bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal impacts of telomerase activity and tumor cell differentiation in neuroblastoma tumor biology
Authors: Yu Eun Young , Zahid Syed S. , Aloe Sarah , Falck-Pedersen Erik , Zhou Xi Kathy , Cheung Nai-Kong V. , Lue Neal F. 
Published: May 2021

AbstractTelomere maintenance and tumor cell differentiation have been separately implicated in neuroblastoma malignancy. Their mechanistic connection is unclear. We analyzed neuroblastoma cell lines and morphologic subclones representing the adrenergic (ADRN) and mesenchymal (MES) differentiation states and uncovered sharp differences in their telomere protein and telomerase activity levels. Pharmacologic conversion of ADRN into MES cells elicited consistent and robust changes in the expression of telomere-related proteins. Conversely, stringent down-regulation of telomerase activity triggers the differentiation of ADRN into MES cells, which was reversible upon telomerase upregulation. Interestingly, the MES differentiation state is associated with elevated levels of innate immunity factors, including key components of the DNA-sensing pathway. Accordingly, MES but not ADRN cells can mount a robust response to viral infectionsin vitro. A gene expression signature based on telomere and cell lineage-related factors can cluster neuroblastoma tumor samples into predominantly ADRN or MES-like groups, with distinct clinical outcomes. Our findings establish a novel mechanistic connection between telomere and differentiation and suggest that manipulating telomeres may suppress malignancy not only by limiting the tumor growth potential but also by inducing tumor cell differentiation and altering its immunogenicity.
Synergistic and offset effects of fungal species combinations on plant performance
Authors: Hori Yoshie , Fujita Hiroaki , Hiruma Kei , Narisawa Kazuhiko , Toju Hirokazu 
Published: May 2021

AbstractIn natural and agricultural ecosystems, survival and growth of plants depend substantially on microbes in the endosphere and rhizosphere. Although numerous studies have reported the presence of plant-growth promoting bacteria and fungi in below-ground biomes, it remains a major challenge to understand how sets of microbial species positively or negatively affect plants’ performance. By conducting a series of single- and dual-inoculation experiments of 13 endophytic and soil fungi targeting a Brassicaceae plant species, we here evaluated how microbial effects on plants depend on presence/absence of co-occurring microbes. The comparison of single- and dual-inoculation experiments showed that combinations of the fungal isolates with the highest plant-growth promoting effects in single inoculations did not yield highly positive impacts on plant performance traits (e.g., shoot dry weight). In contrast, pairs of fungi including small/moderate contributions to plants in single-inoculation contexts showed the greatest effects on plants among the 78 fungal pairs examined. These results on the offset and synergistic effects of pairs of microbes suggest that inoculation experiments of single microbial species/isolates can result in the overestimation or underestimation of microbial functions in multi-species contexts. Because keeping single-microbe systems in outdoor conditions is impractical, designing sets of microbes that can maximize performance of crop plants is an important step for the use of microbial functions in sustainable agriculture.
A new role of low barrier hydrogen bond in mediating protein stability by small molecules
Authors: Yang Jianhong , Li Yong , Qiu Qiang , Wang Ruihan , Yan Wei , Yu Yamei , Niu Lu , Pei Heying , Wei Haoche , Ouyang Liang , Ye Haoyu , Xu Dingguo , Wei Yuquan , Chen Qiang , Chen Lijuan 
Published: May 2021

AbstractLow barrier hydrogen bond (LBHB) is a special type of hydrogen bond which occurs where two heteroatoms with similar pKa values share a single proton resulting in an unusually strong and short hydrogen bond. LBHBs in protein play important roles in enzyme catalysis and maintaining protein structural integrity but its other biochemical roles are unknown. Here we report a novel function of LBHB in selectively inducing tubulin protein degradation. A tubulin inhibitor, 3-(3-Phenoxybenzyl) amino-β-carboline (PAC), promotes selective degradation of αβ-tubulin heterodimers by binding to the colchicine site of β-tubulin. Biochemical studies have revealed that PAC specifically destabilizes tubulin, making it prone to aggregation that then predisposes it to ubiquitinylation and then degradation. Structural activity analyses have indicated that the destabilization is mediated by a single hydrogen bond formed between the pyridine nitrogen of PAC and βGlu198, which is identified as a LBHB. In contrast, another two tubulin inhibitors only forming normal hydrogen bonds with βGlu198 exhibit no degradation effect. Thus, the LBHB accounts for the degradation. Most importantly, we screened for compounds capable of forming LBHB with βGlu198 and demonstrated that BML284, a Wnt signaling activator, also promotes tubulin heterodimers degradation in a PAC-like manner as expected. Our study has identified a novel approach for designing tubulin degraders, providing a unique example of LBHB function and suggests that designing small molecules to form LBHBs with protein residues resulting in the highly specific degradation of a target protein could be a new strategy for drug development.
Prowler: A novel trimming algorithm for Oxford Nanopore sequence data
Authors: Lee Simon , Nguyen Loan T , Hayes Ben J , Ross Elizabeth 
Published: May 2021

AbstractMotivationQuality control (QC) tools are critical in DNA sequencing analysis because they increase the accuracy of sequence alignments and thus the reliability of results. Oxford Nanopore Technologies (ONT) QC is currently rudimentary, generally based on whole read average quality. This results in discarding reads that contain regions of high quality sequence. Here we propose Prowler, a multi-window approach inspired by algorithms used to QC short read data. Importantly, we retain the phase and read length information by optionally replacing trimmed sections with Ns.ResultsProwler was applied to mammalian and bacterial datasets, to assess effects on alignment and assembly respectively. Compared to Nanofilt, alignments of data QC’ed with Prowler had lower error rates and more mapped reads. Assemblies of Prowler QC’ed data had a lower error rate than Nanofilt QCed data however this came at some cost to assembly contiguity.Availability and implementationProwler is implemented in Python and is available at: https://github.com/ProwlerForNanopore/ProwlerTrimmerContacte.ross@uq.edu.auSupplementary informationSupplementary data are available at Bioinformatics online.
Pyruvate kinase M1 suppresses development and progression of prostate adenocarcinoma
Authors: Davidson Shawn M. , Heyman Julia E. , O’Brien James P. , Liu Amy C. , Schmidt Daniel R. , Israelsen William J. , Dayton Talya L. , Sehgal Raghav , Bronson Roderick T. , Freinkman Elizaveta , Mak Howard , Malstrom Scott , Bellinger Gary , Carracedo Arkaitz , Pandolfi Pier P. , Courtney Kevin D. , Frangioni John , Jha Abhishek , DePinho Ronald A. , Horner James W. , Thomas Craig J. , Cantley Lewis C. , Loda Massimo , Vander Heiden Matthew G. 
Published: May 2021

ABSTRACTMost cancers, including prostate cancers, express the M2 splice isoform of pyruvate kinase (Pkm2). This isoform can promote anabolic metabolism to support cell proliferation; however, Pkm2 expression is dispensable for many cancers in vivo. Pyruvate kinase M1 (Pkm1) isoform expression is restricted to relatively few tissues and has been reported to promote growth of select tumors, but the role of PKM1 in cancer has been less studied. Pkm1 is expressed in normal prostate tissue; thus, to test how differential pyruvate kinase isoform expression affects cancer initiation and progression we generated mice harboring a conditional allele of Pkm1 and crossed this allele, as well as a Pkm2 conditional allele, to a Pten loss-driven prostate cancer model. We found that Pkm1 loss leads to Pkm2 expression and accelerates prostate cancer, while deletion of Pkm2 leads to increased Pkm1 expression and suppresses cancer. Consistent with these data, a small molecule pyruvate kinase activator that mimics a PKM1-like state suppresses progression of established prostate tumors. PKM2 expression is retained in most human prostate cancers, arguing that pharmacological PKM2 activation may be beneficial for some prostate cancer patients.
A corpus for differential diagnosis: an eye diseases use case
Authors: Yepes Antonio Jimeno , Iraola David Martinez , Barnard Pieter , Joy Tinu Theckel 
Published: May 2021

AbstractWe have created a corpus for the extraction of information related to diagnosis from scientific literature focused on eye diseases. It was shown that the annotation of entities has a relatively large agreement among annotators, which translates into strong performance of the trained methods, mostly BioBERT. Furthermore it was observed that relation annotation in this domain has challenges, which might require additional exploration.When using the trained models on MEDLINE, we could identify confirmed knowledge about the diagnosis of eye diseases and relevant new information, which supports the developments in this work. The corpus that we have developed is publicly available, thus the scientific community is able to reproduce our work and reuse the corpus in their work.
Regulation of Src tumor activity by its N-terminal intrinsically disordered region
Authors: Aponte Emilie , Lafitte Marie , Sirvent Audrey , Simon Valérie , Barbery Maud , Fourgous Elise , Maffei Mariano , Armand Florence , Hamelin Romain , Pannequin Julie , Fort Philippe , Pons Miquel , Roche Serge 
Published: May 2021

ABSTRACTThe membrane anchored Src tyrosine kinase is involved in numerous pathways and its deregulation is involved in human cancer. Our knowledge on Src regulation relies on crystallography, which revealed intramolecular interactions to control active Src conformations. However, Src contains a N-terminal intrinsically disordered unique domain (UD) whose function remains unclear. Using NMR, we reported that UD forms an intramolecular fuzzy complex involving a conserved region with lipid-binding capacity named Unique Lipid Binding Region (ULBR), which could modulate Src membrane anchoring. Here we show that the ULBR is essential for Src’s oncogenic capacity. ULBR inactive mutations inhibited Src transforming activity in NIH3T3 cells and in human colon cancer cells. It also reduced Src-induced tumor development in nude mice. An intact ULBR was required for MAPK signaling without affecting Src kinase activity nor sub-cellular localization. Phospho-proteomic analyses revealed that, while not impacting on the global tyrosine phospho-proteome in colon cancer cells, this region modulates phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling, including EPHA2 and Fyn. Collectively, this study reveals an important role of this intrinsically disordered region in malignant cell transformation and suggests a novel layer of Src regulation by this unique region via membrane substrate phosphorylation.
Genome size evolution in the diverse insect order Trichoptera
Authors: Heckenhauer Jacqueline , Frandsen Paul B. , Sproul John S. , Li Zheng , Paule Juraj , Larracuente Amanda M. , Maughan Peter J. , Barker Michael S. , Schneider Julio V. , Stewart Russell J. , Pauls Steffen U. 
Published: May 2021

AbstractBackgroundGenome size is implicated in form, function, and ecological success of a species. Two principally different mechanisms are proposed as major drivers of eukaryotic genome evolution and diversity: Polyploidy (i.e., whole genome duplication: WGD) or smaller duplication events and bursts in the activity of repetitive elements (RE). Here, we generated de novo genome assemblies of 17 caddisflies covering all major lineages of Trichoptera. Using these and previously sequenced genomes, we use caddisflies as a model for understanding genome size evolution in diverse insect lineages.ResultsWe detect a ~14-fold variation in genome size across the order Trichoptera. We find strong evidence that repetitive element (RE) expansions, particularly those of transposable elements (TEs), are important drivers of large caddisfly genome sizes. Using an innovative method to examine TEs associated with universal single copy orthologs (i.e., BUSCO genes), we find that TE expansions have a major impact on protein-coding gene regions, with TE-gene associations showing a linear relationship with increasing genome size. Intriguingly, we find that expanded genomes preferentially evolved in caddisfly clades with a higher ecological diversity (i.e., various feeding modes, diversification in variable, less stable environments).ConclusionOur findings provide a platform to test hypotheses about the potential evolutionary roles of TE activity and TE-gene associations, particularly in groups with high species, ecological, and functional diversities.
Do socially responsible firms always disclose high-quality earnings? Evidence from an emerging socialist economy
Authors: Dang Hung Ngoc , Hoang Khanh , Vu Van Thuy , Nguyen Linh Van 
Published: May 2021

PurposeThis paper aims to investigate the linkage between corporate social responsibility (CSR) and earnings quality (EQ) in the context of Vietnam, an Asian emerging economy characterized by high growth for decades and a socialist orientation. As CSR firms are expected to have high EQ, there arise concerns that corporate managers of CSR firms may use the reputation of the firm as a protection mechanism against the cost of earnings management.Design/methodology/approachThe study uses a unique sample of Vietnamese CSR firms listed on Hanoi and Ho Chi Minh Stock Exchanges from 2015 to 2019. Several econometric tests are conducted to investigate whether corporate managers of CSR-active firms actively engage in earnings management and reduce the firms' EQ.FindingsThe empirical results show a negative impact of CSR on EQ, meaning that, in general, corporate managers of CSR firms in Vietnam opportunistically manage earnings. This confirms the paradox of the CSR–EQ relationship. In line with an emerging strand of research in the CSR literature, the finding suggests that the agency problem arises in CSR firms where corporate managers use their managerial discretion over accrual accounting to manipulate reported earnings.Practical implicationsThe finding has practical implications for market participants and policymakers in improving monitoring mechanisms and enhancing the information environment in developing capital markets.Originality/valueThis is the first study in the literature that investigates and shows the paradox of the CSR–EQ relationship in the context of Vietnam, a new emerging economy that follows socialist orientation.
An integrated supply chain – human resource management approach for improved supply chain performance
Authors: Jena Sarat Kumar , Ghadge Abhijeet 
Published: May 2021

PurposeHuman resource management (HRM) is struggling to cope with the increasingly volatile demand for skilled resources in the logistics and supply chain sector. Thus, this study discovers the possible integration of HRM and supply chain management (SCM) practices for improved supply chain performance. The purpose of this study is to explore the effect of intra HRM–SCM and joint HRM–SCM decisions on the performance of the supply chain.Design/methodology/approachAn intra HRM–SCM and joint HRM–SCM model is developed following an empirical study. Survey data collected from 109 supply chain managers from Indian logistics firms are used to test the developed hypotheses. Structural equation modeling is used to analyze and validate the model.FindingsThe results suggest that supply chain performance is significantly influenced by joint HRM–SCM, compared to intra HRM–SCM practices, especially under volatile demand environments. Training and development, recruitment and selection, and performance management affect joint HRM–SCM significantly compared to the other three factors identified. Moreover, HRM and SCM show strong correlation and mutual support in identifying and fulfilling the demand of the logistics and supply chain sector.Practical implicationsWith a growing trend toward globalization and digitalization, a joint HRM–SCM model will help businesses make robust and informed decisions for improved supply chain performance.Originality/valueAn empirical relationship between joint HRM–SCM, intra HRM–SCM, supply chain inhibitors and supply chain performance is established in this study. Although some part of this relationship may already exist, the study provides robust evidence to support this complex, collaborative relationship.
COVID-19 and cyber fraud: emerging threats during the pandemic
Authors: Ma Katelyn Wan Fei , McKinnon Tammy 
Published: May 2021

Purpose
The emergence of the novel coronavirus (COVID-19) has threatened physical and mental health, and changed the behaviour and decision-making processes of individuals, organisations, and institutions worldwide. As many services move online due to the pandemic, COVID-19-themed cyber fraud is also growing. This article explores cyber fraud victimization and cyber security threats during COVID-19 using psychological and traditional criminological theories. It also provides a COVID-19-themed cyber fraud typology using empirical evidence from institutional and agency reports. Through organizing COVID-19-themed cyber fraud into four different categorizations, we aim to offer classification insights to researchers and industry professionals so that stakeholders can effectively manage emerging cyber fraud risks in our current pandemic.

Design/methodology/approach
The approach the study take for this conceptual paper is typology.
CIO reporting structure and firm strategic orientation – a content analysis approach
Authors: Karanja Erastus , Grant Donna , Zaveri Jigish S. 
Published: May 2021

PurposeGrounded in the principal-agent theory, this study aims to develop and test hypotheses too, investigate how the firm’s strategic orientations, namely, innovation, growth, differentiation and cost leadership impact the chief information officer (CIO) reporting relationship and structure.Design/methodology/approachThe study uses content analysis to analyze a data set of press releases collected from the LexisNexis Academic wire index. The press releases were issued by firms when they hired CIOs between 2003 and 2007, yielding 128 firms, which had specific information about the CIO reporting relationship and structure.FindingsThe results reveal that firms seeking an innovation, growth or differentiation strategy have their CIOs reporting to the chief executive officer.Research limitations/implicationsThe current study is motivated by the desire to replicate and extend the works of previous researchers who have assessed various CIO issues. Replication takes several forms such as the use of similar or different data sets, different research environments or reinvestigating research concepts through a different theoretical lens. This study makes use of a multi-firm data set spanning five years and the principal-agent theory as the theoretical framework to explore the CIO reporting relationship and structure. Although this study focuses on the hiring trends and the strategic orientations of the firms, future studies should explore other characteristics associated with the CIOs that might have an impact on the reporting relationship such as the years of experience, age, educational background of CIOs and information technology budgets.Practical implicationsThe existing literature has not settled the debate as to whom the CIO should be reporting to and understanding the reporting relationships is important because, in many firms, the organizational structures and the reporting relationships are indicative of the power dynamics and how the organizational resources are controlled and shared.Originality/valueReplication studies are important because they confirm, reinforce, extend and provide reliability to the paradigms and knowledge in the discipline, as well as offer reliability of the results upon which scientific progress is based.
Inexperienced decision-makers' use of positive heuristics for marketing decisions
Authors: Gilbert-Saad Antoine , McNaughton Rod B. , Siedlok Frank 
Published: May 2021

PurposeResearch has reliably demonstrated that decision-makers, especially expert ones, use heuristics to make decisions under uncertainty. However, whether decision-makers with little or no experience also do, and if so, how? is unknown. This research addresses this issue in the marketing context by studying how a group of young and generally inexperienced entrepreneurs decide when asked to set a price and choose a distribution channel in a scenario involving a hypothetical firm.Design/methodology/approachThe authors used think-aloud protocols to elicit data and then used inductive procedures to code the data for analysis.FindingsThe inexperienced entrepreneurs in the sample used three types of heuristics in their decision-making, forming a structured process that narrows in scope. First, metacognitive heuristics, which specify a decision-making approach, were used, followed by heuristics representing the criteria they considered, and finally, heuristics detailing the execution of a selected option. The authors also found that heuristics relating to a market orientation, especially customer-centric criteria, were the most common, but these were balanced with ones representing an internal orientation or growth.Research limitations/implicationsThe generally inexperienced decision-makers the authors’ studied used heuristics in a structured way that helped them to select and balance several potentially conflicting decision-making criteria. As with most research using qualitative research designs, the generalizability of these findings is unclear. Further research on the mechanisms by which relatively inexperienced decision-makers learn the heuristics they use is recommended.Originality/valueThis research's novelty lies in its focus on heuristic use by nonexpert decision-makers under conditions of uncertainty and the findings about their scope and the order they are used. As the authors collected data from think-aloud protocols with relatively young entrepreneurs with limited experience, they also offer a description of the heuristics used by nascent entrepreneurs when making marketing decisions about pricing and channels. The most surprising conclusion is that even without relevant domain-specific knowledge, decision-makers can use heuristics in an ecologically rational way (i.e. structured to match the environment).