bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of Infinium and Axiom SNP array data in the outcrossing species Malus × domestica and causes for seemingly incompatible calls
Authors: Howard Nicholas P. , Troggio Michela , Durel Charles-Eric , Muranty Hélène , Denancé Caroline , Bianco Luca , Tillman John , van de Weg Eric 
Published: September 2020

AbstractBackgroundSingle nucleotide polymorphism (SNP) array technology has been increasingly used to generate large quantities of SNP data for use in genetic studies. As new arrays are developed to take advantage of new technology and of improved probe design using new genome sequence and panel data, a need to integrate data from different arrays and array platforms has arisen. This study was undertaken in view of our need for an integrated high-quality dataset of Illumina Infinium® 20K and Affymetrix Axiom® 480K SNP array data in apple (Malus × domestica). In this study, we qualify and quantify the compatibility of SNP calling, defined as SNP calls that are both accurate and concordant, across both arrays by two approaches. First, the concordance of SNP calls was evaluated using a set of 417 duplicate individuals genotyped on both arrays starting from a set of 10,295 robust SNPs on the Infinium array. Next, the accuracy of the SNP calls was evaluated on additional germplasm (n=3,141) from both arrays using Mendelian inconsistent and consistent errors across thousands of pedigree links. While performing this work, we took the opportunity to evaluate reasons for probe failure and observed discordant SNP calls.ResultsConcordance among the duplicate individuals was on average of 97.1% across 10,295 SNPs. Of these SNPs, 35% had discordant call(s) that were further curated, leading to a final set of 8,412 (81.7%) SNPs that were deemed compatible. Compatibility was highly influenced by the presence of alternate probe binding locations and secondary polymorphisms. The impact of the latter was highly influenced by their number and proximity to the 3’ end of the probe.ConclusionsThe Infinium and Axiom SNP array data were mostly compatible. However, data integration required intense data filtering and curation. This work resulted in a workflow and information that may be of use in other data integration efforts. Such an in-depth analysis of array concordance and accuracy as ours has not been previously described in literature and will be useful in future work on SNP array data integration and interpretation, and in probe/platform development.
VeTra: a tool for trajectory inference based on RNA velocity
Authors: Weng Guangzheng , Kim Junil , Won Kyoung Jae 
Published: September 2020

ABSTRACTTrajectory inference (TI) for single cell RNA sequencing (scRNAseq) data is a powerful approach to interpret dynamic cellular processes such as cell cycle and development. Still, however, accurate inference of trajectory is challenging. Recent development of RNA velocity provides an approach to visualize cell state transition without relying on prior knowledge. To perform TI and group cells based on RNA velocity we developed VeTra. By applying cosine similarity and merging weakly connected components, VeTra identifies cell groups from the direction of cell transition. Besides, VeTra suggests key regulators from the inferred trajectory. VeTra is a useful tool for TI and subsequent analysis.
Low-level, prediction-based sensory and motor processes are unimpaired in Autism
Authors: Finnemann Johanna , Plaisted-Grant Kate , Moore James , Teufel Christoph , Fletcher Paul 
Published: September 2020

AbstractA new promising account of human brain function suggests that sensory cortices try to optimise information processing via predictions that are based on prior experiences. The brain is thus likened to a probabilistic prediction machine. There has been a growing – though inconsistent – literature to suggest that features of autism spectrum conditions (ASCs) are associated with a deficit in modelling the world through such prediction-based inference. However empirical evidence for differences in low-level sensorimotor predictions in autism is still lacking. One approach to examining predictive processing in the sensorimotor domain is in the context of self-generated (predictable) as opposed to externally-generated (less predictable) effects. We employed two complementary tasks – force-matching and intentional binding – which examine self-versus externally-generated action effects in terms of sensory attenuation and attentional binding respectively in adults with and without autism. The results show that autism was associated with normal levels of sensory attenuation of internally-generated force and with unaltered temporal attraction of voluntary actions and their outcomes. Thus, our results do not support a general deficit in predictive processing in autism.
Effects of N, P, K on Yield and Quality of Jujube in the Loess Hilly Region and Its Fertilization Model
Authors: Ye Shenglan , Liu Tiancheng , Wei Yulu 
Published: September 2020

AbstractThe aim of this study is to explore the optimal N, P and K fertilization model suitable for pear-jujube in the mountain of northern Shaanxi in 2016 years. This experiment use 3-factor, saturated optimal design for quadratic fertilization scheme. The effects of different fertilization treatments on the yield and quality of pear-jujube were studied through field experiments. And comprehensive evaluation based on the quality of pear-jujube. The results showed that N1P3K3has the highest yield, which is 48% higher than the control (CK). The effect of nitrogen, phosphorus, and potassium on yield is potassium fertilizer (positive effect)> phosphate fertilizer (positive effect)> nitrogen fertilizer (negative effect). Phosphate and potassium fertilizers have significant effects on increasing the content of soluble solids. Application of potassium fertilizer alone can significantly increase the content of reduced Vitamins c. The combined application of nitrogen, phosphorus, and potassium reduced the content of reduced Vitamins c. N3P3K1treatment can significantly increase the total sugar content in fruits. Single application of phosphate and potassium increases the content of organic acids in fruits. Other fertilization treatments have significant effects on reducing the content of organic acids in fruits. The sugar-acid ratio of N3P3K1is significantly higher than CK, which had an important effect on improving the taste. A high amount of potassium fertilizer has a significant effect on increasing the total flavonoid content in fruits. The interaction of nitrogen and phosphorus will reduce the total flavonoid content. The effect of nitrogen, phosphorus, and potassium on quality is potassium (positive effect)> nitrogen (positive effect)> phosphate (positive effect). Comprehensive analysis, the optimal fertilization amount when the target yield is 23000 ∼ 27000 kg·hm-2and the quality score is above 85 is nitrogen (N) 406.93 ∼ 499.31 kg·hm-2, phosphorus (P2O5) 203.94 ∼ 297.08 kg·hm-2, and potassium (K2O) 285.47 ∼ 322.82 kg·hm-2.
Mature black alder shows intermittent events of high stem methane emissions
Authors: Köhn Daniel , Günther Anke , Schwabe Ines , Jurasinski Gerald 
Published: September 2020

SummaryTree stems can be a source of the greenhouse gas methane (CH4). However, assessments of the global importance are complicated by a lack of research and a high variability between ecosystems. Here, we determined the contribution of emissions from tree stems of mature black alder (Alnus glutinosa(L.) Gaertn.) to overall CH4exchange in two temperate peatlands.We measured emissions from stems and soils using closed chambers in a drained and a wet alder forest over two years. Further, we studied the importance of alder leaves as substrate for methanogenesis in an incubation experiment.Stem CH4emissions were shortlived and occurred only during times of inundation at the wet site. The drained site did not show stem emissions and the soil acted as a small CH4sink. The contribution of stem emissions to the overall CH4budget was below 0.3% in both sites.Our results show that also mature black alders intermittently can be a source of CH4. However, the low share of stem-mediated CH4emissions in both forests may indicate that this pathway is only of minor relative importance in temperate peatlands.
Metabolic profiling reveals nutrient preferences during carbon utilization inBacillusspecies
Authors: Chang James D. , Vaughan Ellen E. , Liu Carmen Gu , Jelinski Joseph W. , Terwilliger Austen L. , Maresso Anthony W. 
Published: September 2020

AbstractPathogenic bacteria take host nutrients to support their growth, division, survival, and pathogenesis. The genusBacillusincludes species with diverse natural histories, including free-living nonpathogenic heterotrophs such asB. subtilisand host-dependent pathogens such asB. anthracis(the etiological agent of the disease anthrax) andB. cereus, a cause of food poisoning. Although highly similar genotypically, the ecological niches of these three species are mutually exclusive, which raises the untested hypothesis that their metabolism has speciated along a nutritional tract. Here, we employed a quantitative measurement of the number of reducing equivalents as a function of growth on hundreds of different sources of carbon to gauge the “culinary preferences” of three distinctBacillusspecies, and relatedStaphylococcus aureus. We show that each species had widely varying metabolic ability to utilize diverse sources of carbon that correlated to their ecological niches. In addition, carbohydrates are shown to be the preferred sources of carbon when grown under idealin vitroconditions. Rather unexpectedly, these metabolic utilizations did not correspond one-to-one with an increase in biomass, which brings to question what cellular activity should be considered productive when it comes to virulence. Finally, we applied this system to the growth and survival ofB. anthracisin a blood-based environment and find that amino acids become the preferred source of energy while demonstrating the possibility of applying this approach to identifying xenobiotics or host compounds that can promote or interfere with bacterial metabolism during infection.Author summarySuccessful organisms must make nutritional adaptations to thrive in their environment. Bacterial pathogens are no exception, having evolved for survival inside their hosts. The host combats these pathogens by depriving them of potential biochemical resources, termed nutritional immunity. This places pathogens under pressure to utilize their resources efficiently and strategically, and their metabolism must in turn be tailored for this situation. In this study, we examined the carbon metabolism of three human pathogens of varying virulence (Bacillus anthracis, Bacillus cereus, andStaphylococcus aureus) and one nonpathogenicBacillus(Bacillus subtilis) via a phenotype microarray that senses reducing equivalents produced during metabolism. Our analysis shows the existence of distinct preferences by these pathogens towards only a select few carbohydrates and implies reliance on specific metabolic pathways. These metabolic signatures obtained could be distinguished from one bacterial species to another, and we conclude that nutrient preferences offer a new perspective into investigating how pathogens can thrive during infection despite host-induced starvation.
Glibenclamide, ATP and Metformin Increases the Expression of Human Bile Salt Export Pump ABCB11
Authors: Vats Nisha , Dubey Ravi Chandra , Sanal Madhusudana Girija , Taneja Pankaj , Venugopal Senthil Kumar 
Published: September 2020

ABSTRACTBackgroundBile Salt Export Pump (BSEP/ABCB11) is important in the maintenance of the enterohepatic circulation of bile acids and drugs. Drugs such as rifampicin, glibenclamide inhibit BSEP. Progressive Familial Intrahepatic Cholestasis Type-2, a lethal pediatric disease, some forms of intrahepatic cholestasis of pregnancy, and drug-induced cholestasis are associated with BSEP dysfunction.MethodsWe started with a bioinformatic approach to identify the relationship between ABCB11 and other proteins, microRNAs, and drugs. Microarray data set of the liver samples from ABCB11 knockout mice was analyzed by GEO2R tool. Differentially expressed gene pathway enrichment analysis was done by ClueGo v2.5.5 app from Cytoscape. Protein-protein interaction network was constructed by STRING application in Cytoscape. Networks were analyzed using the Cytoscape software v3.7.1. CyTargetLinker v4.1.0 was used to screen the transcription factors, microRNAs and drugs. Predicted drugs were validated on human liver cell line, HepG2. BSEP expression was quantified by Real Time PCR and Western Blot.ResultsABCB11 knockout in mice was associated with a predominant upregulation and downregulation of genes associated with cellular component movement and sterol metabolism respectively. We further identified the hub genes in the network. Genes related to immune activity, cell signaling and fatty acid metabolism were dysregulated. We further identified drugs (glibenclamide and ATP) and a total of 14 microRNAs targeting the gene. Western Blot and Real Time PCR analysis confirmed the upregulation of BSEP on the treatment of HepG2 cells with glibenclamide, ATP, and metformin.ConclusionThe differential expression of cell signaling genes and those related to immune activity in ABCB11 KO animals may be secondary to cell injury. We have found glibenclamide, ATP, and metformin upregulates BSEP. The mechanisms involved and the clinical relevance of these findings need to be investigated.
Negeviruses reduce replication of alphaviruses during co-infection
Authors: Patterson Edward I. , Kautz Tiffany F. , Contreras-Gutierrez Maria A. , Guzman Hilda , Tesh Robert B. , Hughes Grant L. , Forrester Naomi L. 
Published: September 2020

AbstractNegeviruses are a group of insect-specific virus (ISV) that have been found in many arthropods. Their presence in important vector species led us to examine their interactions with arboviruses during co-infections. Wild-type negeviruses reduced the replication of Venezuelan equine encephalitis virus (VEEV) and chikungunya virus (CHIKV) during co-infections in mosquito cells. Negev virus (NEGV) isolates were also used to express GFP and anti-CHIKV antibody fragments during co-infections with CHIKV. NEGV expressing anti-CHIKV antibody fragments was able to further reduce replication of CHIKV during co-infections, while reductions of CHIKV with NEGV expressing GFP were similar to titers with wild-type NEGV alone. These results are the first to show that negeviruses induce superinfection exclusion of arboviruses, and to demonstrate a novel approach to deliver anti-viral antibody fragments with paratransgenic ISVs. The ability to inhibit arbovirus replication and express exogenous proteins in mosquito cells make negeviruses a promising platform for control of arthropod-borne pathogens.
Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon-anticodon pairing
Authors: Hoffer Eric D. , Hong Samuel , Sunita S. , Maehigashi Tatsuya , Gonzalez Ruben L. , Whitford Paul , Dunham Christine M. 
Published: September 2020

ABSTRACTModifications in the tRNA anticodon, adjacent to the three-nucleotide anticodon, influence translation fidelity by stabilizing the tRNA to allow for accurate reading of the mRNA genetic code. One example is the N1-methylguaonosine modification at guanine nucleotide 37 (m1G37) located in the anticodon loop, immediately adjacent to the anticodon nucleotides 34-36. The absence of m1G37 in tRNAProcauses +1 frameshifting on polynucleotide, slippery codons. Here, we report structures of the bacterial ribosome containing tRNAProbound to either cognate or slippery codons to determine how the m1G37 modification prevents mRNA frameshifting. The structures reveal that certain codon-anticodon contexts and m1G37 destabilize interactions of tRNAProwith the peptidyl site, causing large conformational changes typically only seen during EF-G mediated translocation of the mRNA-tRNA pairs. These studies provide molecular insights into how m1G37 stabilizes the interactions of tRNAProwith the ribosome and the influence of slippery codons on the mRNA reading frame.IMPACT STATEMENTChemical modifications near the tRNA anticodon and specific mRNA-tRNA pairs combine to control the ribosomal three-nucleotide mRNA reading frame, essential for the sequential addition of amino acids into polypeptide chains.Data depositionCrystallography, atomic coordinates, and structure factors have been deposited in the Protein Data Bank,www.pdb.org(PDB codes 6NTA, 6NSH, 6NUO, 6NWY, 6O3M, 6OSI)
Tree-Aggregated Predictive Modeling of Microbiome Data
Authors: Bien Jacob , Yan Xiaohan , Simpson Léo , Müller Christian L. 
Published: September 2020

AbstractModern high-throughput sequencing technologies provide low-cost microbiome survey data across all habitats of life at unprecedented scale. At the most granular level, the primary data consist of sparse counts of amplicon sequence variants or operational taxonomic units that are associated with taxonomic and phylogenetic group information. In this contribution, we leverage the hierarchical structure of amplicon data and propose a data-driven and scalable tree-guided aggregation framework to associate microbial subcompositions with response variables of interest. The excess number of zero or low count measurements at the read level forces traditional microbiome data analysis workflows to remove rare sequencing variants or group them by a fixed taxonomic rank, such as genus or phylum, or by phylogenetic similarity. By contrast, our framework, which we calltrac(tree-aggregation ofcompositional data), learns data-adaptive taxon aggregation levels for predictive modeling, greatly reducing the need for user-defined aggregation in preprocessing while simultaneously integrating seamlessly into the compositional data analysis framework. We illustrate the versatility of our framework in the context of large-scale regression problems in human gut, soil, and marine microbial ecosystems. We posit that the inferred aggregation levels provide highly interpretable taxon groupings that can help microbiome researchers gain insights into the structure and functioning of the underlying ecosystem of interest.
Ca2+and Membrane Potential Transitions During Action Potentials are Self-Similar to Each Other and to Variability of AP Firing Intervals Across the Broad Physiologic Range of AP Intervals During Autonomic Receptor Stimulation
Authors: Yang Dongmei , Morrell Christopher H. , Lyashkov Alexey E. , Tagirova Syevda , Zahanich Ihor , Yaniv Yael , Vinogradova Tatiana M. , Ziman Bruce D. , Maltsev Victor A. , Lakatta Edward G. 
Published: September 2020

AbstractCa2+and Vmtransitions occurring throughout AP cycles in sinoatrial nodal (SAN) cells arecuesthat: (1)not only regulateactivation states of molecules operating within criticality (Ca2+domain) and limit-cycle (Vmdomain) mechanisms of a coupled-clock system that underlies SAN cell automaticity; (2) but are alsoregulated bythe activation states of the clock molecules they regulate. In other terms, these cues arebothcauses and effects of clock molecular activation (recursion). Recently, we demonstrated that Ca2+and Vmtransitions during AP cycles in single SAN cells isolated from mice, guinea pigs, rabbits and humans are self-similar (obey a power law) and are also self-similar to trans-species AP firing intervals of these cells invitro, to heart rate invivo, and to body mass.Neurotransmitter stimulation of β adrenergic receptor or cholinergic receptor initiated signaling in SAN cells modulates their AP firing rate and rhythm by impacting on the degree to which SAN clocks couple to each other, creating the broad physiologic range of SAN cell mean AP firing intervals and firing interval variabilities. Here we show that Ca2+and Vmdomain kinetic transitions (time to AP ignition in diastole and 90% AP recovery) occurring within given AP, the mean AP firing intervals, and AP firing interval variabilities within time-series of APs in 230 individual SAN cells are self-similar (obey power laws). In other terms, these long-range correlations inform on self-similar distributions of order among SAN cells across the entire broad physiologic range of SAN AP firing intervals, regardless of whether autonomic receptors of these cells are stimulated or not, and regardless of the type (adrenergic or cholinergic) of autonomic receptor stimulation. These long-range correlations among distributions of Ca2+and Vmkinetic functions that regulate SAN cell clock coupling during each AP cycle in differentindividual, isolated SAN cells not in contact with each other. Our numerical model simulations further extended our perspectives to the molecular scale and demonstrated that many ion currents also behave self-similar across autonomic states.Thus, to ensure rapid flexibility of AP firing rates in response to different types and degrees of autonomic input, nature “did not reinvent molecular wheels within the coupled-clock system of pacemaker cells”, but differentially engaged or scaled the kinetics of gears that regulate the rate and rhythm at which the “wheels spin” in a given autonomic input context.
Local Bilayer Hydrophobicity Modulates Membrane Protein Stability
Authors: Marx Dagan C. , Fleming Karen G. 
Published: September 2020

ABSTRACTThrough the insertion of nonpolar side chains into the bilayer, the hydrophobic effect has long been accepted as a driving force for membrane protein folding. However, how the changing chemical composition of the bilayer affects the magnitude side chain transfer free energieshas historically not been well understood. A particularly challenging region for experimental interrogation is the bilayer interfacial region that is characterized by a steep polarity gradient. In this study we have determined thefor nonpolar side chains as a function of bilayer position using a combination of experiment and simulation. We discovered an empirical correlation between the surface area of nonpolar side chain, the transfer free energies, and the local water concentration in the membrane that allows forto be accurately estimated at any location in the bilayer. Using these water-to-bilayervalues, we calculated the interface-to-bilayer transfer free energy. We find that theare similar to the “biological”, translocon-based transfer free energies, indicating that the translocon energetically mimics the bilayer interface. Together these findings can be applied to increase the accuracy of computational workflows used to identify and design membrane proteins, as well as bring greater insight into our understanding of how disease-causing mutations affect membrane protein folding and function.