bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Mucosal-Associated Invariant T (MAIT) cell function and expansion with human selective serum
Authors: Labuz Daniel , Cacioppo Jackson , Li Kelin , Aubé Jeffrey , Leung Daniel T. 
Published: October 2022

AbstractMucosal-associated invariant T (MAIT) cells are promising innate-like lymphocytes with potential for use in anti-tumor immunotherapy. Existing MAIT cell expansion protocols are associated with potentially decremental phenotypic changes, including increased frequency of CD4+ MAIT cells and higher inhibitory receptor expression. In this study, we compared the effect on expansion of human MAIT cells of a serum replacement, Physiologix XF SR (Phx), with traditional serum fetal bovine serum (FBS) for supplementing RPMI-1640 media. Using flow cytometry, we found that Phx supported a significantly higher proliferative capacity for MAIT cells and resulted in a lower frequency of CD4+ MAIT cells, which have been associated with reduced Th1 effector and cytolytic functions. We saw that culturing MAIT cells in Phx led to better survival of MAIT cells and lower frequency of PD-1+ MAIT cells compared to FBS-supplemented media. Functionally, we saw that Phx supplementation was associated with a higher frequency of IFN-γ+ MAIT cells after stimulation withE. colicompared to FBS-supplemented RPMI. In conclusion, we show that MAIT cells cultured in Phx have higher proliferative capacity, lower expression of inhibitory receptors, and have higher capacity to produce IFN-γ afterE. colistimulation, compared to FBS-supplemented RPMI. This work shows that expanding MAIT cells with Phx compared to FBS-supplemented RPMI result in a more functionally desirable MAIT cell for future anti-tumor immunotherapy.
Developing a standardized but extendable framework to increase the findability of infectious disease datasets
Authors: Tsueng Ginger , Alvarado Cano Marco A. , Bento José , Czech Candice , Kang Mengjia , Pache Lars , Rasmussen Luke V. , Savidge Tor C. , Starren Justin , Wu Qinglong , Xin Jiwen , Yeaman Michael R. , Zhou Xinghua , Su Andrew I. , Wu Chunlei , Brown Liliana , Shabman Reed S. , Hughes Laura D. ,   the NIAID Systems Biology Data Dissemination Working Group
Published: October 2022

AbstractBiomedical datasets are increasing in size, stored in many repositories, and face challenges in FAIRness (findability, accessibility, interoperability, reusability). As a Consortium of infectious disease researchers from 15 Centers, we aim to adopt open science practices to promote transparency, encourage reproducibility, and accelerate research advances through data reuse. To improve FAIRness of our datasets and computational tools, we evaluated metadata standards across established biomedical data repositories. The vast majority do not adhere to a single standard, such asSchema.org, which is widely-adopted by generalist repositories. Consequently, datasets in these repositories are not findable in aggregation projects like Google Dataset Search. We alleviated this gap by creating a reusable metadata schema based onSchema.organd catalogued nearly 400 datasets and computational tools we collected. The approach is easily reusable to create schemas interoperable with community standards, but customized to a particular context. Our approach enabled data discovery, increased the reusability of datasets from a large research consortium, and accelerated research. Lastly, we discuss ongoing challenges with FAIRness beyond discoverability.
The Genome of the WaspAnastatus disparisReveals Energy Metabolism Adaptations for Extreme Aggression
Authors: Liu Pengcheng , Wang Ziyin , Tao Yumei , Yin Siyu , Wei Jianrong , Wang Jianjun , Hu Haoyuan 
Published: October 2022

AbstractExtremely aggressive behavior is rare in most species, as contestants can be severely injured or killed. Such high level of aggression can evolve when critical resources are limited, as the benefits of winning outweigh the potential costs of conflict. Currently, studies of extreme aggression are mainly from the perspectives of behavioral ecology and evolutionary biology, displaying distinct results from common nonextreme aggression. Here, we provide a high-quality genome of the generalist endoparasitoidAnastatus disparis, the males of which exhibit extreme mate-competition aggression, to shed light on possible genomic adaptations for extreme aggressive behavior. We combined Nanopore PromethION sequencing with Hi-C technology to assemble a high-quality chromosome-level genome ofA. disparis. The size of the genome of this species (939.58 Mb) is larger than that of most hymenopterans (ranging from 180 Mb to 340 Mb) due to the expansion of repeated sequences (612.90 Mb, 65.23% of the whole genome). With the aid of RNA sequencing, 19,246 protein-coding genes were identified, and a great expansion of genes involved in detoxification was detected, which could represent an adaptation of this species to exploit a diverse range of known hosts. The integrated multiomics analysis highlighted genes involved in energy metabolism (especially from lipids) and antibacterial activity, both of which are possibly major aspects of adaptation for extreme aggression inA. disparis. Our study provides insight into molecular and evolutionary studies of extreme aggression inA. disparisand provides a valuable genomic resource for further research into the molecular basis of trait evolution in Hymenoptera.
A Cre-Driver Rat Model for Anatomical and Functional Analysis of Glucagon(Gcg)-Expressing Cells in the Brain and Periphery
Authors: Zheng Huiyuan , López-Ferreras Lorena , Krieger Jean-Phillipe , Fasul Stephen , Salazar Valentina Cea , Pena Natalia Valderrama , Skibicka Karolina P. , Rinaman Linda 
Published: October 2022

ABSTRACTObjectiveThe glucagon gene (Gcg) encodes preproglucagon, which is cleaved to form glucagon-like peptide 1 (GLP1) and other mature signaling molecules implicated in metabolic functions. To date there are no transgenic rat models available for precise manipulation of GLP1-expressing cells in the brain and periphery.MethodsTo visualize and manipulateGcg-expressing cells in rats, CRISPR/Cas9 was used to expressiCreunder control of theGcgpromoter. Gcg-Cre rats were bred with tdTomato reporter rats to tagGcg-expressing cells. Cre-dependent AAVs and RNAscopein situhybridization were used to evaluate the specificity ofiCreexpression by GLP1 neurons in the caudal nucleus of the solitary tract (cNTS) and intermediate reticular nucleus (IRt), and by intestinal and pancreatic secretory cells. Food intake was assessed in heterozygous (Het) Gcg-Cre rats after chemogenetic stimulation of cNTS GLP1 neurons expressing an excitatory DREADD.ResultsWhile genotype has minimal effect on body weight or composition in chow-fed Gcg-Cre rats, homozygous (Homo) rats have lower plasma glucose levels. In neonatal and adult Gcg-Cre/tdTom rats, reporter-labeled cells are present in the cNTS and IRt, and in additional brain regions (e.g., basolateral amygdala, piriform cortex) that lack detectableGcgmRNA in adults but display transient developmental or persistently lowGcgexpression. Compared to wildtype (WT) rats, hindbrainGcgmRNA and GLP1 protein in brain and plasma are markedly reduced in Homo Gcg-Cre rats. Chemogenetic stimulation of cNTS GLP1 neurons reduced overnight chow intake in males but not females, the effect in males was blocked by antagonism of central GLP1 receptors, and hypophagia was enhanced when combined with a subthreshold dose of cholecystokinin-8 to stimulate gastrointestinal vagal afferents.ConclusionsGcg-Cre rats are a novel and valuable experimental tool for analyzing the development, anatomy, and function ofGcg-expressing cells in the brain and periphery. In addition, Homo Gcg-Cre rats are a unique model for assessing the role ofGcg-encoded proteins in glucose homeostasis and energy metabolism.HighlightsA transgenic Gcg-Cre rat model expressesiCreunder control of theGcgpromoteriCreis expressed by GLP1-positive cells in the hindbrain, pancreas, and intestineAdditional brain regions display transient and/or very low levels ofGcgexpression+/+ Gcg-Cre rats display a marked knockdown ofGcgmRNA and GLP1 proteinChemogenetic activation ofGcgneurons suppresses food intake in +/- Gcg-Cre rats
The establishment and transmission of novel foraging techniques indicates a capacity for culture in bumblebees (Bombus terrestris)
Authors: Bridges Alice D. , MaBouDi HaDi , Procenko Olga , Lockwood Charlotte , Mohammed Yaseen , Kowalewska Amelia , Romero González José Eric , Woodgate Joseph L. , Chittka Lars 
Published: October 2022

AbstractThe astonishing behavioural repertoires of social insects have been thought largely innate, but these insects have repeatedly demonstrated remarkable capacities for both individual and social learning. Using the bumblebeeBombus terrestrisas a model, we developed a two-option puzzle box task and used open diffusion paradigms to observe the transmission of novel, non-natural foraging behaviours through populations. Box-opening behaviour spread through colonies seeded with a demonstrator trained to perform one of the two possible behavioural variants, and the observers acquired the demonstrated variant. This preference persisted among observers even when the alternative technique was discovered. In control diffusion experiments that lacked a demonstrator, some bees spontaneously opened the puzzle boxes but were significantly less proficient than those that learned in the presence of a demonstrator. This suggested that social learning was crucial to proper acquisition of box-opening. Additional open diffusion experiments where two behavioural variants were initially present in similar proportions ended with a single variant becoming dominant, due to stochastic processes. This could lead to the emergence and maintenance of local cultural variation. These results suggest that bumblebees, like mammals and birds, may have the capacity for culture and to sustain cultural variation.
Annoying noise: effect of anthropogenic underwater sound on the movement and feeding performance in the red cherry shrimp,Neocaridina davidi
Authors: Azarm-Karnagh Sasan , Lopez Greco Laura , Shafiei Sabet Saeed 
Published: October 2022

AbstractAcoustic pollution in aquatic environments has increased dramatically, with adverse effects on many organisms. Benthic organisms, including many invertebrates, can sense underwater sounds, yet the responses they trigger in these organisms have received little attention. This study investigates the impact of underwater sound on the behaviour of the red cherry shrimpNeocaridina davidias a model of freshwater decapod. The effect of underwater sound exposure on the movement behaviour and feeding performance of individual shrimps was assessed. Movement speed decreased significantly upon opening the divider in both the sound and control treatments. However, there were no significant changes in total minutes between the control and sound treatments, implying no sound-related initial changes for releasing movement. The spatial distribution of shrimps in response to the sound treatment showed significant changes; shrimps spent more time at the farthest point from the sound source. The time to find the food source (latency) also increased in the sound treatment compared to the control. Moreover, in terms of the number of successes and failures in finding the food source in the control treatment, significantly more shrimps succeeded in finding the food source. Besides, the number of revisits to the food source decreased in sound treatment compared to control and more shrimps were significantly distracted in sound treatment. Our study highlights the crustacean’s ability to receive human-made sound. Thus, they are prone to the impacts of anthropogenic sound, causing negative impacts on their movement-swimming activities, and feeding behaviour and exposing them to potential predator threats. Affecting foraging performance in this gregarious species may have detrimental impacts on their reproductive success and, subsequently unexpected fitness consequences.
Inferring disease architecture and predictive ability with LDpred2-auto
Authors: Privé Florian , Albiñana Clara , Arbel Julyan , Pasaniuc Bogdan , Vilhjálmsson Bjarni J. 
Published: October 2022

AbstractLDpred2 is a widely used Bayesian method for building polygenic scores (PGS). LDpred2-auto can infer the two parameters from the LDpred model, the SNP heritabilityh2and polygenicityp, so that it does not require an additional validation dataset to choose best-performing parameters. The main aim of this paper is to properly validate the use of LDpred2-auto for inferring multiple genetic parameters. Here, we present a new version of LDpred2-auto that adds an optional third parameterαto its model, for modeling negative selection. We then validate the inference of these three parameters (or two, when using the previous model). We also show that LDpred2-auto provides per-variant probabilities of being causal that are well calibrated, and can therefore be used for fine-mapping purposes. We also derive a new formula to infer the out-of-sample predictive performancer2of the resulting PGS directly from the Gibbs sampler of LDpred2-auto. Finally, we extend the set of HapMap3 variants recommended to use with LDpred2 with 37% more variants to improve the coverage of this set, and show that this new set of variants captures 12% more heritability and provides 6% more predictive performance, on average, in UK Biobank analyses.
OPTIMIZED NEURON TRACING USINGPOST HOCREANALYSIS
Authors: Azzouz Sara , Walker Logan A , Doerner Alexandra , Geisel Kellie L. , Rodríguez Rivera Arianna K. , Li Ye , Roossien Douglas H , Cai Dawen 
Published: October 2022

ABSTRACTOver the last decade, the advances in Brainbow labeling allowed labeling hundreds of neurons with distinct colors in the same field of view of a brain [1, 2]. Reconstruction (or “tracing”) of the 3D structures of these images has been enabled by a growing set of software tools for automatic and manual annotation. It is common, however, to have errors introduced by heuristics used by tracing software, namely that they assume the “best” path is the highest intensity one, a more pertinent issue when dealing with multicolor microscope images. Here, we reportnCorrect, an algorithm for correcting this error by reanalyzing previously created neuron traces to produce more physiologically-relevant ones. Specifically, we use a four dimensional minimization algorithm to identify a more-optimal reconstruction of the image, allowing us to better take advantage of existing manual tracing results. We define a new metric (hyperspectral cosine similarity) for describing the similarity of different neuron colors to each other. Our code is available in an open source license and forms the basis for future improved neuron tracing software.
Effects of parental verbal abuse experience on the Glutamate response to swear words in the ventromedial prefrontal cortex: A functional1H-magnetic resonance spectroscopy study
Authors: Yoo Jae Hyun , Park Young Woo , Kim Dohyun , Park HyunWook , Jeong Bumseok 
Published: October 2022

AbstractSeveral lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established in humans. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23±4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC.A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. Furthermore, the total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words (ΔGluSw e). The interaction term of ΔGluSw eand baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between ΔGluSw ein the AMHC and either pVAQ or emotional states.We conclude that parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.
A suberized exodermis is required for tomato drought tolerance
Authors: Cantó-Pastor Alex , Kajala Kaisa , Shaar-Moshe Lidor , Manzano Concepción , Timilsena Prakash , De Bellis Damien , Gray Sharon , Holbein Julia , Yang He , Mohammad Sana , Nirmal Niba , Suresh Kiran , Ursache Robertas , Mason G. Alex , Gouran Mona , West Donnelly A. , Borowsky Alexander T. , Shackel Kenneth A. , Sinha Neelima , Bailey-Serres Julia , Geldner Niko , Li Song , Franke Rochus Benni , Brady Siobhan M. 
Published: October 2022

SUMMARYPlant roots integrate environmental signals and developmental programs using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates the entry and exit of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation, but we find that it is absent in the tomato endodermis during normal development. Instead, suberin is present in the exodermis, a cell type that is absent in the model organismArabidopsis thaliana. Here, we uncover genes driving exodermal suberization and describe its effects on drought responses in tomato, unravelling the similarities and differences with the paradigmatic Arabidopsis endodermis. Cellular resolution imaging, gene expression, and mutant analyses reveal loss of this program from the endodermis, and its co-option in the exodermis. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response. Controlling the degree of exodermal suberization could be a new strategy for breeding climate-resilient plants.
The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study
Authors: Liu Junxi , Richmond Rebecca C , Anderson Emma L , Bowden Jack , Barry Ciarrah-Jane S , Dashti Hassan S , Daghlas Iyas S , Lane Jacqueline M , Kyle Simon D , Vetter Céline , Morrison Claire L , Jones Samuel E , Wood Andrew R , Frayling Timothy M , Wright Alison K , Carr Matthew J , Anderson Simon G , Emsley Richard A , Ray David W , Weedon Michael N , Saxena Richa , Rutter Martin K , Lawlor Deborah A 
Published: October 2022

AbstractStudy ObjectivesSelf-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar results observed in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other sleep traits, on glycated haemoglobin (HbA1c). Our aims were a) to explore potential effects of accelerometer-derived sleep traits on HbA1c and glucose levels and b) to determine genetic correlations across accelerometer-derived and self-reported sleep traits.MethodsWe used MR methods to explore effects of accelerometer-derived sleep traits (duration, mid-point least active 5-hours, mid-point most active 10-hours, sleep fragmentation, and efficiency) on HbA1c in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 149,054). Cross-trait linkage disequilibrium score regression was also applied to determine genetic correlations across all accelerometer-derived and self-reported sleep traits and HbA1c/glucose.ResultsMain and sensitivity MR analyses showed no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure.ConclusionsTaken together, these findings suggested accelerometer-derived sleep traits do not causally affect HbA1c levels, and accelerometer-derived measures of sleep duration and sleep quality might not simply be ‘objective’ measures of self-reported sleep duration and insomnia, but rather captured different underlying sleep characteristics.Statement of SignificanceSelf-reported and accelerometer-derived sleep disturbance is associated with increased risk of hyperglycaemia and type 2 diabetes in observational analyses. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other self-reported sleep traits, on glycated haemoglobin (HbA1c). This MR study showed little evidence supporting an effect of any accelerometer-derived sleep trait on HbA1c or glucose, but a potential non-linear (e.g., U-shaped) effect cannot be ruled out. The genetic correlation suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different exposures.
Test-retest reliability of functional connectivity in depressed adolescents
Authors: Camp Chris C. , Noble Stephanie , Scheinost Dustin , Stringaris Argyris , Nielson Dylan M. 
Published: October 2022

ABSTRACTThe test-retest reliability of fMRI functional connectivity is a key factor in the identification of reproducible biomarkers for psychiatric illness. Low reliability limits the observable effect size of brain-behavior associations. Despite this important connection to clinical applications of fMRI, few studies have explored reliability in populations with psychiatric illnesses or across age groups. We investigate the test-retest reliability of functional connectivity in a longitudinal cohort of adolescents with and without major depressive disorder (MDD). Measuring reliability is complex and several metrics exist that can offer unique perspectives: for example, univariate metrics capture reliability of a single connection at a time while multivariate metrics reflect stability of the entire connectome. We compare a widely used univariate metric, intraclass correlation coefficient (ICC), and two multivariate metrics, fingerprinting and discriminability. Depressed adolescents were more reliable than healthy adolescents at the univariate level (0.34 > 0.24; Wilcoxon rank-sum:p< .001), and both groups had poor average ICCs (<0.4). Multivariate reliability was high in both groups: fingerprinting (FIHV= 0.53; FIMDD= 0.45; Poisson(1) testp< .001) and discriminability were above chance (DiscrHV= 0.75;DiscrMDD= 0.76; 500-fold permutation testp< .01). Reliability was not associated with symptoms or medication, suggesting that there is not a strong relationship between depression and reliability. These findings support the shift towards multivariate analysis for improved power and reliability.