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PubMed2026

Genomic Structural Equation Modeling Identifies a Shared Inflammatory Genetic Dimension Across Inflammatory Arthritis Phenotypes and Biomarkers.

BACKGROUND: Inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and gout, shares systemic inflammatory features indexed by C-reactive protein (CRP) and interleukin-6 (IL-6), yet the extent of their common genetic basis remains unclear. AIMS: We aimed to delineate the shared genetic architecture across IA phenotypes and inflammatory biomarkers. MATERIALS AND METHODS: We applied genomic structural equation modelling (Genomic SEM) to GWAS summary statistics for RA, PsA, gout, CRP and IL-6, fitted a single common factor, and performed multivariate GWAS followed by fine-mapping, transcriptome-wide association, gene-based analysis, pathway enrichment, and cell-type and spatial mapping. RESULTS: A single common factor was fitted (CFI = 0.990, SRMR = 0.045). The multivariate GWAS identified 56 genome-wide significant SNPs across 10 independent lead loci, including one novel signal. Fine-mapping prioritized high-confidence variants near PTPN22, the CRP gene cluster and a urate-associated locus. Gene-level analyses converged on DCLRE1B, PTPN22, IL6R, NLRP3 and HNF1A, with pathway enrichment implicating inflammasome assembly and metabolic-inflammatory overlap. Cell-type enrichment highlighted myeloid populations, and spatial mapping localized signals to lung, kidney, mucosal epithelium and gastrointestinal tissues. DISCUSSION: These results delineate a shared inflammatory genetic dimension across IA phenotypes and biomarkers, anchored in immune, inflammasome, cytokine-receptor and metabolic pathways. CONCLUSION: Together, these findings provide a valuable framework for prioritizing candidate genes and cellular contexts for future investigation.

TWAS↗
PubMed2026

Spatial Transcriptomics Identifies Characteristic Immunological Niches in Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is primarily driven by a Type 2 immune response, with T helper (TH2) cells producing IL-4 and IL-13, thereby promoting inflammation, itch, and a compromised skin barrier. Yet, the spatial organization of pathogenic immune cells and their interactions with stromal and epithelial compartments in human AD skin remain incompletely understood. METHODS: We performed 10× Genomics Visium spatial transcriptomics on FFPE skin biopsies from patients with AD (n = 6), psoriasis (n = 2), and healthy controls (n = 5). Data were integrated with AD single-cell RNA sequencing (scRNA-seq) datasets and complemented by imaging mass cytometry (IMC) and multiplex immunofluorescence (IF) to validate the spatial localization of immune cells. Cell-cell communication analysis revealed putative signaling interactions within immune niches. RESULTS: Spatial clustering resolved tissue compartments and demonstrated transcriptional dysregulation in keratinocytes in AD and psoriasis. AD lesions showed a conserved spatial organization of immune aggregates within the superficial dermis. Integration of scRNA-seq signatures revealed spatially organized co-localization of T cells and mature migratory dendritic cells (mmDCs). We developed a ring-based neighborhood analysis to characterize the cellular organization of the immune-stromal niches, revealing T cell-enriched regions surrounded by inflammatory fibroblasts and activated keratinocytes. Intercellular communication analysis further identified putative signaling within mmDC-T cell niches that may promote pathogenic T cell recruitment and activation. Application of tertiary lymphoid structure (TLS) signatures indicated the presence of TLS-like regions. IMC and IF validated the close spatial proximity between activated TH2 cells and mmDCs. CONCLUSION: AD lesions contain spatially organized TLS-like immune niches at the dermal-epidermal junction, characterized by the close association of T cells and mmDCs and coordinated interactions with surrounding stromal and epithelial compartments. These mmDC-T cell niches may represent potential targets for future therapeutic strategies aimed at disrupting persistent local inflammatory pathways and improving long-term disease control.

atopic dermatitis↗
PubMed2026

Genomic Insights Into Heterosis: Dominance or Additive × Additive Interaction?

Heterosis was documented in the 18th century, but its biological basis has been debated since. The theoretical framework proposed by Hill, and adapted by Lynch, is based on two central parameters: admixed composition (S), and the heterozygosity (H). Using genomic information, it is now possible to estimate independently the individual realized Si and Hi. In this research, a methodology for estimating the contribution of dominance and additive &#xd7; additive effects to heterosis is proposed. This approach would be especially relevant in cases where there is insufficient phenotypic information available, or an adequate genetic group experimental design, common in humans, wild species and other admixed populations. We also provide theoretical arguments highlighting the enhanced precision of the estimations of heterosis parameters through this method. Furthermore, we exemplify this procedure by analysing data from an experimental F2 pig population, which was initially designed for QTL mapping. Notably, all animals in this population were genotyped (including F1 and parental breeds), but phenotypic information was only available for F2 individuals and included 13 traits related to growth, fat deposition, carcass characteristics and meat quality. Significant additive effects (p&#x2009;<&#x2009;0.05) were detected for longissimus muscle area and carcass temperature, suggesting complementary additive effects for these traits. Significant dominance and additive &#xd7; additive effects were also detected for birth weight and carcass length, respectively (p&#x2009;<&#x2009;0.05), indicating that heterosis for these traits is primarily attributable to dominance and additive &#xd7; additive interactions. These results demonstrate that the proposed methodology can successfully estimate the genetic components underlying heterosis and underscores the utility of this approach in&#xa0;situations where we possess genomic data but limited phenotypic data.

SNP↗
PubMed2026

Transgenerational chromosome repair in the asexual bdelloid rotifer Adineta vaga.

Homologous recombination is an essential DNA repair mechanism that also promotes chromosome pairing and ensures allele segregation during meiosis in sexual organisms. Here, we explore the dual function of homologous recombination in the bdelloid rotifer Adineta vaga, an asexual species known for its remarkable resilience to extreme genotoxic stresses. Genomic analyses reveal that A. vaga uses meiotic recombination to promote spontaneous crossovers and gene conversion during oogenesis and to repair the genome in response to DNA damage. The data also support a model of transgenerational DNA repair, termed break-induced homologous extension repair (BIHER), in which broken chromosomes are progressively restored over multiple generations. Our findings suggest that meiotic BIHER, coupled with the holocentric structure of chromosomes, may represent a key adaptation of life in extreme environments.

Animals↗
PubMed2026

Widespread atypical UV-induced mutations form in single-stranded DNA.

Persistence of common ultraviolet (UV)-induced lesions, like cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4-PPs), typically results in C>T substitutions at dipyrimidines: a mutation pattern that composes the single-base substitution (SBS) signature 7 in cancer. Oncogenic melanoma mutations rarely involve SBS7-like substitutions. We recently identified noncanonical UV-induced mutations in yeast that appear to originate from atypical AC and TA photoproducts. While an AC photoproduct could account for formation of BRAF V600K, other melanoma drivers like BRAF V600E and NRAS Q61K involve other mutation types, suggesting possible existence of additional atypical photoproducts. Here, we couple temperature-induced telomeric end resection in yeast with serial UV irradiation and whole-genome sequencing to show UV light induces an extended array of noncanonical mutations in single-stranded DNA (ssDNA). This includes AT>AM, GT>GV, AC>AA, AT>TT, and TA>TT substitutions that are resistant to photo-reversion, indicating that they likely originate from atypical photoproducts. UV-induced mutation spectra in yeast lacking Rad30 indicated that Pol &#x3b7; plays substantial roles in the bypass of CPDs and 6-4-PPs regardless of telomere proximity. Unexpectedly, expression of a mutant DNA pol &#x3b5; (pol2 M644G) reduced both canonical and noncanonical UV-induced mutations specifically within subtelomeric regions of the genome. This suggests a preferential role for pol &#x3b5; in the resynthesis of uncapped telomeres, with the M644G mutation conferring accurate lesion bypass capabilities to the replicative polymerase. ssDNA-specific UV lesions provide additional damage-mediated mechanisms for the production of oncogenic mutations in melanoma, such as the BRAF V600E mutation that involves a GT>GA substitution.

Ultraviolet Rays↗
PubMed2026

Toxoplasma gondii infection disrupts secondary bile acid transformation in feline gut microbiota.

UNLABELLED: Bile acid (BA) transformation relies on gut microbiota and is vulnerable to Toxoplasma gondii infection, yet feline microbial BA-transforming capacity upon toxoplasmosis remains unclear. Here, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. The results revealed that the feline gut microbiome harbored widespread genetic potential for BA transformation but lacked a complete 7&#x3b1;-dehydroxylation pathway due to the absence of the key gene baiE. The BA transformation-related genomes (2,045 in total) were predominantly from the phyla Bacillota_A and Actinomycetota, among which only 37 encoded baiB, all belonging to Bacillota_A. The distribution of BA transformation-related genes varied across intestinal regions: genes encoding 7&#x3b1;-HSDH were primarily enriched in the small intestine, whereas genes encoding 3&#x3b1;-HSDH, baiCD, and baiH were more abundant in the large intestine. Additionally, the abundance of genes encoding BSH and 3&#x3b1;-HSDH increased significantly in the small intestine on day 3 post-infection, accompanied by increases in the phylum Bacillota_C and genera such as Blautia_A, Enterococcus_E, and Ligilactobacillus. Serum metabolomics revealed a significant increase in cholesterol levels post-infection, supporting the impact of T. gondii infection on intestinal BA transformation. These findings illustrated that the feline gut microbiota played an important role in BA transformation and that T. gondii infection disrupted the microbial potential for secondary BA transformation. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis. IMPORTANCE: Bile acid (BA) transformation plays a critical role in host metabolism and immune regulation. Although studies on BA transformation are increasing, the capacity for BA transformation within the feline gut microbiota and the impact of Toxoplasma gondii infection on this capacity remain unclear. To bridge this gap, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. Our findings revealed that the feline gut microbiome lacked a complete 7&#x3b1;-dehydroxylation pathway, and the specific functions involved in BA transformation may differ between the small and large intestines. Furthermore, integrated metagenomic and serum metabolomic analyses suggested that T. gondii infection disrupted BA transformation capacity in the small intestine. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.

Toxoplasma gondii↗
PubMed2026

Population-level genomic surveillance of human norovirus using wastewater-based whole-genome sequencing.

Wastewater-based surveillance has garnered increasing attention as a valuable approach for capturing community-level infection dynamics that are often difficult to detect through clinical reporting systems alone. In this study, we analyzed human norovirus genotype distributions and whole-genome-level variations in wastewater samples collected in Gwangju, Korea. These results were interpreted in conjunction with a documented foodborne outbreak to evaluate the epidemiological relevance of wastewater-based monitoring. Human norovirus concentrations were quantified using TaqMan Array Card-based RT-qPCR, and whole-genome next-generation sequencing (NGS) was performed to obtain viral read counts and reads per kilobase per million filtered reads values. Overall, strong correlations were observed between RT-qPCR-based concentrations and NGS-derived metrics. Genotype dynamics varied among wastewater treatment plants, reflecting differences in catchment size and local population characteristics. In particular, the relative abundance of GII.17[P17] increased during epidemiological week 50, temporally coinciding with a documented local foodborne outbreak. Variant analysis revealed that wastewater samples exhibited mixed nucleotide patterns, with multiple alleles coexisting at varying relative frequencies rather than fixed substitutions. Notably, some nonsynonymous variants detected in clinical samples were also observed in wastewater samples collected surrounding the outbreak period. Together, these findings demonstrate that wastewater-based whole-genome surveillance can capture both genotype-level shifts and nucleotide-level dynamics at the population scale, highlighting its potential as a complementary tool for monitoring community-level norovirus circulation and outbreak-associated genotype dynamics.IMPORTANCEWastewater-based surveillance is increasingly recognized as a promising approach for capturing community-level infection dynamics that are often missed by clinical surveillance. In this study, we applied whole-genome sequencing to wastewater samples collected in Gwangju, South Korea, to comprehensively characterize human norovirus genotype distributions and genetic variation. Distinct genotype patterns were observed across wastewater treatment plants, reflecting differences in catchment population size and local characteristics. Notably, an increase in the GII.17[P17] genotype detected in wastewater coincided with a foodborne outbreak investigated in Gwangju, demonstrating the potential of wastewater surveillance to reflect ongoing community transmission and emerging outbreak-associated genotypes. In addition, wastewater samples contained diverse and coexisting genetic variants, capturing population-level viral diversity and evolutionary dynamics that are not readily detected through clinical surveillance alone. These findings highlight the value of wastewater-based whole-genome surveillance for monitoring community-level viral circulation and support its integration as a complementary strategy to existing clinical surveillance systems.

genotype dynamics↗
PubMed2026

Bacterial R-bodies with common morphologies and unrolling dynamics are phylogenetically scattered, indicating extensive lateral gene transfer and wide application potential.

Refractile bodies (R-bodies) of gram-negative bacteria are large proteinaceous assemblies, rolled up in the form of an Archimedean spiral. They exhibit rapid rod-like reversible extension in the micrometer range when cued by chemical environmental triggers and have potential for synthetic biology and biochip applications. Initially described for the Paramecium endosymbionts Caedibacter taeniospiralis and Caedimonas varicaedens, R-bodies have since been discovered in many classes of Pseudomonadota, both in endosymbionts and in non-endosymbionts. However, despite the fact that the genetics and morphologies, as well as the unrolling kinetics of R-bodies from different species, show considerable diversity, no recent study has integrated these aspects into a single framework. The latter would be advantageous for the creation of an R-body biotechnology toolbox, where different properties determine the application area. Here, we have examined the R-bodies from six different Pseudomonadota, comprising both phylogenetically diverse endosymbionts and non-endosymbionts. Comparison of the morphologies of the rolled-up and unrolled forms, obtained using electron microscopy and high-quality images, to their corresponding genetic data indicates that extensive lateral gene transfer has occurred, which confounds a common framework based on these data. However, we have also studied the R-body extension and retraction kinetics using high frame-rate light microscopic video recordings, where we show for the first time that R-bodies can be classified into two classes, showing "fast burst" or "slow" acid-induced extension kinetics, respectively. We propose that this criterion may, in fact, be the most useful for the choice of an R-body tool for biotechnological purposes.IMPORTANCER-bodies are unique proteinaceous macromolecular structures capable of massive reversible extension in response to external environmental triggers without the input of chemical energy. They comprise only a few small polypeptides, which makes them potentially highly amenable to tuning via genetic engineering, as well as being exceptionally stable. These properties would be highly desirable in biotechnology and synthetic biology, as well as in biochip applications, where a controlled mechanical extensor might play an integral part in a nanoscale molecular machine. So far, only R-bodies from a single species, Caedibacter taeniospiralis, have been characterized extensively. However, in recent years, genomic information has revealed that a panoply of R-bodies are widely distributed among gram-negative phyla, although studies have generally not included morphological data. This study brings these two areas together to provide a holistic overview of the field and also reveals new insights into key dynamic aspects of R-body extension.

R-bodies↗
PubMed2026

New form of HPV18 L1 found in native virions contributes to virion stability and infectivity.

UNLABELLED: Current dogma states that papillomavirus virions consist of only one form of the L1 major capsid protein. Human papillomaviruses (HPVs) have been studied using recombinant particles, thereby bypassing the need to grow the virus in a model of differentiating epithelium. Expression vectors engineered to produce L1 utilize a consensus methionine found in many HPV types. However, HPV18 has two additional in-frame methionine residues located 61 and 26 amino acids upstream of the consensus methionine. These methionine residues are excluded from the L1 expression vector used to create the recombinant virus. On the other hand, HPV produced from organotypic raft culture allows virions to be assembled in a differentiating epithelium in the presence of its native promoters and complete genome. Here, we have utilized this system to show that the wild-type HPV18, produced in a more natural setting, translates a larger form of L1 from the upstream methionine, which is 61 amino acid residues upstream from the consensus methionine, and a smaller form from the consensus methionine, with both sizes assembled in the newly formed virion. Ablation of the upstream methionine residue at position 61 altered the virion capsid conformation, and also decreased virion stability and infectivity. IMPORTANCE: The present study investigates whether the papillomavirus virions contain more than one isoform of the L1 major capsid protein. By using organotypic raft cultures that mimic the naturally differentiating epithelium, we revealed that wild-type HPV18 expresses and incorporates two distinct L1 isoforms into the virion, including a previously unrecognized longer form translated from an upstream methionine. Our study has further shown that disruption of the upstream methionine impairs virion stability and infectivity, demonstrating that the longer L1 isoform contributes to proper capsid architecture and viral function. These findings offer a new understanding of HPV capsid biology and have significant implications for the future development of HPV vaccines, diagnostics, and antiviral therapies.

HPV18↗
PubMed2026

African swine fever virus A151R protein antagonizes the antiviral activity of barrier-to-autointegration factor (BAF) by targeting its dsDNA-binding activity.

Barrier-to-autointegration factor (BAF) is a ubiquitous double-stranded DNA-binding protein that compacts DNA and can restrict poxvirus replication in the cytoplasm. BAF antiviral DNA-binding activity is tightly regulated by dynamic phosphorylation mediated by viral and cellular enzymes. For example, vaccinia virus counteracts BAF by encoding the B1 kinase, which phosphorylates BAF and abrogates its DNA-binding activity. Some DNA viruses, such as African swine fever virus (ASFV), undergo cytoplasmic replication but appear to lack a B1-like kinase. Interestingly, ASFV encodes A151R, a viral protein recently found to stably interact with BAF. Here, we demonstrate that A151R is capable of counteracting the antiviral properties of BAF. Structural modeling indicates that A151R is not a protein kinase and does not phosphorylate BAF but instead directly targets its double-stranded DNA-binding interface. This interaction enhances genome replication and progeny production of a B1-deficient virus. Mechanistically, A151R markedly impairs BAF DNA binding and disrupts its dimerization, a key requirement for high-affinity DNA association. Importantly, disruption of the A151R-BAF interaction abolishes these effects and restores BAF antiviral function. In addition, expression of the unphosphorylatable BAF mutant, which normally exhibits strong chromatin association, was redistributed to the cytoplasm in the presence of A151R, further supporting phosphorylation-independent regulation of BAF-DNA association. In conclusion, our findings support a previously unrecognized mechanism by which ASFV A151R disables BAF antiviral activity by obscuring its DNA-binding interface and inhibiting DNA binding in a phosphorylation-independent manner.IMPORTANCEDNA viruses replicating in the cytoplasm must overcome host intrinsic defenses to ensure productive replication, yet the mechanisms underlying their antagonism of the DNA-binding antiviral factor BAF remain incompletely understood. Here, we identify African swine fever virus (ASFV) A151R as a novel viral regulator that disables BAF by targeting its double-stranded DNA-binding interface rather than altering its phosphorylation state. We demonstrate that A151R impairs BAF DNA binding, disrupts its dimerization, and promotes viral DNA accumulation and progeny production in a BAF-dependent manner. Importantly, this activity requires A151R-BAF interaction and is independent of BAF phosphorylation status. Our findings reveal a previously unrecognized strategy employed by ASFV to neutralize host DNA-binding restriction factors and expand the molecular framework of BAF-mediated antiviral defense.

A151R↗
PubMed2026

De novo genome assembly of Clonostachys rosea CMAA1284: a fungal strain with biotechnological potential.

Clonostachys rosea is a fungus with significant applications in biological control, plant growth promotion, and secondary metabolite production essential for agriculture. We report the de novo genome assembly of C. rosea strain CMAA1284 (also known as LQC 62), which shows high contiguity and excellent gene completeness, supporting its use for functional genomics and biotechnological studies.

Clonostachys rosea↗
PubMed2026

Draft genome sequence of Brevibacillus borstelensis strain BB2 isolated from a hot spring in the Cocham&#xf3; Valley, Chile.

Brevibacillus borstelensis strain BB2 was isolated from a soil sample collected in the Cocham&#xf3; Valley, Chile. The draft genome comprises 187 contigs totaling 5.25 Mb with a guanine-cytosine (GC) content of 51.7%. Sequencing on an MGI DNBSeq-G400 platform generated 3,406,660 paired-end reads, providing approximately 170&#xd7; coverage for genomic resource reporting.

Brevibacillus borstelensis↗
PubMed2026

VISTA: a classifier for metagenomic subspecies and community state typing of the vaginal microbiome.

Metagenomic community state types (mgCSTs) capture within-species genetic and functional diversity and community structure of the vaginal microbiome, enabling precise links between microbiome composition, function, and health-related risk. VISTA, the Vaginal Inference of Subspecies and Typing Algorithm, is a two-step classifier that assigns mgCSTs to vaginal metagenomes, providing standardized, scalable classifications.

bioinformatics↗
PubMed2026

Draft genome sequence of Bacillus atrophaeus X3, a pigmented subantarctic soil isolate from Magallanes Region, Chile.

Bacillus atrophaeus strain X3, isolated from subantarctic soils near Laguna Amarga, Magallanes Region, Chile, harbors a high-quality genome (three contigs, 4.08 Mb, 43.4% GC content). Its genomic sequence provides insights into cold adaptation mechanisms in the Bacillus subtilis group, with potential relevance for emerging biotechnological applications.

Bacillus atrophaeus↗
PubMed2026

MDV-like endogenous viral elements act as immune rheostats in Aedes cells by modulating defensin A-mediated responses to arboviruses.

Mosquito cell lines are essential tools for arbovirus research. Endogenous viral elements (EVEs) are prevalent in mosquito genomes, yet their functional effects on host immune responses remain unclear, potentially complicating experimental interpretations. In this study, we systematically characterized endogenous mosquito densovirus-like elements (EMLs) within the Aedes aegypti Aag2 cell line and found that these endogenous EMLs are transcriptionally active but translationally defective. The silencing of EML transcripts significantly diminished the replication of Zika virus (ZIKV), Japanese encephalitis virus (JEV), and chikungunya virus (CHIKV), while transiently increasing dengue virus 2 (DENV-2), thereby indicating a virus-dependent regulatory mechanism. Mechanistically, RNA sequencing after EML interference, alongside plasmid-based mimic expression, demonstrated that EML transcripts downregulate defensin A, an antimicrobial peptide produced by mosquitoes. Functional assays using synthetic defensin A showed that this peptide differentially regulates arboviral infection. Binding assays and structural modeling further supported its interaction with viral envelope proteins, while stage-restricted infection assays revealed distinct stages of action: defensin A enhanced adsorption of ZIKV, JEV, and CHIKV, but did not promote DENV-2 adsorption or entry, and instead reduced DENV-2 RNA accumulation at the post-entry replication stage. Our findings highlight a previously unrecognized role of densovirus-derived EVEs in mosquito innate immunity, extending their functional scope from the well-established PIWI-interacting RNA-mediated antiviral defense to the regulation of antimicrobial peptide-associated immune pathways. These findings emphasize the necessity of accounting for EVE activity when analyzing data derived from mosquito cell lines, and suggest that related EVE-mediated immune regulation may contribute to arbovirus dynamics in mosquitoes.IMPORTANCEMosquito-borne viruses such as dengue, Zika, Japanese encephalitis, and chikungunya continue to threaten human health worldwide. Laboratory studies often use Aedes aegypti cell lines to investigate how these viruses interact with their mosquito hosts. Here, we show that the genomes of these cells contain endogenous viral elements derived from mosquito densoviruses. Far from being inert fossils, these sequences are transcriptionally active and regulate mosquito immunity by suppressing the antimicrobial peptide defensin A. This immune modulation influences the replication of different arboviruses in opposite ways, enhancing some while restricting others. Our findings reveal that integrated viral elements can shape the outcome of arbovirus infection, with important implications for interpreting mosquito cell culture experiments and for evaluating endogenous viral element-mediated immune regulation in mosquito-virus interactions.

Aag2 cell↗