bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Suicidal Behavior in Youth and the Impact of SARS-CoV-2 Infection: A Retrospective Case-Control Study
Authors: Heslin Kathleen P. , Montero Michelle , Faraone Stephen V. , Zhang-James Yanli 
Published: December 2024

ABSTRACTBackgroundSuicide and self-harm remain critical concerns in youth. This study compares patients with and without suicidality or self-harm (SOSH), suicidality (SI/SA), and COVID-19 to investigate 53 pre-existing risk factors associated with suicidality in patients with and without COVID-19.MethodsA retrospective case-control study was conducted using TriNetX data from 111,631,250 patients across 78 healthcare networks. This study included patients aged 0-21 with any healthcare visit between January 20, 2020, and May 11, 2023.OutcomesComparison groups shared many risk factors, with specific differences. Children with SOSH and COVID-19 had higher odds of support group problems, personality disorder, thyroid disorders, and insomnia; children with SOSH without COVID-19 had higher odds of upbringing problems, anxiety and nonpsychotic disorders, sleep disorders, and autism. Adolescents with SOSH and COVID-19 had higher odds of parent-child conflict; adolescents with SOSH without COVID-19 had higher odds of education and literacy problems. Children with SI/SA and COVID-19 had higher odds of support group problems, personality disorders, and asthma; children with SI/SA without COVID-19 had higher odds of autism. Adolescents with SI/SA and COVID-19 had higher odds of asthma. The effect size of COVID-19 was not significant. SOSH was associated with increased odds of prior SARS-CoV-2 infection in children (OR 2.42) and adolescents (OR 1.88).InterpretationThis study confirms known SOSH risk factors and demonstrates their association with suicidality. We observed a significant association between SOSH and preceding SARS-CoV-2 infection. This underscores the need to focus on suicide risk in youth affected by COVID-19.
Complexity of Coronary Disease and a Genetic Risk Profile in Patients with Type 2 Diabetes in Colombia
Authors: Giraldo-Gonzalez German Camilo , Fuentes Jheyson Jair , Sepúlveda-Arias Juan Carlos , Castaño Carlos Eduardo 
Published: December 2024

AbstractBackgroundCoronary artery disease (CAD) remains a leading cause of mortality in patients with type 2 diabetes (T2DM). Both conditions share genetic and environmental etiologies, making T2DM a unique risk factor for CAD. Despite advancements, no highly accurate genetic or clinical prediction models exist to identify patients at high risk for complex coronary disease.MethodsA cross-sectional genetic epidemiology study was conducted at a cardiovascular center in Manizales, Colombia, involving 106 T2DM patients with documented coronary heart disease (CHD). Genetic analysis focused on 11 single nucleotide polymorphisms (SNPs) using polymerase chain reaction (PCR) and TaqMan assays. Clinical and genetic data were analyzed to assess associations with CAD complexity, defined as monovascular (one vessel) or polyvascular (≥2 vessels) involvement. Statistical methods included bivariate analyses, binary logistic regression, and Bonferroni correction for significance.ResultsAmong participants (mean age 68.1 ± 8.3 years; 53.7% male), 33 had monovascular disease, and 73 had polyvascular disease. Male sex (p = 0.016) and a significant genetic profile (PRP-5: rs1412830-CDKN2A/B, rs2074192-ACE2, rs4420638-APOE, rs646776-CELSR2, rs7903146-TCF7L2) were associated with polyvascular disease. PRP-5 demonstrated an odds ratio (OR) of 5.2 (p = 0.007) for complex CAD. Other metabolic and clinical parameters showed no significant differences between genetic risk groups.ConclusionsThis study identifies a polygenic risk profile (PRP-5) associated with complex CAD in T2DM patients, independent of traditional clinical factors. These findings support the hypothesis of genetic contributions to CAD severity and suggest the need for longitudinal studies to evaluate this risk profile’s clinical utility. As the first cohort-based genetic study in Hispanoamerica, it highlights the high prevalence of relevant alleles in this population and provides a foundation for future research into personalized cardiovascular risk stratification.Subject Áreasgenetics, cardiometabolic disease, Type 2 diabetes, coronary disease, cardiovascular diseases, polymorphism, single nucleotide.
Dynamic Regulation OF The Chromatin Environment By Ash1L Modulates Human Neuronal Structure And Function
Authors: Jhanji Megha , Ward Joseph A. , Leung Calvin S. , Krall Colleen L. , Ritchie Foster D. , Guevara Alexis , Vestergaard Kai , Yoon Brian , Amin Krishna , Berto Stefano , Liu Judy , Lizarraga Sofia B. 
Published: December 2024

ABSTRACTPrecise regulation of the chromatin environment through post-translational histone modification modulates transcription and controls brain development. Not surprisingly, mutations in a large number of histone-modifying enzymes underlie complex brain disorders. In particular, the histone methyltransferase ASH1L modifies histone marks linked to transcriptional activation and has been implicated in multiple neuropsychiatric disorders. However, the mechanisms underlying the pathobiology of ASH1L-asociated disease remain underexplored. We generated human isogenic stem cells with a mutation in ASH1L’s catalytic domain. We find that ASH1L dysfunction results in reduced neurite outgrowth, which correlates with alterations in the chromatin profile of activating and repressive histone marks, as well as the dysregulation of gene programs important for neuronal structure and function implicated in neuropsychiatric disease. We also identified a novel regulatory node implicating both the SP andKrüppel-like families of transcription factors and ASH1L relevant to human neuronal development. Finally, we rescue cellular defects linked to ASH1L dysfunction by leveraging two independent epigenetic mechanisms that promote transcriptional activation. In summary, we identified an ASH1L-driven epigenetic and transcriptional axis essential for human brain development and complex brain disorders that provide insights into future therapeutic strategies for ASH1L-related disorders.
Identification of Inhibitors ofChikungunyavirus nsP2 ATPase
Authors: Navarro Hernan , Scott John E. , Smith Ginger R. , Ghiabi Pegah , Gibson Elisa , Loppnau Peter , Harding Rachel J. , Hossain Mohammad Anwar , Bose Muthu Ramalingam , Pearce Kenneth H. , Merten Eric M. , Willson Timothy M. , Brown Peter J. 
Published: December 2024

AbstractNon-structural protein 2 (nsP2), which plays an essential role in replication of CHIKV, contains a protease, helicase, and methyltransferase-like domain. We executed a simple a screen using malachite green to detect compounds that decreased ATP hydrolysis and tested a library of diverse compounds to find inhibitors of CHIKV nsP2 helicase.
Mapping the canine microbiome: Insights from the Dog Aging Project
Authors: Bamberger Tal , Muller Efrat , Algavi Yadid M. , Greenier Ashlee , Adjangba Christine , Slikas Elizabeth , Brassington Layla , Mariner Blaise , McCoy Brianah , Harrison Benjamin R. , Partida-Aguilar Maria , Marye Abbey , Harris Adam , Rout Emily ,   DAP Consortium, Avery Anne , Promislow Daniel E.L. , Snyder-Mackler Noah , Borenstein Elhanan 
Published: December 2024

AbstractCompanion dogs (Canis lupus familiaris) offer a unique model for studying the gut microbiome and its relation to aging due to their cohabitation with humans, sharing similar environments, diets, and healthcare practices. Here, we present the Dog Aging Project (DAP) Precision cohort, the largest population-wide study of the canine gut microbiome to date. This cohort encompasses over 900 dogs of diverse breeds, environments, and demographics living across the United States. Coupling fecal shotgun metagenomic sequencing with comprehensive phenotypic and environmental surveys and clinical lab tests, we explore the intricate relationships between microbiome composition, aging, and key factors such as diet, health, and living conditions. Our analyses identify various factors associated with microbiome composition. In addition, we find a gradual shift in microbiome composition with age, which allows us to develop a novel metagenomics-based “clock” to predict biological aging based on microbial signatures. Overall, these findings provide an unprecedented and detailed understanding of the role the microbiome plays in our four-legged companions, offering both potential applications in veterinary medicine and an exciting model for aging research.
Female budgerigars prefer males with foraging skills that differ from their own
Authors: Zou Yuqi , Song Zitan , Chen Jiani , Sun Yuehua , Griesser Michael 
Published: December 2024

AbstractForaging skills influence food intake and may therefore also play a role in mate choice decision. Previous empirical work has shown that individuals benefit from being in groups that include individuals with a variety of foraging skills as this increases foraging success. This idea, formalized in the skill-pool hypothesis, may extend to mate choice. Diverse foraging skills can expand the foraging niche of a pair and benefit offspring through enhanced parental provisioning, and exposure to a broader foraging skillset. To test this idea, we trained captive female and male budgerigars to solve one of two different novel foraging puzzle boxes. Then, females simultaneously observed two males that could solve either the same or the other box, and assessed female preferences in a binary mate choice apparatus. Females preferred males with foraging skills that differed from their own, independent of the skill type and the number of times males solved the foraging puzzle. These findings show that foraging skills can influence social preferences, including in a mate choice context, and support intraspecific diversity in foraging skills.
Control of mitochondrial dynamics by dPGC1 limits Yorkie-induced oncogenic growth inDrosophila
Authors: Sew Wei Qi Guinevere , Li Zhiquan , Rasmussen Lene Juel , Herranz Héctor 
Published: December 2024

AbstractMitochondrial function and dynamics are crucial for maintaining cellular homeostasis and overall health. Disruptions in these processes can lead to various diseases, including cancer. The Hippo signaling pathway, a universal growth regulator, plays central roles in cancer through its main effector, the Yes-associated protein (YAP), known as Yorkie (Yki) inDrosophila. Yki upregulation drives benign tissue overgrowth inDrosophilaimaginal discs. Our research demonstrates that the conserved metabolic regulator dPGC1 limits Yki-driven tissue hyperplasia and maintains tissue homeostasis in vivo. Yki upregulation and dPGC1 depletion lead to tumors characterized by enlarged and hyperfused mitochondria, a condition both necessary and sufficient for Yki-driven oncogenic growth. Our findings demonstrate that mitochondrial hyperfusion elevates the levels of the cell cycle regulator Cyclin E, which is crucial for tumor development. Our findings identify dPGC1 as a context-dependent tumor suppressor that coordinates mitochondrial dynamics and cell cycle regulation in response to oncogene activation. Defects in these processes are commonly found in cancer cells, highlighting major implications for cancer development in humans.
Characterizing vascular function in mouse models of Alzheimer’s disease, atherosclerosis, and mixed Alzheimer’s and atherosclerosis
Authors: Eyre Beth , Shaw Kira , Drew Dave , Rayson Alexandra , Shabir Osman , Lee Llywelyn , Francis Sheila , Berwick Jason , Howarth Clare 
Published: December 2024

AbstractSignificanceAlzheimer’s disease does not occur in isolation and there are many comorbidities associated with the disease – especially diseases of the vasculature. Atherosclerosis is a known risk factor for the subsequent development of Alzheimer’s disease, therefore understanding how both diseases interact will provide a greater understanding of co-morbid disease progression and aid the development of potential new treatments.AimThe current study characterizes hemodynamic responses and cognitive performance in APP/PS1 Alzheimer’s mice, atherosclerosis mice, and a mixed disease group (APP/PS1 & atherosclerosis) between the ages of 9 and 12 months.ApproachWhisker-evoked hemodynamic responses and recognition memory were assessed in awake mice, immunohistochemistry to assess amyloid pathology, and histology to characterize atherosclerotic plaque load.ResultsWe observed hemodynamic deficits in atherosclerosis mice (vs Alzheimer’s, mixed disease or wild-type mice), with reduced short-duration stimulus-evoked hemodynamic responses occurring when there was no concurrent locomotion during the stimulation period. Mixed Alzheimer’s and atherosclerosis models did not show differences in amyloid beta coverage in the cortex or hippocampus or atherosclerotic plaque burden in the aortic arch vs relevant Alzheimer’s or atherosclerosis controls. Consistent with the subtle vascular deficits and no pathology differences, we also observed no difference in performance on the novel object recognition task across groups.ConclusionsThese results emphasize the importance of experimental design for characterizing vascular function across disease groups, as locomotion and stimulus duration impacted the ability to detect differences between groups. Whilst atherosclerosis did reduce hemodynamic responses, these were recovered in the presence of co-occurring Alzheimer’s disease which may provide targets for future studies to explore the potentially contrasting vasodilatory mechanisms these diseases impact.
The marine wormCapitella teletais sensitive to neurochemical manipulation, as revealed via a novel high-throughput behavioural tool
Authors: Hendershot Maxwell , Thompson William Andrew , Ramos Andrea Murillo , Bradshaw Olivia , Wilson Joanna Y. 
Published: December 2024

AbstractAnthropogenic impacts have led to increases in contaminants in marine habitats. The presence of compounds such as pharmaceuticals, personal care products, and pesticides is a concern, as these compounds have been shown to act as neurochemicals in aquatic organisms. However, screens of the multitude of chemicals found environmentally have yet to be carried out.Capitella teletaare marine annelid polychaete worms that live in the sediment of estuarian environments, acting as ecosystem engineers for marine habitats. This study aimed to develop a behaviour tool to identify neurochemical pathways involved in controlling locomotion that could be applied to screen the impacts of toxicants in the environment using this key invertebrate species at multiple life stages. Adult and juvenile life stages (2 weeks post-emergence) ofCapitella teletawere observed in Petri dishes (adults only) or 6-well plates (adults and juveniles), and conserved behavioural responses were isolated, such as their velocity, distance travelled, the time to reach the edge of the arena, and time spent at the periphery. We exposed juvenile and adult worms to nicotine (acetylcholine agonist) as a proof of concept. We noted similar disruptions to locomotion at both life stages, with low doses of nicotine stimulating movement and higher doses reducing locomotion. From here, we exposed juvenile worms to fluoxetine (serotonin reuptake inhibitor), phenobarbital (GABA agonist), and apomorphine (dopamine agonist). The behaviour of juvenile worms can be altered by exposure to fluoxetine, phenobarbital, and apomorphine. Fluoxetine and phenobarbital exposure reduces movement at high doses, but fluoxetine influences the amount of time at the periphery of the arena. Apomorphine produced modest changes in locomotion compared to other chemicals tested. Genome searching, as well as transcriptomics, were used to confirm the presence of neurochemical pathways inCapitella teleta. Our results demonstrate thatCapitella teletais a viable model for behavioural work, that several neurochemical pathways contribute to locomotory behaviour, and that this assay may be useful as a screen for contaminants found in marine habitats.
Single cell migration along and against confined haptotactic gradients
Authors: Fortunato Isabela Corina , Brückner David B. , Grosser Steffen , Rossetti Leone , Bosch-Padrós Miquel , Trebicka Jonel , Roca-Cusachs Pere , Sunyer Raimon , Hannezo Edouard , Trepat Xavier 
Published: December 2024

AbstractDirected cell migration along gradients of extracellular matrix (ECM) density –a process called haptotaxis– plays a central role in morphogenesis, the immune response, and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the regions of highest ligand density. In contrast with this view, here we show that cells exposed to micropatterned fibronectin gradients exhibit a complex repertoire of trajectories, including directed haptotactic migration up the gradient but also linear oscillations and circles with extended periods of migration down the gradient. To explain this behavior, we developed a biophysical model of haptotactic cell migration based on a coarse-grained molecular clutch model coupled to persistent stochastic polarity dynamics. While initial haptotactic migration is explained by the differential friction at the front and back of the cell, the observed complex trajectories over longer time scales arise from the interplay between differential friction, persistence, and physical confinement. Overall, our study reveals that confinement and persistence modulate the ability of cells to sense and respond to haptotactic cues and provides a framework to understand how cells navigate complex environments.
KIF3C Regulates Bergmann Glia Density and Patterning during Cerebellar Development
Authors: Waas Bridget , Allen Benjamin L. 
Published: December 2024

AbstractKinesin-2 motors have been demonstrated to regulate Hedgehog (HH) signaling, particularly within the developing cerebellum (Spassky et al., 2008; Waas et al., 2024). KIF3A/KIF3B are required for ciliogenesis in mice, and loss of this motor complex results in cerebellar hypoplasia due to lack of mitogenic response of HH-responsive cerebellar granule neural progenitors (CGNPs). Homodimeric KIF17 regulates HH-dependent CGNP proliferation through regulating levels of SHH and GLI3 but is not required for ciliogenesis in the developing cerebellum. Germline deletion ofKif3chas previously been reported to have no effect on embryonic development or gross cerebellar morphology in adult mice (Yang et al., 2001). Examination of these mice during neonatal development reveal cerebellar hypoplasia due to reduced CGNP proliferation inKif3cmutant mice. While decreased CGNP proliferation is often associated with reduced Hedgehog (HH) signaling, we did not detect a change in the levels of HH signaling inKif3c-/-cerebella. However, we observed Bergmann glia density and localization is altered inKif3cmutants, a phenotype consistent with disrupted Notch signaling. Further, we detected reduced expression ofHes1inKif3c-/-cerebella. Altogether, these data demonstrate KIF3C is required for proper cerebellar development but in a HH-independent manner.HighlightsKif3cis widely expressed in developing cerebellumKIF3C regulates cerebellar size, but in a HH-independent mannerKif3c-/-mice have increased BG density and abnormal spatial patterning
Voluntary locomotion induces an early and remote hemodynamic decrease in the large cerebral veins
Authors: Eyre Beth , Shaw Kira , Francis Sheila , Howarth Clare , Berwick Jason 
Published: December 2024

AbstractSignificanceBehavior regulates dural and cerebral vessels, with spontaneous locomotion inducing dural vessel constriction and increasing stimulus-evoked cerebral hemodynamic responses. It is vital to investigate the function of different vascular network components, surrounding and within the brain, to better understand the role of the neurovascular unit in health and neurodegeneration.AimWe characterized locomotion-induced hemodynamic responses across vascular compartments of the whisker barrel cortex: artery, vein, parenchyma, draining and meningeal vein.ApproachUsing 2D-OIS, hemodynamic responses during locomotion were recorded in 9–12-month-old awake mice: wild-type, Alzheimer’s disease (AD), atherosclerosis or mixed (atherosclerosis/AD) models. Within somatosensory cortex, responses were taken from pial vessels inside the whisker barrel region ([WBR]: “whisker artery” and “whisker vein”), a large vein from the sagittal sinus adjacent to the WBR (draining vein), and meningeal vessels from the dura mater (which do not penetrate cortical tissue).ResultsWe demonstrate that locomotion evokes an initial decrease in total hemoglobin (HbT) within the draining vein before the increase in HbT within WBR vessels. The locomotion event size influences the magnitude of the HbT increase in the pial vessels of the WBR, but not of the early HbT decrease within the draining veins. Following locomotion onset, an early HbT decrease was also observed in the overlying meningeal vessels, which unlike within the cortex did not go on to exceed baseline HbT levels during the remainder of the locomotion response. We show that locomotion-induced hemodynamic responses are altered in disease in the draining vein and whisker artery, suggesting this could be an important neurodegeneration biomarker.ConclusionThis initial reduction in HbT within the draining and meningeal veins potentially serves as a ‘space saving’ mechanism, allowing for large increases in cortical HbT associated with locomotion. Given this mechanism is impacted by disease it may provide an important target for vascular-based therapeutic interventions.
Modest functional diversity decline and pronounced composition shifts of microbial communities in a uranium-contaminated aquifer
Authors: Fan Yupeng , Wang Dongyu , Yang Joy X. , Ning Daliang , He Zhili , Zhang Ping , Rocha Andrea M. , Xiao Naijia , Michael Jonathan P. , Walker Katie F. , Joyner Dominique C. , Pan Chongle , Adams Michael W. W. , Fields Matthew W. , Alm Eric J. , Stahl David A. , Hazen Terry C. , Adams Paul D. , Arkin Adam P. , Zhou Jizhong 
Published: December 2024

ABSTRACTBackgroundMicrobial taxonomic diversity declines with increased environmental stress. Yet, few studies have explored whether phylogenetic and functional diversities track taxonomic diversity along the stress gradient. Here, we investigated bacterial communities within an aquifer in Oak Ridge, Tennessee, USA, which is characterized by a broad spectrum of stressors, including extremely high levels of nitrate, heavy metals like cadmium and chromium, radionuclides such as uranium, and extremely low pH (<3).ResultsBoth taxonomic and phylogenetic α-diversities were reduced in the most impacted wells, while the decline in functional α-diversity was modest and statistically insignificant, indicating a more robust buffering capacity to environmental stress. Differences in functional gene composition (i.e., functional β-diversity) were pronounced in highly contaminated wells, while convergent functional gene composition was observed in uncontaminated wells. The relative abundances of most carbon degradation genes were decreased in contaminated wells, but genes associated with denitrification, adenylylsulfate reduction, and sulfite reduction were increased. Compared to taxonomic and phylogenetic compositions, environmental variables played a more significant role in shaping functional gene composition, suggesting that niche selection could be more closely related to microbial functionality than taxonomy.ConclusionsOverall, we demonstrated that despite a reduced taxonomic α-diversity, microbial communities under stress maintained functionality underpinned by environmental selection.