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PubMed2026

Hide and seek: de novo identification in sugar beet reveals impact of non-autonomous LTR retrotransposons.

Plant genomes are filled with retrotransposons and their derivatives, constantly undergoing sequence diversification and structural rearrangement. Among them, short, non-autonomous retrotransposons lack full coding capacity and often form subfamilies. As a result, non-autonomous retrotransposons are incompletely identified in most to all genome assemblies.Here, we capitalize on our comprehensive understanding of the transposable element (TE) landscape in sugar beet (Beta vulgaris) to assess the extent of the blind spot for non-autonomous long terminal repeat (LTR) retrotransposons. This use case serves to answer if all of these sequences are derivatives of easier-to-identify full-length elements or if there is more variability that is currently overlooked.For this we applied a semi-automated structural discovery workflow followed by in-depth manual verification to characterize non-autonomous LTR retrotransposons in sugar beet. We retrieve more than 100 non-autonomous LTR retrotransposon families that lack complete autonomous coding capacity, including canonical terminal-repeat retrotransposons in miniature (TRIMs), elongated non-coding derivatives and families retaining fragmented coding remnants. The identified families span a broad range, including elements exceeding 15,000 bp in length and display evidence for reshuffling and modular evolution. Only a subset of families could be confidently linked to autonomous retrotransposons, showing sequence diversification within the non-autonomous LTR retrotransposon fraction beyond the autonomous genomic templates.We highlight that a large fraction of non-autonomous LTR retrotransposons is incompletely recovered with the current TE identification workflows, even if the output is well-curated and condensed into TE libraries and suggest procedures to remedy this gap. This study gives a genome-wide view into the non-autonomous LTR retrotransposon landscape of a single plant genome and highlights the importance of structure-based approaches for their identification and classification.

LTR retrotransposons↗

PubMed2026

Gut microbiota-driven indole-3-propionic acid and kynurenine production is associated with improved metabolic adaptation in periparturient dairy cows.

BACKGROUND: Gastrointestinal microbes convert tryptophan into various bioactive metabolites that influence host energy metabolism; however, these mechanisms are not well understood in periparturient dairy cows, which experience marked metabolic challenges during this period. RESULTS: In this study, we used periparturient dairy cows with rumen and ileal cannulas as in vivo models. Blood, rumen fluid, ileal digesta, and fecal samples were collected at four time points during the periparturient period. By combining metagenome-assembled genomes (MAGs) and targeted metabolite quantification, we characterized microbial tryptophan metabolism and associated metabolite profiles during the periparturient period. The results showed that postpartum cows exhibited significantly increased serum concentrations of triglyceride (TG), aspartate aminotransferase (AST), β-hydroxybutyrate (BHBA), and total bilirubin (T-Bil) compared with prepartum cows, together with decreased levels of several tryptophan metabolites, including indole-3-propionic acid (IPA) and kynurenine (KYN), indicating that tryptophan deficiency might aggravate metabolic disturbances. Metagenomic analysis identified 578 high-quality MAGs, of which 461 contained genes involved in microbial tryptophan metabolic pathways. Among these, the ruminal taxon CAG-791 harbors acdA and contributes to IPA production, whereas the hindgut taxon Treponema_D harbors kynB and promotes KYN formation. Decreases in both taxa were consistent with the reduced levels of these metabolites observed above. In a follow-up in vivo trial with tryptophan supplementation, the abundance of CAG-791 and Treponema_D increased, along with tryptophan-derived metabolites (IPA and KYN), which further partially mitigated metabolic disturbances. CONCLUSIONS: These findings characterize spatial and temporal changes in tryptophan metabolites and gut microbial features in periparturient dairy cows, and provide integrated evidence that alterations in tryptophan metabolism are associated with postpartum metabolic adaptation, thereby supporting the potential of tryptophan-targeted nutritional strategies to improve metabolic health in dairy cows.

Gastrointestinal microbiome↗

PubMed2026

Phylogeographic epidemiology of Dabie bandavirus in East Asia: divergent transmission networks and genotype‑linked clinical severity.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (SFTSV), exhibits geographically decoupled incidence and fatality patterns across East Asia. We aimed to elucidate the distinct ecological drivers and phylogeographic dynamics underlying this inland-coastal epidemiological divergence. METHODS: Integrating 1820 high-quality global genomes of SFTSV with well-characterized clinical cohorts (936 patients) and nationwide surveillance data (27,457 cases) from China, we constructed a comprehensive analytical framework. Ecological modeling, Bayesian phylogeography, and genotype-phenotype association analyses were employed to trace the evolutionary trajectories and clinical implications of the virus. RESULTS: A pronounced "inland-high-incidence vs. coastal-high-fatality" pattern of SFTS was identified. The incidence of SFTS exhibited divergent sensitivities to meteorological factors; inland transmission was sensitive to thermal fluctuations, whereas coastal dynamics were constrained by a sunshine threshold (> 200 h/month). In contrast, spatial divergence in clinical severity correlated with the distribution of regional viral genetic structures. Inland regions mainly co-circulated genotypes A, C, and D, while coastal regions were dominated by genotype B. Zhejiang province was identified as a genetic hub with significantly higher recombination frequencies than inland regions (11.0% vs. 3.5%, P < 0.001). Bayesian phylogeographic inference indicated frequent lineage exchange of Zhejiang province in China with the Republic of Korea and Japan. Clinically, genotypes B and D were associated with elevated mortality in coastal and inland regions, respectively, suggesting that the severe coastal phenotype is shaped by its genotype B-dominated structure. Additionally, the RdRp-N828S mutation emerged as a robust molecular correlate of fatal outcomes, warranting further functional validation. CONCLUSIONS: Divergent meteorological factors and plausible maritime transmission networks may underlie the geographically decoupled epidemiology of SFTS. These findings highlight that risk assessment must extend beyond incidence alone and provide a phylogeographically informed framework for targeted surveillance and genotype-specific interventions in high-risk hotspots.

Humans↗

PubMed2026

Diabetes related genetics and outcomes after total pancreatectomy with islet autotransplantation.

CONTEXT: Approximately 20% of patients with chronic pancreatitis achieve insulin independence one year after total pancreatectomy with islet autotransplantation (TPIAT), an outcome associated with younger age and lower pre-transplant HbA1c. The contribution of diabetes-related genetics to TPIAT outcomes is unknown. Genetic risk scores (GRS) are associated with C-peptide levels in type 1 (T1D) and type 2 (T2D) diabetes. OBJECTIVE: To evaluate whether T1D and T2D GRS and partitioned metabolic polygenic scores (PGS) are associated with diabetes before TPIAT and metabolic outcomes one year after transplant. METHODS: We genotyped 318 patients with chronic pancreatitis undergoing TPIAT in the multicenter "Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT" using a global screening array. Regression models assessed associations of T1D- and T2D-GRS and metabolic PGS with diabetes outcomes one year after TPIAT. RESULTS: Participants were 29±17 years old, 61% female, 84% non-Hispanic White, and 13% had diabetes prior to transplant. T2D-GRS was higher among those with pre-TPIAT diabetes (-0.6±0.3 versus -0.8±0.2, p=0.003) and was associated with higher pre-transplant HbA1c (β=0.19 % per 1-SD [95% CI:0.04, 0.33], p = 0.011). Adjusted for genotype-derived ancestry and islet equivalents/kg, the beta-cell PGS was associated with higher insulin dose (β=0.05 units/kg/day per 1-SD, [95%CI:0.01, 0.09], p=0.016) and higher insulin dose adjusted A1c (IDAA1c) (β=0.34[95%CI:0.03, 0.67], p=0.029) 1-year post-transplant. The lipodystrophy PGS was associated with higher IDAA1c (β=0.38 [95%CI:0.06, 0.69], p=0.019) and lower fasting C-peptide (β=-0.09 [95%CI:-0.18, 0], p=0.041) at 1 year. CONCLUSIONS: T2D genetic risk is associated with diabetes prior to TPIAT, and beta cell and lipodystrophy PGS are associated with post-TPIAT diabetes outcomes. Diabetes-related genetics may influence transplantation outcomes and inform metabolic heterogeneity.

C-peptide↗

PubMed2026

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans↗

PubMed2026

Heat-responsive ONSEN long terminal repeats integrate heat shock factor motifs, DNA methylation and natural sequence variation in Arabidopsis.

ONSEN is a heat-activated Ty1/copia retrotransposon in Arabidopsis thaliana controlled by heat shock factors (HSFs) and epigenetic silencing. Heat shock element (HSE)-like sequences in ONSEN long terminal repeats (LTRs) contribute to heat responsiveness, but relationships among sequence architecture, basal DNA methylation and natural variation remain unclear. We combined transcription-factor motif prediction, transposable-element comparisons, methylome and RNA sequencing (RNA-seq) data, and Arabidopsis genome assemblies. In silico disruption of five HSE cores eliminated HSF-family motif compatibility in the selected design and all 5119 exact-guanine-cytosine (GC) alternatives. Across 16 curated Columbia-0 terminal windows, ONSEN contained 33-49 non-redundant HSF motif-coordinate placements per 800 bp window and was strongly enriched relative to 1930 non-ONSEN transposable elements across score thresholds and continuous metrics. Direct comparison with 779 non-ONSEN LTR retrotransposons showed selectively elevated basal CHH methylation (where H = A, C or T) at ONSEN termini. Genome-wide RNA-seq analysis revealed broad heat-responsive gene and transposable-element changes, including strong ONSEN induction, whereas candidate-window analysis distinguished ONSEN from most HSF-rich non-ONSEN outliers. ONSEN-like variants across eight accessions generally retained HSF-compatible motifs while altering predicted DNA binding with one finger-family motif composition. Together, these findings define ONSEN terminal regions as HSF-rich regulatory sequences that retain heat-responsive potential within a methylated chromatin context and identify candidates for functional analysis.

DNA Methylation↗

PubMed2026

Tailless terminates the neural stem cell temporal cascade in both the optic lobe and central brain.

Temporal patterning is an evolutionarily conserved mechanism to produce neuronal and glial diversity from common cells of origin during neurodevelopment. This process is controlled by a series of temporal transcription factors that are transiently expressed and drive the sequential production of specific progeny subtypes. Intermediate neural progenitors (INPs) and optic lobe neural stem cells (OL NSCs) share striking similarities in temporal factor expression despite divergent cells of origin. Tailless (Tll) is a terminal temporal factor in the visual system in OL NSCs. Its expression coincides with the termination of neurogenesis and onset of gliogenesis. Here, we report that Tll also acts as a terminal factor in Drosophila INPs, demonstrating functional conservation. Tll expression is activated by the preceding temporal factor Scarecrow, and represses odd-paired and hamlet. tll also plays a partial role in promoting gliogenesis in gliogenic NSCs. We performed genome-wide binding analysis of Tll in the OL NSCs and INPs by Targeted DamID, revealing both conserved and divergent targets, reflecting differences in regulatory outcomes. We show that temporal patterning mechanisms are conserved between different brain regions, whilst facilitating lineage-specific outputs.

Animals↗

PubMed2026

Life in sediments fosters 'sexual' speciation in the Shewanella baltica complex.

Understanding how intra- and interspecific differentiation arises in natural microbial populations is central to explaining the processes that drive bacterial evolution. Motivated by the co-occurrence of multiple putative genospecies closely related to Shewanella baltica in Baltic Sea sediments, we investigated the genomic structure of this species complex across fine spatial scales. We analyzed 112 genome sequences from strains collected across several sediment cores and depths (0-6 cm) at Vaxön (Stockholm archipelago, Sweden) as well as earlier isolates from this site and allopatric strains from surrounding locations obtained from both sediments and the water column. Using a reverse-ecology population genomics approach, we found unprecedented genomic diversification among sediment-associated strains, which form a species complex resolving into three cohesive evolutionary groups (G1, G2, and G3) with distinct signatures of metabolic specialization including sulfite respiration. While G1 consists predominantly of a single species (S. baltica) with high gene turnover, G2 and G3 comprise an array of divergent putative genospecies and previously reported species consistently recovered from sediments. Patterns of homologous recombination indicate that diversification of the lineages within G2 and G3 is primarily recombination-driven ('sexual') and is associated with specialization in sulfite reduction and utilization of certain carbon sources. The extent of diversity uncovered here far exceeds that reported for S. baltica from other environments, suggesting that a sediment-associated lifestyle promotes the emergence of novel genotypes. These findings expand the known limits of sympatric speciation in prokaryotes beyond subspecific ecotypes, demonstrating that bacterial species can diverge and persist as distinct lineages in the absence of spatial segregation and at microgeographic scales. Furthermore, our results suggest that collective interactions and ecological differentiation can structure sediment-associated bacterial populations strongly enough to drive divergence at the species level.

Journal Article↗

PubMed2026

Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.

BACKGROUND: Chronic kidney disease (CKD) occurs in 20-50% of the people living with Type 2 diabetes (T2D) and is the leading cause of kidney failure worldwide. The cause of CKD is not fully understood, and few interventions prevent CKD in individuals living with diabetes. Here, we use large-scale proteomics data to identify circulating proteins that mediate the relationship between T2D and kidney disorders. METHODS AND FINDINGS: First, we used two-sample mendelian randomization (MR) and identified 71 circulating proteins whose levels were altered by genetic predisposition to T2D based on circulating proteomic GWAS from deCODE with 35,559 individuals and T2D GWAS with 80,154 cases. Then, we used cis-genetic variants to proxy the causal effect of some of these T2D-influenced circulating proteins and found that, collectively, five proteins (INHBC, GNPTG, LPO, AGRN, and CTSD) affected three kidney traits (blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR] and CKD risk) based on GWAS with up to 1,004,040 participants. Notably, we found that higher levels of circulating INHBC protein were estimated to lead to a lower eGFR and higher BUN based on MR analyses. We then replicated this MR analysis with proteomic GWAS from four additional cohorts, namely, UKB-PPP, Fenland, ARIC, and EPIC-Norfolk. We observed a consistent direction of effect across all four proteomic GWAS datasets, supporting the robustness of our results against platform and cohort variation. In observational analyses, increased circulating INHBC levels were associated with increased hazard for kidney disease diagnosis in 37,854 UK Biobank participants. We estimated that circulating INHBC levels mediate 1.3% (95% confidence interval [0.85%, 1.9%]) of the association between T2D and kidney disease diagnosis. There are important limitations in this study. Firstly, although we observed limited evidence for violations to the MR assumptions, some are untestable. Secondly, our study was not based on individuals with diabetic kidney diseases, but rather independent population-based studies assessing diabetes and kidney function separately. Therefore, additional functional analyses in disease specific cohort are needed. CONCLUSIONS: Collectively, these findings suggest that T2D influences the risk of CKD, in part, through increased circulating INHBC levels.

Humans↗

PubMed2026

Correction: Genetic differentiation of Oncomelania hupensis robertsoni in hilly regions of China: Using the complete mitochondrial genome.

[This corrects the article DOI: 10.1371/journal.pntd.0012094.].

Published Erratum↗

PubMed2026

Executive function in alcohol use disorder with low psychiatric comorbidity: Comparison with a non-clinical sample and predictive value for treatment outcome.

BACKGROUND: Executive functions (EF) encompass abilities such as planning, decision-making, and inhibitory control, critical for learning, establishing and maintaining behavioral change. The association between alcohol use disorder (AUD) and impairments in EF are well established. However, prior research is dominated by studies on convenience samples including individuals with severe AUD with high levels of psychiatric comorbidity, which limits generalizability. The present study therefore aimed to investigate the degree of impairment and predictive ability of EF, on alcohol consumption, among individuals with moderate AUD with low levels of psychiatric comorbidity. METHODS: Adults with moderate AUD (n = 147) were recruited at three specialized addiction outpatient clinics in Stockholm, to a randomized controlled trial investigating the efficacy of two psychological treatments. Participants underwent neuropsychological testing before treatment. Eight tests from the CANTAB® battery were administered at baseline, assessing mental flexibility, sustained attention, visuospatial working memory, response inhibition, and delay discounting. Assessments of alcohol use and related symptoms were conducted at baseline, the 12- and 26-weeks follow-up. A non-clinical reference sample (n = 72) completed corresponding CANTAB® tests. The two groups were compared regarding EF using descriptive statistics and t-tests, and the predictive value of EF for reduction in alcohol consumption, was investigated using multiple regression models. RESULTS: Individuals with AUD did not perform worse on any of the tests on executive function (CANTAB®) as compared to the non-clinical reference sample. Measures of EF were not significant predictors for reduction in alcohol use for the 12-week, or the 26-week follow-up. CONCLUSIONS: EFs were not impaired and were not a clinically relevant predictor of treatment outcomes in this population with AUD. Future research on EF as a predictor in AUD treatment, needs to corroborate the present findings, and include other populations, e.g., with different socio-economic backgrounds and by including other methodologies for measuring EF.

Humans↗

PubMed2026

From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn's disease.

BACKGROUND: Acute pancreatitis (AP) and Crohn's disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear. METHODS: We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases = 8446; Ncontrols = 437,418) and CD (Ncases = 12,194; Ncontrols = 28,072). Firstly, cross-trait genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Secondly, to pinpoint specific pleiotropic loci and prioritize candidate genes, we employed PLACO under a rigorous composite null hypothesis, integrated with Bayesian colocalization and SMR/HEIDI analyses. Finally, we dissected the underlying biological context by mapping tissue-specific regulatory enrichment and pathway convergence using FUMA, MAGMA, and Stratified LD Score Regression (S-LDSC). RESULTS: AP and CD showed significant positive genetic correlation (LDSC: rg = 0.178, SE = 0.079, P = 0.025; HDL: rg = 0.294, SE = 0.096, P = 0.0021). Pleiotropy analyses revealed 86 SNPs and 6 independent genome-wide significant pleiotropic loci (lead variants at 5q33.1, 6q22.33, 7q34, 10q24.2, 15q22.33 and 19q13.11, PPLACO < 5 × 10-8). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4 = 0.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes-RSPO3, ATG16L1, SMAD3, FADS1, ZPBP2, FADS2, PRKAA1 and IRGM. Gene-set analyses highlighted IL-23/Th17-related and broader inflammatory response pathways. CONCLUSIONS: AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-β/SMAD-related biology.

Humans↗

PubMed2026

Toward personalized interventions for preventing depression in primary care: Qualitative and quantitative findings from the e-predictD pilot study.

BACKGROUND: The predictD intervention, delivered by family physicians (FPs), has demonstrated effectiveness and cost-efficiency in preventing depression and anxiety. The e-predictD study aims to design, develop, and evaluate a novel personalized intervention for depression prevention by integrating information and communication technologies (ICTs), risk prediction algorithms, and decision support systems (DSS) for both patients and FPs. OBJECTIVE: To evaluate the satisfaction, usability, and acceptability, of a beta version of the e-predictD intervention in primary care settings. METHODS: The e-predictD intervention follows a biopsychosocial approach, including an initial patient-FP interview, specific FP training, and an app. A β-version was tested in a pilot study without a control group over three months. The app integrates a validated depression risk prediction algorithm, decision algorithms, and a monitoring system supporting the DSS. The DSS generates a personalized prevention plan (PPP) from eight intervention modules: physical exercise, social relationships, problem-solving, communication skills, decision-making, assertiveness, sleep improvement, and cognitive restructuring. Patients and FPs discussed the PPP in a 15-minute baseline interview, selecting modules for implementation over three months. Semi-structured interviews gathered feedback. Assessments included depression (PHQ-9), anxiety (GAD-7), quality of life (SF-12), and major depression risk (predictD algorithm). RESULTS: Six FPs from six Spanish cities enrolled 56 non-depressed patients at moderate-to-high risk of depression; 47 (84%) completed follow-up. The app was used for a median of six days (interquartile range: 1-30). Both FPs and patients expressed satisfaction, leading to incorporated improvements. After three months, significant reductions in major depression risk and anxiety symptoms were observed, alongside improved mental quality of life. However, no significant changes were found in depressive symptoms or physical quality of life. CONCLUSION: This pilot study supports the feasibility and acceptability of the e-predictD β-version, despite lower-than-expected app usability. Health improvements were observed, warranting confirmation in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03990792.

Adult↗

PubMed2026

4D-DIA proteomics reveals distinct proteolytic landscapes induced by mechanical stress, Agrobacterium, and a viral capsid precursor.

Nicotiana benthamiana is a widely used platform for plant molecular farming, yet recombinant protein yields are frequently compromised by the host's innate defense mechanisms, particularly proteolytic degradation. While the general effects of Agroinfiltration are known, the distinct contributions of mechanical injury, bacterial perception, and product-specific stress remain poorly resolved. Here we utilized high-depth 4D-DIA proteomics to dissect the host response across three dimensions: physical stress (buffer infiltration), pathogen-associated stress (Agrobacterium), and product-associated stress (GFP vs. the FMDV capsid precursor P1_2A). We demonstrate that buffer infiltration is not a neutral event but an independent inducer of cell wall remodeling and oxidative stress. By filtering out these background effects, we defined a core Agrobacterium-responsive proteome characterized by a growth-defense trade-off. We also expanded the known protease repertoire of N. benthamiana to 1,505 enzymes through improved genomic annotation. We found that the expression of the FMDV capsid precursor P1_2A was associated with a distinct and more pronounced protease profile compared to soluble GFP, characterized by the upregulation of subtilases and cysteine proteases. These findings suggest that host proteolytic responses vary with the recombinant cargo, a factor worth considering when designing engineering strategies for the production of complex biopharmaceuticals in plants.

Proteomics↗

PubMed2026

Exploring cross-category relationships between symptoms in people with hypermobile EDS (hEDS) to identify disability patterns.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with variable symptom presentation across multiple organ systems and significant morbidity. Little is known about hEDS etiology and identifying patterns of symptom co-occurrence can reveal previously unidentified relationships between phenotypes and inform studies of underlying disease pathophysiology for symptoms that may share functional biological pathways. In this exploratory analysis, we specifically assessed the distribution of symptoms in case and controls to identify clusters of co-occurring symptoms. METHODS: We have interrogated clinically relevant symptom areas in 47 females with hEDS, 36 age-matched female controls and 8 hypermobile patients without chronic pain. Studied symptoms include general health, mental health, body pain, vitality and energy, autonomic symptoms, bleeding, and gastrointestinal symptoms. We conducted hierarchal clustering on principle components (HCPC) to identify groups and compared the groups for the previously described symptoms. Radial plots were used to identify relationships between severe symptom categories. RESULTS: Our analysis reveals statistically significantly more severe symptoms in all categories in people with hEDS compared with age- and sex-matched controls and asymptomatic hypermobile patients. HCPC identified clearly separated Low, Moderate, and High symptom groups within participants. The Low dysfunction groups include nearly all controls and hypermobile patients without chronic pain. The High dysfunction group includes ~60% of people with hEDS, while around 40% are in the Moderate dysfunction cluster. Cluster solutions for all participants were stable with moderate fit (silhouette 0.64; Jaccard boot mean 0.91). Group level radial plots showed high bleeding severity across all symptom clusters, while disproportional severity of general health, physical function, limitation of role due to physical symptoms, pain, and social functioning deficits differentiates the High from Moderate and Low Dysfunction clusters. CONCLUSION: Using this analysis at the group level has revealed patterns suggesting a progression of disease symptoms. People with hypermobility do not uniformly have severe symptoms but instead have some symptoms that differentiate from non-hypermobile individuals. While exploratory, using a radar multi-symptom analysis may be used to evaluate disproportionately severe symptoms contributing to the patterns of global symptom severity. These include pain but also ability to perform roles, suggesting strong utility of physical and occupational therapies to emphasize coping. This may also allow better targeting of etiological studies and may have additional utility at an individual level to develop symptom management strategies.

Humans↗

PubMed2026

GenBank mining reveals novel insights into Rhizobium phylogeny: Identical 16S rRNA sequences are mainly uncoupled from species designation, host plant, and geographic origin: How this search suggested the definition of a direct 'microbial h-index'.

16S rDNA is the historical gold standard for bacterial identification, particularly in metabarcoding approaches reliant on sequence similarity thresholds. We analyzed 6,660 Rhizobium 16S rRNA gene sequences from GenBank to examine the relationship between sequence identity and three metadata: species name, host plant, and geographic origin. Using an iterative BLAST-based pipeline, we detected 116,069 pairwise matches and assessed concordance among sequences (average length 1,328 bp) sharing 100% identity. For those in which the organism name, host plant and country of isolation were present in the record, surprisingly, 66.59% of identical sequence pairs showed full discordance across all three metadata, while only 1.40% shared the same name, host, and country. The most widespread sequence, detected 371 times, was associated with over 56 different host plants across 25 countries and bore multiple species name designations. These results highlight a striking mismatch between the 16S barcode and the taxonomic, ecological, and phenotypic variability it is assumed to reflect, likely arising from the slow evolution of rRNA genes contrasted with the mobility of ecologically relevant genes via horizontal transfer on plasmids, transposons, and phages. Our findings further challenge the limitations of relying on 16S rRNA alone for fine-scale taxonomic and metadata-based inference in capturing the true functional and ecological diversity of bacteria, endorsing the critical importance of polyphasic taxonomic approaches that integrate genomic, phenotypic, and ecological data. An interesting byproduct of the analysis was to realize the possibility of treating these data as if they were 'citations.' The more one finds the same query sequence, the more that sequence can be considered biologically 'cited', i.e., re-proposed elsewhere in the world. Thus, one can also analyze the h-index of such a ranking. In our Rhizobium dataset, we calculated an h-index = 201, meaning the sequence ranked 201st had 202 identical homologues in GenBank. Although the research effort on given species is directly connected with it, this number provides a quantitative indicator of a taxon's sequence recurrence and distribution within public databases, independent of nomenclatural inconsistencies, offering a novel framework for assessing bacterial representation across global datasets.

RNA, Ribosomal, 16S↗

PubMed2026

Small molecule inhibition of the mitochondrial lipid transfer protein STARD7 attenuates influenza viral replication.

The increasing appearance of drug-resistant and zoonotic influenza strains highlights an urgent need for host-directed antivirals that offer broad-spectrum activity and a higher barrier to resistance. Here, we describe the characterization of M4, a small-molecule identified from a high-throughput screen that potently inhibits influenza A and B viruses. Mechanistic studies reveal that M4 suppresses influenza virus replication by preventing formation of export-competent viral ribonucleoprotein (vRNP) complexes in the nucleus. Chemoproteomic profiling identified the lipid transfer protein STARD7 as the primary cellular target, and genetic depletion of STARD7 phenocopies the antiviral effects of M4. Additional studies localized the M4 binding site to cysteine 302 within the lipid-binding domain of STARD7, supporting a model in which STARD7-dependent lipid transfer activity promotes efficient vRNP assembly and nuclear export. Combining M4 with baloxavir enhances antiviral efficacy in a murine infection model, providing in vivo support for a host-directed therapeutic strategy. Together, these results identify STARD7 as a metabolic checkpoint licensing vRNP nuclear export and they establish a proof of concept for therapeutic intervention with small molecule inhibitors.

Journal Article↗

PubMed2026

Somatic-only SDHD variant with tumor-specific loss of heterozygosity in metastatic carotid body tumor: a case report with review of literature.

Carotid body tumors (CBTs) are rare paragangliomas in which genetic predisposition, particularly pathogenic variants in succinate dehydrogenase (SDHx) genes, plays an important role in tumorigenesis. Previous genetic studies of CBTs have primarily focused on germline SDHx variants, whereas somatic alterations remain poorly characterized. Among SDHx genes, SDHB variants are known to be associated with a higher metastatic risk, while SDHD variants are generally linked to a lower metastatic rate. We report the case of a 41-year-old man who presented with a painless right-sided neck mass. Imaging studies demonstrated a hypervascular tumor located at the carotid bifurcation with circumferential encasement of the carotid artery. During surgery, the tumor was classified as a Shamblin type III CBT, and complete surgical resection with vascular reconstruction was performed. Histopathological examination confirmed paraganglioma with metastasis to a single cervical lymph node. Germline genetic testing did not reveal any pathogenic variants. However, comprehensive tumor genomic profiling identified a somatic SDHD c.304C>G (p.His102Asp) variant accompanied by tumor-specific loss of heterozygosity (LOH) and copy-number loss at the SDHD locus, findings compatible with biallelic SDHD inactivation. The patient remained free of recurrence during follow-up. To our knowledge, this represents the first reported case of metastatic CBT harboring a somatic-only SDHD variant with tumor-specific LOH. This case suggests that reliance on germline testing alone may underestimate the molecular drivers of CBT and highlights the potential clinical value of tumor-based genomic profiling for risk stratification and prognostic assessment.

Carotid body tumor↗