bluuebunny/crossref_metadata_2025_split huggingface dataset:
Choosing representative proteins based on splicing structure similarity improves the accuracy of gene tree reconstruction
Authors: Kamela Esaie Kuitche , Degen Marie , Wang Shengrui , Ouangraoua Aïda 
Published: April 2020

AbstractConstructing accurate gene trees is important, as gene trees play a key role in several biological studies, such as species tree reconstruction, gene functional analysis and gene family evolution studies. The accuracy of these studies is dependent on the accuracy of the input gene trees. Although several methods have been developed for improving the construction and the correction of gene trees by making use of the relationship with a species tree in addition to multiple sequence alignment, there is still a large room for improvement on the accuracy of gene trees and the computing time. In particular, accounting for alternative splicing that allows eukaryote genes to produce multiple transcripts/proteins per gene is a way to improve the quality of multiple sequence alignments used by gene tree reconstruction methods. Current methods for gene tree reconstruction usually make use of a set of transcripts composed of one representative transcript per gene, to generate multiple sequence alignments which are then used to estimate gene trees. Thus, the accuracy of the estimated gene tree depends on the choice of the representative transcripts. In this work, we present an alternative-splicing-aware method called Splicing Homology Transcript (SHT) method to estimate gene trees based on wisely selecting an accurate set of homologous transcripts to represent the genes of a gene family. We introduce a new similarity measure between transcripts for quantifying the level of homology between transcripts by combining a splicing structure-based similarity score with a sequence-based similarity score. We present a new method to cluster transcripts into a set of splicing homology groups based on the new similarity measure. The method is applied to reconstruct gene trees of the Ensembl database gene families, and a comparison with current EnsemblCompara gene trees is performed. The results show that the new approach improves gene tree accuracy thanks to the use of the new similarity measure between transcripts. An implementation of the method as well as the data used and generated in this work are available athttps://github.com/UdeS-CoBIUS/SplicingHomologGeneTree/.
The impact of di-2-ethylhexyl phthalate on sperm fertility
Authors: Gabelev Khasin Liliya , Della Rosa John , Petersen Natalie , Moeller Jacob , Kriegsfeld Lance J. , Lishko Polina V. 
Published: April 2020

AbstractA growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2-ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.
Estimating the Probability of Early Afterdepolarization and Predicting Arrhythmic Risk associated with Long QT Syndrome Type 1 Mutations
Authors: Jin Qingchu , Greenstein Joseph L. , Winslow Raimond L. 
Published: April 2020

AbstractEarly after-depolarizations (EADs) are action potential (AP) repolarization abnormalities that can trigger lethal arrhythmias. Simulations using biophysically-detailed cardiac myocyte models can reveal how model parameters influence the probability of these cellular arrhythmias, however such analyses can pose a huge computational burden. We have previously developed a highly simplified approach in which logistic regression models (LRMs) map parameters of complex cell models to the probability of ectopic beats (EBs). Here, we extend this approach to predict the probability of early after-depolarizations (P(EAD)). We use the LRM to investigate how changes in parameters of the slow-activating delayed rectifier current (IKs) affect P(EAD) for 17 different Long QT syndrome type 1 (LQTS1) mutations. We compare P(EAD) for these 17 LQTS1 mutations with two other recently proposed model-based arrhythmia risk metrics. These three model-based risk metrics yield similar prediction performance; however, they all fail to predict relative clinical risk for a significant number of the 17 studied LQTS1 mutations. The consistent successes and failures of all three risk metrics suggest that important functional characteristics of LQTS1 mutations may not yet be fully known.Author summaryAn early after-depolarization (EAD) is an abnormal cellular electrical event which can trigger dangerous arrhythmias in the heart. We use our previously developed method to build a simple logistic regression model (LRM) that estimates the probability of EAD (P(EAD)) as a function of myocyte model parameters. Using this LRM along with two other recently published model-based arrhythmia risk predictors, we estimate risk of arrhythmia for 17 Long QT syndrome type 1 (LQTS1) mutations. Results show that all approaches have similar prediction performance in that there are a set of mutations whose relative clinical risk for arrhythmia are well estimated using these metrics, but that relative risk is consistently over- or under-estimated across all approaches for a significant number of other mutations. We believe this indicates that the functional characterization of the LQTS1 phenotype is incomplete.
Hierarchical fear: parental behaviour and corticosterone release mediate nestling growth in response to predation risk
Authors: de Zwaan Devin R. , Martin Kathy 
Published: April 2020

AbstractNestling development, a critical life-stage for altricial songbirds, is highly vulnerable to predation, particularly for open-cup nesting species. Since nest predation risk increases cumulatively with time, rapid growth may be an adaptive response that promotes early fledging. However, greater predation risk can reduce parental provisioning rate as a risk aversion strategy and subsequently constrain nestling growth, or directly elicit a physiological response in nestlings with adaptive or detrimental effects on development rate. Despite extensive theory, evidence for the relative strength of these effects on nestling development in response to prevailing predation risk and the underlying mechanisms remain unclear. For an alpine population of horned lark (Eremophila alpestris), we elevated perceived predation risk (decoys/playback) during the nestling stage to assess the influence of predator cues and parental care on nestling wing growth and the glucocorticoid hormone corticosterone. We used piecewise path analysis to test a hypothesized causal response structure composed of direct and indirect pathways. Nestlings under greater perceived predation risk reduced corticosterone and increased wing growth, resulting in an earlier age at fledge. This represented both a direct response that was predator-specific, and an indirect response dependent on parental provisioning rate. Parents that reduced provisioning rate most severely in response to predator cues had smaller nestlings with greater corticosterone. Model comparisons indicated the strongest support for a directed, causal influence of corticosterone on nestling wing growth, highlighting corticosterone as a potential physiological mediator of the nestling growth response to predation risk. Finally, cold temperatures prior to the experiment constrained wing growth closer to fledge, illustrating the importance of considering the combined influence of weather and predation risk across developmental stages. We present the first study to separate the direct and indirect effects of predation risk on nestling development in a causal, hierarchical framework that incorporates corticosterone as an underlying mechanism and provides experimental evidence for an adaptive developmental response to predation risk in ground-nesting songbirds.
The regulation of a pigmentation gene in the formation of complex color patterns inDrosophilaabdomens
Authors: Raja Komal K. B. , Shittu Mujeeb O. , Nouhan Peter M. E. , Steenwinkel Tessa. E. , Bachman Evan A. , Kokate Prajakta P. , McQueeney Alexander H. , Mundell Elizabeth A. , Armentrout Alexandri A. , Nugent Amber M. , Werner Thomas 
Published: April 2020

AbstractChanges incis-regulatory modules (CRMs) that control developmental gene expression patterns have been implicated in the evolution of animal morphology1-6. However, the genetic mechanisms underlying complex morphological traits remain largely unknown. Here we investigated the molecular mechanisms that induce the pigmentation geneyellow(y) in a complex spot and shade pattern on the abdomen of the quinaria group speciesDrosophila guttifera. We show that theyexpression pattern is controlled by only one CRM, which contains a stripe-inducing CRM at its core. We identified several developmental genes that may collectively interact with the CRM to orchestrate the patterning in the pupal abdomen ofD. guttifera. We further show that the core CRM is conserved amongD. guttiferaand the closely related quinaria group speciesDrosophila deflecta, which displays a similarly spotted abdominal pigment pattern. Our data suggest that besides direct activation of patterns in distinct spots, abdominal spot patterns inDrosophilaspecies may have evolved through partial repression of an ancestral stripe pattern, leaving isolated spots behind. Abdominal pigment patterns of extant quinaria group species support the partial repression hypothesis and further emphasize the modularity of theD. guttiferapattern.
Comparative ACE2 variation and primate COVID-19 risk
Authors: Melin Amanda D. , Janiak Mareike C. , Marrone Frank , Arora Paramjit S. , Higham James P. 
Published: April 2020

AbstractThe emergence of the novel coronavirus SARS-CoV-2, which in humans is highly infectious and leads to the potentially fatal disease COVID-19, has caused hundreds of thousands of deaths and huge global disruption. The viral infection may also represent an existential threat to our closest living relatives, the nonhuman primates, many of which are endangered and often reduced to small populations. The virus engages the host cell receptor, angiotensin-converting enzyme-2 (ACE2), through the receptor binding domain (RBD) on the spike protein. The contact surface of ACE2 displays amino acid residues that are critical for virus recognition, and variations at these critical residues are likely to modulate infection susceptibility across species. While infection studies are emerging and have shown that some primates, such as rhesus macaques and vervet monkeys, develop COVID-19-like symptoms when exposed to the virus, the susceptibility of many other nonhuman primates is unknown. Here, we show that all apes, including chimpanzees, bonobos, gorillas, and orangutans, and all African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at significant contact residues, and protein modeling predicts that these differences should greatly reduce the binding affinity of the ACE2 for the virus, hence moderating their susceptibility for infection. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, as well as some lemurs are all likely to be highly susceptible to SARS-CoV-2, representing a critical threat to their survival. Urgent actions have been undertaken to limit the exposure of Great Apes to humans, and similar efforts may be necessary for many other primate species.
Classical drug digitoxin inhibits influenza cytokine storm, with implications for COVID-19 therapy
Authors: Pollard Bette S. , Blanco Jorge C. , Pollard John R. , Prince Gregory A. 
Published: April 2020

AbstractInfluenza viruses, corona viruses and related pneumotropic viruses cause sickness and death partly by inducing a hyper-proinflammatory response by immune cells and cytokines in the host airway. Here we show that the cardiac glycoside digitoxin suppresses this response induced by influenza virus strain A/Wuhan/H3N2/359/95 in the cotton rat lung. The cytokines TNFα, GRO/KC, MIP2, MCP1, TGFβ, and IFNγ. are significantly and differentially reduced. Since the hyper-proinflammatory expression of cytokines is a host response, we suggest that digitoxin may have therapeutic potential for not only influenza and but also for coronavirus infections.
Dynamical effects of dendritic pruning implicated in aging and neurodegeneration: Towards a measure of neuronal reserve
Authors: Kirch Christoph , Gollo Leonardo L. 
Published: April 2020

AbstractAging is a main risk factor for neurodegenerative disorders including Alzheimer’s disease. It is often accompanied by reduced cognitive functions, gray-matter volume, and dendritic integrity. Although age-related brain structural changes have been observed across multiple scales, their functional implications remain largely unknown. Here we simulate the aging effects on neuronal morphology as dendritic pruning and characterize its dynamical implications. Utilizing a minimal computational modeling approach, we simulate the dynamics of detailed digitally reconstructed pyramidal neurons of humans obtained from the online repository Neuromorpho.org. We show that as aging progressively affects neuronal integrity, neuronal firing rate is reduced, which causes a reduction in energy consumption, energy efficiency, and dynamic range. Pruned neurons require less energy but their function is often impaired, which can explain the diminished ability to distinguish between similar experiences (pattern separation) in older people. Our measures indicate that the resilience of neuronal dynamics is neuron-specific, heterogeneous, and strongly affected by dendritic topology and the centrality of the soma. Based on the emergent neuronal dynamics, we propose to classify the effects of dendritic deterioration, and put forward that soma centrality measures neuronal reserve. Moreover, our findings suggest that increasing dendritic excitability could partially mitigate the dynamical effects of aging.
Membrane Insertion ofMycobacterium tuberculosisEsxA in Cultured Lung Epithelial Cells
Authors: Zhang Qi , Aguilera Javier , Reyes Salvador Vazquez , Sun Jianjun 
Published: April 2020

AbstractEsxA has long been recognized as an important virulence factor ofMycobacterium tuberculosis(Mtb) that plays an essential role in Mtb cytosolic translocation presumably by penetrating phagosomal membranes with its acidic pH-dependent membrane permeabilizing activity (MPA). However, current data suggest that the observed cytolytic activity of EsxA at neutral pH is due to contamination of ASB-14, a detergent used in EsxA protein purification, and the role of EsxA MPA in Mtb cytosolic translocation is also questionable. Here, we have obtained evidence that it is ASB-14, not EsxA that causes cytolysis at neutral pH. Quantitative liquid chromatography and mass spectrometry showed that even after gel filtration, dialysis, or passing through detergent removal column, the remaining ASB-14 in the EsxA protein solution was still at a concentration enough to kill cultured lung epithelial cells. When treated with trypsin or proteinase K, the digested EsxA protein solution with ASB-14 was still cytotoxic. Interestingly, however, we have found that the exogenously added EsxA is endocytosed into lung epithelial cells and inserts into the host membranes within acidic subcellular compartments, which can be blocked by cytochalasin D and bafilomycin A. It is for the first time EsxA is found to insert into the host membranes within acidic subcellular compartments.ImportanceEsxA has long been recognized as an important virulence factor ofMycobacterium tuberculosis(Mtb) that plays an essential role in Mtb virulence. However, current data regarding to its role in Mtb virulence are controversial. Here, we have obtained evidence showing that the cytolytic activity of EsxA at neutral pH is due to contamination of ASB-14, a detergent used in EsxA preparation. Moreover, it is for the first time we have found that EsxA protein is endocytosed into lung epithelial cells and inserts into the host membranes within acidic subcellular compartments, implicating an important role of the acidic pH-dependent membrane permeabilizing activity of EsxA in Mtb virulence.
Evaluation of nine commercial SARS-CoV-2 immunoassays
Authors: Lassaunière Ria , Frische Anders , Harboe Zitta B. , Nielsen Alex C.Y. , Fomsgaard Anders , Krogfelt Karen A. , Jørgensen Charlotte S. 
Published: April 2020

AbstractDue to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays are rapidly being developed and placed on the market with limited validation on clinical samples. Thorough validation of serological tests are required to facilitate their use in the accurate diagnosis of SARS-CoV-2 infection, confirmation of molecular results, contact tracing, and epidemiological studies. This study evaluated the sensitivity and specificity of nine commercially available serological tests. These included three enzyme-linked immunosorbent assays (ELISAs) and six point-of-care (POC) lateral flow tests. The assays were validated using serum samples from: i) SARS-CoV-2 PCR-positive patients with a documented first day of disease; ii) archived sera obtained from healthy individuals before the emergence of SARS-CoV-2 in China; iii) sera from patients with acute viral respiratory tract infections caused by other coronaviruses or non-coronaviruses; and iv) sera from patients positive for dengue virus, cytomegalovirus and Epstein Barr virus. The results showed 100% specificity for the Wantai SARS-CoV-2 Total Antibody ELISA, 93% for the Euroimmun IgA ELISA, and 96% for the Euroimmun IgG ELISA with sensitivities of 90%, 90%, and 65%, respectively. The overall performance of the POC tests according to manufacturer were in the rank order of AutoBio Diagnostics > Dynamiker Biotechnology = CTK Biotech > Artron Laboratories > Acro Biotech ≥ Hangzhou Alltest Biotech. Overall, these findings will facilitate selection of serological assays for the detection SARS-CoV-2-specific antibodies towards diagnosis as well as sero-epidemiological and vaccine development studies.
“Mental health status of the general population, healthcare professionals, and university students during 2019 coronavirus disease outbreak in Jordan: a cross-sectional study”
Authors: Naser Abdallah Y , Dahmash Eman Zmaily , Al-Rousan Rabaa , Alwafi Hassan , Alrawashdeh Hamzeh Mohammad , Ghoul Imene , Abidine Anwer , Bokhary Mohammed A. , AL-Hadithi Hadeel T. , Ali Dalia , Abuthawabeh Rasha , Abdelwahab Ghada Mohammad , Alhartani Yosra J , Muhaisen Haneen Al , Dagash Ayah 
Published: April 2020

ABSTRACTBackgroundThe emergence of COVID-19 global pandemic coupled with high transmission rate and mortality has created an unprecedented state of emergency worldwide. This global situation may have a negative impact on the psychological well-being of individuals which in turn impacts individuals’ performance.MethodsA cross-sectional study using an online survey was conducted in Jordan between 22nd and 28th of March 2020 to explore the mental health status (depression and anxiety) of the general population, healthcare professionals, and university students during the COVID-19 outbreak. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression and anxiety among the study participants. Logistic regression analysis was used to identify predictors of depression and anxiety.ResultsThe prevalence of depression and anxiety among the entire study participants was 23.8% and 13.1%, respectively. Anxiety was most prevalent across university students 21.5%, followed by healthcare professionals 11.3%, and general population 8.8%. Females among healthcare professionals and university students, divorced healthcare professionals, pulmonologists, and university students with history of chronic disease were at higher risk of developing depression. Females, divorced participants among the general population, and university students with history of chronic disease and those with high income (≥1500 JD) were at higher risk of developing anxiety.ConclusionsDuring outbreaks, individuals are put under extreme stressful condition resulting in higher risk of developing anxiety and depression particularly for students and healthcare professionals. Policymakers and mental healthcare providers are advised to provide further mental support to these vulnerable groups during this pandemic.
Assessing the risk of spread of COVID-19 to the Asia Pacific region
Authors: Shearer Freya M. , Walker James , Tellioglu Nefel , McCaw James M. , McVernon Jodie , Black Andrew , Geard Nic 
Published: April 2020

AbstractDuring the early stages of an emerging disease outbreak, governments are required to make critical decisions on how to respond appropriately, despite limited data being available to inform these decisions. Analytical risk assessment is a valuable approach to guide decision-making on travel restrictions and border measures during the early phase of an outbreak, when transmission is primarily contained within a source country. Here we introduce a modular framework for estimating the importation risk of an emerging disease when the direct travel route is restricted and the risk stems from indirect importation via intermediary countries. This was the situation for Australia in February 2020. The framework was specifically developed to assess the importation risk of COVID-19 into Australia during the early stages of the outbreak from late January to mid-February 2020. The dominant importation risk to Australia at the time of analysis was directly from China, as the only country reporting uncontained transmission. However, with travel restrictions from mainland China to Australia imposed from February 1, our framework was designed to consider the importation risk from China into Australia via potential intermediary countries in the Asia Pacific region. The framework was successfully used to contribute to the evidence base for decisions on border measures and case definitions in the Australian context during the early phase of COVID-19 emergence and is adaptable to other contexts for future outbreak response.