bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence Analysis for SNP Detection and Phylogenetic Reconstruction of SARS-CoV-2 Isolated from Nigerian COVID-19 Cases
Authors: Taiwo Idowu A. , Adeleye Nike , Anwoju Fatimah O. , Adeyinka Adeyemi , Uzoma Ijeoma C. , Bankole Taiwo T. 
Published: September 2020

AbstractBackgroundCoronaviruses are a group of viruses that belong to the Family Coronaviridae, GenusBetacoronavirus. In December 2019, a new coronavirus disease (COVID-19) characterized by severe respiratory symptoms was discovered. The causative pathogen was a novel coronavirus known as 2019-nCoV and later as SARS-CoV-2. Within two months of its discovery, COVID-19 became a pandemic causing widespread morbidity and mortality.MethodologyWhole genome sequence data of SARS-CoV-2 isolated from Nigerian COVID-19 cases were retrieved by downloading from GISAID database. A total of 18 sequences that satisfied quality assurance (length ≥ 29700 nts and number of unknown bases denoted as ‘N’ ≤ 5%) were used for the study. Multiple sequence alignment (MSA) was done in MAFFT (Version 7.471) while SNP calling was implemented in DnaSP (Version 6.12.03) respectively and then visualized in Jalview (Version 2.11.1.0). Phylogenetic analysis was with MEGA X software.ResultsNigerian SARS-CoV-2 had 99.9% genomic similarity with four large conserved genomic regions. A total of 66 SNPs were identified out of which 31 were informative. Nucleotide diversity assessment gave Pi = 0.00048 and average SNP frequency of 2.22 SNPs per 1000 nts. Non-coding genomic regions particularly 5’UTR and 3’UTR had a SNP density of 3.77 and 35.4 respectively. The region with the highest SNP density was ORF10 with a frequency of 8.55 SNPs/1000 nts). Majority (72.2%) of viruses in Nigeria are of L lineage with preponderance of D614G mutation which accounted for 11 (61.1%) out of the 18 viral sequences. Nigeria SARS-CoV-2 revealed 3 major clades namely Oyo, Ekiti and Osun on a maximum likelihood phylogenetic tree.Conclusion and RecommendationNigerian SARS-CoV-2 reveals high mutation rate together with preponderance of L lineage and D614G mutants. Implication of these mutations for SARS-CoV-2 virulence and the need for more aggressive testing and treatment of COVID-19 in Nigeria is discussed. Additionally, attempt to produce testing kits for COVID-19 in Nigeria should consider the conserved regions identified in this study. Strict adherence to COVID-19 preventive measure is recommended in view of Nigerian SARS-CoV-2 phylogenetic clustering pattern, which suggests intensive community transmission possibly rooted in communal culture characteristic of many ethnicities in Nigeria.
On the Origins of Conductive-Pulse Sensing Inside a Nanopore
Authors: Lastra Lauren S. , Bandara Y. M. Nuwan D. Y. , Nguyen Michelle , Farajpour Nasim , Freedman Kevin J. 
Published: September 2020

AbstractNanopore sensing is nearly synonymous with resistive pulse sensing due to the characteristic reduction of ionic flux during molecular occupancy of a pore, particularly at high salt concentrations. However, conductive pulses are widely reported at low salt conditions wherein electroosmotic flow can be quite significant. Aside from transporting molecules like DNA, we investigated whether electroosmotic flow has other potential impacts on sensing attributes such current enhancements due to the analyte molecule. The overwhelming majority of literature reports counterions as the dominant mechanism of conductive events (a moleculecentric theory for conductive events). Conductive events are not well understood due to the complex interplay between (charged) nanopore walls, DNA grooves, ion mobility, and counterion clouds. Yet, the prevailing consensus of counterions being introduced into the pore by the molecule does not fit well with a growing number of experiments including the fact that proteins can generate conductive events despite having a heterogeneous surface charge. Herein, we demonstrate theory and experiments underpinning the translocation mechanism (i.e., electroosmosis or electrophoresis), pulse direction (i.e., conductive or resistive) and shape (e.g., monophasic or biphasic) through fine control of chemical, physical, and electronic parameters. Results from these studies predict strong electroosmosis plays a role in driving DNA events and generating conductive events due to polarization effects (i.e. a pore-centric theory). We believe these findings will stimulate a useful discussion on the nature of conductive events and their impact on molecular sensing in nanoscale pores.
Differential modulation of thermal preference after sensitization by optogenetic or pharmacological activation of heat-sensitive nociceptors
Authors: Li Jerry , Zain Maham , Bonin Robert P. 
Published: September 2020

AbstractCommon approaches to studying chronic pain in pre-clinical animal models paradoxically involve measuring reflexive withdrawal responses that are more indicative of acute nociceptive pain. These methods typically do not capture the ongoing nature of chronic pain nor report on behavioral changes associated with pain. In addition, data collection and analysis protocols are often labour-intensive and require direct investigator interactions, potentially introducing bias. In this study, we develop and characterize a low-cost, easily assembled behavioral assay that yields self-reported temperature preference from mice which is sensitive to peripheral sensitization protocols. This system uses a partially automated and freely available analysis pipeline to streamline the data collection process and enable objective analysis. We found that after intraplantar administration of the TrpV1 agonist, capsaicin, mice preferred to stay in cooler temperatures than control injected mice. We further observed that gabapentin, a non-opioid analgesic commonly prescribed to treat chronic pain, reversed this aversion to higher temperatures. We further observed that optogenetic activation of the central terminals of TrpV1+ primary afferents viain vivospinal light delivery did not induce a similar change in thermal preference, indicating a role for peripheral nociceptor activity in the modulation of temperature preference. We conclude that this easily produced and robust sensory assay provides an alternative approach to investigate the contribution of central and peripheral mechanisms to pathological sensory processing that does not rely on reflexive responses evoked by noxious stimuli.
Regulation of gene transcription by thyroid hormone receptor β agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH)
Authors: Luong Xuan G. , Stevens Sarah K. , Jekle Andreas , Lin Tse-I , Gupta Kusum , Misner Dinah , Chanda Sushmita , Mukherjee Sucheta , Williams Caroline , Stoycheva Antitsa , Blatt Lawrence M. , Beigelman Leonid N. , Symons Julian A. , Raboisson Pierre , McGowan David , Vandyck Koen , Deval Jerome 
Published: September 2020

AbstractThyroid hormones are important modulators of metabolic activity in mammals and alter cholesterol and fatty acid levels through activation of the nuclear thyroid hormone receptor (THR). Currently, there are several THRβ agonists in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) that have demonstrated the potential to reduce liver fat and restore liver function. In this study, we tested three THRβ-agonism-based NASH treatment candidates, GC-1 (sobetirome), MGL-3196 (resmetirom), and VK2809, and compared their selectivity for THRβ and their ability to modulate the expression of genes specific to cholesterol and fatty acid biosynthesis and metabolismin vitrousing human hepatic cells andin vivousing a rat model. Treatment with GC-1 upregulated the transcription ofCPT1Ain the human hepatocyte-derived Huh-7 cell line with a dose-response comparable to that of the native THR ligand, triiodothyronine (T3). VK2809A (active parent of VK2809), MGL-3196, and VK2809 were approximately 30-fold, 1,000-fold, and 2,000-fold less potent than T3, respectively. Additionally, these relative potencies were confirmed by quantification of other direct gene targets of THR, namely,ANGPTL4andDIO1. In primary human hepatocytes, potencies were conserved for every compound except for VK2809, which showed significantly increased potency that was comparable to that of its active counterpart, VK2809A. In high-fat diet fed rats, a single dose of T3 significantly reduced total cholesterol levels and concurrently increased liverDio1andMe1RNA expression. MGL-3196 treatment resulted in concentration-dependent decreases in total and low-density lipoprotein cholesterol with corresponding increases in liver gene expression, but the compound was significantly less potent than T3. In conclusion, we have implemented a strategy to rank the efficacy of THRβ agonists by quantifying changes in the transcription of genes that lead to metabolic alterations, an effect that is directly downstream of THR binding and activation.
Computational design of genes encoding completely overlapping protein domains: Influence of genetic code and taxonomic rank
Authors: Wichmann Stefan , Scherer Siegfried , Ardern Zachary 
Published: September 2020

AbstractOverlapping genes (OLGs) with long protein-coding overlapping sequences are often excluded by genome annotation programs, with the exception of virus genomes. A recent study used a novel algorithm to construct OLGs from arbitrary protein domain pairs and concluded that virus genes are best suited for creating OLGs, a result which fitted with common assumptions. However, improving sequence evaluation using Hidden Markov Models shows that the previous result is an artifact originating from dataset-database biases. When parameters for OLG design and evaluation are optimized we find that 94.5% of the constructed OLG pairs score at least as highly as naturally occurring sequences, while 9.6% of the artificial OLGs cannot be distinguished from typical sequences in their protein family. Constructed OLG sequences are also indistinguishable from natural sequences in terms of amino acid identity and secondary structure, while the minimum nucleotide change required for overprinting an overlapping sequence can be as low as 1.8% of the sequence. Separate analysis of datasets containing only sequences from either archaea, bacteria, eukaryotes or viruses showed that, surprisingly, virus genes are much less suitable for designing OLGs than bacterial or eukaryotic genes. An important factor influencing OLG design is the structure of the standard genetic code. Success rates in different reading frames strongly correlate with their code-determined respective amino acid constraints. There is a tendency indicating that the structure of the standard genetic code could be optimized in its ability to create OLGs while conserving mutational robustness. The findings reported here add to the growing evidence that OLGs should no longer be excluded in prokaryotic genome annotations. Determining the factors facilitating the computational design of artificial overlapping genes may improve our understanding of the origin of these remarkable genetic constructs and may also open up exciting possibilities for synthetic biology.
Sex, Age, and Parental Harmonic Convergence Behavior Affect the Immune Performance ofAedes aegyptiOffspring
Authors: Reitmayer Christine M , Pathak Ashutosh K , Harrington Laura C , Brindley Melinda A. , Cator Lauren J , Murdock Courtney C 
Published: September 2020

AbstractAedes aegyptiis an important vector of several pathogenic arboviruses including dengue, chikungunya and Zika. Innovative approaches to controlAedespopulations, involving synthetic transgenic modifications as well asWolbachiabacteria, appear promising. For the various techniques requiring offspring inheritance of a trait, released males must successfully compete for mating partners against wildtype males. However, very little is known about mechanisms of mate selection in mosquitoes in general and in particular about potential correlations between mating success and offspring immune performance.Harmonic convergence signals have been proposed as a cue for females to predict male quality. We investigated whether offspring of converging parental pairs showed differences in immune competence compared to offspring derived from non-converging parental pairs using three different types of immune assays. We found that offspring immune responses (melanization response and response to a bacterial challenge) differed between offspring from converging and non-converging parents. However, immune responses were shaped by several interacting factors such as sex, age, reproductive status, and parental mating behavior. Parental mating behavior had a stronger effect on the immune response of male offspring than on female offspring. Further, a population of female offspring derived from converging parental pairs reached their peak dengue virus dissemination rate earlier compared to a population of offspring derived from non-converging parental pairs. Our results provide insight into a wide range of selective pressures shaping mosquito immune function. Evolutionary trade-offs between naturally and sexually selected traits can have important implications for disease transmission and control and should be considered in the development of reproductive control strategies.
Genetic diversity, haplotype analysis, and risk factor assessment of hepatitis a virus (HAV) isolates from the West Bank, Palestine during the period between 2014 and 2016
Authors: Dumaidi Kamal , Qaraqe Hayah , Al-Jawabreh Amer , Abu-Helu Rasmi , Samarah Fekri , Al-Jawabreh Hanan 
Published: September 2020

AbstractBackgroundHAV genotypes and its genetic diversity is rarely investigated in our region as well as worldwide.Aimsthe aims of the present study were to determine the HAV genotypes and its risk factors and to investigate the genetic diversity of the HAV isolates in the West bank, Palestine.Study designa cohort of 161 clinically and laboratory confirmed HAV (IgM-positive) cases and 170 IgM negative individuals from all the districts of the West Bank, Palestine during the period of 2014-2016 were tested for VP3/VP1 junction of the HAV genome using RT-PCR and sequence analysis. Phylogenetic analysis, genetic diversity and haplotypes analysis were used to characterize the VP3/VP1 sequences.ResultsOverall, all the 34 sequences of the HAV was found to be HAV-IB sub-genotype. The phylogenetic analysis showed four main clusters with cluster III exclusively consisting of 18 Palestinian isolates (18/23-78%) with weak bootstrap values. A high haplotype diversity (Hd) and low nucleotide diversity (π) were observed. Cluster III showed high number of haplotypes (h=8), but low haplotype (gene) diversity (Hd=0.69). A total of 28 active haplotypes with some consisting of more than one sequence were observed using haplotype network analysis. The Palestinian haplotypes are characterized by closely related viral haplotypes with one SNV away from each other which ran parallel to cluster III in the phylogenetic tree. A smaller Palestinian haplotype (4 isolates) was three SNVs away from the major haplotype cluster (n=10) and closer to haplotypes from Iran, Spain, and South Africa. Young age, low level of parent’s education, poor hand washing and drinking of un-treated water was considered the major HAV risk factors in the present study.ConclusionHAV-IB subgentype is endemic in Palestine. HAV showed low genetic variation and nucleotide diversity. Furthermore, haplotype network analysis revealed haplotype variation among the Palestinian sequences.
FisB relies on homo-oligomerization and lipid-binding to catalyze membrane fission in bacteria
Authors: Landajuela Ane , Braun Martha , Rodrigues Christopher D. A. , Martínez-Calvo Alejandro , Doan Thierry , Horenkamp Florian , Andronicos Anna , Shteyn Vladimir , Williams Nathan D. , Lin Chenxiang , Wingreen Ned S. , Rudner David Z. , Karatekin Erdem 
Published: September 2020

ABSTRACTLittle is known about mechanisms of membrane fission in bacteria despite their requirement for cytokinesis. The only known dedicated membrane fission machinery in bacteria, FisB, is expressed during sporulation inBacillus subtilisand is required to release the developing spore into the mother cell cytoplasm. Here we characterized the requirements for FisB-mediated membrane fission. FisB forms mobile clusters of ∼12 molecules that give way to an immobile cluster at the engulfment pole containing ∼40 proteins at the time of membrane fission. Analysis of FisB mutants revealed that binding to acidic lipids and homo-oligomerization are both critical for targeting FisB to the engulfment pole and membrane fission. Experiments using artificial membranes and filamentous cells suggest FisB does not have an intrinsic ability to sense or induce membrane curvature but can bridge membranes. Finally, modeling suggests homo-oligomerization and trans interactions with membranes are sufficient to explain FisB accumulation at the membrane neck that connects the engulfment membrane to the rest of the mother cell membrane during late stages of engulfment. Together, our results show that FisB is a robust and unusual membrane fission protein that relies on homo-oligomerization, lipid-binding and the unique membrane topology generated during engulfment for localization and membrane scission, but surprisingly, not on lipid microdomains, negative-curvature lipids, or curvature-sensing.
Rapid behavioural response of urban birds to COVID-19 lockdown
Authors: Gordo Oscar , Brotons Lluís , Herrando Sergi , Gargallo Gabriel 
Published: September 2020

AbstractBiodiversity is threatened by the growth of urban areas. However, it is still poorly understood how animals can cope with and adapt to these rapid and dramatic transformations of natural environments. The COVID-19 pandemic provides us with a unique opportunity to unveil the mechanisms involved in this process. Lockdown measures imposed in most countries are causing an unprecedented reduction of human activities giving us an experimental setting to assess the effects of our lifestyle on biodiversity. We studied the birds’ response to the population lockdown by using more than 126,000 bird records collected by a citizen science project in north eastern Spain. We compared the occurrence and detectability of birds during the spring 2020 lockdown with baseline data from previous years in the same urban areas and dates. We found that birds did not increase their probability of occurrence in urban areas during the lockdown, refuting the hypothesis that nature has recovered its space in human emptied urban areas. However, we found an increase in bird detectability, especially during early morning, suggesting a rapid change in the birds’ daily routines in response to quieter and less crowded cities. In conclusion, urban birds showed high behavioural plasticity to rapidly adjust to novel environmental conditions, as those imposed by the COVID-19.
LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior
Authors: Naetar Nana , Georgiou Konstantina , Knapp Christian , Bronshtein Irena , Zier Elisabeth , Fichtinger Petra , Dechat Thomas , Garini Yuval , Foisner Roland 
Published: September 2020

AbstractLamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). We show that lamin A in the nuclear interior is formed from newly expressed pre-lamin A during processing and from soluble mitotic mature lamins in a LAP2α-independent manner. Binding of LAP2α to lamins A/C in the nuclear interior during interphase inhibits formation of higher order structures of lamin A/Cin vitroandin vivo, keeping lamin A/C in a mobile low assembly state independent of lamin A/C S22 phosphorylation. Loss of LAP2α causes formation of larger, less mobile and biochemically stable lamin A/C structures in the nuclear interior, which reduce the mobility of chromatin. We propose that LAP2α is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.
Performance of a phylogenetic independent contrast method and an improved pairwise comparison under different scenarios of trait evolution after speciation and duplication
Authors: Begum Tina , Serrano-Serrano Martha Liliana , Robinson-Rechavi Marc 
Published: September 2020

AbstractDespite the importance of gene function to evolutionary biology, the applicability of comparative methods to gene function is poorly known. A specific case which has crystalized methodological questions is the “ortholog conjecture”, the hypothesis that function evolves faster after duplication (i.e., in paralogs), and conversely is conserved between orthologs. Since the mode of functional evolution after duplication is not well known, we investigate under which reasonable evolutionary scenarios phylogenetic independent contrasts or pairwise comparisons can recover a putative signal of different functional evolution between orthologs and paralogs.We investigate three different simulation models, which represent reasonable but simplified hypotheses about the evolution of a gene function trait. These are time dependent trait acceleration, correlated changes in rates of both sequence and trait evolution, and asymmetric trait jump. For each model we tested phylogenetic independent contrasts and an improved pairwise comparison method which accounts for interactions between events and node age.Both approaches lose power to detect the trend of functional evolution when the functional trait accelerates for a long time following duplication for trees with many duplications, with better power of phylogenetic contrasts under intermediate scenarios. Concomitant increase in evolutionary rates of sequence and of trait after duplication can lead to both an incorrect rejection of the null under null simulations of trait evolution, and a false rejection of the ortholog conjecture under ortholog conjecture simulations, by phylogenetic independent contrasts. Improved pairwise comparisons are robust to this bias. Both approaches perform equally well under rapid shifts in traits.Considering our ignorance of gene function evolution, and the potential for bias under simple models, we recommend methodological pluralism in studying gene family evolution. Functional phylogenomics is complex and results supported by only one method should be treated with caution.