Hereditary ataxia is a neurodegenerative disorder notable for its early onset, with symptoms appearing in patients as young as two years old. Although affected individuals exhibit severe motor deficits and early mortality rates, the timeline of Purkinje cell loss remains unclear. To address this gap, we used the spastic Han-Wistar rat model, which harbors an unknown homozygous recessive variant that causes Purkinje cell loss. Here, we determined the onset and temporal progression of Purkinje neuronal loss in the spastic Han-Wistar model. To achieve this, we employed immunohistochemistry, Hematoxylin and Eosin histology, and neuronal density quantification. Behavioral testing demonstrated early-onset, progressive motor impairment in mutant rats, with motor deficits emerging around P45, following Purkinje cell loss detectable as early as P15. Additionally, guided by pedigree analysis indicating autosomal recessive inheritance for this ataxia, we performed whole-genome shotgun sequencing of a parent-offspring trio to identify amino acid-changing mutations consistent with this pattern. Sanger sequencing excluded Sbf2 as a causal variant, and whole-genome sequencing identified 273 candidate genes consistent with autosomal recessive inheritance. Together, our findings provide new insights into the onset and genetic complexity of ataxia, refining the value of the spastic Han-Wistar rat as a model for investigating mechanisms underlying hereditary ataxia.

The cocirculation of CRF01_AE and CRF07_BC among men who have sex with men (MSM) in China may facilitate the emergence of genetically complex HIV-1 recombinants. Here, we identified and characterized a novel second-generation HIV-1 CRF01_AE/CRF07_BC recombinant, designated GY0192, from a 25-year-old MSM individual in Guiyang, Guizhou Province, southwest China, using near full-length genome (NFLG) analysis. Recombination analyses identified four breakpoints at HXB2 positions 3,125, 5,687, 6,375, and 9,176, generating a distinct five-segment mosaic genome. Subregion phylogenetic analyses showed that the two CRF01_AE-derived fragments clustered with the CRF01_AE cluster 5 lineage, while all three CRF07_BC-derived fragments grouped with CRF07_BC lineages frequently circulating among MSM in China, indicating that both parental components of GY0192 were phylogenetically related to lineages frequently reported among MSM populations in China. The virus was also predicted to be CCR5-tropic, adding epidemiological relevance because CCR5-tropic viruses are commonly involved in transmission and early infection. Together, these findings identify GY0192 as a distinct CRF01_AE/CRF07_BC mosaic and suggest that cocirculating MSM-associated HIV-1 lineages may provide opportunities for interlineage recombination. This case expands the known spectrum of CRF01_AE/CRF07_BC recombinants in Guizhou and underscores the value of NFLG-based surveillance for detecting underrecognized HIV-1 genetic complexity in southwest China.

Tremellafuciformis (T.fuciformis) is consistently found in association with Annulohypoxylonstygium (A.stygium) in natural environments. However, their interaction remains largely cryptic and requires a dedicated in situ sequencing approach for elucidation. Traditional genome sequencing and assembly yield genetic information for only one species at a time. In this study, the interacting community of T.fuciformis was sequenced as an integrated unit, obtaining three complete genomes in a single run, specifically two heterokaryotic genomes of T.fuciformis and one of A.stygium. Validated across four dimensions, these genomes showed excellent continuity, completeness, and accuracy. Interspecifically, the cell ratio of T.fuciformis to A.stygium was estimated at 1:1.09, and no genomic evidence supported DNA exchange through long-term symbiosis. Heterokaryotically, distinct chromosomal structural variations were observed between the core and accessory chromosomes of T.fuciformis, while internal transcribed spacer (ITS) fragment polymorphism indicated that single-locus ITS data may inadequately reflect genetic complexity. Using the community genome as molecular markers enabled strain identification and confirmed interactions. Overall, this study provides methods for studying interactive community genomes and their interspecific and internuclear connections.

ABSTRACT In the face of growing complexity, developing the skills to navigate our daily lives has become a major challenge. In French-speaking Belgium, although the decree of the Education Code emphasises the need to prepare students to become responsible citizens, current teaching practices tend to oversimplify complex phenomena, particularly in genetics. To introduce learners to the complexity of genetics, a didactic framework was developed. This framework integrates reflective, systemic, emergentist, and socio-constructivist approaches, whose impact on students’ thinking and knowledge was analysed. The results show significant progress, both in students’ modes of thinking – marked by critical and nuanced reflection – and in their understanding of key genetic concepts. Among the framework’s components, expert interventions and peer discussions proved effective in deconstructing misconceptions, deepening the understanding of complex genetic interactions, and assimilating new concepts. It would be beneficial to integrate these approaches throughout the school curriculum and across disciplines to help students develop thinking that can grasp complexity.

High-grade serous ovarian carcinoma (HGSC) is the sixth leading cause of cancer-related death among women. Most tumors arise from the Fallopian tubal epithelium (TE), exhibit numerous mutations, and present heterogenous pathological features. However, the contribution of specific mutation combinations to cellular transformation, pathological phenotype, and chemotherapeutic responses remains unclear. We used a mouse TE organoid platform for combinatorial CRISPR mutagenesis of 20 candidate HGSC driver genes. Besides Trp53, mutations in Nf1, Cdkn2a, and Map2k4 were the most prevalent in phenotypically transformed organoids. Map2k4 mutant organoids transplanted into mice predominantly yielded papillary-glandular carcinomas, whereas those with Nf1 mutations were more mesenchymal-like. Map2k4 mutant cells were particularly sensitive to paclitaxel, and Rho kinase inhibitor (ROCKi) increased trametinib sensitivity in both Map2k4- and Nf1-mutant organoids. This organoid mutagenesis strategy is powerful for unraveling the genetic and phenotypic complexity of HGSC, and identified Map2k4 as a potential therapeutic target in select HGSC cases.

Adults with epilepsy and intellectual disabilities (ID) may be at risk of adaptive and cognitive decline due to underlying genetic disorders, seizures, and complex comorbidity. A follow-up study was performed in a cohort of adults with mostly drug-resistant epilepsy and mild-severe ID. Adaptive and cognitive functioning were re-assessed with the Vineland Adaptive Behavior Scales (VABS-II), Wechsler Adult Intelligence Scale short form (WAIS-SF-IV), and Picture Peabody Vocabulary Test (PPVT-III). Medical history, current antiseizure medication, and dementia diagnostics were retrieved from the medical files. Changes in adaptive and cognitive functioning were analyzed using mixed effects models and reliable change indexes. Chi square tests were used to explore associations with comorbidity. A total of 72 adults were re-assessed after a mean of 5.4 (range 4.7-6.5) years, with a mean age of 52 (range 24-76) years. Raw scores of adaptive functioning declined significantly (daily skills: βtime=-1.45, df=71, p<0.001, social skills: βtime=-1.91, df=71, p<0.001). Re-assessment of cognitive functioning was successful in 55 individuals (77.8%) and remained stable in this group (WAIS: βtime=0.75, df=29, p=0.51, PPVT: βtime=-0.02, df=29, p=0.64). A clinical suspicion of dementia was documented for 12 individuals (16.7%). Sensory impairments were associated with adaptive decline (visual: X2=8.71, p=0.003) and suspected dementia (hearing: X2=11.63, p<0.001). Results show significant early adaptive decline and call for more awareness and frequent re-assessments.

Human metapneumovirus (hMPV) is an important cause of acute respiratory infections in children, but genomic surveillance data from Ningbo, a coastal port city of China, remain limited. We investigated the epidemiology, genetic diversity and phylogeographic patterns of hMPV among children in Ningbo from 2020 to 2024 using 6,632 respiratory specimens from paediatric outpatients and 26 hMPV-positive samples. The overall hMPV-positive rate was 3.62% (240/6,632), with a peak in 2022 (6.86%). An atypical summer peak in 2022 and a prolonged 2023-2024 season suggested altered seasonality in the post-COVID-19 period. Preschool-aged children (1-6 years) were the most affected age group and the proportion of viral co-infections among hMPV-positive cases increased significantly over time. Phylogenetic analysis of the 26 genomes showed co-circulation of four lineages, with B2 and A2.2.2 predominating across multiple years. We identified one A2.2.2 strain (20240959) carrying a 111-nt (37-aa) insertion in the G gene, whereas other A2.2.2 strains retained the classical non-duplicated G sequence. Several lineage-associated substitutions in F protein were observed between lineages A, B1 and B2, and mapping suggested that a substantial proportion of these sites fell within predicted linear B-cell epitope-prone regions. Phylogeographic reconstruction indicated multiple introductions of hMPV into Ningbo from other parts of China and from overseas. These findings demonstrate the genetic and epidemiological complexity of hMPV circulation in a major port city and underscore the need for continued, genome-informed surveillance to monitor hMPV evolution.

Understanding how evolutionary history and ecological pressures shape plant chemical diversity is central to ecology and evolution, yet it remains unclear whether metabolomic data can reliably detect fine-scale, intraspecific divergence, particularly in morphologically cryptic taxa. While metabolomics has revealed broad patterns of chemical evolution across lineages, its power to resolve genetically structured variation within species is still underexplored. Here, we investigated the alpine Primula auricula complex, a morphologically uniform but genetically subdivided taxon distributed across the Alps. Using ultra-high-performance liquid chromatography coupled with mass spectrometry, we profiled the metabolomes of individuals sampled from 37 populations spanning three main genetic clades and an outlier group, previously identified through ddRADseq phylogeography. We found that metabolomic diversity carries a strong phylogenetic signal: each clade exhibited distinct chemical profiles, with exclusive or enriched metabolite superclasses such as carotenoids in one clade and phenylpropanoids in another. Outlier populations displayed reduced metabolomic richness, consistent with potential genetic drift or bottlenecks. While phylogenetic structure was the dominant driver of chemical variation, climatic variables, particularly temperature and precipitation, modulated certain stress-related metabolite groups, such as octadecanoids. Our results demonstrate that metabolomic profiling can capture both historical divergence and ecological adaptation in cryptic alpine taxa. By linking chemical, genetic, and environmental variation, this study highlights metabolomics as a cost-effective and high-resolution approach to uncover cryptic diversity, refine taxonomy, and inform conservation strategies in biodiversity hotspots increasingly threatened by climate change. • The metabolomic variation of P. auricula complex is related to its phylogegeography • Climatic and genetic related variation of the metabolome could be disentangled. • Complex history of the Alps shape alpine genetic and metabolomic diversification. • Metabolomics can serve to delineate crypric diversity and infer evolutionary history.

Population genetic structure of zoonotic Toxoplasma gondii in China revealed using multilocus sequence typing

Dedifferentiated liposarcoma (DDLS), myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma (UPS) are the most common types of genetically complex sarcoma. There is an urgent need to develop effective targeted therapy for these deadly sarcoma types. Despite their genetic complexity, these sarcomas share genomic alterations causing PI3K/Akt/mTOR and MAPK pathway activation, and both pathways control translation mediated by the RNA helicase eIF4A. We therefore investigated eIF4A inhibition as a therapeutic strategy. The eIF4A inhibitor CR-1-31B effectively suppressed tumor growth and induced apoptosis in DDLS, MFS, and UPS patient–derived cell lines and mouse xenografts. Transcriptome-scale ribosome footprinting identified eIF4A-dependent mRNAs such as the Hippo pathway transcriptional coactivators YAP1 (YAP) and WWTR1 (TAZ). Combined knockdown of YAP and TAZ induced apoptosis in DDLS, MFS, and UPS cell lines, and their ectopic expression partially rescued cells from apoptosis induced by CR-1-31B. Genomic analysis of patient tumors revealed that YAP and WWTR1 were frequently amplified or gained in DDLS, MFS, and UPS and were associated with worse clinical outcomes. Together, our findings identify a strategy for targeting the Hippo pathway in incurable forms of sarcoma based on inhibition of eIF4A-dependent translation of the key oncogenic transcription factors YAP and TAZ.

To meet the growing demand for agricultural products, optimizing photosynthesis is a promising strategy to improve the crop yields. Phenotypic variance in photosynthesis has been observed within or between species. To explore the potential of integrating photosynthetic parameters into crop breeding programs, we explored the genetic variation in photosynthesis by assessing photosynthesis-related parameters across plant development in 631 barley recombinant inbred lines (RILs) from eight HvDRR sub-populations under field conditions. The genetic complexity of these parameters was resolved by bi-parental and multi-parental quantitative trait loci (QTL) analyses. Finally, we examined the merit of integrating photosynthesis-related parameters in genomic prediction of yield and its components. Significant genotypic variations of the photosynthesis-related parameters were found among the RILs, with their heritability ranging from 0.38 to 0.54. The multiple QTL and dynamic QTL for photosynthesis observed across different developmental stages underlined the complexity of the genetics of photosynthesis in barley. The considerably higher percentage of phenotypic variance explained for genomic prediction than multi-parental QTL analysis illustrates that the photosynthesis-related parameters are inherited in a more complex way than classical agronomic traits. Notably, the prediction ability for yield was increased by integrating the photosynthesis-related parameters of some developmental stages into genomic prediction models. Therewith, our results suggest a novel perspective on increasing the efficiency of crop breeding programs by integrating photosynthesis-related parameters into prediction models.

The catfish genus Pseudecheneis consists of small freshwater catfish that live at the bottom of fast-flowing streams. The genetic information carried by extant freshwater fish can provide new insights into deciphering the evolutionary processes of rivers. However, existing studies often rely on limited molecular markers, which are insufficient to thoroughly resolve genetic information and complex evolutionary relationships. We have deciphered the first high-quality Telomere-to-Telomere (T2T) chromosome-level genome of Pseudecheneis, with a genome size of 574.82 Mb and a contig N50 of 22.76 Mb. A total of 19,787 protein-coding genes were annotated, of which 98.4% were successfully functionally annotated. This study provides important references for clarifying the phylogenetic relationships and evolutionary history of Pseudecheneis, and also offers valuable data support for exploring the interrelationships among structure, function, and adaptation.

Angola is one of the countries with the highest HIV-1 genetic diversity, yet the implications of this diversity for antiretroviral therapy remain insufficiently characterised. Following the introduction of dolutegravir (DTG) in Angola in 2021, evaluating transmitted drug resistance prior to its widespread implementation is essential to inform treatment strategies and establish a baseline for future surveillance. In this study, 243 blood samples were collected from treatment-naïve people living with HIV attending the General Hospital of Benguela, Angola. The integrase coding region of proviral DNA was amplified and sequenced using the Sanger method. Phylogenetic relationships were inferred using a maximum likelihood approach, recombinant forms were characterised by bootscanning analysis, and resistance-associated mutations to integrase strand transfer inhibitors were identified using Stanford HIVdb, ANRS-MIE, and IAS-USA algorithms. A total of 92 integrase sequences were successfully obtained, revealing 16 distinct genetic forms, with unique recombinant forms accounting for 50.0%, followed by subtype C (10.9%) and sub-subtype F1 (8.7%). Five accessory mutations (L74I, L74M, Q95K, T97A, and E157Q) and one major mutation (E92G) were detected, corresponding to an overall prevalence of 28.8% (23/80). These findings highlight the extensive HIV-1 genetic complexity in Angola and support the continued use of DTG-based regimens, while underscoring the importance of sustained surveillance of integrase inhibitor resistance.

Beyond Data: Artificial intelligence, knowledge graphs, and the next revolution in wheat breeding.

Hepatitis C virus (HCV) is believed to cause 130-170 million infections worldwide, or roughly 3% population worldwide, and poses a serious risk to global health. Hepatitis C is an enveloped +ve RNA virus belonging to the family Flaviviridae. All around the world, HCV infection is the main cause of serious liver diseases such as cirrhosis and hepatocellular carcinoma. Even though drugs have been around for a while, only a small number of them have been proven to be effective against every HCV genotype because of their genetic diversity and complexity. The objective of the paper to understand various protein targets of HCV and study various inhibitors from different sources and their scope in the treatment of HCV infection. The terms "core proteins," "structural and non-structural HCV proteins," "treatment strategies of HCV," and "hepatitis C virus" were used to search the scientific database for relevant publications. A selection of reports from PubMed, MEDLINE, Scopus, Web of Science, followed by Science Direct, and Google Scholar that were searched through 2024 are included in this review. In this work, the findings were evaluated, collected, and presented. There were 218 papers in all, and the number of articles published between 2010 and 2024 increased exponentially. This study provides an overview of what is currently known about the virology, transmission, diagnosis, and treatment of HCV. Additionally, it offers a thorough examination of HCV proteins as potential targets for the creation of vaccines and antiviral medications. The NS5B polymerase, NS3/4A protease, entrance receptors, including CD81, and core proteins are among the specific HCV proteins that have been suggested as possible therapeutic targets. Additionally, the potential uses of HCV proteins as prognostic and diagnostic biomarkers. Although successful, the current direct- acting antiviral treatments have drawbacks related to resistance, genotype specificity, and cost. In order to guide future research on better preventive, diagnostic, and therapeutic approaches against this worldwide infectious disease threat, this review attempts to compile crucial knowledge on HCV biology and pathogenesis. The findings of the review indicate the importance of understanding various protein targets of HCV and studying various inhibitors from different sources and their scope in the treatment of HCV infection. In support of the review, an in-silico based meta-analysis study is included to infer the complete antiviral potential of Hepatitis C Virus- Drug Resistance and different proteinsbased therapeutic targets. We intended to highlight the advances gained in managing and preventing HCV infection, as well as the ongoing challenges to HCV prevention. The primary goal was to connect with global health objectives in order to reduce the burden of chronic hepatitis, ultimately eliminating it as a public health hazard in the near future. The PROSPERO registration number for systematic review is 1080028.

Ascorbic acid (AsA), an essential nutrient for human health predominantly obtained from fresh vegetables and fruits, demonstrates considerable genetic complexity in its accumulation mechanisms. This study investigates the genetic regulation of AsA biosynthesis in non-heading Chinese cabbage (NHCC), a crucial leafy vegetable in China. Through comprehensive quantitative trait locus (QTL) analysis across multiple environments, we identified 19 AsA-associated QTLs distributed over 10 linkage groups, explaining 3.15% to 18.04% of phenotypic variance. An environmentally stable QTL (qAsA.A01.1) was prioritized for further investigation. Integrated QTL mapping and comparative transcriptome analysis revealed 297 candidate genes, among which the GATA transcription factor CYTOKININ-RESPONSIVE GATA FACTOR 1 (BcCGA1) emerged as a candidate regulator through allelic variation analysis, gene description analysis, and association analysis. Functional validation via gene silencing and overexpression confirmed the suppressive role of BcCGA1 in AsA biosynthesis. Mechanistic studies established that BcCGA1 plays a direct transcriptional repressor of AsA biosynthesis by binding to the promoters of GDP-L-GALACTOSE PHOSPHORYLASE c (BcGGP.c), GDP-MANNOSE PYROPHOSPHORYLASE b (BcGMP.b), and KONJAC c (BcKJC.c). Furthermore, we identified an interaction between BcCGA1 and the chloroplast-localized protein PS II OXYGEN-EVOLVING COMPLEX 1 (BcPSBO1), which exhibits dual regulatory effects. While BcPSBO1 attenuated BcCGA1's DNA-binding capacity in vitro, it paradoxically enhanced transcriptional repression of target genes in vivo. Our findings elucidate a sophisticated regulatory framework involving transcriptional and protein interaction mechanisms that substantially advances our understanding of AsA accumulation genetics and provides a theoretical basis for nutrient-enhanced NHCC cultivars.

Apple blotch (AB) is an emerging disease in apple production, primarily causing premature defoliation. The rise of orchard management practices reducing fungicide use has coincided with an increase in AB incidence in Europe. Breeding for resistance to AB became important for long-term disease management. Depending on the genetic complexity of the trait, breeding can be supported using either marker-assisted or genomic selection. However, no such tools are currently available for AB. To address this issue, we established two biparental mapping populations, ‘Topaz’ × ‘Granny Smith’ and ‘Topaz’ × ‘Parkapfel’, and a diversity panel of 122 genotypes, all evaluated for their resistance to AB under natural field conditions across three growing seasons. Quantitative trait locus (QTL) mapping identified five associated loci on chromosomes 3, 5, 6, 10, and 11, each explaining a maximum of 12% of phenotypic variance, indicating a polygenic architecture of AB resistance. Strong seasonal effects were observed in disease development, and they were either removed (G model) or explicitly modeled (G + G×E model) using genomic prediction approaches. The average predictive ability reached 0.47 for the G model and 0.38 for the G + G×E model. While the detected QTLs have small individual effects that constrain their use in marker-assisted selection, the moderate predictive ability of genomic prediction models demonstrates the potential of genomic selection for accelerating resistance breeding. These findings provide the first genomic tools to support breeding for resistance to AB and illustrate the utility of genome-wide approaches in managing complex traits.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11032-026-01666-5.

Optimizing Natural Killer Cellular Therapy in Acute Myeloid Leukemia.

RXFP2 gene variation drives horn sexual differences and polledness in sheep.

Extensive cocirculation of CRF01_AE and CRF07_BC in China has created favorable conditions for ongoing intersubtype recombination, contributing to increasing genetic complexity within the local HIV-1 epidemic. In this study, two novel unique recombinant forms composed of CRF01_AE and CRF07_BC were identified in Shenzhen, Guangdong Province. Near-full-length genome sequences were obtained for isolates LS11654 and LS16824. Phylogenetic analysis indicated that both sequences clustered within a CRF01_AE-/CRF07_BC-related lineage but were distinct from previously reported strains. Recombination analysis revealed markedly different mosaic structures: LS11654 contained two recombination breakpoints, whereas LS16824 exhibited a more complex genome with eight breakpoints and multiple inserted fragments. Subregion phylogenetic analysis further confirmed the parental origins of the recombinant segments. These findings reflect ongoing recombination driven by sustained cocirculation of CRF01_AE and CRF07_BC in Shenzhen and highlight the importance of continued molecular surveillance.