bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive profiling of transcription factors in postmortem brains defines genomic occupancy in disease-relevant cell types and links TF activities to neuropsychiatric disorders
Authors: Loupe Jacob M. , Anderson Ashlyn G. , Rizzardi Lindsay F. , Rodriguez-Nunez Ivan , Moyers Belle , Trausch-Lowther Katie , Jain Rashmi , Bunney William E. , Bunney Blynn G. , Cartagena Preston , Sequeira Adolfo , Watson Stanley J. , Akil Huda , Cooper Gregory M. , Myers Richard M. 
Published: June 2023

AbstractTranscription factors (TFs) orchestrate gene expression programs crucial for cell physiology, but our knowledge of their function in the brain is limited. Using bulk tissues and sorted nuclei from multiple human post-mortem brain regions, we generated a multi-omic resource (1121 total experiments) that includes binding maps for more than 100 TFs. We demonstrate improved measurements of TF activity, including motif recognition and gene expression modeling, upon identification and removal of regions of high TF occupancy. Further, we find that predictive TF binding models demonstrate a bias for these high occupancy sites. Neuronal TFs SATB2 and TBR1 bind unique regions depleted for such sites and promote neuronal gene expression. Several TFs, including TBR1 and PKNOX1, are enriched for risk variants associated with neuropsychiatric disorders, predominantly in neurons. These data are a powerful resource for future studies seeking to understand the role of TFs in epigenetic regulation in the human brain.
Coordinated wound responses in a regenerative animal-algal photosymbiotic metaorganism
Authors: Sarfati Dania Nanes , Xue Yuan , Song Eun Sun , Byrne Ashley , Le Daniel , Darmanis Spyros , Quake Stephen R. , Burlacot Adrien , Sikes James , Wang Bo 
Published: June 2023

AbstractAnimal regeneration requires coordinated responses of many cell types throughout the animal body. In animals carrying endosymbionts, cells from the other species may also participate in regeneration, but how cellular responses are integrated across species is yet to be unraveled. Here, we study the acoelConvolutriloba longifissura, which hosts symbioticTetraselmisgreen algae and can regenerate entire bodies from small tissue fragments. We show that animal injury leads to a decline in the photosynthetic efficiency of the symbiotic algae and concurrently induces upregulation of a cohort of photosynthesis-related genes. A deeply conserved animal transcription factor,runt, is induced after injury and required for the acoel regeneration. Knockdown ofruntalso dampens algal transcriptional responses to the host injury, particularly in photosynthesis related pathways, and results in further reduction of photosynthetic efficiency post-injury. Our results suggest that therunt-dependent animal regeneration program coordinates wound responses across the symbiotic partners and regulates photosynthetic carbon assimilation in this metaorganism.
Ex vivoquantification of anti-tumor T-cell activity upon anti-PD-1 treatment in patient-derived lung tumor-on-chip
Authors: Veith Irina , Mencattini Arianna , Nurmik Martin , Damei Isabelle , Lansche Christine , Brosseau Solenn , Gropplero Giacomo , Corgnac Stéphanie , Filippi Joanna , Poté Nicolas , Mordant Pierre , Tosello Jimela , Sedlik Christine , Piaggio Eliane , Girard Nicolas , Camonis Jacques , Shirvani Hamasseh , Mami-Chouaib Fathia , Mechta-Grigoriou Fatima , Descroix Stéphanie , Martinelli Eugenio , Zalcman Gérard , Parrini Maria Carla 
Published: June 2023

ABSTRACTThere is a compelling need for new approaches to predict efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate immune and stromal characteristics of a simplified tumor ecosystem. Here, we present the development and validation of lung-tumor-on-chip platforms to quickly and precisely measureex vivothe effects of immune check-point inhibitors on T-cell-mediated cancer cell death, by exploiting the power of live imaging and advanced image analysis algorithms. These tumor-on-chips were generated with patient-derived autologous primary cells isolated from fresh lung cancer samples, opening the path for applications in personalized medicine. Moreover, cancer-associated fibroblasts were shown to impair the response to anti-PD-1, indicating that tumor-on-chips are capable of recapitulating stroma-dependent mechanisms of immunotherapy resistance. This interdisciplinary combination of microfluidic devices, clinically-relevant cell models, and advanced computational methods, can innovatively improve both the fundamental understanding and clinical efficacy of immuno-oncology drugs.
SCFFBXW11complex targets interleukin-17 receptor A for ubiquitin-proteasome-mediated degradation
Authors: Jin Ben , Moududee Sayed Ala , Ge Dongxia , Zhou Pengbo , Wang Alun R. , Liu Yao-Zhong , You Zongbing 
Published: June 2023

AbstractInterleukin-17 (IL-17) is a pro-inflammatory cytokine, participating in innate and adaptive immune responses, that plays an important role in host defense, autoimmune diseases, tissue regeneration, metabolic regulation, and tumor progression. Post-translational modifications (PTMs) are crucial for protein function, stability, cellular localization, cellular transduction, and cell death. However, PTMs of IL-17 receptor A (IL-17RA) have not been investigated. Here, we showed that human IL-17RA was targeted by F-box and WD repeats domain containing 11 (FBXW11) for ubiquitination, followed by proteasome-mediated degradation. We used bioinformatics tools and biochemical techniques to determine that FBXW11 ubiquitinated IL-17RA through a lysine 27-linked polyubiquitin chain, targeting IL-17RA for proteasomal degradation. Domain 665-804 of IL-17RA was critical for interaction with FBXW11 and subsequent ubiquitination. Our study demonstrates that FBXW11 regulates IL-17 signaling pathways at IL-17RA level.
Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice
Authors: Liu Joyce , Lustberg Daniel J. , Galvez Abigail , Liles L. Cameron , McCann Katharine E. , Weinshenker David 
Published: June 2023

AbstractIn rodents, exposure to predator odors such as cat urine acts as a severe stressor that engages innate defensive behaviors critical for survival in the wild. The neurotransmitters norepinephrine (NE) and dopamine (DA) modulate anxiety and predator odor responses, and we have shown previously that dopamine β-hydroxylase knockout (Dbh -/-), which reduces NE and increases DA in mouse noradrenergic neurons, disrupts innate behaviors in response to mild stressors such as novelty. We examined the consequences ofDbhknockout (Dbh -/-) on responses to predator odor (bobcat urine) and compared them to Dbh-competent littermate controls. Over the first 10 min of predator odor exposure, controls exhibited robust defensive burying behavior, whereasDbh -/-mice showed high levels of grooming. Defensive burying was potently suppressed in controls by drugs that reduce NE transmission, while excessive grooming inDbh -/-mice was blocked by DA receptor antagonism. In response to a cotton square scented with a novel “neutral” odor (lavender), most control mice shredded the material, built a nest, and fell asleep within 90 min.Dbh -/-mice failed to shred the lavender-scented nestlet, but still fell asleep. In contrast, controls sustained high levels of arousal throughout the predator odor test and did not build nests, whileDbh -/-mice were asleep by the 90-min time point, often in shredded bobcat urine-soaked nesting material. Compared with controls exposed to predator odor,Dbh -/-mice demonstrated decreased c-fos induction in the anterior cingulate cortex, lateral septum, periaqueductal gray, and bed nucleus of the stria terminalis, but increased c-fos in the locus coeruleus and medial amygdala. These data indicate that relative ratios of central NE and DA signaling coordinate the type and valence of responses to predator odor.
Scalable phylogenetic Gaussian process models improve the detectability of environmental signals on extinction risks for many Red List species
Authors: Matsuba Misako , Fukasawa Keita , Aoki Satoshi , Akasaka Munemitsu , Ishihama Fumiko 
Published: June 2023

Abstract1. Conservation biologists have a daunting task of understanding the causes of species decline associated with anthropogenic factors and predicting the extinction risk of a growing number of endangered species. By stabilising estimates with information on closely related species, phylogenetic information among species can bridge gaps in information on species with small sample sizes when modelling large numbers of endangered species. However, modelling many species with the Gaussian process (GP), which underlies the evolutionary process of phylogenetic random effects, remains a challenge owing to the computational burden in estimating the large variance–covariance matrix.2. Here, we applied a phylogenetic generalised mixed model with random slopes and random intercepts to 1,010 endangered vascular plant taxa in Japan following phylogenetic GPs implemented by nearest neighbour GP (NNGP) approximation. NNGP enables flexibility in changing the proximity on the phylogenetic tree of species from which information is borrowed to stabilise parameter estimates with a realistic computational burden. We evaluated the effectiveness of phylogenetic models by comparing the predictive performance and descriptive power of phylogenetic and non-phylogenetic models and identified the anthropogenic factors contributing to the decline of each of the studied endangered species.3. We found that the model with phylogenetic information had better prediction performance than the model without phylogenetic information. The results showed that across all explanatory variables, the phylogenetic model could detect interspecific differences in response to environmental factors in a number of species more clearly. Combined with the phylogenetic signal results, we could also detect a phylogenetic bias in the species that could benefit from the positive effects of protected areas but reduce the extinction risk of 95% of all studied taxa.4. In conclusion, our model, considering phylogenetic information with NNGP, allows the elucidation of factors causing the decline of many endangered species. In future analyses, the estimation of extinction probability linked to environmental change using such modelling might be applied to future climate–land use scenarios, advancing the comprehensive assessment of biodiversity degradation and threats to species at multiple scales.
The role of relatedness within a neighborhood in plant-to-plant interaction: effect on height growth and rust damage inPopulus nigra
Authors: Tiret Mathieu , Sánchez Leopoldo , Lascoux Martin 
Published: June 2023

AbstractThe competitive ability of domesticated plants, which may have conferred a fitness advantage in the wild, may result in a reduction of yield in agricultural and forestry contexts, as what matters is the group rather than the individual performance. Traits related to competitive ability can be affected by the presence or absence of related individuals in their neighborhood. Consequently, local relatedness might reveal plant-to-plant interaction that can enhance the predictive abilities of genomic models when accounted for, though it remains difficult to measure. To overcome this difficulty, we analyzed data from the French breeding program ofPopulus nigraL., where 1,452 genotypes were replicated six to eight times, each time encountering a different neighborhood. We assessed local relatedness and investigated genomic estimated breeding values on tree height and vulnerability to rust with a single-step GBLUP incorporating local relatedness as a covariate. The results indicate that incorporating local relatedness as an additional factor in GBLUP models has a significantly greater influence on resistance to rust than on tree height, though its overall effect on genomic predictions themselves was limited. The influence of local relatedness is small but likely trait-specific, and the genetic architecture of the trait under selection could attenuate or improve the efficacy of breeding for group performance.
CRISPR/Cas9 generatedMeSWEET10amutants show reduced susceptibility to cassava bacterial blight and produce viable seed
Authors: Elliott Kiona , Veley Kira M. , Jensen Greg , Gilbert Kerrigan B. , Norton Joanna , Kambic Lukas , Yoder Marisa , Weil Alex , Motomura-Wages Sharon , Bart Rebecca S. 
Published: June 2023

AbstractBacteria from the genusXanthomonasare prolific phytopathogens that elicit disease in over 400 plant species. Xanthomonads carry a repertoire of specialized proteins called transcription activator-like (TAL) effectors that promote disease and pathogen virulence by inducing expression of host susceptibility (S) genes.Xanthomonas phaseolipv.manihotis(Xpm) causes bacterial blight on the staple food crop, cassava. The Xpm effector, TAL20, induces ectopic expression of the S gene,MeSWEET10a, a sugar transporter that contributes to cassava bacterial blight susceptibility. We used CRISPR/Cas9 to generate multiple cassava lines with edits to theMeSWEET10aTAL20 effector binding site and/or coding sequence. In several of the regenerated lines,MeSWEET10aexpression was no longer induced byXpmand in these cases, we observed reduced cassava bacterial blight disease symptoms post Xpm infection.MeSWEET10ais expressed in cassava flowers. Therefore, we investigated flower development and reproductive function in anMeSWEET10amutant line. We found that theMeSWEET10amutant produced phenotypically wildtype cassava flowers and viable F1 seed. Thus, blockingMeSWEET10ainduction is a viable strategy for decreasing cassava susceptibility to CBB.
Omics Scale Quantitative Mass Spectrometry Imaging of Lipids in Brain Tissue using a Multi-Class Internal Standard Mixture
Authors: Vandenbosch Michiel , Mutuku Shadrack M. , Mantas Maria José Q. , Patterson Nathan H. , Hallmark Tucker , Claesen Marc , Heeren Ron M. A. , Hatcher Nathan G. , Verbeeck Nico , Ekroos Kim , Ellis Shane R. 
Published: June 2023

AbstractMass spectrometry imaging (MSI) has accelerated the understanding of lipid metabolism and spatial distribution in tissues and cells. However, few MSI studies have approached lipid imaging quantitatively and those that have focus on a single lipid class. Herein, we overcome limitation of quantitative MSI (Q-MSI) by using a multi-class internal standard lipid mixture that is sprayed homogenously over the tissue surface with analytical concentrations that reflects endogenous brain lipid levels. Using this approach we have performed Q-MSI for 13 lipid classes representing >200 sum-composition lipid species. This was carried out using both MALDI (negative ion mode) and MALDI-2 (positive ion mode) and pixel-wise normalisation of each lipid species signal to the corresponding class-specific IS an approach analogous to that widely used for shotgun lipidomics from biological extracts. This approach allows pixel concentrations of lipids to be reported in pmol/mm2. Q-MSI of lipids covered 3 orders of magnitude in dynamic range and revealed subtle change sin in distribution compared to conventional total-ion-current normalisation approaches. The robustness of the method was evaluated by repeating experiments in two laboratories on biological replicates using both timsTOF and Orbitrap mass spectrometers operated with a ~4-fold difference in mass resolution power. There was a strong overall correlation in the Q-MSI result obtained using the two approaches with outliers mostly rationalised by isobaric interferences that are only resolved with the Orbitrap system or the higher sensitivity of one instrument for particular lipid species, particularly for lipids detected at low intensity. These data provide insight into how mass resolving power can affect Q-MSI data. This approach opens up the possibility of performing large-scale Q-MSI studies across numerous lipid classes and reveal how absolute lipid concentrations vary throughout and between biological tissues.
Design and Evaluation of an Affordable Hypoxic Chamber with Comprehensive Environmental Control for Research Applications
Authors: Roshan Syed Aasish , Jayachandran Swaminathan K , Kandasamy Mahesh , Anusuyadevi Muthuswamy 
Published: June 2023

AbstractPurposeIn-vivo Hypoxia chamber is sought after for research on sleep apnea, among others. Recently hypoxia chambers are utilized to create intermittent hypoxia, thereby utilizing it as a treatment strategy. The commonly used Invivo hypoxic chambers only monitor oxygen levels and fail to read up on vital factors like CO2 buildup, and humidity among others. In addition, these devices are expensive and make them unaffordable for many labs.MethodsHere we report a lab-designed and assembled Arduino microcontroller-based hypoxic chamber with automatic maintenance of O2 level, CO2 level, and Humidity. The entire 650$ setup is inclusive of an Arduino module with sensors for oxygen, CO2, humidity, pressure, and temperature. A detailed software program was also written to help efficiently carry out the parameters set out for use.ResultsThe equipment is capable of automatically regulating the inner environment based on the set parameters. The combined cluster of regulators, efficiently controlled the oxygen levels, CO2 levels, and humidity levels within the experimental parameters.ConclusionThis equipment thus acts as one of the easily reproducible simple assembly units with the integration of complex parameters, thus monitoring and controlling the inner environment with high precision.
PROTOCOL OF A SYSTEMATIC REVIEW AND METAANALYSIS OF CASE-SERIES AND CASE-REPORTS INVOLVING GLUCAGON IN BETA-BLOCKER OVERDOSE
Authors: Domene Ramón Aranda , Esteban-Blanes Alberto 
Published: June 2023

AbstractThe utility of glucagon in human myocardium remains controversial. In the past, some articles have reported inotropic and chronotropic effects of glucagon on the heart, but other studies have found no significant effects. The main cardiovascular indication for glucagon is beta-blocker toxicity (BB), which is listed as recommendation IIb in some guidelines on the basis of some experimental studies and case reports. To our knowledge, no systematic review has been published analyzing the outcomes of glucagon in reports of overdose. This study will attempt to incorporate findings from case series and reports to fill the gap on a topic where experimental and comparative studies have already been conducted. A protocol to the development of this work is provided.
Patient-centered approaches for family planning counseling and support: A systematic review
Authors: Meekers Dominique , Elkins Aaron , Obozekhai Vivian 
Published: June 2023

AbstractBackgroundThis paper identifies how patient-centered family planning care has been defined, conceptualized, and measured, describes tools to make family planning care more patient-centered, and discusses their impact on patient satisfaction and family planning outcomes.MethodsWe systematically searched PubMed and SCOPUS for documents on “patient-centered family planning counseling or support” published between 2013 and 2022. Eligibility criteria included discussion of 1) a strategy for providing patient-centered care, 2) an intervention that used a patient- centered approach, or 3) evidence of the impact of patient-centered approaches. We excluded documents that only recommended using patient-centered approaches. To assess how studies conceptualized patient-centered care, we reviewed how the concept was measured. We identified tools for patient-centered care, and mapped them against the main domains of patient-centered care. We reported the available evidence of the impact on those tools without further statistical analysis.ResultsOur review is based on 33 documents, including three theoretical articles and three systematic reviews. Nine studies addressed women’s experiences with family planning counseling, five discussed instruments for measuring the patient-centeredness of care, ten discussed tools for patient-centered family planning, and three discussed broader counseling programs.We identified important differences in how patient-centered family planning care was defined and measured, although most studies emphasized patients’ needs and preferences, respect for the patient, and informed decision-making. We identified six tools for increasing the patient-centeredness of family planning counseling. None of the tools addressed all domains of patient-centered care. Evidence about the impact of these tools is scarce. Overall, the tools appeared well accepted by both providers and patients. There was some evidence that the tools improved patients’ perception about the quality of care, but no evidence that the tools improved family planning outcomes.DiscussionLimitations of our study include that our search was restricted to two databases, and that the studies predominantly focused on Western countries which may limit the generalizability of the findings. Wider use of existing scales to measure patient-centered family planning care may help standardize the definition of patient-centered care and strengthen the evidence base. Although tools for patient-centered care improve the patient experience, there is a need to identify strategies for translating this into improved family planning outcomes. In addition, there is a need to test patient- centered approaches in a wider range of settings.
Cryptic bacterial pathogens of diatoms peak during senescence of a winter diatom bloom
Authors: Branscombe Laura , Harrison Ellen L. , Daniel Choong Zhi Yi , Keys Matthew , Widdicombe Claire , Wilson William H. , Cunliffe Michael , Helliwell Katherine 
Published: June 2023

AbstractDiatoms are globally abundant algae that form extensive blooms in aquatic ecosystems. Certain bacteria behave antagonistically towards diatoms, killing or inhibiting their growth. Despite their crucial implications to diatom health and bloom control, insight of the prevalence and dynamics of antagonistic bacteria in nature is lacking. We report an ecosystem assessment of the diversity and seasonal patterns of bacterial antagonists of diatoms via regular plaque-assay sampling in the Western English Channel (WEC), where diatoms frequently bloom. Unexpectedly, peaks in antagonist detection did not occur during characteristic spring blooms, but coincided with a winter bloom ofCoscinodiscus, suggesting bacterial pathogens likely influence distinct diatom host populations. We isolated multiple antagonists, spanning 4 classes and 10 bacterial orders. Many species had no prior reports of pathogenicity towards diatoms, and we verified diatom growth inhibitory effects of 8 isolates. In all cases tested, pathogenicity was activated by pre-exposure to diatom organic matter. Discovery of widespread ‘cryptic’ antagonistic activity evident under specific conditions, indicates that bacterial pathogenicity towards diatoms is more prevalent than previously recognised. Finally, miningTaraOceans data revealed the global biogeography of WEC antagonists and co-occurrence patterns with diatom hosts. Our study indicates that multiple, diverse antagonistic bacteria have potential to impact diatom growth and bloom dynamics in marine waters globally.