bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Kallikrein Related Peptidase 3 (KLK3) Gene with Dermatophytosis in the UK Biobank cohort
Authors: Lehrer Steven , Rheinstein Peter H. 
Published: October 2022

AbstractIn a previous genome wide association study (GWAS) of UK Biobank (UKB) data, we identified one susceptibility locus, Tubulointerstitial Nephritis Antigen (TINAG), with genome wide significance for dermatophytosis. We used genotype calls from file UKB22418. These data are derived directly from Affymetrix DNA microarrays but are missing many genotype calls. Using computationally efficient approaches, UKB has entered imputed genotypes into a second dataset, UKB22828, increasing the number of testable variants by over 100-fold to 96 million variants. In the current study, we used UKB imputed genotypes in UKB22828 to identify dermatophytosis susceptibility loci.MethodsTo identify cases of dermatophytosis, we used ICD10 code B35, which covers Tinea barbae, Tinea capitis, Tinea unguium, Tinea manuum, Tinea pedis, Tinea corporis, Tinea imbricata, Tinea cruris, other dermatophytoses, and dermatophytosis, unspecified. We used PLINK, a whole-genome association analysis toolset, to analyze the UKB22828 chromosome files.ResultsGWAS summary (Manhattan) plot of the meta-analysis association statistics highlighted two susceptibility loci, TINAG and Kallikrein Related Peptidase 3 (KLK3), with genome wide significance for dermatophytosis.ConclusionKLK3 may be a dermatophytosis susceptibility gene. KLK3 could affect risk of dermatophytosis, since kallikreins are necessary for normal homeostasis of the skin.
Evidence for a Spoken Word Lexicon in the Auditory Ventral Stream
Authors: Damera Srikanth R. , Chang Lillian , Nikolov Plamen P. , Mattei James A. , Banerjee Suneel , Glezer Laurie S. , Cox Patrick H. , Jiang Xiong , Rauschecker Josef P. , Riesenhuber Maximilian 
Published: October 2022

AbstractThe existence of a neural representation for whole words (i.e., a lexicon) is a common feature of many models of speech processing. Prior studies have provided evidence for a visual lexicon containing representations of whole written words in an area of the ventral visual stream known as the “Visual Word Form Area” (VWFA). Similar experimental support for an auditory lexicon containing representations of spoken words has yet to be shown. Using fMRI rapid adaptation techniques, we provide evidence for an auditory lexicon in the “Auditory Word Form Area” (AWFA) in the human left anterior superior temporal gyrus that contains representations highly selective for individual spoken words. Furthermore, we show that familiarization with novel auditory words sharpens the selectivity of their representations in the AWFA. These findings reveal strong parallels in how the brain represents written and spoken words, showing convergent processing strategies across modalities in the visual and auditory ventral streams.HighlightsIndividual auditory word form areas (AWFA) were defined via an auditory localizerThe AWFA shows tuning for individual real words but not untrained pseudowordsThe AWFA develops tuning for individual pseudowords after training
Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1
Authors: Zhao Li-Hua , Yuan Qingning , Dai Antao , Chen Chuan-Wei , He Xinheng , Zhang Chao , Xu Youwei , Zhou Yan , Wang Ming-Wei , Yang Dehua , Xu H. Eric 
Published: October 2022

ABSTRACTParathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor -1 (PTH1R), a member of class B G protein couple receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide, are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.6 and 3.2 Å, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation and together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders.
Domino-like Effect of C112R Mutation on ApoE4 Aggregation and Its Reduction by Alzheimer’s Disease Drug Candidate
Authors: Nemergut Michal , Marques Sergio M. , Uhrik Lukas , Vanova Tereza , Nezvedova Marketa , Gadara Darshak Chandulal , Jha Durga , Tulis Jan , Novakova Veronika , Planas-Iglesias Joan , Kunka Antonin , Legrand Anthony , Hribkova Hana , Pospisilova Veronika , Sedmik Jiri , Raska Jan , Prokop Zbynek , Damborsky Jiri , Bohaciakova Dasa , Spacil Zdenek , Hernychova Lenka , Bednar David , Marek Martin 
Published: October 2022

AbstractBackgroundApolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer’s Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by the C112R mutation, the molecular mechanism of its proteinopathy is unknown.MethodsHere, we reveal the molecular mechanism of ApoE4 aggregation using a combination of experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering and molecular dynamics simulations. Treatment of ApoE ε3/ε3 and ε4/ε4 cerebral organoids with tramiprosate was used to compare the effect of tramiprosate on ApoE4 aggregation at the cellular level.ResultsWe found that C112R substitution in ApoE4 induces long-distance (>15 Å) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce ApoE3-like conformational behavior in ApoE4 and reduce its aggregation propensity. Analysis of ApoE ε4/ε4 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage products of excess cholesterol.ConclusionsOur results connect the ApoE4 structure with its aggregation propensity, providing a new druggable target for neurodegeneration and ageing.
A first draft genome of Holm oak (Quercus ilexL.), the most representative species of the Mediterranean forest and the Spanish agrosilvopastoral ecosystem “dehesa”
Authors: Rey María-Dolores , Labella-Ortega Mónica , Guerrero-Sánchez Víctor M. , Carleial Rômulo , Castillejo María Ángeles , Rodríguez-Franco Antonio , Buggs Richard G. , Ruggieri Valentino , Jorrín-Novo Jesús V. 
Published: October 2022

AbstractThe holm oak (Quercus ilexL.) is the most representative species of the Mediterranean Basin and the agrosilvopastoral Spanish “dehesa” ecosystem. Being part of our life, culture, and subsistence since ancient times, it has great environmental and economic importance. More recently, there has been a renewed interest in using theQ. ilexacorn as a functional food due to its nutritional and nutraceutical properties. However, the holm oak and its related ecosystems are threatened by different factors, with oak decline syndrome and climate change being the most worrying on the short and medium term. Breeding programs informed by selection of elite genotypes seems to be the only plausible biotechnological solution to rescue populations under threat. To achieve this and other downstream analyses, we need a high-qualityQ. ilexreference genome. Here, we introduce the first draft genome assembly ofQ. ilexusing long-read sequencing (PacBio). The assembled nuclear haploid genome has 530 contigs totaling 842.2 Mbp (N50 = 3.3 Mbp), of which 448.7 Mb (53%) are repetitive sequences. We annotated 39,443 protein-coding genes and Benchmarking Universal Single-Copy Orthologs analysis detected 412 out of 425 expected complete and single-copy genes (94.80%) within theQ. ilexgenome. The chloroplast genome size was 142.3 Kbp with 149 protein-coding genes successfully annotated. This first draft should allow for the validation of - omics data as well as the identification and functional annotation of genes related to phenotypes of interest such as those associated to resilience against oak decline syndrome and climate change, higher acorn productivity and nutraceutical value.
Temperature-induced methylome changes during asexual reproduction trigger transcriptomic and phenotypic changes inFragaria vesca
Authors: Zhang YuPeng , Fan Guangxun , Toivainen Tuomas , Tengs Torstein , Yakovlev Igor , Krokene Paal , Hytönen Timo , Fossdal Carl Gunnar , Grini Paul E. 
Published: October 2022

AbstractPlants must quickly adapt to a changing environment in order to maintain their fitness. One rapid adaptation mechanism that promotes plasticity is epigenetic memory, which may provide long-lived organisms the precious time needed to adapt to climate change. In this study, we used the perennial plantFragaria vescaas a model to determine how the methylome and transcriptome adapt to elevated temperatures (28 vs. 18 °C) over three asexual generations. Changes in flowering time, stolon number, and petiole length were induced in responses to temperature treatment in one or more ecotypes after three asexual generations in a manner indicative of an epigenetic memory. Induced methylome changes differed between four different ecotypes from Norway, Iceland, Italy, and Spain, but there were also some shared responses. Elevated temperature conditions induced significant phenotypic and methylation changes, particularly in the Norwegian ecotype. Most of the differentially methylated regions (DMRs) were in the CHG context, and most CHG and CHH DMRs were hypermethylated. Notably, the four ecotypes shared only eight CHG DMR peaks. Several differentially methylated genes (DMGs) also showed a change in gene expression. Ecotype-specific methylation and expression patterns were observed for genes related to gibberellin metabolism, flowering time, epigenetics. Furthermore, when repetitive elements (REs) were found near (±2 kb) or inside a gene, they showed a negative correlation with gene expression. In conclusion, phenotypic changes induced by elevated temperatures during asexual reproduction were accompanied by changes in DNA methylation patterns. Also, positional influences of REs impacted gene expression, indicating that DNA methylation may be involved in both general and ecotype-specific phenotypic plasticity inF. vesca.
Quantifying orthogonal barcodes for sequence census assays
Authors: Booeshaghi A. Sina , Min Kyung Hoi (Joseph) , Gehring Jase , Pachter Lior 
Published: October 2022

AbstractBarcode-based sequence census assays utilize custom or random oligonucloetide sequences to label various biological features, such as cell-surface proteins or CRISPR perturbations. These assays all rely on barcode quantification, a task that is complicated by barcode design and technical noise. We introduce a modular approach to quantifying barcodes that achieves speed and memory improvements over existing tools. We also introduce a set of quality control metrics, and accompanying tool, for validating barcode designs.
Natural selection and neutral mutations through the lens of viruses
Authors: Chen Ji-Ming , Li Guo-Hui , Gong Huan-Yu , Sun Ming-Hui , Ji Yu-Fei , Chen Rui-Xu , Tan Su-Mei , Chen Ji-Wang 
Published: October 2022

AbstractThe Neutral Theory and the Modern Synthesis, a modified version of Darwin’s theory, have been arguing for decades about the influence of natural selection on molecular evolution1-10. Here we elucidate through the lens of viruses that a frequently used method11-17employing the ratio of nonsynonymous versus synonymous substitution rates has dramatically underestimated the influence of natural selection on molecular evolution. We also find novel evidence from viral sequences to support the co-existence of the crucial role of natural selection in molecular evolution and the ubiquity of neutral mutations. The co-existence has perplexed biologists for decades2,5,7. We then elucidate for the first time the causality between natural selection and the ubiquity of neutral mutations with a novel interpretation of natural selection. This novel interpretation incorporates biochemistry, genetics, epigenetics, physiology, and dynamics. It holds that natural selection acts directly on the overall phenotypic performance of organisms and indirectly on each genomic site or phenotypic trait. It highlights not only restrictions and competitions but also freedom and diversity, besides the overall harmonious development of organisms and human societies. Therefore, this novel interpretation could have far-reaching implications in the natural and social sciences.
Framework for implementing track deterioration analytics into railway asset management
Authors: Sauni Mikko , Luomala Heikki , Kolisoja Pauli , Vaismaa Kalle 
Published: October 2022

Purpose Recent research outputs can be difficult to implement into ongoing safety critical processes. Hence, research is well beyond current practices in railway asset management. This paper demonstrates the process of creating tangible change within a railway asset management organization by introducing a framework for advancing track geometry deterioration analyses (TGDA) in practice.Design/methodology/approach The research was conducted in three parts: (1) maturity models were reviewed and adapted as the basis for the framework, (2) the initial maturity level was investigated by conducting semi-structured expert interviews, and (3) a framework for development was created in cooperation with stakeholders during three workshops. The methodology and findings were tested and applied in the Finnish state rail network asset management.Findings The main output of this study is the framework for advancing TGDA in railway asset management. The novel framework provides structure for controlled incremental development, which is essential when altering a safety critical process.Practical implications The research process was successfully applied in Finland. Following the steps presented in this article, any organization can apply the framework to plan their development schemes for railway asset management.Originality/value Full-scale implementation of novel models and methods is often overlooked, which prevents practical asset management from obtaining tangible benefits from research. This research provides an innovative approach in narrowing the overlooked research gap and brings research results within the reach of practitioners.
The impact of organizational support for the project management process on project and firm performance
Authors: Azevedo Ana , Jugdev Kam , Mathur Gita 
Published: October 2022

PurposeThis research draws on the resource-based view of the firm from strategic management and applies it to a study of competitive advantage in the project management context. The relationship between the characteristics of project management resources, focusing on organizational support for the project management process, and outcomes of the project management process are examined.Design/methodology/approachThis study uses data gathered from 437 North American project management professionals with an existing survey tool that was used in a prior smaller sample study. The study uses Barney’s VRIO framework that assesses resources as valuable (V), rare (R), inimitable (I) and organizationally supported to leverage their value (O). The conceptual model hypothesizes relationships between the project management asset characteristics (valuable, rare, and inimitable), organizational support for the project management process, and project management performance outcomes (both project and firm level). Hypotheses are tested using factors extracted from a confirmatory factor analysis (CFA). The factors extracted include two factors representing valuable project management asset characteristics, one factor representing rare project management asset characteristics, one factor representing inimitable project management asset characteristics, two factors representing organizational support for the project management process, one factor representing project-level performance and one factor representing firm-level performance.FindingsProject management assets that are considered valuable and organizational support for the project management process are found to contribute positively to project management process outcomes. No advantage was perceived from rare and inimitable project management assets. Project-level performance was found to significantly mediate the relationship between organizational support and firm-level performance.Practical implicationsThis study draws managerial attention to organizational support for the project management process as a source of competitive advantage through its positive affect on both project-as well as firm-level performance.Originality/valueThe study uses a survey tool from previous research with a new, larger dataset to contribute to the understanding of the importance of organizational support for the project management process in a quest for both project success as well as a firm's competitive advantage.
Educational approaches to enable marketplace metacognition and social intelligence in subsistence consumers
Authors: Sharma Yukti , Jaikumar Saravana 
Published: October 2022

Purpose
Subsistence marketplace can be characterized as a marketplace with widespread cognitive and social vulnerabilities, due to low income and low literacy levels. This may result in retailers exploiting the consumers. The purpose of this research paper is to develop a holistic learning program to impart marketplace intelligence to overcome these vulnerabilities of subsistence consumers.

Design/methodology/approach
Using vicious cycle approach, the authors illustrate the self-perpetuating nature of consumer vulnerabilities. The authors argue that retailers behave in an opportunistic manner and exploit the consumers. This further reinforces the vulnerabilities of subsistence consumers resulting in a vicious cycle. The authors draw insights from Sen’s capability approach and propose marketplace intelligence as a potential solution to eradicate consumers’ vulnerabilities. The authors apply Biggs’s 3Ps model to design a learning program to impart two types of marketplace intelligence – marketplace metacognition and marketplace social intelligence.

Findings
Based on a review of literature on subsistence marketplace initiatives, persuasive knowledge management and education research, the authors have devised a holistic learning program comprising an integrated learning environment (presage), problem-based approach (process) and assessment strategies for learning outcomes (product).

Originality/value
This study marks a pioneering effort toward liberating subsistence consumers from the vicious cycle of retailers’ exploitation by empowering them with marketplace intelligence. This study’s novelty lies in conceptualizing consumer vulnerabilities in the subsistence marketplace as a self-perpetuating phenomenon and subsequently designing a holistic learning program to impart intelligence toward alleviating these vulnerabilities.
Victimisation of investors from fraudulent investment schemes and their protection through financial education
Authors: Singh Kamakhya Narain , Misra Gaurav 
Published: October 2022

PurposeThe purpose of this study is to identify the significant demographic and socio-economic characteristics of individuals who are likely to invest in a fraudulent investment scheme. It also quantifies the extent to which financial literacy helps in reducing the odds of investments in such schemes. Based on these findings, it provides policy recommendations to regulators and governments.Design/methodology/approachThis study uses nationally representative data from the “India Assessment of Financial Capability 2018” survey. It further uses logistic regression with a binary outcome variable to assess the individual-level odds of investments in fraudulent investment schemes.FindingsThis study concludes that males between 40 and 59 years of age, who are well-educated (are at least graduates), score low in financial literacy, belong to the middle-income group, and SEC A3 households are most vulnerable to victimization by financial fraudulent investment schemes. It finds that financial literacy significantly reduces the odds of investment into fraudulent schemes to the extent of 39.118%.Originality/valueThis study quantifies the extent to which financial literacy helps in reducing the odds of individual investments in a fraudulent investment scheme. As financial literacy has a significant and negative relationship with the likelihood of investment in such schemes, this study provides policy interventions and recommendations to regulators and governments to safeguard the interest of individual investors.
Unexplored themes in expatriate management: inspirations from the new mobilities paradigm
Authors: Guttormsen David S. A. , Lauring Jakob 
Published: October 2022

PurposeThe purpose of this paper is to present a different perspective on the concept of global mobility and apply the multifaceted concept in proposing new themes to explore in expatriate management research.Design/methodology/approachThis study draws upon the theoretical underpinnings relating to the New Mobilities paradigm from sociology to outline a new perspective on global mobility and thereby describe novel themes to include in future expatriate management studies.FindingsThis study identifies four themes in need of further development within the expatriate management research field: materiality, infrastructure and access, inequality and immobility and emotional dynamics. Within each of these themes, this study presents several examples of research questions that can provide new thrust to the theory development of expatriate management research.Originality/valueTo the best of the authors’ knowledge, this paper is the first attempt to draw on central ideas in the New Mobilities paradigm to propose a future research agenda for expatriate management studies. This study aims to enhance the study of “mobility” in new and unorthodox ways.
Professional relationships both within and outside the school: barriers and opportunities from an intergenerational perspective
Authors: Azorín Cecilia , Portela Antonio , Nieto José Miguel , Alfageme María Begoña 
Published: October 2022

PurposeThis paper draws on data from a research project that examined the professional relationships that existed between teachers of different generations within an educational setting, including both those inside and outside school.Design/methodology/approachA qualitative approach was adopted to better understand participants' intergenerational relationships. Data were collected via semi-structured interviews conducted online. Data analysis was carried out using Atlas.ti 22 software. This focused on participants' professional relationships, generationally-inflected professional relationships, links to the school and connections with their environment.FindingsThe paper shows that commitment to the profession and work climate were among the key aspects referred to by the interviewees. The different age groups agreed that they had experienced intergenerational feedback and that there was closer contact between peers of the same generation, which led to greater levels of affinity. The shared responsibility that comes with teaching and the sense of belonging were essential links to the school. The generational groups underlined the importance of building bridges and participating in collaborative networks to form connections with their environment.Originality/valueAlthough several studies have considered various factors influencing professional relationships from an intergenerational perspective, this paper adds value to the existing literature by providing new data and analyzing the barriers and opportunities experienced by teachers of different generations (novice, veteran and retired) in their professional work within and beyond the educational setting.