bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence quantification analysis of heart rate variability is a COVID-safe alternative to gas analysis in the detection of metabolic thresholds
Authors: Zimatore G. , Falcioni L. , Gallotta M.C. , Bonavolontà V. , Campanella M. , De Spirito M. , Guidetti L. , Baldari C. 
Published: March 2021

AbstractThe first aim of the study was to verify if in individuals with different physical fitness levels the Recurrence Quantification Analysis (RQA) of Heart Rate Variability (HRV) time series could be an alternative to Gas Exchange (GE) analysis in the determination of metabolic thresholds. The second aim was to investigate the validity of the RQA method compared to the GE method in thresholds detection. The two metabolic thresholds were estimated in thirty young individuals during Cardiopulmonary Exercise Testing on a cycle-ergometer and HR, VO2and Workload were measured by the two different methods (RQA and GE methods). RM ANOVA was used to assess main effects of methods and methods-by-groups interaction effects for HR, VO2and Workload at the aerobic (AerT) and the anaerobic (AnT) thresholds. Validity of the RQA at both thresholds was assessed for HR, VO2and Workload by Ordinary Least Products (OLP) regression analysis, Typical Percentage Errors (TE), Intraclass Correlation Coefficients (ICC) and the Bland Altman plots. No methods-by-groups interaction effects were detected for HR, VO2and Workload at the AerT and the AnT. The OLP regression analysis showed that at both thresholds RQA and GE methods had very strong correlations (r>0.8) in all variables (HR, VO2and Workload). Slope and intercept values always included the 1 and the 0, respectively. At the AerT the TE ranged from 4.02% to 10.47% (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.85). At the AnT the TE ranged from 2.61% to 6.64% (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.89). Our results suggest that the RQA of HRV time series is a COVID-safe approach for the determination of metabolic thresholds in individuals with different physical fitness levels, therefore, it can be used as a valid method for threshold detection alternative to gas analysis.
SNP- Based Assessment of Genetic Purity and Diversity in Maize Hybrid Breeding
Authors: Josia Chimwemwe , Mashingaidze Kingstone , Amelework Assefa B. , Kondwakwenda Aleck , Musvosvi Cousin , Sibiya Julia 
Published: March 2021

AbstractAssessment of genetic purity of inbred lines and their resultant F1hybrids is an essential quality control check in maize hybrid breeding, variety release and seed production. In this study, genetic purity, parent-offspring relationship and diversity among the inbred lines were assessed using 92 single-nucleotide polymorphism (SNP) markers. A total of 188 maize genotypes, comprising of 26 inbred lines, four doubled haploid (DH) lines and 158 single-cross maize hybrids were investigated in this study using Kompetitive Allele Specific Polymerase Chain Reaction (KASP) genotyping assays. The bi-allelic data was analyzed for genetic purity and diversity parameters using GenAlex software. The SNP markers were highly polymorphic and 90% had polymorphic information content (PIC) values of > 0.3. Pairwise genetic distances among the lines ranged from 0.05 to 0.56, indicating a high level of dissimilarity among the inbred lines. Maximum genetic distance of (0.56) was observed for CKDHL0089, CML443 and CB323, while the lowest (0.05) was between I-42 and I-40. The majority (67%) of the inbred lines studied were genetically pure with residual heterozygosity of <5%, while only 33% were had heterozygosity levels of >5%. Inbred lines, which were not pure, require purification through further inbreeding. Cluster analysis partitioned the lines into three distinct genetic clusters with the potential to contribute new beneficial alleles to the maize breeding program. Out of the 68 hybrids (43%) that passed the parent-offspring test, seven hybrids namely; SCHP29, SCHP95, SCHP94, SCHP134, SCHP44, SCHP114 and SCHP126, were selected as potential candidates for further evaluation and release due to their outstanding yield performance.
The involvement of type IV pili and phytochrome in gliding motility, lateral motility and phototaxis of the cyanobacteriumPhormidium lacuna
Authors: Lamparter Tilman , Babian Jennifer , Fröhlich Katrin , Mielke Marion , Weber Nora , Wunsch Nadja , Zais Finn , Schulz Kevin , Aschmann Vera , Spohrer Nina , Krauß Norbert 
Published: March 2021

AbstractPhormidium lacuna, a filamentous cyanobacterium without heterocysts, can be transformed by natural transformation. These filaments are motile on agar and other surfaces and display rapid lateral movements in liquid culture. Furthermore, they exhibit phototactic response under vertical illumination in Petri dishes. We generated mutants in which a KanR resistance cassette was integrated in the phytochrome genecphAand in various genes of the type IV pilin apparatus.pilM, pilN, pilQandpilTmutants were defective in all three responses, indicating that type IV pili are involved in all three kinds of motility. Rapid movements of wild type in liquid culture requires an extracellular matrix with type IV pili as central player.pilBmutants are only partially blocked in their responses.pilBis the proposed ATPase for expelling of the filament. In the mutant, this function could be overtaken by an alternative protein, likepilT, which regularly mediates retraction of pili. ThecphAmutant revealed a significantly reduced phototactic response towards red light. We assume that together with other photoreceptors, CphA regulates the phototactic response by down regulation of surface attachment.
Salty surfaces deter feeding in a blood-sucking disease vector
Authors: Pontes G , Latorre-Estivalis JM , Gutiérrez ML , Cano A , Berón de Astrada M , Lorenzo MG , Barrozo RB 
Published: March 2021

AbstractSalts are essential nutrients required for many physiological processes, and deficient or excessive salt results in adverse health problems. Taste is the ultimate sensory modality involved in resource quality assessment, resulting in acceptance or rejection. Here, we show that detection of high-salt substrates by a salt-sensitive antennal gustatory receptor neuron, S1-GRN, results in feeding avoidance in the hematophagous bugRhodnius prolixus. Knock-down of two antennal-expressed amiloride-sensitive pickpocket channel receptors (PPKs;RproPPK014276andRproPPK28) using RNA interference, prevents avoidance of bugs to high-salt substrates. Tracing antennal GRNs to the central nervous system reveals the antennal lobes as a gustatory processing center. The identification of the gustatory basis of high-salt detection in a blood feeder provides novel targets to prevent biting and feeding, as well as to promote substrate avoidance in a relevant disease vector.Significance StatementDetection of aversive gustatory stimuli induces avoidance responses in animals. Avoidance acquires particular interest if it reduces the biting rates of blood-feeding insects of medical relevance. Here we describe the molecular and physiological basis of high-salt detection in the blood-sucking disease vectorRhodnius prolixus. We show that detection of high-salt substrates through two PPK receptors expressed in an antennal gustatory receptor neuron produces feeding avoidance. Understanding these gustatory-driven aversive responses allows the hitherto overlooked use of gustatory molecules as a complement to known olfactory repellents.
Replicative fitness SARS-CoV-2 20I/501Y.V1 variant in a human reconstituted bronchial epithelium
Authors: Touret Franck , Luciani Léa , Baronti Cécile , Cochin Maxime , Driouich Jean-Sélim , Gilles Magali , Thirion Laurence , Nougairède Antoine , de Lamballerie Xavier 
Published: March 2021

AbstractSince its emergence in 2019, circulating populations of the new coronavirus continuously acquired genetic diversity. At the end of 2020, a variant named 20I/501Y.V1 (lineage B.1.1.7) emerged and replaced other circulating strains in several regions. This phenomenon has been poorly associated to biological evidence that this variant and original strain exhibit different phenotypic characteristics. Here, we analyse the replication ability of this new variant in different cellular models using for comparison an ancestral D614G European strain (lineage B1). Results from comparative replication kinetics experimentsin vitroand in a human reconstituted bronchial epithelium showed no difference. However, when both viruses were put in competition in a human reconstituted bronchial epithelium, the 20I/501Y.V1 variant outcompeted the ancestral strain. Altogether, these findings demonstrate that this new variant replicates more efficiently and could contribute to better understand the progressive replacement of circulating strains by the SARS-CoV-2 20I/501Y.V1 variant.ImportanceThe emergence of several SARS-CoV-2 variants raised numerous questions concerning the future course of the pandemic. We are currently observing a replacement of the circulating viruses by the variant from the United Kingdom known as 20I/501Y.V1 from B.1.1.7 lineage but there is little biological evidence that this new variant exhibit a different phenotype. In the present study, we used different cellular models to assess the replication ability of the 20I/501Y.V1 variant. Our results showed that this variant replicate more efficiently in a human reconstituted bronchial epithelium, which may explain why it spreads so rapidly in human populations.
Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naïve and COVID-19 recovered individuals
Authors: Camara Carmen , Lozano-Ojalvo Daniel , Lopez-Granados Eduardo , Paz-Artal Estela , Pion Marjorie , Correa-Rocha Rafael , Ortiz Alberto , Lopez-Hoyos Marcos , Iribarren Marta Erro , Portoles Jose , Portoles Pilar , Perez-Olmeda Mayte , Oteo Jesus , Berin Cecilia , Guccione Ernesto , Bertoletti Antonio , Ochando Jordi 
Published: March 2021

AbstractThe rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naïve individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naïve individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naïve and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naïve individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.
A toxic friend: Genotoxic and mutagenic activity of the probiotic strainEscherichia coliNissle 1917
Authors: Nougayrède Jean-Philippe , Chagneau Camille , Motta Jean-Paul , Bossuet-Greif Nadège , Belloy Marcy , Taieb Frédéric , Gratadoux Jean-Jacques , Thomas Muriel , Langella Philippe , Oswald Eric 
Published: March 2021

AbstractThe probioticEscherichia colistrain Nissle 1917 (DSM 6601, Mutaflor), generally considered as beneficial and safe, has been used for a century to treat various intestinal diseases. However, Nissle 1917 hosts in its genome thepkspathogenicity island that codes for the biosynthesis of the genotoxin colibactin. Colibactin is a potent DNA alkylator, suspected to play a role in colorectal cancer development. We show in this study that Nissle 1917 is functionally capable of producing colibactin and inducing interstrand crosslinks in the genomic DNA of epithelial cells exposed to the probiotic. This toxicity was even exacerbated with lower doses of the probiotic, when the exposed cells started to divide again but exhibited aberrant anaphases and increased gene mutation frequency. DNA damage was confirmedin vivoin mouse models of intestinal colonization, demonstrating that Nissle 1917 produces the genotoxin in the gut lumen. Although it is possible that daily treatment of adult humans with their microbiota does not produce the same effects, administration of Nissle 1917 as a probiotic or as a chassis to deliver therapeutics might exert long term adverse effects and thus should be considered in a risk versus benefit evaluation.ImportanceNissle 1917 is sold as a probiotic and considered safe even though it is known since 2006 that it encodes the genes for colibactin synthesis. Colibactin is a potent genotoxin that is now linked to causative mutations found in human colorectal cancer. Many papers concerning the use of this strain in clinical applications ignore or elude this fact, or misleadingly suggest that Nissle 1917 does not induce DNA damage. Here, we demonstrate that Nissle 1917 produces colibactinin vitroandin vivoand induces mutagenic DNA damage. This is a serious safety concern that must not be ignored, for the interests of patients, the general public, health care professionals and ethical probiotic manufacturers.
Pax6 loss alters the morphological and electrophysiological development of mouse prethalamic neurons
Authors: Tian Tian , Quintana-Urzainqui Idoia , Kozić Zrinko , Pratt Thomas , Price David J. 
Published: March 2021

ABSTRACTPax6 is a well-known regulator of early neuroepithelial progenitor development. Its constitutive loss has a particularly strong effect on the developing prethalamus, causing it to become extremely hypoplastic. To overcome this difficulty in studying the long-term consequences of Pax6 loss for prethalamic development, we used conditional mutagenesis to delete Pax6 at the onset of neurogenesis and studied the developmental potential of the mutant prethalamic neurons in vitro. We found that Pax6 loss affected their rates of neurite elongation, the location and length of their axon initial segments and their electrophysiological properties. Our results broaden our understanding of the long-term consequences of Pax6 deletion in the developing mouse forebrain, suggesting that it can have cell autonomous effects on the structural and functional development of some neurons.SUMMARY STATEMENTPax6 impacts neurite extension, axon initial segment properties and ability to fire normal action potentials in maturing neurons, revealing actions extending beyond those previously characterized in progenitors.
Decoding nonspecific interactions between human nuclear transport proteins: A computational study
Authors: Rathod Shravan B. 
Published: March 2021

AbstractThe nuclear protein transport between the nucleus and cytosol can be considered a core process of cell regulation. Specially designed proteins in nature such as importins, exportins, and some other transporters facilitate this transport in the cell and control the cellular processes. Transient and weak protein–protein interactions are basis of these various biomolecular processes. Prior to cargo transports, the transport proteins recognize the Nuclear localization signals (NLSs) and Nuclear export signals (NESs) of cargo proteins and, bind to the RanGTP. Also, these proteins bind with other similar protein subunits along with RanGTP to transport cargos. Cell is enormously crowded place where DNA, RNA, proteins, lipids and small molecules cooperatively facilitate numerous cellular processes. In such environment, existence of nonspecific interactions between proteins is quite obvious. Considering this hypothesis, in this study, protein-protein docking approach was applied to determine the binding affinities of 12 human nuclear transport proteins. Results showed that KPNA1, TNPO1 and TNPO3 have greater affinity to bind with other transport proteins. Also, among 78 complexes (12 homodimers and 66 heterodimers), KPNA1-KPNB1, KPNA1-TNPO1 and KPNA1-TNPO3 complexes have the highest stability.Graphical abstractInitially, 12 human nuclear transport proteins PDB structures were retrieved from the 1. Protein data bank (PDB). These proteins had some missing terminals and residues thus, we used 2. SWISS-MODEL and 3. MODELLER v.10.1 to model those regions in these proteins. Next, we used widely popular web server, 4. ClusPro v.2.0 for protein-protein docking analysis among 12 proteins. Then, we employed 5. PRODIGY web server to calculate the binding affinities of 78 complexes (12 homodimers & 66 heterodimers). Finally, we utilised three web tools, 6. Arpeggio, 7. PIMA and 8. PDBePISA to analyse top-three complexes (KPNA1-KPNB1, KPNA1-TNPO1 & TNPO3) for in-depth interactions and energetics.
Cancer models and statistical analysis of age distribution of cancers
Authors: Tetearing Alexandr N. 
Published: March 2021

AbstractIn this paper, mathematical mutational models of the age distribution of cancers are obtained. These are two models – a simple model and a complex model, which takes into account the growth of the cell population and the transmission of mutations to daughter cells. Using the resulting formulas, we approximated real age-specific cancer incidence datasets in women (colon, lung, mammary, stomach) and men (colon, lung, prostate, stomach). We estimated parameters such as the average number of mutations (per cell per unit of time) and number of mutations required for cancer to occur.The number of mutations averaged (over four types of cancer) required for cancer to occur is 5.5 (mutations per cell for women) and 6.25 (mutations per cell for men) for the complex mutational model.As an alternative to mutational models, we also consider the model of delayed carcinogenic event.
Isochoric supercooled preservation and revival of human cardiac microtissues
Authors: Powell-Palm Matthew J. , Charwat Verena , Charrez Berenice , Siemons Brian , Healy Kevin E. , Rubinsky Boris 
Published: March 2021

AbstractLow-temperatureex vivopreservation and tissue engineering based on human induced pluripotent stem cells (hiPSC) represent two of the most promising routes towards on-demand access to organs for transplantation. While these fields are often considered divergent from one another, advances in both fields present critical new opportunities for crossover. Herein we demonstrate the first-ever sub-zero centigrade preservation and revival of autonomously beating three-dimensional hiPSC-derived cardiac microtissues1via isochoric supercooling2, without the use of chemical cryoprotectants. We show that these tissues can cease autonomous beating during preservation and resume it after warming, that the supercooling process does not affect sarcomere structural integrity, and that the tissues maintain responsiveness to drug exposure following revival. Our work suggests both that functional three dimensional (3D) engineered tissues may provide an excellent high-content, low-risk testbed to study organ preservation in a genetically human context, and that isochoric supercooling may provide a robust method for preserving and reviving engineered tissues themselves.
First come, first served: Superinfection exclusion in Deformed wing virus is dependent upon sequence identity and not the order of virus acquisition
Authors: Gusachenko Olesya N , Woodford Luke , Balbirnie-Cumming Katharin , Evans David J 
Published: March 2021

AbstractDeformed wing virus (DWV) is the most important globally distributed pathogen of honey bees and, when vectored by the ectoparasiteVarroa destructor, is associated with high levels of colony losses. Divergent DWV types may differ in their pathogenicity and are reported to exhibit superinfection exclusion upon sequential infections, an inevitability in aVarroa-infested colony. We used a reverse genetic approach to investigate competition and interactions between genetically distinct or related virus strains, analysing viral load over time, tissue distribution with reporter gene-expressing viruses and recombination between virus variants. Transient competition occurred irrespective of the order of virus acquisition, indicating no directionality or dominance. Over longer periods, the ability to compete with a pre-existing infection correlated with the genetic divergence of the inoculae. Genetic recombination was observed throughout the DWV genome with recombinants accounting for ~2% of the population as determined by deep sequencing. We propose that superinfection exclusion, if it occurs at all, is a consequence of a cross-reactive RNAi response to the viruses involved, explaining the lack of dominance of one virus type over another. A better understanding of the consequences of dual- and superinfection will inform development of cross-protective honey bee vaccines and landscape-scale DWV transmission and evolution.
Single-cell methylation sequencing data reveal succinct metastatic migration histories and tumor progression models
Authors: Liu Yuelin , Li Xuan Cindy , Rashidi Mehrabadi Farid , Schäffer Alejandro A. , Pratt Drew , Crawford David R. , Malikić Salem , Molloy Erin K. , Gopalan Vishaka , Mount Stephen M. , Ruppin Eytan , Aldape Kenneth , Sahinalp S. Cenk 
Published: March 2021

AbstractRecent studies exploring the impact of methylation in tumor evolution suggest that while the methylation status of many of the CpG sites are preserved across distinct lineages, others are altered as the cancer progresses. Since changes in methylation status of a CpG site may be retained in mitosis, they could be used to infer the progression history of a tumor via single-cell lineage tree reconstruction. In this work, we introduce the first principled distance-based computational method,Sgootr, for inferring a tumor’s single-cell methylation lineage tree and jointly identifying lineage-informative CpG sites which harbor changes in methylation status that are retained along the lineage. We applySgootron the single-cell bisulfite-treated whole genome sequencing data of multiregionally-sampled tumor cells from 9 metastatic colorectal cancer patients made available by Bianet al., as well as multiregionally-sampled single-cell reduced-representation bisulfite sequencing data from a glioblastoma patient made available by Chaligneet al.. We demonstrate that the tumor lineages constructed reveal a simple model underlying colorectal tumor progression and metastatic seeding. A comparison ofSgootragainst alternative approaches shows thatSgootrcan construct lineage trees with fewer migration events and more in concordance with the sequential-progression model of tumor evolution, in time a fraction of that used in prior studies. Interestingly, lineage-informative CpG sites identified bySgootrare in inter-CpG island (CGI) regions, as opposed to CGI’s, which have been the main regions of interest in genomic methylation-related analyses.Sgootris implemented as aSnakemakeworkflow, available athttps://github.com/algo-cancer/Sgootr.Abstract Figure