bluuebunny/crossref_metadata_2025_split huggingface dataset:
PaxDB 5.0: curated protein quantification data suggests adaptive proteome changes
Authors: Huang Qingyao , Szklarczyk Damian , Wang Mingcong , Simonovic Milan , von Mering Christian 
Published: April 2023

AbstractThe “Protein Abundances Across Organisms” database (PaxDB) is an integrative meta-resource dedicated to protein abundance levels, in tissue-specific or whole-organism proteomes. PaxDB focuses on computing best-estimate abundances for proteins in normal/healthy contexts, and expresses abundance values for each protein in “parts per million” (ppm) in relation to all other protein molecules in the cell. The uniform data re-processing, quality scoring, and integrated orthology relations have made PaxDB one of the preferred tools for comparisons between individual datasets, tissues or organisms. In describing the latest version 5.0 of PaxDB, we particularly emphasise the data integration from various types of raw data, and how we expanded the number of organisms and tissue groups as well as the proteome coverage. The current collection of PaxDB includes 831 original datasets from 170 species, including 22 Archaea, 81 Bacteria and 67 Eukaryota. Apart from detailing the data update, we also show a comparative analysis of the human proteome subset of PaxDB against the two most widely-used human proteome data resources: Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx). Lastly, we present a use case of PaxDB, showing how protein abundance data can be used to study the evolution of relative amino acid usage in Fungi.
The structure of a hibernating ribosome in a Lyme disease pathogen
Authors: Sharma Manjuli R. , Manjari Swati R. , Agrawal Ekansh K. , Keshavan Pooja , Koripella Ravi K. , Majumdar Soneya , Marcinkiewicz Ashley L. , Lin Yi-Pin , Agrawal Rajendra K. , Banavali Nilesh K. 
Published: April 2023

AbstractThe spirochete bacterial pathogenBorrelia(Borreliella) burgdorferi(Bbu) affects more than 10% of the world population and causes Lyme disease in about half a million people in the US annually. Therapy for Lyme disease includes antibiotics that target theBburibosome. We determined the structure of theBbu70S ribosome by single particle cryo-electron microscopy (cryo-EM) at a resolution of 2.9 Å, revealing its distinctive features. In contrast to a previous study suggesting that the single hibernation promoting factor protein present inBbu(bbHPF) may not bind to its ribosome, our structure reveals a clear density for bbHPF bound to the decoding center of the small ribosomal 30S subunit. The 30S subunit has a non-annotated ribosomal protein, bS22, that has been found only in mycobacteria and Bacteroidetes so far. The protein bL38, recently discovered in Bacteroidetes, is also present in theBbularge 50S ribosomal subunit. The protein bL37, previously seen only in mycobacterial ribosomes, is replaced by an N-terminal α-helical extension of uL30, suggesting that the two bacterial ribosomal proteins uL30 and bL37 may have evolved from one longer uL30 protein. The longer uL30 protein interacts with both the 23S rRNA and the 5S rRNA, is near the peptidyl transferase center (PTC), and could impart greater stability to this region. Its analogy to proteins uL30m and mL63 in mammalian mitochondrial ribosomes also suggests a plausible evolutionary pathway for expansion of protein content in mammalian mitochondrial ribosomes. Computational binding free energies are predicted for antibiotics, bound to the decoding center or PTC and are in clinical use for Lyme disease, that account for subtle distinctions in antibiotic-binding regions in theBburibosome structure. Besides revealing unanticipated structural and compositional features for theBburibosome, our study thus provides groundwork to enable ribosome-targeted antibiotic design for more effective treatment of Lyme disease.
Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: April 2023

AbstractDiabetic patients are prone to diabetic kidney disease (DKD), which may cause cardiovascular damage, hypertension and obesity, and reduce quality of life. As a result, the life quality of patients was seriously reduced. However, the pathogenesis of diabetic kidney disease (DKD) has not been fully elucidated, and current treatments remain inadequate. Therefore, it is essential to explore the molecular mechanism of DKD and its complications. Next Generation Sequancing (GSE217709) dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were picked out by R software. Then Gene ontology (GO) and REACTOME pathway enrichment analysis were performed by g:Profiler database, protein–protein interaction (PPI) of DEGs was constructed by Human Integrated Protein-Protein Interaction rEference (HIPPIE) database. Module analysis was carried out by Cytoscape plug-in PEWCC. Subsequently, miRNA-hub gene regulatory network and TF-hub gene regulatory network were performed by miRNet database and NetworkAnalyst database. Finally, validation of hub genes was performed by receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. In total, 958 DEGs, including 479 up regulated and 479 down regulated genes, were identified. The GO and pathway enrichment changes of DEGs were mainly enriched in biological regulation, multicellular organismal process, signaling by GPCR and extracellular matrix organization. Ten hub genes (HSPA8, HSP90AA1, HSPA5, SDCBP, HSP90B1, VCAM1, MYH9, FLNA, MDFI and PML) associated with DKD and its complications were identified. Bioinformatics analysis is a useful tool to explore the molecular mechanism and pathogenesis of DKD and its complications. The identified hub genes may participate in the onset and development of DKD and its complications and serve as therapeutic targets.
Disulfiram Exerts anti-pulmonary Fibrosis Effect by Activating PGE2 Synthesis
Authors: Pei Xiaolin , Zheng Fangxu , Li Yin , Lin Zhoujun , Zhang Yupeng , Han Xiao , Feng Ya , Li Fei , Yang Juan , Li Tianjiao , Tian Zhenhuan , Cao Ke , Ren Dunqiang , Li Chenggang 
Published: April 2023

AbstractIdiopathic pulmonary fibrosis (IPF) is marked with the replacement of normal alveolar tissue by thicker and harder fibrous material, damaged exchange ability. Currently, nintedanib and pirfenidone, are the only FDA-approved drugs with limited efficacy for IPF, which indicated an urgent need to explore new therapies. Disulfiram (DSF), an acetaldehyde dehydrogenase inhibitor, used as anti-alcohol treatment. Despite reported with anti-hepatic fibrosis effect of DSF, the underlying mechanism remains unclear. In our study, DSF exhibited regulative impact on abnormal proliferation, EMT and ECM production in cell models of IPF including primary DHLF-IPF cells and TGF-β1-stimulated A549 cells. The absence of COX-2 was restored by DSF treatment, together with elevated prostaglandin biosynthesis both in vitro and in vivo models of IPF. Furthermore, the anti-fibrotic effect of DSF was impeded with COX-2 knockdown or pharmacological inhibition in TGF-β1-stimulated A549 cells, however, exogenous PGE2 reclaimed with anti-EMT function. In established animal model of IPF, DSF ameliorated declined lung function and histopathological changes, and restrained the lung hydroxyproline content. Together, these findings suggest that the anti-fibrotic effect of DSF was achieved through re-activation of COX-2 mediated PGE2 biosynthesis. The above results suggest that DSF can be applied therapeutically in fibrotic conditions.
The effect of removing repeat-induced overlaps inde novoassembly
Authors: Shirali Hossein Zade Ramin , Abeel Thomas 
Published: April 2023

AbstractDetermining accurate genotypes is important for associating phenotypes to genotypes.De novogenome assembly is a critical step to determine the complete genotype for species for which no reference exists yet. The main challenge ofde novoeukaryote genome assembly, particularly plant genomes, are repetitive DNA sequences within their genomes. The introduction of third generation sequencing and corresponding long reads has promised to resolve repeat-related problems. While there have been notable improvements, reads originating from these repeats are still creating errors because they introduce false overlaps in the assembly graph. This study focuses on analyzing the effect of repeats onde novoassembly and improving performance of existingde novoassembly algorithms by removing repeat-induced overlaps. First, we show the possible improvements in de novo assembly with removing repeat-induced overlaps. Then we propose several methods for detecting and removing repeat-induced overlaps and evaluate their performance on several simulated datasets.
Genetic insights into the association between inflammatory bowel disease and Alzheimer’s disease
Authors: Zeng Lu , White Charles C. , Bennett David A. , Klein Hans-Ulrich , De Jager Philip L. 
Published: April 2023

AbstractMyeloid cells, including monocytes, macrophages, microglia, dendritic cells and neutrophils are a part of innate immune system, playing a major role in orchestrating innate and adaptive immune responses. Both Alzheimer’s disease (AD) and inflammatory bowel disease (IBD) susceptibility loci are enriched for genes expressed in myeloid cells, but it is not clear whether these myeloid risk factors are shared between the two diseases. Leveraging results of genome-wide association studies, we investigated the causal effect of IBD (including ulcerative colitis (UC) and Crohn’s disease (CD)) variants on AD and its endophenotypes. Microglia and monocyte expression Quantitative Trait Locus (eQTLs) were used to examine the functional consequences of IBD and AD variants. Our results revealed distinct sets of genes and pathways of AD and IBD susceptibility loci. Specifically, AD loci are enriched for microglial eQTLs, while IBD loci are enriched for monocyte eQTLs. However, we also found that genetically determined IBD is associated with a protective effect against AD (p<0.03). Yet, a genetic propensity for the CD subtype is associated with increased amyloid accumulation (beta=7.14, p-value=0.02) and susceptibility to AD. Susceptibility to UC was associated with increased deposition of TDP-43 (beta=7.58, p-value=6.11×10-4). The relation of these gastrointestinal inflammatory disease to AD is therefore complex; while the different subsets of susceptibility variants preferentially affect different myeloid cell subtypes, there do appear to be certain shared pathways and the possible protective effect of IBD susceptibility on the risk of AD which may provide therapeutic insights.
Facilitating Healing for Black Women Experiencing Gendered Racism and Traumatic Stress: The Moderation of Psychosocial Resources
Authors: Williams Tiffany R. , Erving Christy L. , Frierson Whitney , Gao Fanchen , Bass Jeffery E , Martin Reniece , Mitchell Taeja 
Published: April 2023

AbstractBlack women must navigate a tumultuous sociopolitical terrain while simultaneously managing their psychological health. Experiences of gendered racism increase Black women’s vulnerability to psychological distress. Gendered racial microaggressions, a specific type of microaggression, account for the intricate ways racism and sexism intersect. The association between Black women’s experiences of gendered racial microaggressions and traumatic stress was investigated among 201 Black female-identified undergraduate and graduate students attending a Historically Black College or University. Whether psychosocial resources (i.e., resilience, social support, mastery, self-esteem) moderated the linkage between gendered racial microaggressions and traumatic stress was also examined. Gendered racial microaggressions were positively associated with traumatic stress. The microaggression Assumptions of Beauty and Sexual Objectification was the most strongly associated with traumatic stress, followed by Angry Black Woman. Resilience and mastery were protective factors, reducing the influence of gendered racial microaggressions on traumatic stress. In addition, high levels of social support reduced the impact of Assumptions of Beauty and Sexual Objectification on traumatic stress. To foster healing and posttraumatic growth for Black women, psychologists must decolonize their understanding and treatment of mental illness. Practice and research implications are discussed.
nELISA: A high-throughput, high-plex platform enables quantitative profiling of the secretome
Authors: Dagher Milad , Ongo Grant , Robichaud Nathaniel , Kong Jinglin , Rho Woojong , Teahulos Ivan , Tavakoli Arya , Bovaird Samantha , Merjaneh Shahem , Tan Andrew , Edwardson Kiran , Scheepers Christelle , Ng Andy , Hajjar Andy , Sow Baly , Vrouvides Michael , Lee Andy , DeCorwin-Martin Philippe , Rasool Shafqat , Huang JiaMin , Erps Timothy , Coffin Spencer , Han Yu , Chandrasekaran Srinivas Niranj , Miller Lisa , Kost-Alimova Maria , Skepner Adam , Singh Shantanu , Carpenter Anne E. , Munzar Jeffrey , Juncker David 
Published: April 2023

AbstractWe present the nELISA, a high-throughput, high-fidelity, and high-plex protein profiling platform. DNA oligonucleotides are used to pre-assemble antibody pairs on spectrally encoded microparticles and perform displacement-mediated detection. Spatial separation between non-cognate antibodies prevents the rise of reagent-driven cross-reactivity, while read-out is performed cost-efficiently and at high-throughput using flow cytometry. We assembled an inflammatory panel of 191 targets that were multiplexed without cross-reactivity or impact on performance vs 1-plex signals, with sensitivities as low as 0.1pg/mL and measurements spanning 7 orders of magnitude. We then performed a large-scale secretome perturbation screen of peripheral blood mononuclear cells (PBMCs), with cytokines as both perturbagens and read-outs, measuring 7,392 samples and generating ∼1.5M protein datapoints in under a week, a significant advance in throughput compared to other highly multiplexed immunoassays. We uncovered 447 significant cytokine responses, including multiple putatively novel ones, that were conserved across donors and stimulation conditions. We also validated the nELISA’s use in phenotypic screening, and propose its application to drug discovery.
Neural speech tracking benefit of lip movements predicts behavioral deterioration when the speaker’s mouth is occluded
Authors: Reisinger Patrick , Gillis Marlies , Suess Nina , Vanthornhout Jonas , Haider Chandra Leon , Hartmann Thomas , Hauswald Anne , Schwarz Konrad , Francart Tom , Weisz Nathan 
Published: April 2023

AbstractObserving lip movements of a speaker is known to facilitate speech understanding, especially in challenging listening situations. Converging evidence from neuroscientific studies shows enhanced processing of audiovisual stimuli. However, the interindividual variability of this visual benefit and its consequences on behavior are unknown. Here, we analyzed source-localized magnetoencephalographic (MEG) responses from normal-hearing participants listening to audiovisual speech with or without an additional distractor speaker. Using temporal response functions (TRFs), we show that neural responses to lip movements are, in general, enhanced when speech is challenging. After conducting a crucial control for speech acoustics, we show that lip movements effectively contribute to higher neural speech tracking, particularly when a distractor speaker is present. However, the extent of this visual benefit varied greatly among participants. Probing the behavioral relevance, we show that individuals who benefit more from lip movement information in terms of neural speech tracking, show a stronger drop in performance and an increase in perceived difficulty when the mouth is occluded by a surgical face mask. By contrast, no effect was found when the mouth was not occluded. We provide novel insights on how the benefit of lip movements in terms of neural speech tracking varies among individuals. Furthermore, we reveal its behavioral relevance by demonstrating negative consequences for behavior when visual speech is absent. Our results also offer potential implications for future objective assessments of audiovisual speech perception.
A new ‘CFS tracking’ paradigm reveals uniform suppression depth regardless of target complexity or salience
Authors: Alais David , Coorey Jacob , Blake Randolph , Davidson Matthew J. 
Published: April 2023

AbstractWhen the eyes view separate and incompatible images, the brain suppresses one image and promotes the other into visual awareness. Periods of interocular suppression can be prolonged during continuous flash suppression (CFS) - when one eye views a static ‘target’ while the other views a complex dynamic stimulus. Measuring the time needed for a suppressed image to break CFS (bCFS) has been widely used to investigate unconscious processing, and the results have generated controversy regarding the scope of visual processing without awareness. Here, we address this controversy with a new ‘CFS tracking’ paradigm (tCFS) in which the suppressed monocular target steadily increases in contrast until breaking into awareness (as in bCFS) after which it decreases until it again disappears (reCFS), with this cycle continuing for many reversals. Unlike bCFS, tCFS provides a measure of suppression depth by quantifying the difference between breakthrough and suppression thresholds. tCFS confirms that: (i) breakthrough thresholds indeed differ across target types (e.g., faces vs gratings, as bCFS has shown) – but (ii) suppression depth does not vary across target types. Once the breakthrough contrast is reached for a given stimulus, all stimuli require a strikingly uniform reduction in contrast to reach the corresponding suppression threshold. This uniform suppression depth points to a single mechanism of CFS suppression, one that likely occurs early in visual processing because suppression depth was not modulated by target salience or complexity. More fundamentally, it shows that variations in bCFS thresholds alone are insufficient for inferring whether the barrier to achieving awareness exerted by interocular suppression is weaker for some categories of visual stimuli compared to others.Significance statementResearch on unconscious vision has proliferated recently, often employing the continuous flash suppression (CFS) method in which rapidly changing shapes viewed by one eye suppress the other eye’s image from awareness. If that suppressed image is progressively strengthened in contrast it will eventually break suppression and emerge into visible awareness. Low breakthrough thresholds are claimed to indicate unconscious processing during suppression. We introduce a method that quantifies breakthrough thresholds and suppression thresholds, thus providing a lower bound missing from previous CFS research. Comparing various image types, including those claimed to undergo unconscious processing, all images show equal suppression when both thresholds are measured. We thus find no evidence of differential unconscious processing and conclude reliance on breakthrough thresholds is misleading without considering suppression thresholds and leads to spurious claims about unconscious processing.
Botanicals impact the bifidogenic effect and metabolic outputs ofin vitrofiber fermentation by gut-derived microbiota in individual-specific ways
Authors: Deemer Dane G. , Voreades Noah , Goodwin Ben , Bron Peter A. , Lindemann Stephen R. 
Published: April 2023

AbstractModern diets typically contain dramatically lower fiber content compared to traditional hunter-gatherer and agrarian diets, and this trend is paralleled by an enhanced frequency of chronic diseases. Despite national nutrition policy and education instructing Americans on the beneficial health value of increasing daily fiber consumption, a “fiber gap” still persistently exists. Fortification of product groups frequently consumed by a large proportion of society provides an attractive strategy to close this “fiber gap” and may have the potential to concomitantly reverse the detrimental health effects exacerbated by our modern diets. Besides prebiotic fibers, products can contain several other functional components, such as botanicals. However, the vast majority of studies have investigated functional components in isolation. For instance, preferential fermentation of specific prebiotic fibers by bifidobacteria has been clearly established, both in terms of their increased abundance in the gut microbiome and the elevated levels of beneficial metabolites, including short chain fatty acids (SCFAs) produced directly (acetate) or through interactions with other microbiota members (resulting in butyrate and propionate production). The impact of other components present in functional product blends on this bifidogenic effect are largely unexplored. Here, we investigated the fiber and botanical blends included in OLIPOP, a functional soda, in anin vitrogut fermentation model. Our data revealed that the blend of inulins and resistant dextrins promoted growth of bifidobacteria across gut microbiota from four donors, even those with small initial populations. In addition, botanicals interacted with fiber fermentation in donor-specific ways, in some cases strongly enhancing fermentation rate and production of SCFAs. Our data suggest that botanicals can modify the rate and microbial and metabolic fates of prebiotic fiber fermentation, and suggest that future studies should examine such interactions in greater detail.
A 1.5 Mb continuous endogenous viral region in the arbuscular mycorrhizal fungusRhizophagus irregularis
Authors: Zhao Hongda , Zhang Ruixuan , Wu Junyi , Meng Lingjie , Okazaki Yusuke , Hikida Hiroyuki , Ogata Hiroyuki 
Published: April 2023

AbstractMost fungal viruses are RNA viruses and no double-stranded DNA virus that infects fungi is known to date. A recent study detected DNA polymerase genes that originated from large dsDNA viruses in the genomes of basal fungi, suggestive of the existence of dsDNA viruses capable of infecting fungi. In this study, we searched for viral infection signatures in chromosome-level genome assemblies of the arbuscular mycorrhizal fungusRhizophagus irregularis. We identified a continuous 1.5 Mb putative viral region on a chromosome inR. irregularisstrain 4401. Phylogenetic analyses revealed that the viral region is related to viruses in the familyAsfarviridaeof the phylumNucleocytoviricota. Single-copy marker genes fromNucleocytoviricotawere detected as single-copy genes in the viral region. Furthermore, this viral region was absent in the genomes of four otherR. irregularisstrains and had fewer signals of fungal transposable elements than the other genomic regions. These results suggest a recent and single insertion of a large dsDNA viral genome in the genome of this fungal strain, providing strong evidence of the recent infection of the fungus by a dsDNA virus.