bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular insights into electroreceptor ribbon synapses from differential gene expression in sturgeon lateral line organs
Authors: Campbell Alexander S. , Minařík Martin , Buckley David , Anand Tanmay , Gela David , Pšenička Martin , Baker Clare V. H.
Published: February 2025

In fishes and aquatic-stage amphibians, mechanosensory neuromasts are arranged in characteristic lines in the skin of the head and trunk, with afferent innervation from anterior or posterior lateral line nerves. In electroreceptive non-teleost jawed fishes and amphibians, fields of electrosensory ampullary organs flank some or all of the cranial neuromast lines, innervated by the anterior lateral line nerve. Like the mechanosensory hair cells found in neuromasts and the inner ear, electroreceptor cells in ampullary organs form specialised ribbon synapses with afferent nerve terminals. Ribbon synapses in hair cells are distinct from other glutamatergic synapses, including the ribbon synapses in photoreceptors: otoferlin is the Ca2+sensor for synaptic vesicle exocytosis and synaptic vesicles are loaded with glutamate by vGlut3. We previously showed that the genes encoding otoferlin and vGlut3 are expressed by ampullary organs as well as neuromasts in a chondrostean ray-finned fish, the Mississippi paddlefish (Polyodon spathula), suggesting that electroreceptor ribbon synapses are very similar to those in hair cells. In this study, we selected seven additional synapse-related candidate genes from our previously published dataset of putatively lateral line organ-enriched genes from late-larval paddlefish, and examined their expression in developing lateral line organs in a related chondrostean, the sterlet sturgeon (Acipenser ruthenus). We found that genes encoding the presynaptic cell adhesion molecule Nrxn3, the calcium-independent synaptotagmin Syt14, the high-affinity glutamate re-uptake transporter EAAT1 (GLAST), calmodulin regulator protein PCP4 (PEP-19) and cell adhesion molecule DSCAML1 were expressed in both neuromasts and ampullary organs. In contrast,Cbln18, encoding a secreted trans-synaptic scaffolding protein, was only expressed in neuromasts andTulp1, encoding tubby-related protein 1 (required for the development and function of photoreceptor ribbon synapses), was only expressed in ampullary organs. Our results support electroreceptor ribbon synapses being glutamatergic and suggest further commonalities, but also some differences, with hair cell ribbon synapses.
Bclaf1 biomolecular condensates protect nuclear PTK2 from ubiquitin-proteasome system promoting cardiomyocyte survival during oxidative stress
Authors: Aparecida Moretto Isabela , Rodrigues Beatriz Rocha Ilidio , Víctor-Carvalho Pedro , Carvalho Maria das Graças de Souza , Silva Mariana Conceição da , Valdivieso-Rivera Fernando B , Araújo Giovanna Lopes de , Samogim Ana Paula , Novais Lara Basseres , de Brito Ingridi Rafaela , Reis-de-Oliveira Guilherme , Amaral Alan Gonçalves , Baratti Mariana Ozello , Basei Fernanda Luisa , Geraldo Murilo Vieira , Carvalho Paulo Costa , Santos Marlon Dias Mariano , Duran Rosario , Sponton Carlos , Kobarg Jörg , Gozzo Fabio C. , Carvalho Hernandes F , Thomaz Andre Alexandre de , Santos Aline Mara dos
Published: February 2025

PTK2, a non-receptor tyrosine kinase, is essential for regulating pivotal cellular functions, including survival by reducing p53 levels and activating PI3K/AKT pathway. However, the mechanism underlying PTK2 stabilization during stress remained unclear. Here, we identified Bclaf1, a multifunctional protein known to stabilize partners, as a PTK2 interactor. Using advanced microscopy techniques we identified nuclear Bclaf1 biomolecular condensates containing PTK2 in cardiomyocytes under oxidative stress. While PTK2 diffused through the nucleus was susceptible to ubiquitination, PTK2 sequestered in the Bclaf1 condensates was protected from the ubiquitin-proteasome system (UPS). The PTK2 ubiquitination site K926 was identified, and proteasome inhibition confirmed the UPS role in PTK2 homeostasis. Furthermore, the disruption of Bclaf1 biomolecular condensates culminates in PTK2 degradation, ultimately increasing p53 levels and activating apoptosis. Our findings support the role of Bclaf1 driving the formation of pro-survival nuclear condensates that sequester and stabilize PTK2, promoting cardiomyocyte survival during oxidative stress.
Regional heterothermy inMegasoma gyasis not related to active heat dissipation by the horns
Authors: Giacometti Danilo , Lima Silva Luiz Henrique , Gomes Guilherme , de Carvalho José Eduardo , Palaoro Alexandre V.
Published: February 2025

Animals rely on physiological and behavioral processes to maintain thermal balance. Some animals, however, bear structures that help dissipate excess heat when body temperatures rise. Although widespread in animals, animal weapons—exaggerated morphological structures with multiple characteristics that can make them good at dissipating heat—have rarely been studied in the context of thermoregulation. Here, we investigated whether the horns of the Rhinoceros Beetle (Megasoma gyas) acted as a thermal window. We heated live and dead beetles to 30ºC and allowed them to cool to 20ºC while measuring surface temperature changes in four body regions: the cephalic and thoracic horns, the scutellum, and the abdomen. If horns actively dissipated heat, they would show the lowest cooling rate among body regions. Contrary to this expectation, we found that the cephalic horn had the highest cooling rate, followed by the abdomen, thoracic horn, and scutellum, respectively. This suggests that the horns are not used for active heat dissipation inM. gyas. The low cooling rate of the scutellum can be explained by the presence of large flight muscles in the thorax, which play a role in heat generation, but could also aid in heat dissipation by pumping hemolymph across tagmata or through the low-insulated cuticle to prevent thoracic overheating. We also demonstrate that beetles show regional heterothermy even in the absence of exercise or stress. As such, we propose that regional heterothermy may result from both active (control of hemolymph flow) and passive (heat dissipation through poorly insulated structures) processes within individuals.
Comprehensive phylogenetic reconstructions support ancestral omnivory in the ecologically diverse bat family Phyllostomidae
Authors: Yi Xueling , Kontopoulos Dimitrios-Georgios , Hiller Michael
Published: February 2025

Adaptive radiations often occur with an early burst of ecological diversification, which requires not only various available niches but also a generalist ancestor with wide ecological niche breadths. However, ancestral generalism remains hard to test in empirical cases. The New World leaf-nosed bats (family Phyllostomidae) represent an unparalleled mammalian adaptive radiation with diverse dietary niches including arthropods, blood, terrestrial vertebrates, nectar, and fruits. However, when and how often phyllostomid bats transitioned from insectivory to fruit or nectar feeding remains unclear. Here we tested the hypotheses of ancestral insectivory versus ancestral omnivory in Phyllostomidae (141 species) using improved trait reconstructions based on multi-response phylogenetic threshold models, while explicitly accounting for phylogenetic uncertainty. Our results indicate that complementary fruit feeding has fully evolved at the early burst of the phyllostomid radiation and started to evolve in the most recent common ancestor of the family, supporting the ancestral omnivory hypothesis. In addition, fruit feeding probably evolved before nectar eating in Phyllostomidae, in contrast to the claims of previous studies. Extending this analysis to all bat families (621 species) reveals independent evolution of ancestral fruit feeding in four families, namely the Pteropodidae (Old World fruit bats) and three families from the Noctilionoidea superfamily. Despite the ancestral omnivory of these fruit-eating families, only Phyllostomidae and Pteropodidae show high species diversity and evolved predominant and strict fruit feeding. Therefore, our results reveal that ancestral generalism (i.e., omnivory) may be a precondition of but does not necessarily lead to adaptive radiations which also require subsequent niche partitioning and speciation.
DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication
Authors: Feng Fei , Chen Jiannan , Li Rong , Zhu Yunkai , Ma Yanlong , Wang Ziqiao , Wang Yuyan , Gao Zhichao , Yang Lulu , Yu Yin , Liu Yanfeng , Sun Yingjie , Liao Ying , Huang Xinxin , Zhang Qisheng , Huang Yongheng , Qiu Lin , Wu Jiayu , Zhao Jingxian , Liu Chao , Ding Qiang , Xie Youhua , Yuan Zhenghong , Hong Yue , Zhang Ping , Sun Jing , Zhao Jincun , Zhang Rong
Published: February 2025

The SARS-CoV-2 pandemic and the emergence of novel variants underscore the need to understand host-virus interactions and identify host factors that restrict viral infection. Here, we perform a genome-wide CRISPR knockout screen to identify host restriction factors for SARS-CoV-2, revealing DAZAP2 as a potent antiviral gene. DAZAP2, previously implicated in SARS-CoV-2 restriction, is found to inhibit viral entry by blocking virion fusion with both endolysosomal and plasma membranes. Additionally, DAZAP2 suppresses genomic RNA replication without affecting the primary translation of viral replicases. We demonstrate that DAZAP2 functions as a pan-coronavirus restriction factor across four genera of coronaviruses. Importantly, knockout ofDAZAP2enhances SARS-CoV-2 infection in mouse models and in human primary airway epithelial cells, confirming its physiological relevance. Mechanistically, antiviral activity of DAZAP2 appears to be indirect, potentially through the regulation of host gene expression, as it primarily localizes to the nucleus. Our findings provide new insights into the host defense system against coronaviruses and highlight DAZAP2 as a potential target for host-directed antiviral therapies.

IMPORTANCE

During viral infection, the host defense response is mediated by a variety of host factors through distinct mechanisms that have yet to be fully elucidated. AlthoughDAZAP2was previously implicated in SARS-CoV-2 restriction, its mechanisms of action andin vivorelevance remain unclear. In this study, we identify the DAZAP2 as a potent pan-coronavirus restriction factor that inhibits viral infection through dual mechanisms: blocking virion fusion with both endolysosomal and plasma membranes, and suppressing genomic RNA replication. We confirm its physiological relevance in host defense using mouse models and primary cell cultures. This study advances our understanding of host-pathogen interactions. Targeting DAZAP2 or its regulatory pathways could provide a new approach to enhance host defense against current and future coronavirus threats.
Do you really want to see a 2-year-old suffer? Understanding people’s views on the relative value of health gains by age
Authors: De Silva Ashwini , Bailey Cate , Devlin Nancy , Norman Richard , Pan Tianxin , Peasgood Tessa
Published: February 2025

Objectives

Standard economic evaluation methods assume that quality-adjusted life years (QALYs) have equal social value, regardless of recipient. However, evidence suggests that people place greater social value on health gains for children. This study examines the factors driving age-related preferences for health gains.

Methods

Think-aloud, semi-structured interviews were conducted with Australian adolescents (n=7), non-parents (n=11), parents with healthy children (n=8) and parents of children with health conditions (n=15). Participants completed Person Trade-Off (PTO) and attitudinal questions about resource allocation for improvements in life extension, mental health, mobility, and pain/discomfort choosing between interventions for adults (ages 40 or 55) and younger people (ages one month to 24).

Results

Eleven themes emerged, illustrating participants’ complex reasoning. They considered differences in the impact of health loss at various ages, with difficulty envisaging mental health impacts for very young children. Emotional responses were strongest around children in pain. Adolescents tended to prioritize younger people, while parents often emphasized adults’ caregiving role. Most participants prioritized based on age in PTO questions, though some adults objected to prioritizing healthcare based on age.

Conclusion

Choices were shaped by perceptions of the impact of the health states. These findings provide insight into interpreting quantitative results from PTO tasks.
Maternal-antenatal attachment is higher in young pregnant women with more social support, mentors, and lower fear of childbirth
Authors: Alavala Vishnupriya , De Genna Natacha M.
Published: February 2025

The goal of this study was to examine correlates of maternal-fetal attachment in a diverse sample of young pregnant mothers. Although studies have looked at social determinants of health and maternal-fetal attachment, none have examined correlates that may be more prevalent in younger populations including prenatal drug use or fear of childbirth. We analyzed data from a prospective cohort of 154 pregnant adolescents and young adults (75.5% Black/African American, 15.6% white, 7.5% biracial, 1.4% other) ranging from 14-21 years old. Participants were recruited early in pregnancy and completed online surveys during each trimester of pregnancy. Maternal fetal attachment was measured with the Maternal Antenatal Attachment Scale (MAAS) between 30-36 weeks gestation. A linear regression model was constructed to determine the independent contributions of demographic variables (age, race, sexual minority status), maternal mental health, substance use, and social support to maternal-fetal attachment. Third trimester social support, presence of a natural mentor, not having a younger partner, and lower fear of childbirth were associated with higher MAAS scores, and therefore greater maternal fetal attachment, accounting for 32% of the variance in MAAS scores. Maternal age, substance use, and psychological symptoms were not significantly related to maternal fetal attachment in this sample. Social support and patient education to lessen fear of childbirth should be the target of interventions to improve maternal-fetal attachment in adolescent and young adult women. Fostering and supporting mentorship may also be a promising avenue to improve maternal-fetal bonding in younger patients. More research is needed to better understand the impact of perceived health, body dissatisfaction, physical fitness, healthcare access, pre-existing OB/GYN conditions, fear of breastfeeding, history of emotional neglect, and future child rearing support to address gaps in knowledge within this field.
Global, Regional, and National Burden of Non-Rheumatic Calcified Aortic Valve Disease from 1990 to 2021 and Projections to 2050
Authors: Wang Zhenglong , Li Hao , Wei Hongwei , Chen Ming , Liu Xiaobo
Published: February 2025

Background

non-rheumatic calcific aortic valve disease (nrCAVD) is a valvular disease characterized by progressive calcification of the aortic valve that can lead to progressive left heart failure and death. This study reports on the global burden of CAVD, utilizing all available data and using the Global Burden of Disease (GBD) study methodology to understand the epidemiology of this widely prevalent disease.

Methods

Prior to the current effort, the burden of CAVD was included in GBD as a non-specific contributor to “valvular heart disease” burden. In this study, CAVD was distinguished as its own cause of death and disability in GBD, producing comparable and consistent estimates of CAVD burden. We used epidemiological and vital registry data to estimate the non-fatal and fatal burden of CAVD in 204 countries and 21 territories from 1990 to 2021 using standard GBD modelling approaches.

Results

In 2021, there were an estimated 13,320,896.13 (95% uncertainty interval [UI] 11,422,539.18 to 15,249,410.95) prevalent cases of CAVD globally. Of these, 6,018,666.77 (5,139,855.53 to 6,897,468.51) were in females (45%) and 7,302,229.37 (6,260,246.93 to 8,340,870.42) in males (55%). The age-standardised prevalence was 158.35 cases per 100 000 population (95% UI 135.92 – 181.00). Prevalence increased with age such that the highest prevalence was among individuals aged 90–94 years. In 2021, there were 142,205.00 例 (120,674.91 – 155,574.74) attributed to PAH globally, with an age-standardised mortality rate of 1.83 deaths from CAVD per 100 000 population (1.54 – 2.00). The burden of disease appears to be improving over time.
Impact of Aspirin Therapy on Progression of Thoracic and Abdominal Aortic Aneurysms
Authors: Mohammadmoradi Shayan , Heier Kory , Driehaus Elizabeth R. , Alfar Hammodah R. , Tyagi Sam , McQuerry Kristen , Whiteheart Sidney W.
Published: February 2025

Background and Objective

Aortic aneurysms, including abdominal (AAA) and thoracic (TAA), pose significant challenges due to their rupture risk and complex pathophysiology. While aspirin has been proposed to manage aneurysm progression, evidence remains limited. This retrospective, single-center study used AI-driven methods to examine the association between aspirin therapy and aneurysm growth.

Methods

The study, at the University of Kentucky Healthcare, utilized de-identified electronic health record data from 2010 to 2023. To evaluate platelet counts changes, Cohort 1 included patients with AAA or TAA and matched healthy controls. Cohort 2 included AAA or TAA patients who had at least two imaging studies. Extraction of aortic diameters utilized an advanced AI-based natural language processing (NLP) algorithm to identify and extract relevant text strings related to aortic dimensions. Multivariable-adjusted linear regression analyses assessed the impact of aspirin on aneurysm progression.

Results

Cohort 1 included 11,538 participants: 5,774 controls, 3,439 with AAA, and 2,325 with TAA. Platelet counts were significantly lower in patients with aortic aneurysms compared to controls, though they were not considered thrombocytopenic. Cohort 2 included 302 AAA and 141 TAA patients. Subgroup analysis revealed that aspirin use was associated with increased AAA progression in females with small aneurysms (<50 mm). Further, aspirin therapy showed no significant impact on the annualized change in aneurysm diameter for TAA or for males with AAA.

Conclusion

Our findings suggest aspirin’s effectiveness varies by sex and potentially aneurysm size, underscoring the need for further research to refine antiplatelet therapy guidelines for aortic aneurysms.
Integrating HiTOP and RDoC Frameworks Part II: Shared and Distinct Biological Mechanisms of Externalizing and Internalizing Psychopathology
Authors: Davis Christal N. , Khan Yousef , Toikumo Sylvanus , Jinwala Zeal , Boomsma Dorret I. , Levey Daniel F. , Gelernter Joel , Kember Rachel L. , Kranzler Henry R.
Published: February 2025

Background

The Hierarchical Taxonomy of Psychopathology (HiTOP) and Research Domain Criteria (RDoC) frameworks emphasize transdiagnostic and mechanistic aspects of psychopathology, respectively. We used a multi-omics approach to examine how externalizing (EXT), internalizing (INT), and shared EXT+INT liability map onto these models.

Methods

We conducted analyses across five RDoC units of analysis: genes, molecules, cells, circuits, and physiology. Using genome-wide association studies from the companion Part I article, we identified genes and tissue-specific expression patterns. We used drug repurposing analyses that integrate gene annotations to identify potential therapeutic targets and single-cell RNA sequencing data to implicate brain cell types. We then used magnetic resonance imaging data to examine brain regions and circuits associated with each psychopathology spectrum. Finally, we tested causal relationships between each spectrum and physical health conditions.

Results

Using five gene identification methods, EXT was associated with 1,759 genes, INT with 454 genes, and EXT+INT with 1,138 genes. Drug repurposing analyses identified potential therapeutic targets, including those that affect dopamine and serotonin pathways. Expression of EXT genes was enriched in GABAergic, cortical, and hippocampal neurons, while INT genes were more narrowly linked to GABAergic neurons. EXT+INT liability was associated with reduced gray matter volume in the amygdala and subcallosal cortex. Using Mendelian randomization, INT showed stronger causal effects on physical health—including chronic pain and cardiovascular diseases—than EXT.

Conclusions

Our findings revealed shared and distinct pathways underlying psychopathology. Integrating genomic insights with the RDoC and HiTOP frameworks advanced our understanding of mechanisms that underlie EXT and INT psychopathology.
Enhancing Diagnostic Precision in Thyroid Nodule Classification: A Deep Learning Approach to Automated Ultrasound Image Analysis
Authors: de Oliveira Andrade Luís Jesuino , Matos de Oliveira Gabriela Correia , Nunes Carneiro Andrade João Cláudio , Vinhaes Bittencourt Alcina Maria , de Figueiredo Adriana Malta , de Oliveira Luís Matos
Published: February 2025

Introduction

Escalating thyroid nodule prevalence necessitates precise ultrasonographic diagnosis, which is constrained by operator-dependent variability. Convolutional neural network (CNN)-based artificial intelligence (AI)/machine learning (ML) frameworks can improve segmentation, malignancy prediction, and interobserver concordance, yet they often lack real-world clinical validation, interpretable architectures, and actionable validation frameworks for translational integration.

Objective

To improve diagnostic accuracy in thyroid nodule classification using a deep learning (DL) approach for automated analysis of ultrasound images.

Method

This methodology employed a multicenter, retrospective cohort of anonymized thyroid ultrasound images (benign/malignant, histopathology-confirmed) sourced from PubMed®. Images were preprocessed (normalization, denoising) with expert-annotated regions of interest (ROIs). A CNN-based DL framework (ResNet-50, EfficientNet-B0) was fine-tuned via transfer learning for automated nodule detection, segmentation, and malignancy classification aligned with ACR TI-RADS™ criteria. Validation utilized an independent test set, diagnostic metrics (sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC)), and interobserver analysis (Cohen’s kappa) against three sonographers. Statistical rigor included PSPP-driven paired t-tests, chi-square tests, and McNemar’s tests to quantify AI-human concordance and optimize ACR TI-RADS™ integration for risk stratification.

Results

The AI model demonstrated high diagnostic efficacy: sensitivity 92.5%, specificity 88.3%, accuracy 90.4%, and AUC-ROC 0.94, surpassing sonographers in both sensitivity (p<0.001) and specificity (p<0.01). Interobserver concordance (Cohen’s κ=0.89) exceeded human variability (κ=0.72–0.85). ACR TI-RADS™ integration achieved 91.2% agreement, enhancing objectivity in the assessment of intermediate-risk nodules (categories 3–4). Feature analysis highlighted robust detection of hypoechoic patterns (94.2% sensitivity) and irregular margins (91.8% sensitivity), aligning with ACR TI-RADS™ criteria and confirming the AI’s potential to standardize risk stratification and reduce diagnostic subjectivity.

Conclusion

Advanced AI enhances thyroid ultrasound diagnostics through precise nodule detection and classification, reduced interobserver variability, and ACR TI-RADS™-aligned feature extraction, thereby boosting diagnostic confidence and clinical decision-making.
Protein Synthesis Blockade Prevents Fear Memory Reactivation via Inhibition of Engram Synapse Strengthening
Authors: Hong Ilgang , Kim Yeonjun , Jung Hyunsu , Kim Chang-Ho , Cho Jun-Hyeong , Kaang Bong-Kiun
Published: February 2025

Memory relies on ensembles of engram cells in the brain. While previous studies have established the existence of these cells, the relationship between cellular and synaptic activity remains unclear. To address this, we applied the dual e-GRASP technique in mice to examine synaptic connectivity between the ventral CA1 and the basal amygdala during memory formation. We found that contextual fear conditioning increased engram-to-engram synapse (engram synapse) density and induced structural potentiation, underscoring their importance in associative memory. Additionally, we investigated the role of protein synthesis in memory formation by inducing retrograde amnesia using anisomycin, a protein synthesis inhibitor. Mice injected with anisomycin once (1xANI) showed impaired natural recall but still displayed fear responses upon optogenetic reactivation of engram cells. In contrast, mice that received four anisomycin injections over six hours (4xANI) showed significantly impaired natural recall and failed to exhibit fear responses upon optogenetic reactivation. This behavioural phenotype was correlated with synaptic changes: 1xANI mice exhibited no significant reduction in engram synapse density but had significantly smaller spine sizes, whereas 4xANI mice showed both a significant reduction in engram synapse density and spine size. Our results indicate that protein synthesis inhibition significantly reduces engram synapse density and spine size, changes that correlate with reductions in fear memory during both natural recall and artificial reactivation.
HSCs and Tregs cooperate to preserve extramedullary hematopoiesis under chronic inflammation
Authors: Kuzmina Maria , Grusanovic Srdjan , Brezina Jiri , Milosevic Mirko , Vanickova Karolina , Pavliuchenko Nataliia , Ruzickova Sarka , Rohlena Jakub , Filipp Dominik , Rohlenova Katerina , Brdicka Tomas , Alberich-Jorda Meritxell
Published: February 2025

Hematopoietic stem cells (HSCs) are localized within specialized niches of the bone marrow (BM). However, during hematological disorders or infections, the functionality of HSCs in the BM is compromised, leading to extramedullary hematopoiesis (EMH). Chronic inflammation drives EMH, yet its impact on HSCs outside the BM is poorly understood. Using a mouse model of chronic autoinflammatory disease, we demonstrated the presence of extramedullary HSCs in blood, spleen, and inflamed tails and paws. Single-cell transcriptomics revealed a unique expression profile in extramedullary HSCs, with significant upregulation ofCd53, MHCII-associated, and immunosuppressive genes. We further demonstrated that extramedullary CD53+ HSCs act as antigen-presenting cells, promoting the development of regulatory T cells (Tregs) to control chronic inflammation at extramedullary sites. Conversely, Tregs exert a protective role on extramedullary HSCs. Altogether, our findings revealed a mutually supportive relationship between a unique subset of HSCs and T cells in inflamed tissues during chronic inflammation.
Genomic Insights into the Demographic History and Local Adaptation of Wild Boars Across Eurasia
Authors: Wang Zishuai , Li Zixin , Huang Tao , Chen Jianhai , Xu Pan , Qiao Ruimin , Yin Hongwei , Song Chengyi , Zhang Dongjie , Liu Di , Zhao Shuhong , Groenen Martien A. M. , Madsen Ole , Zhang Yanlin , Bai Lijing , Li Kui
Published: February 2025

Wild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Its expansion across Eurasia, especially in central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split ∼3.6 Mya, with Central Asian and Southern Chinese ancestors diverging ∼1.8 Mya. The split between Central Asian and European-Near East ancestors occurred ∼0.9 Mya, followed by a European-Near East divergence ∼0.6 Mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants inLPIN1, associated with cold adaptation, and a missense mutation inALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation, and shed light on domestic pigs breeding.
Network Biomarkers of Alzheimer’s Disease Risk Derived from Joint Volume and Texture Covariance Patterns in Mouse Models
Authors: Bridgeford Eric W. , Chung Jaewon , Anderson Robert J. , Mahzarnia Ali , Stout Jacques A. , Moon Hae Sol , Han Zay Yar , Vogelstein Joshua T. , Badea Alexandra
Published: February 2025

Alzheimer’s disease (AD) lacks effective cures and is typically detected after substantial pathological changes have occurred, making intervention challenging. Early detection and understanding of risk factors and their downstream effects are therefore crucial. Animal models provide valuable tools to study these prodromal stages. We investigated various levels of genetic risk for AD using mice expressing the three major human APOE alleles in place of mouse APOE. We leverage these mouse models utilizing high-resolution magnetic resonance diffusion imaging, due to its ability to provide multiple parameters that can be analysed jointly. We examine how APOE genotype interacts with age, sex, diet, and immunity to yield jointly discernable changes in regional brain volume and fractional anisotropy, a sensitive metric for brain water diffusion. Our results demonstrate that genotype strongly influences the caudate putamen, pons, cingulate cortex, and cerebellum, while sex affects the amygdala and piriform cortex bilaterally. Immune status impacts numerous regions, including the parietal association cortices, thalamus, auditory cortex, V1, and bilateral dentate cerebellar nuclei. Risk factor interactions particularly affect the amygdala, thalamus, and pons. APOE2 mice on a regular diet exhibited the fewest temporal changes, suggesting resilience, while APOE3 mice showed minimal effects from a high-fat diet (HFD). HFD amplified aging effects across multiple brain regions. The interaction of AD risk factors, including diet, revealed significant changes in the periaqueductal gray, pons, amygdala, inferior colliculus, M1, and ventral orbital cortex. Future studies should investigate the mechanisms underlying these coordinated changes in volume and texture, potentially by examining network similarities in gene expression and metabolism, and their relationship to structural pathways involved in neurodegenerative disease progression.
Machine Learning Reveals Immediate Disruption in Mosquito Flight when exposed to Olyset Nets
Authors: Qureshi Yasser M. , Voloshin Vitaly , Guy Amy , Ranson Hilary , McCall Philip J. , Towers Cathy E. , Covington James A. , Towers David P.
Published: February 2025

Insecticide-treated nets (ITNs) remain a critical intervention in controlling malaria transmission, yet the behavioural adaptations of mosquitoes in response to these interventions are not fully understood. This study examined the flight behaviour of insecticide-resistant (IR) and insecticide-susceptible (IS) Anopheles gambiae strains around an Olyset net (OL), a permethrin-impregnated ITN, versus an untreated net (UT). Using machine learning (ML) models, we classified mosquito flight trajectories with high accuracy (0.838) and ROC AUC (0.925). Contrary to assumptions that behavioural changes at OL would intensify over time, our findings show an immediate onset of convoluted, erratic flight paths for both IR and IS mosquitoes around the treated net. SHAP analysis identified three key predictive features of OL exposure: frequency of zero-crossings in flight angle change, first quartile of flight angle change, and zero-crossings in horizontal velocity. These suggest disruptive flight patterns, indicating insecticidal irritancy. While IS mosquitoes displayed rapid, disordered trajectories and mostly died within 30 minutes, IR mosquitoes persisted throughout the 2-hour experiments but exhibited similarly disturbed behaviour, suggesting resistance does not fully mitigate disruption. Our findings challenge literature suggesting permethrin’s repellency in solution form, instead supporting an irritant or contactdriven effect when incorporated into net fibres. This study highlights the value of ML-based trajectory analysis for understanding mosquito behaviour, refining ITN configurations and evaluating novel active ingredients aimed at disrupting mosquito flight behaviour. Future work should extend these methods to other ITNs to further illuminate the complex interplay between mosquito behaviour and insecticidal intervention.
Disease as a mediator of somatic mutation – life history coevolution
Authors: Hochberg Michael E.
Published: February 2025

Multicellular organisms are confronted not only with mutation in germline, but also mutations emerging in somatic cells. Somatic mutations can lead cancers and possibly contribute to aging phenotypes. Prevailing wisdom suggests somatic mutations are limited by evolved defences, either targeting DNA or post-mutational cellular states. Here, I analyse simple models for metazoans and humans in particular, incorporating the possibility that mutation rate trades-off of organism longevity, defined as the age at which natural selection becomes negligible. The models assume selection acts to reduce mutation rate and prevent disease, both of which contribute to selecting for longer lifespan. We detail equilibrium conditions and find coevolutionary oscillations under certain parameter combinations. Notably, disease prevention can lead to mutational tolerance and this can contribute to explaining empirical cross-species patterns in longevity vs. mutation rate. We conclude that mutational disease and cancer in particular have required characteristics to be mediators of mutation rate – lifespan coevolution. The mutational tolerance that results from this coevolution can contribute to explaining the incidences of other diseases and conditions, including aging.
NovelEscherichia coliPhages Representing a Distinct Genus withinStephanstirmvirinae: Genome and Host Range Characteristics
Authors: Kaneko Tomoyoshi , Uchiyama Jumpei , Osaka Toshifumi , Tsuneda Satoshi
Published: February 2025

Bacteriophages play crucial roles in microbial ecosystems and have potential biotechnological applications. However, our understanding of culturable phages remains limited. This study characterized six novelEscherichia coliphages isolated from pig farm wastewater and urban sewage using comprehensive genomic, morphological, and host-range analyses. Using multiple comparative approaches, including gene-sharing network analysis, average nucleotide identity (ANI), and nucleotide intergenomic similarity (NIS), we demonstrated that five of these phages form a distinct group within the subfamilyStephanstirmvirinae, potentially representing a novel genus provisionally named "Wecvirus”. These phages were further classified into two distinct species within the proposed genus, each of which exhibits a unique host range pattern. This host specificity is reflected in the species-specific differences in the amino acid sequences of tail fibers, which are crucial for infection. The remaining phage, which was not classified as Wecvirus exhibited characteristics that challenged the current classification criteria, highlighting the need for more flexible taxonomic approaches. Our findings expand the understanding of phage diversity withinStephanstirmvirinaeand contribute to the evolving phage taxonomy framework.
Background color matching influences sexual behavior, growth, and mortality rate in an African cichlid fish
Authors: Moore Travis I. , Bright William G. , Bell William E. , Solomon-Lane Tessa K. , Alvarado Sebastian G. , Dijkstra Peter D.
Published: February 2025

Phenotypic plasticity allows organisms to adapt to changing environments within their lifetimes. The cost of plastic adaptations may constrain the persistence of plasticity over evolutionary time. One potential cost is the possibility that phenotypic adjustment to specific environments can cause correlated responses that are not necessarily adaptive. Males in the African cichlidAstatotilapia burtoniare blue or yellow, and males are able adjust their body coloration to the color of the background, presumably to increase crypsis. To test whether background color influences fitness-related traits, we raised mix-sex groups of juvenileA. burtonito adulthood in yellow or blue tanks. We found that fish in blue tanks were darker and more bluish, whereas fish reared in yellow tanks were paler and more yellow in body coloration. Males, but not females, from blue tanks showed earlier sexual maturation than those held in yellow tanks. However, across the duration of the experiment, there was a higher frequency of females mouthbrooding in groups housed in yellow tanks than those that were housed in blue tanks. In addition, fish in blue tanks exhibited reduced growth rate but higher survivorship relative to their yellow-reared counterparts. Our data suggests that background color affects important fitness-related traits in a color polymorphic cichlid, which may influence the evolution of phenotypic plasticity.
Olfactory preferences and chemical differences of fruit scents forAedes aegyptimosquitoes
Authors: Leon-Noreña Melissa , Tauxe Genevieve M. , Riffell Jeffrey A.
Published: February 2025

Feeding on the sugar of fruits and flowers is vital for mosquitoes and increases their lifespan, reproduction, and flight activity. Olfaction is a key sensory modality in mediating mosquito responses to sugar sources. Previous studies have demonstrated that natural nectar sources from fruits and flowers can vary in attractiveness to mosquitoes, with some sources preferred over others. However, how the attractiveness of different fruits relates to the chemical composition of their scent and the responses they evoke from the mosquito’s peripheral olfactory system, is still not understood. In this study, we use closely related fruit species and their varieties to examine how changes in scent chemistry can influence the fruit’s attractiveness toAedes aegyptimosquitoes and examine how the mosquito’s olfactory responses (via electroantennogram recordings, or EAG) correlate with those differences. Our results show that mosquitoes are attracted to the scents of certain fruits (Mangifera indica, Prunus perspica, Psidium guajava, Musa acuminata), whereas others (Pyrus communis, Citrus limon) elicited responses not significantly different from the negative control. Chemical analyses of the scents showed that attractive fruits have distinct chemical profiles, and amongst closely related fruits, minor changes in the relative proportions of scent compounds can modify the attractiveness. These minor differences in the fruit scent were not reflected in the EAG responses, which showed similar responses to scents from different fruit species and closely related varieties. Experimentally altering the chemical proportion of a single compound in attractive scents caused a significant decrease in attraction to levels similar to the less attractive cultivars. Our results demonstrate that mosquitoes are sensitive to compound proportions in attractive odors, which have implications for the olfactory processing of complex odor sources, like those from plants or blood hosts.

Summary Statement

Aedes aegyptimosquitoes show specific and selective fruit scent preferences related to differences in the proportion of compounds in the scent.
Effects of GlobalRipk2Genetic Deficiency in Aged Mice following Experimental Ischemic Stroke
Authors: Howell John Aaron , Larochelle Jonathan , Gunraj Rachel E. , Stansbury Sofia M. , Liu Lei , Yang Changjun , Candelario-Jalil Eduardo
Published: February 2025

Besides the loss of blood and oxygen reaching the ischemic tissue, many secondary effects of ischemic stroke can cause additional tissue death, including inflammation, oxidative stress, and proteomic disturbances. Receptor-interacting serine/threonine kinase 2 (RIPK2) is an important mediator in the post-stroke inflammatory cascade that responds to signals and molecular patterns released by dead or dying cells in the ischemic area. We hypothesize that RIPK2 signaling worsens injury and neurological recovery post-stroke and that global deletion ofRipk2will be protective following ischemic stroke in aged mice. Aged (18-24 months) male mice were subjected to permanent middle cerebral artery occlusion (pMCAO). Vertical grid, weight grip, and open field were conducted at baseline and on days 1, 2, 3, 8, 15, and 22 post-stroke. Cognitive tests (novel object recognition and Y-maze) were performed at baseline and day 28 post-stroke. Infarct size was measured using cresyl violet staining, and reactive gliosis was measured using Iba1 and GFAP staining at day 28 post-stroke. Global deletion ofRipk2(Ripk2-/-) in aged mice resulted in smaller infarct volume and improved performance on vertical grid and weight grip tests compared to aged wildtype (WT) mice. Additionally, agedRipk2-/-mice had less Iba1 staining in the ipsilateral cortex than the aged WT control mice. This study further elucidates the role of RIPK2 signaling in the ischemic cascade and expands our knowledge of RIPK2 in stroke to aged mice. These results support the hypothesis that RIPK2 signaling worsens injury post-stroke and may be an attractive candidate for therapeutic intervention.
Influence of past climate changes and human-mediated introduction on patterns of genetic diversity distribution of the Papuan nutmeg (Myristica argentea) Warb
Authors: Kusuma Jakty , Milaba Adinda C. , Paramitha Amalia , Malaval Victoria , Sari Mei Nita , Nurhuda Cahya , Couderc Marie , Scarcelli Nora , Watts John , Duminil Jérôme
Published: February 2025

Understanding the distribution of genetic diversity of endemic food tree species holds significant importance for conservation planning and the formulation of effective management strategies. Natural and anthropogenic factors can influence species’ geographic range and distribution of genetic diversity. Here, we tested the relative influence of barriers to gene flow (rivers, mountains and past climate change) and recent human activities on the evolutionary history of an endemic species from Fakfak district, Papua Island,Myristica argenteaWarb (Myristicaceae), better known as Papuan nutmeg.Myristica argenteais a spice tree species used by local populations since centuries/millennia. The species has been introduced in other locations from the region. Fourteen microsatellite markers (nSSRs), whole chloroplast (cp) genome, and nuclear-targeted sequence genes (nrDNA sequence) were used to characterize the genetic diversity, population structure, and demographic history of the species across its distribution range (native and introduced populations). We found that native populations of the species in Fakfak present higher levels of genetic diversity than introduced populations. We further detected the presence of a moderate genetic structure (FST= 0.143), and the presence of three intraspecific genetic clusters. Additionally, our findings indicate that population fragmentation within the native range of the species in Fakfak, may have been influenced by the presence of riparian networks, mountain ranges and by Pleistocene climatic fluctuations. Our results suggest that all introduced populations were sourced mainly from the native population of Raduria, in the South of Fakfak region. Given the population genetic variation across the ranges of Papuan nutmeg, management plans should not treat them as single populations, but rather consider the broader genetic diversity within its range.
Selecting a Window Size for the Analysis of Whole Genome Alignments using AIC
Authors: Ivan Jeremias , Frandsen Paul , Lanfear Rob
Published: February 2025

Abstract

The variation of evolutionary histories along the genome presents a challenge for phylogenomic methods to identify the non-recombining regions and reconstruct the phylogenetic tree for each region. To address this problem, many studies used the non-overlapping window approach, often with an arbitrary selection of fixed window sizes that potentially include intra-window recombination events. In this study, we proposed an information theoretic approach to select a window size that best reflects the underlying histories of the alignment. First, we simulated chromosome alignments that reflected the key characteristics of an empirical dataset and found that the AIC is a good predictor of window size accuracy in correctly recovering the tree topologies of the alignment. Due to the issue of missing data in empirical datasets, we then designed a stepwise non-overlapping window approach and applied this method to the genomes oferato-sara Heliconiusbutterflies and great apes. We found that the best window sizes for the butterflies’ chromosomes ranged from<125bp to 250bp, which are much shorter than those used in a previous study even though this difference in window size did not significantly change the most common topologies across the genome. On the other hand, the best window sizes for great apes’ chromosomes ranged from 500bp to 1kb with the proportion of the major topology (grouping human and chimpanzee) falling between 60% and 87%, consistent with previous findings. Additionally, we observed a notable impact of stochastic error and concatenation when using small and large windows, respectively. For instance, the proportion of the major topology for great apes was 50% when using 250bp windows, but reached almost 100% for 64kb windows. In conclusion, our study highlights the challenges associated with selecting a window size in non-overlapping window analyses and proposes the AIC as a more objective way to select the optimal window size for whole genome alignments.
Averted mortality by COVID-19 vaccination in Belgium between 2021 and 2023
Authors: Stouten Veerle , Van Evercooren Izaak , Vernemmen Catharina , Braeye Toon , Catteau Lucy , Roelants Mathieu , Billuart Matthieu , Lamot Thomas , Sierra Natalia Bustos , Hammami Naïma , Vermeiren Elias , Rosas Angel , Blot Koen , Schmelz Anna I. , Nasiadka Léonore , Nganda Serge , van Loenhout Joris A.F.
Published: February 2025

Background

Vaccination campaigns were rolled out primarily to limit the impact of COVID-19 on severe health outcomes, including mortality.

Aim

We aimed to estimate the number of averted deaths by COVID-19 vaccination in the Belgian population aged 65 years and older, between January 2021 and January 2023.

Methods

Nationwide data on COVID-19 infections, vaccine administrations and all-cause mortality were individually linked. We estimated Vaccine Effectiveness against COVID-19 mortality (VE) among persons having received a vaccine dose in the last 6 months, using a Cox proportional hazards model adjusted for age, sex, time since vaccination, previous infection, underlying health conditions, province and income. COVID-19 death was defined as a person with a laboratory-confirmed SARS-CoV-2 infection who died within a specified interval. Based on obtained VE estimates, vaccine coverage and national COVID-19 mortality data, we estimated the number of averted deaths.

Results

We estimated VE (0-59 days after vaccination) for 65-79 year and ≥80 year-olds respectively, at 81.9% (78.1%-85.1%) and 74.7% (71.2%-77.7%) during Alpha, at 90.5% (88.8%-91.9%) and 91.4% (90.4%- 92.4%) during Delta and at 84.0% (81.8%-85.9%) and 74.5% (72.4%-76.5%) during Omicron period. Among the Belgian population aged 65 years and older, we estimated 12,806 deaths averted (11,633- 13,982), representing a 54% reduction (51%-56%) in the expected deaths (without vaccination). During the Delta period COVID-19 deaths were reduced by 68%, during Omicron by 54% and during Alpha by 31%.

Discussion

Vaccinating against COVID-19 reduced deaths by 54% among the Belgian population aged 65 years and older, underscoring the importance of COVID-19 vaccines in reducing mortality.