bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural landscape of the complete genomes of Dengue serotypes and other viral hemorrhagic fevers
Authors: Delli-Ponti Riccardo , Mutwil Marek 
Published: April 2020

ABSTRACTBackgroundWith more than 300 million potentially infected people every year, and with the expanded habitat of mosquitoes due to climate change, dengue cannot be considered anymore only a tropical disease. The RNA secondary structure is a functional characteristic of RNA viruses, and together with the accumulated high-throughput sequencing data could provide general insights towards understanding virus biology. Here, we profiled the RNA secondary structure of >7500 complete viral genomes from 11 different species of viral hemorrhagic fevers, including dengue serotypes, ebola, and yellow fever.ResultsWe achieved hig prediction scores (AUC up to 0.85 with experimental data), and computed consensus secondary structure profiles using hundreds of structuralin silicomodels. We observed that virulent viruses such as DENV-2 and ebola tend to be less structured than the other viruses. Furthermore, we observed virus-specific correlations between secondary structure and the number of interaction sites with human proteins, reaching a correlation of 0.89 in the case of zika. We demonstrate that the secondary structure and presence of protein-binding domains in the genomes can be used as intrinsic signature to further classify the viruses. We also used structural data to study the geographical distribution of dengue, finding a significant difference between DENV-3 from Asia and South-America, which could imply different evolutionary routes of this subtype.ConclusionsOur massive computational analysis provided novel results regarding the secondary structure and the interaction with human proteins, not only for Dengue serotypes, but also for other viral hemorrhagic fevers. We also provided a new approach to classify viruses according ot their structure, which could be useful for future cassifications. We envision that these approaches can be used by the scientific community to further classify and characterise these complex viruses.
Development of a SYBR Green quantitative PCR assay for detection ofLates calcarifer herpesvirus(LCHV) in farmed barramundi
Authors: Meemetta Watcharachai , Domingos Jose A. , Dong Ha Thanh , Senapin Saengchan 
Published: April 2020

ABSTRACTLates calcariferherpes virus (LCHV) is a new virus of farmed barramundi in Southeast Asia. However, a rapid detection method is yet to be available for LCHV. This study, therefore, aimed to develop a rapid quantitative PCR (qPCR) detection method for LCHV and made it timely available to public for disease diagnostics and surveillance in barramundi farming countries. A newly designed primer set targeting a 93-bp fragment of the LCHV putative major envelope protein encoding gene (MEP) was used for developing and optimizing a SYBR Green based qPCR assay. The established protocol could detect as low as 10 viral copies per µl of DNA template in a reaction containing spiked host DNA. No cross-amplification with genomic DNA extracted from host as well as common aquatic pathogens (12 bacteria and 3 viruses) were observed. Validation test of the method with clinical samples revealed that the virus was detected in multiple organs of the clinically sick fish but not in the healthy fish. We thus recommend that barramundi farming countries should promptly initiate active surveillance for LCHV in order to understand their circulation for preventing possibly negative impact to the industry.HighlightsThis study reported a new SYBR Green qPCR method for detection of LCHVThe qPCR method had detection limit of 10 copies per µl plasmid DNA template when spiked with genomic DNA from the hostThe aforementioned method is highly specific to LCHVValidation with clinical samples revealed that LCHV could be detected from multiple organs with fin and brain the best organs for qPCR detection
G protein-regulated endocytic trafficking of adenylyl cyclase type 9
Authors: Lazar André M. , Irannejad Roshanak , Baldwin Tanya A. , Sundaram Aparna A. , Gutkind J. Silvio , lnoue Asuka , Dessauer Carmen W. , von Zastrow Mark 
Published: April 2020

SummaryGPCRs are increasingly recognized to initiate signaling via heterotrimeric G proteins as they move through the endocytic network, but little is known about how relevant G protein effectors are localized. Here we report dynamic trafficking of adenylyl cyclase type 9 (AC9) from the plasma membrane to endosomes, while adenylyl cyclase type 1 (AC1) remains in the plasma membrane, and stimulation of AC9 trafficking by ligand-induced activation of Gs-coupled GPCRs or Gs. AC9 transits a similar dynamin-dependent early endocytic pathway as activated GPCRs but, in contrast to GPCR trafficking which is regulated by β-arrestin but not Gs, AC9 trafficking is regulated by Gs but not β-arrestin. We also show that AC9, but not AC1, contributes to cAMP production from endosomes. These results reveal dynamic and isoform-specific trafficking of adenylyl cyclase in the endocytic network, and a discrete role of a heterotrimeric G protein in controlling subcellular location of a relevant effector.
ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from anin silicostudy
Authors: Calcagnile Matteo , Forgez Patricia , Iannelli Antonio , Bucci Cecilia , Alifano Marco , Alifano Pietro 
Published: April 2020

AbstractThe current SARS covid-19 epidemic spread appears to be influenced by ethnical, geographical and sex-related factors that may involve genetic susceptibility to diseases. Similar to SARS-CoV, SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells, notably type II alveolar epithelial cells. Importantly, ACE2 gene is highly polymorphic. Here we have usedin silicotools to analyze the possible impact of ACE2 single-nucleotide polymorphisms (SNPs) on the interaction with SARS-CoV-2 spike glycoprotein. We found that S19P (common in African people) and K26R (common in European people) were, among the most diffused SNPs worldwide, the only two SNPs that were able to potentially affect the interaction of ACE2 with SARS-CoV-2 spike. FireDock simulations demonstrated that while S19P may decrease, K26R might increase the ACE2 affinity for SARS-CoV-2 Spike. This finding suggests that the S19P may genetically protect, and K26R may predispose to more severe SARS-CoV-2 disease.
SQMtools: automated processing and visual analysis of ’omics data with R and anvi’o
Authors: Puente-Sánchez Fernando , García-García Natalia , Tamames Javier 
Published: April 2020

AbstractBackgroundThe dramatic decrease in sequencing costs over the last decade has boosted the adoption of high-throughput sequencing applications as a standard tool for the analysis of environmental microbial communities. Nowadays even small research groups can easily obtain raw sequencing data. After that, however, non-specialists are faced with the double challenge of choosing among an ever-increasing array of analysis methodologies, and navigating the vast amounts of results returned by these approaches.ResultsHere we present a workflow that relies on the SqueezeMeta software for the automated processing of raw reads into annotated contigs and reconstructed genomes (bins). A set of custom scripts seamlessly integrates the output into the anvi’o analysis platform, allowing filtering and visual exploration of the results. Furthermore, we provide a software package with utility functions to expose the SqueezeMeta results to the R analysis environment.ConclusionsAltogether, our workflow allows non-expert users to go from raw sequencing reads to custom plots with only a few powerful, flexible and well-documented commands.
Fat1 regulates astrocyte maturation and angiogenesis in the retina
Authors: Helmbacher Françoise 
Published: April 2020

AbstractAngiogenesis is a stepwise process leading to blood vessel formation. In the vertebrate retina, endothelial cells are guided by astrocytes migrating along the inner surface, and the two processes are coupled by a tightly regulated cross-talk between the two cell types. Here, we investigated how the FAT1 Cadherin, a regulator of tissue morphogenesis governing tissue cross-talks, influences retinal vascular development. Through late-onset inactivation in the neural lineage in mice, we bypassed an early contribution of Fat1 to eye development, and assessed its requirement for postnatal retina angiogenesis. We found that neural Fat1 expression, by controlling the polarity of astrocyte progenitor migration, regulates astrocyte maturation. By interfering with astrocyte migration and maturation, neural Fat1 deletion deregulates the astrocyte/endothelial cell coupling, and delays retinal angiogenesis. Mice with neural-Fat1 ablation exhibit persistent abnormalities of the retinal vascular architecture, such as an increased vascular density in deep layers. Altogether, this study identifies Fat1 as a regulator of neurovascular communication, essential for retinal vascular development and integrity.
Detecting rare copy number variants (CNVs) from Illumina genotyping arrays with the CamCNV pipeline: segmentation of z-scores improves detection and reliability
Authors: Dennis Joe , Walker Logan , Tyrer Jonathan , Michailidou Kyriaki , Easton Douglas F. 
Published: April 2020

AbstractBackgroundThe intensities from genotyping array data can be used to detect CNVs but a high level of noise in the data and overlap between different copy-number intensity distributions produces unreliable calls, particularly when only a few probes are covered by the CNV.ResultsWe present a novel pipeline (CamCNV) with a series of steps to reduce noise and detect more reliably rare CNVs covering as few as three probes. The method uses the information from all samples to convert intensities to z-scores, thus adjusting for variance between probes. We tested the sensitivity of our pipeline by looking for known CNVs from the 1000 Genomes project in our genotyping of 1000 Genomes samples. We also compared the CNV calls for 1,661 pairs of genotyped replicate samples. At the chosen mean z-score cut-off, sensitivity to detect the 1000 Genomes CNVs was approximately 85% for deletions and 65% for duplications. From the replicates we estimate the false discovery rate is controlled at ∼10% for deletions (falling to below 3% with more than five probes) and ∼28% for duplications. The pipeline demonstrates improved sensitivity when compared to calling with PennCNV, particularly for short deletions covering only a few probesConclusionThe CamCNV pipeline provides a reliable method of detecting rare CNVs from Illumina array data and can be used for CNVs that only cover a few probes. For each called CNV the mean z-score is a useful metric for controlling the false discovery rate.
Respiration modulates oscillatory neural network activity at rest
Authors: Kluger Daniel S. , Gross Joachim 
Published: April 2020

AbstractDespite recent advances in understanding how respiration affects neural signalling to influence perception, cognition, and behaviour, it is yet unclear to what extent breathing modulates brain oscillations at rest. We acquired respiration and resting state magnetoencephalography (MEG) data from human participants to investigate if, where, and how respiration cyclically modulates oscillatory amplitudes (2 – 150 Hz). Using measures of phase-amplitude coupling, we show respiration-modulated brain oscillations (RMBOs) across all major frequency bands. Sources of these modulations spanned a widespread network of cortical and subcortical brain areas with distinct spectro-temporal modulation profiles. Globally, high-frequency gamma modulation increased with distance to the head centre, whereas delta and theta modulation decreased with height in the sagittal plane. Overall, we provide the first comprehensive mapping of RMBOs across the entire brain, highlighting respiration-brain coupling as a fundamental mechanism to shape neural processing within canonical resting-state and respiratory control networks.
A polyetic modelling framework for plant disease emergence
Authors: Willocquet Laetitia , Savary S. , McDonald B.A. , Mikaberidze A. 
Published: April 2020

AbstractPlant disease emergences have dramatically increased recently as a result of global changes, especially with respect to trade, host genetic uniformity, and climate change. A better understanding of the conditions and processes determining epidemic outbreaks caused by the emergence of a new pathogen, or pathogen strain, is needed to develop strategies and inform decisions to manage emerging diseases. A polyetic process-based model is developed to analyse conditions of disease emergence. This model simulates polycyclic epidemics during successive growing seasons, the yield losses they cause, and the pathogen survival between growing seasons. This framework considers an immigrant strain coming into a system where a resident strain is already established. Outcomes are formulated in terms of probability of emergence, time to emergence, and yield loss, resulting from deterministic and stochastic simulations. An analytical solution to determine a threshold for emergence is also derived. Analyses focus on the effects of two fitness parameters on emergence: the relative rate of reproduction (speed of epidemics), and the relative rate of mortality (decay of population between seasons). Analyses revealed that stochasticity is a critical feature of disease emergence. The simulations suggests that: (1) emergence may require a series of independent immigration events before a successful invasion takes place; (2) an explosion in the population size of the new pathogen (or strain) may be preceded by many successive growing seasons of cryptic presence following an immigration event, and; (3) survival between growing seasons is as important as reproduction during the growing season in determining disease emergence.
Shared neuronal bases of inhibition and economic choice in orbitofrontal cortex
Authors: Balasubramani Pragathi Priyadharsini , Hayden Benjamin Y. 
Published: April 2020

ABSTRACTEconomic choice and inhibition are two important elements of our cognitive repertoires that may be closely related. We and others have noted that during economic choice, options are typically considered serially; this fact provides important constraints on our understanding of choice. Notably, asynchronous contemplation means that each individual option is subject to an accept-reject decision. We have proposed that these component accept-reject decisions may have some kinship with stopping decisions. One prediction of this idea is that stopping and choice may reflect similar neural processes occurring in overlapping brain circuits. To test the idea, we recorded neuronal activity in orbitofrontal cortex (OFC) Area 13 while macaques performed a stop signal task interleaved with a structurally matched choice task. Using neural network decoders, we find that OFC ensembles have overlapping codes for stopping and choice: the decoder that was only trained to identify accept vs. reject trials performed with higher efficiency even when tested on the stop trials. These results provide tentative support for the idea that mechanisms underlying inhibitory control and choice selection may be subject to theoretical unification.
Degradation of Alzheimer’s amyloid-β by a catalytically inactive insulin-degrading enzyme
Authors: Sahoo Bikash R. , Panda Pritam Kumar , Liang Wenguang , Tang Wei-Jen , Ahuja Rajeev , Ramamoorthy Ayyalusamy 
Published: April 2020

AbstractIt is known that insulin-degrading-enzyme (IDE) plays a crucial role in the clearance of Alzheimer’s amyloid-β (Aβ). The cysteine-free IDE mutant (cf-E111Q-IDE) is catalytically inactive against insulin, but its effect on Aβ degradation is unknown that would help in the allosteric modulation of the enzyme activity. Herein, the degradation of Aβ(1-40) by cf-E111Q-IDE via a non-chaperone mechanism is demonstrated by NMR and LC-MS, and the aggregation of fragmented peptides is characterized using fluorescence and electron microscopy. cf-E111Q-IDE presented a reduced effect on the aggregation kinetics of Aβ(1-40) when compared with the wild-type IDE. Whereas LC-MS and diffusion ordered NMR spectroscopy revealed the generation of Aβ fragments by both wild-type and cf-E111Q-IDE. The aggregation propensities and the difference in the morphological phenotype of the full-length Aβ(1-40) and its fragments are explained using multi-microseconds molecular dynamics simulations. Notably, our results reveal that zinc binding to Aβ(1-40) inactivates cf-E111Q-IDE’s catalytic function, whereas zinc removal restores its function as evidenced from high-speed AFM, electron microscopy, chromatography, and NMR results. These findings emphasize the catalytic role of cf-E111Q-IDE on Aβ degradation and urge the development of zinc chelators as an alternative therapeutic strategy that switches on/off IDE’s function.
Tracking crystallophore nucleating properties: setting-up a database for statistical analysis
Authors: Jiang Tao , Roux Amandine , Engilberge Sylvain , Alsalman Zaynab , Di Pietro Sebastiano , Franzetti Bruno , Riobé François , Maury Olivier , Girard Eric 
Published: April 2020

ABSTRACTIn this article, the principle of a database aimed at facilitating the understanding of the unique protein nucleating properties of the Crystallophore is presented. A first analysis allows us to compare the efficiency of Tb-Xo4 with the new Lu-Xo4 variant, featuring improved phasing properties. Then, the concept ofsubset-of-interestis introduced to reveal potential antagonistic/synergistic effects between Tb-Xo4 and physico-chemical parameters of the crystallisation kits such as pH. The overall approach may be of interest for any studies working on solutions dedicated to improve the nucleating step in protein crystallization.TOC GraphicSynopsisA database and associated representation tools are highlighted to understand nucleating properties of the crystallophore.
Cassava common mosaic viruscauses photosynthetic alterations associated with changes in chloroplast ultrastructure and carbohydrate metabolism of cassava plants
Authors: Zanini Andrea A. , Di Feo Liliana , Luna Dario F. , Paccioretti Pablo , Collavino Agostina , Rodriguez Marianela S. 
Published: April 2020

AbstractCassava common mosaic virus(CsCMV) is a potexvirus that causes systemic infections in cassava plants, leading to chlorotic mosaic and producing significant yield losses. To date, the physiological alterations and the mechanism underlying biotic stress during the cassava-CsCMV compatible interaction remains unknown. In this study, we found that CsCMV infection adversely modified chloroplast structure and had functional effects on chloroplasts in source leaves during the course of viral infection. Extrusion of the chloroplast membrane with amoeboid-shaped appearance was observed in infected mesophyll cells. These alterations were associated with lower relative chlorophyll content, and reduced PSII efficiency and CO2fixation. Moreover, an oxidative stress process was observed in CsCMV-infected plants. Strong declines in the maximum quantum yield of primary photochemistry (Fv/Fm) were observed in infected plants. Furthermore, the analysis of Chlorophyll-a fluorescence (ChlF) evidenced a progressive loss of both oxygen evolving complex activity and “connectivity” within the tripartite system (core antenna-LHCII-Reaction Centre). Other effects of the pathogen included reduction of starch and maltose content in source leaves, and a significant increase of the sucrose/starch ratio, which indicates alteration pattern of carbon. Our results suggest that CsCMV induces chloroplast distortion associated with progressive chloroplast function loss and diversion of carbon flux in source leaf tissue, which should be key in inducing yield losses of infected crops.Main conclusionCsCMV infection adversely modified chloroplast structure and had functional effects on chloroplasts during the course of viral infection, associated with metabolic adjustment in cassava source leaves, which would partly explain cassava root yield losses.
The coronavirus proofreading exoribonuclease mediates extensive viral recombination
Authors: Gribble Jennifer , Pruijssers Andrea J. , Agostini Maria L. , Anderson-Daniels Jordan , Chappell James D. , Lu Xiaotao , Stevens Laura J. , Routh Andrew L. , Denison Mark R. 
Published: April 2020

SUMMARYCoronaviruses (CoVs) emerge as zoonoses and cause severe disease in humans, demonstrated by the SARS-CoV-2 (COVID-19) pandemic. RNA recombination is required during normal CoV replication for subgenomic mRNA (sgmRNA) synthesis and generates defective viral genomes (DVGs) of unknown function. However, the determinants and patterns of CoV recombination are unknown. Here, we show that divergent β-CoVs SARS-CoV-2, MERS-CoV, and murine hepatitis virus (MHV) perform extensive RNA recombination in culture, generating similar patterns of recombination junctions and diverse populations of DVGs and sgmRNAs. We demonstrate that the CoV proofreading nonstructural protein (nsp14) 3’-to-5’ exoribonuclease (nsp14-ExoN) is required for normal CoV recombination and that its genetic inactivation causes significantly decreased frequency and altered patterns of recombination in both infected cells and released virions. Thus, nsp14-ExoN is a key determinant of both high fidelity CoV replication and recombination, and thereby represents a highly-conserved and vulnerable target for virus inhibition and attenuation.
The impacts of body mass on immune cell concentrations in birds
Authors: Ruhs Emily Cornelius , Martin Lynn B. , Downs Cynthia J. 
Published: April 2020

ABSTRACTBody mass affects many biological traits, but its impacts on immune defenses are fairly unknown. Recent research on mammals found that neutrophil concentrations scaled hypermetrically with body mass, a result not predicted by any existing theory. Although this mammalian model might predict how leukocyte concentrations scale with body mass in other vertebrates, vertebrate classes are distinct in many ways that might affect their current and historic interactions with parasites and hence the evolution of their immune systems. Subsequently, here, we asked which existing scaling hypothesis best-predicted relationships between body mass and lymphocyte, eosinophil, and heterophil concentrations—the avian functional equivalent of neutrophils—among >100 species of birds. We then examined the predictive power of body mass relative to life-history variation, as an extensive literature indicates that the scheduling of key life events has influenced immune system variation among species. Finally, we ask whether these scaling patterns differ from the patterns we observed in mammals. We found that an intercept-only model best-explained lymphocyte and eosinophil concentrations among birds; body mass minimally influenced these two cell types. For heterophils, however, body mass explained over 30% of the variation in concentrations among species, much more than life-history variation (~8%). As with mammalian neutrophils, avian heterophils scaled hypermetrically (b=0.19 ± 0.05), but significantly steeper than mammals (~1.5x). As such, we discuss why birds might require more broadly-protective cells compared to mammals of the same body size. Body mass appears to have strong influences on the architecture of immune systems, which could impact host-parasite coevolution and even zoonotic disease risk for humans.