bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microhabitat use of northern and southern flying squirrels in a recent hybrid zone
Authors: O’Brien Paul P , Bowman Jeff , Newar Sasha , Garroway Colin J 
Published: May 2023

AbstractSecondary contact of closely related species may lead to hybridization if reproductive isolation is incomplete. Selection against hybrids may become reinforced if hybrid fitness is low. This can be evident from the divergence of isolating traits. We examined habitat use of northern (Glaucomys sabrinus(Shaw, 1801)) and southern (Glaucomys volans(Linnaeus, 1758)) flying squirrels in an area of secondary contact in Ontario, Canada. We looked at summer microhabitat use within sites of sympatry and allopatry to test for evidence of reinforcement due to diverging habitat use. We also examined differences in broad-scale habitat features at woodlots to determine predictors of species occurrence across sites. We used 18 years (2002 - 2019) of flying squirrel summer capture data from 6 sites along a north-south transect. Vegetation surveys were conducted at trap locations during summer 2016 to characterize the available microhabitats within sites. Site-level habitat variables were calculated using the collected microhabitat variables. We found microhabitat variables to be weak predictors of trap-level flying squirrel presence and we found no evidence of divergence in microhabitat use over the 18 years. Further, we found latitude, not broad-scale habitat, was the strongest predictor of site-level flying squirrel occurrence. Overall, our findings suggest that microhabitat-based isolation is not being reinforced between flying squirrels; however, hybridization may be limited to areas where climate and habitat is suitable for both species.
Signaling mechanisms and agricultural applications of (Z)-3-Hexenyl Butyrate-mediated stomatal closure
Authors: Payá Celia , Belda-Palazón Borja , Vera-Sirera Francisco , Pérez-Pérez Julia , Jordá Lucía , Rodrigo Ismael , Bellés José M , López-Gresa M Pilar , Lisón Purificación 
Published: May 2023

AbstractBiotic and abiotic stresses can severely limit crop productivity. In response to drought, plants close stomata to prevent water loss. Besides, stomata are considered the main entrance of several pathogens. Therefore, the development of natural products to control stomata closure can be considered a sustainable strategy to cope with stresses in agriculture. Plants respond to different stresses by releasing volatile organic compounds (VOCs). Green leaf volatiles (GLVs), which are commonly produced across different plant species after tissue damage, comprise an important group within VOCs. Among them, (Z)-3-hexenyl butyrate (HB) was described as a natural inducer of stomatal closure, playing an important role in stomatal immunity, although its mechanism of action is still unknown. Here, through different genetic, pharmacological, and biochemical approaches, we uncover that HB perception initiates various defense signaling events such as activation of Ca2+permeable channels, mitogen-activated protein kinases (MPKs) and production of NADPH oxidase-mediated reactive oxygen species (ROS). Furthermore, HB-mediated stomata closure resulted to be independent of abscisic acid (ABA) biosynthesis and signaling. Additionally, exogenous treatments with HB alleviate water stress and improve fruit productivity in tomato plants. The efficacy of HB was also tested under open field conditions, leading to enhanced resistance againstPhytophthoraspp. andPseudomonas syringaeinfection in potato and tomato plants, respectively. Taken together, our results provide insights into HB signaling transduction pathway, confirming its role in stomatal closure and plant immune system activation, and proposing HB as a new phytoprotectant for the sustainable control of biotic and abiotic stresses in agriculture.
No Replication of Direct Neuronal Activity-related (DIANA) fMRI in Anesthetized Mice
Authors: Choi Sang-Han , Im Geun Ho , Choi Sangcheon , Yu Xin , Bandettini Peter A. , Menon Ravi S. , Kim Seong-Gi 
Published: May 2023

AbstractToi et al. (Science, 378, 160-168, 2022) reported direct imaging of neuronal activity (DIANA) by fMRI in anesthetized mice at 9.4 T, which could be a revolutionary approach for advancing systems neuroscience research. There have been no independent replications of this observation to date. We performed fMRI experiments in anesthetized mice at an ultrahigh field of 15.2 T using the identical protocol as in their paper. The BOLD response to whisker stimulation was reliably detected in the primary barrel cortex before and after DIANA experiments; however, no direct neuronal activity-like fMRI peak was observed in individual animals’ data with the 50–300 trials used in the DIANA publication. Extensively averaged data involving 1,050 trials in 6 mice (1,050×54 = 56,700 stimulus events) and having a temporal signal-to-noise ratio of 7,370, showed a flat baseline and no detectable neuronal activity-like fMRI peak. Thus we were unable to replicate the previously reported results using the same methods, despite a much higher number of trials, a much higher temporal signal-to-noise ratio, and a much higher magnetic field strength. We were able to demonstrate spurious, non-replicable peaks when using a small number of trials. It was only when performing the inappropriate approach of excluding outliers not conforming to the expected temporal characteristics of the response did we see a clear signal change; however, these signals were not observed when such a outlier elimination approach was not used.
Compositional analysis of microbiome data using the linear decomposition model (LDM)
Authors: Hu Yi-Juan , Satten Glen A. 
Published: May 2023

AbstractSummaryThere are compelling reasons to test compositional hypotheses about microbiome data. We present here LDM-clr, an extension of our linear decomposition model (LDM) approach to allow fitting linear models to centered-log-ratio-transformed taxa count data. As LDM-clr is implemented within the existing LDM program, it enjoys all the features supported by LDM, including a compositional analysis of differential abundance at both the taxon and community levels, while allowing for a wide range of covariates and study designs for either association or mediation analysis.Availability and ImplementationLDM-clr has been added to the R package LDM, which is available on GitHub athttps://github.com/yijuanhu/LDM.Contactyijuan.hu@emory.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Biochemical, biomarker, and behavioral characterization of theGrnR493Xmouse model of frontotemporal dementia
Authors: Smith Denise M. , Aggarwal Geetika , Niehoff Michael L. , Jones Spencer A. , Banerjee Subhashis , Farr Susan A. , Nguyen Andrew D. 
Published: May 2023

ABSTRACTHeterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, theGrnR493Xmouse model has not been characterized completely. Additionally, while homozygousGrnR493XandGrnknockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygousGrnR493Xknockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygousGrnR493Xmice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. HeterozygousGrnR493Xmice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits inGrnR493Xmice that mirror those observed inGrnknockout mouse models, as well as impairment in memory and executive function. Overall, theGrnR493Xknockin mouse model closely phenocopiesGrnknockout models. Lastly, in contrast to homozygous knockin mice, heterozygousGrnR493Xmice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use thisGrnknockin mouse model and otherGrnknockout models.
Pseudouridine guides germline small RNA transport and epigenetic inheritance
Authors: Herridge Rowan P , Dolata Jakub , Migliori Valentina , de Santis Alves Cristiane , Borges Filipe , Schorn Andrea J , Van Ex Frédéric , Parent Jean-Sebastien , Lin Ann , Bajczyk Mateusz , Leonardi Tommaso , Hendrick Alan , Kouzarides Tony , Martienssen Robert A 
Published: May 2023

SummaryEpigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes1. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation2,3. InC. elegans, these inherited small RNAs have poly (UG) tails4, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop novel assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse andArabidopsismicroRNAs and their precursors. We also detect substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) inArabidopsispollen, and piwi-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are localized to sperm cells, and we found thatPAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that Exportin-t is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.One-Sentence SummaryPseudouridine marks germline small RNAs in plants and mammals, impacting epigenetic inheritance via nuclear transport.
Multiple myeloma long-term survivors display sustained immune alterations decades after first line therapy
Authors: Lutz Raphael , Grünschläger Florian , Simon Malte , Bauer Marcus , Yousefian Schayan , Beumer Niklas , Jopp-Saile Lea , Awwad Mohamed H.S. , Steinbuss Georg , Sedlmeier Anastasia , Boch Tobias , Vonficht Dominik , Baertsch Marc-Andrea , Durie Brian G.M. , Weinhold Niels , Raab Marc S. , Wickenhauser Claudia , Trumpp Andreas , Müller-Tidow Carsten , Hübschmann Daniel , Brors Benedikt , Goldschmidt Hartmut , Imbusch Charles D. , Hundemer Michael , Haas Simon 
Published: May 2023

AbstractThe long-term consequences of cancer or cancer therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we have performed an in-depth characterization of the bone marrow ecosystem of multiple myeloma long-term survivors at initial diagnosis and up to 17 years following cancer-free survival. Using comparative single-cell analyses in combination with molecular, genomic and functional approaches, we demonstrate that multiple myeloma long-term survivors display pronounced alterations in their bone marrow microenvironment associated with impaired immunity. These immunological alterations were frequently driven by an inflammatory immune circuit fueled by the long-term persistence or resurgence of residual myeloma cells. Notably, even in the complete absence of any detectable residual disease for decades, sustained changes in the immune system were observed, suggesting an irreversible ‘immunological scarring’ caused by the initial exposure to the cancer and therapy. Collectively, our study provides key insights into the molecular and cellular bone marrow ecosystem of multiple myeloma long-term survivors, revealing reversible and irreversible alterations of the immune compartment, which can serve as diagnostic and predictive tools.Statement of significanceLarge-scale single-cell profiling of a unique cohort of multiple myeloma long-term survivors uncovered that exposure to cancer and its treatment causes both reversible and irreversible immune alterations associated with impaired immunity. These findings have far-reaching implications for the understanding of long-term immune alterations in cancer, which need to be considered also in the context of immune therapeutic approaches. Furthermore, our study demonstrates how cancer-associated immune trafficking can be used to predict disease re-initiation in the bone marrow, opening new avenues for minimally invasive disease monitoring.
autoStreamTree: Genomic variant data fitted to geospatial networks
Authors: Chafin Tyler K. , Mussmann Steven M. , Douglas Marlis R. , Douglas Michael E. 
Published: May 2023

ABSTRACTSummaryLandscape genetics is a statistical framework that parses genetic variation within the context of spatial covariates, but current analytical methods typically fail to accommodate the unique topologies and autocorrelations inherent to network-configured habitats (e.g., streams or rivers). autoStreamTree analyzes and visualizes genome-wide variation across dendritic networks (i.e., riverscapes).Availability and ImplementationautoStreamTree is an open source workflow (https://github.com/tkchafin/autostreamtree) that automatically extracts a minimal graph representation of a geospatial network from a provided shapefile, then ‘fits’ the components of genetic variation using a least-squares algorithm. To facilitate downstream population genomic analyses, genomic variation can be represented per-locus, per-SNP, or via microhaplotypes (i.e., phased data). We demonstrate the workflow by quantifying genetic variation in Speckled Dace (Rhinichthys osculus)versusenvironmental covariates, with putative adaptive variants subsequently identified.Contacttyler.chafin@bioss.ac.uk
Dual-color GRAB sensors for monitoring spatiotemporal serotonin releasein vivo
Authors: Deng Fei , Wan Jinxia , Li Guochuan , Dong Hui , Xia Xiju , Wang Yipan , Li Xuelin , Zhuang Chaowei , Zheng Yu , Liu Laixin , Yan Yuqi , Feng Jiesi , Zhao Yulin , Xie Hao , Li Yulong 
Published: May 2023

AbstractThe serotonergic system plays important roles in both physiological and pathological processes, and is a widely used therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB5-HT) sensors and developed a new red fluorescent GRAB5-HTsensor. These sensors have excellent cell surface trafficking, high specificity, sensitivity, and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamicsin vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both physiological and pathological states.
Does the Wim Hof Method have a beneficial impact on physiological and psychological outcomes in healthy and non-healthy participants? A systematic review
Authors: Almahayni Omar , Hammond Lucy 
Published: May 2023

AbstractIntroduction:Wim Hof, also known as the iceman, developed a method called Wim Hof Method which he claims to have several benefits on physical and mental health. The aim of this systematic review is to identify and synthesise the results of the studies conducted on Wim Hof Method on physiological and psychological health-related outcomes.Materials and Methods:Medline and Web of Science were searched. Studies were included if they met the predetermined inclusion/exclusion criteria. Data extraction and quality assessment were performed on the included studies. The effects of Wim Hof Method were categorised into physiological or psychological related outcomes and narrative synthesis was conducted.Results:Nine papers were included in this review which consisted of eight individual trials. The findings of this systematic review suggest that the Wim Hof Method may affect the reduction of inflammation in healthy and non-healthy participants as it increases epinephrine levels, causing an increase in interleukin-10 and a decrease in pro-inflammatory cytokines. Additionally, Wim Hof breathing method was suggested to not enhance the performance of an exercise as minute ventilation, tidal volume, and breathing frequency were statistically insignificant.Conclusion:Taken together, the findings of this review show promising use of Wim Hof Method in the inflammatory response category. The focus of future studies should move away from investigating the use of Wim Hof breathing method to enhance exercise performance and towards exploring the benefits of Wim Hof Method in non-healthy participants with inflammatory disorders.
Pattern-centric transformation of omics-data sources grounded on multi-wise gene associations aids predictive tasks in TCGA while ensuring interpretability
Authors: Patrício André , Costa Rafael S. , Henriques Rui 
Published: May 2023

AbstractMotivationThe increasing prevalence of omics data sources is pushing the study of regulatory mechanisms underlying complex diseases such as cancer. However, the vast quantities of features produced and the inherent interplay between them lead to a level of complexity that hampers both descriptive and predictive tasks, requiring custom-built algorithms that can extract relevant information from these sources of data.ResultsWe propose a transformation that moves data centered on molecules (e.g. transcripts and proteins) to a new data space focused on putative regulatory modules given by statistically relevant patterns of coexpression. The proposed transformation extracts patterns from the data through biclustering and uses them to create new variables with guarantees of interpretability and discriminative power. The transformation is shown to achieve dimensionality reductions of up to 99% and to increase the predictive performance of various classifiers across multiple omics layers. Our results suggest that a transformation of omics data from gene-centric to pattern-centric data provides benefits to both prediction tasks and human interpretation. The proposed approach is expected to greatly support further bioinformatic analyses for precision medicine applications.AvailabilitySoftware code and the raw results generated are available atgithub.com/Andrempp/Pattern-Centric-Transformation.Contactandremppatricio@tecnico.ulisboa.ptSupplementary informationSupplementary data are available atJournal Nameonline.
Imaging the microscopic viscoelastic anisotropy in living cells
Authors: Keshmiri Hamid , Cikes Domagoj , Samalova Marketa , Schindler Lukas , Appel Lisa-Marie , Urbanek Michal , Yudushkin Ivan , Slade Dea , Weninger Wolfgang J. , Peaucelle Alexis , Penninger Josef , Elsayad Kareem 
Published: May 2023

AbstractMaintaining and modulating the mechanical anisotropy is essential for biological processes. How this is achieved on the microscopic scale in living soft matter is however not always clear. Here we introduce Brillouin Light Scattering Anisotropy Microscopy (BLAM) for mapping the high-frequency viscoelastic anisotropy inside living cells. Following proof-of-principle experiments on muscle myofibers, we apply this to study two fundamental biological processes. In plant cell walls we show how a phase-transition driven switch between anisotropic-isotropic wall properties may lead to asymmetric growth. In mammalian cell nuclei we uncover a spatio-temporally oscillating elastic anisotropy correlated to chromatin condensation, with long range orientational correlations that may provide a dynamic framework for coordinating intra-nuclear processes. Our results highlight the direct and indirect role the high-frequency mechanics can play in providing dynamic structure that lead to the regulation of diverse fundamental processes in biological systems, and offer a means for studying these. BLAM should find diverse biomedical and material characterization applications.
Adaptor protein complex 2 in the orbitofrontal cortex predicts alcohol use disorder
Authors: Mulholland Patrick J. , Berto Stefano , Wilmarth Phillip A. , McMahan Christopher , Ball Lauren E. , Woodward John J. 
Published: May 2023

ABSTRACTAlcohol use disorder (AUD) is a life-threatening disease characterized by compulsive drinking, cognitive deficits, and social impairment that continue despite negative consequences. The inability of individuals with AUD to regulate drinking may involve functional deficits in cortical areas that normally balance actions that have aspects of both reward and risk. Among these, the orbitofrontal cortex (OFC) is critically involved in goal-directed behavior and is thought to maintain a representation of reward value that guides decision making. In the present study, we analyzed post-mortem OFC brain samples collected from age- and sex-matched control subjects and those with AUD using proteomics, bioinformatics, machine learning, and reverse genetics approaches. Of the 4,500+ total unique proteins identified in the proteomics screen, there were 47 proteins that differed significantly by sex that were enriched in processes regulating extracellular matrix and axonal structure. Gene ontology enrichment analysis revealed that proteins differentially expressed in AUD cases were involved in synaptic and mitochondrial function, as well as transmembrane transporter activity. Alcohol-sensitive OFC proteins also mapped to abnormal social behaviors and social interactions. Machine learning analysis of the post-mortem OFC proteome revealed dysregulation of presynaptic (e.g., AP2A1) and mitochondrial proteins that predicted the occurrence and severity of AUD. Using a reverse genetics approach to validate a target protein, we found that prefrontalAp2a1expression significantly correlated with voluntary alcohol drinking in male and female genetically diverse mouse strains. Moreover, recombinant inbred strains that inherited the C57BL/6J allele at theAp2a1interval consumed higher amounts of alcohol than those that inherited the DBA/2J allele. Together, these findings highlight the impact of excessive alcohol consumption on the human OFC proteome and identify important cross-species cortical mechanisms and proteins that control drinking in individuals with AUD.