bluuebunny/crossref_metadata_2025_split huggingface dataset:
CBEA: Competitive balances for taxonomic enrichment analysis
Authors: Nguyen Quang P. , Hoen Anne G. , Frost H. Robert 
Published: September 2021

AbstractResearch in human associated microbiomes often involves the analysis of taxonomic count tables generated via high-throughput sequencing. It is difficult to apply statistical tools as the data is high-dimensional, sparse, and compositional. An approachable way to alleviate high-dimensionality and sparsity is to aggregate variables into pre-defined sets. Set-based analysis is ubiquitous in the genomics literature, and has demonstrable impact in improving interpretability and power of downstream analysis. Unfortunately, there is a lack of sophisticated set-based analysis methods specific to microbiome taxonomic data, where current practice often employs abundance summation as a technique for aggregation. This approach prevents comparison across sets of different sizes, does not preserve inter-sample distances, and amplifies protocol bias. Here, we attempt to fill this gap with a new single sample taxon enrichment method that uses a novel log-ratio formulation based on the competitive null hypothesis commonly used in the enrichment analysis literature. Our approach, titled competitive balances for taxonomic enrichment analysis (CBEA), generates sample-specific enrichment scores as the scaled log ratio of the subcomposition defined by taxa within a set and the subcomposition defined by its complement. We provide sample-level significance testing by estimating an empirical null distribution of our test statistic with valid p-values. Herein we demonstrate using both real data applications and simulations that CBEA controls for type I error even under high sparsity and high inter-taxa correlation scenarios. Additionally, it provides informative scores that can be inputs to downstream analyses such as prediction tasks.Author summaryThe study of human associated microbiomes relies on genomic surveys via high-throughput sequencing. However, microbiome taxonomic data is sparse and high dimensional which prevents the application of standard statistical techniques. One approach to address this problem is to perform analyses at the level of taxon sets. Set-based analysis has a long history in the genomics literature, with demonstrable impact in improving both power and interpretability. Unfortunately, there is limited interest in developing new set-based tools tailored for microbiome taxonomic data given its unique features compared to other ‘omics data types. We developed a new tool to generate taxon set enrichment scores at the sample level through a novel log-ratio formulation based on the competitive null hypothesis. Our scores can be used for statistical inference at both the sample and population levels, as well as inputs to other downstream analyses such as prediction models. We demonstrate the performance of our method against competing approaches across both real data analyses and simulation studies.
Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2
Authors: Cui Haissi , Diedrich Jolene K. , Wu Douglas C. , Lim Justin J. , Nottingham Ryan M. , Moresco James J. , Yates John R. , Blencowe Benjamin J. , Lambowitz Alan M. , Schimmel Paul 
Published: September 2021

AbstractCells respond to perturbations like inflammation by sensing changes in metabolite levels. Especially prominent is arginine, which has known connections to the inflammatory response. Here, we found that depletion of arginine during inflammation decreased levels of a nuclear form of arginyl-tRNA synthetase (ArgRS). Surprisingly, we found that nuclear ArgRS interacts with serine/arginine repetitive matrix protein 2 (SRRM2), a spliceosomal protein and nuclear speckle component and that arginine depletion impacted both condensate-like nuclear trafficking of SRRM2 and splice-site usage in certain genes. These splice-site usage changes cumulated in synthesis of different protein isoforms that altered cellular metabolism and peptide presentation to immune cells. Our findings uncover a novel mechanism whereby a tRNA synthetase cognate to a key amino acid that is metabolically controlled during inflammation modulates the splicing machinery.
Cumulative effects of mutation and selection on susceptibility to bacterial pathogens inCaenorhabditis elegans
Authors: Saber Sayran , Johnson Lindsay M. , Rifat Md. Monjurul Islam , Rouse Sydney , Baer Charles F. 
Published: September 2021

AbstractUnderstanding the evolutionary and genetic underpinnings of susceptibility to pathogens is of fundamental importance across a wide swathe of biology. Much theoretical and empirical effort has focused on genetic variants of large effect, but pathogen susceptibility often appears to be a polygenic complex trait. Here we investigate the quantitative genetics of survival over 120 hours of exposure ("susceptibility") ofC. elegansto three bacterial pathogens of varying virulence, along with the standard laboratory food, the OP50 strain ofE. coli. We compare the genetic (co)variance input by spontaneous mutations accumulated under minimal selection to the standing genetic (co)variance in a set of 47 wild isolates. Three conclusions emerge. First, mutations increase susceptibility to pathogens, and susceptibility is uncorrelated with fitness in the absence of pathogens. Second, the orientation in trait space of the heritable (co)variance of wild isolates is sufficiently explained by mutation. However, with the possible exception ofS. aureus, pathogen susceptibility is clearly under purifying, directional, selection of magnitude roughly similar to that of competitive fitness in the MA conditions. The results provide no evidence for fitness tradeoffs between pathogen susceptibility and fitness in the absence of pathogens.
Canopy health, but not Candidatus Liberibacter asiaticus Ct values, are correlated with fruit yield in Huanglongbing affected sweet orange trees
Authors: Levy Amit , Livingston Taylor , Wang Chunxia , Achor Diann , Vashisth Tripti 
Published: September 2021

AbstractIn Florida, almost all citrus trees are infected with Huanglongbing (HLB), caused by the gram-negative, intracellular phloem limited bacteria Candidatus liberibacter asiaticus (CLas). Distinguishing between the severely and mildly sick trees is important for managing the groves and testing new HLB therapies. A mildly sick tree is one that produces higher fruit yield, compared to a severely sick tree, but measuring yields is laborious and time consuming. Here we characterized HLB affected sweet orange trees in the field in order to identify the specific traits that are correlated with the yields. We found that canopy volume, fruit detachment force (FDF) and the percentage of photosynthetically active radiation interception in the canopy (%INT) were positively correlated with fruit yields. Specifically, %INT measurements accurately distinguished between mild and severe trees in independent field trials. We could not find a difference in the Ct value between high and low producing HLB trees. Moreover, Ct values did not always agree with the number of CLas in the phloem that were visualized by transmission electron microscopy. Overall, our work identified an efficient way to distinguish between severe and mild HLB trees in Florida by measuring %INT and suggests that health of the canopy is more important for yields than the Ct value.
Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis, and Arrest of Cell Cycle
Authors: Wahab Atia-tul- , Fayyaz Sharmeen , Irshad Rimsha , Siddiqui Rafat A. , Rahman Atta-ur- , Choudhary M. Iqbal 
Published: September 2021

AbstractBreast cancer is one the most aggressive cancer worldwide, especially Pakistan due to limited therapeutic options. This study was conducted to repurpose the use of selective serotonin reuptake inhibitors (SSRIs), in the treatment of breast cancers, and merit to pursue drug re-positioning in oncology. Anti-proliferative activity of SSRIs, such as fluoxetine, paroxetine, and sertraline hydrochloride on the growth of AU-565, MCF-7, MDA-MB-231, and BT-474 breast cancer cell lines, along with human fibroblast BJ cells was determined in vitro. Changes in nuclear morphology (DAPI staining), and induction of apoptosis (flow cytometry, and caspase-3 activation) were also studied. Sertraline hydrochloride most effectively inhibited the growth of breast cancer cells in vitro. Therefore, pharmacological mechanism involved in sertraline mediated cell death was investigated in HER2+ AU565 cell line. Enhanced nuclear fragmentation, increased Annexin (+) cells, and caspase-3/7 activation indicated that sertraline-mediated cell death could be a result of BCl2-independent apoptosis as evidenced by expression of Bax, and BCl2 genes. Taken together, our results identified sertraline hydrochloride, as a potential candidate for the treatment of HER2-positive breast cancer. Even though these are in vitro results, this study opens great opportunity in the field of drug repurposing for the development of chemotherapeutic agents.
Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex
Authors: Liu Shuang , Won Hyejung , Clarke Declan , Matoba Nana , Khullar Saniya , Mu Yudi , Wang Daifeng , Gerstein Mark 
Published: September 2021

AbstractPsychiatric disorders exact immense human and economic tolls in societies globally. Underlying many of these disorders is a complex repertoire of genomic variants that influence the expression of genes involved in pathways and processes in the brain. Identifying such variants and their associated brain functions is thus essential for understanding the molecular underpinnings of psychiatric disorders. Genome-wide association studies (GWASes) have provided many variants associated with these disorders; however, our knowledge of the precise biological mechanisms by which these contribute to disease remains limited. In connection with this, expression quantitative trait loci (eQTLs) have provided useful information linking variants to genes and functions. However, most eQTL studies on human brain have focused exclusively on cis-eQTLs. A complete understanding of disease etiology should also include trans-regulatory mechanisms. Thus, we conduct one of the first genome-wide surveys of trans-eQTLs in the dorsolateral prefrontal cortex (DLPFC) by leveraging the large datasets from the PsychENCODE consortium. We identified ∼80,000 trans-eQTLs. We found that a significant number of these overlap with cis-eQTLs, thereby implicating cis-mediators as key players in trans-acting regulation. We show, furthermore, that trans-regulatory mechanisms provide novel insights into psychiatric disease. Particularly, colocalization analysis between trans-eQTLs and schizophrenia (SCZ) GWAS loci identified 90 novel SCZ risk genes and 23 GWAS loci previously uncharacterized by cis-eQTLs. Moreover, these 90 genes tend to be more central in transcriptome-wide co-expression networks and more susceptible to rare variants than SCZ-risk genes associated by cis-variation.
Tafazzin deficiency in mouse mesenchymal stem cells potentiates their immunosuppression and impairs activated B lymphocyte immune function
Authors: Zegallai Hana M. , Abu-El-Rub Ejlal , Olayinka-Adefemi Folayemi , Cole Laura K. , Sparagna Genevieve C. , Marshall Aaron J. , Hatch Grant M. 
Published: September 2021

AbstractBarth Syndrome (BTHS) is a rare X-linked genetic disorder caused by mutation in the TAFAZZIN gene which encodes the cardiolipin (CL) transacylase tafazzin (Taz). Taz deficiency in BTHS patients results in reduced CL in their tissues and a neutropenia which contributes to the risk of infections. However, the impact of Taz deficiency in other cells of the immune system is poorly understood. Mesenchymal stem cells (MSCs) are well known for their immune inhibitory function. We examined whether Taz-deficiency in murine MSCs impacted their ability to modulate lipopolysaccharide (LPS)-activated wild type (WT) murine B lymphocytes. MSCs from tafazzin knockdown (TazKD) mice exhibited a 50% reduction in CL compared to wild type (WT) MSCs. However, mitochondrial oxygen consumption rate and membrane potential were unaltered. In contrast, TazKD MSCs exhibited increased glycolysis compared to WT MSCs and this was associated with elevated proliferation, phosphatidylinositol-3-kinase expression and expression of the immunosuppressive markers indoleamine-2,3-dioxygenase, cytotoxic T-lymphocyte-associated protein 4, interleukin-10, and cluster of differentiation 59. When co-cultured with LPS-activated WT B cells, TazKD MSCs inhibited B cell proliferation and growth rate and reduced B cell secretion of IgM to a greater extent than B cells co-cultured with WT MSCs. In addition, co-culture of LPS-activated WT B cells with TazKD MSCs induced B cell differentiation toward potent immunosuppressive phenotypes including interleukin-10 secreting plasma cells and B regulatory cells compared to activated B cells co-cultured with WT MSCs. These results indicate that Taz deficiency in MSCs enhances MSCs-mediated immunosuppression of activated B lymphocytes.
Magnetic fluctuations affect circadian patterns of locomotor activity in zebrafish
Authors: Krylov Viacheslav V. , Izvekov Evgeny I. , Pavlova Vera V. , Pankova Natalia A. , Osipova Elena A. 
Published: September 2021

AbstractThe locomotor activity of zebrafish (Danio rerio) has a pronounced, well-studied circadian rhythm. Under constant illumination, the period of free-running locomotor activity in this species usually becomes less than 24 hours. To evaluate the entraining capabilities of slow magnetic variations, zebrafish locomotor activity was evaluated at constant illumination and fluctuating magnetic field with a period of 26.8 hours. Lomb-Scargle periodogram revealed significant free-running rhythms of locomotor activity and related behavioral endpoints with a period close to 27 hours. Obtained results reveal the potential of slow magnetic fluctuations for entrainment of the circadian rhythms in zebrafish. The putative mechanisms responsible for the entrainment are discussed, including the possible role of cryptochromes.
Crystal structure of a constitutive active mutant of adenosine A2A receptor
Authors: Cui Min , Zhou Qingtong , Weng Yuan , Yao Deqiang , Zhao Suwen , Song Gaojie 
Published: September 2021

AbstractPreviously we reported a common activation pathway of the class A G protein-coupled receptors (GPCRs) in which a series of conserved residues/motifs undergo conformational change during extracellular agonist binding and finally induce the coupling of intracellular G protein, and successfully predicted several novel constitutive active or inactive mutations for A2A adenosine receptor (A2AAR) through this mechanism (Zhou et al., 2019). Here we determined the crystal structure of a typical A2AAR constitutive active mutant I92N in complex with agonist UK-432097 to reveal the molecular mechanism of mutation-induced constitutive activity. The mutated I92N forms a hydrophilic interaction network with nearby residues including W6.48 of the CWxP motif, which is absent in the wild type A2AAR. Although the mutant structure is overall similar to the previously determined intermediate state A2AAR structure (PDB ID: 3QAK), the molecular dynamics simulations suggested that the I92N mutant stabilizes the metastable intermediate state through the hydrophilic interaction network and favors the receptor conformational transition towards the active state. This research provides a structural template toward the special pharmacological outcome triggered by conformational mutation and sheds light on future structural or pharmacological studies among class A GPCRs.
cDNA display coupled with next-generation sequencing for rapid activity-based screening: Comprehensive analysis of transglutaminase substrate preference
Authors: Damnjanović Jasmina , Odake Nana , Fan Jicheng , Jia Beixi , Kojima Takaaki , Nemoto Naoto , Hitomi Kiyotaka , Nakano Hideo 
Published: September 2021

AbstractcDNA display is an in vitro display technology based on a covalent linkage between a protein and its corresponding mRNA/cDNA, where a stable complex is formed suitable for a wide range of selection conditions. A great advantage of cDNA display is the ability to handle enormous library size (1012) in a microtube scale, in a matter of days. To harness its benefits, we aimed at developing a platform which combines the advantages of cDNA display with high-throughput and accuracy of next-generation sequencing (NGS) for the selection of preferred substrate peptides of transglutaminase 2 (TG2), a protein cross-linking enzyme. After the optimization of the platform by the repeated screening of binary model libraries consisting of the substrate and non-substrate peptides at different ratios, screening and selection of combinatorial peptide library randomized at positions -1, +1, +2, and +3 from the glutamine residue was carried out. Enriched cDNA complexes were analyzed by NGS and bioinformatics, revealing the comprehensive amino acid preference of the TG2 at targeted positions of the peptide backbone. This is the first report on the cDNA display/NGS screening system to yield comprehensive data on TG substrate preference. Although some issues remain to be solved, this platform can be applied to the selection of other TGs and easily adjusted for the selection of other peptide substrates and even larger biomolecules.
Stress corrosion cracking of A517 steel in marine environments
Authors: Chen Lin , Yang Huisheng , Su Yanjing , Qiao Lijie 
Published: September 2021

Purpose
The purpose of this study is to develop the existence and mechanism of stress corrosion cracking (SCC) for A517 steel in marine environments.

Design/methodology/approach
Slow strain rate test (SSRT) and constant load tests were used to investigate the SCC susceptibility of A517 steel. In addition, the additive stresses caused by the corrosion film and hydrogen entering into steel were applied to reveal the fundamental mechanism of the SCC.

Findings
The SCC susceptibility increased due to anodic dissolution and additive stress caused by the corrosion-produced film under anode polarization. Furthermore, the SCC susceptibility increased with increasing cathodic polarization, which is due to the increased additional stress caused by hydrogen entering into the steel. However, when the cathode polarization further increased, the additional stress remained due to the constant hydrogen content, thus the SCC susceptibility did not vary. Moreover, the SCC susceptibility of A517 steel under an alternate immersion environment (AIE) was lower than that under a full immersion environment and the steel under the AIE with 0.5 W/D had the lowest SCC susceptibility.

Originality/value
The stress corrosion behaviors of A517 in marine environments under various conditions were systematically analyzed.
Predicting the response and perforation of fibre metal laminates subjected to projectile impact
Authors: Liu Y.J. , Wang Z.H. , Wen H.M. 
Published: September 2021

Purpose
The purpose of this paper is to predict the response and perforation of fibre metal laminates (FMLs) subjected to impact by projectiles at different velocities.

Design/methodology/approach
A finite element (FE) model is constructed in which recently proposed dynamic constitutive models for fibre reinforced plastic (FRP) laminates and metals are used. Moreover, a recently developed dynamic cohesive element constitutive model is also used to simulate the debonding between FRP laminates and metal sheets. The FE model is first validated against the test data for glass laminate aluminum reinforced epoxy (GLARE) both under dropped object loading and ballistic impact, then used to perform a parametric study on the influence of projectile nose shape on the perforation of FMLs.

Findings
It is found that the present model predicts well the response and perforation of GLARE subjected to impact loading in terms of load-time history, load-displacement curve, residual velocity and failure pattern. It is also found that projectile nose shape has a considerable effect on the perforation of GLARE FMLs and that the ballistic limit is the highest for a flat-ended projectile whilst for a conical-nosed missile the resistance to perforation is the least.

Originality/value
Recently developed constitutive models for FRPs and metals, together with cohesive element model which considers strain rate effect, are used in the FE model to predict the behaviour of FMLs struck by projectiles in a wider range of impact velocities; the present model is advantageous over such existing models as Johnson-Cook (JC) + Chang-Chang and JC (+BW) + MAT162 in terms of failure pattern though they produce similar results for residual velocity.
Estimation of the virtual masses of a large unconventional airship based on purely analytical method to aid in the preliminary design
Authors: Chaabani Said , Azouz Naoufel 
Published: September 2021

Purpose
This paper presents preliminary results of the modeling of a large autonomous quad-rotor airship, with flying wing shape. This airship is supposed to be a flexible body. This study promotes an entirely analytical methodology with some assumptions. In this study and as first assumption, the shape of the careen is supposed to be an elliptic cone. To retrieve the velocity potential shapes, this paper solved the Laplace’s equation by using the sphero-conal coordinates. This leads to the Lamé’s equations. The whole system equations governing the interaction of air–structure, including the boundary conditions, is solved in an analytical setting.

Design/methodology/approach
This paper opted for a modeling and determination of the added masses of a flexible airship by an analytical method illustrated by a comparison with a geometric method. This analytical method includes the study of complex functions which are the Lamé functions.

Findings
This paper provides an analytical way to estimate an aerodynamic phenomenon which acts on the airship and in particular on its envelope and known as the phenomenon of added masses or virtual masses, as well as the means of defining it and the calculation analytically for the case of the flexible airship.

Research limitations/implications
Considering that the calculation of the added masses is very difficult and the numerical methods increase the number of degrees of freedom, the analytical method established in this paper has become a solution of calculations of these virtual masses.

Practical implications
This paper includes an application for determining the added masses of a new generation MC500 airship.

Originality/value
This paper allows defining an analytical method which determines the added masses of an airship, which helps the automation engineer to develop a control strategy to stabilize this airship.