bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal forebrain cholinergic circuits orchestrate diverse cell types in the adult dentate gyrus to support neural stem cell function and spatial memory
Authors: Quintanilla Luis , Su Yijing , Simon Jeremy M. , Luo Yan-Jia , Asrican Brent , Tart Seth , Sheehy Ryan N. , Li Ya-Dong , Ming Guo-li , Song Hongjun , Song Juan 
Published: May 2022

SummaryDentate gyrus (DG) is a critical structure involved in spatial memory and adult neurogenesis, two distinct processes dynamically regulated by local circuits comprising diverse populations of DG cells. It remains unknown how these DG cells are orchestrated to regulate these distinct hippocampal functions. Here we report activation of a cholinergic circuit from the Diagonal Band of Broca to DG promotes quiescent radial neural stem cell (rNSC) activation and spatial memory. Furthermore, single-nucleus RNA-sequencing reveals broad transcriptomic changes across DG mature and adult-born cells in response to cholinergic-circuit activation. Notably, neuronal populations exhibit cholinergic-activity-induced molecular changes related to synaptic functions crucial for spatial memory; while rNSCs exhibit changes related to structural remodeling and neurogenic proliferation crucial for hippocampal neurogenesis. Electrophysiology and NicheNet analyses reveal granule cells, endothelial cells, and astrocytes as potential intermediaries for cholinergic regulation of rNSCs. Our findings reveal cell-type-specific signaling mechanisms underlying cholinergic regulation of distinct DG functions.
Bayesian analyses of radiocarbon dates on rice reveal geographic variations in the rate of agricultural dispersal in prehistoric Japan
Authors: Crema Enrico R. , Stevens Chris J. , Shoda Shinya 
Published: May 2022

AbstractThe adoption of rice farming during the 1st millennium BC was a turning point in Japanese prehistory, defining the subsequent cultural, linguistic, genetic variation in the archipelago. Here we employ a suite of novel Bayesian techniques to estimate the regional rates of dispersal and arrival time of rice farming using radiocarbon dates on charred rice remains. Our results indicate substantial variations in the pace of agricultural adoption within the Japanese islands, hinting at the presence of a mixture of demic and cultural diffusion, geographic variations in the suitability of rice cultivation, as well as the possible role of existing social networks in facilitating or hindering the adoption of the new subsistence economy.TeaserThe adoption of rice farming in prehistoric Japan was characterised by regional episodes of slowdowns and accelerations.
Integrative metabolomics reveal the organisation of alkaloid biosynthesis in Daphniphyllum macropodum
Authors: Eljounaidi Kaouthar , Radzikowska Barbara , Whitehead Caragh , Conde Susana , Davis William , Dowle Adam , Langer Swen , Larson Tony , Unsworth William P. , Ezer Daphne , Lichman Benjamin R. 
Published: May 2022

AbstractDaphniphyllum alkaloids are structurally diverse nitrogen-containing compounds with polycyclic, stereochemically rich carbon skeletons. Understanding how plants biosynthesise these compounds may lead to greater access to allow exploration of bioactivities; however, very little is known about their biosynthetic origins. Here, we integrated metabolomics approaches to map alkaloid distribution across Daphniphyllum macropodum plants and tissues. We generated a novel untargeted metabolomics workflow to highlight trends in alkaloid distribution across tissues, using a holistic approach that does not rely on ambiguous peak annotations. Both liquid-chromatography-mass spectrometry and mass-spectrometry imaging analyses independently revealed that alkaloids have a pattern of spatial distribution based on their skeletal subtypes. The distinct alkaloid subtype localisation suggests the biosynthetic pathway is controlled spatially with intermediates transported from the phloem to the epidermis where they undergo additional derivatization. This study sets the stage for the future work on Daphniphyllum alkaloid biosynthesis and highlights how integrating different metabolomics strategies can reveal valuable insights on these compounds’ distribution within the plant.
ADOPT: intrinsic protein disorder prediction through deep bidirectional transformers
Authors: Redl Istvan , Fisicaro Carlo , Dutton Oliver , Hoffmann Falk , Henderson Louie , Owens Benjamin M.J. , Heberling Matthew , Paci Emanuele , Tamiola Kamil 
Published: May 2022

ABSTRACTIntrinsically disordered proteins (IDP) are important for a broad range of biological functions and are involved in many diseases. An understanding of intrinsic disorder is key to develop compounds that target IDPs. Experimental characterization of IDPs is hindered by the very fact that they are highly dynamic. Computational methods that predict disorder from the amino acid sequence have been proposed. Here, we present ADOPT, a new predictor of protein disorder. ADOPT is composed of a self-supervised encoder and a supervised disorder predictor. The former is based on a deep bidirectional transformer, which extracts dense residue level representations from Facebook’s Evolutionary Scale Modeling (ESM) library. The latter uses a database of NMR chemical shifts, constructed to ensure balanced amounts of disordered and ordered residues, as a training and test dataset for protein disorder. ADOPT predicts whether a protein or a specific region is disordered with better performance than the best existing predictors and faster than most other proposed methods (a few seconds per sequence). We identify the features which are relevant for the prediction performance and show that good performance can already gained with less than 100 features. ADOPT is available as a standalone package athttps://github.com/PeptoneLtd/ADOPT.
Rapid and precise genome engineering in a naturally short-lived vertebrate
Authors: Nath Ravi D. , Bedbrook Claire N. , Nagvekar Rahul , Deisseroth Karl , Brunet Anne 
Published: May 2022

AbstractThe African turquoise killifish is a powerful vertebrate system to study complex phenotypes at scale, including aging and age-related disease. Here we develop a rapid and precise CRISPR/Cas9-mediated knock-in approach in the killifish. We show its efficient application to precisely insert fluorescent reporters of different sizes at various genomic loci, to drive cell-type- and tissue-specific expression. This knock-in method should allow the establishment of humanized disease models and the development of cell-type-specific molecular probes for studying complex vertebrate biology.
Obesity-Associated Alterations in Lung Function in Mice Measured with Head-Out Plethysmography
Authors: Bruggink Stephanie M , Pederson William P , Kentch Kyle P , Kronenfeld Jason M , Ledford Julie G , Renquist Benjamin J 
Published: May 2022

AbstractDeclines in lung function worsen quality of life and increase the risk of mortality. Obesity and non-alcoholic fatty liver disease are associated with worsened lung function. To investigate this association, we assessed lung function in lean and diet-induced obese conscious mice using our newly developed leak-free head-out plethysmography system. Obesity was associated with increased volume (P<0.0001), minute ventilation (volume per minute; P<0.0001), mid-expiratory flow (flow rate at 50% expiratory volume; P<0.0001), end-inspiratory pause (pause at end of inspiration; P<0.0001) and decreased expiratory time (P<0.0001). We next compared the response to methacholine (0, 25, 50, 100 mg/ml in PBS flow 0.2ml/30sec) measured using our head-out plethysmography system with forced oscillation technique (using the standard flexiVent system) measures taken in the same mice. Many of the measures gathered using head-out plethysmography were associated with measures collected using the forced oscillation technique. Minute ventilation was most significantly associated with maximal airway resistance, maximal airway elastance, tissue damping, and tissue elastance (r=-0.59 P<0.0001; r=-0.54 P<0.005; r=-0.48 P<0.005; r=-0.40 P<0.005 respectively). Volume, corrected for energy expenditure, was most significantly associated with maximal resistance of the conducting airways (r=-0.57 P<0.0001). Although fatty liver is associated with changes in lung function, we found neither hepatic vagotomy nor knocking down obesity-induced hepatic GABA production improved lung function in obese mice. Still, our head-out plethysmography system is ideal for assessing the response to interventions aimed at improving obesity-associated declines in lung function.
UNDESRTANDING MESENCHYMAL STEM CELL IMMUNE POTENCY: A MORPHOLOMIC AND LIPIDOMIC PERSPECTIVE
Authors: Priyadarshani Priyanka , DeVeaux S’Dravious , Leitmann Bobby , Rui Kejie , Botchwey Edward A , Mortensen Luke J. 
Published: May 2022

AbstractInterest in human mesenchymal stem cells (MSCs) as an immune therapy has been on the rise for the past two decades with cutting edge research yielding promising results, but there are currently no MSC therapies approved by the food and drug administration (FDA). Failure of MSCs to translate as a therapy has been reported by the National Cell Manufacturing Consortium (NCMC) to be due to a lack of reliable potency metrics and sufficient understanding of the mechanism of action. Here we show that cell membrane components are a good candidate to interrogate the MSC immunomodulatory mechanism of action and provide a method to increase MSC potency through the sphingolipid pathway. We found that high and low indolamine-2,3-deoxygenase (IDO) potency cells have distinct morphological signatures that is also reflected in the sphingolipid activity, with low IDO potency cell lines having low sphingomyelinase activity and high IDO potency cell lines having high sphingomyelinase activity. Perturbation of the salvage pathway with the addition of exogenous neutral sphingomyelinase not only shifted morphological signatures to a high potency profile, but also significantly increased IDO activity within both high and low IDO potency donors. These results provide a proof of concept for the engineering of MSC immunomodulation and provides further evidence for the role sphingolipids in MSC immunomodulation that can enable further investigation.
PervasiveListeria monocytogenesare common in the Norwegian food system and associated with increased prevalence of stress survival and resistance determinants
Authors: Fagerlund Annette , Wagner Eva , Møretrø Trond , Heir Even , Moen Birgitte , Rychli Kathrin , Langsrud Solveig 
Published: May 2022

AbstractTo investigate the diversity, distribution, persistence, and prevalence of stress survival and resistance genes ofListeria monocytogenesclones dominating in food processing environments in Norway, genome sequences from 769L. monocytogenesisolates from food industry environments, foods, and raw materials (of which 512 were sequenced in the present study) were subjected to wgMLST, SNP, and comparative genomic analyses. The dataset comprised isolates from nine meat and six salmon processing facilities in Norway collected over a period of three decades. The most prevalent clonal complex (CC) was CC121, found in ten factories, followed by CC7, CC8, and CC9, found in seven factories each. Overall, 72% of the isolates were classified as persistent, showing 20 or fewer wgMLST allelic differences towards an isolate found in the same factory in a different calendar year. Moreover, over half of the isolates (56%) showed this level of genetic similarity towards an isolate collected from a different food processing facility. These were designated as pervasive strains, defined as clusters with the same level of genetic similarity as persistent strains but isolated from different factories. The prevalence of genetic determinants associated with increased survival in food processing environments, including heavy metal and biocide resistance determinants, stress response genes andinlAtruncation mutations, showed a highly significant increase among pervasive isolates, but not among persistent isolates. Furthermore, these genes were significantly more prevalent among the isolates from food processing environments compared to in isolates from natural and rural environments (n=218) and clinical isolates (n=111) from Norway.ImportanceListeria monocytogenescan persist in food processing environments for months to decades and spread through the food system by e.g., contaminated raw materials. Knowledge about the distribution and diversity ofL. monocytogenesis of importance in outbreak investigations and essential to effectively track and control this pathogen in the food system. The current study presents a comprehensive overview of the prevalence of persistent clones and of the diversity ofL. monocytogenesin Norwegian food processing facilities. The results demonstrate extensive spread of highly similar strains throughout the Norwegian food system, in that 56% of the 769 collected isolates from food processing factories belonged to clusters ofL. monocytogenesidentified in more than one facility. These strains were associated with an overall increase in the prevalence of plasmids and determinants of heavy metal and biocide resistance as well as other genetic elements associated with stress survival mechanisms and persistence.
Shared within-host SARS-CoV-2 variation in households
Authors: Walter Katharine S. , Kim Eugene , Verma Renu , Altamirano Jonathan , Leary Sean , Carrington Yuan J. , Jagannathan Prasanna , Singh Upinder , Holubar Marisa , Subramanian Aruna , Khosla Chaitan , Maldonado Yvonne , Andrews Jason R. 
Published: May 2022

AbstractBackgroundThe limited variation observed among SARS-CoV-2 consensus sequences makes it difficult to reconstruct transmission linkages in outbreak settings. Previous studies have recovered variation within individual SARS-CoV-2 infections but have not yet measured the informativeness of within-host variation for transmission inference.MethodsWe performed tiled amplicon sequencing on 307 SARS-CoV-2 samples from four prospective studies and combined sequence data with household membership data, a proxy for transmission linkage.ResultsConsensus sequences from households had limited diversity (mean pairwise distance, 3.06 SNPs; range, 0-40). Most (83.1%, 255/307) samples harbored at least one intrahost single nucleotide variant (iSNV; median: 117; IQR: 17-208), when applying a liberal minor allele frequency of 0.5% and prior to filtering. A mean of 15.4% of within-host iSNVs were recovered one day later. Pairs in the same household shared significantly more iSNVs (mean: 1.20 iSNVs; 95% CI: 1.02-1.39) than did pairs in different households infected with the same viral clade (mean: 0.31 iSNVs; 95% CI: 0.28-0.34), a signal that increases with increasingly liberal thresholds.ConclusionsAlthough only a subset of within-host variation is consistently shared across likely transmission pairs, shared iSNVs may augment the information in consensus sequences for predicting transmission linkages.
High Intelligence is not a Risk Factor for Mental Health Disorders
Authors: Michèle Williams Camille , Peyre Hugo , Labouret Ghislaine , Fassaya Judicael , Guzmán García Adoración , Gauvrit Nicolas , Ramus Franck 
Published: May 2022

AbstractObjectiveStudies reporting that highly intelligent individuals have more mental health disorders often have sampling bias, no or inadequate control group, or insufficient sample size. We addressed these caveats by examining the difference in the prevalence of mental health disorders between individuals with high and average general intelligence (g-factor) in the UK Biobank.MethodsParticipants with general intelligence (g-factor) scores standardized relative to the same-age UK population, were divided into 2 groups: a high g-factor group (g-factor 2 SD above the UK mean; N=16,137) and an average g-factor group (g-factor within 2 SD of the UK mean; N=236,273). Using self-report questionnaires and medical diagnoses, we examined group differences in prevalence across 32 phenotypes, including mental health disorders, trauma, allergies, and other traits.ResultsHigh and average g-factor groups differed across 15/32 phenotypes and did not depend on sex and/or age. Individuals with high g-factors had less general anxiety (OR=0.69) and PTSD (OR=0.67), were less neurotic (β=-0.12), less socially isolated (OR=0.85), and were less likely to have experienced childhood stressors and abuse, adulthood stressors, or catastrophic trauma (OR=0.69-0.90). They did not differ in any other mental health disorder or trait. However, they generally had more allergies (e.g., eczema; OR=1.13-1.33).ConclusionsThe present study provides robust evidence that highly intelligent individuals have no more mental health disorders than the average population. High intelligence even appears as a protective factor for general anxiety and PTSD.Key PointsQuestionAre high IQ individuals at increased risk of mental health disorders?FindingsIn the UK Biobank (N ≃ 7,266 - 252,249), highly intelligent individuals (2SD above the population mean) were less likely to suffer from general anxiety and PTSD, and no more likely to have depression, social anxiety, a drug use disorder, eating disorders, obsessive-compulsive disorder, bipolar disorder, and schizophrenia.MeaningContrary to popular belief, high intelligence is not a risk factor for psychiatric disorders and even serves as a protective factor for general anxiety and PTSD.
The relationship between the prevalence and severity of Non-suicidal self-injury (NSSI) and personality traits among Chinese junior high school students
Authors: Jiang Zhongliang , Wang Zhiyi , Zhao Miao , He Long , He Qiang , Cheng Xiaojing , Chen Jie , Tian Geng , Li Xianbin , Haider Muhammad Imran , Liu Jintong 
Published: May 2022

AbstractBackgroundNon-suicidal self-injury (NSSI) is more common in adolescents and its occurrence may be influenced by personality traits. Children and adolescents are a high-risk group for NSSI. Although there are some studies on the prevalence of NSSI, however, there are fewer studies on the factors associated with the severity of NSSI and the specific causes of the influence of NSSI and personality traits.MethodsParticipants of this study were junior high school students enrolled in three different schools of a Chinese province. NSSI was evaluated using the Adolescents Self-Harm Scale and their personality traits were assessed using the Neuroticism Extraversion Openness Five-factor Inventory (NEO-FFI).Results2376 junior high school students participated, and the annual incidence of NSSI was 37.1% (n=881). The mean age of the NSSI-detected individuals was 13.61 years (SD=1.017). Out of total number of detections, 56.6% (n=499) were female and 67.4% (n=594) were individuals who self-injured using multiple means. Hair pulling, scratching the skin, and whacking harder objects with the hand were the most common modes of NSSI, with incidences of 51.0%, 43.0%, and 42.8% respectively in the NSSI-detected population. There was a negative association between grade and NSSI severity (p < 0.05), and NSSI was more severe in females. The scores in the Neuroticism dimension were higher in the group with NSSI than in the group without NSSI, while the scores in the extraversion, openness, agreeableness and conscientiousness dimensions were lower than in the group without NSSI (p < 0.01). Neuroticism and openness were significantly positively correlated with NSSI severity, and extraversion, agreeableness, conscientiousness were significantly negatively correlated with NSSI severity (p < 0.01).ConclusionThe severity of NSSI was relatively higher in lower grades among junior grades and females, and the number of self-injury using multiple means was significantly higher; hair pulling, skin scratching and whacking harder objects with hands were the most common NSSI modalities. Among the personality traits, for the incidence of NSSI, high neuroticism was a risk factor, and high extraversion, openness, agreeableness, and conscientiousness were protective factors. For the severity of NSSI, high neuroticism and high openness were risk factors, and high extraversion, high agreeableness, and high conscientiousness were protective factors.
Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance
Authors: Fazakerley Daniel J. , van Gerwen Julian , Cooke Kristen C. , Duan Xiaowen , Needham Elise J. , Madsen Søren , Norris Dougall M. , Shun-Shion Amber S. , Krycer James R. , Burchfield James G. , Yang Pengyi , Wade Mark R. , Brozinick Joseph T. , James David E. , Humphrey Sean J. 
Published: May 2022

AbstractThe failure of metabolic tissues to appropriately respond to insulin (“insulin resistance”) is an early marker in the pathogenesis of type 2 diabetes. Protein phosphorylation is central to the adipocyte insulin response, but how adipocyte signaling networks are dysregulated upon insulin resistance is unknown. Here we employed phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults triggering insulin resistance, we observed marked rewiring of the insulin signaling network. This included both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying signaling changes common to multiple insults revealed subnetworks likely containing causal drivers of insulin resistance. Focusing on defective GSK3 signaling initially observed in a relatively small subset of well-characterized substrates, we employed a pipeline for identifying context-specific kinase substrates. This facilitated robust identification of widespread dysregulated GSK3 signaling. Pharmacological inhibition of GSK3 partially reversed insulin resistance in cells and tissue explants. These data highlight that insulin resistance is a multi-nodal signaling defect that encompasses dysregulated GSK3 activity.
Development of Non-invasive ABPP-BRET Platform Technology Enable Real-Time Detection of Post-Translational Modification and Target Engagement with Absolute Specificity in Living Systems
Authors: Bathla Punita , Mujawar Aaiyas , De Abhijit , Sandanaraj Britto S 
Published: May 2022

AbstractNon-invasive, real-time, longitudinal imaging of protein functions in living systems with unprecedented specificity is one of the critical challenges of modern biomedical research. Despite several advancements, it is estimated that nearly 35% of the human proteome is not completely characterized. Therefore, the development of new technologies is imperative for shining more light on so-called “dark proteomes”. Towards that goal, here we report a platform fusion technology called activity-based protein profiling-bioluminescence resonance energy transfer (ABPP-BRET). This method provides an opportunity to study the post-translational modification of a target protein in real-time in living systems in a longitudinal manner with a high spatio-temporal resolution. This semi-synthetic BRET biosensor method is used for target engagement studies and further for inhibitor profiling in live cells. The simplicity of this method coupled with the critical physical distance dependent BRET read-out turned out to be a powerful method, thus pushing the activity-based protein profiling technology to the next level.