bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the relationship betweenGBA1host genotype and gut microbiome in theGBA1L444P/WTmouse model: Implications for Parkinson disease pathogenesis
Authors: Menozzi Elisa , Geiger Mallia , Meslier Victoria , Fierli Federico , Gilles Marine , Chau Kai-Yin , David Aymeric , Golan Revi Shahar , Famechon Alexandre , Koletsi Sofia , Morabito Christian , Quinquis Benoit , Pons Nicolas , Ehrlich Stanislav Dusko , Macnaughtan Jane , Almeida Mathieu , Schapira Anthony HV 
Published: December 2024

AbstractBackgroundHeterozygous variants inGBA1are the commonest genetic risk factor for Parkinson disease (PD) but penetrance is incomplete.GBA1dysfunction can cause gastrointestinal disturbances and microbiome changes in preclinical models. Mounting evidence suggests that the microbiota-gut-brain axis is potentially implicated in PD pathogenesis. Whether the gut microbiome composition is influenced by hostGBA1genetics in heterozygosis has never been explored.ObjectivesTo evaluate whether heterozygosity for theGBA1pathogenic L444P variant can cause perturbations in gut microbiome composition.MethodsFaecal samples collected fromGBA1L444P/WTandGBA1WT/WTmice at 3 and 6 months of age were analysed through shotgun metagenomic sequencing.ResultsNo differences in α- and β-diversity were detected between genotyped groups, at either time points. Overall, we found a little variation of the gut microbiome composition and functional potential betweenGBA1L444P/WTandGBA1WT/WTmice over time.ConclusionHostGBA1genotype does not impact gut microbiome structure and composition in the presentedGBA1L444P/WTmouse model. Studies investigating the effect of a second hit on gut physiology and microbiome composition could explain the partial penetrance ofGBA1variants in PD.
One-Year Clinical Outcomes of Biodegradable Polymer Coated Everolimus-Eluting Coronary Stent: Results From a Prospective, Open-Label, Non-Randomized Study
Authors: Kasturi Sridhar , Singh Shailender , Reddy Vijay Kumar , Pratap Vikram , Masalawala Abhishek , Mishra Anil Kumar 
Published: December 2024

ABSTRACTPurposeNewer-generation biodegradable polymer coated drug-eluting stents have been developed to optimize the outcomes of percutaneous coronary intervention. Everoshine everolimus eluting coronary stent (EECS) is a newer-generation, ultrathin (65 µm) biodegradable polymer–coated drug-eluting stent designed on a cobalt– chromium stent platform. This study aimed to evaluate safety and efficacy of the newer generation polymercoated Everoshine EECS in patients with coronary artery disease (CAD) attributable to native coronary artery stenosis.MethodsThis was a single-center, single-arm, prospective study, which enrolled patients aged ≥ 18 years who had at least one native coronary artery lesions and were eligible for Everoshine EECS implantation. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and target lesion revascularization, assessed at the 30-day follow-up.ResultsA total of 193 patients were enrolled (mean age 57.8 ± 11.0 years; 142 (73.6%) male). Of these, 92 (47.7%) patients had ST-segment elevation MI (STEMI) and 39 (20.2%) had non-STEMI. A total of 267 stents were deployed, with a mean diameter of 2.9 ± 0.4 mm and a mean length of 27.0 ± 9.9 mm. At 30-day, 3 (1.6%) patients experienced MACE, and 2 (1.0%) patients experienced stent thrombosis. Cumulative MACE was observed in 5 (2.6%) patients at 1 year.ConclusionOne-year clinical outcomes demonstrated satisfactory efficacy and safety of the novel biodegradable polymer-coated Everoshine EECS in patients with CAD attributable to native coronary artery stenosis.The trial is registered retrospectively <trial registration number:ISRCTN13284341dated 2 December 2024>.
Mechanisms of Alpha-Synuclein Seeded Aggregation in Neurons Revealed by Fluorescence Lifetime Imaging
Authors: Ivey Paula-Marie E. , Sosa Magaly Guzman , Salem Abdelrahman , Min Sehong , Qi Wenzhu , Scott Alicia N. , Ejendal Karin F. K. , Kinzer-Ursem Tamara L. , Rochet Jean-Christophe , Webb Kevin J. 
Published: December 2024

1AbstractThe brains of Parkinson’s disease (PD) patients are characterized by the presence of Lewy body inclusions enriched with fibrillar forms of the presynaptic protein alpha-synuclein (aSyn). Despite related evidence that Lewy pathology spreads across different brain regions as the disease progresses, the underlying mechanism hence the fundamental cause of PD progression is unknown. The propagation of aSyn pathology is thought to potentially occur through the release of aSyn aggregates from diseased neurons, their uptake by neighboring healthy neurons via endocytosis, and subsequent seeding of native aSyn aggregation in the cytosol. A critical aspect of this process is believed to involve the escape of internalized ag-gregates from the endolysosomal compartment, though direct evidence of this mechanism in cultured neuron models remains lacking. In this study, we utilize a custom-built, time-gated fluorescence lifetime imaging microscope (FLIM) to investigate the progression of seeded ag-gregation over time in live cortical neurons. By establishing fluorescence lifetime sensitivity to aSyn aggregation level, we are able to monitor the protein’s aggregation state. Through a FLIM analysis of neurons expressing aSyn-mVenus and exposed to aSyn preformed fibrils labeled with the acid-responsive dye pHrodo, we reveal the protein’s aggregation state in both the cytosol and the endolysosomal compartment. The results indicate that aSyn seeds undergo partial disassembly prior to escaping the endocytic pathway, and that this escape is closely linked to the aggregation of cytosolic aSyn. In certain neurons, monomeric aSyn is found to translocate from the cytosol into the endolysosomal compartment, where it appar-ently forms aggregates in proximity to retained seeds. Additional analyses reveals zones of neuritic aSyn aggregates that overlaps with regions of microtubule disruption. Collectively, these findings enhance our understanding of aSyn pathology propagation in PD and other synucleinopathies, motivate additional experiments along these lines, and offer a path to guide the development of disease-modifying therapies.
A New Approach to Monitoring Protein Transfer via Extracellular Vesicles
Authors: Chabronova Alzbeta , Pigden Olivia , Jenkins Rosalind , Jensen Anders , Clarke Emily , James Victoria , Peffers Mandy J 
Published: December 2024

AbstractExtracellular vesicles (EVs) allow the exchange of protein, lipids and genetic material for communication between cells. We developed a method to track protein exchange between cells via EVs, using stable isotope labelling of amino acids in cell culture (SILAC).We compared EV isolation methods: ultracentrifugation and size exclusion chromatography (SEC) and undertook characterisation through nanoparticle tracking analysis (NTA), then optimised the requirement (0-10%) for foetal calf serum (FCS) and EV application concentration (6.5 million-200 EVs/cell seeded). We employed heavy amino acids L-Arg-HCl and L-Lys-2HCl to label donor cells and subsequent EV proteins. Unlabelled recipient cells were treated for 12 hours with EVs, at various concentrations. Mass spectrometry proteomics was used to assess uptake of heavy labelled EVs into recipient cells.A labelling efficiency of 62% was achieved. There was no relationship between the number of EVs applied to cells and the number of heavy proteins detected in the recipient cells. Pathway analysis indicated an inflammatory effect of applying EVs to cells, but the potential cause of this was unclear.We identified transferred protein cargo from EVs in recipient cells. Further optimisation of this method is still necessary.
Small-molecule inhibitor of C-terminal HSP90 dimerization modulates autophagy and functions synergistically with mTOR inhibition to kill cisplatin-resistant cancer cells
Authors: David Céline , Sun Yadong , Woloschin Vitalij , Vogt Melina , Dienstbier Niklas , Schlütermann David , Berning Lena , Lungerich Beate , Friedrich Annabelle , Akgün Seda , Mendiburo María José , Gertzen Christopn G.W. , Borkhardt Arndt , Wesselborg Sebastian , Gohlke Holger , Bhatia Sanil , Kurz Thomas , Stork Björn 
Published: December 2024

AbstractBackgroundA major obstacle for the successful treatment of cancer is the primary presence or development of resistance mechanisms toward therapeutic intervention. In urothelial cancer, cisplatin-based regimens are still routinely employed, and multiple cellular pathways contribute to chemoresistance. Since the identification of heat shock protein 90 (HSP90) as potential cancer target, various HSP90 inhibitors (HSP90i) have been developed and evaluated in clinical trials. However, limited efficacy has been observed, mainly caused by dose-limiting toxicity and the concomitant induction of a cytoprotective heat shock response (HSR). To avoid this effect, inhibitors targeting the C-terminal domain (CTD) of HSP90 that do not elicit an HSR have been put forward. Additionally, the crosstalk between autophagy and HSP90 is currently being explored, since both processes work together in proteostasis, and the modulation of autophagic responses might be helpful in order to improve the efficacy of HSP90 inhibitors.MethodsThe second-generation small-molecule inhibitor VWK147 targeting HSP90 CTD dimerization was synthesized and characterized in detail by biochemical cell-free and cellular assays and molecular modeling. Specifically, HSP90 inhibition, cell viability, and autophagy were monitored in mono- and combined treatments.ResultsWe demonstrate that VWK147 induces cell death in both cisplatin-sensitive and cisplatin-resistant urothelial carcinoma cells. The treatment with VWK147 in these cells led to the destabilization of classical HSP90 client proteins without triggering an HSR. Additionally, we observe that VWK147 re-sensitizes resistant urothelial carcinoma cells to cisplatin and—in combination with mTOR inhibition—synergistically kills cisplatin-sensitive and -resistant cells, in contrast to what is observed upon treatment with the N-terminal domain-targeting HSP90 inhibitor 17-AAG. This synergy may be explained by VWK147-mediated inhibition of late autophagy events, and thus a blockade of autophagic flux. Finally, we also observed that VWK147 induces non-canonical LC3 lipidation, indicating that this compound possibly exerts a broader effect on ion balance or pH of the endolysosomal system.ConclusionVWK147 is a promising inhibitor that targets the C-terminal dimerization of HSP90 and simultaneously exhibits autophagy-modulating effects. This compound could potentially be an effective option for improving anti-cancer therapies and/or overcoming treatment resistance.
Time-Resolved Neural Oscillations Across Sleep Stages: Associations with Sleep Quality and Aging
Authors: Passaro Antony D , Poltorak Alexander 
Published: December 2024

AbstractSleep is a fundamental physiological process critical to cognitive function, memory consolidation, emotional regulation, and overall health. This study investigates the relationship between EEG spectral power dynamics and key sleep metrics, including percentage of N3, biological age, percentage of REM, and total sleep time (TST). Using high-resolution spectral analysis, we examine how power across multiple frequency bands (0.1–50 Hz) evolves temporally across sleep stages and influences sleep architecture. Our results reveal an inverse relationship between high-frequency power (sigma, beta, and gamma) during the N1 and N2 stages and the subsequent percentage of N3, suggesting that excessive low-frequency power in N2 may disrupt the smooth progression into deep sleep. Additionally, we identify a negative correlation between low delta power (0.1–0.5 Hz) during N2 and both percentages of N3 and TST, challenging traditional views on the role of delta activity in sleep regulation. These findings advance the understanding of how brain activity across frequencies modulates sleep depth and duration, with implications for addressing age-related sleep declines.
How bats exit a crowded colony when relying on echolocation only - a modeling approach
Authors: Mazar Omer , Yovel Yossi 
Published: December 2024

AbstractBats face a complex navigation challenge when emerging from densely populated roosts, where vast numbers take off at once in dark, confined spaces. Each bat must avoid collisions with walls and conspecifics while locating the exit, all amidst overlapping acoustic signals. This crowded environment creates the risk of acoustic jamming, in which the calls of neighboring bats interfere with echo detection, potentially obscuring vital information. Despite these challenges, bats navigate these conditions with remarkable success. Although bats have access to multiple sensory cues, here we focused on whether echolocation alone could provide sufficient information for orientation under such high-interference conditions. To explore whether they manage this challenge, we developed a sensorimotor model that mimics the bats’ echolocation behavior under high-density conditions. Our findings suggest that the problem of acoustic jamming may be less severe than previously thought. Bats can compensate for potential interference by emitting frequent calls with short inter-pulse intervals (IPI), creating a redundancy in the sensory information that allows them to aggregate echoes over multiple calls. This redundancy, combined with simple pathfinding strategies, such as following walls and avoiding nearby obstacles, enables bats to exit the roost effectively, even when faced with significant sensory interference. Our model indicates that bats’ echolocation strategies are robust enough to mitigate the effects of jamming and demonstrates the critical role of signal redundancy in successful navigation. These insights not only enhance our understanding of bat behavior but also offer implications for swarm robotics and collective movement in complex environments.
Characterization of theTuta absolutavirome reveals higher viral diversity in field populations
Authors: Becerra-García Rosa Esmeralda , Hernández-Pelegrín Luis , Crava Cristina , Herrero Salvador 
Published: December 2024

AbstractA significant number of insect-specific viruses (ISVs) have been discovered in agriculturally important insect pests, facilitated by high-throughput sequencing (HTS). Despite its global impact on tomato crops, the RNA virome of the South American tomato pinworm,Tuta absoluta, remains uncharacterized. In this study, we utilized meta-transcriptomics and bioinformatic approaches to discover the RNA virome ofT. absolutaacross worldwide populations. We identified ten novel ISVs, classified into six groups: Nidovirales, Bunyavirales, Mononegavirales,Virgaviridae,Iflaviridae,Nodaviridae,Solemoviridae, andPhasmaviridae. Notably, no core virus was consistently present across the studied populations, and field-collected samples revealed a greater diversity of ISVs compared to those from laboratory samples. In addition, we detected plant-infecting viruses and mycoviruses associated with the pest. This study represents the first description of the RNA virome associated withT. absoluta, providing valuable insights into its biological and ecological interactions. It also lay the foundation for future studies aimed to clarify the biological roles of ISVs.
Maf1 Cooperates with Progesterone Receptor to Repress RNA Polymerase III Transcription of Select tRNAs
Authors: Finlay-Schultz Jessica , Paul Kiran V. , Erickson Benjamin , Fettig Lynsey M. , Hastings Benjamin S. , Johnson Deborah L. , Bentley David L. , Kabos Peter , Sartorius Carol A. 
Published: December 2024

ABSTRACTProgesterone receptors (PR) can regulate transcription by RNA Polymerase III (Pol III), which transcribes small non-coding RNAs, including all transfer RNAs (tRNAs). We have previously demonstrated that PR is associated with the Pol III complex at tRNA genes and that progestins downregulate tRNA transcripts in breast tumor models. To further elucidate the mechanism of PR-mediated regulation of Pol III, we studied the interplay between PR, the Pol III repressor Maf1, and TFIIIB, a core transcription component. ChIP-seq was performed for PR, the Pol III subunit POLR3A, the TFIIIB component Brf1, and Maf1 in breast cancer cells with or without progestin treatment. Upon progestin exposure, PR localized to approximately half of POLR3A-occupied tRNA genes, with Maf1 co-recruited to many of these PR-POLR3A sites. While progestin treatment did not significantly alter the number of tRNA genes occupied by Pol III or Brf1, Brf1 occupancy was stabilized, as indicated by increased peak amplitudes. Analysis of nascent tRNA transcription revealed a specific progestin-induced downregulation of approximately one-third of highly expressed tRNA genes. This repression was significantly reduced by Maf1 knockdown, indicating that Maf1 is necessary for PR-mediated tRNA transcription downregulation. Overall, these findings demonstrate a ligand-dependent PR-mediated repression of tRNA transcription through Maf1.
Pyrophosphate-containing Calcium Phosphates Negatively Impact Heterotopic Bone Quality
Authors: Jolic Martina , Åberg Isabella , Omar Omar , Engqvist Håkan , Engstrand Thomas , Palmquist Anders , Thomsen Peter , Shah Furqan A. 
Published: December 2024

AbstractIn bone, critical size defects pose substantial challenge in maxillofacial and orthopaedic reconstructions as they are incapable of spontaneous regeneration. Autologous bone grafts remain the “gold standard” in bone repair but their limitations and associated morbidities drive the development of bone graft substitute materials. Assessing the osteoinductive properties of these substitutes can help predict their success in bone regeneration applications. Calcium phosphates (CaP) are widely used bone graft substitutes due to their biocompatibility, osteoconductive properties, and potential for osteoinductivity. CaP materials containing monetite, beta-tricalcium phosphate (β-TCP), and a small amount of calcium pyrophosphate (Ca-PP) possess both osteoconductive and osteoinductive properties. However, the role of Ca-PP in osteoinduction and material degradation remains unexplored. This study investigates heterotopic bone formation in response to five CaP material compositions, maintaining a constant monetite and β-TCP ratio, with varying amounts of Ca-PP (0 – 12.5%). Twelve adult female sheep (Ovis aries) were subcutaneously implanted with constructs made of six CaP tiles interconnected by a Ti6Al4V frame and a control implant. Histological analysis, backscattered electron scanning electron microscopy, and Raman spectroscopy of samples retrieved at 12- and 52 weeks reveal that Ca-PP does not hinder heterotopic bone formation and minimally impacts CaP degradation. While monetite and β-TCP transform into apatite, the Ca-PP phase remains unchanged. The addition of Ca-PP to the CaP material influences heterotopic bone quality and inflammatory response during tissue regeneration.
Relationships between wellbeing polygenic scores, brain structure, and psychopathology in children
Authors: Tamnes Christian K. , Dahl Andreas , van der Meer Dennis , Agartz Ingrid , Alnaes Dag , Andreassen Ole A. , Mills Kathryn L. , Norbom Linn B. , Richard Geneviève , Dahl Ronald E. , Røysamb Espen , Westlye Lars T. , Ferschmann Lia 
Published: December 2024

AbstractWellbeing is shaped by an interplay of genetic and environmental factors and is associated with both health and functioning. It remains unclear whether genetic influences on wellbeing are linked to brain structure and, in turn, early-life psychopathology. Here, we investigated associations between wellbeing polygenic scores (PGS), magnetic resonance imaging (MRI)-derived measures of brain structure, and parent-reported measures of child psychopathology in a large cross-sectional sample of children from the Adolescent Brain Cognitive Development (ABCD) Study (n = 10,471; 8.9-11.1 years old). Preregistered analyses revealed no significant associations between wellbeing PGS and regional cortical surface area, cortical thickness, or subcortical volumes, while an exploratory analysis identified a small positive association with intracranial volume (ICV; β = 0.03, p<.001). Preregistered analyses showed small negative associations between wellbeing PGS and general psychopathology (β = −0.08, p<.001) and both internalizing (β = −.08, p<.001) and externalizing problems (β = −0.07, p<.001). ICV partially mediated the relationships between wellbeing PGS and psychopathology, accounting for 3-7% of these relationships. The findings suggest that while wellbeing PGS have limited associations with regional brain structure in children, they exhibit small protective effects against psychopathology.
Brain maps of general cognitive function and spatial correlations with neurobiological cortical profiles
Authors: Moodie Joanna E. , Buchanan Colin , Furtjes Anna , Conole Eleanor , Stolicyn Aleks , Corley Janie , Ferguson Karen , Hernandez Maria Valdes , Maniega Susana Munoz , Russ Tom C. , Luciano Michelle , Whalley Heather , Bastin Mark E. , Wardlaw Joanna , Deary Ian , Cox Simon 
Published: December 2024

AbstractIn this paper, we attempt to answer two questions: 1) which regions of the human brain, in terms of morphometry, are most strongly related to individual differences in domain-general cognitive functioning (g)? and 2) what are the underlying neurobiological properties of those regions? We meta-analyse vertex-wiseg-cortical morphometry (volume, surface area, thickness, curvature and sulcal depth) associations using data from 3 cohorts: the UK Biobank (UKB), Generation Scotland (GenScot), and the Lothian Birth Cohort 1936 (LBC1936), with the meta-analyticN= 38,379 (age range = 44 to 84 years old). Theseg-morphometry associations vary in magnitude and direction across the cortex (|β| range = -0.12 to 0.17 across morphometry measures) and show good cross-cohort agreement (mean spatial correlationr =0.57,SD= 0.18). Then, to address (2), we bring together existing -and derive new -cortical maps of 33 neurobiological characteristics from multiple modalities (including neurotransmitter receptor densities, gene expression, functional connectivity, metabolism, and cytoarchitectural similarity). We discover that these 33 profiles spatially covary along four major dimensions of cortical organisation (accounting for 65.9% of the variance) and denote aspects of neurobiological scaffolding that underpin the spatial patterning of MRI-cognitive associations we observe (significant |r| range = 0.21 to 0.56). Alongside the cortical maps from these analyses, which we make openly accessible, we provide a compendium of cortex-wide and within-region spatial correlations among general and specific facets of brain cortical organisation and higher order cognitive functioning, which we hope will serve as a framework for analysing other aspects of behaviour-brain MRI associations.