bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loop 1 of human cardiac myosin regulates the rate of ATP induced actomyosin dissociation but not the rate of ADP release
Authors: Gargey Akhil , Nesmelov Yuri E. 
Published: October 2021

AbstractDouble mutation D208Q:K450L was introduced in the beta isoform of human cardiac myosin to remove the salt bridge D208:K450 connecting loop 1 and the seven-stranded beta sheet within the myosin head. Beta isoform-specific salt bridge D208:K450 was previously discovered in the molecular dynamics simulations. It was proposed that loop 1 modulates nucleotide affinity to actomyosin and we hypothesized that the electrostatic interactions between loop 1 and myosin head backbone regulates ATP binding to and ADP dissociation from actomyosin, and therefore, the time of the strong actomyosin binding. Wild type and the mutant of the myosin head construct (1–843 amino acid residues) were expressed in differentiated C2C12 cells, and the kinetics of ATP induced actomyosin dissociation and ADP release were characterized using transient kinetics spectrophotometry. Both constructs exhibit a fast rate of ATP binding to actomyosin and a slow rate of ADP dissociation, showing that ADP release limits the time of the strongly bound state of actomyosin. We observed a faster rate of ATP-induced actomyosin dissociation with the mutant, compared to the wild type actomyosin. The rate of ADP release from actomyosin remains the same for the mutant and the wild type actomyosin. We conclude that the flexibility of loop 1 is a factor affecting the rate of ATP binding to actomyosin and actomyosin dissociation. We observed no effect of loop 1 flexibility on the rate of ADP release from actomyosin.HighlightsHuman cardiac myosin has the isoform-specific salt bridge, electrostatically linking loop 1 and myosin head backbone.Absence of loop 1 – backbone salt bridge increases rate of ATP-induced actomyosin dissociationThe rate of ADP dissociation from actomyosin is not affected by the isoform-specific salt bridge.
Reliability and Stability Challenges in ABCD Task fMRI Data
Authors: Kennedy James T. , Harms Michael P. , Korucuoglu Ozlem , Astafiev Serguei V. , Barch Deanna M. , Thompson Wesley K. , Bjork James M. , Anokhin Andrey P. 
Published: October 2021

AbstractTrait stability of measures is an essential requirement for individual differences research. Functional MRI has been increasingly used in studies that rely on the assumption of trait stability, such as attempts to relate task related brain activation to individual differences in behavior and psychopathology. However, recent research using adult samples has questioned the trait stability of task-fMRI measures, as assessed by test-retest correlations. To date, little is known about trait stability of task fMRI in children. Here, we examined within-session reliability and longitudinal stability of task-fMRI using data from the Adolescent Brain Cognitive Development (ABCD) Study using its tasks focused on reward processing, response inhibition, and working memory. We also evaluated the effects of factors potentially affecting reliability and stability. Reliability and stability [quantified via an intraclass correlation (ICC) that focuses on rank consistency] was poor in virtually all brain regions, with an average ICC of .078 and .054 for short (within-session) and long-term (between-session) ICCs, respectively, in regions of interest (ROIs) historically-recruited by the tasks. ICC values in ROIs did not exceed the ‘poor’ cut-off of .4, and in fact rarely exceeded .2 (only 5.9%). Motion had a pronounced effect on estimated ICCs, with the lowest motion quartile of participants having a mean reliability/stability three times higher (albeit still ‘poor’) than the highest motion quartile. Regions with stronger activation tended to show higher ICCs, with the absolute value of activity and reliability/stability correlating at .53. Across regions, the magnitude of age-related longitudinal (between-session) changes positively correlated with the longitudinal stability of individual differences, which suggests developmental change was not necessarily responsible for poor stability. Poor reliability and stability of task-fMRI, particularly in children, diminishes potential utility of fMRI data due to a drastic reduction of effect sizes and, consequently, statistical power for the detection of brain-behavior associations. This essential issue needs to be addressed through optimization of preprocessing pipelines and data denoising methods.
Taste loss as a distinct symptom of COVID-19: A systematic review and meta-analysis
Authors: Hannum Mackenzie E. , Koch Riley J. , Ramirez Vicente A. , Marks Sarah S. , Toskala Aurora K. , Herriman Riley D. , Lin Cailu , Joseph Paule V. , Reed Danielle R. 
Published: October 2021

AbstractChemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19, taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020–2021, with 241 meeting all inclusion criteria. Additionally, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct prevalence measures of taste loss would be the most valid because they avoid the taste/smell confusion of self-report. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% CI: 35.34–43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, p = 0.45). Generally, males reported lower rates of taste loss than did females and taste loss was highest in middle-aged groups. Thus, taste loss is a bona fide symptom COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.
Metabolomic and transcriptomic analyses reveal the effects of grafting on anthocyanin synthesis in grapevine
Authors: Zhong Haixia , Liu Zhongjie , Zhang Fuchun , Zhou Xiaoming , Sun Xiaoxia , Liu Wenwen , Xiao Hua , Wang Nan , Pan Mingqi , Wu Xinyu , Zhou Yongfeng 
Published: October 2021

ABSTRACTThe grafting has been commonly used in viticulture, which joints the scion from a cultivar with the stem of a rootstock. Grafting has crucial impacts on various phenotypes of the cultivar including berry metabolome and berry coloring, however, the genetics and regulation mechanisms are largely unexplored. In this study, we analyzed the phenotypic, metabolomic and transcriptomic profiles at three stages (45, 75 and105 days after flowering) of the Crimson Seedless (Vitis vinifera, CS) cultivar grafted to four rootstocks (three heterografting: CS/101-14MG, CS/SO4, CS/110R and one self-grafting CS/CS) with an own-rooted grafting-free Crimson Seedless (CS) as a control. All the heterografting plants had a significant influence on berry reddening as early as ~45 days after flowering. The grafting of rootstocks promoted anthocyanin synthesis and accumulation in grape berries. The metabolomic features showed that Cyanidin 3-O-glucoside, Delphinidin 3-O-glucosid, Malvidin 3-O-glucoside, Peonidin 3-O-glucoside and Petunidin 3-O-glucoside were the pigments responsible for the purplish-red color peels. Transcriptomic analyses revealed that the anthocyanins biosynthetic related genes from the upstream (phenylalanine ammonia-lyase) to the downstream (anthocyanidin 3-O-glucosyltransferase and anthocyanidin synthase) were upregulated with the accumulations of anthocyanins in CS/101-14MG, CS/SO4 and CS/110R. At the same time, all these genes were also highly expressed and more anthocyanin was accumulated in CS/CS samples compared to CS samples, suggesting that self-grafting rootstocks might also have promoted berry reddening in grapevine. Our results provide global transcriptomic and metabolomic features in berry coloring regulation under different grafting conditions for improving the berry quality in grapevine production.
Polygenic sex determination produces modular sex polymorphism in an African cichlid fish
Authors: Moore Emily C. , Ciccotto Patrick J. , Peterson Erin N. , Lamm Melissa S. , Albertson R. Craig , Roberts Reade B. 
Published: October 2021

For many vertebrates, a single genetic locus initiates a cascade of developmental sex differences in the gonad and throughout the organism, resulting in adults with two, phenotypically distinct sexes. Species with polygenic sex determination (PSD) have multiple interacting sex determination alleles segregating within a single species, allowing for more than two genotypic sexes, and scenarios where sex genotype at a given locus can be decoupled from gonadal sex. Here we investigate the effects of PSD on secondary sexual characteristics in the cichlid fish Metriaclima mbenjii, where one female (W) and one male (Y) sex determination allele interact to produce siblings with four possible sex classes: ZZXX females, ZWXX females, ZWXY females, and ZZXY males. We find that PSD in M. mbenjii produces an interplay of sex-linkage and sex-limitation resulting in modular variation in morphological and behavioral traits. Further, the evolution or introgression of a novel sex determiner creates additional axes of phenotypic variation for varied traits, including genital morphology, craniofacial morphology, gastrointestinal morphology, and home tank behaviors. In contrast to single-locus sex determination, which broadly results in sexual dimorphism, polygenic sex determination can induce higher-order sexual polymorphism. The modularity of secondary sexual characteristics produced by PSD provides novel context for understanding the evolutionary causes and consequences of maintenance, gain, or loss of sex determination alleles in populations.Significance StatementSex differences in traits can occur when those traits are modified by genetic factors inherited on sex chromosomes. We investigated how sex differences emerge in a species with more than one set of sex chromosomes, measuring a variety of morphological, physiological, and behavioral traits. Rather than exhibiting sexual dimorphism associated with primary sex, the species has higher-order sexual polymorphism in secondary sexual characteristics, or more than two phenotypic sexes. Variation in secondary sexual characteristics is modular, involving the interplay of sex-linked and sex-limited traits. Our findings provide novel implications for how sex determination systems and whole-organism fitness traits co-evolve, including that significant creation or loss of variation in diverse traits can occur during transitions among sex chromosome systems.
The initiation of the wound healing program is regulated by the convergence of mechanical and epigenetic cues
Authors: Bhatt Tanay , Dey Rakesh , Hegde Akshay M. , Ketkar Alhad Ashok , Pulianmackal Ajai J. , Deb Ashim P. , Rampalli Shravanti , Jamora Colin 
Published: October 2021

ABSTRACTWound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the downregulation of caspase-8 as a biomarker of a cell entering the wound-healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be downregulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.Graphical Abstract
Efficient Suppression of Endogenous CFTR Nonsense Mutations Using Anticodon Engineered Transfer RNAs
Authors: Ko Wooree , Porter Joseph J. , Sipple Matthew T. , Edwards Katherine M. , Lueck John D. 
Published: October 2021

AbstractNonsense mutations or premature termination codons (PTCs) comprise ∼11% of all genetic lesions, which result in over 7,000 distinct genetic diseases. Due to their outsized impact on human health, considerable effort has been made to find therapies for nonsense-associated diseases. Suppressor tRNAs have long been identified as a possible therapeutic for nonsense-associated diseases, however their ability to inhibit nonsense-mediated mRNA decay (NMD) and support significant protein translation from endogenous transcripts has not been determined in mammalian cells. Here we investigated the ability of anticodon edited (ACE)-tRNAs to suppress cystic fibrosis (CF) causing PTCs in the cystic fibrosis transmembrane regulator (CFTR) gene in gene-edited immortalized human bronchial epithelial (16HBEge) cells. Delivery of ACE-tRNAs to 16HBEge cells harboring three common CF mutations G542X-, R1162X- and W1282X-CFTR PTCs significantly inhibited NMD and rescued endogenous mRNA expression. Furthermore, delivery of our highly active leucine encoding ACE-tRNA resulted in rescue of W1282X-CFTR channel function to levels that significantly exceed the necessary CFTR channel function for therapeutic relevance. This study establishes the ACE-tRNA approach as a potential stand-alone therapeutic for nonsense-associated diseases due to its ability to rescue both mRNA and full-length protein expression from PTC containing endogenous genes.One Sentence SummarySuppression of endogenous CFTR nonsense mutations by anticodon engineered tRNAs significantly increases mRNA expression and channel function.
Astrocytes encode complex behaviorally relevant information
Authors: Merten Katharina , Folk Robert W. , Duarte Daniela , Nimmerjahn Axel 
Published: October 2021

AbstractAstrocytes, glial cells of the central nervous system, help to regulate neural circuit operation and adaptation. They exhibit complex forms of chemical excitation, most prominently calcium transients, evoked by neuromodulator and -transmitter receptor activation1–4. However, whether and how astrocytes contribute to cortical processing of complex behavior remains unknown1. One of the puzzling features of astrocyte calcium transients is the high degree of variability in their spatial and temporal patterns under behaving conditions. Here, we provide mechanistic links between astrocytes’ activity patterns, molecular signaling, and behavioral cognitive and motor activity variables by employing a visual detection task that allows for in vivo calcium imaging, robust statistical analyses, and machine learning approaches. We show that trial type and performance levels deterministically shape astrocytes’ spatial and temporal response properties. Astrocytes encode the animals’ decision, reward, and sensory properties. Our error analysis confirms that astrocytes carry behaviorally relevant information depending on and complementing neuronal coding. We also report that cell-intrinsic mechanisms curb astrocyte calcium activity. Additionally, we show that motor activity-related parameters strongly impact astrocyte responses and must be considered in sensorimotor study designs. Our data inform and constrain current models of astrocytes’ contribution to complex behavior and brain computation beyond their established homeostatic and metabolic roles.
Trade-off between competition ability and invulnerability to predation in marine microbes; protist grazing versus viral lysis effects
Authors: Yang Jinny Wu , Chang Feng-Hsun , Yeh Yi-Chun , Tsai An-Yi , Chiang Kuo-Ping , Shiah Fuh-Kwo , Gong Gwo-Ching , Hsieh Chih-hao 
Published: October 2021

AbstractTrade-offs between competition ability and invulnerability to predation are important mechanisms explaining how predation promotes bacterial diversity. However, existence of these trade-offs has apparently not been investigated in natural marine bacterial communities. Here, we address this question with growth-based measurements for each marine bacterial taxon by conducting on-board dilution experiments to manipulate predation pressure and using high-throughput sequencing to assess the response of bacterial communities. We determined that bacterial taxa with a higher predation-free growth rate were accompanied with higher predation-caused mortality, supporting existence of competitiveness-invulnerability trade-off. This trade-off was stronger and more consistent under viral lysis than protist grazing. In addition, predation generally flattened out the rank-abundance distribution and increased the evenness and richness of the bacterial community. These findings supported the “Kill-the-Winner” hypothesis. All experiments supported a significant competitiveness-invulnerability trade-off, but there was substantial variation among bacterial communities in response to predation across experiments conducted in various sites and seasons. Therefore, we inferred that the Kill-the-Winner hypothesis is important but likely not the only deterministic mechanism explaining how predation shapes bacterial assemblages in natural marine systems.
Purchasing power parity in GIIPS countries: evidence from unit root tests with breaks and non-linearity
Authors: Nazlioglu Saban , Altuntas Mehmet , Kilic Emre , Kucukkkaplan Ilhan 
Published: October 2021

PurposeThis paper aims to test purchasing power parity (PPP) hypothesis for Greece, Italy, Ireland, Portugal and Spain, which are known as the GIIPS countries.Design/methodology/approachThe authors conduct a comprehensive analysis by using unit root approaches without and with structural breaks and non-linearity.FindingsThe PPP is valid for the GIIPS countries. Considering structural breaks in non-linear framework plays a crucial role.Originality/valueThere is no empirical study testing PPP hypothesis by focusing on the GIIPS countries. This study further takes into account for structural breaks and non-linearity in the real exchange rates of these countries.
Analyzing online discussion data for understanding the student's critical thinking
Authors: Yang Juan , Du Xu , Hung Jui-Long , Tu Chih-hsiung 
Published: October 2021

PurposeCritical thinking is considered important in psychological science because it enables students to make effective decisions and optimizes their performance. Aiming at the challenges and issues of understanding the student's critical thinking, the objective of this study is to analyze online discussion data through an advanced multi-feature fusion modeling (MFFM) approach for automatically and accurately understanding the student's critical thinking levels.Design/methodology/approachAn advanced MFFM approach is proposed in this study. Specifically, with considering the time-series characteristic and the high correlations between adjacent words in discussion contents, the long short-term memory–convolutional neural network (LSTM-CNN) architecture is proposed to extract deep semantic features, and then these semantic features are combined with linguistic and psychological knowledge generated by the LIWC2015 tool as the inputs of full-connected layers to automatically and accurately predict students' critical thinking levels that are hidden in online discussion data.FindingsA series of experiments with 94 students' 7,691 posts were conducted to verify the effectiveness of the proposed approach. The experimental results show that the proposed MFFM approach that combines two types of textual features outperforms baseline methods, and the semantic-based padding can further improve the prediction performance of MFFM. It can achieve 0.8205 overall accuracy and 0.6172 F1 score for the “high” category on the validation dataset. Furthermore, it is found that the semantic features extracted by LSTM-CNN are more powerful for identifying self-introduction or off-topic discussions, while the linguistic, as well as psychological features, can better distinguish the discussion posts with the highest critical thinking level.Originality/valueWith the support of the proposed MFFM approach, online teachers can conveniently and effectively understand the interaction quality of online discussions, which can support instructional decision-making to better promote the student's knowledge construction process and improve learning performance.
Deep learning-based detection of tax frauds: an application to property acquisition tax
Authors: Lee Changro 
Published: October 2021

PurposeSampling taxpayers for audits has always been a major concern for policymakers of tax administration. The purpose of this study is to propose a systematic method to select a small number of taxpayers with a high probability of tax fraud.Design/methodology/approachAn efficient sampling method for taxpayers for an audit is investigated in the context of a property acquisition tax. An autoencoder, a popular unsupervised learning algorithm, is applied to 2,228 tax returns, and reconstruction errors are calculated to determine the probability of tax deficiencies for each return. The reasonableness of the estimated reconstruction errors is verified using the Apriori algorithm, a well-known marketing tool for identifying patterns in purchased item sets.FindingsThe sorted reconstruction scores are reasonably consistent with actual fraudulent/non-fraudulent cases, indicating that the reconstruction errors can be utilized to select suspected taxpayers for an audit in a cost-effective manner.Originality/valueThe proposed deep learning-based approach is expected to be applied in a real-world tax administration, promoting voluntary compliance of taxpayers, and reinforcing the self-assessing acquisition tax system.