bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extraction Optimization, Characterization, and Antioxidant Capacity of Phenolics from Cowpeas (Vigna Unguiculata)
Authors: Webber Daniel M. , Hettiarachchy Navam S. , Horax Ronny 
Published: October 2022

ABSTRACTEthanol-water extraction of phenolics from cowpeas was modeled and optimized by response surface methodology (RSM). The ethanol concentration and extraction temperature were shown to have a significant effect on phenolic extraction and antioxidant capacity. Modeling predicted that extraction of phenolics from cowpea flour for 42.8 minutes at 58.6°C with 58.4% ethanol would maximize the radical scavenging capacity of solutes. Extraction of phenolics under these optimized conditions yielded 11.05 ± 0.10 mg chlorogenic acid equivalents (CAE)/g cowpea flour. These extracts contained 10.41 % ± 0.11% phenolics by weight and had an antioxidant capacity of 0.45 ± 0.02, closely approximating the predicted phenolic content of 10.11% ± 0.44% and antioxidant capacity of 0.42 ± 0.04. Extracted material was characterized by HPLC, and the predominant phenolic compounds detected were epicatechin and ferulic acid. Cowpea’s low cost, ease of storage, and high antioxidant capacity reflect their potential for use as a naturally-derived antioxidant additive in foods.
The role of consciously timed movements in shaping and improving auditory timing
Authors: De Kock Rose , Zhou Weiwei , Datta Poorvi , Joiner Wilsaan Mychal , Wiener Martin 
Published: October 2022

AbstractOur subjective sense of time is intertwined with a plethora of perceptual, cognitive, and motor functions, and likewise, the brain is equipped to expertly filter, weight, and combine these signals for seamless interactions with a dynamic world. Until relatively recently, the literature on time perception has excluded the influence of motor activity, yet, it has been found that motor circuits in the brain are at the core of most timing functions. Several studies have now identified that concurrent movements exert robust effects on perceptual timing estimates, but critically, have not assessed how humans consciously judge the duration of their own movements. This creates a gap in our understanding of the mechanisms driving movement-related effects on sensory timing. We sought to address this gap by administering a sensorimotor timing task in which we explicitly compared the timing of isolated auditory tones and arm movements, or both simultaneously. We contextualized our findings within a Bayesian cue combination framework, in which separate sources of temporal information are weighted by their reliability and integrated into a unitary time estimate that is more precise than either unisensory estimate. Our results revealed differences in accuracy between auditory, movement, and combined trials, and crucially, that combined trials were the most accurately timed. Under the Bayesian framework, we found that participants’ combined estimates were more precise than isolated estimates in a way that trended towards optimality, while being overall less optimal than the model’s prediction. These findings elucidate previously unknown qualities of conscious motor timing, and proposes computational mechanisms that can describe how movements combine with perceptual signals to create unified, multimodal experiences of time.
Bayesian Accounts of Perceptual Decisions in the Nonclinical Continuum of Psychosis: Greater Imprecision in Both Top-down and Bottom-up Processes
Authors: Goodwin Isabella , Kugel Joshua , Hester Robert , Garrido Marta I. 
Published: October 2022

AbstractNeurocomputational accounts of psychosis propose mechanisms for how information is integrated into a predictive model of the world, in attempts to understand the occurrence of altered perceptual experiences. Conflicting Bayesian theories postulate aberrations in either top-down or bottom-up processing. The top-down theory predicts an overreliance on prior beliefs or expectations resulting in aberrant perceptual experiences, whereas the bottom-up theory predicts an overreliance on current sensory information, as aberrant salience is directed towards objectively uninformative stimuli. This study empirically adjudicates between these models. We use a perceptual decision-making task in a neurotypical population with varying degrees of psychotic-like experiences. Bayesian modelling was used to compute individuals’ reliance on prior relative to sensory information. Across two datasets (discovery dataset n=363; independent replication in validation dataset n=782) we showed that psychotic-like experiences were associated with an overweighting of sensory information relative to prior expectations, which seem to be driven by decreased precision afforded to prior information. However, when prior information was more uncertain, participants with greater psychotic-like experiences encoded sensory information with greater noise. Greater psychotic-like experiences were also associated with generally heightened perceptions of task instability, which we suggest may be the cause for the observed aberrant precision in the encoding both prior and likelihood information. Our study lends empirical support to notions of both weaker bottom-up and weaker (rather than stronger) top-down perceptual processes, as well as aberrancies in belief updating that extend into the non-clinical continuum of psychosis.
Ratio-based quantitative multiomics profiling using universal reference materials empowers data integration
Authors: Zheng Yuanting , Liu Yaqing , Yang Jingcheng , Dong Lianhua , Zhang Rui , Tian Sha , Yu Ying , Ren Luyao , Hou Wanwan , Zhu Feng , Mai Yuanbang , Han Jinxiong , Zhang Lijun , Jiang Hui , Lin Ling , Lou Jingwei , Li Ruiqiang , Lin Jingchao , Liu Huafen , Kong Ziqing , Wang Depeng , Dai Fangping , Bao Ding , Cao Zehui , Chen Qiaochu , Chen Qingwang , Chen Xingdong , Gao Yuechen , Jiang He , Li Bin , Li Bingying , Li Jingjing , Liu Ruimei , Qing Tao , Shang Erfei , Shang Jun , Sun Shanyue , Wang Haiyan , Wang Xiaolin , Zhang Naixin , Zhang Peipei , Zhang Ruolan , Zhu Sibo , Scherer Andreas , Wang Jiucun , Wang Jing , Xu Joshua , Hong Huixiao , Xiao Wenming , Liang Xiaozhen , Jin Li ,   The Quartet Project Team, Tong Weida , Ding Chen , Li Jinming , Fang Xiang , Shi Leming 
Published: October 2022

AbstractMultiomics profiling is a powerful tool to characterize the same samples with complementary features orchestrating the genome, epigenome, transcriptome, proteome, and metabolome. However, the lack of ground truth hampers the objective assessment of and subsequent choice from a plethora of measurement and computational methods aiming to integrate diverse and often enigmatically incomparable omics datasets. Here we establish and characterize the first suites of publicly available multiomics reference materials of matched DNA, RNA, proteins, and metabolites derived from immortalized cell lines from a family quartet of parents and monozygotic twin daughters, providing built-in truth defined by family relationship and the central dogma. We demonstrate that the “ratio”-based omics profiling data,i.e., by scaling the absolute feature values of a study sample relative to those of a concurrently measured universal reference sample, were inherently much more reproducible and comparable across batches, labs, platforms, and omics types, thus empower the horizontal (within-omics) and vertical (cross-omics) data integration in multiomics studies. Our study identifies “absolute” feature quantitation as the root cause of irreproducibility in multiomics measurement and data integration, and urges a paradigm shift from “absolute” to “ratio"-based multiomics profiling with universal reference materials.
Neuroinvasive flavivirus pathogenesis is restricted by host genetic factors in Collaborative Cross mice, independently of Oas1b
Authors: Jasperse Brittany A. , Mattocks Melissa D. , Noll Kelsey M. , Ferris Martin T. , Heise Mark T. , Lazear Helen M. 
Published: October 2022

ABSTRACTPowassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive disease, including encephalitis, meningitis, and paralysis. Similar to other neuroinvasive flaviviruses, such as West Nile virus (WNV) and Japanese encephalitis virus (JEV), POWV disease presentation is heterogeneous, and the factors influencing disease outcome are not fully understood. We used Collaborative Cross (CC) mice to assess the impact of host genetic factors on POWV pathogenesis. We infected a panel ofOas1b-null CC lines with POWV and observed a range of susceptibility phenotypes, indicating that host factors other than the well-characterized flavivirus restriction factorOas1bmodulate POWV pathogenesis in CC mice. AmongOas1b-null CC lines, we identified multiple highly susceptible lines (0% survival), including CC071, and a single resistant line (78% survival), CC045. Susceptibility phenotypes generally were concordant among neuroinvasive flaviviruses, although we identified one line, CC006, that was resistant specifically to JEV, suggesting that both pan-flavivirus and virus-specific mechanisms contribute to susceptibility phenotypes in CC mice. We found that POWV replicated to higher titers in bone marrow-derived macrophages from CC071 mice compared to CC045 mice, suggesting that resistance could result from cell-intrinsic restriction of viral replication. Although serum viral loads at 2 days post-infection were equivalent between CC071 and CC045 mice, clearance of POWV from the serum was significantly slower in CC071 mice. Furthermore, CC045 mice had significantly lower viral loads in the brain at 7 days post-infection compared to CC071 mice, suggesting that reduced CNS infection contributes to the resistant phenotype of CC045 mice.IMPORTANCENeuroinvasive flaviviruses, such as WNV, JEV, and POWV, are transmitted to humans by mosquitoes or ticks, can cause neurologic disease, such as encephalitis, meningitis, and paralysis, and can result in death or long-term sequelae. Although potentially severe, neuroinvasive disease is a rare outcome of flavivirus infection. The factors that determine whether someone develops severe disease after flavivirus infection are not fully understood, but host genetic differences in polymorphic antiviral response genes likely contribute to disease outcome. We evaluated a panel of genetically diverse mice and identified lines with distinct outcomes following infection with POWV. We found that resistance to POWV pathogenesis corresponded to reduced viral replication in macrophages, more rapid clearance of virus in peripheral tissues, and reduced viral infection in the brain. These susceptible and resistant mouse lines will provide a system for investigating the pathogenic mechanisms of POWV and identifying polymorphic host genes that contribute to resistance.
Consistent Under-reporting of Task Details in Motor Imagery Research
Authors: Van Caenegem Elise E , Hamoline Gautier , Waltzing Baptiste M , Hardwick Robert M 
Published: October 2022

AbstractMotor Imagery is a subject of longstanding scientific interest. However, critical details of motor imagery protocols are not always reported in full, hampering direct replication and translation of this work. The present review provides a quantitative assessment of the prevalence of under-reporting in the recent motor imagery literature. Publications from the years 2018-2020 were examined, with 695 meeting the inclusion criteria for further examination. Of these studies, 64% (445/695) did not provide information about the modality of motor imagery (i.e., kinesthetic, visual, or a mixture of both) used in the study. When visual or mixed imagery was specified, the details of the visual perspective to be used (i.e., first person, third person, or combinations of both) were not reported in 24% (25/103) of studies. Further analysis indicated that studies using questionnaires to assess motor imagery reported more information than those that did not. We conclude that studies using motor imagery consistently under-report key details of their protocols, which poses a significant problem for understanding, replicating, and translating motor imagery effects.
Identification of Tumor Antigens and Immune Subtypes of Acute Myeloid Leukemia for mRNA Vaccine Development
Authors: Wang Fan 
Published: October 2022

AbstractBackgroundAcute myeloid leukemia (AML) is a highly aggressive hematological malignancy, and there has not been any significant improvement in therapy of AML over the past several decades. The mRNA vaccines have become a promising strategy against multiple cancers, however, its application on AML remains undefined. In this study, we aimed to identify novel antigens for developing mRNA vaccines against AML and explore the immune landscape of AML to select appropriate patients for vaccination.MethodsThe genomic data and clinical information were retrieved from TCGA and GEO, respectively. The gene mutation data of AML were obtained from cBioPortal. GEPIA2 was used to analyze differentially expressed genes. The single cell RNA-seq database Tumor Immune Single-cell Hub (TISCH) was used to explore the association between the potential tumor antigens and the infiltrating immune cells in the bone marrow. Consensus clustering analysis was applied to identify distinct immune subtypes. The correlation between the abundance of antigen presenting cells and the expression level of antigens was evaluated using Spearman correlation analysis. The characteristics of the tumor immune microenvironment in each subtype were investigated based on single-sample gene set enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules and screen the hub genes.ResultsFive potential tumor antigens were identified for mRNA vaccine from the pool of overexpressed and mutated genes, including CDH23, LRP1, MEFV, MYOF and SLC9A9, which were associated with infiltration of antigen-presenting immune cells (APCs). AML patients were stratified into two immune subtypes Cluster1 (C1) and Cluster2 (C2), which were characterized by distinct molecular and clinical features. Patients with C1 subtype showed higher expression level of the five candidate genes and worse prognosis compared with C2 subtype. Moreover, C1 subtype demonstrated an immune-hot and immunosuppressive phenotype, while the C1 subtype had an immune-cold phenotype. Furthermore, the two immune subtype showed remarkably different expression of immune checkpoints, immunogenic cell death modulators and human leukocyte antigens. Finally, WCGNA identified a module and five hub genes that can be used for predicting the response of AML patients to mRNA vaccine.ConclusionCDH23, LRP1, MEFV, MYOF and SLC9A9 were potential antigens for developing AML mRNA vaccine, and AML patients in immune subtype 1 were suitable for vaccination.
Transmission ofXylella fastidiosasubsp. pauca ST53 by the sharpshooterCicadella viridisfrom different source plants and artificial diets
Authors: Bodino Nicola , Cavalieri Vincenzo , Saponari Maria , Dongiovanni Crescenza , Altamura Giuseppe , Bosco Domenico 
Published: October 2022

AbstractThe sharpshooterCicadella viridisL. (Hemiptera: Cicadellidae) is the most common sharpshooter in Europe and, given its xylem feeding behaviour, is considered a potential vector of the plant pathogenic bacteriumXylella fastidiosaWells et al. (Xanthomonadales:Xanthomonadaceae). We testedX. fastidiosasubsp. pauca ST53 (Xfp) transmission capabilities ofC. viridisadults, namely i) acquisition efficiency from four host plant species – periwinkle, milkwort, lavender, alfalfa – and from two artificial diets (PD3 and Xfm), ii) inoculation efficiency to periwinkle at different times post acquisition from different plant and artificial diet sources. The main European vector species –Philaenus spumarius– was used as a control.Cicadella viridiswas able to acquireXfpfrom periwinkle, milkwort, and lavender, although with low efficiency (3–16%) and from artificial diets (23–25%). Successful inoculation on periwinkle was extremely rare, being observed only three times, following feeding on milkwort plant and PD3 artificial diet sources. Our study shows thatC. viridisis not a relevant vector ofXfp, given the very low transmission rate in controlled conditions and the inability to feed on olive. The low efficiency reported here sums also to ecological constraints (mainly monocots host plants, humid environments) that make difficult to forecast a relevant role in dispersingX. fastidiosa, at least within the present distribution of the exotic bacterium in Europe. However, a possible role of this species in spreadingXfin other agroecosystems, e.g. vineyard and stone fruits grown in humid areas, cannot be excluded.
mutscan - a flexible R package for efficient end-to-end analysis of multiplexed assays of variant effect data
Authors: Soneson Charlotte , Bendel Alexandra M , Diss Guillaume , Stadler Michael B 
Published: October 2022

AbstractMultiplexed assays of variant effect (MAVE) experimentally measure the fitness of large numbers of sequence variants by selective enrichment of sequences with desirable properties followed by quantification by sequencing.mutscanis an R package for flexible analysis of such experiments, covering the entire workflow from raw reads up to statistical analysis and visualization. Core components are implemented in C++ for efficiency. Various experimental designs are supported, including single or paired reads with optional unique molecular identifiers. To find variants with changed relative abundance,mutscanemploys established statistical models provided in theedgeRandlimmapackages.mutscanis available fromhttps://github.com/fmicompbio/mutscan.
Nuclear proteins acquiring Germinal Center B cells are specifically suppressed by follicular regulatory T cells
Authors: Ke Fang , Benet Zachary L. , Maz Mitra P. , Liu Jianhua , Dent Alexander L. , Kahlenberg J. Michelle , Grigorova Irina L. 
Published: October 2022

AbstractFollicular regulatory T cells (Tfrs) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfrs can directly repress germinal center (GC) B cells that acquire auto-antigens is unclear. Moreover, TCR specificity of Tfrs to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfrs. Targeting of these proteins to antigen-specific B cells triggers rapid accumulation of Tfrs with immunosuppressive characteristics. Tfrs then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.
A cellular and transcriptomic dissection of the human breast for studying mechanisms of cell and tissue function
Authors: Toro Katelyn Del , Sayaman Rosalyn W. , Thi Kate , Licon-Munoz Yamhilette , Hines William C. 
Published: October 2022

AbstractA fundamental question in biology, central to our understanding of cancer and other pathologies, is determining how different cell types coordinate to form and maintain tissues. Recognizing the distinct features and capabilities of the cells that compose these tissues is critical. Unfortunately, the complexity of tissues often hinders our ability to distinguish between neighboring cell types and, in turn, scrutinize their transcriptomes and generate reliable and tractable cell models for studying their inherently different biologies. In a companion article, we introduced a novel method that permits the identification and purification of the twelve cell types that compo se the human breast—nearly all of which could be reliably propagated in the laboratory. Here, we explore the nature of these cell types. We sequence mRNAs from each purified population and investigate transcriptional patterns that reveal their distinguishing features. We describe the differentially expressed genes and enriched biological pathways that capture the essence of each cell type, and we highlight transcripts that display intriguing expression patterns. These data, analytic tools, and transcriptional analyses form a rich resource whose exploration provides remarkable insights into the inner workings of the cell types composing the breast, thus furthering our understanding of the rules governing normal cell and tissue function.
Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4+T cell response
Authors: Chudnovskiy Aleksey , Castro Tiago BR , Nakandakari-Higa Sandra , Cui Ang , Lin Chia-Hao , Sade-Feldman Moshe , Phillips Brooke K. , Pae Juhee , Mesin Luka , Bortolatto Juliana , Schweitzer Lawrence D. , Pasqual Giulia , Lu Li-Fan , Hacohen Nir , Victora Gabriel D. 
Published: October 2022

AbstractDendritic cells (DCs) are uniquely capable of transporting tumoral antigens to tumor-draining lymph nodes (tdLNs), and also interact with effector T cells within the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)-based single-cell transcriptomics, we identify individual DCs capable of presenting antigen to CD4+T cells in the tdLN as well as inside the tumor microenvironment (TME). Our findings reveal that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both within tumors and in the tdLN, and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation within the tdLN and TME to both CD4+and CD8+tumor-specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.
The global anaerobic metabolism regulatorfnris necessary for the degradation of food dyes and drugs byEscherichia coli
Authors: Pieper Lindsey M. , Spanogiannopoulos Peter , Volk Regan F. , Miller Carson J. , Wright Aaron T. , Turnbaugh Peter J. 
Published: October 2022

ABSTRACTThe microbiome is an underappreciated contributor to intestinal drug metabolism with broad implications for drug efficacy and toxicity. While considerable progress has been made towards identifying the gut bacterial genes and enzymes involved, the role of environmental factors in shaping their activity remains poorly understood. Here, we focus on the gut bacterial reduction of azo bonds (R-N=N-R’), found in diverse chemicals in both food and drugs. Surprisingly, the canonicalazoRgene inEscherichia coliwas dispensable for azo bond reduction. Instead, azo reductase activity was controlled by the fumarate and nitrate reduction (fnr) regulator, consistent with a requirement for the anoxic conditions found within the gastrointestinal tract. Paired transcriptomic and proteomic analysis of thefnrregulon revealed that in addition to altering the expression of multiple reductases, FNR is necessary for the metabolism of L-Cysteine to hydrogen sulfide, enabling the degradation of azo bonds. Taken together, these results show how gut bacteria sense and respond to their intestinal environment to enable the metabolism of chemical motifs found in both dietary and pharmaceutical compounds.IMPORTANCEThis work has broad relevance due to the ubiquity of dyes containing azo bonds in food and drugs. We report that azo dyes can be degraded by human gut bacteria through both enzymatic and non-enzymatic mechanisms, even from a single gut bacterial species. Furthermore, we revealed that environmental factors, oxygen and cysteine, control the ability ofE. colito degrade azo dyes due to their impacts on bacterial transcription and metabolism. These results open up new opportunities to manipulate the azoreductase activity of the gut microbiome through the manipulation of host diet, suggest that azoreductase potential may be altered in patients suffering from gastrointestinal disease, and highlight the importance of studying bacterial enzymes for drug metabolism in their natural cellular and ecological context.