bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Capsaicin-Induced Mechanical Allodynia and Neuronal Responses in the DRG in the Presence ofShp1Overexpression
Authors: Vroman Robin , Ishihara Shingo , Fullam Spencer , Wood Matthew J. , Adamczyk Natalie S. , Lomeli Nolan , Malfait Fransiska , Malfait Anne-Marie , Miller Rachel E. , Markovics Adrienn 
Published: January 2024

AbstractTransient Receptor Potential Vanilloid 1 (TRPV1) is a nonselective cation channel expressed by pain-sensing neurons and has been an attractive target for the development of drugs to treat pain. Recently, Src homology region 2 domain-containing phosphatase-1 (SHP-1) was shown to dephosphorylate TRPV1 in dorsal root ganglia (DRG) neurons, which was linked with alleviating different pain phenotypes. These previous studies were performed in male rodents only and did not directly investigate the role of SHP-1 in TRPV-1 mediated sensitization. Therefore, our goal was to determine the impact ofShp1overexpression on TRPV1-mediated neuronal responses and capsaicin-induced pain behavior in mice of both sexes. Twelve-week-old male and female mice overexpressingShp1(Shp1-Tg) and their wild type (WT) littermates were used.Shp1overexpression was confirmed in the DRG of Shp1-Tg mice by RNAin situhybridization and RT-qPCR.Trpv1andShp1were found to be co-expressed in DRG sensory neurons in both genotypes. Functionally, this overexpression resulted in lower magnitude intracellular calcium responses to 200 nM capsaicin stimulation in DRG cultures from Shp1-Tg mice compared to WTs.In vivo, we tested the effects ofShp1overexpression on capsaicin-induced pain through a model of capsaicin footpad injection. While capsaicin injection evoked nocifensive behavior (paw licking) and paw swelling in both genotypes and sexes, only WT mice developed mechanical allodynia after capsaicin injection. We observed similar level of TRPV1 protein expression in the DRG of both genotypes, however, a higher amount of tyrosine phosphorylated TRPV1 was detected in WT DRG. These experiments suggest that, while SHP-1 does not mediate the acute swelling and nocifensive behavior induced by capsaicin, it does mediate a protective effect against capsaicin-induced mechanical allodynia in both sexes. The protective effect of SHP-1 might be mediated by TRPV1 dephosphorylation in capsaicin-sensitive sensory neurons of the DRG.
GTDrift: A resource for exploring the interplay between genetic drift, genomic and transcriptomic characteristics in eukaryotes
Authors: Bénitière Florian , Duret Laurent , Necsulea Anamaria 
Published: January 2024

AbstractWe present GTDrift, a comprehensive data resource that enables explorations of genomic and transcriptomic characteristics alongside proxies of the intensity of genetic drift in individual species. This resource encompasses data for 1,506 eukaryotic species, including 1,413 animals and 93 green plants, and is organized in three components. The first two components contain approximations of the effective population size, which serve as indicators of the extent of random genetic drift within each species. In the first component, we meticulously investigated public databases to assemble data on life history traits such as longevity, adult body length and body mass for a set of 979 species. The second component includes estimations of the ratio between the rate of non-synonymous substitutions and the rate of synonymous substitutions (dN/dS) in protein-coding sequences for 1,324 species. This ratio provides an estimate of the efficiency of natural selection in purging deleterious substitutions. Additionally, we present polymorphism-derivedNeestimates for 66 species. The third component encompasses various genomic and transcriptomic characteristics. With this component, we aim to facilitate comparative transcriptomics analyses across species, by providing easy-to-use processed data for more than 16,000 RNA-seq samples across 491 species. These data include intron-centered alternative splicing frequencies, gene expression levels and sequencing depth statistics for each species, obtained with a homogeneous analysis protocol. To enable cross-species comparisons, we provide orthology predictions for conserved single-copy genes based on BUSCO gene sets. To illustrate the possible uses of this database, we identify the most frequently used introns for each gene and we assess how the sequencing depth available for each species affects our power to identify major and minor splice variants.
Sertraline modulates hippocampal plasticity and learning via sigma 1 receptors, cellular stress and neurosteroids
Authors: Izumi Yukitoshi , Reiersen Angela M. , Lenze Eric J. , Mennerick Steven J. , Zorumski Charles F. 
Published: January 2024

ABSTRACTIn addition to modulating serotonin transport, selective serotonin reuptake inhibitors (SSRIs) have multiple other effects that may contribute to clinical effects, and some of these latter actions prompt repurposing of SSRIs for non-psychiatric indications. We recently observed that the SSRIs fluvoxamine and fluoxetine prevent the acute adverse effects of pro-inflammatory stimulation on long-term potentiation (LTP) in the CA1 hippocampal region. Sertraline showed markedly different effects, acutely inhibiting LTP at a low micromolar concentration through inverse agonism of sigma 1 receptors (S1Rs). In the present studies, we pursued mechanisms contributing to sertraline modulation of LTP in rat hippocampal slices. We found that sertraline partially inhibits synaptic responses mediated by N-methyl-D-aspartate receptors (NMDARs) via effects on NMDARs that express GluN2B subunits. A selective S1R antagonist (NE-100), but not an S1R agonist (PRE-084) blocked effects on NMDARs, despite the fact that both S1R ligands were previously shown to prevent LTP inhibition. Both NE-100 and PRE-084, however, prevented adverse effects of sertraline on one-trial learning. Because of the important role that S1Rs play in modulating endoplasmic reticulum stress, we examined whether inhibitors of cellular stress alter effects of sertraline. We found that two stress inhibitors, ISRIB and quercetin, prevented LTP inhibition, as did inhibitors of the synthesis of endogenous neurosteroids, which are homeostatic regulators of cellular stress. These studies highlight complex effects of sertraline, S1Rs and neurosteroids on hippocampal function and have relevance for understanding therapeutic and adverse drug actions.
Automatic Geometry-based Estimation of the Locus Coeruleus Region on T1-Weighted Magnetic Resonance Images
Authors: Aganj Iman , Mora Jocelyn , Fischl Bruce , Augustinack Jean C. 
Published: January 2024

AbstractThe locus coeruleus (LC) is a key brain structure implicated in cognitive function and neurodegenerative disease. Automatic segmentation of the LC is a crucial step in quantitative non-invasive analysis of the LC in large MRI cohorts. Most publicly available imaging databases for training automatic LC segmentation models take advantage of specialized contrast-enhancing (e.g., neuromelanin-sensitive) MRI. Segmentation models developed with such image contrasts, however, are not readily applicable to existing datasets with conventional MRI sequences. In this work, we evaluate the feasibility of using non-contrast neuroanatomical information to geometrically approximate the LC region from standard 3-Tesla T1-weighted images of 20 subjects from the Human Connectome Project (HCP). We employ this dataset to train and internally/externally evaluate two automatic localization methods, the Expected Label Value and the U-Net. We also test the hypothesis that using thephaseimage as input can improve the robustness of out-of-sample segmentation. We then apply our trained models to a larger subset of HCP, while exploratorily correlating LC imaging variables and structural connectivity with demographic and clinical data. This report contributes and provides an evaluation of two computational methods estimating neural structure.
Large ungulates will be present in most of Japan by 2050 owing to natural expansion and human population shrinkage
Authors: Morosawa Takahiro , Iijima Hayato , Kawamoto Tomonori , Kanno Takahisa , Araki Ryota , Oka Teruki 
Published: January 2024

AbstractThe aims of this study were to elucidate factors contributing to the expansion of the distributions of sika deer and wild boar in Japan and to predict the expansion of their distributions by 2025, 2050, and 2100. A site occupancy model was constructed using information on species distribution collected by the Ministry of the Environment in 1978, 2003, 2014, and 2018, days of snow cover, forested and road areas, elevation, human population, and distance from occupied grid cells as covariates to calculate the probability of distribution change. Factors contributing to distribution expansion were elucidated and distribution expansion was predicted. Distance from occupied grid cells had the strongest influence on distribution expansion, followed by the inherent ability of each species to expand its distribution. For sika deer, human population had a strong negative effect and elevation and number of days of snow cover were important. For wild boar, forest area and elevation had high importance. Predictions of future distribution showed that both species will be distributed over 90% of Japan by 2050 and over 100% by 2100.
Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases
Authors: Li Celine Man Ying , Briggs Matthew T , Lee Yea-Rin , Tin Teresa , Young Clifford , Pierides John , Kaur Gurjeet , Drew Paul , Maddern Guy J , Hoffmann Peter , Klingler-Hoffmann Manuela , Fenix Kevin 
Published: January 2024

AbstractColorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentifiedm/zvalues (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Tenm/zvalues were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Hemoglobin subunit alpha, and Inosine-5’-monophosphate dehydrogenase 2) and two unidentifiedm/zvalues (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
Investigating Sensitivity, Specificity and Accuracy of Variant Calling Pipelines for Analyzing SARS-CoV-2 Data
Authors: Krishna Aadi C. , Choi Judy S. 
Published: January 2024

AbstractThe rapidly increasing popularity of Next Generation Sequencing and analysis methods in clinical and research settings necessitates an understanding of ideal combinations in identifying genomic variants. Especially with the importance of detecting accurate variants for the development of targeted SARS-CoV-2 vaccines. This research compares the results of two ‘Mapping Algorithms ‘, BWA-MEM and Bowtie2, and two ‘Variant Calling Algorithms ‘, LoFreq and FreeBayes, and their combinatory Variant Calling Pipelines on the analyses of Next Generation Sequencing (NGS) data of five SARS-CoV-2 samples collected from patients in the USA, India, Italy, and Malawi and sourced for this research from the publicly available NCBI SRA database. Our analysis of mapping algorithms found that BWA-MEM likely has higher sensitivity and specificity than Bowtie2 for mapping reads, and their specificity and sensitivity vary with read length. Furthermore, the accuracy of variant calling algorithms increases with the number of reads, while higher read length possibly leads to divergence in accuracy and sensitivity. Overall, FreeBayes was found to likely be more sensitive to detecting variants when used with Bowtie2 rather than BWA-MEM for analyzing SARS-CoV-2 data.
Comparative genomics reveals intra and inter species variation in the pathogenic fungusBatrachochytrium dendrobatidis
Authors: Yacoub Mark N. , Stajich Jason E. 
Published: January 2024

AbstractThe Global Pandemic Lineage (GPL) of the amphibian pathogenBatrachochytrium dendrobatidis(Bd) has been described as a main driver of amphibian extinctions on nearly every continent. Near complete genome of threeBd-GPL strains have enabled studies of the pathogen but the genomic features that setBd-GPL apart from otherBdlineages is not well understood due to a lack of high-quality genome assemblies and annotations from other lineages. We used long-read DNA sequencing to assemble high-quality genomes of threeBd-BRAZIL isolates and one non-pathogen outgroup speciesPolyrhizophydium stewartii(Ps) strain JEL0888, and compared these to genomes of previously sequencedBd-GPL strains. TheBd-BRAZIL assemblies range in size between 22.0 and 26.1 Mb and encode 8495-8620 protein-coding genes for each strain. Our pan-genome analysis provided insight into shared and lineage-specific gene content. The core genome ofBdconsists of 6278 conserved gene families, with 202Bd-BRAZIL and 172Bd-GPL specific gene families. We discovered gene copy number variation in pathogenicity gene families betweenBd-BRAZIL andBd-GPL strains though none were consistently expanded inBd-GPL orBd-BRAZIL strains. Comparison within the Batrachochytrium genus and two closely related non-pathogenic saprophytic chytrids identified variation in sequence and protein domain counts. We further test these new Bd-BRAZIL genomes to assess their utility as reference genomes for transcriptome alignment and analysis. Our analysis examines the genomic variation between strains inBd-BRAZIL andBd-GPL and offers insights into the application of these genomes as reference genomes for future studies.
Unravelling the ancient fungal DNA from the Iceman’s gut
Authors: Oskolkov Nikolay , Sandionigi Anna , Göterström Anders , Canini Fabiana , Turchetti Benedetta , Zucconi Laura , Mimmo Tanja , Buzzini Pietro , Borruso Luigimaria 
Published: January 2024

AbstractHere, we explore the possible ancient fungal species in the gut of Ötzi, the Iceman, a naturally mummified human found in the Tyrolean Alps (border between Italy and Austria). While ancient DNA (aDNA) has been extensively used to study human, animal, and plant evolution, this research focuses on ancient microbial diversity, specifically fungi. Fungal DNA is often underestimated in metagenomic samples, however here we hypothesise the possibility of retrieving ancient fungal sequences from Ötzi’s gut. A robust bioinformatic pipeline has been developed to detect and authenticate fungal aDNA from stomach, small intestine, and large intestine samples. We revealed the presence ofPseudogymnoascusgenus, withP. destructansandP. verrucosusas possible species, that were particularly abundant in the stomach and small intestine. We suggest that Ötzi may have consumed these fungi accidentally, likely in association with other elements of his diet, and they thrived in his gut after his death due to their adaptability to harsh and cold environments. This research provides insight into the coexistence of ancient humans with specific fungal species and proposes and validates a conservative bioinformatic approach for detecting fungal aDNA in historical metagenomic samples.Significance statementDespite their essential interactions with all kingdoms of life, limited molecular studies have focused on ancient fungi. Here, we developed a thorough bioinformatic pipeline that allowed us to detect the presence of ancient DNA likely belonging toPseudogymnoascus destructansandP. verrucosusin the gut of Ötzi, a human naturally mummified over 3,000 years ago in the Tyrolean Alps. Both species can survive harsh environmental conditions, andP. destructansis known for its pathogenicity, suggesting that Ötzi may have accidentally ingested them and providing valuable insights into how ancient humans coexisted with specific fungal species. We propose a highly reliable methodology for detecting ancient fungal DNA in metagenomic studies of historical samples that can have broader applications to understand ancient ecosystems and their interactions.
Adaptation to complex environments reveals pervasive trade-offs and genomic targets with large pleiotropic effects
Authors: Rêgo Alexandre , Stajic Dragan , Bautista Carla , Rouot Sofia , de la Paz Celorio-Mancera Maria , Stelkens Rike 
Published: January 2024

AbstractPopulations in nature rarely adapt to a single stress at a time. Various biotic and abiotic factors come together to produce a complex environment to which populations must adapt. How populations adapt to multiple stressors simultaneously, and how trade-offs evolve between these stressors has been of interest to evolutionary biologists for decades. But natural populations often present logistical challenges to understanding the dynamics of evolution and isolating the genetic basis of adaptation. Here we use methods in experimental evolution to test how adaptation proceeds in the presence of co-occurring stressors, and to quantify the evolution of trade-offs between stressors in a complex environment. We adapted populations of the yeast Saccharomyces cerevisiae to a full-factorial combination of four stressors over the course of 15 serial transfers. We observed rapid increases in fitness paired with the accumulation of mutations related to specific stressors. Trade-offs evolved rapidly and dynamics of trade-off evolution varied between stressors, likely due to the inherent physiological and genetic basis of resistance to each stressor. The degree of parallelism at the phenotypic level showed evidence of being modified by the degree of environmental complexity, while parallelism at the genic level was apparent between populations which shared stressors.
Occurrence of non-apical mitoses at the primitive streak, induced by relaxation of actomyosin and acceleration of the cell cycle, contributes to cell delamination during mouse gastrulation
Authors: Despin-Guitard Evangéline , Plunder Steffen , Mathiah Navrita , Theveneau Eric , Migeotte Isabelle 
Published: January 2024

ABSTRACTDuring the epithelial-mesenchymal transition driving mouse embryo gastrulation, cells at the primitive streak divide more frequently that in the rest of the epiblast, and half of those divisions happen away from the apical pole. These observations suggests that non-apical mitoses might play a role in cell delamination and/or mesoderm specification. We aimed to uncover and challenge the molecular determinants of mitosis position in the different regions of the epiblast through a combination of computational modeling and pharmacological treatments of embryos.Blocking basement membrane degradation at the streak had no impact on the asymmetry in mitosis frequency and position. By contrast disturbance of actomyosin cytoskeleton or cell cycle dynamics elicited ectopic non-apical mitosis and showed that the streak region is characterized by local relaxation of the actomyosin cytoskeleton and less stringent regulation of cell division. These factors are essential for normal dynamics at the streak but are not sufficient to promote acquisition of mesoderm identity or ectopic cell delamination in the epiblast. Exit from the epithelium requires additional events, such as detachment from the basement membrane.Altogether, our data indicate that cell delamination at the streak is a morphogenetic process which results from a cooperation between EMT events and the local occurrence of non-apical mitoses driven by specific cell cycle and contractility parameters.
Kangaroo Mother Care prior to clinical stabilisation: Implementation barriers and facilitators reported by caregivers and health care providers in Uganda
Authors: Tumukunde Victor S. , Katongole Joseph , Namukwaya Stella , Medvedev Melissa M. , Nyirenda Moffat , Tann Cally J. , Seeley Janet , Lawn Joy E. 
Published: January 2024

AbstractKangaroo mother care (KMC) is an evidence-based method to improve newborn survival. However, scale-up even for stable newborns has been slow, with reported barriers to implementation. We examined facilitators and barriers to initiating KMC before stabilisation amongst neonates recruited to the OMWaNA study in Uganda.A qualitative sub-study was conducted during the OMWaNA randomized controlled trial examining the mortality effect of KMC prior to stabilisation amongst newborns (700-2000g). At the four trial site hospitals, focus group discussions (FGDs) were conducted with caregivers, and separately with healthcare providers and in-depth interviews (IDIs) with caregivers (admitted/recently discharged), and key informant interviews (KII) with hospital administrators/neonatal healthcare providers. The WHO Building Blocks was used to guide thematic analysis.Eight FGDs (4 caregivers, 4 healthcare workers), 41 caregiver IDIs (26 mothers, 8 grandmothers and 7 fathers) and 23 KIIs were conducted. Key themes based on the building blocks were family and community support and involvement, health workforce, medical supplies and commodities, infrastructure and design, financing, and health facility leadership. We found availability of an additional family member in the hospital, and support from healthcare workers, were facilitators for KMC before stability. The caregiver’s positive attitude towards KMC facilitated KMC practice but was impeded by the lack of knowledge on the benefits of KMC or how to perform it. Implementation barriers included: Fear of inadvertently causing harm to the newborn, inadequate space to perform KMC in the neonatal care unit and a limited number of trained healthcare workers coupled with insufficient medical supplies.In the Ugandan government hospital setting, the presence of a family member in the hospital, adequate provision of healthcare workers knowledgeable in supporting KMC prior to stability, and adequate space for KMC beds where neonatal care is being delivered, can enable implementation of KMC before stability.