bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social family structure and biogeography contribute to genomic divergence and cryptic speciation in the only eusocial beetle species,Austroplatypus incompertus(Curculionidae: Platypodinae)
Authors: Bickerstaff James R. M. , Jordal Bjarte H. , Riegler Markus 
Published: November 2024

AbstractEusociality in insects has arisen multiple times independently in Hymenoptera (bees, wasps, ants), Blattodea (termites) and Coleoptera (beetles). In Hymenoptera and Blattodea, the evolution of eusociality led to massive species proliferation. In the hyperdiverse Coleoptera, eusociality evolved only once, in the ancient Australian ambrosia beetle speciesAustroplatypus incompertus(Curculionidae: Platypodinae). This species occurs in mesic eucalypt forests of eastern Australia, from Victoria to northern New South Wales. Based on few individuals collected from the southern and northern edges of the species’ distribution it was initially described as two distinct species; however, the names were later synonymised as no morphological differences were found in analyses of more specimens. Recent mitochondrial haplotype analyses revealed substantial latitudinal divergence across the distribution ofA. incompertus. To address this apparent disparity between morphological and molecular data, we sequenced and analysed a SNP panel of over 6,656 biallelic markers from 187 individuals of 11 sites across 1000 km of this species’ range. Our data indicate that eusocial demographic processes such as low colony establishment success rate, limited dispersal and reliance on few reproductive individuals, together with substantial habitat fragmentation contributed to the population genetic structure of this species. We further identified that the Hunter Valley biogeographic barrier split the species into two distinct clades, with both clades in secondary close contact on the Barrington Tops plateau without any discernible admixture. Our results support the resurrection of a second species ofAustroplatypuswhich has important consequences for the evolution eusociality in Coleoptera and the systematics of Platypodinae.
Unraveling the Mysteries of Sleep: Exploring Phylogenomic Sleep Signals in the Recently Characterized Archaeal Phylum Lokiarchaeota near Loki’s Castle
Authors: Pandi-Perumal Seithikurippu R , Saravanan Konda Mani , Paul Sayan , Spence David Warren , Chidambaram Saravana Babu 
Published: November 2024

AbstractSleep is a universally conserved behavior with an elusive origin and an uncertain evolutionary purpose. Leveraging phylogenomics, we investigate the evolutionary foundations of sleep by identifying orthologs of Human sleep-related genes in the Lokiarchaeota of the Asgard superphylum. Our findings indicate a conserved suite of genes associated with energy metabolism and cellular repair, suggesting a primordial role of sleep in cellular maintenance. This data lends credence to the idea that sleep improves organismal fitness across evolutionary time by acting as a restorative process. Notably, our approach demonstrates that phylogenomics is more useful than standard phylogenetics for clarifying common evolutionary traits. By offering insight into the evolutionary history of sleep and putting forth a novel model framework for sleep research across taxa, these findings contribute to our growing understanding of the molecular foundation of sleep. This study lays the groundwork for further investigations into the importance of sleep in various organisms, which could have consequences for human health and a deeper comprehension related to the fundamental processes of life.Graphical Abstract
Policy optimization emerges from noisy representation learning
Authors: Brenner Jonah W. , Li Chenguang , Kreiman Gabriel 
Published: November 2024

AbstractNervous systems learn representations of the world and policies to act within it. We present a framework that uses reward-dependent noise to facilitate policy opti- mization in representation learning networks. These networks balance extracting normative features and task-relevant information to solve tasks. Moreover, their representation changes reproduce several experimentally observed shifts in the neural code during task learning. Our framework presents a biologically plausible mechanism for emergent policy optimization amid evidence that representation learning plays a vital role in governing neural dynamics. Code is available at: NeuralThermalOptimization.
Disease-linked mutations dysregulate neuronal condensate physical properties, composition, and RNA translation
Authors: Ahangama Liyanage Leshani , McCready Fraser , Chung Steve , Arsenault Jason , Wei Wei , Lin Xusheng , Wang Lu-Yang , Ellis James , Ditlev Jonathon A. 
Published: November 2024

AbstractLocal RNA translation is essential for development. In neurons, deficient local translation linked with mutations in scaffold proteins results in dysregulated dendrite and dendritic spine growth. However, mechanisms by which these proteins control translation and how disease-linked mutations induce aberrant translation were unclear. We use biochemical reconstitution and neuronal assays to show that mutations to the neuronal condensate scaffold shank2 cause physical hardening and altered composition of condensates; a key RNA translation-modulator FMRP is excluded from mutant condensates. Functionally, shank2 condensates repress translation while condensates composed of shank2 with intrinsically disordered region-localized missense mutations promote translation. These results demonstrate that disease-linked dysregulation of condensate physical properties and composition is an underlying mechanism of aberrant RNA translation often observed in disease.One Sentence SummaryDisease-linked missense mutations in the postsynaptic density scaffold protein shank2 dysregulate phase separated biomolecular condensate physical properties and composition resulting in aberrant RNA translation.
Constitutive expression of CX3CR1-BAC-Cre introduces minimal off-target effects in microglia
Authors: Mroue-Ruiz Fadya H. , Desai Bhoomi , Garvin Madison , Shehu Jonila , Kamau Faith , Kar Urjoshi , Bolton Jessica L. 
Published: November 2024

SUMMARYCX3CR1-Cre mouse lines have produced important advancements in our understanding of microglial biology. Recent studies have demonstrated the adverse effects of tamoxifen-induced CX3CR1-Cre expression during development, which include changes in microglial density, phenotype, and DNA damage, as well as anxiety-like behavior. However, the unintended effects of constitutive CX3CR1-BAC-Cre expression remain unexplored. Here, we characterized the effects of CX3CR1-BAC-Cre expression on microglia in CX3CR1-BAC-Cre+/- and CX3CR1-BAC-Cre-/-male and female littermates during early postnatal development and adulthood in multiple brain regions. Additionally, we performed anxiety-like behavior tests to assess changes caused by Cre expression. We found that CX3CR1-BAC-Cre expression causes subtle region- and sex-specific changes in microglial density, volume, and morphology during development, but these changes normalized by adulthood in all brain regions except the hippocampus. No behavioral effects were found. Our findings suggest that the constitutive-Cre model might be less detrimental than the inducible model, and highlight the need for proper controls.
Accuracy of computed tomography in diagnosing temporomandibular joint osteoarthritis relative to histopathological findings – an ex–vivo study of 41 horses
Authors: Jasinski Tomasz , Zdrojkowski Łukasz , Turek Bernard , Kaczorowski Michał , Pawliński Bartosz , Brehm Walter , Domino Małgorzata 
Published: November 2024

AbstractComputed tomography (CT) is commonly used for imaging the equine head, particularly when diseases of temporomandibular joint (TMJ), including osteoarthritis (OA), are suspected. However, certain CT findings have been proposed as ’anatomical variations’, and their clinical significance remains unknown. The objectives of this prospective descriptive cross-sectional study were to describe the CT and histopathological findings of TMJ OA in relation to horse age, evaluate the accuracy of TMJ OA diagnosis with regard to ’CT anatomical variations’, and explore the correlations between specific CT and histopathological findings. CT images and tissue samples from 41 heads (82 TMJs) were independently and simultaneously reviewed by two observers. Descriptive statistics on both findings, their age–related frequency, and accuracy of TMJ OA diagnosis were calculated. Based on histopathological assessment, TMJ OA was confirmed in 18% of joints in horses aged 1–4 years, 63% of joints in horses aged 5–15 years, and 83% of joints in horses over 15 years. Considering entire CT findings, TMJ OA was radiologically recognized in 76% of joints, with a sensitivity of 0.95 and a specificity of 0.37. When ’CT anatomical variations’ were excluded, TMJ OA was recognized in 30% of joints, with a sensitivity of 0.51 and a specificity of 0.88. Findings suggest that the equine TMJ may undergo both age–related and disease–related remodeling, detectable through CT and histopathology, and that the inclusion or exclusion of certain ’CT anatomical variations’ in the diagnostic protocol affects the sensitivity and specificity of CT–based TMJ OA recognition.
A Deep Attention-Based Encoder for the Prediction of Type 2 Diabetes Longitudinal Outcomes from Routinely Collected Health Care Data
Authors: Manzini Enrico , Vlacho Bogdan , Franch-Nadal Josep , Escudero Joan , Génova Ana , Reixach Elisenda , Andrés Erich , Pizarro Israel , Mauricio Dídac , Perera-Lluna Alexandre 
Published: November 2024

AbstractRecent evidence indicates that Type 2 Diabetes Mellitus (T2DM) is a complex and highly heterogeneous disease involving various pathophysiological and genetic pathways, which presents clinicians with challenges in disease management. While deep learning models have made significant progress in helping practitioners manage T2DM treatments, several important limitations persist. In this paper we propose DARE, a model based on the transformer encoder, designed for analyzing longitudinal heterogeneous diabetes data. The model can be easily fine-tuned for various clinical prediction tasks, enabling a computational approach to assist clinicians in the management of the disease. We trained DARE using data from over 200,000 diabetic subjects from the primary healthcare SIDIAP database, which includes diagnosis and drug codes, along with various clinical and analytical measurements. After an unsupervised pre-training phase, we fine-tuned the model for predicting three specific clinical outcomes: i) occurrence of comorbidity, ii) achievement of target glycaemic control (defined as glycated hemoglobin<7%) and iii) changes in glucose-lowering treatment. In cross-validation, the embedding vectors generated by DARE outperformed those from baseline models (comorbidities prediction taskAUC= 0.88, treatment prediction taskAUC= 0.91, HbA1c target prediction taskAUC= 0.82). Our findings suggest that attention-based encoders improve results with respect to different deep learning and classical baseline models when used to predict different clinical relevant outcomes from T2DM longitudinal data.
Alu overexpression leads to increased double-stranded RNA in dermatomyositis
Authors: Najjar Rayan , Mammen Andrew , Mustelin Tomas 
Published: November 2024

AbstractDermatomyositis is an autoimmune condition characterized by a high interferon signature of unknown etiology. Because genes constitute only <2% of our genomes, there is a need to explore the role of the non-coding genome in disease pathogenesis. Our genomes include roughly 1.2 million Alu elements occupying about 10% of the genome and can form double-stranded (ds)RNA capable of triggering MDA5 leading to interferon production. We aligned muscle biopsy RNA sequencing data to the Telomere-to-Telomere reference genome and quantified short interspersed elements including Alus. Dermatomyositis muscle (n=39) showed a global elevation in Alu expression as well as an increased expression of unique Alu elements (n=557, p<0.05) compared to healthy controls (n=34), in a pattern not seen in other myositis types (n=81). The majority (75.3%) of these Alus originated from genomic regions outside genes, with a hot spot of expression on chromosome 19. A subset of the uniquely overexpressed Alus (n=167) correlated strongly with interferon stimulated genes and markers of myositis activity. Since Alu transcripts have a propensity to form dsRNA and are the major targets of both ADAR and MDA5, we quantified the A-to-I RNA editomes inside Alus and found a uniquely expanded Alu editome in dermatomyositis compared to other myositis types, reflecting an increase in dsRNA. Edited Alus clustered on chromosome 19, which is known to have the highest concentration of dsRNA. We hypothesize that overexpressed Alus in dermatomyositis form endogenous dsRNA that exceed the capacity of RNA editing enzymes and trigger dsRNA sensors leading to interferon production.
Emerging pathogens associated with acute respiratory infections in children before, during and after the COVID-19 pandemic in Hanoi, Vietnam
Authors: Ho Nhan Thi , Nguyen Hang Thi Thuy , Hoang Ha Thi , Pham Dung Van , Nguyen Quang Ngoc , Le Huong Thi Minh , Pham An Nhat , Doan Phuong Mai 
Published: November 2024

ABSTRACTThe COVID-19 pandemic has caused changes in respiratory infectious disease patterns. We analyzed de-identified data of microbiology assays of nasopharyngeal samples and blood samples of children with acute respiratory infection (ARI) visited Vinmec Times City International hospital in Hanoi, Vietnam from January 2019 to December 2023 to examine the overall pattern of viral and bacterial emerging pathogens associated with ARI in children before, during and after the COVID-19 pandemic. The data was aggregated by month and time series analysis and visualization was done. Bacterial Polymerase Chain Reaction (PCR) panel was done for 4125 samples,Mycoplasma pneumonia(MP) IgM was done for 5049 samples, bacterial culture was done for 10280 samples and viral PCR or rapid test was done for 42041 samples. After the COVID-19 pandemic,Haemophilus influenzae(HI) andStreptococcus pneumoniae(SP) have re-emerged as epidemic pathogens associated with lower respiratory tract infection (LRI).Influenza type Aandtype Bhave reestablished regular cycles of peaks in winter-spring months after an early rebound together with an unprecedented newly emergence ofHuman Adenovirus(HAdV) soon after the relief of COVID-19 restriction. Late after the COVID-19 pandemic, from middle of 2023, atypical pneumonia pathogenMycoplasma pneumonia(MP) has emerged remarkably and becoming epidemic and there was also a small, brief emergence ofChlamydophila pneumoniae(CP) infection. Our data is useful to understand the influence of COVID-19 pandemic on the emergence or re-emergence of viral and bacterial respiratory infection pathogens in children and is useful for disease surveillance and public health intervention.
Post-stroke changes in brain structure and function can both influence acute upper limb function and subsequent recovery
Authors: Zich Catharina , Ward Nick S , Forss Nina , Bestmann Sven , Quinn Andrew J , Karhunen Eeva , Laaksonen Kristina 
Published: November 2024

AbstractImproving outcomes after stroke depends on understanding both the causes of initial function/impairment and the mechanisms of recovery. Recovery in patients with initially low function/high impairment is variable, suggesting the factors relating to initial function/impairment are different to the factors important for subsequent recovery. Here we aimed to determine the contribution of altered brain structure and function to initial severity and subsequent recovery of the upper limb post-stroke.The Nine-Hole Peg Test was recorded in week 1 and one-month post-stroke and used to divide 36 stroke patients (18 females, age: M = 66.56 years) into those with high/low initial function and high/low subsequent recovery. We determined differences in week 1 brain structure (Magnetic Resonance Imaging) and function (Magnetoencephalography, tactile stimulation) between high/low patients for both initial function and subsequent recovery. Lastly, we examined the relative contribution of changes in brain structure and function to recovery in patients with low levels of initial function.Low initial function and low subsequent recovery are related to lower sensorimotor β power and greater lesion-induced disconnection of contralateral [ipsilesional] white-matter motor projection connections. Moreover, differences in intra-hemispheric connectivity (structural and functional) are unique to initial motor function, while differences in inter-hemispheric connectivity (structural and functional) are unique to subsequent motor recovery.Function-related and recovery-related differences in brain function and structure after stroke are related, yet not identical. Separating out the factors that contribute to each process is key to identifying potential therapeutic targets for improving outcomes.
“In Situ Resistance Insulin – Localized Type 2 Diabetes Mellitus or Type 6 Diabetes Mellitus?”: A Scoping Review
Authors: de Oliveira Andrade Luís Jesuino , Matos de Oliveira Gabriela Correia , Nunes Carneiro Andrade João Cláudio , Vinhaes Bittencourt Alcina Maria , Matos de Oliveira Luís 
Published: November 2024

ABSTRACTIn the context of type 2 diabetes mellitus (T2DM), the concept of organ-specific insulin resistance (IR) as a localized manifestation has garnered increasing attention. A scoping review was conducted to investigate the clinical relevance of IR confined to individual organs without systemic metabolic implications. Utilizing a methodological framework adapted from Arksey and O’Malley, a comprehensive search of PubMed was performed, focusing on the period between January 1990 and October 2024. The search strategy combined Medical Subject Headings terms and keywords related to IR and specific organs. Notably, while “insulin resistance” yielded a substantial number of results, the subset of “organ-specific insulin resistance” returned a more limited dataset, highlighting a gap in current literature. The systematic selection process encompassed identification, screening, eligibility, and inclusion stages to ensure robust inclusion criteria. This scoping review underscores the importance of exploring organ-specific IR in the diabetic milieu and sets the stage for further research to elucidate its role in the pathogenesis of T2DM. Conclusion: The findings suggest that investigating organ-specific IR in the context of T2DM is a promising avenue for future research to deepen our understanding of disease pathophysiology. Thus, this scoping review answers the following question “In Situ Resistance Insulin - Localized Type 2 Diabetes Mellitus or Type 6 Diabetes Mellitus?”, emphasizing the need for targeted investigations into localized manifestations of IR and their implications for DM management strategies.
Polymorphic tandem repeats shape single-cell gene expression across the immune landscape
Authors: Tanudisastro Hope A. , Cuomo Anna S.E. , Weisburd Ben , Welland Matthew , Spenceley Eleanor , Franklin Michael , Xue Angli , Bowen Blake , Wing Kristof , Tang Owen , Gray Michael , Reis Andre L.M. , Margoliash Jonathan , Kurtas Edibe Nehir , Pullin Jeffrey , Lee Arthur S. , Brand Harrison , Harper Michael , Bobowik Katalina , Silk Michael , Marshall John , Bakiris Vivian , Madala Bindu Swapna , Uren Caitlin , Bartie Caitlin , Senabouth Anne , Dashnow Harriet , Fearnley Liam , Dolzhenko Egor , Qiao Zhen , Grieve Stuart , Nguyen Tung , Talkowski Michael , Alexander Stephen I. , Siggs Owen M. , Gruenschloss Leonhard , Nicholas Hannah R. , Piscionere Jennifer , Simons Cas , Wallace Chris , Gymrek Melissa , Deveson Ira W. , Hewitt Alex W. , Figtree Gemma A. , de Lange Katrina M. , Powell Joseph E. , MacArthur Daniel G. 
Published: November 2024

AbstractTandem repeats (TRs) – highly polymorphic, repetitive sequences dispersed across the human genome – are crucial regulators of gene expression and diverse biological processes. Yet, due to historical challenges in their accurate calling and analysis, TRs have remained underexplored compared to single nucleotide variants (SNVs). Here, we introduce a cell type-specific resource exploring the impact of TR variation on human gene expression. Leveraging whole genome and single-cell RNA sequencing, we catalog over 1.7 million polymorphic TR loci and their associations with gene expression across more than 5 million blood-derived cells from 1,790 individuals. We identify over 58,000 single-cell expression quantitative trait TR loci (sc-eTRs), 16.6% of which are specific to one of 28 distinct immune cell types. Further fine-mapping uncovers 6,210 sc-eTRs as candidate causal drivers of gene expression in 21% of genes tested genome-wide. We show through colocalization that TRs are likely regulators of over 2,000 GWAS loci associated with immune-mediated and hematological traits, and further identify novel TRs warranting investigation in rare disease cohorts. TRs are pivotal, yet long-overlooked, contributors to cell type-specific gene expression, with promising implications for understanding rare disease pathogenesis and the genetic architecture of complex traits.
Computational modelling shows evidence in support of both sensory and frontal theories of consciousness
Authors: Bandara Kavindu H. , Rowe Elise G. , Garrido Marta I. 
Published: November 2024

AbstractThe role of the prefrontal cortex (PFC) in consciousness is hotly debated. Frontal theories argue that the PFC is necessary for consciousness, while sensory theories propose that consciousness arises from recurrent activity in the posterior cortex alone, with activity in the PFC resulting from the mere act of reporting. To resolve this dispute, we re-analysed an EEG dataset of 30 participants from a no-report inattentional blindness paradigm where faces are (un)consciously perceived. Dynamic causal modelling was used to estimate the effective connectivity between the key contended brain regions, the prefrontal and the posterior cortices. Then, a second-level parametric empirical Bayesian model was conducted to determine how connectivity was modulated by awareness and task-relevance. While an initial data-driven search could not corroborate neither sensory nor frontal theories of consciousness, a more directed hypothesis-driven analysis revealed strong evidence that both theories could explain the data, with a very slight preference for frontal theories. Specifically, a model with backward connections switched off within the posterior cortex explained awareness better (53%) than a model without backward connections from the PFC to sensory regions. Our findings provide some support for a subtle, yet crucial, contribution of the frontal cortex in consciousness, and highlight the need to revise current theories of consciousness.
Sleep Disruption Improves Performance in Simple Olfactory and Visual Decision-Making Tasks
Authors: Pflitsch Paula , Oury Nadine , Krishnan Kumaresh , Joo William , Lyons Declan G. , Capelle Maxim , Herrera Kristian J. , Bahl Armin , Rihel Jason , Engert Florian , Zwaka Hanna 
Published: November 2024

ABSTRACTSleep disruption drastically impacts cognitive functions including decision-making and attention across many different species. In this study, we leveraged the small size and conserved vertebrate brain structure of larval zebrafish to investigate how sleep disruption modulates visual- and olfactory-decision-making. Strikingly, sleep disruption improved performance in both paradigms. Specifically, sleep disruption lengthens reaction times and increases correct decisions in a visual motion discrimination task, an effect that we attribute to longer integration periods in disrupted animals. Using a drift diffusion model, we predict specific circuit changes underlying these effects. Additionally, we demonstrate that sleep disruption heightens odor sensitivity in an olfactory decision-making task, likely mediated by cortisol. Our findings lay essential groundwork for investigating the brain circuit changes that arise from sleep disruption across species.