bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transposable elements are constantly exchanged by horizontal transfer reshaping mosquito genomes
Authors: de Melo Elverson Soares , Luz Wallau Gabriel da 
Published: June 2020

AbstractTransposable elements (TEs) are a set of mobile elements within a genome. Due to their complexity, an in-depth TE characterization is only available for a handful of model organisms. In the present study, we performed ade novoand homology-based characterization of TEs in the genomes of 24 mosquito species and investigated their mode of inheritance. More than 40% of the genome ofAedes aegypti, Aedes albopictus, andCulex quinquefasciatusis composed of TEs, varying substantially amongAnophelesspecies (0.13%–19.55%). Class I TEs are the most abundant among mosquitoes and at least 24 TE superfamilies were found. Interestingly, TEs have been continuously exchanged by horizontal transfer (212 TE families of 18 different superfamilies) among mosquitoes since 30 million years ago, representing around 6% of the genome inAedesgenomes and a small fraction inAnophelesgenomes. Most of these horizontally transferred TEs are from the three ubiquitous LTR superfamilies: Gypsy, Bel-Pao and Copia. Searching more 32,000 genomes, we also uncover transfers between mosquitoes and two different Phyla—Cnidaria and Nematoda—and two subphyla—Chelicerata and Crustacea, identifying a vector, the wormWuchereria bancrofti, that enabled the horizontal spread of a Tc1-mariner element ofirritanssubfamily among variousAnophelesspecies. These data also allowed us to reconstruct the horizontal transfer network of this TE involving more than 40 species. In summary, our results suggest that TEs are constantly exchanged by common phenomena of horizontal transfers among mosquitoes, influencing genome variation and contributing to genome size expansion.Author SummaryMost eukaryotes have DNA fragments inside their genome that can multiply by inserting themselves in other regions of the genome, generating variability. These fragments are called Transposable Elements (TEs). Since they are a constituent part of the eukaryote genomes, these pieces of DNA are usually inherited vertically by the offspring. To avoid damage to the genome caused by the replication and insertion of TEs, organisms usually control them, leading to their inactivation. However, TEs sometimes get out of control and invade other species through a horizontal transfer mechanism. This dynamic is not known in mosquitoes, a group of organisms that acts as vectors of many human diseases. We collected mosquito genomes available in public databases and characterized the whole content of TEs. Using a statistic supported method, we investigate TE relations among mosquitoes and discover that horizontal transfers of transposons are common and occurred in the last 30 million years among these species. Although not as common as transfers among closely related species, transposon transfer to distant species also occur. We also identify a parasite, a filarial worm, that may have facilitated the transfer of TE to many mosquitoes. Together, horizontally transferred TEs contribute to increasing mosquito genome size and variation.
The RNA-binding protein Igf2bp3 is critical for embryonic and germline development in zebrafish
Authors: Vong Yin Ho , Sivashanmugam Lavanya , Zaucker Andreas , Jones Alex , Sampath Karuna 
Published: June 2020

AbstractThe ability to reproduce is essential in all branches of life. In metazoans, this process is initiated by formation of the germline, a group of cells that are destined to form the future gonads, the tissue that will produce the gametes. The molecular mechanisms underlying germline formation differs between species. In zebrafish, development of the germline is dependent on the specification, migration and proliferation of progenitors called the primordial germ cells (PGCs). PGC specification is dependent on a maternally provided cytoplasmic complex of ribonucleoproteins (RNPs), the germplasm. Here, we show that the conserved RNA-binding protein (RBP), Igf2bp3, has an essential role during early embryonic development and germline development. Loss of Igf2bp3 leads to an expanded yolk syncytial layer (YSL) in early embryos, reduced germline RNA expression, and mis-regulated germline development. Maternal mutants affecting igf2bp3 exhibit abnormal PGCs and adult igf2bp3 mutants show male biased sex ratios. Therefore, Igf2bp3 is required for normal embryonic and germline development.
A highly stable, nondigestible lectin fromPomacea diffusaunveils clade-related protection systems in apple snail eggs
Authors: Brola TR , Dreon MS , Qiu JW , Heras H 
Published: June 2020

AbstractThe acquisition of egg protection is vital for species survival. Poisonous eggs fromPomaceaapple snails have defensive macromolecules for protection. Here we isolated and characterized a novel lectin called PdPV1 that is massively accumulated in the eggs ofPomacea diffusaand seems part of its protective cocktail. The native protein, an oligomer of ca. 256 kDa, has high structural stability, withstanding 15 min boiling and denaturing by sodium dodecyl sulphate. It resistsin vitroproteinase digestion and displays structural stability between pH 2.0–12.0 and up to 85 °C. These properties, as well as its subunit sequences, glycosylation pattern, presence of carotenoids, size, and global shape resemble those of its orthologs from otherPomacea. Further, like members of thecanaliculataclade, PdPV1 is recovered unchanged in faeces of mice ingesting it, supporting an antinutritive defensive function. PdPV1 also displays a strong hemagglutinating activity specifically recognizing selected ganglioside motifs with high affinity. This activity is only shared with PsSC, a perivitelline from the same clade (bridgesiiclade). As a whole, these results indicate that species in the genusPomaceahave diversified their eggs defences: Those from thebridgesiiclade are protected mostly by non-digestible lectins that lower the nutritional value of eggs, in contrast with protection by neurotoxins of otherPomaceaclades, indicating apple snail egg defensive strategies are clade-specific. The harsh gastrointestinal environment of predators would have favoured their appearance, extending by convergent evolution the presence of plant-like highly stable lectins, a strategy not reported in other animals.Summary statementAnalysis of key snail egg proteins shows evolutionary defensive trends associated with the phylogenetic position, extending by convergent evolution the presence of plant-like defensive strategies not reported in other animals
An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19
Authors: Shrimp Jonathan H. , Kales Stephen C. , Sanderson Philip E. , Simeonov Anton , Shen Min , Hall Matthew D. 
Published: June 2020

AbstractSARS-CoV-2 is the viral pathogen causing the COVID19 global pandemic. Consequently, much research has gone into the development of pre-clinical assays for the discovery of new or repurposing of FDA-approved therapies. Preventing viral entry into a host cell would be an effective antiviral strategy. One mechanism for SARS-CoV-2 entry occurs when the spike protein on the surface of SARS-CoV-2 binds to an ACE2 receptor followed by cleavage at two cut sites (“priming”) that causes a conformational change allowing for viral and host membrane fusion. TMPRSS2 has an extracellular protease domain capable of cleaving the spike protein to initiate membrane fusion. A validated inhibitor of TMPRSS2 protease activity would be a valuable tool for studying the impact TMPRSS2 has in viral entry and potentially be an effective antiviral therapeutic. To enable inhibitor discovery and profiling of FDA-approved therapeutics, we describe an assay for the biochemical screening of recombinant TMPRSS2 suitable for high throughput application. We demonstrate effectiveness to quantify inhibition down to subnanomolar concentrations by assessing the inhibition of camostat, nafamostat and gabexate, clinically approved agents in Japan. Also, we profiled a camostat metabolite, FOY-251, and bromhexine hydrochloride, an FDA-approved mucolytic cough suppressant. The rank order potency for the compounds tested are: nafamostat (IC50= 0.27 nM), camostat (IC50= 6.2 nM), FOY-251 (IC50= 33.3 nM) and gabexate (IC50= 130 nM). Bromhexine hydrochloride showed no inhibition of TMPRSS2. Further profiling of camostat, nafamostat and gabexate against a panel of recombinant proteases provides insight into selectivity and potency.
S1-Domain RNA-Binding Protein (CvfD) Is a New Post-Transcriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence inStreptococcus pneumoniaeD39
Authors: Sinha Dhriti , Zheng Jiaqi J. , Tsui Ho-Ching Tiffany , Richardson John D. , De Lay Nicholas R. , Winkler Malcolm E. 
Published: June 2020

ABSTRACTPost-transcriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogenStreptococcus pneumoniaeD39 (pneumococcus) does not encode homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. However, the pneumococcal genome contains genes for other RNA-binding proteins, including at least six S1-domain proteins; ribosomal protein S1 (rpsA), polynucleotide phosphorylase(pnpA), RNase R (rnr), and three proteins of unknown functions. Here, we characterize the function of one of these conserved, yet uncharacterized S1-domain proteins, SPD_1366, which we have renamed CvfD (ConservedvirulencefactorD), since loss of this protein results in an attenuation of virulence in a murine pneumonia model. We report that deletion ofcvfDimpacts expression of 144 transcripts including thepst1operon, encoding the phosphate transport system 1 inS. pneumoniae. We further show that CvfD post-transcriptionally regulates the PhoU2 master regulator of the pneumococcal dual phosphate transport system by bindingphoU2mRNA and impacting PhoU2 translation. CvfD not only controls expression of phosphate transporter genes, but also functions as a pleiotropic regulator that impacts cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data show that CvfD exerts a broad impact on pneumococcal physiology and virulence, partly by post-transcriptional gene regulation.SIGNIFICANCERecent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen,S. pneumoniae. However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1-domain RNA-binding protein CvfD, a homolog of “general-stress protein 13” identified, but not extensively characterized in otherFirmicutespecies. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.
Identification and characterization of centromeric sequences inXenopus laevis
Authors: Smith Owen K , Limouse Charles , Fryer Kelsey A , Teran Nicole A , Sundararajan Kousik , Heald Rebecca , Straight Aaron F 
Published: June 2020

AbstractCentromeres play an essential function in cell division by specifying the site of kinetochore formation on each chromosome for mitotic spindle attachment. Centromeres are defined epigenetically by the histone H3 variant CEntromere Protein A (CENP-A). CENP-A nucleosomes maintain the centromere by designating the site for new CENP-A assembly after dilution by replication. Vertebrate centromeres assemble on tandem arrays of repetitive sequences but the function of repeat DNA in centromere formation has been challenging to dissect due to the difficulty in manipulating centromeres in cells.Xenopus laevisegg extracts assemble centromeresin vitro, providing a system for studying centromeric DNA functions. However, centromeric sequences inX. laevishave not been extensively characterized. In this study we combine CENP-A ChIP-seq with a k-mer based analysis approach to identify theX. laeviscentromere repeat sequences. Byin situhybridization we show thatX. laeviscentromeres contain diverse repeat sequences and we map the centromere position on eachX. laevischromosome using the distribution of centromere enriched k-mers. Our identification ofX. laeviscentromere sequences enables previously unapproachable centromere genomic studies. Our approach should be broadly applicable for the analysis of centromere and other repetitive sequences in any organism.
Super LeArner Prediction of NAb Panels (SLAPNAP): A Containerized Tool for Predicting Combination Monoclonal Broadly Neutralizing Antibody Sensitivity
Authors: Benkeser D , Williamson BD , Magaret CA , Nizam S , Gilbert PB 
Published: June 2020

AbstractSummarySingle broadly neutralizing antibody (bnAb) regimens are currently being evaluated in randomized trials for prevention efficacy against HIV-1 infection. Subsequent trials will evaluate combination bnAb regimens (e.g., cocktails, multi-specific antibodies), which demonstrate higher potency and breadth in vitro compared to single bnAbs. Given the large number of potential regimens in the research pipeline, methods for down-selecting these regimens into efficacy trials are of great interest. To aid the down-selection process, we developed Super LeArner Prediction of NAb Panels (SLAPNAP), a software tool for training and evaluating machine learning models that predict in vitro neutralization resistance of HIV Envelope pseudoviruses to a given single or combination bnAb regimen, based on Envelope amino acid sequence features. SLAPNAP also provides measures of variable importance of sequence features. These results can rank bnAb regimens by their potential prevention efficacy and aid assessments of how prevention efficacy depends on sequence features.Availability and ImplementationSLAPNAP is a freely available docker image that can be downloaded from DockerHub (https://hub.docker.com/r/slapnap/slapnap). Source code and documentation are available at GitHub (respectively,https://github.com/benkeser/slapnapandhttps://benkeser.github.io/slapnap/).ContactDavid Benkeser,benkeser@emory.edu
Response preparation involves a release of intracortical inhibition in task-irrelevant muscles
Authors: Gomez Isaac N. , Ormiston Kara , Greenhouse Ian 
Published: June 2020

AbstractAction preparation involves widespread modulation of motor system excitability, but the precise mechanisms are unknown. In this study, we investigated whether intracortical inhibition changes in task-irrelevant muscle representations during action preparation. We used transcranial magnetic stimulation (TMS) combined with electromyography in healthy human adults to measure motor evoked potentials (MEPs) and cortical silent periods (CSPs) in task-irrelevant muscles during the preparatory period of simple delayed response tasks. In Experiment 1, participants responded with the left-index finger in one task condition and the right-index finger in another task condition, while MEPs and CSPs were measured from the contralateral non-responding and tonically contracted index finger. During Experiment 2, participants responded with the right pinky finger while MEPs and CSPs were measured from the tonically contracted left-index finger. In both experiments, MEPs and CSPs were compared between the task preparatory period and a resting intertrial baseline. The CSP duration during response preparation decreased from baseline in every case. A laterality difference was also observed in Experiment 1, with a greater CSP reduction during the preparation of left finger responses compared to right finger responses. MEP amplitudes showed no modulation during movement preparation in any of the three response conditions. These findings indicate cortical inhibition associated with task-irrelevant muscles is transiently released during action preparation and implicate a novel mechanism for the controlled and coordinated release of motor cortex inhibition.New & NoteworthyIn this study we observed the first evidence of a release of intracortical inhibition in task-irrelevant muscle representations during response preparation. We applied transcranial magnetic stimulation to elicit cortical silent periods in task-irrelevant muscles during response preparation and observed a consistent decrease in the silent period duration relative to a resting baseline. These findings address the question of whether cortical mechanisms underlie widespread modulation in motor excitability during response preparation.
Visual mismatch responses index surprise signalling but not expectation suppression
Authors: Feuerriegel Daniel , Yook Jane , Quek Genevieve L. , Hogendoorn Hinze , Bode Stefan 
Published: June 2020

AbstractThe ability to distinguish between commonplace and unusual sensory events is critical for efficient learning and adaptive behaviour. This has been investigated using oddball designs in which sequences of often-appearing (i.e. expected) stimuli are interspersed with rare (i.e. surprising) deviants. Resulting differences in electrophysiological responses following surprising compared to expected stimuli are known as visual mismatch responses (VMRs). VMRs are thought to index co-occurring contributions of stimulus repetition effects, expectation suppression (that occurs when one’s expectations are fulfilled), and expectation violation (i.e. surprise) responses; however, these different effects have been conflated in existing oddball designs. To better isolate and quantify effects of expectation suppression and surprise, we adapted an oddball design based on Fast Periodic Visual Stimulation (FPVS) that controls for stimulus repetition effects. We recorded electroencephalography (EEG) while participants (N=48) viewed stimulation sequences in which a single face identity was periodically presented at 6 Hz. Critically, one of two different face identities (termed oddballs) appeared as every 7th image throughout the sequence. The presentation probabilities of each oddball image within a sequence varied between 10-90%, such that participants could form expectations about which oddball face identity was more likely to appear within each sequence. We also included ‘expectation neutral’ 50% probability sequences, whereby consistently biased expectations would not be formed for either oddball face identity. We found that VMRs indexed surprise responses, and effects of expectation suppression were absent. That is, ERPs were more negative-going at occipitoparietal electrodes for surprising compared to neutral oddballs, but did not differ between expected and neutral oddballs. Surprising oddball-evoked ERPs were also highly similar across the 10-40% appearance probability conditions. Our findings indicate that VMRs which are not accounted for by repetition effects are best described as an all-or-none surprise response, rather than a minimisation of prediction error responses associated with expectation suppression.Highlights-We used a recently-developed oddball design that controls for repetition effects-We found effects of surprise but not expectation suppression on ERPs-Surprise responses did not vary by stimulus appearance probability
Condensation tendency of connected contractile tissue with planar isotropic actin network
Authors: Xie Tianfa , Pierre Sarah R. St. , Olaranont Nonthakorn , Brown Lauren E. , Wu Min , Sun Yubing 
Published: June 2020

ABSTRACTIt has been found that many types of cells form nematic symmetry on confined planar substrates. Such observation has been satisfactorily explained by modeling cells as crowded self-propelled rods. In this work, we report that rat embryonic fibroblast (REF) cells when confined in circular mesoscale patterns, form a new type of symmetry where cells align radially at the boundary. Unlike NIH-3T3 and MDCK monolayers, the REF monolayer presents a supracellular actin gradient with isotropic meshwork. In addition, the contractile REF cells present strong adhesive interactions with neighboring cells, which confers the monolayer with significant condensation tendency. We found the loss of condensation tendency by inhibiting the cell contractility or disrupting cell-cell adhesion led to the disappearance of the radial alignment. In theory, we found the prestretch due to condensation tendency with differential cell stiffness is sufficient to explain the new symmetry within a confined tissue continuum.
Development and Validation of a web-based Postoperative Clostridioides difficile infection risk prediction model
Authors: Woo Sang H. , Hess Bryan , Ackermann Lily , Cowan Scott W. , Valentine Jennifer 
Published: June 2020

AbstractBackgroundClostridioides difficile infection is associated with significant morbidity, mortality and increased costs. Assessment of the postoperative C. difficile infection risk is necessary to improve the outcome of surgical patients.ObjectiveTo develop and validate a risk prediction tool for C. difficile infection after surgery.MethodsIn this retrospective cohort study, 2,451,169 surgical patients from the American College of Surgeons National Surgical Quality Improvement Program Database (ACS-NSQIP) over 2015-2017 were included. Nine predictors were selected for the model: age, preoperative leukocytosis (>12 ×109/L), hematocrit (≤30%), chronic dialysis, insulin dependent diabetes, weight loss, steroid use, presence of preoperative sepsis, and surgery type. A second model included hospital length of stay as a predictor. A predictive model was developed using ACS-NSQIP 2015-2016 training cohort (n=1,435,157) and tested using 2017 validation cohort (n=1,016,012). Multivariate logistic regression was used for the model.Main outcomeThe primary outcome was postoperative 30-day C. difficile infection (CDI).Results0.39% of the patients (n=9,675) developed CDI and 42.3% (n=4,091) of CDI occurred post-discharge. The Clostridioides difficile risk prediction model had excellent AUC (area under the receiver operating characteristic curve) for postoperative C. difficile infection (training cohort=0.804, test cohort= 0.803). The model that includes hospital length of stay has a high AUC (training cohort=0.841, test cohort=0.838).ConclusionThe C. difficile prediction model provides a robust predictive tool for postoperative C. difficile infection.