bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the nematodeStrongyloides stercoralisa zoonosis from dogs? – a population genetics approach
Authors: Liu Yuchen , Raihan Sarker A. H. M. , Sripa Banchob , Tangkawatta Sirikachorn , Khieu Virak , Nevin William , Paterson Steve , Viney Mark 
Published: December 2024

AbstractGut nematode worms are important parasites of people and other animals. The parasitic nematodeStrongyloides stercoralisinfects an estimated 600 million people worldwide, and is one of the soil-transmitted helminthiases, a WHO-defined neglected tropical disease. It has long been suggested that humanS. stercoralisinfection may be a zoonosis from dogs. We investigated this by whole genome sequence analysis ofS. stercoralisfrom sympatric human and dog populations in Asia. We find that human- and dog-derivedS. stercoralishave genetically distinct nuclear genomes, but we also find evidence of rare cross infection. Analysis of theS. stercoralismitochondrial genome reveals evidence of historical introgression between human- and dog-derived parasites. Based on these data we suggest thatS. stercoraliswas originally a parasite of canids, that began to infect humans when people domesticated dogs, since when human- and dog-derived parasites have differentiated, but have not become separate species.Significance StatementNematode worms infect approximately a quarter of the world’s human population;Strongyloides stercoralisinfects some 600 million people. It has been suggested thatS. stercoralisin people and dogs is the same parasite, such that some human infection is acquired zoonotically from dogs. It is important to understand the source of humanStrongyloidesinfection to be able to control it and the harm that it causes. Our population genomic analyses of human- and dog-derivedS. stercoralisin Asia show that these parasites are distinct, but also reveal rare cross infection events. Our results are consistent withS. stercoralisancestrally being a parasite of dogs that began infecting people when dogs became domesticated.
Untangling the contribution of adaptiveversusnon-adaptive processes in the evolution of reproductive isolation betweenCoenonymphabutterflies
Authors: Capblancq Thibaut , Roux Camille , Boyer Frédéric , Legeai Fabrice , Joron Mathieu , Després Laurence 
Published: December 2024

ABSTRACTSpeciation is a key evolutionary process which has been studied in numerous organisms and at multiple scales, from lineage radiation to gene expression. However, the factors explaining the rise of new species are not yet fully understood, and the relative contribution of neutralversusselective evolutionary processes in triggering and maintaining reproductive isolation between lineages is still debated. To explore this question, we study the divergence of two butterfly species,Coenonympha arcaniaandC. gardetta(Nymphalidae), which diverged relatively recently but show strong ecological differences. Whole genome sequence data reveal high overall differentiation between the two lineages, best explained by a long period of isolation at the early stage of their divergence. Demographically explicit approaches identify that 6.6% of the genome (32.7 Mbp) is impermeable to gene flow between the two species. Lots of these barrier loci are located on the Z chromosome, potentially spanning 75% of its length which would indicate that a large Z effect is at play in this speciation. Moreover, only a small proportion of barriers showed signatures of selection, suggesting that non-adaptive processes largely contributed to the build-up of reproductive isolation. Therefore, although genes involved in stress response and response to hypoxia are interesting candidates under selection, the adaptation ofC. gardettato alpine conditions may not to be the main driver of speciation. Our study brings an original example of intertwined adaptive and non-adaptive processes leading to reproductive isolation in a speciation with secondary contact and improves our understanding of the genomic underpinnings of species divergence.
Increased NFAT and NFκB signalling contribute to the hyperinflammatory phenotype in response toAspergillus fumigatusin cystic fibrosis
Authors: Bercusson Amelia , Williams Thomas J , Simmonds Nicholas J , Alton Eric WFW , Griesenbach Uta , Shah Anand , Warris Adilia , Armstrong-James Darius 
Published: December 2024

AbstractAspergillus fumigatus(Af) is a major mould pathogen found ubiquitously in the air. It commonly infects the airways of people with cystic fibrosis (CF) leading toAspergillusbronchitis or allergic bronchopulmonary aspergillosis. Resident alveolar macrophages and recruited neutrophils are important first lines of defence for clearance ofAfin the lung. However, their contribution to the inflammatory phenotype in CF duringAfinfection is not well understood. Here, utilising CFTR deficient mice we describe a hyperinflammatory phenotype in both acute and allergic murine models of pulmonary aspergillosis. We show that during aspergillosis, CFTR deficiency leads to increased alveolar macrophage death and persistent inflammation of the airways in CF, accompanied by impaired fungal control. Utilising CFTR deficient murine cells and primary human CF cells we show that at a cellular level there is increased activation of NFκB and NFAT in response toAfwhich, as inin vivomodels, is associated with increased cell death and reduced fungal control. Taken together, these studies indicate that CFTR deficiency promotes increased activation of inflammatory pathways, the induction of macrophage cell death and reduced fungal control contributing to the hyper-inflammatory of pulmonary aspergillosis phenotypes in CF.Author SummaryThe airways of people with cystic fibrosis (pwCF) are commonly colonised withAspergillus fumigatus(Af) resulting in a persistent hyperinflammatory state and the development of allergy. Understanding how first line defence innate cells, such as alveolar macrophages and neutrophils, contribute to this hyperinflammatory phenotype is important in developing novel treatments to preserve lung function in pwCF. In this study, we report that CFTR deficiency leads to increased alveolar macrophage death and persistent inflammation of the airways in pwCF, which is associated with impaired control of infection. We identify the increased activation of the transcription factors NFκB and NFAT as the mechanism of increased inflammatory cytokine production in CFTR deficient cells. This work is the first step in describing molecular mechanisms of hyperinflammation in CF in response to fungal infection and lays the groundwork for further dissection of inflammatory pathways to target with immunotherapeutic approaches.
A powerful framework for differential co-expression analysis of general risk factors
Authors: Bass Andrew J. , Cutler David J. , Epstein Michael P. 
Published: December 2024

AbstractDifferential co-expression analysis (DCA) aims to identify genes in a pathway whose shared expression depends on a risk factor. While DCA provides insights into the biological activity of diseases, existing methods are limited to categorical risk factors and/or suffer from bias due to batch and variance-specific effects. We propose a new framework, Kernel-based Differential Co-expression Analysis (KDCA), that harnesses correlation patterns between genes in a pathway to detect differential co-expression arising from general (i.e., continuous, discrete, or categorical) risk factors. Using various simulated pathway architectures, we find that KDCA accounts for common sources of bias to control the type I error rate while substantially increasing the power compared to the standard eigengene approach. We then applied KDCA to The Cancer Genome Atlas thyroid data set and found several differentially co-expressed pathways by age of diagnosis andBRAFmutation status that were undetected by the eigengene method. Collectively, our results demonstrate that KDCA is a powerful testing framework that expands DCA applications in expression studies.
Selection strengthens the relationship between plant diversity and the metabolic profile ofPlantago lanceolata
Authors: Medina-van Berkum Pamela , De Giorgi Francesca , Rothe Beate , Durka Walter , Gershenzon Jonathan , Roscher Christiane , Unsicker Sybille B. 
Published: December 2024

SummaryPlants growing in biodiverse communities often increase productivity, but how plant diversity impacts the metabolome and the underlying ecological and evolutionary processes remains unclear. This study investigated how plant species diversity and selection for growing in different diversity environments affects the leaf metabolome ofPlantago lanceolata.We compared the metabolites of plants derived from those that had beenselectedin the “Jena Experiment” for 17 years in plant communities with differing plant diversity with the metabolites ofnaïveplants not subjected to this selection. The metabolic profiles ofselected P. lanceolataphytometers were also compared after growing in experimental environments varying in plant species richness, soil history, and community plant history.Results showed volatile compound diversity inP. lanceolatadecreased with plant species richness, primarily due to phenotypic plasticity rather than selection. Soil history further strengthened this relationship. Conversely, non-volatile compound diversity increased with plant species richness, but only in phytometers subjected diversity-driven selection. These effects were more pronounced when plants shared soil-plant history with their community.In summary, our study revealed that both plastic and adaptative responses shape the metabolome ofP. lanceolatain relation to plant diversity with these effects becoming stronger as plant and soil communities mature.
Integrated phenomenology and brain connectivity demonstrate changes in nonlinear processing in jhana advanced meditation
Authors: Potash Ruby M. , van Mil Sean D. , Estarellas Mar , Canales-Johnson Andres , Sacchet Matthew D. 
Published: December 2024

AbstractWe present a neurophenomenological case study investigating distinct neural connectivity regimes during an advanced concentrative absorption meditation called jhana (ACAM-J),characterized by highly-stable attention and mental absorption. Using EEG recordings and phenomenological ratings (29 sessions) from a meditator with +20,000 hours of practice, we evaluated connectivity metrics tracking distinct large-scale neural interactions: nonlinear (WSMI and Directed Information), capturing non-oscillatory dynamics; and linear (WPLI) connectivity metrics, capturing oscillatory synchrony. Results demonstrate ACAM-J are better distinguished by non-oscillatory compared to oscillatory dynamics across multiple frequency ranges. Furthermore, combining attention-related phenomenological ratings with WSMI improves Bayesian decoding of ACAM-J compared to neural metrics alone. Crucially, deeper ACAM-J indicate an equalization of feedback and feedforward processes, suggesting a balance of internallyand externally-driven information processing. Our results reveal distinct neural dynamics during ACAM-J, offering insights into refined conscious states and highlighting the value of nonlinear neurophenomenological approaches to studying attentional states.
Hyperactive neuronal networks facilitate tau spread in an Alzheimer’s disease mouse model
Authors: Barbour Aaron J. , Hoag Keegan , Cornblath Eli J. , Chavez Abigail , Lucas Alfredo , Li Xiaofan , Zebrowitz Sydney , Hassman Chloe , Lee Edward B. , Davis Kathryn A. , Lee Virginia M.Y. , Talos Delia M. , Jensen Frances E. 
Published: December 2024

AbstractPathological tau spreads throughout the brain along neuronal connections in Alzheimer’s disease (AD), but the mechanisms that underlie this process are poorly understood. Given the high incidence and deleterious consequences of epileptiform activity in AD, we hypothesized neuronal hyperactivity and seizures are key factors in tau spread. To examine these interactions, we created a novel mouse model involving the cross of targeted recombination in active populations (TRAP) mice and the 5 times familial AD (5XFAD; 5X-TRAP) model allowing for the permanent fluorescent labelling of neuronal activity. To establish a causal role of seizures in tau spread, we seeded mice with human AD brain-derived tau lysate and induced seizures with pentylenetetrazol (PTZ) kindling. Comprehensive brain mapping of tau pathology and neuronal activity revealed that basal hyperactivity in 5X-TRAP mice was associated with increased tau spread, which was exacerbated by seizure induction through activated networks and correlated with memory deficits. Computational modeling revealed that anterograde tau spread was elevated in 5X-TRAP mice and that regional neuronal activity was predictive of tau spread to that brain region. On a cellular level, we found that in both saline and PTZ-treated 5X-TRAP mice, hyperactive neurons disproportionately contributed to the spread of tau. Further, we found that Synaptogyrin-3, a synaptic vesicle protein that interacts with tau, was increased following PTZ kindling in 5X-TRAP mice, possibly indicative of a synaptic mechanism underlying seizure-exacerbated tau spread. Importantly, postmortem AD brain tissue from patients with a history of seizures showed increased tau pathology in patterns indicative of increased spread and increased Synaptogyrin-3 levels compared to those without seizures. Overall, our study identifies neuronal hyperactivity and seizures as key factors underlying the pathobiological and cognitive progression of AD. Therapies targeting these factors should be tested clinically to slow tau spread and AD progression.
The efficacy of resting-state fMRI denoising pipelines for motion correction and behavioural prediction
Authors: Pavlovich Kane , Pang James , Holmes Alexander , Constable Toby , Fornito Alex 
Published: December 2024

AbstractResting-state functional magnetic resonance imaging (rs-fMRI) is a pivotal tool for mapping the functional organization of the brain and its relation to individual differences in behaviour. One challenge for the field is that rs-fMRI signals are contaminated by multiple sources of noise that can contaminate these rs-fMRI signals, affecting the reliability and validity of any derivative phenotypes and attenuating their correlations with behaviour. Here, we investigate the efficacy of different noise mitigation pipelines, including white-matter and cerebrospinal fluid regression, independent component analysis (ICA) – based artefact removal, volume censoring, global signal regression (GSR), and diffuse cluster estimation and regression (DiCER), in simultaneously achieving two objectives: mitigating motion-related artifacts and augmenting brain-behaviour associations. Our analysis, which employed three distinct quality control metrics to evaluate motion influence and a kernel ridge regression for behavioural predictions of 81 different behavioural variables across two independent datasets, revealed that no single pipeline universally excels at achieving both objectives consistently across different cohorts. Pipelines combining ICA-FIX and GSR demonstrate a reasonable trade-off between motion reduction and behavioural prediction performance, but inter-pipeline variations in predictive performance are modest.
Humans use overconfident estimates of auditory spatial and temporal uncertainty for perceptual inference
Authors: Hong Fangfang , Xu Jiaming , Landy Michael S. , Badde Stephanie 
Published: December 2024

AbstractMaking decisions based on noisy sensory information is a crucial function of the brain. Various decisions take each sensory signal’s uncertainty into account. Here, we investigated whether perceptual inferences rely on accurate estimates of sensory uncertainty. Participants completed a set of auditory, visual, and audiovisual spatial as well as temporal tasks. We fitted Bayesian observer models of each task to every participant’s complete dataset. Crucially, in some model variants the uncertainty estimates employed for perceptual inferences were independent of the actual uncertainty associated with the sensory signals. Model comparisons and analysis of the best-fitting parameters revealed that, in unimodal and bimodal contexts, participants’ perceptual decisions relied on overconfident estimates of auditory spatial and audiovisual temporal uncertainty. These findings challenge the ubiquitous assumption that human behavior optimally accounts for sensory uncertainty regardless of sensory domain.
Ischemic Stroke Burden from Dietary Risks in China: 1990-2019 GBD Study
Authors: Duan Kui , Cheng Yongran , Wang Mingwei , Peng Shang , Zhang Min , Wang Jifeng , Ye Lan , Xu Zucai , Feng Zhanhui 
Published: December 2024

AbstractBackgroundIn China, economic growth and lifestyle shifts have made dietary risks a major public health issue for ischemic stroke. This study examines the link between six dietary risks and ischemic stroke in China from 1990 to 2019, using 2019 Global Burden of Disease (GBD) data.MethodsData from GBD 2019 was primarily derived from Chinese monitoring systems, and the KaiLuan study focused on trends in ischemic stroke mortality and disability-adjusted life years (DALYs) associated with six dietary risks. Age-period-cohort and join-point regression methods were utilized, accounting for age, period, and cohort effects.ResultsIn 2019, deaths and DALYs attributable to six dietary risks were 283,083 and 7,082,849, respectively, marking a significant increase of 124.7% and 108.4% since 1990. Despite overall declines in mortality and DALY rates from 1990 to 2019 (annual average percentage change (AAPC): −0.5% for DALYs and −0.6% for deaths), ischemic stroke rates due to diets high in red meat (AAPC: 1.4% for DALYs and 1.3% for deaths). For five dietary risks, local drift curves indicated increasing trends with age, except for low fiber intake. DALYs rates peaked at 85–89 years for all except sodium, which peaked at 75–79 years. Mortality rates slightly increased under 79 years, but rose noticeably over 79. Men had higher numbers and rates of dietary risk-related strokes, but they experienced smaller declines than women.ConclusionsThe study reveals an increasing ischemic stroke burden due to high red meat diets and decreasing trends due to low vegetable intakes. Dietary risks associated with high sodium, low fruit, vegetable, and whole grain intakes led to increased numbers but decreased rates of ischemic stroke outcomes.
Greater host influence and promiscuity: How an invasive seaweed host has advantages over co-occurring natives
Authors: Ghotbi Marjan , Bonthond Guido , Ghotbi Mitra , Künzel Sven , Needham David M , Weinberger Florian 
Published: December 2024

AbstractThe surface microbiome of seaweed hosts is a multi-domain biofilm regulated by host-microbe and microbe-microbe interactions. The extent to which hosts influence these interactions, and potentially affect their resilience and invasion success, remains unclear. We experimentally tested whether hosts with invasion history exert more influence over their biofilms than native hosts. Biofilm formation on proxy surfaces adjacent to one invasive (Gracilaria vermiculophylla) and two native (Fucus serratus, Fucus vesiculosus) co-occurring hosts was monitored and compared to mature epiphytic biofilms of the same hosts. OnlyGracilaria’sproxy biofilms were significantly different in community composition compared to control surfaces.Gracilaria’s proxy biofilms also showed the highest similarity to their adjacent algae sharing certain bacterial taxa that were absent in control treatments, indicating that colonization of the proxy surface was influenced by the host.Gracilariaand its proxy biofilm showed highest similarity in microbial network variables, suggesting a higher ability of the invader to influence connectivity and microbial associations within its biofilm. MeanwhileGracilaria’s mature biofilm also showed higher variability in its prokaryotic composition over experiments, which was also reflected in a less robust microbial network in bothGracilariaand its proxy biofilms. This suggests that in addition to stronger influence in the invasive host, it was also more promiscuous towards potential symbionts from the environment. Ultimately, through examining microbial interactions, in line with previous research we found that host influence and promiscuity may play an important role in seaweed hosts to acclimate to different environmental condition and successfully thrive in new ecosystems.
Overactivation of prefrontal astrocytes impairs cognition through the metabolic pathway of central kynurenines
Authors: Beilmann Viktor , Furrer Johanna , Schalbetter Sina M. , Weber-Stadlbauer Ulrike , Wyss Matthias T. , Saab Aiman S. , Weber Bruno , Meyer Urs , Notter Tina 
Published: December 2024

ABSTRACTAstrocyte dysfunctions have long been implicated in psychiatric and cognitive disorders, yet the precise mechanisms underlying this association remain elusive. Here, we show that chemogenetic activation of prefrontal astrocytes in mice impairs short-term memory and sensorimotor gating and attenuates the activation of parvalbumin (PV) interneurons in the prefrontal cortex. These alterations are accompanied by increases in prefrontal levels of kynurenic acid (KYNA), a key metabolite of the kynurenine (KYN) pathway, known to be produced by astrocytes, which serves as an endogenous antagonist of NMDA receptors. Pharmacological inhibition of kynurenine aminotransferase II, the key enzyme mediating the transamination of KYN to KYNA, reinstates the astrocyte-mediated impairments in short-term memory and sensorimotor gating, and normalizes the deficits in prefrontal PV interneuron activation. Our study identifies a mechanistic link between overactivation of prefrontal astrocytes, increased production of KYNA, and cognitive as well as cellular dysfunctions involved in major psychiatric disorders and beyond.