bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covid-19 in Chile. The experience of a Regional reference Center. Preliminary report
Authors: Olivares Felipe , Muñoz Daniel , Fica Alberto , Delama Ignacio , Alvarez Ignacia , Navarrete Maritza , Blackburn Eileen , Garrido Pamela , Grandjean Juan 
Published: June 2020

AbstractDuring the first pandemic wave Covid-19 reached Latin America cities.AimTo report clinical features and outcomes associated to Covid-19 in a group of patients admitted during the first wave in a regional reference Center in southern Chile designated to severe and critical cases.MethodsCases were identified by a compatible clinical picture associated to positive RT-PCR or serological testing. A standard protocol was applied.Results21 adult patients (20 diagnosed by PCR, one by serology) were admitted between epidemiological weeks 13 to 20, involving 8.8% of total regional cases. Hospitalization occurred at a median of 11 days after symptoms onset. Patients ≥60 years old predominated (57.1%). Hypertension (61.9%), obesity (57.1%) and diabetes mellitus 2 (38.1%) were prevalent but 19% had no comorbid conditions nor were elderly. Two cases involved second-trimester pregnant women. Positive IgM or IgM/IgG results obtained by rapid serological testing were limited (19% at 1st week; 42.9% at 2nd week). Nine patients (42.9%, critical group) were transferred to ICU and connected to mechanical ventilation due to respiratory failure. By univariate analysis admission to ICU was significantly associated to tachypnea and higher plasmatic LDH values. One pregnant woman required urgent cesarean section given birth to a premature neonate without vertical transmission. Two patients died (in-hospital mortality 9.5%) and length of stay was ≥ 14 days in 57.9% of patients.ConclusionIn our regional Center, Covid 19 was associated to known risk factors, had a prolonged stay and in-hospital mortality. Tachypnea ≥30/min is predictive of transfer to ICU.
Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera
Authors: Pape Constantin , Remme Roman , Wolny Adrian , Olberg Sylvia , Wolf Steffen , Cerrone Lorenzo , Cortese Mirko , Klaus Severina , Lucic Bojana , Ullrich Stephanie , Anders-Össwein Maria , Wolf Stefanie , Cerikan Berati , Neufeldt Christopher J. , Ganter Markus , Schnitzler Paul , Merle Uta , Lusic Marina , Boulant Steeve , Stanifer Megan , Bartenschlager Ralf , Hamprecht Fred A. , Kreshuk Anna , Tischer Christian , Kräusslich Hans-Georg , Müller Barbara , Laketa Vibor 
Published: June 2020

AbstractEmergence of the novel pathogenic coronavirus SARS-CoV-2 and its rapid pandemic spread presents numerous questions and challenges that demand immediate attention. Among these is the urgent need for a better understanding of humoral immune response against the virus as a basis for developing public health strategies to control viral spread. For this, sensitive, specific and quantitative serological assays are required. Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in specific, sensitive and unbiased assay which complements the portfolio of SARS-CoV-2 serological assays. The procedure described here has been used for clinical studies and provides a general framework for the application of quantitative high-throughput microscopy to rapidly develop serological assays for emerging virus infections.
Metabolic but not transcriptional regulation by PKM2 is important for Natural Killer cell responses
Authors: Walls Jessica F. , Subleski Jeff J. , Palmieri Erika M. , Cotto Marieli Gonzalez , Gardiner Clair M. , McVicar Daniel W. , Finlay David K. 
Published: June 2020

AbstractNatural Killer (NK) cells have an important role in immune responses to viruses and tumours. Integrating changes in signal transduction pathways and cellular metabolism is essential for effective NK cells responses. The PKM2 isoform of the glycolytic enzyme Pyruvate Kinase Muscle has described roles in regulating glycolytic flux and signal transduction, especially gene transcription. While PKM2 expression is robustly induced in activated NK cells, mice lacking PKM2 in NK cells showed no defect in NK cell metabolism or anti-viral responses to MCMV infection. This maintenance of function is explained by compensatory PKM1 expression in PKM2-null NK cell cells demonstrating that PKM2 is not a signalling molecule in this immune cell type. To further investigate the role of PKM2 we forced the tetramerization of the protein with TEPP-46, which increases its catalytic activity while inhibiting any signalling functions mediated by mono/dimeric conformations. NK cells activated with TEPP-46 had reduced effector function due to TEPP-46-induced increases in oxidative stress. Overall, PKM2-regulated glycolytic metabolism and redox status, not transcriptional control, facilitate optimal NK cells responses.
Interfacial Water Molecules Make RBD of SPIKE Protein and Human ACE2 to Stick Together
Authors: Malik Ashish , Prahlad Dwarakanath , Kulkarni Naveen , Kayal Abhijit 
Published: June 2020

AbstractA novel coronavirus (SARS-CoV-2; COVID-19) that initially originates from Wuhan province in China has emerged as a global pandemic, an outbreak that started at the end of 2019 which claims 431,192 (Date: 15th June 2020 (https://covid19.who.in) life till now. Since then scientists all over the world are engaged in developing new vaccines, antibodies, or drug molecules to combat this new threat. Here in this work, we performed an in-silico analysis on the protein-protein interactions between the receptor-binding (RBD) domain of viral SPIKE protein and human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between these two viruses by using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations show SARS-CoV-2 binds little more firmly to the hACE2 receptor than that of SARS-CoV. Analysis of simulation trajectories reveals that enhanced hydrophobic contacts or the van der Waals interaction play a major role in stabilizing the protein-protein interface. The major finding obtained from molecular dynamics simulations is that the RBD-ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. We also emphasize that the interfacial water molecules play a critical role in binding and maintaining the stability of the RBD/hACE2 complex. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.
piRNAs prevent runaway amplification of siRNAs from ribosomal RNAs and histone mRNAs
Authors: Montgomery Brooke E. , Vijayasarathy Tarah , Marks Taylor N. , Reed Kailee J. , Montgomery Taiowa A. 
Published: June 2020

ABSTRACTPiwi-interacting RNAs (piRNAs) are a largely germline-specific class of small RNAs found in animals. Although piRNAs are best known for silencing transposons, they regulate many different biological processes. Here we identify a role for piRNAs in preventing runaway amplification of small interfering RNAs (siRNAs) from certain genes, including ribosomal RNAs (rRNAs) and histone mRNAs. InCaenorhabditis elegans, rRNAs and some histone mRNAs are heavily targeted by piRNAs, which facilitates their entry into an endogenous RNA interference (RNAi) pathway involving a class of siRNAs called 22G-RNAs. Under normal conditions, rRNAs and histone mRNAs produce relatively low levels of 22G-RNAs. But if piRNAs are lost, 22G-RNA production is highly elevated. We show that 22G-RNAs produced downstream of piRNAs likely function in a feed-forward amplification circuit. Thus, our results suggest that piRNAs facilitate low-level 22G-RNA production while simultaneously obstructing the 22G-RNA machinery to prevent runaway amplification from certain RNAs. Histone mRNAs and rRNAs are unique from other cellular RNAs in lacking polyA tails, which may promote feed-forward amplification of 22G-RNAs. In support of this, we show that the subset of histone mRNAs that contain polyA tails are largely resistant to silencing in piRNA mutants.
Dissecting Autism Genetic Risk Using Single-cell RNA-seq Data
Authors: Chen Siying , Zhou Xueya , Byington Eve , Bruce Samuel L. , Zhang Haicang , Shen Yufeng 
Published: June 2020

AbstractAutism spectrum disorder (autism) is a condition with strong but heterogenous genetic contribution. Recent exome and genome sequencing studies have uncovered many new risk genes throughde novovariants. However, a large fraction of enrichment ofde novovariants observed in cases are not accounted for by known or candidate risk genes, suggesting that the majority of risk genes are still unknown. Here we hypothesize that autism risk genes share a few common cell-type specific gene expression patterns during brain development, and such information can be quantified to improve statistical power of detecting new risk genes. We obtained large-scale single-cell RNA-seq data from human fetal brain collected through a range of developmental stages, and developed a supervised machine-learning approach “A-risk” (Autism risk), to predict the plausibility of autism risk genes across the genome. Using data from recent exome sequencing studies of autism, A-risk achieves better performance in prioritizingde novovariants than other methods, especially for genes that are less intolerant of loss of function variants. We stratified genes based on A-risk and mutation intolerance metrics to improve estimation of priors in extTADA and identified 71 candidate risk genes. In particular,CLCN4, PRKAR1B, and NR2F1are potentially new risk genes with further support from neurodevelopmental disorders. Expression patterns of both known and candidate risk genes reveals the important role of deep-layer excitatory neurons from adult human cortex in autism etiology. With the unprecedented revolution of single-cell transcriptomics and expanding autism cohorts with exome or genome sequencing, our method will facilitate systematic discovery of novel risk genes and understanding of biological pathogenesis in autism.
A molecular lid mechanism of K+channel blocker action revealed by a cone peptide
Authors: Saikia Chandamita , Dym Orly , Altman-Gueta Hagit , Gordon Dalia , Reuveny Eitan , Karbat Izhar 
Published: June 2020

AbstractMany venomous organisms carry in their arsenal short polypeptides that block K+channels in a highly selective manner. These toxins may compete with the permeating ions directly via a “plug” mechanism or indirectly via a “pore-collapse” mechanism. An alternative “lid” mechanism was proposed but remained poorly defined. Here we study the block of the Drosophila Shaker channel by Conknunitzin-S1 and Conkunitzin-C3, two highly similar toxins derived from cone venom. Despite their similarity, the two peptides exhibited differences in their binding poses and in biophysical assays, implying discrete modes of action. We show that while Conknunitzin-S1 binds tightly to the channel turret and acts via a “pore-collapse” mechanism, Conkunitzin-C3 does not contact this region. Instead, Conk-C3 uses a non-conserved Arg to divert the permeant ions and trap them in off-axis cryptic sites above the SF, a mechanism we term a “molecular-lid”. Our study provides an atomic description of the “lid” K+blocking mode and offers valuable insights for the design of therapeutics based on venom peptides.
The ribbon-helix-helix domain proteins CdrS and CdrL regulate cell division in archaea
Authors: Darnell Cynthia L. , Zheng Jenny , Wilson Sean , Bertoli Ryan M. , Bisson-Filho Alexandre W. , Garner Ethan C. , Schmid Amy K. 
Published: June 2020

AbstractPrecise control of the cell cycle is central to the physiology of all cells. In prior work we demonstrated that archaeal cells maintain a constant size; however, the regulatory mechanisms underlying the cell cycle remain unexplored in this domain of life. Here we use genetics, functional genomics, and quantitative imaging to identify and characterize the novel CdrSL gene regulatory network in a model species of archaea. We demonstrate the central role of these ribbon-helix-helix family transcription factors in the regulation of cell division through specific transcriptional control of the gene encoding FtsZ2, a putative tubulin homolog. Using time lapse fluorescence microscopy in live cells cultivated in microfluidics devices, we further demonstrate that FtsZ2 is required for cell division but not elongation. The cdrS-ftsZ2 locus is highly conserved throughout the archaeal domain, and the central function of CdrS in regulating cell division is conserved across hypersaline adapted archaea. We propose that the CdrSL-FtsZ2 transcriptional network coordinates cell division timing with cell growth in archaea.ImportanceHealthy cell growth and division are critical for individual organism survival and species long-term viability. However, it remains unknown how cells of the domain Archaea maintain a healthy cell cycle. Understanding archaeal cell cycle is of paramount evolutionary importance given that an archaeal cell was the host of the endosymbiotic event that gave rise to eukaryotes. Here we identify and characterize novel molecular players needed for regulating cell division in archaea. These molecules dictate the timing of cell septation, but are dispensable for growth between divisions. Timing is accomplished through transcriptional control of the cell division ring. Our results shed light on mechanisms underlying the archaeal cell cycle, which has thus far remained elusive.
Arabidopsis mTERF9 protein promotes chloroplast ribosomal assembly and translation by establishing ribonucleoprotein interactionsin vivo
Authors: Méteignier Louis-Valentin , Ghandour Rabea , Zimmerman Aude , Kuhn Lauriane , Meurer Jörg , Zoschke Reimo , Hammani Kamel 
Published: June 2020

ABSTRACTThe mitochondrial transcription termination factor proteins are nuclear-encoded nucleic acid binders defined by degenerate tandem helical-repeats of ~30 amino acids. They are found in metazoans and plants where they localize to mitochondria or chloroplasts. In higher plants, the mTERF family comprises ~30 members and several of these have been linked to plant development and response to abiotic stress. However, knowledge of the molecular basis underlying these physiological effects is scarce. We show that the Arabidopsis mTERF9 protein promotes the accumulation of the16Sand23SrRNAs in chloroplasts, and interacts predominantly with the16SrRNAin vivoandin vitro. Furthermore, mTERF9 is found in large complexes containing ribosomes and polysomes in chloroplasts. The comprehensive analysis of mTERF9in vivoprotein interactome identified many subunits of the 70S ribosome whose assembly is compromised in the nullmterf9mutant, putative ribosome biogenesis factors and CPN60 chaperonins. Protein interaction assays in yeast revealed that mTERF9 directly interact with these proteins. Our data demonstrate that mTERF9 integrates protein-protein and protein-RNA interactions to promote chloroplast ribosomal assembly and translation. Besides extending our knowledge of mTERF functional repertoire in plants, these findings provide an important insight into the chloroplast ribosome biogenesis.
The role of HRM in the innovation of performance measurement and management systems: a multiple case study in SMEs
Authors: Sardi Alberto , Sorano Enrico , Garengo Patrizia , Ferraris Alberto 
Published: June 2020

PurposeLiterature identifies the key relevance of human resource management (HRM) in the creation of an organisational performance measurement and management system, while, in practice, small and medium-sized enterprises (SMEs) continue to prioritise financial and operational aspects. This study aims to identify the main characteristics that typify an advanced performance measurement and management system in SMEs, according to the literature dedicated to performance measurement and HRM.Design/methodology/approachThrough a multiple-case study methodology, the research deeply investigates four European SMEs. Empirical data were collected through interviews, company documents and direct observations. Then, within- and cross-case analysis were implemented to analyse the data.FindingsIn designing organisational performance measurement and management systems in SMEs, HRM emerges as essential in supporting the enhancement of the maturity of performance measurement and the improvement of performance management. Through a framework based on the relevant literature, this research identifies three conceptual propositions that highlight the main characteristics that typify advanced performance measurement and management systems in SMEs.Research limitations/implicationsThe research identifies a conceptual framework suitable to investigate empirically the role of HRM in developing performance measurement and management systems at SMEs, and it lays the foundation for future broader empirical studies in this field.Originality/valueThis paper underlines HRM as an important driver in the creation of organisational performance measurement and management systems. Moreover, it suggests some key characteristics that such a system should develop to be effective in the target enterprises.
Overcoming the challenge of “fuzzy” assessment and feedback
Authors: Boyle Brendan , Mitchell Rebecca , McDonnell Anthony , Sharma Narender , Biswas Kumar , Nicholas Stephen 
Published: June 2020

PurposeThis paper explores the challenge of “fuzzy” assessment criteria and feedback with a view to aiding student learning. The paper untangles three guiding principles as mechanisms to enhance the effectiveness of assessment and feedback through overcoming the inherent challenges which stem from tacit judgement during assessment.Design/methodology/approachThe paper applies a realistic evaluation methodology, with a framework for assessment and feedback consisting of three principles – Means, Opportunity and Motivation (MOM). Through in-depth interviews with undergraduate and postgraduate management students the paper identifies how and when the means, opportunity and motivation principles impact student learning through assessment and the utility of the feedback received on their learning.FindingsThe findings in the paper illustrate that students do not always understand the feedback they receive on their learning because they do not fully understand the criteria to which it refers due to the tacit dimensions of assessment. The findings substantiate the proposition that effective assessment processes must ensure that students have the means, opportunity and motivation to use feedback and to understand the criteria, a central component of which is understanding tacit dimensions of assessment.Practical implicationsThe paper deciphers three practical implications for instructors related to (1) teaching, (2) course and program design and (3) the nature of the feedback instructors should provide.Originality/valueWhile prior scholarship has flagged the challenge of “fuzzy” assessment and feedback, this paper identifies when and how the means, opportunity and motivation principles are manifested in the process of making the tacit components of assessment codified and actionable, a critical process in developing expert learners.
Passion meets procrastination: comparative study of negative sales associate behaviours
Authors: Jones Robert Paul 
Published: June 2020

PurposeThis study explores procrastination, a negative work behaviour, and its unlikely source, job passion. A dualistic conceptualization of job passion is explored in retail sales associate samples from the United States and China. The study tests relationships between harmonious job passion (HJP) and obsessive job passion (OJP) and the contingent effects of job satisfaction and salary level on their relationship to procrastination.Design/methodology/approachData came from an online survey issued in the United States and China. The hypotheses were tested using hierarchical linear regression.FindingsThe analyses provide mixed findings. HJP is negatively associated with procrastination in both countries, while OJP's positive relationship is mixed. A post-hoc analysis testing the three-way interaction effect of OJP, job satisfaction and salary level on procrastination reveals a positive relationship to OJP in both countries.Research limitations/implicationsThe study demonstrates that job passion can have both positive (HJP) and negative (OJP) work behaviour outcomes.Practical implicationsBrick-and-mortar retailers facing a saturated and highly competitive environment need HJP employees to drive superior customer service. This study demonstrates that employees with OJP may engage in negative behaviours which could further impair retail performance. Expanding empowerment and flexibility may heighten HJP and minimize OJP.Originality/valueThis study explores the dualistic conceptualization of job passion in a retail environment using cross-cultural samples.
Incoming and outgoing academic mobility in Russia and abroad: main trends, administrative challenges
Authors: Rostovskaya Tamara K. , Skorobogatova Vera I. , Pismennaya Elena E. , Bezverbny Vadim A. 
Published: June 2020

PurposeThe goal of research consists in identifying trends in academic mobility in Russia and abroad, primarily that of academic staff; contributing suggestions on improving the management of academic mobility processes.Design/methodology/approachThe research uses methods of observation, comparative analysis, as well as statistical method and generalization method supported by the facts. A comparative analysis of statistical data is made; these data were taken from the publicly available reliable sources of the Organization for Economic Cooperation and Development, Human Resource Development Department of the Asia–Pacific and others.FindingsIt was found that the level of academic mobility rises with the rising level of education. The overall mobility of tertiary students – in particular, students and postgraduate students, is growing throughout the world. Mobile postgraduate students demonstrate better research results during training. Even short-term academic internships for postgraduate students contribute to the successful implementation of research projects at their host university and the spread of new knowledge in general. In general, academic mobility contributes to the accumulation of human and cultural scientific capital that makes a connection between research communities in different countries. Based on the research findings, it was found that no statistics are collected on the foreign academic mobility of postgraduate students and young researchers in Russia. Based on the analysis, it may be deduced that the scope of academic mobility is extremely small. European countries are the main countries of prevailing academic mobility.Originality/valueGiven the importance of participation in foreign academic mobility for the development of the competitiveness of national science in Russia, it appears that there is a need to monitor the foreign academic mobility of Russian postgraduate students and young researchers. The monitoring of foreign academic mobility of Russian postgraduate students and young researchers is a systematic observation of the status and conditions of training highly qualified personnel in Russian educational establishments and scientific organizations, providing educational authorities of Russia with up-to-date information on the status of outgoing academic mobility necessary for analyzing and forecasting the development of the national education system and national labor market.