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Discovering common and population-specific QTLs for leaf rust resistance in different Barley populations.

Multi-population GWAS lead to identification of common and population-specific QTLs for leaf rust resistance in barley. Genome-wide association studies (GWAS) are a powerful tool for detecting genetic markers associated with traits of interest. However, these studies are typically restricted to a single population, and transferability of identified marker effects across populations is challenged by population differences in linkage, allele frequencies, epistatic effects, and environmental context. When comparing GWAS results between populations, a lack of overlapping signals is often interpreted as a lack of common quantitative trait loci (QTLs), although such discrepancies may result from differences in statistical power to detect signals. In barley (Hordeum vulgare L.), where genetic leaf rust resistance is rapidly overcome by evolving pathogens, identification of cross-population robust and potentially transferable resistance loci is a key task. Here, we present a mixed model approach for multi-population GWAS that estimates correlated marker effects in multiple populations and use this to test for significant effects across and within populations. Applying this model to four barley breeding populations revealed both common and population-specific QTL effects for leaf rust resistance, including loci colocalizing with known Rph genes and novel regions with plausible candidate genes. Multi-population GWAS increased power, revealing signals not detected by GWAS within populations. We categorized the reported QTLs into three groups based on marker-associated allele effects: (1) consistent effect direction across populations, (2) differing effect direction across populations, and (3) present in a single population. The study highlights the transferability and limitations of leaf rust resistance QTLs across different barley populations and provides a general statistical framework to support robust marker-assisted selection across populations.

Quantitative Trait Loci↗

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans↗

Electro-clinical efficacy and safety of midazolam in neonatal seizures: a systematic review with individual level exploratory analysis of gestational age-related treatment response.

UNLABELLED: Neonatal seizures are the most common neurological emergency during the neonatal period and are associated with increased mortality and adverse neurodevelopmental outcomes. Despite current recommendations supporting phenobarbital as first-line therapy, seizure control remains suboptimal in a large proportion of neonates, prompting the use of second-line antiseizure medications. Midazolam is increasingly administered in refractory neonatal seizures but evidence regarding its electro-clinical efficacy and safety remains limited and heterogeneous. To systematically review the available evidence on the electro-clinical efficacy and safety of midazolam in neonatal seizures and to perform an exploratory individual-level analysis investigating the association between gestational age and treatment response. A systematic review was conducted according to PRISMA 2020 guidelines. Studies including neonates with EEG- or aEEG-confirmed seizures treated with midazolam were included. Binary logistic regression was performed to assess the individual-level association between gestational age and treatment response. Eleven studies involving 146 neonates treated with midazolam were included. Electro-clinical response was observed in 101/146 neonates (69.2%), while seizure cessation was achieved in 61/146 neonates (41.8%). In an exploratory complete-case logistic regression analysis, higher gestational age appeared to be associated with a greater probability of electro-clinical response. The predicted probability curve crossed the 50% response probability at approximately 36.5 weeks of gestation. Hypotension was the most frequently reported adverse event, while respiratory depression, sedation-related effects, and transient EEG/aEEG suppression were reported less frequently. CONCLUSIONS: Midazolam may have a role as an add-on antiseizure medication in neonatal seizures, particularly in refractory cases. However, the evidence remains limited by heterogeneity in study design, EEG monitoring strategies, outcome definitions, and incomplete individual-level data. The observed association between gestational age and response is hypothesis-generating and requires prospective validation. WHAT IS KNOWN: • Phenobarbital often provides incomplete seizure control in neonates, making second-line antiseizure therapies necessary in refractory cases. • Evidence supporting midazolam for neonatal seizures remains limited and heterogeneous. WHAT IS NEW: • This systematic review summarizes the electro-clinical efficacy and safety of midazolam and includes an exploratory patient-level analysis suggesting that higher gestational age may be associated with improved treatment response. • These findings support further prospective studies on developmental determinants of response to GABAergic therapy.

Humans↗

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1 month (OR = 0.58, 95% CI 0.39-0.84) and 6 months (OR = 0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3 months, and no significant benefit at 12 months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3 months (SMD = -0.70, 95% CI -1.08 to -0.32) and 6 months (SMD = -0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12 months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD = -0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans↗

Proteomic profile of the dentine pellicle modified with plant polyphenols and fluoride.

OBJECTIVES: Despite its protective role, the dentine pellicle has rarely been studied, therefore we aimed to map out the proteomic profile of in vitro dentine pellicles before and after modification. MATERIALS AND METHODS: A total of 135 human dentine specimens were prepared. After initial pellicle formation with 150 µl pooled human saliva (37 °C, 30 min), the dentine specimens were immersed in one of 9 pellicle modification solutions (2 ml/specimen): deionized water (non-modified pellicle), SnCl2/NaF/AmF (commercial solution containing 800 ppm Sn2+ and 500 ppm F-), NaF solution (500 ppm F- ), and six polyphenol solutions (2 mg / ml) with or without 500 ppm F-: blueberry extract (BBE and BBE + F-), green tea extract (GTE and GTE + F-) and grape seed extract (GSE and GSE + F-). After another aliquot of saliva (150 µl, 37 °C, 60 min), the pellicles were harvested with sodium dodecyl sulphate by rubbing with cotton balls, and taken to proteomic analyses by Liquid Chromatography-Tandem Mass Spectrometry after tryptic digestion. RESULTS: A total of 382 proteins were identified in all the proteomic analyses for all groups. Pellicle modification with fluoride, either NaF or SnCl2/NaF/AmF, led to the presence of 12 or 14 exclusive proteins, respectively, whereas modification with the solutions containing polyphenols presented less exclusive proteins (4-6 proteins). The number of exclusive proteins was even lower for when polyphenols and fluoride (GTE + F- and GSE + F-) were used, with lower abundance of proteases. CONCLUSIONS: We conclude that NaF and SnCl2/NaF/AmF significantly modify the proteome of the dentine pellicle. The combination of fluoride with polyphenols further lowers the abundance of proteins and proteases, which explains the positive effect of these solutions on the dentine pellicles. CLINICAL RELEVANCE: Plant extract solutions with fluoride can significantly modify the proteomic structure of the dentine pellicle, which clarifies the mechanism of action of polyphenols on the protection of dentine demineralization.

Humans↗

LncRNA H19 promotes vascular remodeling by inhibiting MFN2.

Neointimal hyperplasia, featuring excessive proliferation and migration of vascular smooth muscle cells (VSMCs), is crucial in vascular remodeling diseases. Long non-coding RNA (lncRNA) H19 promotes vascular remodeling, yet underlying mechanisms remain incompletely elucidated. Here, we investigated whether H19 acts via its derivative miR-675-5p. Bioinformatics found a conserved H19/miR-675-5p/MFN2 (mitofusin 2) axis. Cell assays were performed to evaluate the effects of H19 and miR-675-5p on VSMC proliferation and migration. The dual-luciferase reporter gene assay was used to assess the interaction between miR-675-5p and Mfn2 mRNA. The mouse model of common carotid artery ligation was used to evaluate the role of H19 in neointimal hyperplasia. Our data suggested that knockdown of H19 inhibited VSMC proliferation and migration, as well as neointimal hyperplasia. Mechanistically, H19 regulated MFN2 through miR-675-5p, leading to ERK1/2 (extracellular signal-regulated kinase 1/2) activation. In conclusion, we suggest that targeting the H19/miR-675-5p/MFN2/ERK1/2 axis may help to treat vascular remodeling diseases.

Animals↗

Outcomes of stereotactic radiosurgery for spine multiple myeloma-a systematic review.

Spinal involvement in multiple myeloma (MM) commonly results in pain, vertebral instability, epidural spinal cord compression, and neurological deficits. Although conventional external beam radiation therapy (EBRT) remains the standard radiation modality because of the radiosensitive nature of MM, stereotactic radiosurgery (SRS) has emerged as a highly conformal treatment option capable of delivering focal high-dose radiation while sparing adjacent spinal cord structures and uninvolved bone marrow. This systematic review evaluated the clinical outcomes and safety profile of SRS for spinal MM. A systematic review of the literature was performed to identify studies evaluating SRS for spinal MM. Extracted variables included patient demographics, tumor characteristics, treatment parameters, radiographic outcomes, pain response, neurological outcomes, local control, overall survival, and adverse events. Three retrospective studies comprising 133 patients and 181 treated spinal lesions met the inclusion criteria. Median patient age ranged from 59 to 65 years, with a slight male predominance across studies. Thoracic spine lesions represented the most treated region (55.5-67.7%). Median prescribed SRS dose was 14-16 Gy, predominantly delivered in a single fraction. Median follow-up ranged from 11.2 to 27.8 months. Local control rates ranged from 89.4 to 100%, with 6- and 12-month local control rates of 94% and 91%, respectively, in one study. Pain improvement was reported in 41-88% of treated patients/sites, with a median time to pain relief of 1.6 months in one cohort. Neurological improvement occurred in 56-71.4% of patients with preexisting deficits. Reported adverse events included vertebral compression fractures, fracture progression, pain flare, and tracheoesophageal fistula. De novo vertebral fractures ranged from 3.6 to 7%, while fracture progression ranged from 14 to 18%. SRS appears to provide excellent local control and meaningful pain and neurological improvement in patients with spinal MM, with acceptable toxicity profiles. The highly conformal nature of SRS may preserve uninvolved bone marrow and facilitate continuation of systemic therapy. However, the current evidence is limited to small retrospective studies with heterogeneous reporting, and further prospective comparative studies are needed to better define the role of SRS relative to conventional EBRT in spinal MM.

Humans↗

Stratifying lung adenocarcinoma: a novel prognostic model based on mitochondrial outer membrane permeabilization activity.

UNLABELLED: Mitochondrial outer membrane permeabilization (MOMP) is a core apoptotic regulatory event that dictates mitochondrial integrity, where full activation drives cell death and sublethal dysregulation contributes to tumor genomic instability. We used the Cancer Genome Atlas lung adenocarcinoma cohort (TCGA-LUAD) as the training cohort and the Gene Expression Omnibus dataset GSE42127 as the validation cohort to identify prognostic genes related to MOMP activity in lung adenocarcinoma (LUAD) and to evaluate their potential biological significance. By intersecting MOMP-related genes with differentially expressed genes, combined with survival analysis, Mendelian randomization analysis, and 101 machine-learning algorithm combinations, seven prognostic genes, namely BIRC5, PSMD11, TNFRSF13C, YWHAZ, YWHAG, CYCS, and LTB, were identified. Next, an optimal prognostic model was constructed based on the gradient boosting machine (GBM) algorithm. Based on the risk score, LUAD patients were stratified into high- and low-risk groups, and patients in the high-risk group exhibited poorer overall survival in both the training and validation cohorts. Furthermore, a nomogram integrating the risk score and clinicopathological factors was developed and showed favorable predictive performance for 1-, 3-, and 5-year survival. Meanwhile, functional and immune analyses revealed that the high-risk group was enriched in DNA replication-related pathways and demonstrated a higher tumor mutation burden (TMB). Correlation analysis indicated that TNFRSF13C was positively correlated with activated B cells, whereas BIRC5 was negatively correlated with eosinophils, suggesting that MOMP-related genes might be involved in remodeling the immune microenvironment of LUAD. Drug sensitivity analysis showed differences in predicted half-maximal inhibitory concentration (IC50) values between the risk groups, suggesting the potential value of this model in assisting therapeutic stratification. Single-cell RNA sequencing (scRNA-seq) further identified T lymphocytes as a key cell type, with numerous prognostic genes exhibiting differential expression in T cells or dynamic changes during differentiation. We suggest that the MOMP-related signature established in this study may provide a reference for prognostic stratification in LUAD and offers candidate prognostic genes for subsequent experimental and clinical validation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05058-6.

Lung adenocarcinoma↗

Genome-wide identification of CHY zinc finger and RING finger (CHYR) genes in pepper and functional characterization of CaCHYR5 in response to Phytophthora capsici infection.

CHY zinc finger and RING finger (CHYR) proteins play crucial roles in the growth and development, as well as stress response. To date, no systematic or comprehensive analysis of the CHYR gene family has been performed in pepper (Capsicum annuum L.). In this study, we identified 8 CaCHYR genes (CaCHYR1-CaCHYR8), which were classified into 3 groups based on phylogenetic relationships. CaCHYR members within the same group exhibited similar distributions of conserved motifs and exon-intron structures. Chromosomal localization analysis showed that 8 CaCHYR genes were unevenly distributed on 6 chromosomes. Segmental duplication, rather than tandem duplication, was found to be the major contributor to the expansion of this gene family. CaCHYR genes feature a variety of cis-elements involved in developmental processes, phytohormone responses, and stress adaptation. Expression analysis based on RNA-seq data revealed that CaCHYR genes exhibited distinct spatial expression patterns across different tissues and in response to Phytophthora capsici infection (PCI), and quantitative real-time PCR (qRT-PCR) further confirmed that three of them (CaCHYR2, CaCHYR3, and CaCHYR5) exhibited altered expression under PCI. Furthermore, transient overexpression of CaCHYR5 in pepper leaves increased susceptibility to PCI, suggesting its potential negative regulatory role in pepper defense against P. capsici. Collectively, these findings reveal the expression patterns and regulatory functions of pepper CHYR genes in growth and development, laying a groundwork for breeding pepper cultivars tolerant to PCI.

Phytophthora capsici infection (PCI)↗

Oropouche virus infection: clinical spectrum, geographic expansion, and emerging maternal-fetal implications.

Oropouche virus (OROV), an emerging arbovirus of the genus Orthobunyavirus, has become a growing public health concern following its recent expansion across the Americas and its potential to cause severe clinical outcomes in maternal and child health. Although Oropouche fever has classically been described as an acute self-limited febrile illness, accumulating evidence indicates that OROV is associated with meningitis and fatal infection, as well as evidence of vertical transmission associated with adverse fetal outcomes, including microcephaly and other congenital abnormalities, spontaneous abortion, stillbirth, and neuropathological alterations resembling those observed in congenital Zika syndrome. The OROV presents two transmission cycles, namely sylvatic and urban, with Culicoides paraensis as its main vector. The absence of specific vaccines or treatments, together with the wide distribution of competent vectors and the possibility of sexual transmission, underscores the urgent need to strengthen epidemiological surveillance, elucidate the mechanisms of fetal pathogenesis, and develop effective prevention and control strategies to protect vulnerable populations.

Orthobunyavirus↗

Biologic Therapies for Alleviating Neurodegeneration in Lysosomal Storage Diseases.

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders characterized by lysosomal dysfunction and progressive accumulation of undegraded substrates, leading to multisystem involvement and, in many cases, severe neurodegeneration. Because the blood-brain barrier (BBB) restricts central nervous system (CNS) access for most therapeutic modalities, neurological manifestations remain the major unmet need across LSDs. In this review, we summarize current and emerging strategies aimed at correcting CNS pathology, including enzyme replacement therapy (ERT), adeno-associated virus (AAV)-mediated gene therapy, allogeneic hematopoietic stem cell transplantation (HSCT), and autologous HSCT with gene-modified hematopoietic stem cells. While ERT provides limited CNS benefits and allogeneic HSCT mitigates neurodegeneration only partially, their overall impact on CNS outcomes remains restricted. Newer approaches, such as BBB-shuttling ERTs, CNS-tropic AAV capsids, and genetically modified autologous hematopoietic stem and progenitor cells capable of sustained supraphysiological enzyme production, offer promising avenues for enhanced CNS delivery and cross-correction. Together, these advances underscore a shift toward integrated therapeutic strategies that combine systemic and CNS-directed interventions, with the potential to transform outcomes for patients with LSDs and other neurodegenerative disorders amenable to cross-correction.

Journal Article↗

Genomic detection of highly pathogenic avian influenza H5N1 in Antarctic seabirds reveals connectivity with South American viral lineages.

Emerging avian viruses increasingly threaten Antarctic wildlife, raising concerns about ecosystem health and biodiversity. In this study, we conducted a comprehensive investigation of avian influenza virus (influenza A virus, IAV) in both resident and migratory birds inhabiting the South Shetland Islands, Antarctica. During the 2024-2025 austral summer, 278 samples were collected and screened using real-time RT-PCR targeting the IAV M gene. IAV RNA was detected in 30 samples, and eight of these were found to be positive for H5. Complete genome sequencing was performed on samples from a gentoo penguin (Pygoscelis papua) and a southern giant petrel (Macronectes giganteus), revealing the presence of highly pathogenic avian influenza virus H5N1, clade 2.3.4.4b. Phylogenetic analysis demonstrated that these viral genomes closely cluster with contemporary South American strains, indicating a direct connectivity between Antarctic seabirds and the broader H5N1 transmission network. Our findings highlight the heightened vulnerability of Antarctic ecosystems to emerging infectious diseases and emphasize the critical need for sustained genomic surveillance. These efforts are essential to monitor wildlife health, inform conservation strategies, and implement effective biosecurity measures to safeguard Antarctic biodiversity.

Animals↗

Remdesivir maintains antiviral potency against clinically relevant SARS-CoV-2 Nsp12 substitutions.

Remdesivir (RDV) is a nucleotide analog prodrug approved for COVID-19 treatment that inhibits the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; nsp12). Although RDV maintains activity against circulating variants of concern, ongoing evaluation of resistance-associated substitutions is critical for clinical care, particularly in settings of prolonged viral replication such as immunocompromised individuals. We assessed the phenotypic impact of nsp12 substitutions identified from in vitro resistance selection, RDV clinical reports, and global sequence surveillance. Using a recombinant infectious SARS-CoV-2 reporter virus, we compared susceptibility of these nsp12 substitutions to RDV and its parent nucleoside, GS-441524. After confirming concordant resistance profiles between RDV and GS-441524, we assessed RDV susceptibility in a complementary non-infectious replicon system. In both systems, single nsp12 substitutions remained fully susceptible to RDV within their respective assay variability limits. Of the double substitutions tested, S759A/V792I conferred the largest reduction in antiviral susceptibility (∼15-fold) but was associated with impaired replication kinetics. Given the strong concordance between the two assays, the replicon system also enabled phenotypic characterization of substitutions E802A, E802D, and P323L/E802D that could not be rescued as infectious virus. Analysis of >17 million SARS-CoV-2 genomes in GISAID showed that all tested nsp12 substitutions had low prevalence (≤0.1%), except P323L (98.8%). Collectively, these data reinforce the high genetic barrier to RDV resistance, as reduced susceptibility is typically accompanied by substantial reductions in replication. Our findings support the continued clinical utility of RDV and highlight the complementary value of SARS-CoV-2 infectious virus and replicon systems for antiviral resistance surveillance and phenotyping.

COVID-19↗

Pancreatic ductal adenocarcinoma: The Vision of Heracles.

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, as tumors evolve faster than therapies. Resistance is ecological, not merely KRAS driven, involving overlooked players like high-grade pancreatic intraepithelial neoplasias (PanINs), peripancreatic fat, stromal mechanics, myeloid-neural circuits, metabolic rewiring, and systemic host responses. We propose precision interception targeting PanIN/intraductal papillary mucinous neoplasm (IPMN) biology, spatial-functional-proteogenomic classification beyond transcriptomics, the Heracles Protocol (measure, prime, strike, and adapt), and integrated technologies from AI pathology to exosomal delivery and CRISPR-based synergy mapping, together making PDAC more tractable.

Humans↗

Spatial analysis reveals the evolving organization of IDH-mutant glioma.

Adult diffuse gliomas are composed of malignant cell states interwoven with the non-malignant brain microenvironment. Here, we combine spatial transcriptomics and spatial proteomics of isocitrate dehydrogenase (IDH)-mutant gliomas to define organizational principles across histological grades. In low-grade tumors, spatial organization is shaped by underlying brain anatomy. We identify a functional white-gray matter junction that restricts cortical invasion and is associated with marked changes in tumor composition and cellular phenotypes. This junction is preferentially traversed by oligodendrocyte progenitor (OPC)-like malignant cells, suggesting a role in tumor expansion. In contrast, tumors with intermediate histological features are largely disorganized, with few recurring interactions between cancer cell states and microenvironmental cell types. In high-grade tumors, hypoxia-associated structure emerges, resembling IDH-wild-type glioblastoma. Together, these findings reveal two independent axes of spatial organization-from anatomy-driven structure in low-grade tumors to hypoxia-driven organization in high-grade tumors-and establish a framework linking tumor grade to recurrent spatial interactions.

Isocitrate Dehydrogenase↗

Programmed ribosomal frameshifting triggers translational stress to promote viral replication.

Programmed ribosomal frameshifting (PRF) is a conserved viral strategy for expressing polyproteins from compact genomes. Although PRF is traditionally viewed as a structural mechanism, here we show that it functions as a regulatory signal that rewires host translation in favor of viral replication. A minimal SARS-CoV-2 PRF element is sufficient to activate the GCN2 arm of the integrated stress response (ISR) independently of the canonical ISR sensor ZAKα. This activation serves as a temporal switch during early infection to shut off host translation and is required for viral propagation in cells and human airway organoids. Proteomic and genetic screens identify DRG1 and IGF2BP3 as key mediators of PRF-induced GCN2 activation. We further show that this PRF-GCN2 axis is conserved in human immunodeficiency virus (HIV)-1 and West Nile virus, highlighting its broad relevance across RNA viruses. These findings reveal a sophisticated mechanism of viral translational control, highlighting PRF as a stress-inducing module that enhances viral replication.

RNA virus↗

Internal Bayesian precision modulates the neural representation of social attention: Disentangling implicit and explicit components via model-informed multivariate EEG analysis.

Social attention integrates sensory cues with high-level cognitive expectations, yet the generative mechanisms through which implicit orienting and explicit belief-driven modulation interact remain poorly understood. This ambiguity complicates the distinction between specialized social modules and domain-general attentional processes. We combined a dynamic cueing task with hierarchical Bayesian modeling and model-informed multivariate EEG decoding to address this. Behavioral results revealed a computational double dissociation: symbolic arrow cues elicited heterogeneous strategies, whereas averted gaze recruited a consistent, surprise-driven computational phenotype. At the neural level, time-resolved decoding and temporal generalization revealed a critical representational shift starting approximately 400 ms post-cue. Initial activity related to physical cue features was rapidly replaced by stable neural templates of predicted spatial intent. Crucially, topographical activation patterns showed that this intentional template, characterized by a lateralized temporo-occipital distribution, emerged exclusively under high internal certainty. Furthermore, partial representational similarity analysis demonstrated that late-stage neural manifolds were overwhelmingly organized around integrated spatial goals rather than isolated sensory or motivational signals. These findings suggest that social attention is a specialized generative process, where internal certainty modulates the transformation of social perceptions into actionable top-down intentions.

Bayesian computational modeling↗

The Adaptive Roles of Active Transposable Elements in Insect Hosts.

Active transposable elements (TEs) are capable of generating new insertions in genomes and have historically been viewed as genomic parasites due to their largely detrimental or neutral effects. However, emerging evidence suggests that these elements also play a crucial role in driving adaptive evolution in insects. This mini-review synthesizes recent findings on how active TEs contribute to insect adaptation through various mechanisms, including regulation of gene expression, structural variation, and epigenetic effects. Notable examples of adaptation driven by active TEs include their roles in insecticide resistance, morphological adaptations, tolerance to harsh climates, and antiviral immune responses. We argue that while host silencing mechanisms, such as the piRNA pathway, tightly regulate TE activity to minimize harmful effects, the context-dependent activation of active TEs can generate beneficial genetic variation that enhances insect adaptations to anthropogenic and climatic pressures. Future research that integrates long-read sequencing, single-cell omics, and gene editing techniques will provide a robust mechanistic foundation for understanding the adaptive significance of active TEs in insects, with important implications for pest management, pollinator protection, and evolutionary biology.

Journal Article↗