bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetitive Mild Head Trauma Induces Activity-Mediated Lifelong Brain Deficits in a NovelDrosophilaModel
Authors: Behnke Joseph A. , Ye Changtian , Setty Aayush , Moberg Kenneth H. , Zheng James Q. 
Published: February 2021

AbstractMild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms inDrosophila melanogaster. We find thatDrosophilasubjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validateDrosophilaas a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability in brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.
Comprehensive Analysis of Ubiquitously Expressed Genes in Human, From a Data-Driven Perspective
Authors: Gu Jianlei , Dai Jiawei , Lu Hui , Zhao Hongyu 
Published: February 2021

AbstractComprehensive characterization of spatial and temporal gene expression patterns in humans is critical for uncovering regulatory codes of the human genome and understanding molecular mechanisms of human diseases. The ubiquitously expressed genes (UEGs) refer to those genes expressed across a majority, if not all, phenotypic and physiological conditions of an organism. It is known that many human genes are broadly expressed across tissues. However, most previous UEG studies have only focused on providing a list of UEGs without capturing their global expression patterns, thus limiting the potential use of UEG information. In this article, we propose a novel data-driven framework to leverage the extensive collection of ∼40,000 human transcriptomes to derive a list of UEGs and their corresponding global expression patterns, which offers a valuable resource to further validate and characterize human UEGs. Our results suggest that about half (12,234; 49.01%) of the human genes are expressed in at least 80% of human transcriptomes and the median size of the human transcriptome is 16,342 (65.44%). This suggests that the average difference in gene content between human transcriptomes is only 16.43%. Through gene clustering, we identified a set of UEGs, named LoVarUEGs, that have stable expression across human transcriptomes and can be used as internal reference genes for expression measurement. To further demonstrate the usefulness of this resource, we evaluated the uniqueness of repression for 16 previously predicted disallowed genes in islets beta cells and found that seven of these genes showed relatively more varied expression patterns, suggesting that the repression of these genes may not be unique to islets beta cells. We have made our resource publicly available athttps://github.com/macroant/HumanUEGs.
Reward enhances online participants’ engagement with a demanding auditory task
Authors: Bianco Roberta , Mills Gordon , de Kerangal Mathilde , Rosen Stuart , Chait Maria 
Published: February 2021

AbstractOnline recruitment platforms are increasingly utilized for experimental research. Crowdsourcing is associated with numerous benefits but also notable constraints, including lack of control over participants’ environment and engagement. In the context of auditory experiments, these limitations may be particularly detrimental to threshold-based tasks that require effortful listening. Here, we ask whether incorporating a performance-based monetary bonus will improve speech reception performance of online participants. In two experiments, participants performed an adaptive matrix-type speech-in-noise task (where listeners select two key words out of closed sets). In Experiment 1, our results revealed worse performance in online (N = 49) compared with in-lab (N = 81) groups. Specifically, relative to the in-lab cohort, significantly fewer participants in the online group achieved very low (< -17dB) thresholds. In Experiment 2 (N = 200), we show that a monetary reward improved listeners’ threshold to levels similar to those observed in the lab setting. Overall the results suggest that providing a small performance-based bonus increases participants’ task-engagement, facilitating a more accurate estimation of auditory ability under challenging listening conditions.
A catalytic-independent function of human DNA polymerase Kappa controls the pool of the Checkpoint Kinase 1
Authors: Dall’Osto Marina , Pierini Laura , Valery Nicolas , Hoffmann Jean-Sébastien , Pillaire Marie-jeanne 
Published: February 2021

ABSTRACTDNA polymerase kappa (Pol κ) has been well documented thus far for its specialized DNA synthesis activity during translesion replication, progression of replication forks through regions difficult to replicate and replication checkpoint at stalled forks.Here we unveiled an unexpected role for Pol κ in controlling the stability and abundance of Chk1, the major mediator of the replication checkpoint. We found that loss of Pol κ decreased the Chk1 protein level in the nucleus of four human cell lines. Pol κ and not the other Y‐family polymerase members is required to maintain the Chk1 protein pool all along the cell cycle. We showed that Pol κ depletion affected the protein stability of Chk1 and protected it from proteasome degradation and the replication recovery defects observed in Pol κ-depleted cells could be overcome by the re-expression of Chk1. Importantly, this new function of Pol κ does not require its catalytic activity, revealing that in addition to its known roles in the replication process, Pol κ can contribute to the maintenance of genome stability independently of its DNA synthesis activity.
Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system
Authors: Hart Thomas M. , Dupuis Alan P. , Tufts Danielle M. , Blom Anna M. , Starkey Simon , Rego Ryan O. M. , Ram Sanjay , Kraiczy Peter , Kramer Laura D. , Diuk-Wasser Maria A. , Kolokotronis Sergios-Orestis , Lin Yi-Pin 
Published: February 2021

ABSTRACTMicroparasites selectively adapt in some hosts, known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. LD bacteria species vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different LD bacteria species, utilizing feeding chambers and live mice and quail, we found species-level differences of bacterial transmission. These differences localize on the tick blood meal, and complement, a defense in vertebrate blood, and a bacterial polymorphic protein, CspA, which inactivates complement by binding to a host complement inhibitor, FH. CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. Phylogenetic analyses revealed convergent evolution as the driver of such findings, which likely emerged during the last glacial maximum. Our results identify LD bacterial determinants of host tropism, defining an evolutionary mechanism that shapes host-microparasite associations.
Tandem mass spectrum similarity-based network analysis using13C-labeled and non-labeled metabolome data to identify the biosynthesis pathway of the blood pressure-lowering asparagus metabolite asparaptine A
Authors: Nakabayashi Ryo , Yamada Yutaka , Nishizawa Tomoko , Mori Tetsuya , Asano Takashi , Kuwabara Masanari , Saito Kazuki 
Published: February 2021

AbstractAsparaptine, a conjugate of arginine and asparagusic acid, was found in asparagus (Asparagus officinalis) as a naturally occurring inhibitor of angiotensin-converting enzyme (ACE)in vitro.The biosynthetic pathway to asparaptine is largely unknown; however, it is suggested that asparagusic acid may be biosynthesized from valine. To determine which metabolites are involved in the asparaptine biosynthetic pathway, we performed tandem mass spectrometry similarity-based metabolome network analysis using13C labeled and non-labeled valine-fed asparagus calluses. We determined that valine is used as a starting material,S(2-carboxy-n-propyl)-cysteine as an intermediate, and two new metabolites as asparaptine analogs, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogs were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse species showed that this metabolite lowers both blood pressure and heart rate within two hours and both of which were back to normal two days later. These results suggest that asparaptine A may not only have effects as an ACE inhibitor, but also has β-antagonistic effects, which are well-known to be preventive for cardiovascular diseases.
An integrated strategy reveals complex glycosylation of erythropoietin using top-down and bottom-up mass spectrometry
Authors: Guan Yudong , Zhang Min , Gaikwad Manasi , Voss Hannah , Fazel Ramin , Ansari Samira , Shen Huali , Wang Jigang , Schlüter Hartmut 
Published: February 2021

ABSTRACTThe characterization of glycoproteins, like erythropoietin, is challenging due to the structural micro- and macro-heterogeneity of the protein glycosylation. This study presents an in-depth strategy for glycosylation analysis of a first-generation erythropoietin (epoetin beta), including a developed top-down mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation and a LC-MS approach for O-glycan identification. Permethylated N-glycans, peptides and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation). Extending the coverage of our newly developed Python script to phosphorylated N-glycans enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin. The site-specificity of N-glycans was revealed at glycopeptide level by pGlyco software using different proteases. In total, 215 N-glycan compositions were identified from N-glycan and glycopeptide analysis. Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two different O-glycan compositions, based on the mass shifts between non-O-glycosylated and O-glycosylated species. This integrated strategy allows the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
Specialization of actin isoforms derived from the loss of key interactions with regulatory factors
Authors: Sanders Micaela Boiero , Toret Christopher P. , Antkowiak Adrien , Robinson Robert C. , Michelot Alphée 
Published: February 2021

AbstractA paradox of eukaryotic cells is that while some species assemble a complex actin cytoskeleton from a single ortholog, other species utilize a greater diversity of actin isoforms. The physiological consequences of using different actin isoforms, and the molecular mechanisms by which highly conserved actin isoforms are segregated into distinct networks, are poorly known. Here, we sought to understand how a simple biological system, composed of a unique actin and a limited set of actin-binding proteins, reacts to a switch to heterologous actin expression. Using yeast as a model system and biomimetic assays, we show that such perturbation causes drastic reorganization of the actin cytoskeleton. Our results indicate that defective interaction of a heterologous actin for important regulators of actin assembly limits certain actin assembly pathways while reinforcing others. Expression of two heterologous actin variants, each specialized in assembling a different network, rescues cytoskeletal organization and confers resistance to external perturbation. Hence, while species using a unique actin have homeostatic actin networks, actin assembly pathways in species using several actin isoforms may act more independently.
Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease
Authors: Brissac Terry , Martínez Eriel , Kruckow Katherine L. , Riegler Ashleigh N. , Ganaie Feroze , Im Hansol , Bakshi Sayan , Arroyo-Diaz Nicole M. , Spencer Brady L. , Saad Jamil S. , Nahm Moon H. , Orihuela Carlos J. 
Published: February 2021

ABSTRACTStreptococcus pneumoniae(Spn) is a leading cause of invasive disease. Chief among its virulence determinants is capsular polysaccharide which protects the bacterium from phagocytosis. While 100 antigenically distinct capsule types are produced bySpn, i.e. serotypes, only 20-30 are commonly associated with invasive disease. A frequency that suggests serotypespecific properties of the capsule influence virulence. Herein, we show capsule has strong antioxidant properties. Moreover, that this property promotes invasive disease by protectingSpntaken up by vascular endothelial cells during bacteremia from endosome-killing and enhancing the translocation rate into organs. Crucially, isogenic capsule-switch mutants ofSpnvaried considerably in their resistance to H2O2-killing in culture and measured levels correlated positively with intracellular survival ratesin vitro, organ invasion ratesin vivo, and epidemiologically-established human attack rates for the corresponding serotype. The amount of capsule produced and specific biochemical features of a serotype, such as acetylation, also influencedSpnresistance to oxidative stress. Autolysin-mediated shedding was also found to be necessary, indicating that capsule worked as a distal sink for reactive oxygen species. Our results outline a new role for capsular polysaccharide, as an intracellular antioxidant. They help to explain why certain serotypes ofSpnhave greater propensity for human disease.
The climate benefits of yield increases in genetically engineered crops
Authors: Kovak Emma , Qaim Matin , Blaustein-Rejto Dan 
Published: February 2021

AbstractThe benefits of genetically engineered (GE) crops are systematically underestimated because previous studies did not incorporate the reduction in greenhouse gas (GHG) emissions associated with yield increases. We estimate this impact using the carbon opportunity cost of land use. Our results suggest that the GHG emissions reductions from the yield increases in GE crops are substantial and should be included in future analyses.
Bifurcated monocyte states are predictive of mortality in severe COVID-19
Authors: Cillo Anthony R. , Somasundaram Ashwin , Shan Feng , Cardello Carly , Workman Creg J. , Kitsios Georgios D. , Ruffin Ayana , Kunning Sheryl , Lampenfeld Caleb , Onkar Sayali , Grebinoski Stephanie , Deshmukh Gaurav , Methe Barbara , Liu Chang , Nambulli Sham , Andrews Lawrence , Duprex W. Paul , Joglekar Alok V. , Benos Panayiotis V. , Ray Prabir , Ray Anuradha , McVerry Bryan J. , Zhang Yingze , Lee Janet S. , Das Jishnu , Singh Harinder , Morris Alison , Bruno Tullia C. , Vignali Dario A.A. 
Published: February 2021

AbstractCoronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection presents with varied clinical manifestations1, ranging from mild symptoms to acute respiratory distress syndrome (ARDS) with high mortality2,3. Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in severe COVID-19. We performed high-dimensional cellular and molecular profiling of blood and respiratory samples from critically ill COVID-19 patients to define immune cell genomic states that are predictive of outcome in severe COVID-19 disease. Critically ill patients admitted to the intensive care unit (ICU) manifested increased frequencies of inflammatory monocytes and plasmablasts that were also associated with ARDS not due to COVID-19. Single-cell RNAseq (scRNAseq)-based deconvolution of genomic states of peripheral immune cells revealed distinct gene modules that were associated with COVID-19 outcome. Notably, monocytes exhibited bifurcated genomic states, with expression of a cytokine gene module exemplified byCCL4(MIP-1β) associated with survival and an interferon signaling module associated with death. These gene modules were correlated with higher levels of MIP-1β and CXCL10 levels in plasma, respectively. Monocytes expressing genes reflective of these divergent modules were also detectable in endotracheal aspirates. Machine learning algorithms identified the distinctive monocyte modules as part of a multivariate peripheral immune system state that was predictive of COVID-19 mortality. Follow-up analysis of the monocyte modules on ICU day 5 was consistent with bifurcated states that correlated with distinct inflammatory cytokines. Our data suggests a pivotal role for monocytes and their specific inflammatory genomic states in contributing to mortality in life-threatening COVID-19 disease and may facilitate discovery of new diagnostics and therapeutics.
SPARC Data Structure: Rationale and Design of a FAIR Standard for Biomedical Research Data
Authors: Bandrowski Anita , Grethe Jeffrey S. , Pilko Anna , Gillespie Tom , Pine Gabi , Patel Bhavesh , Surles-Zeigler Monique , Martone Maryann E. 
Published: February 2021

AbstractThe NIH Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiative is a large-scale program that seeks to accelerate the development of therapeutic devices that modulate electrical activity in nerves to improve organ function. Integral to the SPARC program are the rich anatomical and functional datasets produced by investigators across the SPARC consortium that provide key details about organ-specific circuitry, including structural and functional connectivity, mapping of cell types and molecular profiling. These datasets are provided to the research community through an open data platform, the SPARC Portal. To ensure SPARC datasets are Findable, Accessible, Interoperable and Reusable (FAIR), they are all submitted to the SPARC portal following a standard scheme established by the SPARC Curation Team, called the SPARC Data Structure (SDS). Inspired by the Brain Imaging Data Structure (BIDS), the SDS has been designed to capture the large variety of data generated by SPARC investigators who are coming from all fields of biomedical research. Here we present the rationale and design of the SDS, including a description of the SPARC curation process and the automated tools for complying with the SDS, including the SDS validator and Software to Organize Data Automatically (SODA) for SPARC. The objective is to provide detailed guidelines for anyone desiring to comply with the SDS. Since the SDS are suitable for any type of biomedical research data, it can be adopted by any group desiring to follow the FAIR data principles for managing their data, even outside of the SPARC consortium. Finally, this manuscript provides a foundational framework that can be used by any organization desiring to either adapt the SDS to suit the specific needs of their data or simply desiring to design their own FAIR data sharing scheme from scratch.
Dung beetles as vertebrate samplers – a test of high throughput analysis of dung beetle iDNA
Authors: Drinkwater Rosie , Clare Elizabeth L. , Chung Arthur Y. C. , Rossiter Stephen J. , Slade Eleanor M. 
Published: February 2021

AbstractThe application of environmental DNA (eDNA) sampling in biodiversity surveys has gained widespread acceptance, especially in aquatic systems where free eDNA can be readily collected by filtering water. In terrestrial systems, eDNA-based approaches for assaying vertebrate biodiversity have tended to rely on blood-feeding invertebrates, including leeches and mosquitoes (termed invertebrate-derived DNA or iDNA). However, a key limitation of using blood-feeding taxa as samplers is that they are difficult to trap, and, in the case of leeches, are highly restricted to humid forest ecosystems. Dung beetles (superfamily Scarabaeoidea) feed on the faecal matter of terrestrial vertebrates and offer several potential benefits over blood-feeding invertebrates as samplers of vertebrate DNA. Importantly, these beetles can be easily captured in large numbers using simple, inexpensive baited traps; are globally distributed; and also occur in a wide range of biomes, allowing mammal diversity to be compared across habitats. In this exploratory study, we test the potential utility of dung beetles as vertebrate samplers by sequencing the mammal DNA contained within their guts. First, using a controlled feeding experiment, we show that mammalian DNA can be retrieved from the guts of large dung beetles (Catharsius renaudpauliani) for up to 10 hours after feeding. Second, by combining high-throughput sequencing of a multi-species assemblage of dung beetles with PCR replicates, we show that multiple mammal taxa can be identified with high confidence. By providing preliminary evidence that dung beetles can be used as a source of mammal DNA, our study highlights the potential for this widespread group to be used in future biodiversity monitoring surveys.
The integrity and assay performance of tissue mitochondrial DNA is considerably affected by choice of isolation method
Authors: Marçal Repolês Bruno , Gorospe Choco Michael , Tran Phong , Nilsson Anna Karin , Wanrooij Paulina H. 
Published: February 2021

AbstractThe integrity of mitochondrial DNA (mtDNA) isolated from solid tissues is critical for analyses such as long-range PCR, but is typically assessed under conditions that fail to provide information on the individual mtDNA strands. Using denaturing gel electrophoresis, we show that commonly-used isolation procedures generate mtDNA containing several single-strand breaks per strand. Through systematic comparison of DNA isolation methods, we identify a procedure yielding the highest integrity of mtDNA that we demonstrate displays improved performance in downstream assays. Our results highlight the importance of isolation method choice, and serve as a resource to researchers requiring high-quality mtDNA from solid tissues.