bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered astrocytic and microglial homeostasis characterizes a decreased proinflammatory state in bipolar disorder
Authors: Amossé Quentin , Tournier Benjamin B. , Badina Aurélien M. , Marchand-Maillet Lilou , Abjean Laurene , Lengacher Sylvain , Fancy Nurun , Smith Amy M. , Leung Yeung-Yeung , Santer Verena , Garibotto Valentina , Owen David R. , Piguet Camille , Ceyzériat Kelly , Tsartsalis Stergios , Millet Philippe 
Published: November 2023

AbstractMultiple lines of evidence point to peripheral immune alterations in bipolar disorder (BD) although the activity of brain immune mechanisms remain largely unexplored. To identify the cell type-specific immune alterations in the BD brain, we performed a proteomic and single nuclear transcriptomic analysis ofpostmortemcingulate cortex samples from BD and control subjects. Our results showed that genes associated to the genetic risk for BD are enriched in microglia and astrocytes. Transcriptomic alterations in microglia point to a reduced proinflammatory phenotype, associated to reduced resistance to oxidative stress and apoptosis, which was confirmed with immunohistochemical quantification of IBA1 density. Astrocytes show transcriptomic evidence of an imbalance of multiple metabolic pathways, extracellular matrix composition and downregulated immune signalling. These alterations are associated toADCY2andNCAN,two GWAS genes upregulated in astrocytes. Finally, cell-cell communication analysis prioritized upregulated SPP1-CD44 signalling to astrocytes as a potential regulator of the transcriptomic alterations in BD. Our results indicate that microglia and astrocytes are characterized by downregulated immune responses associated to a dysfunction of core mechanisms via which these cells contribute to brain homeostasis.
Safety Assessment of Intravenous Injection of Rat Embryonic Proteome Extract forin-vivoRegenerative Therapies
Authors: Darsi Siva Rama Prasad , Kandula Siva Kumar , Bharani Kala Kumar , Pasupalati Anil Kumar , Cheekatla Satyanarayana Swamy , Darsi Sujesh Kumar , Kamireddy Adi Reddy , Barra Ram Reddy , Devarasetti Ashok Kumar , Surampudi Sreedhar , Singireddy Jaya Ram Raddy 
Published: November 2023

SummaryBack groundTissue differentiation and organogenesis are exclusively embryonic-phase activities, and these two activities are strictly under the control of the embryonic proteome, the developing embryo is a prime source of molecules for regenerative therapy. Manyex-vivorudimentary organoid culture studies confirmed the inherent biological function of embryonic factors. Before using embryonic proteins for in vivo therapies, their safety should be confirmed first. Hence, we aimed for anin vivostudy to inject rat embryonic proteome extract (EPE) through the intravenous route and investigate the impact on immunological, biochemical, and hematological parameters in the adult rats.MethodsIn this study, we isolated rat embryonic proteins from the 14th, 16th, and 19thembryonic days by homogenization of embryos and isolated protein extracts through ultra-centrifugation. Six pairs of rats have been taken; six are allotted for control, and six are for the embryonic extract injection. The isolated embryonic protein extract was injected intravenously into the treatment group of rats and the normal saline into the control group. After the injections, blood samples are collected from both the treated and control groups to analyse immunological markers Il6, CRP, biochemical parameters creatinine, urea, sugar, proteins, albumin, globulin, and hematological parameters total leucocyte count, neutrophils, and lymphocyte percentageResultAfter the EPE injection, biochemical parameters, immunological markers, and hematological parameters were analyzed in both control and treated groups. All the above mentioned parameters are within normal limits. Statistical analyses were done using the t-test for unequal variance (p< 0.05). We observed no significant difference between the control and treated groups, soin vivoinjections of embryonic protein extract is safe for the use ofin vivoregenerative therapies.ConclusionDespite extensivein vitrostudies confirmed the biological function of embryonic growth factors for organ differentiations and rudimentary organoids, butin vivoclinical applications are not yet started because of immunogenicity, heterogeneity, and tumorigeniety. In our study we injected EPE intravenously and showed that EPE is non-immunogenic, non-heterogeneic, and non-tumorigenic. This study concludes that EPE is safe for in vivo injection, so that further studies can be continued for intra-organ injections for organ regenerative therapy.
Pepid: a Highly Modifiable, Bioinformatics-Oriented Peptide Search Engine
Authors: Zumer Jeremie , Lemieux Sébastien 
Published: November 2023

AbstractMotivationCurrent peptide search engines are optimized for wet-lab workflows, i.e. they operate in an “end-to-end” manner to achieve good identification results, not to be modified or provide algorithmic insight. This makes developing new software methods to solve problems in peptide identification methods difficult, often requiring a full engine rewrite. Recently, many deep learning methods were proposed as solutions to various parts of the peptide identification task, but virtually none of those methods have been implemented in any actual peptide search process. We believe that the lack of a reliable bioinformatics research platform for peptide identification that enables such integrations is slowing down proteomics research as a whole.ResultsWe present pepid, a bioinformatics research-oriented peptide search engine. Unlike other search engines, pepid is specifically designed with ease of computational research in mind. Our design is highly flexible and allows easy modifications with little required software development expertise, allowing researchers to focus on analysing and improving peptide identification methods.It also takes recent computational trends into account, such as the recent slew of deep learning publications in proteomics, and features a multi-phased batched operations design that is more appropriate than the spectrum batch “end-to-end” designs of existing search engines for those approaches. We show that pepid is competitive with common engines in terms of both identification rates and runtime, forming a minimum required baseline to enable further identification research.Availability and ImplementationPepid is available as open source software under the MIT license athttps://github.com/lemieux-lab/pepid. Other data referenced in the text is 3rd party. The selected yeast proteome can be found on SwissProt with accession ID UP000002311 while the human proteome’s accession ID is UP0000005640. The ProteomeTools spectra can be found in the PRIDE archive under accession D PXD004732 and the One Hour Yeast Proteome can be found at the ChorusProject athttps://chorusproject.org/anonymous/download/experiment/-8823069691100997209andhttps://chorusproject.org/anonymous/download/experiment/449795368199176159.
cisDynet: an integrated platform for modeling gene-regulatory dynamics and networks
Authors: Zhu Tao , Zhou Xinkai , You Yuxin , Wang Lin , He Zhaohui , Chen Dijun 
Published: November 2023

AbstractChromatin accessibility sequencing has been widely used for uncovering genetic regulatory mechanisms and inferring gene regulatory networks. However, effectively integrating large-scale chromatin accessibility datasets has posed a significant challenge. This is due to the lack of a comprehensive end-to-end solution, as many existing tools primarily emphasize data pre-processing and overlook downstream analyses. To bridge this gap, we have introduced cisDynet, a holistic solution that combines streamlined data pre-processing using Snakemake and R functions with advanced downstream analysis capabilities. cisDynet excels in conventional data analyses, encompassing peak statistics, peak annotation, differential analysis, motif enrichment analysis and more. Additionally, it allows to perform sophisticated data exploration such as tissue-specific peak identification, time-course data fitting, integration of RNA-seq data to establish peak-to-gene associations, constructing regulatory networks, and conducting enrichment analysis of GWAS variants. As a proof of concept, we applied cisDynet to re-analyze the comprehensive ATAC-seq datasets across various tissues from the ENCODE project. The analysis successfully delineated tissue-specific open chromatin regions (OCRs), established connections between OCRs and target genes, and effectively linked these discoveries with 1,861 GWAS variants. Furthermore, cisDynet was instrumental in dissecting the time-course open chromatin data of mouse embryonic development, revealing the dynamic behavior of OCRs over time and identifying key transcription factors governing differentiation trajectories. In summary, cisDynet offers researchers a user-friendly solution that minimizes the need for extensive coding, ensures the reproducibility of results, and greatly simplifies the exploration of epigenomic data.Graphical AbstractcisDynet enables the exploration of the cis-regulatory chromatin dynamics and networks. It offers a streamlined preprocessing pipeline built on Snakemake, along with an R package for advanced downstream data analysis and visualization. It is free to access on GitHub (https://github.com/tzhu-bio/cisDynet).HighlightsThe cisDynet enables comprehensive and efficient processing of chromatin accessibility data, including pre-processing, advanced downstream data analysis and visualization.cisDynet provides a range of analytical features such as processing of time course data, co-accessibility analysis, linking OCRs to genes, building regulatory networks, and GWAS variant enrichment analysis.cisDynet simplifies the identification of tissue/cell type-specific OCRs or dynamic OCR changes over time and facilitates the integration of RNA-seq data to depict temporal trajectories.
FlyVISTA, an Integrated Machine Learning Platform for Deep Phenotyping of Sleep inDrosophila
Authors: Keleş Mehmet F. , Sapci Ali Osman Berk , Brody Casey , Palmer Isabelle , Le Christin , Taştan Öznur , Keleş Sündüz , Wu Mark N. 
Published: November 2023

AbstractAnimal behavior depends on internal state. While subtle movements can signify significant changes in internal state, computational methods for analyzing these “microbehaviors” are lacking. Here, we present FlyVISTA, a machine-learning platform to characterize microbehaviors in freely-moving flies, which we use to perform deep phenotyping of sleep. This platform comprises a high-resolution closed-loop video imaging system, coupled with a deep-learning network to annotate 35 body parts, and a computational pipeline to extract behaviors from high-dimensional data. FlyVISTA reveals the distinct spatiotemporal dynamics of sleep-associated microbehaviors in flies. We further show that stimulation of dorsal fan-shaped body neurons induces micromovements, not sleep, whereas activating R5 ring neurons triggers rhythmic proboscis extension followed by persistent sleep. Importantly, we identify a novel microbehavior (“haltere switch”) exclusively seen during quiescence that indicates a deeper sleep stage. These findings enable the rigorous analysis of sleep inDrosophilaand set the stage for computational analyses of microbehaviors.
Ultrahigh Resolution Lipid Mass Spectrometry Imaging of High-Grade Serous Ovarian Cancer Mouse Models
Authors: Ma Xin , Botros Andro , Yun Sylvia R. , Park Eun Young , Kim Olga , Chen Ruihong , Palaniappan Murugesan , Matzuk Martin M. , Kim Jaeyeon , Fernández Facundo M. 
Published: November 2023

AbstractNo effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights on how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n= 4) and a triple mutant mouse models (n= 4) of high-grade serous ovarian cancer (HGSC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes compared to those in healthy mouse reproductive tissue (n= 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide a direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissuesviaa number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.
Nuclear deformation and dynamics of migrating cells in 3D confinement reveal adaptation of pulling and pushing forces
Authors: Stöberl Stefan , Flommersfeld Johannes , Kreft Maximilian M. , Benoit Martin , Broedersz Chase P. , Rädler Joachim O. 
Published: November 2023

AbstractEukaryotic cells show an astounding ability to migrate through pores and constrictions smaller than their nuclear diameter. However, the forces engaged in nuclear deformation and their effect on confined cell dynamics remain unclear. Here, we study the mechanics and dynamics of nuclei of mesenchymal cancer cells as they spontaneously and repeatedly transition through 3D compliant hydrogel channels. We find a biphasic dependence of migration speed and transition frequency on channel width, revealing maximal transition rates at widths comparable to the nuclear diameter. Using confocal imaging and hydrogel bead displacement, we determine the nuclear deformation and corresponding forces during spontaneous confined migration. We find the nucleus to reversibly deform with an elastic modulus not adapting to the confinement. Instead, with decreasing channel width, the nuclear shape during transmigration changes biphasically concomitant with the transitioning dynamics. The nucleus exhibits a prolate form along the migration direction in wide channels and a more compressed oblate shape in narrow channels. We propose a physical model for confined cell migration that explains the observed nuclear shapes and slowing down in terms of the cytoskeletal force-generation adapting from a pulling-to a pushing-dominated mechanism with increasing nuclear confinement.
Looking for a needle in a haystack: de novo phenotypic target identification reveals Hippo pathway-mediated miR-202 regulation of egg production
Authors: Janati-Idrissi Sarah , Roza de Abreu Mariana , Guyomar Cervin , de Mello Fernanda , Nguyen Thaovi , Mechkouri Nazim , Gay Stéphanie , Montfort Jérôme , Gonzalez Anne Alicia , Abbasi Marzieh , Bugeon Jérôme , Thermes Violette , Seitz Hervé , Bobe Julien 
Published: November 2023

AbstractUnderstanding microRNA (miRNA) functions has been hampered by major difficulties in identifying their biological target(s). Currently, the main limitation is the lack of a suitable strategy to identify biologically relevant targets among a high number of putative targets. Here we provide a proof of concept of successfulde novo(i.e., without prior knowledge of its identity) miRNA phenotypic target (i.e., target whose de-repression contributes to the phenotypic outcomes) identification from RNA-seq data. Using the medakamir-202knock-out (KO) model in which inactivation leads to a major organism-level reproductive phenotype, including reduced egg production, we introduced novel criteria including limited fold-change in KO and low interindividual variability in gene expression to reduce the list of 2,853 putative targets to a short list of 5. We selectedtead3b,a member of the evolutionarily-conserved Hippo pathway, known to regulate ovarian functions, due to its remarkably strong and evolutionarily conserved binding affinity for miR-202-5p. Deleting the miR-202-5p binding site in the 3’ UTR oftead3b, but not of other Hippo pathway memberssav1andvgll4b, triggered a reduced egg production phenotype. This is one of the few successful examples ofde novofunctional assignment of a miRNA phenotypic targetin vivoin vertebrates.
Unusual 1-3 peptidoglycan cross-links inAcetobacteraceaeare made by L,D-transpeptidases with a catalytic domain distantly related to YkuD domains
Authors: Alaman-Zarate Marcel G , Rady Brooks J , Evans Caroline A , Pian Brooke , Greetham Darren , Marecos-Ortiz Sabrina , Dickman Mark J , Lidbury Ian DEA , Lovering Andrew L , Barstow Buz M , Mesnage Stéphane 
Published: November 2023

AbstractPeptidoglycan is an essential component of the bacterial cell envelope that contains glycan chains substituted by short peptide stems. Peptide stems are polymerized by D,D-transpeptidases, which make bonds between the amino acid in position 4 of a donor stem and the third residue of an acceptor stem (4-3 cross-links). Some bacterial peptidoglycans also contain 3-3 cross-links that are formed by another class of enzymes called L,D-transpeptidases. In this work, we investigate the formation of unusual bacterial 1-3 peptidoglycan cross-links. We describe a version of the PGFinder software which can identify 1-3 cross-links and report the high-resolution peptidoglycan structure ofGluconobacter oxydans(a model organism within theAcetobacteraceaefamily). We reveal thatG. oxydanspeptidoglycan contains peptide stems made of a single alanine as well as several dipeptide stems with unusual amino acids at their C-terminus. Using a Sudoku transposon library, we identified aG. oxydansmutant with a drastic reduction in 1-3 cross-links. Through complementation experiments inG. oxydansand recombinant protein production in a heterologous host, we identify an L,D-transpeptidase enzyme with a domain distantly related to the YkuD domain responsible for these non-canonical reactions. This work revisits the enzymatic capabilities of L,D-transpeptidases, a versatile family of enzymes that play a key role in bacterial peptidoglycan remodelling.
Revealing motor behavior patterns and functional improvement trajectories following spinal cord injury using unsupervised machine learning
Authors: Eisdorfer Jaclyn Taylor , Lin Sherry , Thackray Joshua K , Theis Thomas , Vivinetto Ana , Oputa Olisemeka , Martinez Alana M , Nacht Hannah D , Tschang Monica , Mahmood Malaika , Tucker Ashley , Ruven Carolin , Pusuloori Shailee , Zmoyro Lance , Kumar Suneel ,   Abraira Lab Computational Group, Schachner Melitta , Sahni Vibhu , Popovich Phillip , Ferguson Adam R. , McTigue Dana , Tysseling Vicki M , Dulin Jennifer , Hollis Edmund , Datta Sandeep Robert , Abraira Victoria Eugenia Guadalupe 
Published: November 2023

ABSTRACTSpinal cord injury (SCI) disrupts motor function, with recovery involving complex adaptive motor behaviors that cannot be fully assessed with traditional manual recovery assessments and their predefined recovery criteria. To move beyond these constraints, we employed motion sequencing (MoSeq), a machine learning-driven framework that automatically segments freely moving mouse behavior into discrete, repeated behavioral “syllables”, effectively capturing entire behavioral repertoires and dynamic behavioral sequences observed throughout SCI recovery. We observed that functional improvements involved the reemergence of preinjury behaviors, emergence of adaptive behaviors, and subtle individual differences between mice. Interestingly, the temporal organization of behavioral sequences evolved consistently across injury severities, suggesting a ceiling effect in sequence reorganization. MoSeq syllables also correlated with the Basso Mouse Scale (BMS) and outperformed BMS in correlation to several injury-related histological findings. We also introduced the “Recovery Score,” a new metric derived from aggregated MoSeq data that quantifies recovery based on syllable usage patterns. The Recovery Score identified clusters of syllables with high usages, which highlights the potential of using hallmark syllables as behavioral biomarkers for assessing recovery and informing therapies. Future research should incorporate more complex experimental designs to refine this aggregation approach and advance the pursuit of a new gold standard in recovery assessment.
Swine influenza A virus infection dynamics and evolution in intensive pig production systems
Authors: Lagan Paula , Hamil Michael , Cull Susan , Hanrahan Anthony , Wregor Rosanna M. , Lemon Ken 
Published: November 2023

AbstractSwine influenza A virus is one of the main viral pathogens responsible for respiratory disease in farmed pigs. Whilst outbreaks are often epidemic in nature, increasing reports suggest that continuous, endemic infection of herds is now common. The move towards larger herd sizes and increased intensification in the commercial pig industry may promote endemic infection, however, the impact that intensification has on swine influenza A virus infection dynamics and evolution is unclear. We carried out a longitudinal surveillance study over 18 months on two endemically infected, intensive pig farms. Frequent sampling of all production stages using individual and group sampling methods was performed, followed by virological and immunological testing and whole genome sequencing. We identified weaned pigs between 4-12 weeks old as the main reservoir of swine influenza A virus on the farms, with continuous, year-round infection. Despite the continuous nature of viral circulation, infection levels were not uniform, with increasing immunity at the herd level associated with reduced viral prevalence followed by subsequent rebound infection. A single virus subtype persisted on each farm for the entire duration of the study. Viral evolution was characterised by long periods of stasis punctuated by periods of rapid change coinciding with increasing immunity within the herd. An accumulation of mutations in the surface glycoproteins consistent with antigenic drift was observed, in addition to amino acid substitutions in the internal gene products as well as reassortment exchange of internal gene segments from newly introduced strains. These data demonstrate that long-term, continuous infection of herds with a single subtype is possible and document the evolutionary mechanisms utilised to achieve this.Author SummaryInfection with influenza A virus is widespread in pigs and contributes towards poor health and loss of productivity. Effective infection control measures are necessary to limit the impact of influenza on farms. However, modern farming practices are increasingly characterised by larger herd sizes and higher stocking densities. It is unclear how the move towards increased intensification impacts infectious diseases such as influenza. Accumulating evidence suggests that long-term infection of herds may be common. How influenza A virus can persist long-term is poorly understood. The aim of the current study was to monitor the infection status of pigs at each stage of the production process, measure the extent of the developing immune response and to characterise the evolutionary changes in the circulating influenza A viruses over time. Our findings provide insights into the dynamics of viral infection and evolution and may contribute to improved infection control strategies.