bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of COVID-19 data: An evaluation and reflection
Authors: Miller April R. , Charepoo Samin , Yan Erik , Frost Ryan W. , Sturgeon Zachary J. , Gibbon Grace , Balius Patrick , Thomas Cedonia S. , Schmitt Melanie A. , Sass Daniel A. , Walters James B. , Flood Tracy L. , Schmitt Thomas A. 
Published: April 2021

AbstractImportanceThe rapid proliferation of COVID-19 has left governments scrambling, and several data aggregators are now assisting in the reporting of county cases and deaths. The different variables affecting reporting (e.g., time delays in reporting) necessitates a well-documented reliability study examining the data methods and discussion of possible causes of differences between aggregators.ObjectiveTo statistically evaluate the reliability of COVID-19 across aggregators.Design, Setting, and ParticipantsCases and deaths were collected daily by volunteers via state and local health departments, as primary sources and newspaper reports, as secondary sources. In an effort to begin comparison for reliability statistical analysis, BroadStreet collected data from other COVID-19 aggregator sources, including USAFacts, Johns Hopkins University, New York Times, The COVID Tracking Project.Main Outcomes and MeasuresCOVID-19 cases and death counts at the county and state levels.ResultsLower levels of inter-rater agreement were observed across aggregators associated with the number of deaths, which manifested itself in state level Bayesian estimates of COVID-19 fatality rates.Conclusions and RelevanceA national, publically available data set is needed for current and future disease outbreaks and improved reliability in reporting.
Interneuronal dynamics facilitate the initiation of cortical spreading depression
Authors: Stein Wolfgang , Harris Allison L. 
Published: April 2021

AbstractCortical spreading depression (CSD) is thought to precede migraine attacks with aura and is characterized by a slowly traveling wave of inactivity through cortical pyramidal cells. During CSD, pyramidal cells experience hyperexcitation with rapidly increasing firing rates, major changes in electrochemistry, and ultimately spike block that propagates slowly across the cortex. While the identifying characteristic of CSD is the pyramidal cell hyperexcitation and subsequent spike block, it is currently unknown how the dynamics of the cortical microcircuits and inhibitory interneurons affect the initiation of CSD.We tested the contribution of cortical inhibitory interneurons to the initiation of spike block using a cortical microcircuit model that takes into account changes in ion concentrations that result from neuronal firing. Our results show that interneuronal inhibition provides a wider dynamic range to the circuit and generally improves stability against spike block.Despite these beneficial effects, strong interneuronal firing contributed to rapidly changing extracellular ion concentrations, which facilitated hyperexcitation and led to spike block first in the interneuron and then in the pyramidal cell. In all cases, a loss of interneuronal firing triggered pyramidal cell spike block. However, preventing interneuronal spike block was insufficient to rescue the pyramidal cell from spike block. Our data thus demonstrate that while the role of interneurons in cortical microcircuits is complex, they are critical to the initiation of pyramidal cell spike block and CSD. We discuss the implications that localized effects on cortical interneurons have beyond the isolated microcircuit.
Curating and translating the evidence about SARS-CoV-2 and COVID-19 for frontline public health and clinical care: The Novel Coronavirus Research Compendium (NCRC)
Authors: Redd Andrew D. , Peetluk Lauren , Jarrett Brooke , Hanrahan Colleen , Schwartz Sheree , Rao Amrita , Jaffe Andrew , Jones Carli , Lutz Chelsea , McKee Clif , Patel Eshan , Rosen Greg , Desany Henri Garrison , McKay Heather , Muschelli John , Andersen Kayte , Link Malen A. , Wada Nikolas , Baral Prativa , Young Ruth , Boon Denali , Grabowski M. Kate , Gurley Emily S. ,   the NCRC Team
Published: April 2021

AbstractThe public health crisis created by the SARS-CoV-2 pandemic has spurred a deluge of scientific research aimed at informing public health and medical response to the COVID-19 pandemic. However, those working in frontline public health and clinical care had insufficient time to parse the rapidly evolving evidence and use it for decision making. Academics in public health and medicine were well-placed to translate the evidence for use by frontline clinicians and public health practitioners. The Novel Coronavirus Research Compendium (NCRC), a group of >50 faculty and trainees, began in March 2020 with the goal to quickly triage and review the large volume of preprints and peer-reviewed publications on SARS-CoV-2 and COVID-19, and to summarize the most important, novel evidence to inform pandemic response. From April 6, 2020 through January 1, 2021, 54,192 papers and preprints were screened by NCRC teams and 527 were selected for review and uploaded to the NCRC website for public consumption. The majority of papers reviewed were peer-reviewed publications (n=395, 75%), published in 102 journals; 25% (n=132) of papers reviewed were of preprints. The NCRC is a successful model of how academics can support practitioners by translating scientific knowledge into action and help to build capacity among students for this work. This approach could be used for health problems beyond COVID-19, but the effort is resource intensive and may not be sustainable over the long term.
Is large-scale rapid CoV-2 testing a substitute for lockdowns?
Authors: Diederichs Marc , Glawion René , Kremsner Peter G. , Mitze Timo , Müller Gernot J. , Papies Dominik , Schulz Felix , Wälde Klaus 
Published: April 2021

BACKGROUNDVarious forms of contact restrictions have been adopted in response to the Covid-19 pandemic. Around February 2021, rapid testing appeared as a new policy instrument. Some claim it may serve as a substitute for contact restrictions.OBJECTIVES/METHODSWe evaluate the effects of a unique policy experiment: In March and April 2021, the city of Tübingen set up a testing scheme while relaxing contact restrictions. We compare case rates in Tübingen county to an appropriately identified control unit.CONCLUSIONSThe experiment led to an increase in the reported case rate. This increase is robust across alternative statistical specifications. An epidemiological model that corrects for ‘more cases due to more testing’ and ‘reduced testing and reporting during the Easter holiday’ also confirms the finding.
Measuring the tolerance of the genetic code to altered codon size
Authors: DeBenedictis E. , Söll D. , Esvelt K. 
Published: April 2021

SummaryProtein translation using four-base codons occurs in both natural and synthetic systems. What constraints contributed to the universal adoption of a triplet-codon, rather than quadruplet-codon, genetic code? Here, we investigate the tolerance of theE. coligenetic code to tRNA mutations that increase codon size. We found that tRNAs from all twenty canonical isoacceptor classes can be converted to functional quadruplet tRNAs (qtRNAs), many of which selectively incorporate a single amino acid in response to a specified four-base codon. However, efficient quadruplet codon translation often requires multiple tRNA mutations, potentially constraining evolution. Moreover, while tRNAs were largely amenable to quadruplet conversion, only nine of the twenty aminoacyl tRNA synthetases tolerate quadruplet anticodons. These constitute a functional and mutually orthogonal set, but one that sharply limits the chemical alphabet available to a nascent all-quadruplet code. Our results illuminate factors that led to selection and maintenance of triplet codons in primordial Earth and provide a blueprint for synthetic biologists to deliberately engineer an all-quadruplet expanded genetic code.
Direct Nanopore Sequencing of Individual Full Length tRNA Strands
Authors: Thomas Niki , Poodari Vinay , Jain Miten , Olsen Hugh , Akeson Mark , Abu-Shumays Robin 
Published: April 2021

ABSTRACTWe describe a method for direct tRNA sequencing using the Oxford Nanopore MinION. The principal technical advance is custom adapters that facilitate end-to-end sequencing of individual tRNA molecules. A second advance is a Nanopore sequencing pipeline optimized for tRNA. We tested this method using purifiedE. colitRNAfMet, tRNALys, and tRNAPhesamples. 76-to-92% of individual aligned tRNA sequence reads were full length. As proof of concept, we showed that Nanopore sequencing detected all 42 expected tRNA isoacceptors in totalE. colitRNA. Alignment-based comparison between the three purified tRNAs and their synthetic controls revealed systematic miscalls at or adjacent to the positions of known nucleotide modifications. Systematic miscalls were also observed proximal to known modifications in totalE. colitRNA alignments.
Rcompadre and Rage - two R packages to facilitate the use of the COMPADRE and COMADRE databases and calculation of life history traits from matrix population models
Authors: Jones Owen R. , Barks Patrick , Stott Iain , James Tamora D. , Levin Sam , Petry William K. , Capdevila Pol , Che-Castaldo Judy , Jackson John , Römer Gesa , Schuette Caroline , Thomas Chelsea C. , Salguero-Gómez Roberto 
Published: April 2021

SummaryMatrix population models (MPMs) are an important tool for biologists seeking to understand the causes and consequences of variation in vital rates (e.g., survival, reproduction) across life cycles. Empirical MPMs describe the age- or stage-structured demography of organisms and usually represent the life history of a population during a particular time frame at a specific geographic location.The COMPADRE Plant Matrix Database and COMADRE Animal Matrix Database are the most extensive resources for MPM data, collectively containing >12,000 individual projection matrices for >1,100 species globally. Although these databases represent an unparalleled resource for researchers, land managers, and educators, the current computational tools available to answer questions with MPMs impose significant barriers to potential COM(P)ADRE database users by requiring advanced knowledge to handle diverse data structures and program custom analysis functions.To close this knowledge gap, we present two interrelated R packages designed to (i) facilitate the use of these databases by providing functions to acquire, quality control, and manage both the MPM data contained in COMPADRE and COMADRE, and a user’s own MPM data (Rcompadre), and (ii) present a range of functions to calculate life history traits from MPMs in support of ecological and evolutionary analyses (Rage). We provide examples to illustrate the use of both.RcompadreandRagewill facilitate demographic analyses using MPM data and contribute to the improved replicability of studies using these data. We hope that this new functionality will allow researchers, land managers, and educators to unlock the potential behind the thousands of MPMs and ancillary metadata stored in the COMPADRE and COMADRE matrix databases, and in their own MPM data.
Evolution of a cytoplasmic determinant: evidence for the biochemical basis of functional evolution of a novel germ line regulator
Authors: Blondel Leo , Besse Savandara , Extavour Cassandra G. 
Published: April 2021

AbstractGerm line specification is essential in sexually reproducing organisms. Despite their critical role, the evolutionary history of the genes that specify animal germ cells is heterogeneous and dynamic. In many insects, the geneoskaris required for the specification of the germ line. However, the germ line role ofoskaris thought to be a derived role resulting from co-option from an ancestral somatic role. To address how evolutionary changes in protein sequence could have led to changes in the function of Oskar protein that enabled it to regulate germ line specification, we searched foroskarorthologs in 1565 publicly available insect genomic and transcriptomic datasets. The earliest-diverging lineage in which we identified anoskarortholog was the order Zygentoma (silverfish and firebrats), suggesting thatoskaroriginated before the origin of winged insects. We noted some order-specific trends inoskarsequence evolution, including whole gene duplications, clade-specific losses, and rapid divergence. An alignment of all known 379 Oskar sequences revealed new highly conserved residues as candidates that promote dimerization of the LOTUS domain. Moreover, we identified regions of the OSK domain with conserved predicted RNA binding potential. Furthermore, we show that despite a low overall amino acid conservation, the LOTUS domain shows higher conservation of predicted secondary structure than the OSK domain. Finally, we suggest new key amino acids in the LOTUS domain that may be involved in the previously reported Oskar-Vasa physical interaction that is required for its germ line role.
Integrative biology defines novel biomarkers of resistance to strongylid infection in horses
Authors: Sallé Guillaume , Canlet Cécile , Cortet Jacques , Koch Christine , Malsa Joshua , Reigner Fabrice , Riou Mickaël , Perrot Noémie , Blanchard Alexandra , Mach Nuria 
Published: April 2021

AbstractThe widespread failure of anthelmintic drugs against nematodes of veterinary interest requires novel control strategies. Selective treatment of the most susceptible individuals could reduce drug selection pressure but requires appropriate biomarkers of the intrinsic susceptibility potential. To date, this has been missing in livestock species. Here, we selected Welsh ponies with divergent intrinsic susceptibility to cyathostomin infection and found that their potential was sustained across a 10-year time window. Using this unique set of individuals, we monitored variations in their blood cell populations, plasma metabolites and faecal microbiota over a grazing season to isolate core differences between their respective responses under worm-free or natural infection conditions. Our analyses identified the concomitant rise in plasmatic phenylalanine level and faecal Prevotella abundance and the reduction in circulating monocyte counts as biomarkers of the need for drug treatment. This biological signal was replicated in other independent populations. We also unravelled an immunometabolic network encompassing plasmatic beta-hydroxybutyrate level, short-chain fatty acid producing bacteria and circulating neutrophils that forms the discriminant baseline between susceptible and resistant individuals. Altogether our observations open new perspectives on the susceptibility of equids to cyathostomin infection and leave scope for both new biomarkers of infection and nutritional intervention.
Antiviral defense via nucleotide depletion in bacteria
Authors: Tal Nitzan , Millman Adi , Stokar-Avihail Avigail , Fedorenko Taya , Leavitt Azita , Melamed Sarah , Yirmiya Erez , Avraham Carmel , Amitai Gil , Sorek Rotem 
Published: April 2021

AbstractDNA viruses and retroviruses need to consume large quantities of deoxynucleotides (dNTPs) when replicating within infected cells. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral life cycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. In this study we report that bacteria employ a similar strategy to defend against phage infection. We found a family of defensive dCTP deaminase proteins that, in response to phage infection, convert dCTP into deoxy-uracil nucleotides. A second family of phage resistance genes encode dGTPase enzymes, which degrade dGTP into phosphate-free deoxy-guanosine (dG) and are distant homologs of the human SAMHD1. Our results show that the defensive proteins completely eliminate the specific deoxynucleotide (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Both defensive genes are found in a diverse set of bacterial species and are specifically enriched inVibriogenomes. Our study demonstrates that manipulation of the deoxynucleotide pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes.
Mitochondrial ribosomal proteins developed unconventional mitochondrial targeting signals due to structural constraints
Authors: Bykov Yury S. , Flohr Tamara , Boos Felix , Herrmann Johannes M. , Schuldiner Maya 
Published: April 2021

AbstractMitochondrial ribosomes are complex molecular machines indispensable for respiration. Their assembly involves the import of several dozens of mitochondrial ribosomal proteins (MRPs), encoded in the nuclear genome, into the mitochondrial matrix. Available proteomic and structural data as well as computational predictions indicate that up to 25% of MRPs do not have a conventional N-terminal mitochondrial targeting signal (MTS). We characterized a set of 15 yeast MRPsin vivoand showed that 30% of them use internal mitochondrial targeting signals. We isolated a novel internal targeting signal from the conserved MRP Mrp17 (bS6). The Mrp17 targeting signal shares some properties as well as import components with conventional MTS-containing proteins but is not reliably predicted indicating that mitochondrial protein targeting is more versatile than expected. We hypothesize that internal targeting signals arose in MRPs when the N-terminus extension was constrained by ribosome assembly interfaces.
Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
Authors: Sabino João C. , de Almeida Madalena R. , Abreu Patricia L. , Ferreira Ana M. , Domingues Marco M. , Santos Nuno C. , Azzalin Claus M. , Grosso Ana R. , de Almeida Sérgio F. 
Published: April 2021

AbstractDNA oxidation by ten-eleven translocation (TET) family enzymes is essential for epigenetic reprogramming. The conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) initiates developmental and cell-type-specific transcriptional programs through mechanisms that include changes in the chromatin structure. Here, we show that the presence of 5hmC in the transcribed DNA promotes the annealing of the nascent RNA to its template DNA strand, leading to the formation of an R-loop. The genome-wide distribution of 5hmC and R-loops show a positive correlation in mouse and human embryonic stem cells and overlap in half of all active genes. Moreover, R-loop resolution leads to differential expression of a subset of genes that are involved in crucial events during stem cell proliferation. Altogether, our data reveal that epigenetic reprogramming via TET activity promotes co-transcriptional R-loop formation, and disclose novel links between R-loops and the regulation of gene expression programs in stem cells.
Mechanical vibration patterns elicit behavioral transitions and habituation in crawlingDrosophilalarvae
Authors: Berne Alexander , Zhang Tom , Shomar Joseph , Ferrer Anggie J. , Valdes Aaron , Ohyama Tomoko , Klein Mason 
Published: April 2021

AbstractHow animals respond to repeatedly applied stimuli, and how animals respond to mechanical stimuli in particular, are important questions in behavioral neuroscience. We study adaptation to repeated mechanical agitation using theDrosophilalarva. Vertical vibration stimuli elicit a discrete set of responses in crawling larvae: continuation, pause, turn, and reversal. Through high-throughput larva tracking, we characterize how the likelihood of each response depends on vibration intensity and on the timing of repeated vibration pulses. By examining transitions between behavioral states at the population and individual levels, we investigate how the animals habituate to the stimulus patterns. We identify time constants associated with desensitization to prolonged vibration, with re-sensitization during removal of a stimulus, and additional layers of habituation that operate in the overall response. Known memory-deficient mutants exhibit distinct behavior profiles and habituation time constants. An analogous simple electrical circuit suggests possible neural and molecular processes behind adaptive behavior.
Fasting reduces inhibitory and attentional control of food-related cues
Authors: Ballestero-Arnau M , Rodríguez-Herreros B , Nuño-Bermúdez N , Cunillera T. 
Published: April 2021

AbstractThe metabolic and cognitive systems interact to create the motivational drive that occasionally leads to disrupted consummatory eating behaviors. In this study, we investigated whether stimulus-specific alterations of the inhibitory function are present following a period of food deprivation. Twenty-six participants with normal weight performed the Stop Signal Task (SST) and the Go/No-go (GNG) task to measure response inhibition to food images containing high or low caloric content after following –or not- a 12-hour fasting period. Response inhibition performance in the SST did not exhibit significant differences when considering neither fasting, stimulus type nor food caloric content. We instead found a higher percentage of commission errors in the No-go trials of the GNG task in the fasting session, and specially with high-caloric food items. In contrast, the accuracy in the Go trials was similar between conditions. A mixed logistic regression model confirmed the remarkable impact of fasting on the performance of response inhibition. Overall, our findings support an interpretation of the motivational drive to eat strongly associated with aspects of the inhibitory function underlying high attentional control, rather than to a proper response inhibition per se.
Evaluating the Anti-aging Effects of Chinese Herbal MedicineRhodiola roseaL. in Cultured Keratinocytes
Authors: Toh Wu Han , Chen Chun-Bing , Clapper Jude , Hsu Cheng-Chang , Lee Hua-en , Chung Wen-Hung 
Published: April 2021

ABSTRACTAmong the many health benefits Chinese herbal medicine (CHM) presents, anti-aging is of special interest (Shen, Jiang, Yang, Wang, & Zhu, 2017; Zhao & Luo, 2017). Reported to possess anti-aging effects, the CHMRhodiola roseaL., known colloquially as the “golden root”, has been widely incorporated in various drinks, daily supplements, and even cosmetics. This study investigates the effects of commercialR. roseaextracts and naturalR. rosearoots on preventing UV-induced photoaging of the skin and correlates such effects with the composition of active ingredients in the extracts. To simulate the photoaging process, drug treated HaCaT cells were exposed to UVA and UVB radiation. The pharmacological anti-aging effects ofR. roseaextracts were evaluated qualitatively and quantitatively through confocal immunofluorescence images with γ-H2A.X marker and telomerase activity assay (Telo TAGGG Telomerase PCR-ELISA). Preparatory thin layer chromatography and high-performance liquid chromatography were performed to isolate and quantify active ingredients. Cultured HaCaT cells showed morphological change after exposure to both UVA (>15.0 J) and UVB (>2000 mJ). The photoaging of keratinocytes was rescued by pretreating cells withR. roseaextracts as well as salidroside and rosavin active ingredients (P < 0.05).R. rosea-treated cells were characterized by increased telomerase activity and fewer γ-H2A.X foci compared to that of the control. Extracts with better preventative effects contained higher salidroside and rosavin content. The findings in this study reaffirmR. rosea’sefficacy as an anti-aging remedy and provide a basis for CHM’s integration into the mainstream of global healthcare.