bluuebunny/crossref_metadata_2025_split huggingface dataset:
PolyA-modulating antisense oligonucleotides reveal opposing functions for long non-coding RNA NEAT1 isoforms in neuroblastoma
Authors: Naveed Alina , Cooper Jack , Li Ruohan , Hubbard Alysia , Liu Tao , Wilton Steve , Fletcher Sue , Fox Archa 
Published: May 2020

ABSTRACTMany long non-coding RNAs (lncRNA) are highly dysregulated in cancer and are emerging as therapeutic targets. One example is NEAT1, which consists of two overlapping lncRNA isoforms, NEAT1_1 (3.7kb) and NEAT1_2 (23kb), that are functionally distinct. The longer NEAT1_2 is responsible for scaffolding gene-regulatory nuclear bodies termed paraspeckles, whereas NEAT1_1 is involved in paraspeckle-independent function. The NEAT1 isoform ratio is dependent on the efficient cleavage and polyadenylation of NEAT1_1 at the expense of NEAT1_2. Here we developed a targeted antisense oligonucleotide (ASO) approach to sterically block NEAT1_1 polyadenylation processing, achieving upregulation of NEAT1_2 and abundant paraspeckles. We have applied these ASOs to cells of the heterogeneous infant cancer, neuroblastoma, as we found higher NEAT1_1:NEAT1_2 ratio and lack of paraspeckles in high-risk neuroblastoma cells. These ASOs decrease NEAT1_1 levels, increase NEAT1_2/paraspeckles and concomitantly reduce cell viability in high-risk neuroblastoma specifically. In contrast, overexpression of NEAT1_1 has the opposite effect, increasing cell-proliferation. Transcriptomic analyses of high-risk neuroblastoma cells with altered NEAT1 ratios and increased paraspeckle abundance after ASO treatment showed an upregulation of differentiation pathways, as opposed to the usual aggressive neuroblastic phenotype. Thus, we have developed potential anti-cancer ASO drugs that can transiently increase growth-inhibiting NEAT1_2 RNA at the expense of growth-promoting NEAT1_1 RNA. These ASOs, unlike others that degrade lncRNAs, provide insights into the importance of altering lncRNA polyadenylation events to suppress tumorigenesis as a strategy to combat cancer.
Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms
Authors: von Loeffelholz Ottilie , Purkiss Andrew , Cao Luyan , Kjaer Svend , Kogata Naoko , Romet-Lemonne Guillaume , Way Michael , Moores Carolyn A. 
Published: May 2020

AbstractThe Arp2/3 complex regulates many cellular processes by stimulating formation of branched actin filament networks. Because three of its seven subunits exist as two different isoforms, mammals produce a family of Arp2/3 complexes with different properties that may be suited to different physiological contexts. To shed light on how isoform diversification affects Arp2/3 function, we determined a 4.2 Å resolution cryo-EM structure of the most active human Arp2/3 complex containing ARPC1B and ARPC5L, and compared it with the structure of the least active ARPC1A-ARPC5-containing complex. The architecture of each isoform-specified Arp2/3 is the same. Strikingly, however, the N-terminal half of ARPC5L is partially disordered compared to ARPC5, suggesting that this region of ARPC5/ARPC5L is an important determinant of complex activity. Confirming this idea, the nucleation activity of Arp2/3 complexes containing hybrid ARPC5/ARPC5L subunits is higher when the ARPC5L N-terminus is present, thereby explaining activity differences between the different Arp2/3 complexes.
α-Synuclein aggregation intermediates form fibril polymorphs with distinct prion-like properties
Authors: Mehra Surabhi , Ahlawat Sahil , Kumar Harish , Singh Nitu , Navalkar Ambuja , Patel Komal , Kadu Pradeep , Kumar Rakesh , Jha Narendra N. , Udgaonkar Jayant B. , Agarwal Vipin , Maji Samir K. 
Published: May 2020

Abstractα-Synuclein (α-Syn) amyloid fibrils in synucleinopathies (such as Parkinson’s disease (PD), multiple system atrophy (MSA)) are structurally and functionally different, reminiscent of prion-like strains. However, how a single protein can form different fibril polymorphs in various synucleinopathies is not known. Here, we demonstrate the structure-function relationship of two distinct α-Syn fibril polymorphs, the pre-matured fibrils (PMF) and helix-matured fibrils (HMF) based on α-Syn aggregation intermediates. These polymorphs not only display the structural differences, including their fibril core structure as demonstrated by solid-state nuclear magnetic resonance (NMR) spectroscopy and H/D-exchange coupled with mass spectrometry but also possess different cellular activities such as seeding, cellular internalization, and cell-to-cell transmission. The HMF with a compact core structure exhibits low seeding potencyin cellsbut readily internalizes and transmits from one cell to another. Whereas the less structured PMF lacks the cell-to-cell transmission ability but induces abundant α-Syn pathology and triggers the formation of aggresomesin cells. Overall, the study highlights how the conformational heterogeneity in the aggregation pathway may lead to fibril polymorphs with distinct prion-like behavior in PD.
Genome-wide off-rates reveal how DNA binding dynamics shape transcription factor function
Authors: de Jonge Wim J. , Brok Mariël , Lijnzaad Philip , Kemmeren Patrick , Holstege Frank C.P. 
Published: May 2020

AbstractProtein-DNA interactions are dynamic and these dynamics are an important aspect of chromatin-associated processes such as transcription or replication. Due to a lack of methods to study on- and off-rates across entire genomes, protein-DNA interaction dynamics have not been studied extensively. Here we determinein vivooff-rates for theSaccharomyces cerevisiaechromatin organising factor Abf1, at 191 sites simultaneously across the yeast genome. Average Abf1 residence times span a wide-range, varying between 4.5 and 37 minutes. Sites with different off-rates are associated with different functional characteristics. This includes their transcriptional dependency on Abf1, nucleosome positioning and the size of the nucleosome-free region, as well as the ability to roadblock RNA polymerase II for termination. The results show how off-rates contribute to transcription factor function and that DIVORSEQ (DeterminingIn VivoOff-Rates by SEQuencing) is a meaningful way of investigating protein-DNA binding dynamics genome-wide.
Cellular Stress Signaling Activates Type-I IFN Response Through FOXO3-regulated Lamin Posttranslational Modification
Authors: Hwang Inah , Dai Ziwei , Li Fei , Sanchez Teresa , Locasale Jason W , Cantley Lewis L , Zheng Hongwu , Paik Jihye 
Published: May 2020

AbstractNeural stem/progenitor cells (NSPCs) persist over the lifespan while encountering constant challenges from age or injury related brain environmental changes, including elevated oxidative stress. A time-dependent stress response that regulates the dynamic balance between quiescence and differentiation is thus essential to preserve NSPC long-term regenerative potential. Here we report that acutely elevated cellular oxidative stress in NSPCs suppresses neurogenic differentiation through induction of FOXO3-mediated cGAS/STING and type I interferon (IFN-I) responses. We show that oxidative stress activates FOXO3 promoting upregulation of its transcriptional target glycine-N-methyltransferase (GNMT) and thus depletion of s-adenosylmethionine (SAM), a key co-substrate involved in methyl group transfer reactions. Mechanistically, we demonstrate that reduced intracellular SAM availability disrupts carboxymethylation and maturation of nuclear lamin, which trigger cytosolic release of chromatin fragments and subsequent activation of the cGAS/STING/IFN-I cascade. Together, our findings suggest the FOXO3-GNMT/SAM-lamin-cGAS/STING-IFN-I signaling cascade as a critical stress response program that preserves its long-term regenerative potential.
Determinants of non-performing loans in the banking sector in developing state
Authors: Khan Muhammad Asif , Siddique Asima , Sarwar Zahid 
Published: May 2020

PurposeThe size of non-performing loans (NPLs) plays a key role in the stability of the banking sector of a country. The factors that explain the NPLs contain very important information for banks. Studies in this regard with respect to developing states such as Pakistan have received little attention. This study aimed to scrutinize the determinants of NPLs observing a case of the banking sector in Pakistan over the period from 2005 to 2017.Design/methodology/approachThe sample consists of the banking sector (i.e., commercial banks) listed in Pakistan Stock Exchange over the period of 2005–2017. The banking factors, including profitability, operating efficiency, capital adequacy and income diversification, were evaluated. The estimations were done by regression modeling using random and fixed effects through STATA software.FindingsResults show that the operating efficiency and profitability indicators have a negative association with NPLs but were statistically significant, while capital adequacy and income diversification have a negative association with NPLs but were statistically insignificant.Research limitations/implicationsThe present study has considered limited banking indicators as determinants of NPLs and was limited to a specific time period from 2005 to 2017.Originality/valueThe study is an attempt to investigate various banking factors that affect the NPLs with respect to developing economies such as Pakistan.
Inadequately educated workforce and financing obstacles: international evidence from SMEs in developing countries
Authors: Jabbouri Imad , Farooq Omar 
Published: May 2020

PurposeThis paper aims to document the impact of inadequately educated workforce on the extent of financing obstacles experienced by firms.Design/methodology/approachThe authors use the data provided by the World Bank's Enterprise Surveys to test our arguments. The data were collected during the period between 2008 and 2018 in 141 developing countries. A pooled ordered logit regression analysis is performed to arrive at the results.FindingsThe study’s results show that firms with inadequately educated workforce are more likely to experience financing obstacles than other firms. The authors argue that poor performance and lack of technical expertise required to access finance are some of the reasons behind greater financing obstacles experienced by these firms. The study’s results are robust across different geographic regions. The authors also show that firms with inadequately educated workforce are more likely to seek informal credit for financing their short-term (working capital) and long-term (capital expenditures) capital requirements.Practical implicationsUnderstanding the factors that affect the financing constraints faced by small and medium enterprises (SMEs) should be valuable to managers of SMEs and policy-makers. By removing these constraints, managers can improve their access to financing, and policy-makers can facilitate higher economic growth and better economic conditions.Originality/valuePrior studies have largely been silent on the impact of inadequately educated workforce on the access to finance. This paper draws attention to this issue within the context of SMEs in an international setting. SMEs are the drivers of economic growth in any country. However, their contributions to economic growth cannot materialize without fulfilling their capital needs.
Income structure, diversification strategy and owners’ benefit in cooperative financial institutions
Authors: Cuong Hoang Van , Ngoc Luu Hiep , Quynh Thi Nguyen Loan , Chu Vu Tuan 
Published: May 2020

PurposeThe purposes of this paper are twofold. First, it analyses the income structure in cooperative financial institutions and examines how traditional and non-traditional incomes are related. Second, it evaluates whether increasing diversification towards non-traditional incomes facilitates or hampers the benefits of financial cooperative owners.Design/methodology/approachData are collected from over 3,100 US credit unions over the period of 1994–2016. A number of modern econometric techniques are employed throughout the analysis, including the use of panel fixed effect, generalised method of moments (GMM) and two-stage least square (2SLS) methodologies.FindingsUsing US credit unions as the empirical setting, the empirical results reveal that the expansion of traditional income leads to a corresponding increase in income from non-traditional activities. However, an increasing reliance on non-traditional income causes a significant drop in interest margins. The authors also find that the extent to which income diversification affects owner benefit varies across credit union types and period of time. While income diversification negatively affects owners' benefits in single common bond credit unions, it has no significant influence on multiple common bond and community credit union owners' benefits. Third, diversification can be beneficial during crisis time, but can be detrimental to owner benefit during normal time.Originality/valueThis paper provides some of the first empirical investigations on the diversification strategy of cooperative financial institutions. Therefore, the results offer significant policy implications for policymakers and market participants on whether financial cooperatives should diversify or specialise.
Fatigue damage assessment of reinforced concrete beam using average frequency and rise angle value of acoustic emission signal
Authors: Md Nor Noorsuhada , Mat Saliah Soffian Noor , Hashim Khairul Afinawati 
Published: May 2020

PurposeIn civil engineering construction, the reinforced concrete (RC) structure is generally used and exposed to fatigue loading as it is in service. The assessment of the RC structure is required to maintain the service life of the structure.Design/methodology/approachThis paper presents the behaviour of RC beam specimens under increasing maximum fatigue loading until failure. Simultaneously the acoustic emission (AE) was recorded. Twelve phases of maximum fatigue loading at Stage 1 and Stage 2 were applied to the beam with the frequency of 1 Hz and 5,000 load cycles were applied for each load phase. Two AE parameters were analysed and discussed, namely average frequency and rise angle value at CH4 and CH5.FindingsThe results found that the load and crack are closely related to the AE activities in the RC beam specimen when subjected to increasing fatigue loading.Originality/valueTo investigate the AE characteristics of RC beam specimens subjected to 12 phases of maximum fatigue loading using the average frequency and rise angle value.
Explaining the complexity relationship of CSR and financial performance using neo-institutional theory
Authors: P Golrida Karyawati , Subroto Bambang , T Sutrisno , Saraswati Erwin 
Published: May 2020

PurposeThis study aims to prove the complexity of the relationship between CSR and financial performance (FP) and to decompose the complexity of the relationship using neo-institutional theory.Design/methodology/approachThis research employs a meta-analysis that integrates 55 various contexts studied between 1998 and 2017 using correlation coefficient as the effect size.FindingsThis study proves that the nature of the relationship between CSR and FP is complex and suggests that the analysis of the relationship between the two variables includes institutional factors to produce generalizable conclusions. Country characteristics, forms and dimensions of CSR, CSR measurements and FP measurements explain the complexity of the relationship between CSR and FP.Research limitations/implicationsFuture research is expected to include industry characteristics and the corporate governance model in the analysis of the relationship between CSR and FP. Differences in industry characteristics affect the selection of CSR forms and dimensions, bringing it the potential to influence the relationship between CSR and FP. The corporate governance model adopted by developing countries and developed countries also has the potential to be an institutional factor to influence the relationship between CSR and FP.Originality/valueThis research proves that the complexity of the relationship between CSR and FP is nature given. This research explores the factors causing the complexity of the relationship using neo-institutional theory, which, to the author's knowledge, has not been done by other researchers.
The familiar stranger of mental health
Authors: Long Matthew Sydney 
Published: May 2020

Purpose
This paper aims to contribute to the debate about the closure of institutional mental health-care facilities, from an experiential perspective of a former mental health inpatient, ongoing service user and campaigner for retention of such facilities. It argues that auto-ethnographic accounts of mental illness by those with multiple social identities can have a greater role in terms of future training of mental health-care professionals.

Design/methodology/approach
The paper offers an experiential account of the impact of mental health facility bed closures as a patient admitted to institutional mental health facilities; as a mental health campaigner, fighting for the provision of both places of safety and “safe space” within his own local community; and as an ongoing service user. The research is in the interpretivist tradition of social science in taking an auto-ethnographical methodological stance.

Findings
This paper is underpinned by two key theoretical notions. Firstly, Stuart Hall’s concept of the Familiar Stranger (2017) is used to explore the tensions of self-identity as the author SHIFTS uncomfortably between his three-fold statuses. Secondly, the notion of “ontological insecurity” offered by Giddens (1991) is used with the paper exploring the paradox that admission to a mental health facility so-called “place of safety” is in fact itself a disorientating experience for both patient and carer(s).

Research limitations/implications
No positivistic claims to reliability, representativeness or generalisability can be made. It is the authenticity of the account which the reader feels should be afforded primacy in terms of its original contribution to knowledge.

Practical implications
This paper should have practical use for those tasked with developing educational and training curriculums for professionals across the mental health-care sector.

Social implications
This paper implicitly assesses the political wisdom of the policy of mental health bed closures within the wider context of the deinstitutionalisation movement.

Originality/value
This paper is underpinned by original experiential accounts from the author as patient, campaigner for places of safety and onging service-user of mental health care provision.
Strategies for preventing illicit financial flows in developing countries
Authors: Umar Bello , Abu Martins Mustapha , Mohammed Zayyanu 
Published: May 2020

Purpose
This paper aims to critically review the strategies for prevention of illicit financial flows to and from developing countries with a view of ascertaining the most effective strategies to be selected and implemented by developing countries to stem the scourge.

Design/methodology/approach
The peer-reviewed journal articles were studied; those that discussed illicit financial flows were selected and reviewed critically using the systematic quantitative assessment techniques together with an output table.

Findings
The critical review deduced that enacting effective trade laws, trade regulations, creating a beneficial ownership registry, multinational companies disclosing information on business, automatic exchange of information on tax issues, the Financial Action Task Force 40 guidelines on anti-money laundering and countering financing of terrorism and domestic and international cooperation are the most reliable strategies that should be implemented by developing countries.

Research limitations/implications
The wide geographic scope of developing countries, use of only high-quality databases that restricted the use of other articles and use of public sector perspective are the limitations for this paper.

Originality/value
This study is amongst the limited works to discuss the most reliable and effective strategies to prevent illicit financial flows in developing countries.
Leadership humility and managing a multicultural workforce
Authors: Hutt Camille , Gopalakrishnan Shanthi 
Published: May 2020

PurposeThe purpose of this paper is to understand how CEO Joseph Abraham of Commercial Bank, Qatar, has shaped the culture of the bank and driven increased success during his tenure there. This is one of a series of interview-based studies that are focused on South Asian CEOs, with the goal of better understanding their management style in a multinational context. This short paper explores how leadership style can impact the development of workplace culture among a multinational workforce to build a collaborative, innovative and high-performing organization.Design/methodology/approachThis paper uses primary interviews and supplements the analyses with secondary data sources and published research on leadership, organizational identity, culture and organizational ambidexterity.FindingsThe study found that cultural values and learned behaviors impact one's leadership and vision. In this instance, the CEO's leadership style demonstrated humility, an appreciation of diverse national cultures, and an ability to create organizational identity and cultivate a culture of ambidexterity, providing comfort to the organization in dynamically opposite contexts. All of these leadership features have enabled the organization to become more adaptive and perform better.Originality/valueThe narrative provides a glimpse of leadership humility and the implementation of those ideals in the workplace. The global experience of this South Asia-raised CEO provides an insider's view to decision-making and helps us understand how family, cultural background, and diverse work experience shape leadership behavior and culture in a multinational context.
Spatial genet dynamics of a dwarf bamboo: Clonal expansion into shaded forest understory contributes to regeneration after an episodic die‐off
Authors: Tomimatsu Hiroshi , Matsuo Ayumi , Kaneko Yuichiro , Kudo Eri , Taniguchi Ryotaro , Saitoh Tomoyuki , Suyama Yoshihisa , Makita Akifumi 
Published: May 2020

AbstractThe ability of clonal plants to spread horizontally and to share resources within genets has long been considered advantageous in spatially heterogeneous environments, yet our understanding of how such traits relate to its widespread success and dominance is still limited. Using a dwarf bamboo, Sasa kurilensis, that often dominates cool‐temperate forest understorys, we investigated how population recovery over 20 years after an episodic die‐off may be augmented by clonal expansion via rhizomes. Previous analyses on genet demography using 9‐m2 plots showed that more productive genets were more likely to survive, spread laterally, and replace less productive ones. In this study, we examined whether the recovery of biomass in lower light microsites, where biomass recovery was initially slower, was supported by the spread of productive genets at larger scales, from surrounding higher‐light microsites. We found that the biomass recovery in lower‐light plots was more supported by genets that spread clonally into the plots. Such genets that spread from outside plots produced larger culms than those that had originally germinated there. Whereas genets that contributed much to the biomass of the low‐light plots spread extensively from higher‐light microsites, the spatial extent of genets that originally germinated in these plots was quite limited, so that the patterns of clonal expansion appeared to be unidirectional along the light gradient. Our findings suggest that clonal expansion of productive genets from higher‐light into shaded microsites may be important for S. kurilensis to proliferate across heterogeneous light environments.