bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Effects of Early Adolescent Second-Generation Antipsychotic Exposure on Body Weight, Caloric Intake, and Metabolism-Associated Gene Expression
Authors: Soto Paul L. , Young Michael E. , Nguyen Serena , Federoff Megan , Goodson Mia , Morrison Christopher D. , Batdorf Heidi M. , Burke Susan J. , Collier J. Jason 
Published: October 2024

AbstractThe use of second-generation antipsychotic (SGA) medications in pediatric patients raises concerns about potential long-term adverse outcomes. The current study evaluated the long-term effects of treatment with risperidone or olanzapine on body weight, caloric intake, serum insulin, blood glucose, and metabolism-associated gene expression in C57Bl/6J female mice. Compared to mice treated with vehicle, female mice treated with risperidone or olanzapine gained weight at higher rates during treatment and maintained higher body weights for months following treatment cessation. During high-fat diet feeding, some groups of treated mice gained weight at higher rates than their respective control groups, but the finding was not consistent across experiments. Finally, female mice previously treated with olanzapine also exhibited increased expression of genes associated with inflammation and lipogenesis. These findings suggest that pediatric use of SGA medications that induce excess weight gain during treatment may exert persistent effects on body weight and gene expression and such outcomes may form an important aspect of assessing risk-to-benefit ratios in prescribing decisions.
Phytochemical Analysis and Nematicidal Activity of Medicinal Plants AgainstMeloidogyne javanica
Authors: Maher Saima , Naheed Nadra , Khan Noureen , Ishtiaq Hina , Solangi Ghulam Sarwar , karim Aasia , Imran Muhammad , Iqbal Erum , Mukhtar Farah , Bakhshi Mahganj , Mina Gul , Alarfaji Saleh S 
Published: October 2024

AbstractThis study examined the nematicidal potential of ethanol extracts derived from four plants, namelyActinidia deliciosa(Chev.),Carica papaya, Citrus paradise, andRaphanus sativus, against the root-knot nematodeMeloidogyne javanica. Experimental results indicated a significant reduction in the survival of second-stage juveniles ofM. javanicawhen exposed to these plant extracts. Notably, concentrations of 2% and 1% were found to be more effective in comparison to 0.5% and 0.25%, yielding statistically significant outcomes. Furthermore, the mortality rate of the nematodes exhibited a direct correlation with the duration of exposure for most plant extracts. The fruit extracts obtained fromA. deliciosa, C. papaya, C. paradise, andR. sativusdemonstrated a substantial decrease in nematode infestation compared to the control group. The nematicidal activity of KI3a (BuOH) significant from 0.1356 to 1.9076 over 72 hours, while P-KI-2a (EtOAc) showed rose from 0.1206 to 0.6456. In compare, GF-3 (EtOAc) and Carbofuran to 0.0179 and 0.0098, respectively. PA-1 (MeOH) and RS-3 (EtOAc) showed modest nematicidal potential. This research emphasizes the efficacy of plant extract in mitigating root-knot nematode infestation, offering a promising alternative to chemical managements. Additionally, comprehensive phytochemical analysis should be achieved to recognize the active chemical constituents responsible for their effects. Exploring synergistic effects between these compounds and other natural or synthetic agents could further improve their potential applications in sustainable agriculture, improving crop protection and promoting eco-friendly practices.
Complex motion trajectories are represented by a population code from the ensemble activity of multiple motion-sensitive descending interneurons in locusts
Authors: Zhang Sinan , Gray John R. 
Published: October 2024

AbstractAdaptive locust flight relies on rapid detection and processing of objects moving in the visual field. One identified neural pathway, comprised of the lobula giant movement detector (LGMD) and the descending contralateral movement detector (DCMD), responds preferentially to approaching objects. The LGMD receives retinotopic inputs from ipsilateral ommatidia and generates spikes in a 1:1 ratio in the DCMD, which synapses contralaterally with multiple locomotion-related neurons. Other motion-sensitive neurons have also been identified in locusts but are not as well characterized. To better understand how locusts process visual information, we used multichannel neural recordings within a stimulus arena and presented various complex visual stimuli to investigate the neural encoding of complex object motion. We found multiple discriminated units that responded uniquely to visual motion and categorized the responses. More units responded to motion trajectories with a looming component, compared to translations across the visual field. Dynamic factor analysis (DFA) of discriminated units revealed common trends that reflect the activity of neural ensembles. The numbers and types of common trends varied among motion trajectories. These results increase the understanding of complex visual motion processing in this tractable system.
Design and evaluation of an automated real-time SOFA score calculator in an electronic health record system, for early sepsis diagnosis
Authors: Smitt Einarson Gustaf , Nordqvist Hampus , Marking Ulrika , Jonmarker Sandra , Parke Åsa , Unge Christian , Yu David , Sundén-Cullberg Jonas , Strålin Kristoffer 
Published: October 2024

AbstractBackgroundIn patients with infections, the Sequential Organ Failure Assessment (SOFA) score should be used to diagnose sepsis. However, manual SOFA calculation is time consuming. Thus, we developed an automated real-time SOFA score application that has been fully implemented into the major electronic health record (EHR) system (TakeCare) in Stockholm. We aimed to describe the method and evaluate its performance for detection of sepsis.MethodWe developed an automated SOFA application that presents a total score (SOFATotal) over time and a baseline score (SOFAChronic) based on outpatient data prior to hospital admission. We evaluated its performance on 583 sepsis alert patients in an emergency department, including 472 with sepsis according to manually calculated SOFA (SOFAManual). SOFATotal at 30 minutes and 3 hours, and quick-SOFA (qSOFA) were compared with SOFAManual for detection of sepsis. The acute SOFA score (SOFAAcute) was calculated by subtracting SOFAChronic from SOFATotal.ResultsSOFATotal at 3 hours showed moderate-good agreement with SOFAManual (R² = 0.76). Areas under receiver operating characteristic curves for sepsis detection were 0.83 at 30 minutes, 0.94 at 3 hours for SOFATotal, and 0.67 for qSOFA. Among patients with SOFAChronic ≥1 (21% of cases), SOFATotal of ≥2 was observed in 90% of cases (mortality 13.5%), although SOFAAcute of ≥2 was noted in 63% (mortality 16.7%).ConclusionThe automated SOFA score demonstrated effectiveness in early sepsis detection, outperforming qSOFA, but adjustments for chronic baseline scores were necessary to avoid over-diagnosis. Further studies on broader patient populations would be useful to validate its clinical use.
Risk of cardiovascular disease in patients with classical Hodgkin lymphoma: a Danish nationwide register-based cohort study
Authors: Godtfredsen Sissel J. , Yonis Harman , Baech Joachim , Al-Hussainy Nour R. , Riddersholm Signe , Kober Lars , Schou Morten , Christensen Jacob Haaber , Hutchings Martin , Dahl-Sørensen Rasmus Bo , Kamper Peter , Dietrich Caroline E. , Andersen Mikkel Porsborg , Torp-Pedersen Christian , Sogaard Peter , El-Galaly Tarec Christoffer , Kragholm Kristian H. 
Published: October 2024

AbstractAimTo describe the risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment.MethodsIncluding all patients with cHL ≥18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000-2022. Patients were matched with comparators in a 1:5 ratio on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥1). A composite of CVDs including coronary artery disease, heart failure, valvular stenoses, restrictive pericarditis, arrythmias, or any procedures related to these was the primary outcome. Follow-up started on date of cHL diagnosis (i.e., the matching date). The cause-specific cumulative incidence and 95% confidence intervals (CIs) were computed with all-cause death and lymphoma relapse as competing events using the Aalen-Johansen estimator.ResultsA total of 1,905 patients with cHL and 9,525 comparators were included. Median age was 39 years (interquartile range, [IQR]: 27-56), 58% were males, most were treated with ABVD (83%), and the median cumulative doxorubicin dose was 250 mg/m2(IQR: 200-300). Median follow-up was 10 years (IQR: 5.9-17.4). The cumulative incidences of CVD were 4.7% (95% CI: 3.6-5.7) for patients vs. 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) vs. 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) vs. 8.2% (95% CI: 7.4-9.0) at 15 years.ConclusionsCVD remains a substantial late effect after contemporary treatment for cHL, suggesting that awareness of cardiac symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.
The neurodevelopmental spectrum ofCASK-related disorder
Authors: Martin Jessica , Mavrogalou-Foti Alkistis , Eck Josefine , Hattersley Laura , Baker Kate 
Published: October 2024

AbstractBackgroundPathogenicCASKvariants are associated with neurodevelopmental disorders of variable severity including X-linked intellectual disability (XLID) and microcephaly with pontocerebellar hypoplasia (MICPCH). Although the number of diagnosed cases is rising, current understanding of theCASK-related neurodevelopmental spectrum is limited. Here, we systematically review the published characteristics of individuals withCASK-related disorder, and compare these to a more recently-diagnosed group. We provide quantitative information about the ranges of adaptive abilities, motor function, visual function and social-emotional-behavioural characteristics, and explore within-group associations.Methods151 individuals withCASKvariants were identified in published literature. 31 children and young people withCASKvariants were recruited to the UK-based Brain and Behaviour in Neurodevelopmental disorder of Genetic Origin (BINGO) project. BINGO-participating caregivers completed a bespoke medical history questionnaire and battery of standardised neurodevelopmental measures.ResultsComparing the recently diagnosed BINGOCASK-related disorder group to previously reported individuals, we found consistent prevalence of tone abnormalities, sensorineural hearing loss and epilepsy, but lower prevalence of severe/profound ID, MICPCH, optic atrophy and nystagmus. Areas of frequent difficulty not highlighted in previous reports include sleep difficulties and cerebral visual impairment (CVI). Neurodevelopmental characteristics were highly variable within the BINGOCASK-related disorder group, and group-wide patterns were similar to those observed in other rare genetic conditions. Within the BINGOCASK-related group, epilepsy is significantly associated with ID severity, after controlling for age. Sub-groups with MICPCH or microcephaly only have equivalent ranges of adaptive function, but MICPCH may be associated with more severe motor difficulties.ConclusionThe spectrum of neurodevelopmental characteristics associated withCASK-related disorder appears to be broadening with increased access to genome-wide diagnostic testing. Further studies are needed to elucidate the relationships betweenCASKvariants, structural brain development, epilepsy, and neurodevelopmental characteristics.
Nucleoporin Nup153 docks the splicing machinery to the nuclear pore for efficient mRNA processing
Authors: de Castro IJ , Schuster L , Patiño-Gomez C , Glavas D , Udupa A , Ríos Vázquez M , Symens T , Tulcan G , Heinze J , de las Heras J , Reinhardt Robert , Trojanowski Jorge , Harz H , Stumberger G , Leonhardt H , Schirmer E , Saka S , Laketa V , Lusic M 
Published: October 2024

SummaryThe nuclear pore complex (NPC), composed of proteins termed nucleoporins (Nups), intercalates the nuclear envelope, and is primarily involved in protein trafficking and mRNA export. At the nuclear basket, Nups have been associated with chromatin organization and postulated to function as transcriptional hubs, working in tandem with mRNA export machinery. However, little is known about the intermediate process of RNA splicing at the NPC. Here, we used BioID to screen for interactors of basket-Nups Nup153 and TPR and discovered the enrichment of splicing proteins across all spliceosome complexes (E, A, B, B*, P). The peripheral nature of the interaction between Nup153 and selected splicing components was confirmed byin-situproximity ligation assay and STED microscopy. The presence of splicing components at the NPC, reduced upon splicing inhibition, is partly dependent on Nup153 and functionally correlated to the splicing of Nup153-bound genes. Assessed by DamID, Nup153-bound genes (∼500) are characterized by multiple long introns with lower-than-average GC content. Positioned at the periphery but distinct from the neighbouring lamina-associated domain (LADs) in chromatin signatures and expression levels, these genes showed Nup153-dependent splicing defect, suggesting that splicing occurs at the NPC.Altogether, our data substantiates the gene gating theory bringing transcription and export, now accompanied by speckle-distant splicing events, at the level of the NPC.
Independent evolution of atypical sperm morphology in a passerine bird, the red-browed finch (Neochmia temporalis temporalis)
Authors: Rowe Melissah , Hooper Daniel M. , Hofgaard Antje , Hurley Laura L. , McDiarmid Callum S. , Pataraia Ioanna , Lifjeld Jan T. , Griffith Simon C. 
Published: October 2024

AbstractSpermatozoa exhibit striking morphological variation across the animal kingdom. In passerine birds, sperm exhibit considerable variation in size, yet the basic sperm phenotype is highly conserved; sperm are filiform, the head is corkscrew-shaped, and the midpiece is elongated and twisted around the flagellum. A significant departure from this typical sperm morphology has been reported in the sister species, the Eurasian bullfinch (Pyrrhula pyrrhula) and Azores bullfinch (P. murina). Here, we report a second evolutionary shift in passerine sperm phenotype in the nominate subspecies of the red-browed finch (Neochmia temporalis temporalis); sperm are non-filiform, with an ellipsoid head, and an extremely short midpiece restricted to the nuclear-axoneme junction. Additionally, we show that the sperm phenotype of the red-browed finch is similar to the putatively neotenous sperm described in the two bullfinch species. Using whole-genome data, we found no evidence that the unusual sperm phenotype of the red-browed finch is associated with reduced genetic variation or a population bottleneck. In contrast, we find some support for the hypothesis that relaxed post-copulatory sexual selection may, at least in part, explain the unusual sperm of the red-browed finch. We also discuss the possible roles of mutation, genetic drift, and genetic hitchhiking, in the evolutionary origins and maintenance of neotenous sperm phenotypes. Finally, we suggest that these dramatic evolutionary shifts in sperm phenotype warrant further investigation and highlight the need for a greater understanding of the developmental and genomic basis of sperm phenotype.
Natural variations of aging of cardiac performance in Drosophila identifies a central function for the PAR domain bZIP transcription factorPdp1/dHLFin cardiac senescence
Authors: Audouin Katell , Saha Saswati , Röder Laurence , Krifa Sallouha , Arquier Nathalie , Perrin Laurent 
Published: October 2024

SummaryThe identification of genetic factors influencing cardiac senescence in natural populations is central to our understanding of cardiac aging and to identify the etiology of associated cardiac disorders in human populations. However, the genetic underpinning of complex traits in human is almost impossible, due to the infeasibility to control genetic background and gene-environment interactions.Drosophilahas striking similarities in cardiac aging with humans, highlighting the conserved nature of cardiac aging for organisms with a heart. Leveraging on a large collection of inbred lines from the Drosophila Genetic Reference Panel (DGRP), we provide an accurate analysis of cardiac senescence in a natural population of flies. This permitted the discovery of an unprecedented number of variants and associated genes significantly associated to the natural variation of cardiac aging. We focused on the function of the PAR domain bZIP transcription factor Pdp1 for which several variants were found associated with natural variation of the aging of multiple cardiac functional traits. We demonstrated thatPdp1cell autonomously plays a central role in cardiac senescence and might do so by regulating mitochondria homeostasis. Overall, our work provides a unique resource regarding the genetics of cardiac aging in a natural population.
SC-MAMBA2: Leveraging State-Space Models for Efficient Single-Cell Ultra-Long Transcriptome Modeling
Authors: Zhao Yalong , Zhao Bowen , Zhang Fan , He Chenfeng , Wu Wendao , Lai Lipeng 
Published: October 2024

AbstractThe rapid advancement of single-cell sequencing technology has significantly deepened our understanding of cellular heterogeneity, yet it concurrently presents substantial challenges for the unified modeling of single-cell data. Simultaneously, pre-trained foundation models have achieved notable success in domains such as natural language processing and image analysis. However, extending these models to accommodate ultra-long single-cell transcriptome sequences, characterized by an extensive number of genes, remains a formidable task. In this study, we introduce SC-MAMBA2, based on the MAMBA2 architecture, meticulously designed with a bidirectional modeling approach tailored for single-cell transcriptomics data. As the first single-cell foundation model to integrate state-space models (SSMs) underlying MAMBA2 architecture, SC-MAMBA2 features over 625 million parameters, covers more than 60,000 genes, and was pre-trained on a dataset of over 57 million cells, making it the most comprehensive solution for processing ultra-long transcriptome sequences. Extensive bench-marking across a diverse array of downstream tasks consistently demonstrates that SC-MAMBA2 surpasses state-of-the-art models, delivering superior accuracy and enhanced computational efficiency.
FIGL1 limits the formation of meiotic non crossover events inArabidopsis thaliana
Authors: Charif Delphine , Mercier Raphaël , Tran Joseph , Mézard Christine 
Published: October 2024

AbstractMeiotic recombination produces both crossover and non crossover events that are essential in the history of population genetics and evolution of species. In Arabidopsis thaliana, several pathways control the rate and distribution of crossovers. Here, by sequencing the four products of a series of tetrads, we confirm the antiCO role ofRECQ4A, RECQ4B, FIGL1andFANCM. Moreover, when one of this gene is mutated, complex chimeric gene conversion events associated to crossover are observed suggesting a role of these proteins in limiting the multiple strand invasions. Nothing was known about the factors that could limit or increase NCOs. Here, we show thatFIGL1plays a major role in controlling the NCO number.
The first complete 3D reconstruction and morphofunctional mapping of an insect eye
Authors: Makarova Anastasia A. , Chua Nicholas J. , Diakova Anna V. , Desyatirkina Inna A. , Gunn Pat , Pang Song , Xu C. Shan , Hess Harald , Chklovskii Dmitri B. , Polilov Alexey A. 
Published: October 2024

AbstractThe structure of compound eyes in arthropods has been the subject of many studies, revealing important biological principles. Until recently, these studies were constrained by the two-dimensional nature of available ultrastructural data. By taking advantage of the novel three-dimensional ultrastructural dataset obtained using volume electron microscopy (vEM), we present the first cellular-level reconstruction of the whole compound eye of an insect, the miniaturized parasitoid waspMegaphragma viggianii. The compound eye of the femaleM. viggianiiconsists of 29 ommatidia and contains 478 cells. Despite the almost anucleate brain, all cells of the compound eye contain nuclei. As in larger insects, the dorsal rim area (DRA) of the eye inM. viggianiicontains ommatidia that are believed to be specialized in polarized light detection as reflected in their corneal and retinal morphology. We report the presence of three ‘ectopic’ photoreceptors. Our results offer new insights into the miniaturization of compound eyes and scaling of sensory organs in general.
Hierarchy of prediction errors shapes the learning of context-dependent sensory representations
Authors: Tsai Matthias C. , Teutsch Jasper , Wybo Willem A.M. , Helmchen Fritjof , Banerjee Abhishek , Senn Walter 
Published: October 2024

AbstractHow sensory information is interpreted depends on context. Yet, how context shapes sensory processing in the brain, remains elusive. To investigate this question we combined computational modeling andin vivofunctional imaging of cortical neurons in mice during reversal learning of a tactile sensory discrimination task. During learning, layer 2/3 somatosensory neurons enhanced their response to reward-predictive stimuli, explainable as gain amplification from apical dendrites. Reward-prediction errors were reduced and confidence in the outcome prediction increased. Upon rule-reversal, the lateral orbitofrontal cortex, through disinhibitory VIP interneurons, encoded a context-prediction error signaling a loss of confidence. The hierarchy of prediction errors in cortical areas is mirrored in top-down signals modulating apical activity in the primary sensory cortex. Our model explains how contextual changes are detected in the brain and how errors in different cortical regions interact to reshape and update the sensory representation.
A MOUSE ORGANOID PLATFORM FOR MODELING CEREBRAL CORTEX DEVELOPMENT AND CIS-REGULATORY EVOLUTION IN VITRO
Authors: Medina-Cano Daniel , Islam Mohammed T. , Petrova Veronika , Dixit Sanjana , Balic Zerina , Yang Marty G. , Stadtfeld Matthias , Wong Emily S. , Vierbuchen Thomas 
Published: October 2024

SUMMARYNatural selection has shaped the gene regulatory networks that orchestrate the development of the neocortex, leading to diverse neocortical structure and function across mammals, but the molecular and cellular mechanisms driving phenotypic changes have proven difficult to characterize. Here, we develop a reproducible protocol to generate neocortical organoids from mouse epiblast stem cells (EpiSCs) that gives rise to diverse cortical cell types, including distinct classes of excitatory neurons (pre-plate, deep-layer, and upper-layer) and glia (oligodendrocyte precursor cells, myelinating oligodendrocytes, astrocytes, ependymal cells). Cortical organoids develop with similar kinetics to the mouse cortex in vivo and begin to exhibit features of maturation in glia and neuronal cell types relatively rapidly compared to human brain organoids. Using this new protocol, we generated cortical organoids from F1 hybrid EpiSCs derived from crosses between standard laboratory mice (C57BL/6J) and four wild-derived mouse strains from distinct sub-species spanning ∼1M years of evolutionary divergence. This allowed us to comprehensively map cis-acting transcriptional regulatory variation across developing cortical cell types using scRNA-seq. We identify hundreds of genes that exhibit dynamic allelic imbalances during cortical neurogenesis, providing the first insight into the developmental mechanisms underpinning changes in cortical structure and function between mouse strains. These experimental methods and cellular resources represent a powerful new platform for investigating mechanisms of gene regulation in the developing cerebral cortex.