bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYRI-A regulates macropinocytic cup maturation and mediates integrin uptake, limiting invasive migration
Authors: Le Anh Hoang , Yelland Tamas , Paul Nikki R. , Fort Loic , Nikolaou Savvas , Ismail Shehab , Machesky Laura M. 
Published: December 2020

AbstractThe Scar/WAVE complex is the major driver of actin nucleation at the plasma membrane, resulting in lamellipodia and membrane ruffles. While lamellipodia aid migration, membrane ruffles can generate macropinosomes - cup-like structures - important for nutrient uptake and regulation of cell surface receptor levels. How macropinosomes are formed and the role of the actin machinery in their formation and resolution is still not well understood. Mammalian CYRI-B is a recently described negative regulator of the Scar/WAVE complex by RAC1 sequestration, but its other paralogue, CYRI-A has not been characterised. Here we implicate CYRI-A as a key regulator of macropinosome maturation and integrin internalisation from the cell surface. We find that CYRI-A is recruited to nascent macropinosomes in a transient but distinct burst, downstream of PIP3-mediated RAC1 activation and the initial burst of actin assembly driving cup formation, but upstream of internalisation and RAB5 recruitment to the macropinosome. Together, our data place CYRI-A as a local suppressor of actin dynamics, enabling the resolution of the macropinocytic cup. The failure of CYRI-depleted cells to resolve their macropinocytic cups results in reduced integrin a5b1 internalisation, leading to enhanced spreading, invasive behaviour and anchorage-independent 3D growth. We thus describe a new role for CYRI-A as a highly dynamic regulator of RAC1 activity at macropinosomes, modulating homeostasis of integrin surface presentation, with important functional consequences.
Surveying the vampire bat (Desmodus rotundus) serum proteome: a resource for identifying immunological proteins and detecting pathogens
Authors: Neely Benjamin A. , Janech Michael G. , Fenton M. Brock , Simmons Nancy B. , Bland Alison M. , Becker Daniel J. 
Published: December 2020

AbstractBats are increasingly studied as model systems for longevity and as natural hosts for some virulent viruses. Yet our ability to characterize immune mechanisms of viral tolerance and to quantify infection dynamics in wild bats is often limited by small sample volumes and few species-specific reagents. Here, we demonstrate how proteomics can overcome these limitations by using data-independent acquisition-based shotgun proteomics to survey the serum proteome of 17 vampire bats (Desmodus rotundus) from Belize. Using just 2 μL of sample and relatively short separations of undepleted serum digests, we identified 361 proteins across five orders of magnitude. Data are available via ProteomeXchange with identifier PXD022885. Levels of immunological proteins in vampire bat serum were then compared to human plasma via published databases. Of particular interest were anti-viral and anti-bacterial components, circulating 20S proteasome complex, and proteins involved in redox activity; whether any results are specific to vampire bats could be assessed by future pan-mammalian analyses. Lastly, we used known virus proteomes to identify Rh186 fromMacacine herpesvirus 3and ORF1a from Middle East respiratory syndrome-related coronavirus, indicating that mass spectrometry-based techniques show promise for pathogen detection. Overall, these results can be used to design targeted mass-spectrometry assays to quantify immunological markers and detect pathogens. More broadly, our findings also highlight the application of proteomics in advancing wildlife immunology and pathogen surveillance.
Tissue-Specific Regulation of Translational Readthrough Tunes Functions of the Traffic Jam Transcription Factor
Authors: Karki Prajwal , Carney Travis D. , Maracci Cristina , Yatsenko Andriy S. , Shcherbata Halyna R. , Rodnina Marina V. 
Published: December 2020

SummaryTranslational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR is pervasive in eukaryotic organisms; however, its biological significance remains unclear. In this study, we quantify the TR potential of several candidate genes inDrosophila melanogasterand characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). We used CRISPR/Cas9 generated mutant flies to show that the TR-generated Tj isoform is expressed in the nuclei of a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads, which express the short Tj isoform only. Translational control of TR is critical for preservation of neuronal integrity and maintenance of reproductive health. Fine-tuning of the gene regulatory functions of transcription factors by TR provides a new potential mechanism for cell-specific regulation of gene expression.HighlightsTj undergoes tissue-specific TR in neural cells of the central nervous system.Strict control of TR is crucial for neuroprotection and maintenance of reproductive capacity.TR selectively fine-tunes the gene regulatory functions of the transcription factor.TR in Tj links transcription and translation of tissue-specific control of gene expression.
ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation
Authors: de Reuver Richard , Dierick Evelien , Wiernicki Bartosz , Staes Katrien , Seys Leen , De Meester Ellen , Muyldermans Tuur , Botzki Alexander , Lambrecht Bart , Van Nieuwerburgh Filip , Vandenabeele Peter , Maelfait Jonathan 
Published: December 2020

SummaryLoss-of-function of ADAR1 causes the severe autoinflammatory disease Aicardi-Goutières Syndrome (AGS). ADAR1 converts adenosines into inosines within double-stranded (ds) RNA. This process called A-to-I editing masks self-dsRNA from detection by the antiviral dsRNA sensor MDA5. ADAR1 binds to dsRNA in both the canonical A-form and in the poorly defined Z-conformation (Z-RNA). Mutations in the Z-RNA binding Zα-domain of ADAR1 are common in AGS patients. How loss of ADAR1/Z-RNA interaction contributes to disease development is unknown. Using ADAR1 Zα-domain mutant human cells and knock-in mice, we demonstrate that abrogated binding of ADAR1 to Z-RNA leads to reduced A-to-I editing of dsRNA structures formed by pairing of inversely oriented SINEs. As a result, ADAR1 Zα-domain mutant human cells and transgenic mice develop a spontaneous MDA5-dependent immune response. This shows that the interaction between ADAR1 and Z-RNA restricts sensing of self-dsRNA and prevents AGS development.
Integrated transcriptional analysis of the cellular and extracellular vesicle RNA content of Candida auris in response to caspofungin
Authors: Zamith-Miranda Daniel , Amatuzzi Rafaela F. , Martins Sharon T. , Vieira Alexandre Z. , da Rocha Isadora M. , Rodrigues Marcio L. , Trentin Gabriel , Almeida Fausto , Nakayasu Ernesto S. , Nosanchuk Joshua D. , Alves Lysangela R. 
Published: December 2020

ABSTRACTCandida aurishas emerged as a serious worldwide threat by causing invasive infections in humans that are frequently resistant to one or more conventional antifungal medications, resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understandingC. aurisfungal biology and effective treatment approaches to combat this fungus. To date, there is little information aboutC. aurisgene expression regulation in response to antifungal treatment. Our integrated analyses focused on the comparative transcriptomics ofC. aurisin the presence and absence of caspofungin as well as a detailed analysis of the yeast’s extracellular vesicle (EV)-RNA composition. The results showed that genes coding oxidative stress response, ribosomal proteins, cell wall, and cell cycle were significantly upregulated in the presence of caspofungin, whereas transcriptional regulators and proteins related to the nucleus were downregulated. The mRNAs in the EVs were associated with stress responses induced by caspofungin and the ncRNA content of the EVs shifted during caspofungin treatment. Altogether, the results provide further insights into the fungal response to caspofungin and demonstrate that analyses ofC. aurisgrowth under antifungal stress can elucidate resistance and survival mechanisms of this fungus in response to medical therapy.
A First-in-class, Highly Selective and Cell-active Allosteric Inhibitor of Protein Arginine Methyltransferase 6 (PRMT6)
Authors: Shen Yudao , Li Fengling , Szewczyk Magdalena M. , Halebelian Levon , Chau Irene , Eram Mohammad S. , Seña Carlo Dela , Park Kwang-Su , Meng Fanye , Chen He , Zeng Hong , McLeod David , Zepeda-Velázquez Carlos A. , Campbell Robert M. , Mader Mary M. , Watson Brian M. , Schapira Matthieu , Arrowsmith Cheryl H. , Al-Awar Rima , Barsyte-Lovejoy Dalia , Kaniskan H. Ümit , Brown Peter J. , Vedadi Masoud , Jin Jian 
Published: December 2020

AbstractPRMT6 catalyzes monomethylation and asymmetric dimethylation of arginine residues in various proteins, plays important roles in biological processes and is associated with multiple cancers. While there are several reported PRMT6 inhibitors, a highly selective PRMT6 inhibitor has not been reported to date. Furthermore, allosteric inhibitors of protein methyltransferases are rare. Here we report the discovery and characterization of a first-in-class, highly selective allosteric inhibitor of PRMT6, SGC6870. SGC6870 is a potent PRMT6 inhibitor (IC50= 77 ± 6 nM) with outstanding selectivity for PRMT6 over a broad panel of other methyltransferases and non-epigenetic targets. Notably, the crystal structure of the PRMT6–SGC6870 complex and kinetic studies revealed SGC6870 binds a unique, induced allosteric pocket. Additionally, SGC6870 engages PRMT6 and potently inhibits its methyltransferase activity in cells. Moreover, SGC6870’s enantiomer, SGC6870N, is inactive against PRMT6 and can be utilized as a negative control. Collectively, SGC6870 is a well-characterized PRMT6 chemical probe and valuable tool for further investigating PRMT6 functions in health and disease.
The innate immunity protein C1QBP functions as a negative regulator of circulative transmission ofPotato leafroll virusby aphids
Authors: DeBlasio Stacy L. , Wilson Jennifer , Tamborindeguy Cecilia , Johnson Richard S. , Pinheiro Patricia V. , MacCoss Michael J. , Gray Stewart M. , Heck Michelle 
Published: December 2020

ABSTRACTThe vast majority of plant viruses are transmitted by insect vectors with many crucial aspects of the transmission process being mediated by key protein-protein interactions. Yet, very few vector proteins interacting with virus have been identified and functionally characterized.Potato leafroll virus(PLRV) is transmitted most effectively byMyzus persicae, the green peach aphid, in a circulative, non-propagative manner. Using an affinity purification strategy coupled to high-resolution mass spectrometry (AP-MS), we identified 11 proteins fromM. persicaedisplaying high probability of interaction with PLRV and an additional 23 vector proteins with medium confidence interaction scores. Two of these proteins were confirmed to directly interact with the structural proteins of PLRV and other luteovirid species via yeast two-hybrid with an additional vector protein displaying binding specificity. Immunolocalization of one of these direct PLRV-interacting proteins, an orthologue of the human innate immunity protein complement component 1 Q subcomponent-binding protein (C1QBP), shows that MpC1QBP partially co-localizes with PLRV within cytoplasmic puncta and along the periphery of aphid gut epithelial cells. Chemical inhibition of C1QBP in the aphid leads to increased PLRV acquisition and subsequently increased titer in inoculated plants, supporting the role of C1QBP as a negative regulator of PLRV accumulation inM. persicae. We hypothesize that the innate immune function of C1QBP is conserved in aphids and represents the first instance of aphids mounting an immune response to a non-propagative plant virus. This study presents the first use of AP-MS for thein vivoisolation of functionally relevant insect vector-virus protein complexes.
Professional competencies for librarians working in special libraries: the case of Pakistan
Authors: Khan Shakeel Ahmad , Parveen Abida 
Published: December 2020

PurposeThe purpose of this study is to identify the core competencies for librarians working in special libraries. It also measures the competencies of librarians working in special libraries of the Punjab Province against the checklist developed by the Special Library Association (SLA) Task Force. The study also identifies the training needs of librarians working in special libraries and the problems they face in acquiring SLA competencies.Design/methodology/approachA peer-reviewed questionnaire based on the list of competencies for special librarians prepared by the SLA Task Force was used to collect quantitative data from a targeted population. An online survey was administered to approach the population working in special libraries of Punjab Province. Collected data was analyzed statistically through SPSS software.FindingsA review of literature highlighted the various competencies for librarians working in special libraries (Figure 1). The findings of the study showed that the competencies identified by SLA Task Force are imperative for librarians working in special libraries of Punjab Province. The results showed that librarians working in special libraries of Punjab possessed an intermediate level of competencies identified by the SLA. However, they had a good level of basic professional and interpersonal skills. The study highlights the training needs of librarians working in special libraries to enable them in acquiring relevant competencies.Research limitations/implicationsThe study measures the competencies of librarians in special libraries of the Punjab Province. During the data collection phase, it was observed that there were some libraries where the non-professional/supporting staff was deputed, and due to this, data could not be collected from these libraries.Practical implicationsThis study has practical implications for librarians and information professionals working in special libraries to acquire the relevant competencies identified by the SLA. This study has identified various competencies areas that are essential for librarians working in special libraries.Social implicationsLibrarians working in any special library can use the results of this study as a checklist to improve their competencies level and work efficiently.Originality/valueIn contrast to other studies conducted on professional competencies of library professionals working in academic libraries, this study particularly identifies and measures the competencies of librarians working in special libraries.
In search of 21st-century high-quality health education teachers
Authors: Cardina Catherine , Panek-Shirley Leah 
Published: December 2020

PurposeTeachers with subject-area knowledge and certification in their teaching content areas positively contribute to student academic achievement. This study aims to identify the trends in academic majors and subject-area certifications of K-12 US public school staff teaching health education during this century.Design/methodology/approachData were extracted from a comprehensive nationally representative survey of school employees conducted regularly by the National Center for Educational Statistics of the US Department of Education.FindingsApproximately 60% of the health education teachers indicated they were certified in health education during the study period. Nearly two-thirds of staff teaching health education did not have an academic major in health education. These findings suggest an ongoing trend of granting teachers state certification in health education devoid of any academic major in health education. Other increasing trends include staff with an academic major in physical education and no academic major in health education teaching health classes and certified in physical education teachers who were not certified in health education teaching health classes. Overall, students in the USA were not taught health education by quality or qualified health education teachers as defined by having an academic major and certification in health education.Originality/valueThe findings are a call to action to hire health education teachers who not only have certification in health education but also an academic major in health education, which is imperative to increase healthy behaviors, reduce risk behaviors and increase academic achievement among youth.
Co-designing multidisciplinary telehealth education for online learning
Authors: Cox Jennifer L. , Seaman Claire Ellen , Hyde Sarah , Freire Katharine M. , Mansfield Jacqueline 
Published: December 2020

PurposeThere are growing expectations that students graduating from health courses and current health professionals have some proficiency in using telehealth. However, there is limited accessibility to multidisciplinary-based material to meet this need. This paper describes the development of an online telehealth education resource using a co-design approach and the strengths and challenges of embedding authentic learning principles in an open-access online course with a broad target audience.Design/methodology/approachThe authors first describe the co-design process of the course and discuss the pedagogy underpinning the course design. Then learner enrolment data is discussed to evidence uptake across key characteristics. Finally, the authors assess the efficacy of the co-design approach by analysing feedback collected from learners at the end of the course.FindingsThe course is structured across four modules and comprises interactive content, reflective tasks, case studies and purposefully developed digital material. Responses from the working group and from learner feedback indicate that the course is an authentic and relevant introduction to telehealth practice for both health students and current health professionals, despite some limitations.Originality/valueThis case study demonstrates the value of a co-design process and key learning design choices in online course development to meet the educational needs of learners from broad disciplinary backgrounds, in various stages of learning/understanding of telehealth and/or requiring a practice-based resource in the context of a rapidly changing policy environment.
Peer support in prehospital emergency: the first responders' point of view
Authors: Oliveira Ana , Teixeira Filipa , Neto Félix , Maia Ângela 
Published: December 2020

PurposeBeing a first responder involves facing a wide variety of stressful situations that could affect health and well-being. Peer support appears as a beneficial strategy to deal with work-related stress. Despite this support approach have been implemented in a variety of contexts, these interventions must to be adapted to specific needs. In this sense, the aim of this study was to explore, from a first responders' perspective, what they think about peer support and how it can be put into practiceDesign/methodology/approachThe authors interviewed in-depth 14 first responders of Portuguese Red Cross branches from the north of Portugal. Data was analyzed according to Thematic Analysis procedures.FindingsThe authors found two main themes: (1) a valuable, sustainable and ongoing support and (2) overcome barriers and rooted resistances. Participants highlighted the importance of peer support along the Red Cross path, and as daily routine. Moreover, they considered that peers should have some personal characteristics, skills and training in order to provide support to colleagues more effectively. Additionally, they made suggestions to overcome some anticipated barriers.Practical implicationsBy considering mental health and well-being of workers, a priority and by being developed based on international recommendations and professionals testimonies, peer support appears as a valuable tool possible to be implemented and able to tailor the emergency branches' needs.Originality/valueThis is the first qualitative study about the first responder's perceptions of peer support.
The assessment of collaboration quality: a case of sugar supply chain in Indonesia
Authors: Dania Wike Agustin Prima , Xing Ke , Amer Yousef 
Published: December 2020

PurposeThis paper aims to evaluate the collaboration quality performance of sugar company Z and its stakeholders (farmers and distributors) by considering the sustainability aspects. This assessment shall be able to integrate qualitative and quantitative factors in the model, which is critical in sugar supply chains involving multi-stakeholders.Design/methodology/approachIntegration of quality function deployment (QFD), the fuzzy analytical network process (FANP) and the data envelopment analysis (DEA) is administered to assess the efficiency score of each stakeholder involved. The evaluation encompasses collaboration behaviour factors since the input of collaboration activities will result in sustainability aspects such as revenue, green house gas (GHG) emissions and social impact. The analysis has been conducted in two scenarios, those are the basic scenario by utilising original data and the extended scenario by using projection data.FindingsThe result clarifies that the most influential behaviour factor in the collaboration activities is commitment (0.116), while the least important behaviour factors are power (0.008) and adaptation (0.008). Furthermore, by using the extended scenario, the overall efficiency for each benchmarking is higher compared to the condition before the improvement (basic scenario).Research limitations/implicationsThe result of this study is only relevant to the particular sugar supply chain and involving limited sustainability variables. Therefore, in a further study, more variables such as technical and financial aspects could be explored further in the assessment process.Practical implicationsThe result of this study is available for each stakeholder and can be fundamental for the constant improvement in sustainable supply chain (SSC) practices. It shows that an improvement of one stakeholder will positively impact the entire system.Social implicationsSmallholders and sugarcane farmers will recognise the significance of collaboration behaviour. Thus, they can enhance their mutual benefits by using the existing resources.Originality/valueThis paper arranges for a practical contribution by implementing advanced assessment methods in the sugar supply chain by taking into account the economic, environmental and social aspects. This comprehensive assessment process in the sugar supply chain is the novelty of this paper.
COVID-19 and performance: beyond a social construction
Authors: Mai Kate Thuy 
Published: December 2020

Purpose
The purpose of this essay is to reflect on my personal experience on my teaching performance during the COVID-19 pandemic and to share my investigation into the nature of performance phenomenon.

Design/methodology/approach
I reflected on my personal experience and thoughts about the phenomenon of performance.

Findings
My reflection points to an understanding that performance is a social-natural phenomenon, which can only be enabled and directed but cannot be controlled.

Originality/value
I shared some implications for understanding the nature of performance and performance management from an integrated worldview of physics, biology, psychology and neuroscience.