/straw (84.4%), while multiparous does reached peak values at 25–55 million/straw (78.1–81.3%). Litter size and live-born kits were consistently higher in multiparous than in nulliparous does. Offspring body weight at 19 and 60 days was influenced by both sperm concentration and maternal parity, with better growth generally observed in multiparous groups. Weaning success remained high across all groups. Our results indicate that sperm concentrations ranging from 15 to 35 × 10⁶/straw are the most suitable for cryopreservation, as they maintain high fertility, prolificacy, and offspring growth, comparable to fresh semen. These results confirm that optimizing sperm concentration during cryopreservation improves reproductive efficiency and that tailoring insemination strategies to the physiological status of the female enhances outcomes. The results provide useful recommendations for improving cryopreservation techniques in rabbit breeding programs. Full article

Reproductive efficiency is a critical determinant of productivity and profitability in sheep farming. Traditional selection methods have largely relied on phenotypic traits and historical reproductive records, which are often limited by subjectivity and delayed feedback. Recent advancements in artificial intelligence (AI), including video tracking, wearable sensors, and machine learning (ML) algorithms, offer new opportunities to identify behavior-based indicators linked to key reproductive traits such as estrus, lambing, and maternal behavior. This review synthesizes the current research on AI-powered behavioral monitoring tools and proposes a conceptual model, ReproBehaviorNet, that maps age- and sex-specific behaviors to biological processes and AI applications, supporting real-time decision-making in both intensive and semi-intensive systems. The integration of accelerometers, GPS systems, and computer vision models enables continuous, non-invasive monitoring, leading to earlier detection of reproductive events and greater breeding precision. However, the implementation of such technologies also presents challenges, including the need for high-quality data, a costly infrastructure, and technical expertise that may limit access for small-scale producers. Despite these barriers, AI-assisted behavioral phenotyping has the potential to improve genetic progress, animal welfare, and sustainability. Interdisciplinary collaboration and responsible innovation are essential to ensure the equitable and effective adoption of these technologies in diverse farming contexts. Full article

Mitochondria are currently of great interest to scientists. The role of mitochondrial DNA (mtDNA) mutations has been proven in the genesis of more than 200 pathologies, which are called mitochondrial disorders. Therefore, the study of mitochondria and mitochondrial DNA is of great interest not only for understanding cell biology but also for the treatment and prevention of many mitochondria-related pathologies. There are two main trends of mitochondrial therapy: mitochondrial replacement therapy (MRT) and mitochondrial transplantation therapy (MTT). Also, there are two main categories of MRT based on the source of mitochondria. The heterologous approach includes the following methods: pronuclear transfer technique (PNT), maternal spindle transfer (MST), Polar body genome transfer (PBT) and germinal vesicle transfer (GVT). An alternative approach is the autologous method. One promising autologous technique was the autologous germline mitochondrial energy transfer (AUGMENT), which involved isolating oogonial precursor cells from the patient, extracting their mitochondria, and then injecting them during ICSI. Transmission of defective mtDNA to the next generation can also be prevented by using these approaches. The development of a healthy child, free from genetic disorders, and the prevention of the occurrence of lethal mitochondrial disorders are the main tasks of this method. However, a number of moral, social, and cultural objections have restricted its exploration, since humanity first encountered the appearance of a three-parent baby. Therefore, this review summarizes the causes of mitochondrial diseases, the various methods involved in MRT and the results of their application. In addition, a new technology, mitochondrial transplantation therapy (MTT), is currently being actively studied. MTT is an innovative approach that involves the introduction of healthy mitochondria into damaged tissues, leading to the replacement of defective mitochondria and the restoration of their function. This technology is being actively studied in animals, but there are also reports of its use in humans. A bibliographic review in PubMed and Web of Science databases and a search for relevant clinical trials and news articles were performed. A total of 81 publications were selected for analysis. Methods of MRT procedures were reviewed, their risks described, and the results of their use presented. Results of animal studies of the MTT procedure and attempts to apply this therapy in humans were reviewed. MRT is an effective way to minimize the risk of transmission of mtDNA-related diseases, but it does not eliminate it completely. There is a need for global legal regulation of MRT. MTT is a new and promising method of treating damaged tissues by injecting the body’s own mitochondria. The considered methods are extremely good in theory, but their clinical application in humans and the success of such therapy remain a question for further study. Full article

Background: Vaccines have revolutionized disease prevention, yet their effectiveness is challenged by variable immunogenicity, individual response differences, and emerging variants. Biomimetic strategies, inspired by natural immune processes, offer new avenues to enhance vaccine performance. Objectives: This narrative review examines how bioinspired approaches—grounded in evolutionary medicine, immunology, and host–microbiota interactions—can improve vaccine immunogenicity and long-term protection. We further examine the evolutionary foundations of immune responses, highlighting how an evolutionary perspective can inform the development of durable, broadly protective, and personalized vaccines. Furthermore, mechanistic insights at the molecular and cellular level are explored, including Toll-like receptor (TLR) engagement, dendritic cell activation pathways, and MHC-I/MHC-II-mediated antigen presentation. These mechanisms are often mimicked in biomimetic systems to enhance uptake, processing, and adaptive immune activation. Results: The review highlights how immunosenescence, maternal immunity, genetic variation, and gut microbiota composition influence vaccine responses. Biomimetic platforms—such as nanoparticle carriers and novel adjuvants—enhance antigen presentation, boost adaptive immunity, and may overcome limitations in traditional vaccine approaches. Additionally, co-administration strategies, delivery systems, and microbiota-derived immunomodulators show promise in improving vaccine responsiveness. Conclusions: Integrating biomimetic and evolutionary principles into vaccine design represents a promising path toward safer, longer-lasting, and more effective immunizations Full article

Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications. Full article

The increasing incidence of autism spectrum disorder (ASD) increases the urgency of establishing the mechanism of its development for effective prevention and treatment. ASD’s etiology includes genetic predisposition and environmental triggers, both of which can play a role in the changed microbiota. Recent research has proved the impact of maternal microbiota on the neurodevelopment of the child. To investigate the co-play of genetic and microbiota factors in ASD development, we performed fecal microbiota transplantation (FMT) from children with ASD to female Shank3b^+/− mice and studied the autism-like symptoms in the male Shank3b^−/− and wild-type (WT) offspring. WT animals with prenatal exposure to ASD microbiota had delayed neurodevelopment and impaired food intake behavior, but also elevated plasma leptin concentration and body weight. Shank3b^−/− mice after FMT ASD exhibited impaired learning and exacerbated anxiety-like behavior in adulthood. Interestingly, FMT ASD improved learning in adolescent Shank3b^−/− mice. Prenatal exposure to ASD microbiota decreased the activity of hypocretin neurons of the lateral hypothalamic area in both genotypes. The combination of genetic predisposition and FMT ASD led to an increased colon permeability, evaluated by zonula occludens (ZO1, ZO3) and claudin factors. These results suggest the effect of parental FMT exposure on shaping offspring behavior in Shank3b^−/− mice and the potential of microbiota in the modulation of ASD. Full article

The alpine musk deer (Moschus chrysogaster) is a critically endangered species in China whose wild populations have precipitously declined due to habitat degradation and poaching. In response, China established the world’s first captive breeding facility for this species in 1990. Despite over three decades of closed breeding, the genetic consequences of long-term captivity remain unclear. Here, we present the first comprehensive assessment of mitochondrial genetic diversity in a captive population of 409 individuals, using three mitochondrial markers (D-loop, Cytb, and COI) and comparative data from wild conspecifics. Our results reveal a pronounced reduction in genetic diversity in the captive population compared to wild populations. Nucleotide diversity (π) and haplotype diversity (Hd) were consistently lower across all markers in captivity, with D-loop Hd = 0.639 and π = 0.01073. Further combined sequence analysis revealed a single dominant haplotype (Hap4) representing 56.99% of individuals, indicative of severe haplotype loss and homogenization. Although some haplotypes are shared with wild populations, captive populations exhibit strong genetic differentiation from wild populations, with the captive populations retaining only a limited fraction of the species’ maternal lineages. This pronounced genetic erosion driven by strong founder effects and genetic drift raises concerns about the viability and reintroduction success of this species. These findings highlight the inherent limitations of closed captive populations in preserving evolutionary potential and adaptive capacity. Our study emphasizes the urgent need for evidence-based genetic management, including founder augmentation and population exchange, to mitigate inbreeding and maintain genetic diversity. Full article

Understanding the genetic and phenotypic basis of economically important traits is essential for designing effective breeding programs in livestock. This study aimed to evaluate the phenotypic performance and estimate genetic parameters for one reproductive trait—litter size at birth (LSB)—and three pre-weaning growth traits—birth weight (BW), weaning weight (WW), and average daily gain (ADG)—in a population of 1888 Zaraibi kids born between 2018 and 2023. Genetic parameters were estimated using animal models implemented in the MTDFREML software. The overall least squares means (±standard error) for LSB, BW, WW, and ADG were 2.22 ± 0.02, 2.03 ± 0.01 kg, 10.22 ± 0.05 kg, and 90.00 ± 0.50 g/day, respectively. Statistical analyses indicated that month of birth, year of birth, and type of birth had significant (p < 0.05) effects on all traits, while the sex of the kids had no significant effect (p > 0.05) on LSB. Direct heritability estimates (h²_d) derived from Model 1 (including additive genetic, permanent environmental, and residual effects) were 0.13 ± 0.01 for LSB, 0.30 ± 0.04 for BW, 0.38 ± 0.01 for WW, and 0.30 ± 0.10 for ADG. Under Model 2 (which incorporated maternal genetic effects and their covariance with direct genetic effects), maternal heritability (h²_m) estimates for LSB, BW, WW, and ADG were 0.05 ± 0.01, 0.15 ± 0.01, 0.12 ± 0.01, and 0.14 ± 0.01, respectively. Overall, the results emphasize the importance of maternal genetic effects in influencing pre-weaning growth traits. Therefore, maternal genetic components should be explicitly considered in genetic evaluation and selection strategies aimed at improving early growth performance in Zaraibi goats. Full article

Background: Preeclampsia remains a leading cause of maternal morbidity worldwide. There is a critical need for predictive systems that not only perform accurately but also provide interpretable insights for clinical decision-making. This work introduces SK-MOEFS, an explainable framework based on fuzzy logic and multi-objective evolutionary optimization, designed to classify preeclampsia risk while generating clinically interpretable rules. Methods: The model integrates fuzzy decision trees with a genetic algorithm to identify a compact and relevant set of rules, optimized for both accuracy and interpretability. The system was trained and evaluated on third-trimester pregnancy data from a publicly available, multi-ethnic cohort comprising 574 individuals. All processes, including preprocessing, training, and evaluation, were conducted using open-source tools, ensuring reproducibility. Results: SK-MOEFS achieved 91% classification accuracy, an AUC of 0.89, and a recall of 0.88—outperforming other standard interpretable models while maintaining high transparency. The model emphasizes minimizing false negatives, which is critical in clinical risk stratification for preeclampsia. Conclusions: Beyond predictive performance, SK-MOEFS offers a rule translation and defuzzification layer that outputs probabilistic interpretations in natural language, enhancing its suitability for clinical use. This framework provides an effective bridge between algorithmic inference and human clinical judgment, supporting transparent and reliable decision-making in maternal care. Full article

This study aimed to identify the best model and method for the genomic selection of early growth traits in Inner Mongolian cashmere goats (IMCGs). Using data from 50,728 SNPs, the phenotypes (birth weight, BW; weaning weight, WW; daily weight gain, DWG; and yearling weight, YW) of 2256 individuals, and pedigree information from 14,165 individuals, fixed effects were analyzed using a generalized linear model. Four single-trait animal models with varying combinations of individual and maternal effects were evaluated using the ABLUP, GBLUP, and ssGBLUP methods. The best model was selected based on a likelihood ratio test. Five-fold cross-validation was used to assess the accuracy and reliability of the genomic estimated breeding values (GEBVs). Birth year and herd significantly affected BW (p < 0.05) and WW, DWG, and YW (p < 0.01), while sex, birth type, and dam age had highly significant effects on all traits (p < 0.01). Model 4, incorporating direct and maternal additive genetic effects, maternal environmental effects, and their covariance, was optimal. Additionally, ssGBLUP achieved the highest GEBV accuracy (0.61–0.70), outperforming the GBLUP and ABLUP methods. Thus, ssGBLUP is recommended for enhancing the genetic progress in IMCGs. Under the best method, the heritability estimates for BW, WW, DGW, and YW were 0.11, 0.25, 0.15, and 0.23, respectively. Full article

Amazonian parrots (Psittacidae) are essential to ecosystem balance. Already vulnerable to habitat fragmentation and weak environmental regulations, they are now increasingly threatened by heavy metal contamination. This review synthesizes evidence on the sources, transgenerational bioaccumulation, and physiological impacts of metals such as mercury (Hg), lead (Pb), cadmium (Cd), zinc (Zn), and arsenic (As) in these birds. Anthropogenic activities, including illegal gold mining, agricultural intensification, and urban expansion, release metals that biomagnify along food webs. Parrots, as long-lived, high-trophic consumers, accumulate metals in vital tissues, leading to severe neurotoxic effects, immunosuppression, reproductive failure, and reduced survival. Furthermore, maternal transfer of contaminants to eggs exacerbates genetic erosion and threatens population viability. While biomonitoring tools and habitat restoration have been proposed, current strategies are insufficient against the synergistic pressures of pollution and climate change. Addressing heavy metal exposure is critical to conserving Amazonian biodiversity and safe-guarding ecosystem services. Future efforts should prioritize multidisciplinary predictive models, bioremediation actions, and the strengthening of international environmental governance to ensure the survival of these sentinel species. Full article