bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Factor Authentication of Potential 5’ Splice Sites by the Saccharomyces cerevisiae U1 snRNP
Authors: Hansen Sarah R. , Scalf Mark , Corrêa Ivan R. , Smith Lloyd M. , Hoskins Aaron A. 
Published: May 2021

ABSTRACTIn eukaryotes, splice sites define the introns of pre-mRNAs and must be recognized and excised with nucleotide precision by the spliceosome to make the correct mRNA product. In one of the earliest steps of spliceosome assembly, the U1 small nuclear ribonucleoprotein (snRNP) recognizes the 5’ splice site (5’ SS) through a combination of base pairing, protein-RNA contacts, and interactions with other splicing factors. Previous studies investigating the mechanisms of 5’ SS recognition have largely been done in vivo or in cellular extracts where the U1/5’ SS interaction is difficult to deconvolute from the effects of trans-acting factors or RNA structure. In this work we used co-localization single-molecule spectroscopy (CoSMoS) to elucidate the pathway of 5’ SS selection by purified yeast U1 snRNP. We determined that U1 reversibly selects 5’ SS in a sequence-dependent, two-step mechanism. A kinetic selection scheme enforces pairing at particular positions rather than overall duplex stability to achieve long-lived U1 binding. Our results provide a kinetic basis for how U1 may rapidly surveil nascent transcripts for 5’ SS and preferentially accumulate at these sequences rather than on close cognates.IMPACT STATEMENTThe yeast U1 snRNP recognizes multiple features of target RNAs to reversibly identify splicing-competent 5’ splice sites.
Bimodal Endocytic Probe for Three-Dimensional Correlative Light and Electron Microscopy
Authors: Fermie Job , de Jager Leanne , Foster Helen , Veenendaal Tineke , de Heus Cecilia , van Dijk Suzanne , ten Brink Corlinda , Oorschot Viola , Yang Lin , Li Wei , Müller Wally , Howes Stuart , Carter Andrew , Förster Friedrich , Posthuma George , Gerritsen Hans , Klumperman Judith , Liv Nalan 
Published: May 2021

AbstractCorrelative light and electron microscopy (CLEM) can infer molecular, functional and dynamic information to ultrastructure by linking information of different imaging modalities. One of the main challenges, especially in 3D-CLEM, is the accurate registration of fluorescent signals to electron microscopy (EM). Here, we present fluorescent BSA-gold (fBSA-Au), a bimodal endocytic tracer as fiducial marker for 2D and 3D CLEM applications. fBSA-Au consists of colloidal gold (Au) particles stabilized with fluorescent bovine serum albumin (BSA). The conjugate is efficiently endocytosed and distributed throughout the 3D endo-lysosomal network of the cells, and has an excellent visibility both in fluorescence microscopy (FM) and EM. We demonstrate the use of fBSA-Au in several 2D and 3D CLEM applications using Tokuyasu cryosections, resin-embedded material, and cryo-EM. As a fiducial marker, fBSA-Au facilitates rapid registration of regions of interest between FM and EM modalities and enables accurate (50-150 nm) correlation of fluorescence to EM data. Endocytosed fBSA-Au benefits from a homogenous 3D distribution throughout the endosomal system within the cell, and does not obscure any cellular ultrastructure. The broad applicability and visibility in both modalities makes fBSA-Au an excellent endocytic fiducial marker for 2D and 3D (cryo-)CLEM applications.
Latent disease similarities and therapeutic repurposing possibilities uncovered by multi-modal generative topic modeling of human diseases
Authors: Kozawa Satoshi , Yokoyama Hirona , Urayama Kyoji , Tejima Kengo , Doi Hotaka , Sato Thomas N. 
Published: May 2021

SummaryHuman diseases are characterized by multiple features such as their pathophysiological, molecular, and genetic changes. The rapid expansion of such multi-modal disease-omics space provides an opportunity to re-classify diverse human diseases and uncover their latent molecular similarities, which could be exploited to repurpose a therapeutic-target for one disease to another. Herein, we probe this underexplored space by soft-clustering 6,955 human diseases by multi-modal generative topic-modeling. Focusing on chronic kidney disease and myocardial infarction, two most life-threatening diseases, unveiled are their previously underrecognized molecular similarities to neoplasia and mental/neurological-disorders, and 69 repurposable therapeutic-targets for these diseases. Using an edit-distance based pathway-classifier, we also find molecular pathways by which these targets could elicit their clinical effects. Importantly, for the 17 targets, the evidence for their therapeutic usefulness is retrospectively found in the pre-clinical and clinical space, illustrating the effectiveness of the method, and suggesting its broader applications across diverse human diseases.
Astrocyte Ca2+ Signaling is Facilitated in an Scn1a+/− Mouse Model of Dravet Syndrome
Authors: Uchino Kouya , Ikezawa Wakana , Tanaka Yasuyoshi , Deshimaru Masanobu , Kubota Kaori , Watanabe Takuya , Katsurabayashi Shutaro , Iwasaki Katsunori , Hirose Shinichi 
Published: May 2021

AbstractDravet syndrome (DS) is an infantile-onset epileptic encephalopathy. More than 80% of DS patients have a heterozygous mutation in SCN1A, which encodes a subunit of the voltage-gated sodium channel, Nav1.1, in neurons. The roles played by astrocytes, the most abundant glial cell type in the brain, have been investigated in the pathogenesis of epilepsy; however, the specific involvement of astrocytes in DS has not been clarified. In this study, we evaluated Ca2+ signaling in astrocytes using genetically modified mice that have a loss-of-function mutation in Scn1a. We found that the slope of spontaneous Ca2+ spiking was increased without a change in amplitude in Scn1a+/− astrocytes. In addition, ATP-induced transient Ca2+ influx and the slope of Ca2+ spiking were also increased in Scn1a+/− astrocytes. These data indicate that perturbed Ca2+ dynamics in astrocytes may be involved in the pathogenesis of DS.
Intratumoural heterogeneity and immune modulation in lung adenocarcinoma of female smokers and never smokers
Authors: Trefzer Timo , Schneider Marc A. , Jechow Katharina , Chua Lorenz , Muley Thomas , Winter Hauke , Kriegsmann Mark , Meister Michael , Eils Roland , Conrad Christian 
Published: May 2021

AbstractLung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.
PAK1 and PAK2 in cell metabolism regulation
Authors: Kořánová Tereza , Dvořáček Lukáš , Grebeňová Dana , Röselová Pavla , Obr Adam , Kuželová Kateřina 
Published: May 2021

AbstractP21-activated kinases (PAKs) regulate processes associated with cytoskeletal rearrangements, such as cell division, adhesion, and migration. The possible regulatory role of PAKs in cell metabolism has not been well explored, but increasing evidence suggests that a cell metabolic phenotype is related to cell interactions with the microenvironment. We analyzed the impact of PAK inhibition by small molecule inhibitors, small interfering RNA, or gene knockout on the rates of mitochondrial respiration and aerobic glycolysis. Pharmacological inhibition of PAK group I by IPA-3 induced a strong decrease in metabolic rates in human adherent cancer cell lines, leukemia/lymphoma cell lines, and primary leukemia cells. The immediate effect of FRAX597, which inhibits PAK kinase activity, was moderate, indicating that PAK nonkinase functions are essential for cell metabolism. Selective downregulation or deletion of PAK2 was associated with a shift toward oxidative phosphorylation. Alternatively, PAK1 knockout resulted in increased glycolysis. However, the overall metabolic capacity was not substantially reduced by PAK1 or PAK2 deletion, possibly due to partial redundancy in PAK1/PAK2 regulatory roles or to activation of other compensatory mechanisms.
A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oocyte maturation and wing development
Authors: Vasudevan Deepika , Katow Hidetaka , Tang Grace , Ryoo Hyung Don 
Published: May 2021

AbstractMetazoans have evolved various stress response mechanisms to cope with cellular stress inflicted by external and physiological conditions. The Integrated Stress Response (ISR) is an evolutionarily conserved pathway that mediates adaptation to cellular stress via the transcription factor, ATF4. Loss of function of Drosophila ATF4, encoded by the gene cryptocephal (crc), results in lethality during pupal development. The roles of crc in Drosophila disease models and adult tissue homeostasis thus remain poorly understood. Here, we report that a protein-trap MiMIC insertion in the crc locus generates a crc-GFP fusion protein that allows visualization of crc activity in vivo, and acts as a hypomorphic mutant that uncovers previously unknown roles for crc. Specifically, the crc protein-trap line shows crc-GFP induction in a Drosophila model for Retinitis Pigmentosa (RP). This crc allele renders photoreceptors more vulnerable to age-dependent retinal degeneration. crc mutant adult animals also show greater susceptibility to amino acid deprivation and reduced levels of known crc transcriptional targets. Furthermore, this mutant allele shows defects in wing veins and oocyte maturation, uncovering previously unknown roles for crc in the development of these tissues. Together, our data establish physiological and pathological functions of crc-mediated ISR in adult Drosophila tissues.
Red, white and green: environmental communication on wine bottle labels from New York's Hudson River Region
Authors: Visconti Kevin 
Published: May 2021

PurposeNew York is the third top wine producing state in America. Competitive wine production across the United States has challenged New York winemakers to secure a place in the domestic market in order to support the long-term viability of the local economy. As businesses of agriculture become increasingly disrupted by the changing natural environment and consumer demand for sustainable products grows, vintners may distinguish themselves through the production and promotion of strategic initiatives on wine bottle labels.Design/methodology/approachFueled by the distinct fields of green marketing and environmental communication, this research investigates the promotion of sustainable practices on wine bottle labels. Through the methodology of content analysis, this project examines all 13 wineries on the Shawangunk Wine Trail located in the Hudson River Region of New York.FindingsThe findings from this study show that less than half of wineries in the sample selection employ environmental marketing as a communication strategy.Research limitations/implicationsThis research carries practical, business and social implications for the local Hudson River Region, the larger New York wine industry, and any organization looking to remain viable in a competitive marketplace.Originality/valueThis paper reveals the potential for the Hudson River Region wine industry to promote its “distinctive” and “innovative” environmental philosophy of “terroir driven and sustainably produced” winemaking on wine bottle labels to differentiate themselves in a crowded and expanding marketplace and build a Basis of Legitimacy with consumers.
Numerical investigation of the flow characteristics and permeability of 2D irregular columnar jointed rock masses
Authors: Cheng Zhichao , Wang Huanling , Xu Weiya , Yan Long 
Published: May 2021

PurposeThe objective of this paper is to provide a better understanding of the effect of irregular columnar jointed structure on the permeability and flow characteristics of rock masses.Design/methodology/approachAn efficient numerical procedure is proposed to investigate the permeability and fluid flow in columnar jointed rock masses (CJRMs), of which the columnar jointed networks are generated by a modified constrained centroid Voronoi algorithm according to the field statistical results. The fractures are represented explicitly by using the lower-dimensional zero thickness elements. And the modeling scheme is validated by a benchmark test for flow in fractured porous media. The effective permeability and representative elementary volume (REV) size of CJRMs are estimated using finite element method (FEM). The influences of joint density and variation coefficient of columnar joint structure on the permeability of the rock mass are discussed.FindingsThe simulation results indicate that the permeability is scale-dependent and tends to be stable with increase of model size. The hydraulic REV size is determined as 3.5 m for CJRMs in the present study. Moreover, the joint density is a dominant factor affecting the permeability of CJRMs. The average permeability of columnar jointed structures increases linearly with the joint density under the same REV size, while the influence from the coefficient of variation can be neglected.Originality/valueThe present paper investigates the REV size of the CJRMs and the effect of joint parameters on the permeability. The proposed method and the results obtained are useful on understanding the hydraulic characteristic of the irregular CJRMs in engineering projects.
Identifying design guidelines for online information resources: a study of expectant and new mothers
Authors: Mahony Carolanne , Heavin Ciara , Sammon David 
Published: May 2021

PurposeThe purpose of this article is to identify design guidelines for online resources based on the subjective assessment criteria used by individuals to assess and process information resources. This method of creating design guidelines targeted at precise user groups has the potential to aid designers and developers to create more user-centred information resources.Design/methodology/approachThe authors gathered data using a prospective longitudinal study investigating the information behaviour of expectant and new mothers. Women were asked to report on their information-seeking activities in a series of semi-structured interviews covering pregnancy and early motherhood.FindingsThis research identified 15 assessment criteria that were utilised by women to assess and process information resources. The most popular resource criteria amongst participants were credibility and convenience, while completeness and relevance were the most popular information content criteria. The authors found that assessment criteria were not considered in isolation, with criteria such as formatting and search engine ranking impacting on participants' perception of other criteria.Practical implicationsThis research demonstrates the potential of linking a user groups subjective assessment criterion to design guidelines. The authors propose that these guidelines could be used to help design an online information resource. They could also be used to assess if an existing online resource met the needs of a user group. The methodology used in this study could be leveraged to create design guidelines for user groups.Originality/valueThis research uses subjective assessment criteria as a means of understanding how expectant new mothers process information resources. People use subjective judgements when processing information resources, and this should be incorporated into the design of information resources. Analysing longitudinal data allowed the authors to build a rich picture of how participants evaluated and compared different information resources.
The influencing factors of enterprise resource planning (ERP) readiness stage on enterprise resource planning project success: a project manager’s perspective
Authors: Kirmizi Mehmet , Kocaoglu Batuhan 
Published: May 2021

PurposeThis study explores the influencing factors of the enterprise resource planning (ERP) readiness stage on project success immediately after go-live from the project manager’s perspective.Design/methodology/approachThe influencing factors of the ERP readiness stage are explored through the literature and expert review sessions and are embedded in Kotter’s change management model. A survey-based empirical study is conducted among ERP project managers in Turkey in 2019 utilizing principal component analysis and multiple regression analysis to reveal the direct relation of influencing factors and project success.FindingsResults show that the proposed model explains 65.179% of the variation with four components. The association of components through regression analysis reveals that project planning and management, employee commitment and change management directly relate to the ERP project success. Yet, surprisingly top management support is not directly correlated. Therefore, the results suggest that influencing factors of such long projects are to be evaluated by the stages of the project life cycle.Research limitations/implicationsThis research is limited to the project managers’ perspective in Turkey and the readiness stage of the project life cycle.Practical implicationsThe objectives of this research serve as a guideline for ERP project managers to consider the success factors in terms of ERP project phases. This ensures that the project manager allocates optimum resources to the right factors at the right time.Originality/valueDespite numerous studies in the ERP readiness stage, this study opens new ways of future research while filling several gaps. First, the ERP readiness phase is discussed with a theoretical approach through Kotter’s change management model. Second, the influencing factors of the ERP readiness stage on ERP project success from the project manager’s perspective are explored, and factor structures are revealed. Then, the association of the factors with ERP project success of “immediately after go-live” is empirically tested.
Competitive advantage of data-driven analytical capabilities: the role of big data visualization and of organizational agility
Authors: Medeiros Mauricius Munhoz de , Maçada Antônio Carlos Gastaud 
Published: May 2021

PurposeIn the digital age, the use of data and analytical capabilities to guide business decisions and operations plays a strategic role for organizations to gain competitive advantage (CA). However, the paths by which analytical capabilities convey their effect to CA are not yet fully known and few studies address the role of behavioral and cultural aspects of related of analytical capabilities. The purpose of this paper is to analyze how data-driven culture (DDC) and business analytics (BA) affect CA, considering the mediating effects of big data visualization (BDV) and organizational agility (OA).Design/methodology/approachA survey was conducted with 173 managers who are BDV and BA users in Brazilian organizations of various economic segments. The data were analyzed through structural equation modeling and mediation tests.FindingsThe evidence indicates that DDC and BDV are antecedents of BA. The following complementary mediations were discovered: BDV in the relationship between DDC and BA; BA in the relationship between DDC and CA; and OA in the relationship between BA and CA. It was also discovered that OA explains the transmission of most of the effect of BA to CA.Practical implicationsThis study can help organizations to understand the importance of cultural and behavioral aspects related to the use of the analytical capabilities. Thereby, managers can establish policies and strategies to extract value from data and leverage business agility and competitiveness through use BDV and BA.Originality/valueThis study fills an important research gap by developing an original research model and discussing empirical evidence on how DDC and BA affect CA, considering the mediating effects of BDV and OA.
Quantifying human resource management: a literature review
Authors: Coron Clotilde 
Published: May 2021

PurposeWith a focus on the evolution of human resource management (HRM) quantification over 2000–2020, this study addresses the following questions: (1) What are the data sources used to quantify HRM? (2) What are the methods used to quantify HRM? (3) What are the objectives of HRM quantification? (4) What are the representations of quantification in HRM?Design/methodology/approachThis study is based on an integrative synthesis of 94 published peer-reviewed empirical and non-empirical articles on the use of quantification in HRM. It uses the theoretical framework of the sociology of quantification.FindingsThe analysis shows that there have been several changes in HRM quantification over 2000–2020 in terms of data sources, methods and objectives. Meanwhile, representations of quantification have evolved relatively little; it is still considered as a tool, and this ignores the possible conflicts and subjectivity associated with the use of quantification.Originality/valueThis literature review addresses the use of quantification in HRM in general and is thus larger in scope than previous reviews. Notably, it brings forth new insights on possible differences between the main uses of quantification in HRM, as well as on artificial intelligence and algorithms in HRM.
Effects of person-organization fit objective feedback and subjective perception on organizational attractiveness in online recruitment
Authors: Huang Jui-Chieh 
Published: May 2021

PurposeThis study applies a person-environment fit (PEF) framework to examine the extent to which organizational attractiveness may be influenced by person-organization fit (POF) feedback and person-job fit (PJF) feedback in web-based recruitment. Furthermore, the potential mediating roles of subjective POF and subjective PJF perceptions were examined.Design/methodology/approachSenior undergraduate business administration students participated in a two-stage experiment by completing a paper-and-pencil survey during a campus career fair and then reviewing a recruitment website.FindingsResearch findings showed that online assessment feedback on PJF was positively related to organizational attractiveness. The higher the level PJF, the more organizational attractiveness participants reported. Second, both POF and PJF feedback information can affect organizational attractiveness indirectly through subjective POF and PJF perceptions, respectively. Fresh graduates were more sensitive to PJF feedback in deciding organizational attractiveness.Originality/valueThis study contributes to the recruitment literature in at least three ways. First, online recruitment messages concerning can affect organizational attractiveness. Second, in support of the PEF framework, fresh graduates can distinguish subjective POF perceptions from subjective PJF perceptions. Third, fresh graduates are more sensitive to PJF information and perceptions in deciding organizational attractiveness.