bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topoisomerase VI is a chirally-selective, preferential DNA decatenase
Authors: McKie Shannon J. , Desai Parth , Seol Yeonee , Maxwell Anthony , Neuman Keir 
Published: February 2021

AbstractDNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase found predominantly in archaea and some bacteria, but also in plants and algae. Since its discovery, topo VI has been proposed to be a DNA decatenase, however robust evidence and a mechanism for its preferential decatenation activity was lacking. Using single-molecule magnetic tweezers measurements and supporting ensemble biochemistry, we demonstrate thatMethanosarcina mazeitopo VI preferentially unlinks, or decatenates, DNA crossings, in comparison to relaxing supercoils, through a preference for certain DNA crossing geometries. In addition, topo VI demonstrates a dramatic increase in ATPase activity, DNA binding and rate of strand passage, with increasing DNA writhe, providing further evidence that topo VI is a DNA crossing sensor. Our study strongly suggests that topo VI has evolved an intrinsic preference for the unknotting and decatenation of interlinked chromosomes by sensing and preferentially unlinking DNA crossings with geometries close to 90°.
massiveGenesetsTest: a web tool to run enrichment analysis
Authors: Cerulo Luigi , Pagnotta Stefano Maria 
Published: February 2021

AbstractMotivationInferring biological phenotypes from genomic data and sample clusters is a routinely task usually performed with Gene-Set Enrichment Analysis (GSEA), a tool that queries gene-profiles. In previous work, we scrutinized the approach based on Mann-Witney for Gene-Sets test. We highlighted the Mann-Witney test-statistics sensitivity to uncover weak signals and the drastic decreasing of time complexity.ResultsWe propose web implementation of the Gene-sets testing based on the Mann-Witney procedure. The test-procedure has reshaped to decrease the computational expense, now about tens of seconds, even if a large collection of gene-sets queries the same gene-profile. The probabilistic interpretation of the normalized test-statistic has been investigated to a better understanding of the enrichment results. A novel prioritization method across enrichment-scores, gene-set dimensions, and p-values, draws attention to relevant gene-sets. The web tool provides both tabular and graphical enrichment results. A complimentary R function allows integrating the enrichment procedure in a complex context.Contactpagnotta@unisannio.itSupplementary informationExample data and guidelines are included in the supporting material of the web-site.
Shared genetic influences on resting-state functional networks of the brain
Authors: Guimaraes JPOFT , Sprooten E , Beckmann CF , Franke B , Bralten J 
Published: February 2021

AbstractThe amplitude of activation in brain resting state networks (RSNs), measured with resting-state functional MRI, is heritable and genetically correlated across RSNs, indicating pleiotropy. Recent univariate genome-wide association studies (GWAS) explored the genetic underpinnings of individual variation in RSN activity. Yet univariate genomic analyses do not describe the pleiotropic nature of RSNs. In this study we used a novel multivariate method called genomic SEM to model latent factors that capture the shared genomic influence on RSNs and to identify SNPs and genes driving this pleiotropy. Using summary statistics from GWAS of 21 RSNs reported in UK Biobank (N = 31,688), the genomic latent factor analysis was first conducted in a discovery sample (N = 21,081), and then tested in an independent sample from the same cohort (N = 10,607). In the discovery sample, we show that the genetic organization of RSNs can be best explained by two distinct but correlated genetic factors that divide multimodal association networks and sensory networks. Eleven of the 17 factor loadings were replicated in the independent sample. With the multivariate GWAS, we found and replicated nine independent SNPs associated with the joint architecture of RSNs. Further, by combining the discovery and replication samples, we discovered additional SNP and gene associations with the two factors of RSN amplitude. We conclude that modelling the genetic effects on brain function in a multivariate way is a powerful approach to learn more about the biological mechanisms involved in brain function.
How to achieve a higher selection plateau in forest tree breeding? Fostering Heterozygote x Homozygote relationships in Optimal Contribution Selection in the case study of Populus nigra
Authors: Tiret Mathieu , Pégard Marie , Sánchez Leopoldo 
Published: February 2021

AbstractIn breeding, Optimal Contribution Selection (OCS) is one of the most effective strategies to balance short- and long-term genetic responses, by maximizing genetic gain and minimizing global coancestry. Considering genetic diversity in the selection dynamic – through coancestry – is undoubtedly the reason for the success of OCS, as it avoids initial loss of favorable alleles. Originally formulated with the pedigree relationship matrix, global coancestry can nowadays be assessed with one of the possible formulations of the realized genomic relationship matrix. Most formulations were optimized for genomic evaluation, but few for the management of coancestry. We introduce here an alternative formulation specifically developed for Genomic OCS (GOCS), intended to better control heterozygous loci, and thus better account for Mendelian sampling. We simulated a multi-generation breeding program with mate allocation and under GOCS for twenty generations, solved with quadratic programming. With the case study ofPopulus nigra, we have shown that, although the dynamic was mainly determined by the trade-off between genetic gain and genetic diversity, better formulations of the genomic relationship matrix, especially those fostering individuals carrying multiple heterozygous loci, can lead to better short-term genetic gain and a higher selection plateau.
SARS-CoV2 envelop proteins reshape the serological responses of COVID-19 patients
Authors: Martin Sophie , Heslan Christopher , Jégou Gwénaële , Eriksson Leif A. , Le Gallo Matthieu , Thibault Vincent , Chevet Eric , Godey Florence , Avril Tony 
Published: February 2021

AbstractThe SARS-CoV-2 pandemic has elicited a unique international mobilization of the scientific community to better understand this coronavirus and its associated disease and to develop efficient tools to combat infection. Similar to othercoronavirae, SARS-CoV-2 hijacks the host cell complex secretory machinery to produce properly folded viral proteins that will compose the nascent virions; including Spike, Envelope and Membrane proteins, the most exposed membrane viral proteins to the host immune system. Antibody response is part of the anti-viral immune arsenal that infected patients develop to fight viral particles in the body. Herein, we investigate the immunogenic potential of Spike (S), Envelope (E) and Membrane (M) proteins using a human cell-based system to mimic membrane insertion and N-glycosylation. We show that both S and M proteins elicit the production of specific IgG, IgM and IgA in SARS-CoV-2 infected patients. Elevated Ig responses were observed in COVID+ patients with moderate and severe forms of the disease. Finally, when SARS-CoV-2 Spike D614 and G614 variants were compared, reduced Ig binding was observed with the Spike G614 variant. Altogether, this study underlines the needs for including topological features in envelop proteins to better characterize the serological status of COVID+ patients, points towards an unexpected immune response against the M protein and shows that our assay could represent a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.
A farewell to EQ: A new brain size measure for comparative primate cognition
Authors: van Schaik Carel P. , Triki Zegni , Bshary Redouan , Heldstab Sandra Andrea 
Published: February 2021

AbstractBoth absolute and relative brain size vary greatly among and within the major vertebrate lineages. Scientists have long debated how larger brains in primates and hominins translate into greater cognitive performance, and in particular how to control for the relationship between the non-cognitive functions of the brain and body size. One solution to this problem is to establish the slope of cognitive equivalence, that is the line connecting organisms with an identical bauplan but different body sizes. Here, we suggest that intraspecific slopes provide the best available estimate of this measure. This approach was abandoned because slopes were too low by an unknown margin due to estimation error. We control for the error problem by focusing on highly dimorphic primate species with large sample sizes and fitting a line through the mean values for adult females and males. We obtain the best estimate for the slope of ca 0.27, a value much lower than those constructed using all mammal species, and close to the value expected based on the genetic correlation between brain size and body size. We also find that the estimate of cognitive brain size based on cognitive equivalence fits empirical cognitive studies better than the encephalization quotient (EQ), which should therefore be avoided in future studies on primates, and presumably mammals and birds in general. The use of residuals from the line of cognitive equivalence may change conclusions concerning the cognitive abilities of extant and extinct primate species, including hominins.
Molecular epidemiology of human respiratory syncytial virus with severe acute respiratory infection in Huzhou from 2016 to 2019
Authors: Xu Deshun , Ji Lei , Wu Xiaofang , Yan Wei , Chen Liping 
Published: February 2021

AbstractBackgroundHuman respiratory syncytial virus (HRSV) is one of the major cause of acute lower respiratory infection in infants, the elderly and people with low immunity worldwide. Based on antigenic and genetic variations, Human respiratory syncytial virus is divided into two subgroups (A and B). Each of the subgroups is further categorized into genotypes based on the phylogenetic analyses of the sequences of the second hypervariable region.MethodsNasopharyngeal swabs (NPSs) were collected from patients of the First People’s Hospital in Huzhou from January 2016 to December 2019. Real-time RT-PCR (qPCR) was performed using double nucleic acid detection kit for respiratory syncytial virus (A\B) (Shenzhen shengkeyuan) with the ABI Q7 (Applied Biosystems). For genotyping, the primer set A-F/A-R was used to amplify the G protein of HRSV-A. Primer set B-F/B-R was used to amplify the G protein of HRSV-B. The phylogenetic analysis was constructed using the neighbor-joining algorithm with the Kimura two-parameter model and supported statistically by bootstrapping with 1000 replicates with MEGA software (version 7.0) with 1000 bootstrap replicates.ResultsA total of 973 nasopharyngeal swab samples were collected from January 2016 to December 2019, and 63 samples were positive for RSV nucleic acid, with the detection rate of 6.47%. Of the positive specimens, 28 were belonged to HRSV-A, and 35 were belonged to HRSV-B. Infection with RSV was found in all age groups tested, with the 0-1 year age group having the highest detection rate 15.2%. The detection rate was high from November to next March. Phylogenetic analysis clustered HRSV-A strains identified in Huzhou into ON1genotype. All 17 of the HRSV-B strains belonged to BA9 genotype.ConclusionsWe analyzed the HRSV strains circulation in Huzhou from January 2016 to December 2019 in Huzhou, China. This is the first molecular analysis on HRSV in Huzhou. We found Subgroup A and B of RSV were co-circulating and the 0-1 year age group having the highest infection rate.
Hybrid Support Vector Regression Model and K-Fold Cross Validation for Water Quality Index Prediction in Langat River, Malaysia
Authors: Mamat Naeimah , Hamzah Firdaus Mohamad , Jaafar Othman 
Published: February 2021

AbstractWater quality analysis is an important step in water resources management and needs to be managed efficiently to control any pollution that may affect the ecosystem and to ensure the environmental standards are being met. The development of water quality prediction model is an important step towards better water quality management of rivers. The objective of this work is to utilize a hybrid of Support Vector Regression (SVR) modelling and K-fold cross-validation as a tool for WQI prediction. According to Department of Environment (DOE) Malaysia, a standard Water Quality Index (WQI) is a function of six water quality parameters, namely Ammoniacal Nitrogen (AN), Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Dissolved Oxygen (DO), pH, and Suspended Solids (SS). In this research, Support Vector Regression (SVR) model is combined with K-fold Cross Validation (CV) method to predict WQI in Langat River, Kajang. Two monitoring stations i.e., L15 and L04 have been monitored monthly for ten years as a case study. A series of results were produced to select the final model namely Kernel Function performance, Hyperparameter Kernel value, K-fold CV value and sets of prediction model value, considering all of them undergone training and testing phases. It is found that SVR model i.e., Nu-RBF combined with K-fold CV i.e., 5-fold has successfully predicted WQI with efficient cost and timely manner. As a conclusion, SVR model and K-fold CV method are very powerful tools in statistical analysis and can be used not limited in water quality application only but in any engineering application.
SecSel, a new software tool for conservation prioritization that is applicable to ordinal-scale data for multiple biodiversity features
Authors: Akio Takenaka , Hiroyuki Oguma , Yukihiro Amagai , Fumiko Ishihama 
Published: February 2021

AbstractSecSel, a protected-area prioritization tool, has been developed to help design areas that efficiently protect multiple features, including conservation of biodiversity and use of ecosystem services. The prioritization by SecSel is based on evaluation of the local units of each feature. The evaluation metrics should be quantitative but need not be ratio scale. The minimum requirement of the input data is that they are ordinal. The conservation target is the number of local units with high values of each feature to be protected in the area. SecSel can handle conflicts among features, including conflicts between conservation and utilization of land or specific ecosystem functions. Before the selection procedure, one of a conflicting pair of features in a site is discarded. That decision is based on the dispensability of the local unit to fulfilling the conservation target of each feature. SecSel also considers the cost of including each site in the protected area and the compactness of the area in terms of total boundary length or the distance to the nearest site. To demonstrate the functionality of Secsel, we used it to design land use in an alpine region of northern Japan where conservation of alpine vegetation and its recreational use are important considerations.
A conserved role of the duplicatedMasculinizergene in sex determination of the Mediterranean flour moth,Ephestia kuehniella
Authors: Visser Sander , Voleníková Anna , Nguyen Petr , Verhulst Eveline C. , Marec František 
Published: February 2021

AbstractSex determination in the silkworm,Bombyx mori, is based onFeminizer(Fem), a W-linkedFempiRNA that triggers female development in WZ individuals, and the Z-linkedMasculinizer(Masc), which initiates male development and dosage compensation in ZZ individuals. WhileFempiRNA is missing in a close relative ofB. mori,Mascdetermines sex in several representatives of distant lepidopteran lineages. We studied the molecular mechanisms of sex determination in the Mediterranean flour moth,Ephestia kuehniella(Pyralidae). We identified anE. kuehniella Mascortholog,EkMasc, and its paralog resulting from a recent duplication,EkMascB. Both genes are located on the Z chromosome and encode a similar Masc protein that contains two conserved domains but has lost the conserved double zinc finger domain. We developed PCR-based genetic sexing and demonstrated a peak in the expression ofEkMascandEkMascBgenes only in early male embryos. Simultaneous knock-down experiments of bothEkMascandEkMascBusing RNAi during early embryogenesis led to a shift from male- to female-specific splicing of theE. kuehniella doublesex gene (Ekdsx), their downstream effector, in ZZ embryos and resulted in a strong female-biased sex-ratio. Our results thus confirmed the conserved role of bothEkMascandEkMascBgenes in masculinization. We suggest that the C-terminal proline-rich domain, we have identified in all functionally confirmed Masc proteins, in conjunction with the masculinizing domain, is important for transcriptional regulation of sex determination in Lepidoptera. The function of the Masc double zinc finger domain is still unknown, but appears to have been lost inE. kuehniella.Author summaryThe sex-determining cascade in the silkworm,Bombyx mori, differs greatly from those of other insects. InB. mori, female development is initiated byFempiRNA expressed from the W chromosome during early embryogenesis.FempiRNA silencesMasculinizer(Masc) thereby blocking the male pathway resulting in female development. It is currently unknown whether this cascade is conserved across Lepidoptera. In the Mediterranean flour moth,Ephestia kuehniella, we identified an ortholog ofMascand discovered its functional duplication on the Z chromosome, which has not yet been found in any other lepidopteran species. We provide two lines of evidence that both theEkMascandEkMascBgenes play an essential role in masculinization: (i) they show a peak of expression during early embryogenesis in ZZ but not in WZ embryos and (ii) their silencing by RNAi results in female-specific splicing of theE. kuehniella doublesexgene (Ekdsx) in ZZ embryos and in a female-biased sex ratio. Our results suggest a conserved role of the duplicatedMascgene in sex determination ofE. kuehniella.
Exploring MEG brain fingerprints: evaluation, pitfalls, and interpretations
Authors: Sareen Ekansh , Zahar Sélima , Van De Ville Dimitri , Gupta Anubha , Griffa Alessandra , Amico Enrico 
Published: February 2021

AbstractIndividual characterization of subjects based on their functional connectome (FC), termed “FC fingerprinting”, has become a highly sought-after goal in contemporary neuroscience research. Recent functional magnetic resonance imaging (fMRI) studies have demonstrated unique characterization and accurate identification of individuals as an accomplished task. However, FC fingerprinting in magnetoencephalography (MEG) data is still widely unexplored. Here, we study resting-state MEG data from the Human Connectome Project to assess the MEG FC fingerprinting and its relationship with several factors including amplitude- and phase-coupling functional connectivity measures, spatial leakage correction, frequency bands, and behavioral significance. To this end, we first employ two identification scoring methods, differential identifiability and success rate, to provide quantitative fingerprint scores for each FC measurement. Secondly, we explore the edgewise and nodal MEG fingerprinting patterns across the different frequency bands (delta, theta, alpha, beta, and gamma). Finally, we investigate the cross-modality fingerprinting patterns obtained from MEG and fMRI recordings from the same subjects. We assess the behavioral significance of FC across connectivity measures and imaging modalities using partial least square correlation analyses. Our results suggest that fingerprinting performance is heavily dependent on the functional connectivity measure, frequency band, identification scoring method, and spatial leakage correction. We report higher MEG fingerprints in phase-coupling methods, central frequency bands (alpha and beta), and in the visual, frontoparietal, dorsal-attention, and default-mode networks. Furthermore, cross-modality comparisons reveal a certain degree of spatial concordance in fingerprinting patterns between the MEG and fMRI data, especially in the visual system. Finally, the multivariate correlation analyses show that MEG connectomes have strong behavioral significance, which however depends on the considered connectivity measure and temporal scale. This comprehensive, albeit preliminary investigation of MEG connectome test-retest identification offers a first characterization of MEG fingerprinting in relation to different methodological and electrophysiological factors and contributes to the understanding of fingerprinting cross-modal relationships. We hope that this first investigation will contribute to setting the grounds for MEG connectome identification.
Variability in scRNA-Seq analysis is mitigated by regularized or supervised approaches
Authors: Durmaz Arda , Scott Jacob G. 
Published: February 2021

ABSTRACTTranscriptional dynamics of evolutionary processes through time are highly complex and require single-cell resolution datasets. This is especially important in cancer during the evolution of resistance, where stochasticity can lead to selection for divergent transcriptional mechanisms. Statistical methods developed to address various questions in single-cell datasets are prone to variability and require careful adjustments of multiple parameter space. To assess the impact of this variation, we utilized commonly used single-cell RNA-Seq analysis tools in a combinatorial fashion to evaluate how repeatable the results are when different methods are combined. In the context of clustering and trajectory estimation, we benchmark the combinatorial space and highlight ares and methods that are sensitive to parameter changes. We have observed that utilizing temporal information in a supervised framework or regularization in latent modeling reduces variability leading to improved overlap when different parameters/methods are used. We hope that future studies can benefit from the results presented here as use of scRNA-Seq analysis tools as out of the box is becoming a standard approach in cancer research.
Enzyme engineering andin vivotesting of a formate-reduction pathway
Authors: Wang Jue , Anderson Karl , Yang Ellen , He Lian , Lidstrom Mary E. 
Published: February 2021

AbstractFormate is an attractive feedstock for sustainable microbial production of fuels and chemicals, but its potential is limited by the lack of efficient assimilation pathways. The reduction of formate to formaldehyde would allow efficient downstream assimilation, but no efficient enzymes are known for this transformation. To develop a 2-step formate-reduction pathway, we screened natural variants of acyl-CoA synthetase (ACS) and acylating aldehyde dehydrogenase (ACDH) for activity on one-carbon substrates and identified active and highly expressed homologs of both enzymes. We then performed directed evolution, increasing ACDH specific activity by 2.5-fold and ACS lysate activity by 5-fold. To test forin vivoactivity of our pathway, we expressed it in a methylotroph which can natively assimilate formaldehyde. Although the enzymes were active in cell extracts, we could not detect formate assimilation into biomass, indicating that further improvement will be required for formatotrophy. Our work provides a foundation for further development of a versatile pathway for formate assimilation.