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PubMed2024

Large enrichments in fatty acid 2H/1H ratios distinguish respiration from aerobic fermentation in yeast Saccharomyces cerevisiae.

Shifts in the hydrogen stable isotopic composition (2H/1H ratio) of lipids relative to water (lipid/water 2H-fractionation) at natural abundances reflect different sources of the central cellular reductant, NADPH, in bacteria. Here, we demonstrate that lipid/water 2H-fractionation (2εfattyacid/water) can also constrain the relative importance of key NADPH pathways in eukaryotes. We used the metabolically flexible yeast Saccharomyces cerevisiae, a microbial model for respiratory and fermentative metabolism in industry and medicine, to investigate 2εfattyacid/water. In chemostats, fatty acids from glycerol-respiring cells were >550‰ 2H-enriched compared to those from cells aerobically fermenting sugars via overflow metabolism, a hallmark feature in cancer. Faster growth decreased 2H/1H ratios, particularly in glycerol-respiring cells by 200‰. Variations in the activities and kinetic isotope effects among NADP+-reducing enzymes indicate cytosolic NADPH supply as the primary control on 2εfattyacid/water. Contributions of cytosolic isocitrate dehydrogenase (cIDH) to NAPDH production drive large 2H-enrichments with substrate metabolism (cIDH is absent during fermentation but contributes up to 20 percent NAPDH during respiration) and slower growth on glycerol (11 percent more NADPH from cIDH). Shifts in NADPH demand associated with cellular lipid abundance explain smaller 2εfattyacid/water variations (<30‰) with growth rate during fermentation. Consistent with these results, tests of murine liver cells had 2H-enriched lipids from slower-growing, healthy respiring cells relative to fast-growing, fermenting hepatocellular carcinoma. Our findings point to the broad potential of lipid 2H/1H ratios as a passive natural tracker of eukaryotic metabolism with applications to distinguish health and disease, complementing studies that rely on complex isotope-tracer addition methods.

Saccharomyces cerevisiae↗

PubMed2025

An Evolutionary Framework Exploiting Virologs and Their Host Origins to Inform Poxvirus Protein Functions.

Poxviruses represent evolutionary successful infectious agents. As a family, poxviruses can infect a wide variety of species including humans, fish, and insects. While many other viruses are species-specific, an individual poxvirus species is often capable of infecting diverse hosts and cell types. For example, the prototypical poxvirus, vaccinia, is well known to infect numerous human cell types but can also infect cells from divergent hosts like frog neurons. Notably, poxvirus infections result in both detrimental human and animal diseases. The most infamous disease linked to a poxvirus is smallpox caused by variola virus. Poxviruses are large double-stranded DNA viruses, which uniquely replicate in the cytoplasm of cells. The model poxvirus genome encodes ~200 nonoverlapping protein-coding open reading frames (ORFs). Poxvirus gene products impact various biological processes like the production of virus particles, the host range of infectivity, and disease pathogenesis. In addition, poxviruses and their gene products have biomedical application with several species commonly engineered for use as vaccines and oncolytic virotherapy. Nevertheless, we still have an incomplete understanding of the functions associated with many poxvirus genes. In this chapter, we outline evolutionary insights that can complement ongoing studies of poxvirus gene functions and biology, which may serve to elucidate new molecular activities linked to this biomedically relevant class of viruses.

Animals↗

PubMed2026

A transcriptome-wide approach for rapid pathotype discrimination of Puccinia striiformis f. sp. tritici in north-western India.

Stripe rust of wheat caused by Puccinia striiformis f. sp. tritici (Pst) remains a major constraint to wheat production in India due to the rapid evolution and frequent emergence of virulent pathotypes. Rapid and reliable discrimination of Pst pathotypes is essential for effective resistance deployment and surveillance. In the present study, transcriptome-wide simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs) were exploited to develop and validate molecular markers for pathotype-specific detection of Pst pathotypes prevalent in North India (110S119, 238S119, 46S119, 110S84 and 78S84). Microsatellite mining from 6103 core orthologous clusters comprising 51,127 transcripts mined 14,634 SSR loci, from which 93 primer pairs were synthesized. However, only three SSR markers exhibited polymorphism indicating limited discrimination potential of expressed sequence-derived (EST) SSRs for pathotype differentiation. In contrast, SNP discovery through stringent variant calling and filtration yielded 186 pathotype-specific homokaryotic SNPs, of which 56 high-confidence loci were selected for Kompetitive Allele-Specific PCR (KASP) assay development. A total of 48 KASP markers were synthesized and 14 demonstrated clear pathotype- or cluster-specific polymorphism representing substantially higher resolution than SSR markers. The high SNP-to-KASP conversion efficiency (~ 95%) and reproducible fluorescence-based clustering emphasize the robustness of KASP assay. Comparative evaluation revealed that SNP-based KASP markers provide superior discriminatory capacity for closely related Pst pathotypes and represent a promising complementary molecular approach for rapid identification of predominant Indian Pst pathotypes. The validated marker panel developed in this study can complement conventional virulence phenotyping and field pathogenomics approaches for surveillance of currently known pathotypes, while continued refinement may accommodate future changes in pathogen populations.

India↗

PubMed2026

Disruption of GxxxG motifs in pATOM36 impairs biogenesis of the mitochondrial protein translocase of the outer membrane in Trypanosoma brucei.

Mitochondrial biogenesis requires efficient import of cytosolically produced proteins and correct segregation of the mitochondrial genome during cytokinesis. In Trypanosoma brucei, a parasitic protozoan with a single mitochondrion harboring a single-unit mitochondrial genome, protein import across the outer membrane is mediated by the ATOM complex. An important, yet poorly understood role is played by the integral membrane protein pATOM36 of the outer mitochondrial membrane, which is essential for both ATOM complex assembly and mitochondrial DNA segregation. Here, we combined in vivo functional mutational analysis and structural modeling to investigate the function of pATOM36. AlphaFold3-based models predict five highly tilted helices forming a funnel-shaped cavity open toward the cytoplasm, reminiscent of membrane protein insertases. In the model, the protein is sealed towards the mitochondrial intermembrane space by tight helix packing, with conserved GxxxG motifs potentially facilitating these helix-helix interactions. Progressive replacement of these glycines by isoleucines does not affect protein production or correct localization but leads to defective ATOM complex biogenesis and arrest of growth, while mitochondrial DNA segregation is largely unaffected. Based on the predicted structure, these effects can be rationalized by hydrophobic bulking that interferes with associated electrostatic interactions. This hypothesis is supported by experimental mutational analysis of the respective electrostatic interactions in the presence of native GxxxG motifs. Together, our data support the hypothesis that pATOM36 functions as an outer mitochondrial insertase and arose by convergent evolution. The GxxxG motifs, also found in unrelated yeast and human outer membrane insertases, are crucial for protein activity.

Trypanosoma brucei brucei↗

PubMed2026

A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants.

Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70 mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).

Humans↗

PubMed2026

Public opinion survey on heritable human genome editing in South Africa: a study protocol.

Heritable human genome editing (HHGE) presents new possibilities for the prevention of genetic diseases but also raises ethical and societal questions. While international surveys have explored public attitudes, particularly in high-income countries, there is a lack of large-scale empirical data from the Global South. In South Africa, previous work used deliberative public engagement to examine public perspectives. The present study aims to complement this by capturing public opinion through a cross-sectional survey, enabling direct comparison with deliberative findings. This study will recruit 400 adult participants residing in South Africa using targeted Facebook advertisements. A two-phase sampling process will be employed: initial screening for demographic information, followed by stratified sampling to ensure a representative South African population. The opinion survey consists of 19 HHGE scenarios, each explored through private and public moral lenses. Additionally, participants will indicate their interpretation of 'safe and effective' genome editing. Quantitative data will be analysed using descriptive statistics, chi-square tests, and logistic regression. Qualitative responses will undergo thematic analysis using both manual coding and generative AI tools under human oversight. The study includes two stages of informed consent and ensures data confidentiality through strict data handling protocols. Results will be disseminated in peer-reviewed journals and policy forums. The study will also generate a secondary dataset for evaluating AI-assisted qualitative analysis, to be conducted under separate ethical clearance.

Humans↗

PubMed2026

Qingfei Dayuan granules alleviate the inflammatory response in lipopolysaccharide-induced acute lung injury mice by inhibiting the Nf-κB signaling pathway and regulating the complement pathway.

OBJECTIVES: The study aimed to explore the effects and mechanisms by which Qingfei Dayuan granules (QFDY) mitigate pulmonary inflammation in lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: We established an ALI mouse model by intraperitoneal injection of LPS. HE, Transmission electron microscopy, ELISA assay of inflammatory cytokines, and immunohistochemistry (IHC) were used to assess the degree of lung injury and inflammation. Utilizing network analysis and proteomics analysis, the potential targets and pathways of QFDY were identified. Western blot, IHC, and qRT-PCR analysis were used to evaluate the potential mechanism of QFDY. Additionally, the chemical composition of QFDY were performed using UPLC-MS/MS. KEY FINDINGS: QFDY reduced the pathologic changes and inflammatory cell infiltration in lung tissue inflammation. Network and proteomic analysis showed that the mechanism of QFDY protection against ALI is closely related to the Nuclear factor-kappa B (NF-κB) signaling pathway and complement pathway. Animal experiments showed that Qingfei Dayuan granules (QFDY) significantly reduced the levels of IL-1β, IL-6, TNF-α, and lung tissue F4/80-positive alveolar macrophages. Additionally, western blot and qRT-PCR analyses showed the inhibition of the NF-κB pathway. Notably, the levels of mannose-binding lectin (MBL2) were significantly increased, while complement C3a and complement C5a proteins were reduced in the QFDY group compared to the LPS group. CONCLUSIONS: QFDY suppressed the inflammation in LPS-induced ALI by inhibiting the NF-κB and complement pathway.

Animals↗

PubMed2026

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans↗

PubMed2026

Clinical impact of 16S rRNA RC-PCR NGS on infectious disease management.

16S rRNA metagenomics provides a culture-independent method for diagnosing infections with fastidious or uncultivable organisms, guiding targeted therapy, and detecting polymicrobial communities. This study utilizes reverse complement (RC)-PCR next-generation sequencing (NGS) to accurately identify bacterial pathogens from clinical specimens and assess its impact on clinical decision-making, setting it apart from conventional 16S sequencing approaches. A retrospective analysis of an ISO 15189 accredited 16S RC-PCR NGS diagnostic workflow targeting the V1-6 and V9 regions of the 16S rRNA gene was conducted over a 2-year period, including 390 clinical specimens from 316 patients. 16S RC-PCR NGS results were discussed in a multidisciplinary consultation and subsequently reported to the clinic. In total, 1,283 RC-PCR results were analyzed, of which 517 were from clinical specimens, 284 were negative controls, 66 were positive controls, and 416 were from wet lab and bioinformatic pipeline validation. 16S RC-PCR NGS assay detected bacterial taxa in 179/390 (45.9%) of clinical specimens, while 201/390 (51.5%) were negative, and 10/390 (2.6%) yielded uninterpretable results. The specimen types pus, pleural fluid, and heart valves exhibited the highest positivity rate (68% to 70%). Overall, 16S RC-PCR NGS influenced diagnostic decision making in 145/282 (51.4%) clinical cases and guided therapeutic management in 77/282 (27.3%) cases. Results providing definite evidence for either the presence or absence of bacterial infection were considered clinically valuable. Integration of 16S RC-PCR NGS pathogen detection with multidisciplinary consultation markedly improved clinical management, directly impacting diagnosis and treatment of complex clinical cases in a tertiary care setting. The effect was most pronounced in brain abscess patients, where RC-PCR results guided treatment decisions in 9/13 (69.2%) of cases.IMPORTANCETimely and accurate diagnosis is essential for managing serious infections, yet clinicians often face situations where routine laboratory tests do not provide clear answers. This study demonstrates that next-generation sequencing (NGS) of the bacterial 16S rRNA gene can decisively resolve these uncertainties. By revealing whether bacteria are present in clinical specimens, this approach influenced clinical reasoning and supported treatment decisions across a variety of challenging cases. 16S reverse-complement PCR was especially powerful for brain abscesses and infections where the causative microorganism was unclear, providing clarity that directly improved patient care. These findings show that integrating advanced sequencing with expert clinical interpretation can enhance the management of complex infections and support more confident, evidence-based therapy.

Humans↗

PubMed2026

Single-cell spatial transcriptomic atlas of the mouse adrenal gland reveals sexual dimorphism in steroidogenic enzyme and hormone receptor expression.

The adrenal cortex shows sexual dimorphism in structure and function. We analysed adrenal glands from 7-week-old male and female BALB/c mice using Visium HD with Cellpose 3 segmentation, comprising 236,077 cells across eleven populations, including four cortical zones. Using curated marker-gene-based zonal annotation, we focused on steroidogenic enzymes and hormone receptors, complementing our companion study based on the same primary dataset. The X-zone was nearly absent in males but prominent in females. Females showed higher Hsd3b1 expression across cortical zones and higher Cyp11b1 expression in outer cortical compartments. The strongest sex difference involved Srd5a2, with markedly higher expression in male zona fasciculata (inner: 77.1% vs. 28.9%), independently supported by RNAscope and immunohistochemistry. Mc2r and Mrap showed discordant spatial distributions, with limited co-expression, suggesting potential MC2R-independent MRAP roles. Agtr1a dominated angiotensin II receptor expression in zona glomerulosa without major sex differences, providing a zone-resolved reference for adrenal sexual dimorphism.

Adrenal cortex↗

PubMed2025

Transcriptional signature of induced neurons differentiates virologically suppressed people with HIV from people without HIV.

Neurocognitive impairment is a prevalent comorbidity in virologically suppressed people living with HIV (PLWH), yet the underlying mechanisms remain elusive and treatments lacking. We explored use of participant-derived directly induced neurons (iNs) to model neuronal biology and injury in PLWH. iNs retain age- and disease-related donor features, providing unique opportunities to reveal important aspects of neurological disorders. We obtained primary dermal fibroblasts from 6 virologically suppressed PLWH and 7 matched people without HIV (PWOH). iNs were generated using transcription factors NGN2 and ASCL1 and validated by immunocytochemistry, single-cell RNA-Seq, and electrophysiological recordings. Transcriptomic aging analyses confirmed retention of donor age-related signatures. Bulk RNA-Seq identified 29 significantly differentially expressed genes between PLWH and PWOH iNs. Of these, 16 were downregulated and 13 upregulated in PLWH iNs. Protein-protein interaction network mapping indicated iNs from PLWH exhibited differences in extracellular matrix organization and synaptic transmission. IFI27 was upregulated in PLWH iNs, complementing independent postmortem studies demonstrating elevated IFI27 expression in PLWH-derived brain tissue. FOXL2NB-FOXL2-LINC01391 expression was reduced in PLWH iNs and negatively correlated with neurocognitive impairment. Thus, we identified an iN gene signature of HIV revealing mechanisms of neurocognitive impairment in PLWH.

Humans↗

PubMed2025

Lentiviral-mediated gene complementation rescues pathogenic ABCA3 variants.

The ATP-binding cassette subfamily A member 3 (ABCA3) protein on the limiting membrane of lamellar bodies in alveolar type 2 (AT2) cells transports phospholipids required for pulmonary surfactant assembly. ABCA3 deficiency results from biallelic pathogenic variants in ABCA3 and causes progressive neonatal respiratory failure or childhood interstitial lung disease (chILD). Supportive/compassionate care or lung transplantation are the only current definitive treatments for ABCA3 deficiency and progressive respiratory failure. Complementing dysfunctional ABCA3 by gene addition has therapeutic potential. Previous studies show that repairing or complementing ABCA3 in induced pluripotent stem cell (iPSC)-derived AT2 cells rescues lamellar body morphology and surfactant phospholipid composition. Pathogenic variants disrupt ABCA3 function through altered protein trafficking (type 1) or by impaired phospholipid transport (type 2) into lamellar bodies. Here we tested ABCA3 gene complementation using a human pulmonary epithelial cell line (A549) with a genomically silenced ABCA3 locus (ABCA3 KO). From this line, additional cell lines that stably express individual ABCA3 variant cDNA constructs from a single genomic locus were tested: L101P (type 1), E292V (type 2), E690K (type 2), or wild-type ABCA3. Lentiviral-mediated ABCA3 delivery to each cell line partially rescued localization to LAMP3+ vesicles, lamellar body-like structure morphology, and cell proliferation. A functional assay measuring NF-κB signaling suggested that ABCA3 complementation ameliorated aberrant inflammatory signaling in E292V or E690K (type 2) mutant lines, but not in L101P (type 1) or knockout lines. These studies highlight the therapeutic potential of gene addition as well as differences between ABCA3 pathogenic variants that may influence genetic therapy outcomes.

ABCA3 deficiency↗

PubMed2026

Hyperthyroidism Is Genetically Associated With Reduced Risk of Parkinson's Disease: A Mendelian Randomization Analysis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose aetiology involves an intricate interplay of genetic, immune, metabolic and environmental factors. Endocrine dysfunction-particularly disturbances of thyroid hormone signalling-has been proposed as a contributor to neurodegeneration, but conventional observational studies have produced inconsistent results, and prior Mendelian randomization (MR) work has largely focused on continuous thyroid biomarkers rather than clinically defined hyperthyroid disease states. To clarify this relationship, we performed a two-sample bidirectional and multivariable MR (MVMR) analysis using large-scale genome-wide association study (GWAS) summary statistics from the FinnGen and IEU Open GWAS databases (European ancestry). Single-nucleotide polymorphisms (SNPs) reaching genome-wide significance (p < 5 × 10-8) for Graves' disease and thyrotoxicosis with diffuse goitre served as instrumental variables. The inverse-variance weighted (IVW) method was the primary analysis, complemented by MR-Egger, weighted median, weighted mode and simple mode estimators, and MVMR adjusted for smoking, alcohol consumption, and body mass index (BMI). In forward analyses, genetically proxied Graves' disease (OR = 0.942, 95% CI 0.901-0.985, p = 0.008) and thyrotoxicosis with diffuse goitre (OR = 0.929, 95% CI 0.879-0.982, p = 0.009) were associated with a lower risk of PD, whereas reverse analyses showed no significant effect of genetic liability to PD on either thyroid trait. The inverse associations remained stable across MVMR models, and sensitivity analyses (Cochran's Q, MR-Egger intercept, MR-PRESSO, leave-one-out) showed no evidence of heterogeneity or horizontal pleiotropy. Collectively, these findings provide genetic evidence consistent with a protective relationship between hyperthyroid disease states and PD, independent of major lifestyle confounders. By focusing on clinically defined hyperthyroid entities rather than continuous thyroid indices, our study complements prior MR work and highlights the thyroid-brain axis-encompassing thyroid hormone signalling and autoimmune-mediated immune modulation-as a biologically plausible and potentially modifiable contributor to PD risk that warrants further mechanistic and translational investigation.

Humans↗

PubMed2026

The complement system in inflammatory bowel disease: from early observations to emerging frontiers.

PURPOSE OF REVIEW: The complement system is one of the most evolutionarily conserved arms of innate immunity and has re-emerged as an important regulator of intestinal inflammation in inflammatory bowel disease (IBD). Early observations from the mid-1970 s such as complement deposition in diseased bowel tissue and elevated serum complement levels in patients with ulcerative colitis and Crohn's disease have evolved into a nuanced understanding of how individual complement components can exert both protective and pathogenic effects in IBD. This review highlights recent advances in complement biology and examines how complement shapes intestinal immune responses, particularly in the setting of ongoing inflammation. RECENT FINDINGS: The complement system consists of more than 60 proteins that act as rapid first responders to infection. Although traditionally considered primarily liver-derived circulating effectors, recent work has demonstrated local synthesis and activation of key complement components at mucosal sites, including the colon. In parallel, genome-wide association studies have identified variants in complement genes associated with severe IBD complications. Collectively, these findings reveal a dichotomous role for complement in IBD, whereby excessive activation promotes inflammation, while impaired function compromises host defense and worsens disease outcomes. SUMMARY: Complement-targeted therapies have been effective in other diseases but have not yet translated to IBD. A deeper understanding of context-dependent protective versus pathogenic complement functions will be essential for developing future therapeutic strategies.

Humans↗

PubMed2025

Defining the host dependencies and the transcriptional landscape of RSV infection and bystander activation.

Respiratory syncytial virus (RSV) is a globally prevalent pathogen, causes severe disease in older adults, and is the leading cause of bronchiolitis and pneumonia in the United States for children during their first year of life [1]. Despite its prevalence worldwide, RSV-specific treatments remain unavailable for most infected patients. Here, we leveraged a combination of genome-wide CRISPR knockout screening and single-cell RNA sequencing to improve our understanding of the host determinants of RSV infection and the host response in both infected cells, and uninfected bystanders. These data reveal temporal transcriptional patterns that are markedly different between RSV infected and bystander activated cells. Our data show that expression of interferon-stimulated genes is primarily observed in bystander activated cells, while genes implicated in the unfolded protein response and cellular stress are upregulated specifically in RSV infected cells. Furthermore, genome-wide CRISPR screens identified multiple host factors important for viral infection, findings which we contextualize relative to 29 previously published screens across 17 additional viruses. These unique data complement and extend prior studies that investigate the proinflammatory response to RSV infection, and juxtaposed to other viral infections, provide a rich resource for further hypothesis testing.

CRISPR screen↗

PubMed2026

Larval Genomics as a Viable, Fisheries-Independent Tool for Investigating Population Structure in Tropical Pacific Tunas.

Understanding how dispersal, life history, and environmental variability shape genetic connectivity in the open ocean remains a central challenge in evolutionary biology. Highly migratory marine predators like tunas have traditionally been considered genetically homogeneous across ocean basins, yet emerging genomic evidence suggests that cryptic population structure can persist even in species with high gene flow and large effective population sizes. We used 2bRAD sequencing of 348 larval and subadult skipjack (Katsuwonus pelamis), yellowfin (Thunnus albacares), and bigeye tuna (T. obesus) collected from the central Pacific across 7 years of sampling to examine species boundaries, population genetic information, genetic structure, and connectivity. Larval sampling revealed consistent spawning by all three species and enabled unbiased detection of genetic patterns prior to recruitment bottlenecks. We found strong divergence amongst species, no evidence of structuring within skipjack or bigeye, and a divergent yellowfin population detected in 2 consecutive sampling years north of American Samoa. Comparisons between larvae and subadults suggest that sampling early life history stages can be a valuable tool for assessing population genetic information before recruitment bottlenecks, selective harvest by fisheries, adult dispersal, and selective pressures acting on adult populations, thereby contributing novel insights to the research and effective management of these species. These results highlight how larval genomics can complement traditional population genomic studies of adult tunas and reveal fine-scale structure in highly vagile species, providing new perspectives on connectivity in the open ocean.

Animals↗

PubMed2023

Genetic variants in the complement system and their potential link in the aetiology of type 1 diabetes.

Type 1 diabetes is an autoimmune disease in which one's own immune system destroys insulin-secreting beta cells in the pancreas. This process results in life-long dependence on exogenous insulin for survival. Both genetic and environmental factors play a role in disease initiation, progression, and ultimate clinical diagnosis of type 1 diabetes. This review will provide background on the natural history of type 1 diabetes and the role of genetic factors involved in the complement system, as several recent studies have identified changes in levels of these proteins as the disease evolves from pre-clinical through to clinically apparent disease.

Humans↗

PubMed2026

Can Psychiatric Genetics Advance Without Incorporating a Life Course Perspective?

Psychiatric disorders unfold over the life course; however, genomic studies of these conditions overwhelmingly rely on phenotypes collected at a single time point, often in adulthood. Therefore, genome-wide association studies (GWASs) of psychiatric conditions may miss genetic variants with time-varying relevance to etiology, prevention, and treatment, such as those that influence trajectories of symptoms and behaviors, age at onset, course of treatment response, and the co-evolution of comorbidities. With recent advances in longitudinal biobanks and analytic tools, we posit that incorporating a life course perspective in psychiatric genetics will enable critically relevant insights into each of these areas of investigation. We propose that the current inconsistent portability of polygenic scores across age groups can be reconciled through the design of carefully considered longitudinal GWASs in age-diverse samples. Pioneering longitudinal GWASs in psychiatry have revealed novel genomic signals associated with time-dependent phenotypes that are distinct from those influencing lifetime diagnosis, suggesting that the study of longitudinal phenotypes will complement cross-sectional approaches and empower biological and therapeutic discoveries. Advances in post-GWAS functional annotation resources and analytic approaches now enable us to contextualize the genetic contributions to psychiatric disorders as dynamic age- and exposure-dependent processes. Although longitudinal GWASs pose unique challenges with regard to data availability, selection bias, and missing data, integrating temporality into psychiatric genetics at scale is now attainable and promises to reveal novel biology and therapeutic opportunities for psychiatric conditions.

Cohort study↗