bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP® Quant 500 kit
Authors: Zararsiz Gözde Ertürk , Lintelmann Jutta , Cecil Alexander , Kirwan Jennifer , Poschet Gernot , Gegner Hagen M. , Schuchardt Sven , Guan Xue Li , Saigusa Daisuke , Wishart David , Zheng Jiamin , Mandal Rupasri , Adams Kendra , Thompson J. Will , Snyder Michael P. , Contrepois Kevin , Chen Songjie , Ashrafi Nadia , Akyol Sumeyya , Yilmaz Ali , Graham Stewart F. , O’Connell Thomas M. , Kalecký Karel , Bottiglieri Teodoro , Limonciel Alice , Pham Hai Tuan , Koal Therese , Adamski Jerzy , Kastenmüller Gabi 
Published: November 2024

ABSTRACTMetabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies. Here we evaluated the performance and reproducibility of the MxP® Quant 500 kit across 14 laboratories. The kit allows quantification of 634 different metabolites from 26 compound classes using triple quadrupole MS. Each laboratory analysed twelve samples, including human plasma and serum, lipaemic plasma, NIST SRM 1950, and mouse and rat plasma, in triplicates. 505 out of the 634 metabolites were measurable above the limit of detection in all laboratories, while eight metabolites were undetectable in our study. Out of the 505 metabolites, 412 were observed in both human and rodent samples. Overall, the kit exhibited high reproducibility with a median coefficient of variation (CV) of 14.3 %. CVs in NIST SRM 1950 reference plasma were below 25 % and 10 % for 494 and 138 metabolites, respectively. To facilitate further inspection of reproducibility for any compound, we provide detailed results from the in-depth evaluation of reproducibility across concentration ranges using Deming regression. Interlaboratory reproducibility was similar across sample types, with some species-, matrix-, and phenotype-specific differences due to variations in concentration ranges. Comparisons with previous studies on the performance of MS-based kits (including the AbsoluteIDQ p180 and the Lipidyzer) revealed good concordance of reproducibility results and measured absolute concentrations in NIST SRM 1950 for most metabolites, making the MxP® Quant 500 kit a relevant tool to apply metabolomics and lipidomics in multi-center studies.
Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gutBacteroides
Authors: Kabonick Seth , Verma Kamalesh , Modesto Jennifer L. , Pearce Victoria H. , Winokur Kailyn M. , Groisman Eduardo A. , Townsend Guy E. 
Published: November 2024

AbstractHuman dietary choices control the gut microbiome. Industrialized populations consume abundant glucose and fructose, resulting in microbe-dependent intestinal disorders. Simple sugars inhibit the carbohydrate utilization regulator (Cur), a transcription factor in the prominent gut bacterial phylum,Bacteroidetes. Cur encodes products necessary for carbohydrate utilization, host immunomodulation, and intestinal colonization. Here, we demonstrate how simple sugars decrease Cur activity in the mammalian gut. Our findings in twoBacteroidesspecies show that ATP-dependent fructose-1,6-bisphosphate (FBP) synthesis is necessary for glucose or fructose to inhibit Cur, but dispensable for growth because of an essential pyrophosphate (PPi)-dependent enzyme. Furthermore, we show that ATP-dependent FBP synthesis is required to regulate Cur in the gut but does not contribute to fitness whencuris absent, indicating PPi is sufficient to drive glycolysis in these bacteria. Our findings reveal how sugar-rich diets inhibit Cur, thereby disruptingBacteroidesfitness and diminishing products that are beneficial to the host.
Brain functional network connectivity interpolation characterizes neuropsychiatric continuum and heterogeneity
Authors: Li Xinhui , Geenjaar Eloy , Fu Zening , Pearlson Godfrey D. , Calhoun Vince D. 
Published: November 2024

AbstractPsychiatric disorders such as schizophrenia (SZ) and autism spectrum disorder (ASD) are challenging to characterize in part due to their heterogeneous presentation in individuals, with psychotic symptoms now thought to exist on a continuum from the general population to chronic SZ. Conventional diagnostic and neuroimaging analytical approaches rely on subjective assessment or group differences, but typically ignore progression between groups or heterogeneity within a group. Here, we propose a functional network connectivity (FNC) interpolation framework based on an unsupervised generative model, a variational autoencoder (VAE), to estimate the neuropsychiatric continuum and heterogeneity using static FNC (sFNC) and dynamic FNC (dFNC) data from controls and patients with SZ or ASD. We first demonstrate that VAEs significantly outperform a linear baseline and a semi-supervised counterpart in the interpolation task. We next utilize VAEs to perform sFNC and dFNC interpolation separately. For sFNC interpolation, we observe a high degree of correspondence between the generated sFNC and the corresponding original sFNC. We display the sFNC matrices on a two-dimensional grid to examine individual- and group-specific patterns, as well as pattern alterations. Specifically, the interpolated continua from patients to controls in both disorders show increased hyper-connectivity within the auditory, sensorimotor and visual networks, and between the subcortical and cerebellar domains, as well as hypo-connectivity between the subcortical domain and the sensory domains, and between the cerebellar domain and the sensory regions. For dFNC interpolation, we find that the generated dFNC states effectively capture representative and generalizable dynamic properties for each group. Finally, we show examples of how to leverage interpolation in the VAE latent space, following pathological, state-based, or temporal trajectories. The proposed framework offers added advantages over traditional methods, including data-driven discovery of hidden relationships, visualization of individual differences, imputation of missing values along a continuous spectrum, and estimation of the stage where an individual falls within the continuum. Further, it could potentially be applied to identify patient subgroups and predict future disorder progression.
Predictability of next elements in chimpanzee gesture sequences
Authors: Mielke Alexander , Badihi Gal , Donnellan Ed , Graham Kirsty E. , Hashimoto Chie , Mine Joseph G. , Piel Alex K. , Safryghin Alexandra , Slocombe Katie E. , Soldati Adrian , Stewart Fiona A. , Townsend Simon W. , Wilke Claudia , Zuberbühler Klaus , Zulberti Chiara , Hobaiter Catherine 
Published: November 2024

AbstractRecent research has produced evidence for basic combinatorial abilities in the vocal systems of different animal species. Here, we investigate the structure of gesture sequences in Eastern chimpanzees (Pan troglodytes schweinfurthii) to detect whether gestural communication shows non-random combinations and how combinatorial rules influence predictability. Gesture, as compared to vocalization, offers greater flexibility in how signals are combined—for example overlapping in time — and as the parsing of signals into sequences is dependent on researcher decisions, we employ a multiverse approach, considering four different definitions of what constitutes a ‘sequence’ based on varying time thresholds. Our results indicate that sequences tend to be short (even with the most liberal time-window) and that transitions between some gesture types occur more frequently than expected by chance, with some transitions showing significant association across all time-windows. These transitions often involve repetition, suggesting persistence as a key aspect of chimpanzee gestural sequences. Information about previous gestures reduced uncertainty in predicting subsequent gestures. The order of gestures within sequences appears to be less critical than their cooccurrence, challenging assumptions based on the linear patterning derived from vocal communication. Our findings highlight the importance of methodological choices in sequence definition and suggest that chimpanzee gestural communication is characterised by a mix of predictability and flexibility, with implications for understanding the evolution of complex communication systems.
A Unified Approach for Identifying PET-based Neuronal Activation and Molecular Connectivity with the functional PET toolbox
Authors: Hahn Andreas , Reed Murray B. , Milz Christian , Falb Pia , Murgaš Matej , Lanzenberger Rupert 
Published: November 2024

ABSTRACTPurposeFunctional PET (fPET) enables the identification of stimulation-specific changes of various physiological processes (e.g., glucose metabolism, neurotransmitter synthesis) as well as computation of individual molecular connectivity and group-level molecular covariance. However, currently no consistent analysis approach is available for these techniques. We present a versatile, freely available toolbox designed for the analysis of fPET data, thereby filling a gap in the assessment of neuroimaging data.MethodsThe fPET toolbox supports analyses for a variety of radiotracers, scanners, experimental protocols, cognitive tasks and species. It includes general linear model (GLM)-based assessment of task-specific effects, percent signal change and absolute quantification, as well as independent component analysis (ICA) for data-driven analyses. Furthermore, it allows computation of molecular connectivity via temporal correlations of PET signals between regions and molecular covariance as between-subject covariance using static images.ResultsToolbox performance was validated by analysis protocols established in previous work. Stimulation-induced changes in [18F]FDG metabolic demands and neurotransmitter dynamics obtained with 6-[18F]FDOPA and [11C]AMT were robustly detected across different cognitive tasks. Molecular connectivity analysis demonstrated metabolic interactions between different networks, whereas group-level covariance analysis highlighted interhemispheric relationships. These results underscore the flexibility of fPET in capturing dynamic molecular processes.ConclusionsThe toolbox offers a comprehensive, unified and user-friendly platform for analyzing fPET data across a variety of experimental settings. It provides a reproducible analysis approach, which in turn facilitates sharing of analyses pipelines and comparison across centers to advance the study of brain metabolism and neurotransmitter dynamics in health and disease.
A Comparison of Nanopore Data Types, Basecalling, and Assembly Algorithms: Whole Plant Genome Assembly and Methylation Analysis from a Single MinION Flow cell
Authors: Martin Samuel , Heavens Darren , Lan Yuxuan , Peel Ned , Irish Naomi , Horsfield Samuel , Giolai Michael , Clark Matthew D. , Leggett Richard M. 
Published: November 2024

AbstractBackgroundOxford Nanopore Technologies’ MinION sequencer is a compact, USB-powered device that has been available since 2014. Since the release of the earliest model, the throughput and error rate of the platform have improved dramatically and it has become possible to consider sequencing and assembly of eukaryotic organisms using a single nanopore flow cell. Here, we present MinION sequence data, assembly and methylation analysis for the Columbia (Col-0) accession of the model plantArabidopsis thaliana. Further, we demonstrate the effect that recent developments (specifically the Q20+ chemistry and basecaller improvements) have had on read accuracy and assembly quality.FindingsDNA extracted from leaves ofA. thalianaCol-0 was sequenced on two MinION flow cells, together amounting to 115x coverage of the 135 Mb genome. Reads were assembled and polished using several bioinformatics pipelines for nanopore sequence data. We performed CpG methylation analysis directly from the nanopore data, and this correlated well with a previously published bisulfite dataset.ConclusionsOur results suggest that a single MinION flow cell can generate sufficient data to assemble a genome of 135Mb, indicate functional elements, and unlock genomics for researchers of novel species from $600 in under 5 days. Here we release the full nanopore read sets for both flow cells, together with the nanopore-only assemblies. The data presented here is expected to be of particular interest to those in theArabidopsiscommunity, designing genome projects (with functional annotations), expanding our understanding of epigenetics across the tree of life, and for designing university or high school practicals teaching genomics and epigenomics.HighlightWe evaluate the effect of recent nanopore chemistry and software improvements on the ability to assemble a complete genome and conduct methylation analysis using data from a single MinION flow cell.
Spatial Transcriptomic Analysis Identifies aSERPINA3-Expressing Astrocytic State Associated with the Human Neuritic Plaque Microenvironment
Authors: Karaahmet Berke , Zhang Ya , Duquesne Laurine , Sigalov Alina , Yung Christina , Kroshilina Alexandra , Bennett David A. , Taga Mariko , Klein Hans-Ulrich 
Published: November 2024

AbstractSingle-nucleus transcriptomic studies have revealed glial cell states associated with Alzheimer’s disease; however, these nuclei are dissociated from the complex architecture of the human neocortex. Here, we successfully performed an unbiased distance-based analytic strategy on spatially-registered transcriptomic data. Leveraging immunohistochemistry in the same tissue section, our analyses prioritizedSERPINA3and other genes, such as metallothioneins, as altered in the vicinity of neuritic amyloid plaques. Results were validated at the protein level by immunofluorescence, highlighting that a reactive SERPINA3+astrocyte subtype, Ast.5, plays a role in the plaque microenvironment.
An integrative layer-resolved atlas of the adult human meninges
Authors: Degenhard Theresa , Groh Adam M.R. , Afanasiev Elia , Luo Michael , Yaqubi Moein , Stratton Jo Anne , Petrecca Kevin 
Published: November 2024

AbstractThe human meninges are a dynamic tri-layered brain border that plays a key role in brain development, CSF homeostasis, immune regulation, and higher-level brain function. The meninges have also been implicated in central nervous system (CNS) pathologies such as infection, autoimmunity, and brain trauma. To understand how the meningeal microenvironment is altered under pathological conditions it is necessary to have a complete understanding of its normotypic cellular architecture and function. To date, there is no complete atlas of the normotypic adult human meninges. By surgically extracting each human meningeal layer during surgery, we generated the first layer-resolved map of all meningeal cell types via an integration of whole cell single cell RNA sequencing, multiplexed error-robust fluorescencein situhybridization (MERFISH), and protein immunolabelling. Since fibroblasts play key roles in meningeal homeostasis yet remain less well-characterised than other meningeal cell types, we deeply phenotyped these cells in all layers. We identified 10 fibroblast subpopulations with unique predicted functions that localise to distinct neuroanatomical niches. Fibroblast interaction analysis in the dura and subarachnoid space (SAS) uncovered novel interactions with vascular cell populations mediated by insulin growth factor signaling. Together, these data serve as a comprehensive resource for future investigations of meningeal function in the healthy and diseased brain.
Impaired proteasome induces mitochondrial DNA release to activate the cGAS-STING signaling pathway and cause necroptosis in mouse brain
Authors: Dwamena Abena , Asadi Yasin , Gilstrap Erin , Wang Hongmin 
Published: November 2024

AbstractImpaired proteasome function is consistently associated with many neurodegenerative disorders, including Alzheimer’s disease (AD), showing neuroinflammation and neurodegeneration; however, how impaired proteasome causes neuroinflammation and neuronal death remains less understood. Here, we studied the effect of impaired proteasome on neuroinflammation and neuronal death in a knockout (KO) mouse model with reduced proteasome activity in the brain. We discovered that impaired proteasome led to the release of mitochondrial dsDNA into the cytosol, activating the cGAS-STING signaling pathway, and upregulating pro-inflammatory cytokines in the KO mouse brain relative to the control brain. Importantly, we also observed reduced brain weight, elevation of the mixed lineage kinase domain-like (MLKL) protein, phosphorylated MLKL, and receptor-interactive protein kinases (RIPK) 1 and 3 in the KO mouse brain compared to the control brain, suggesting activation of necroptosis in the KO brains. These data indicate that impaired proteasome activates the cGAS-STING pathway to induce neuroinflammation and neurodegeneration via a necroptotic manner. Our results suggest that neuroinflammation and necroptosis may be generalized factors caused by reduced proteasome activity observed in diverse neurodegenerative disorders.
Structural insights into SSNA1 self-assembly and its microtubule binding for centriole maintenance
Authors: Agostini Lorenzo , Pfister Jason , Basnet Nirakar , Ding Jienyu , Zhang Rui , Biertümpfel Christian , O’Connell Kevin F. , Mizuno Naoko 
Published: November 2024

AbstractSSNA-1 is a fibrillar protein localized at the area where dynamic microtubule remodeling occurs including centrosomes. Despite the important activities of SSNA1 to microtubules such as nucleation, co-polymerization, and lattice sharing microtubule branching, the underlying molecular mechanism have remained unclear due to a lack of structural information. Here, we determined the cryo-EM structure ofC. elegansSSNA-1 at 4.55 Å resolution and evaluated its role during embryonic development inC. elegans. We found that SSNA1 forms an anti-parallel coiled-coil, and its self-assembly is facilitated by the overhangs of 16 residues at its C-terminus, which dock on the adjacent coiled-coil to form a triple-stranded helical junction. Notably, the microtubule-binding region is within the triple-stranded junction, highlighting that self-assembly of SSNA-1 facilitates effective microtubule interaction by creating hubs along a fibril. Furthermore, our genetical analysis elucidated that deletion of SSNA-1 resulted in a significant reduction in embryonic viability and the formation of multipolar spindles during cell division. Interestingly, when the ability of SSNA-1 self-assembly was impaired, embryonic viability stayed low, comparable to that of the knockout strain. Our study provides molecular insights into the self-assembly mechanisms of SSNA-1, shedding light on its role in controlling microtubule binding and cell division through the regulation of centriole stability.
Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases
Authors: Chakraborty Anirban , Mitra Joy , Maloji Rao Vikas H. , Kodavati Manohar , Mandal Santi M. , Gill Satkarjeet K. , Sreenivasmurthy Sravan Gopalkrishnashetty , Vasquez Velmarini , Mankevich Mikita , Krishnan Balaji , Ghosh Gourisankar , Hegde Muralidhar L. , Hazra Tapas 
Published: November 2024

AbstractTAR DNA-binding protein 43 (TDP-43) proteinopathy plays a critical role in neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia (FTD). In our recent discovery, we identified that TDP-43 plays an essential role in DNA double-strand break (DSB) repair via the non-homologous end joining (NHEJ) pathway. Here, we found persistent DNA damage in the brains of ALS/FTD patients, primarily in the transcribed regions of the genome. We further investigated the underlying mechanism and found that polynucleotide kinase 3’-phosphatase (PNKP) activity was severely impaired in the nuclear extracts of both patient brains and TDP-43-depleted cells. PNKP is a key player in DSB repair within the transcribed genome, where its 3’-P termini processing activity is crucial for preventing persistent DNA damage and neuronal death. The inactivation of PNKP in ALS/FTD was due to reduced levels of its interacting partner, phosphofructo-2-kinase fructose 2,6 bisphosphatase (PFKFB3), and its biosynthetic product, fructose-2,6-bisphosphate (F2,6BP), an allosteric modulator of glycolysis. Recent work from our group has shown that F2,6BP acts as a positive modulator of PNKP activityin vivo. Notably, exogenous supplementation with F2,6BP restored PNKP activity in nuclear extracts from ALS/FTD brain samples and patient-derived induced pluripotent stem (iPS) cells harboring pathological mutations. Furthermore, we demonstrate that supplementation of F2,6BP restores genome integrity and partially rescues motor phenotype in aDrosophilamodel of ALS. Our findings underscore the possibility of exploring the therapeutic potential of F2,6BP or its analogs in TDP-43 pathology-associated motor neuron diseases.
Genome content in the non-model ciliateChilodonella uncinata: insights into nuclear architecture, gene-sized chromosomes among the total DNA in their somatic macronuclei during their development
Authors: Ahsan Ragib , Maurer-Alcalá Xyrus X. , Katz Laura A. 
Published: November 2024

AbstractCiliates are a model lineage for studies of genome architecture given their unusual genome structures. All ciliates have both somatic macronuclei (MAC) and germline micronuclei (MIC), both of which develop from a zygotic nucleus following sex (i.e., conjugation). Nuclear developmental stages are not as well explored among non-model ciliate genera, includingChilodonella uncinata(Class-Phyllopharyngea), the focus of our work. Here, we characterize nuclear architecture and genome dynamics inC. uncinataby combining DAPI (4′,6-diamidino-2-phenylindole) staining and fluorescencein situhybridization (FISH) techniques with confocal microscopy. We developed a telomere probe for staining alongside DAPI, which allows for the identification of fragmented somatic chromosomes among the total DNA in the nuclei. We quantify both total DNA and telomere-bound signals to explore changes in DNA content and chromosome maturation acrossChilodonella’s nuclear life cycle. Specifically, we find that MAC developmental stages in the ciliateC. uncinataare different than the data reported from other ciliate species. These data provide insights into nuclear dynamics during nuclear development and enrich our understanding of genome evolution in non-model ciliates.