bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splice-switching of the insulin receptor in rhabdomyosarcoma: Rescuing theIR-Bisoform for better treatment options
Authors: Khurshid Safiya , Montes Matias , Comiskey Daniel F. , Shane Brianne , Matsa Eleftheria , Brown Chelsea , Bid Hemant Kumar , Wang Ruoning , Houghton Peter , Rigo Frank , Chandler Dawn 
Published: October 2020

ABSTRACTRhabdomyosarcoma (RMS) is an aggressive pediatric tumor with poor prognosis for metastasis and recurrent disease. Large scale sequencing endeavors demonstrate that RMS tumors have limited mutations and a dearth of driver mutations that are precisely targetable. However, IGF2 signaling is known to be grossly altered in RMS. The IGF2 signalling molecule binds both its innate IGF1 receptor as well as the insulin-receptor-variant-A (IR-A) with high affinity. Mitogenic and proliferative signalling via the canonical IGF2 pathway is therefore augmented byIR-A. The insulin receptor (IR) which is a transmembrane tyrosine-kinase receptor exists in two alternatively spliced isoforms,IR-AandIR-B. In this study, we show that RMS patients express increasedIR-Acompared to control tissues that express predominantly theIR-Bisoform. We also found thatHif1ais significantly increased in RMS tumors, portraying their hypoxic phenotype. Furthermore, the alternative-splicing ofIRadapts to produce moreIR-Ain response to hypoxic stress. Upon examining the pre-mRNA structure of the gene, we identified a hypoxia-responsive-element, which is also the binding site for the RNA-binding proteinCUG-BP1. We designed Splice-Switching-Oligonucleotides (SSO) against this binding site to decrease the levels ofIR-Ain RMS cell-lines and consequently rescue theIR-Bexpression levels. SSO treatment resulted in significant reductions in proliferation, migration and angiogenesis. Our data show promising insight into how impeding the IGF-2 pathway by reducingIR-Aexpression mitigates tumor growth. Our data reveal that RMS tumors useIRalternative-splicing as yet another survival strategy which can be exploited as therapeutic intervention in conjunction with already established anti-IGF-1 receptor therapies.
Genetic or toxicant induced disruption of vesicular monoamine storage and global metabolic profiling inCaenorhabditis elegans
Authors: Bradner Joshua M. , Kalia Vrinda , Lau Fion K. , Sharma Monica , Bucher Meghan L. , Johnson Michelle , Chen Merry , Walker Douglas I. , Jones Dean P. , Miller Gary W. 
Published: October 2020

AbstractThe proper storage and release of monoamines contributes to a wide range of neuronal activity. Here, we examine the effects of altered vesicular monoamine transport in the nematodeC. elegans. The genecat-1is responsible for the encoding of the vesicular monoamine transporter (VMAT) inC. elegansand is analogous to the mammalian vesicular monoamine transporter 2 (VMAT2). Our laboratory has previously shown that reduced VMAT2 activity confers vulnerability on catecholamine neurons in mice. The purpose of this paper was to determine whether this function is conserved and to determine the impact of reduced VMAT activity inC. elegans. Here we show that deletion ofcat-1/VMAT increases sensitivity to the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) as measured by enhanced degeneration of dopamine neurons. Reducedcat-1/VMAT also induces changes in dopamine-mediated behaviors. High-resolution mass spectrometry-based metabolomics in the whole organism reveals changes in amino acid metabolism, including tyrosine metabolism in thecat-1/VMAT mutants. Treatment with MPP+disrupted tryptophan metabolism. Both conditions altered glycerophospholipid metabolism, suggesting a convergent pathway of neuronal dysfunction. Our results demonstrate the evolutionarily conserved nature of monoamine function inC. elegansand further suggest that HRMS-based metabolomics can be used in this model to study environmental and genetic contributors to complex human disease
SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus
Authors: Chen Jungang , Dai Lu , Barrett Lindsey , Post Steven R. , Qin Zhiqiang 
Published: October 2020

SummaryAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected over 34,000,000 people since the end of 2019, killed over 1,000,000, and caused worldwide social and economic disruption. Due to the mechanisms of SARS-CoV-2 infection to host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Besides severe respiratory and systematic symptoms, several comorbidities may also increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. In the current study, we have reported that SARS-CoV-2 encoded proteins and some anti-COVID-19 drugs currently used are able to induce lytic reactivation of Kaposi’s sarcoma-associated herpesvirus (KSHV), one of major human oncogenic viruses through manipulation of intracellular signaling pathways. Our data indicate that those KSHV+ patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop virus-associated cancers, even after they have fully recovered from COVID-19.
The X-linked intellectual disability gene product and E3 ubiquitin ligase KLHL15 degrades doublecortin proteins to constrain neuronal dendritogenesis
Authors: Song Jianing , Merrill Ronald A. , Usachev Andrew Y. , Strack Stefan 
Published: October 2020

ABSTRACTProper brain development and function requires finely controlled mechanisms for protein turnover and disruption of genes involved in proteostasis is a common cause of neurodevelopmental disorders. Kelch-like 15 (KLHL15) is a substrate adaptor for cullin3 (Cul3)-containing E3 ubiquitin ligases andKLHL15gene mutations were recently described as a cause of severe X-linked intellectual disability. Here, we used a bioinformatics approach to identify a family of neuronal microtubule-associated proteins (MAPs) as KLHL15 substrates, which are themselves critical for early brain development. We biochemically validated doublecortin (DCX), also an X-linked disease gene, and doublecortin-like kinases 1 and 2 (DCLK1/2) asbona fideKLHL15 interactors and mapped KLHL15 interaction regions to their tandem DCX domains. Shared with two previously identified KLHL15 substrates, a FRY tripeptide at the C-terminal edge of the second DCX domain is necessary for KLHL15-mediated ubiquitination of DCX and DCLK1/2 and subsequent proteasomal degradation. Conversely, silencing endogenous KLHL15 markedly stabilizes these DCX domain-containing proteins and prolongs their half-life. Functionally, overexpression of KLHL15 in the presence of wild-type DCX reduces dendritic complexity of cultured hippocampal neurons, whereas neurons expressing FRY-mutant DCX are resistant to KLHL15. Collectively, our findings highlight the critical importance of the E3 ubiquitin ligase adaptor KLHL15 in proteostasis of neuronal MAPs and identify a regulatory network important for development of the mammalian nervous system.
Silencing of ATP synthase β reduces phytoplasma multiplication in the leafhopper vectorEuscelidius variegatus
Authors: Galetto Luciana , Abbà Simona , Rossi Marika , Ripamonti Matteo , Palmano Sabrina , Bosco Domenico , Marzachì Cristina 
Published: October 2020

AbstractThe leafhopperEuscelidius variegatusis a natural vector of the chrysanthemum yellows phytoplasma (CYp) and a laboratory vector of the Flavescence dorée phytoplasma (FDp). Previous studies indicated a crucial role for insect ATP synthase α and β subunits during phytoplasma infection of the vector species. Gene silencing of ATP synthase β was obtained by injection of specific dsRNAs inE. variegatus.Here we present the systemic and long-lasting nature of such silencing, its effects on the small RNA profile, the significant reduction of the corresponding protein expression, and the impact on phytoplasma acquisition capability. The specific transcript expression was silenced at least up to 37 days post injection with an average reduction of 100 times in insects injected with dsRNAs targeting ATP synthase β (dsATP) compared with those injected with dsRNAs targeting green fluorescent protein (dsGFP), used as negative controls. Insects injected either with dsATP or dsGFP successfully acquired CYp and FDp during feeding on infected plants. However, the average phytoplasma amount in dsATP insects was significantly lower than that measured in dsGFP specimens, indicating a probable reduction of the pathogen multiplication rate when ATP synthase β was silenced. The role of the insect ATP synthase β during phytoplasma infection process is discussed.
Parametric cognitive load reveals hidden costs in the neural processing of perfectly intelligible degraded speech
Authors: Ritz Harrison , Wild Conor , Johnsrude Ingrid 
Published: October 2020

AbstractSpeech is often degraded by environmental noise or hearing impairment. People can compensate for degradation, but this requires cognitive effort. Previous research has identified frontotemporal networks involved in effortful perception, but materials in these works were also less intelligible, and so it is not clear whether activity reflected effort or intelligibility differences. We used functional magnetic resonance imaging to assess the degree to which spoken sentences were processed under distraction, and whether this depended on speech quality even when intelligibility of degraded speech was matched to that of clear speech (i.e., 100%). On each trial, participants either attended to a sentence, or to a concurrent multiple object tracking (MOT) task that imposed parametric cognitive load. Activity in bilateral anterior insula reflected task demands: during the MOT task, activity increased as cognitive load increased, and during speech listening, activity increased as speech became more degraded. In marked contrast, activity in bilateral anterior temporal cortex was speech-selective, and gated by attention when speech was degraded. In this region, performance of the MOT task with a trivial load blocked processing of degraded speech whereas processing of clear speech was unaffected. As load increased, responses to clear speech in these areas declined, consistent with reduced capacity to process it. This result dissociates cognitive control from speech processing: substantially less cognitive control is required to process clear speech than is required to understand even very mildly degraded, 100% intelligible, speech. Perceptual and control systems clearly interact dynamically during real-world speech comprehension.Significance StatementSpeech is often perfectly intelligible even when degraded, e.g., by background sound, phone transmission, or hearing loss. How does degradation alter cognitive demands? Here, we use fMRI to demonstrate a novel and critical role for cognitive control in the processing of mildly degraded but perfectly intelligible speech. We compare speech that is matched for intelligibility but differs in putative control demands, dissociating cognitive control from speech processing. We also impose a parametric cognitive load during perception, dissociating processes that depend on tasks from those that depend on available capacity. Our findings distinguish between frontal and temporal contributions to speech perception and reveal a hidden cost to processing mildly degraded speech, underscoring the importance of cognitive control for everyday speech comprehension.
Online education during COVID-19: perception of academic stress and emotional intelligence coping strategies among college students
Authors: Chandra Yamini 
Published: October 2020

PurposeDue to COVID-19 pandemic, the government around the world has closed all the educational institutions to control the spread of disease, which is creating a direct impact on students, educators and institutions. The sudden shift from the physical classroom to virtual space is creating a disruption among students. The purpose of this study was to analyze the perception of academic stress experienced by students during current online education and coping strategies using emotional intelligence adopted by them.Design/methodology/approachUsing a purposive sampling method, data were collected on a sample of 94 students pursuing undergraduation and postgraduation from two Indian cities, Ahmedabad, and Mumbai. The survey was conducted using two online questionnaires, Perceptions of Academic Stress Scale and Emotional Intelligence Scale and analyzed using descriptive statistics with chi-square analysis. A telephonic discussion was also conducted with some respondents to understand different coping strategies used by them to handle the stress.FindingsThe findings indicated significant differences were observed between the fear of academic failure and online and home environment among male and female students. Many of them have started diverting themselves to various creative activities and taking up courses that are helping them to learn new technical skills. By using emotional intelligence and distancing from boredom and depressive thoughts, students were trying to cope with negative effects arising from the current pandemic situation.Research limitations/implicationsThis research study will be beneficial to educators, scholars, students, parents and will add a contribution to its field. However, the key factors studied were limited to a small sample from selected institutions and cities, which cannot be used to generalize to a large population.Practical implicationsThe findings of this paper will be useful to assess the key challenges of online education especially at the time when it is the only option.Social implicationsThe findings of this paper will be beneficial to understand the academic stress experienced by students and how a cultural and educational modification will be implemented.Originality/valueThis research study was conducted during the lockdown in India (April–May 2020), and the results derived through it are original in nature.
Impact of contexts, resource types and perceptions on information management within the personal domain among college students
Authors: Syn Sue Yeon , Sinn Donghee , Kim Sujin 
Published: October 2020

PurposeThis study aims to investigate how college students' personal information behaviors were impacted by contexts, resource types and perceptions of personal information management.Design/methodology/approachUsing an online survey, a total of 1,194 valid responses were collected from college students. The three contexts used for this study include academic, health and personal digital history. Specific scenarios, along with sets of resource types, were provided for each context.FindingsThe findings show that college students' perceptions and contexts strongly influence their activities related to personal information, and that resource types impact their activities depending on the context in which the resource types are situated. The findings of this study provide evidence of how varying factors influence personal information behaviors at different levels. Information professionals need to design their services and programs in a way that is cognizant of the factors that influence users and the challenges that users meet with in different contexts and resource types.Originality/valueThe findings of this study contribute to personal information research by providing an understanding of how context, perceptions and resource types intertwiningly influence personal information behaviors. This study provides an insight into widely accepted patterns and perceptions of personal information behavior with particular information resource types and within specific contexts.
Multidisciplinarity in internal communication and the challenges ahead
Authors: Araújo Milena , Miranda Sandra 
Published: October 2020

PurposeConsidering the impact internal communication has on the performance of organizations, studies about internal communication are revisited in order to generate a deeper understanding about the disciplines that shape the topic and the main trends influencing both the academic and professional fields.Design/methodology/approachDeparting from a communicational background, the authors integrate dispersed contributions from disciplines such as organizational communication, public relations, corporate communication and marketing communications, to the literature on internal communication.FindingsThe significant role played by internal communication is supported by scholars with different theoretical backgrounds. Despite the clear differences between disciplines, the defense of a strategized internal communication and a focus on the employee is widely accepted.Practical implicationsBoth scholars and practitioners will need to keep adapting to a reality where: internal communication practices are not only managerial but also dependent on the inputs of the employees; the ability to listen and collect feedback is sacred, and internal communication plans are expected to be strategically implemented and measured.Originality/valueBy showing the plurality of disciplines that influence internal communication, a strategized multidisciplinary focus on the topic is encouraged.
A qualitative approach to investigate emergency preparedness state for the built environment in the UAE
Authors: Rashid Alteneiji Hamdan , Ahmed Vian , Saboor Sara 
Published: October 2020

PurposeEmergency preparedness (EP) is one of the crucial phases of the disaster management cycle for the built environment. The body of knowledge, therefore, reports on different preparedness standards adopted by developed countries such as the United Kingdom (UK), the United States of America (USA), Canada, Japan and Australia. Other countries, however, such as the United Arab Emirates (UAE) (in the absence of its preparedness framework), have long adapted the UK preparedness standards. This has called for this study to investigate the state of EP practices in the UAE to identify the limitations and challenges it has been facing during its preparedness phase when adopting the UK preparedness standards.Design/methodology/approachQualitative methods of data collection and documentation with the content analysis were adopted to identify the barriers faced by the preparedness phase of emergency management (EM) in the UAE. A Pilot study was therefore conducted to validate eight key elements of the EP phase identified from the literature. The state of EP phase and the extent to which the eight key elements of EP elements were practiced and the barriers in their implementation in the UAE were explored through interviews at federal (National Crisis and Emergency Management Authority) and local levels (local team of crisis and emergency management).FindingsThe study identified eight key elements of the EP phase and the associated barriers related to their implementation in the UAE. The barriers were ranked based on their severity by interviewing experts at both federal and local levels.Practical implicationsThis paper addresses the need to investigate the state of the EP phase, its key elements and the barriers faced during its implementation in the UAE.Originality/valueDue to the absence of any EP frameworks or systems in the UAE, this paper aims to validate the EP elements identified by adopting a qualitative approach.
Exploring talent management in practice: an Arab country-specific empirical investigation
Authors: Tlaiss Hayfaa 
Published: October 2020

PurposeDespite the proliferation of studies on talent management (TM), few studies focus on the perspectives of human resource management (HRM) representatives. Furthermore, there is a dearth of studies that explore talent philosophies and TM in practice in private organizations in emerging economies, such as those of the Arab Middle East (AME) region. Consequently, the purpose of this study is to explore talent philosophies and TM in practice in the country-specific context of Lebanon.Design/methodology/approachThis study was exploratory in nature and followed a qualitative interpretive methodology. It capitalized on in-depth, semi-structured interviews with HRM representatives.FindingsThe findings of this study indicated relative consensus in talent philosophies across organizations in four industries; talent was largely perceived as exclusive, despite disagreements on whether it was stable or developable. Differences were identified in terms of how TM was understood in organizations and also how it was executed in practice in terms of talent identification and recruitment, training and development, performance assessment and talent retention.Originality/valueThis study is the first to empirically explore talent philosophies and TM in practice in the context of Lebanon. It is also among the few studies to extend the use of institutional theory (IT) to talent philosophies and TM practices. The originality of this study is also derived from its focus on the practices of HRM departments through using feedback from HRM representatives.
Graduate employability post-COVID-19: the case of a Malaysian public university
Authors: Kamaruddin Muhammad Iqmal Hisham , Ahmad Azuan , Husain Mohd Asri , Abd Hamid Saffa Nasuha 
Published: October 2020

PurposeThis study presents an effort to identify and understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on the graduate employability (GE) of Universiti Sains Islam Malaysia (USIM) final year students. It examines the readiness of USIM's final year students to the internship during the lockdown period, the readiness to join GE programs and also employment prospects in the future.Design/methodology/approachA questionnaire survey was employed, and 1,445 USIM final year students participated in this study.FindingsThe findings reveal that USIM final year students are ready to perform their internship even during the lockdown period. Besides, the students are also ready to join GE programs conducted by USIM, even while COVID-19 pandemic still currently occurs. Meanwhile, for the employment prospects in the future, results show that they believed that the employment prospects in the future after COVID-19 is low. In addition, academic background and internship areas exacerbate COVID-19's impact on the perceptions of USIM final year students on the employment prospects in the future.Originality/valueThis study is believed to be a pioneering study in identifying the impact of COVID-19 on the GE. It also contributes by identifying students' readiness to perform their internship during lockdown period via work from home (WFH) approach as well as their perceptions on the employment prospects in the future.