bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and evaluation of a loop-mediated isothermal amplification (LAMP) assay for the detection ofTomato brown rugose fruit virus(ToBRFV)
Authors: Sarkes Alian , Fu Heting , Feindel David , Harding Michael W. , Feng Jie 
Published: March 2020

AbstractTomato brown rugose fruit virus(ToBRFV) is a member ofTobamovirusinfecting tomato and pepper. Within North America, both the United States and Mexico consider ToBRFV to be a regulated pest. In Canada, the presence of ToBRFV has been reported, but an efficient diagnostic system has not yet been established. Here, we describe the development and assessment of a loop-mediated isothermal amplification (LAMP)-based assay to detect ToBRFV. The LAMP test was efficient and robust, and results could be obtained within 35 min with an available RNA sample. Amplification was possible when either water bath or oven were used to maintain the temperature at isothermal conditions (65°C), and results could be read by visual observation of colour change. Detection limit of the LAMP was eight target RNA molecules. Under the experimental conditions tested, LAMP was as sensitive as qPCR and 100 times more sensitive than the currently used rt-PCR. We recommend this sensitive, efficient LAMP protocol to be used for routine lab testing of ToBRFV.
Stress-induced tyrosine phosphorylation of RtcB modulates IRE1 activity and signaling outputs
Authors: Papaioannou Alexandra , Centonze Federica , Metais Alice , Maurel Marion , Negroni Luc , González-Quiroz Matías , Mahdizadeh Sayyed Jalil , Svensson Gabriella , Golchesmeh Ensieh Zare , Blondel Alice , Koong Albert C , Hetz Claudio , Pedeux Rémy , Tremblay Michel L. , Eriksson Leif A. , Chevet Eric 
Published: March 2020

AbstractEndoplasmic Reticulum (ER) stress is a hallmark of various diseases, which is dealt with through the activation of an adaptive signaling pathway named the Unfolded Protein Response (UPR). This response is mediated by three ER-resident sensors and the most evolutionary conserved, IRE1α signals through its cytosolic kinase and endoribonuclease (RNase) activities. IRE1α RNase activity can either catalyze the initial step of XBP1 mRNA unconventional splicing or degrade a number of RNAs through Regulated IRE1- Dependent Decay (RIDD). The balance between these two activities plays an instrumental role in cells’ life and death decisions upon ER stress. Until now, the biochemical and biological outputs of IRE1α RNase activity have been well documented, however, the precise mechanisms controlling whether IRE1 signaling is adaptive or pro-death (terminal) remain unclear. This prompted us to further investigate those mechanisms and we hypothesized that XBP1 mRNA splicing and RIDD activity could be co-regulated by the IRE1α RNase regulatory network. We showed that a key nexus in this pathway is the tRNA ligase RtcB which, together with IRE1α, is responsible for XBP1 mRNA splicing. We demonstrated that RtcB is tyrosine phosphorylated by c-Abl and dephosphorylated by PTP1B. Moreover, we identified RtcB Y306 as a key residue which, when phosphorylated, perturbs RtcB interaction with IRE1α, thereby attenuating XBP1 mRNA splicing and favoring RIDD. Our results demonstrate that the IRE1α RNase regulatory network is dynamically fine-tuned by tyrosine kinases and phosphatases upon various stresses and that the nature of the stress determines cell adaptive or death outputs.
Structural and functional characterization of the Severe fever with thrombocytopenia syndrome virus L protein
Authors: Vogel Dominik , Thorkelsson Sigurdur Rafn , Quemin Emmanuelle R. J. , Meier Kristina , Kouba Tomas , Gogrefe Nadja , Busch Carola , Reindl Sophia , Günther Stephan , Cusack Stephen , Grünewald Kay , Rosenthal Maria 
Published: March 2020

ABSTRACTTheBunyaviralesorder contains several emerging viruses with high epidemic potential, including Severe fever with thrombocytopenia syndrome virus (SFTSV). The lack of medical countermeasures, such as vaccines and antivirals, is a limiting factor for the containment of any virus outbreak. To develop such antivirals a profound understanding of the viral replication process is essential. The L protein of bunyaviruses is a multi-functional and multi-domain protein performing both virus transcription and genome replication and, therefore, would be an ideal drug target. We established expression and purification procedures for the full-length L protein of SFTSV. By combining single-particle electron-cryo microscopy and X-ray crystallography, we obtained 3D models covering ∼70% of the SFTSV L protein in the apo-conformation including the polymerase core region, the endonuclease and the cap-binding domain. We compared this first L structure of thePhenuiviridaefamily to the structures of La Crosse peribunyavirus L protein and influenza orthomyxovirus polymerase. Together with a comprehensive biochemical characterization of the distinct functions of SFTSV L protein, this work provides a solid framework for future structural and functional studies of L protein-RNA interactions and the development of antiviral strategies against this group of emerging human pathogens.
Exifone is a Potent HDAC1 Activator with Neuroprotective Activity in Human Neuronal Models of Neurodegeneration
Authors: Patnaik Debasis , Pao Ping-Chieh , Zhao Wen-Ning , Silva M. Catarina , Hylton Norma K. , Chindavong Peter S. , Pan Ling , Tsai Li-Huei , Haggarty Stephen J. 
Published: March 2020

AbstractGenomic instability caused by a deficiency in the DNA damage response and repair has been linked to age-related cognitive decline and neurodegenerative diseases. Preventing genomic instability that ultimately leads to neuronal death may provide a broadly effective strategy to protect against multiple potential genotoxic stressors. Recently, the zinc-dependent, class I histone deacetylase HDAC1 has been identified as a critical factor for protecting neurons from deleterious effects of DNA damage in Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Translating these observations to a novel neuroprotective therapy for AD, ALS, and FTD may be advanced by the identification of small molecules capable of increasing the deacetylase activity of HDAC1 selectively over other structurally similar HDACs. Here, we demonstrate that exifone, a drug previously shown to be effective in treating cognitive deficits associated with AD and Parkinson’s disease, the molecular mechanism of which has remained poorly understood, potently activates the deacetylase activity of HDAC1 and provides protection against genotoxic stress. We show that exifone acts as a mixed, non-essential activator of HDAC1 that is capable of binding to both free and substrate-bound enzyme resulting in an increased relative maximal rate of HDAC1-catalyzed deacetylation. Exifone can directly bind to HDAC1 based upon biolayer interferometry assays with kinetic and selectivity profiling suggesting HDAC1 is preferentially targeted compared to other class I HDACs and the kinase CDK5 that have also been implicated in neurodegeneration. Consistent with a mechanism of deacetylase activation intracellularly, treatment of human induced pluripotent stem cell (iPSC)-derived neuronal cells resulted in globally decreased histone acetylation. Moreover, exifone treatment was neuroprotective in a tauopathy patient iPSC-derived neuronal model subject to oxidative stress. Taken together, these findings reveal exifone as a potent activator of HDAC1-mediated deacetylation, thereby offering a lead for novel therapeutic development aiming to protect genomic integrity in the context of neurodegeneration and aging.Graphical Abstract
Characterization of interstitial heterogeneity in the developing kidney
Authors: England Alicia R. , Chaney Christopher P. , Das Amrita , Patel Mohita , Malewsak Alicia , Armendariz Daniel , Hon Gary , Strand Douglas , Drake Keri , Carroll Thomas J. 
Published: March 2020

ABSTRACTKidney formation requires the coordinated growth of multiple cell types including the collecting ducts, nephrons, vasculature and interstitium. There has been a long-held belief that interactions between the progenitors of the collecting ducts and nephrons are primarily responsible for development of this organ. However, over the last several years, it has become increasingly clear that multiple aspects of kidney development require signaling from the interstitium. How the interstitium orchestrates these various roles is still poorly understood. We show that during development, the interstitium is a highly heterogeneous, patterned population of cells that occupies distinct positions correlated to the adjacent parenchyma. Our analysis indicates that the heterogeneity is not a mere reflection of different stages in a linear developmental trajectory but instead represents several novel differentiated cell states. Further, we find that beta-catenin has a cell autonomous role in the development of a medullary subset of the interstitium and that this non-autonomously affects the development of the adjacent epithelia. These findings suggest the intriguing possibility that the different interstitial subtypes may create microenvironments that play unique roles in development of the adjacent epithelia and endothelia.Graphical AbstractThe developing interstitium is a highly heterogeneous, patterned population of cells that occupies distinct positions correlated to the adjacent parenchyma.
Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2)
Authors: Feng Ye , Qiu Min , Liu Liang , Zou Shengmei , Li Yun , Luo Kai , Guo Qianpeng , Han Ning , Sun Yingqiang , Wang Kui , Zhuang Xinlei , Zhang Shanshan , Chen Shuqing , Mo Fan 
Published: March 2020

AbstractA new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides.ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.
Endothelial cell response to Hedgehog ligands depends on their processing
Authors: Hollier Pierre-Louis , Chapouly Candice , Diop Aissata , Guimbal Sarah , Cornuault Lauriane , Gadeau Alain-Pierre , Renault Marie-Ange 
Published: March 2020

AbstractRationaleThe therapeutic potential of Hedgehog (Hh) signaling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signaling in vascular biology remain poorly understood.ObjectiveThe purpose of the present paper is to clarify some conflicting literature data.FindingsWith this goal we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hedgehog (N-Shh) and endogenous endothelial-derived Desert Hedgehog (Dhh) induce opposite effects in endothelial cells. (ECs). Notably, endothelial Dhh acts under its full-length soluble form (FL-Dhh) and activates Smoothened in ECs, while N-Shh inhibits it. At molecular level, N-Shh prevents FL-Dhh binding to Patched-1 demonstrating that N-Shh acts as competitive antagonist to FL-Dhh. Besides, we found that even though FL-Hh ligands and N-Hh ligands all bind Patched-1, they induce specific Patched-1 localization. Finally, we confirmed that in a pathophysiological setting i.e. brain inflammation, astrocyte-derived N-Shh act as a FL-Dhh antagonist.ConclusionThe present study highlights for the first time that FL-Dhh and N-Hh ligands have antagonistic properties especially in ECs, and demonstrates that Hh ligands or forms of Hh ligands cannot be used instead of another for therapeutic purposes.
Mechanical properties of near alpha titanium alloys for high-temperature applications - a review
Authors: Tabie Vitus Mwinteribo , Li Chong , Saifu Wang , Li Jianwei , Xu Xiaojing 
Published: March 2020

PurposeThis paper aims to present a broad review of near-a titanium alloys for high-temperature applications.Design/methodology/approachFollowing a brief introduction of titanium (Ti) alloys, this paper considers the near-α group of Ti alloys, which are the most popular high-temperature Ti alloys developed for a high-temperature application, particularly in compressor disc and blades in aero-engines. The paper is relied on literature within the past decade to discuss phase stability and microstructural effect of alloying elements, plastic deformation and reinforcements used in the development of these alloys.FindingsThe near-a Ti alloys show high potential for high-temperature applications, and many researchers have explored the incorporation of TiC, TiB SiC, Y2O3, La2O3and Al2O3reinforcements for improved mechanical properties. Rolling, extrusion, forging and some severe plastic deformation (SPD) techniques, as well as heat treatment methods, have also been explored extensively. There is, however, a paucity of information on SiC, Y2O3and carbon nanotube reinforcements and their combinations for improved mechanical properties. Information on some SPD techniques such as cyclic extrusion compression, multiaxial compression/forging and repeated corrugation and straightening for this class of alloys is also limited.Originality/valueThis paper provides a topical, technical insight into developments in near-a Ti alloys using literature from within the past decade. It also outlines the future developments of this class of Ti alloys.
A cooperative crowdsourcing framework for knowledge extraction in digital humanities – cases on Tang poetry
Authors: Hong Liang , Hou Wenjun , Wu Zonghui , Han Huijie 
Published: March 2020

PurposeThe purpose of this paper is to propose a knowledge extraction framework to extract knowledge, including entities and relationships between them, from unstructured texts in digital humanities (DH).Design/methodology/approachThe proposed cooperative crowdsourcing framework (CCF) uses both human–computer cooperation and crowdsourcing to achieve high-quality and scalable knowledge extraction. CCF integrates active learning with a novel category-based crowdsourcing mechanism to facilitate domain experts labeling and verifying extracted knowledge.FindingsThe case study shows that CCF can effectively and efficiently extract knowledge from multi-sourced heterogeneous data in the field of Tang poetry. Specifically, CCF achieves higher accuracy of knowledge extraction than the state-of-the-art methods, the contribution of feedbacks to the training model can be maximized by the active learning mechanism and the proposed category-based crowdsourcing mechanism can scale up the effective human–computer collaboration by considering the specialization of workers in different categories of tasks.Research limitations/implicationsThis research proposes CCF to enable high-quality and scalable knowledge extraction in the field of Tang poetry. CCF can be generalized to other fields of DH by introducing domain knowledge and experts.Practical implicationsThe extracted knowledge is machine-understandable and can support the research of Tang poetry and knowledge-driven intelligent applications in DH.Originality/valueCCF is the first human-in-the-loop knowledge extraction framework that integrates active learning and crowdsourcing mechanisms; he human–computer cooperation method uses the feedback of domain experts through the active learning mechanism; the category-based crowdsourcing mechanism considers the matching of categories of DH data and especially of domain experts.
Blood flow of MHD non-Newtonian nanofluid with heat transfer and slip effects
Authors: Elelamy Asmaa F. , Elgazery Nasser S. , Ellahi R. 
Published: March 2020

Purpose
This paper aims to investigate a mathematical model with numerical simulation for bacterial growth in the heart valve.

Design/methodology/approach
For antibacterial activities and antibodies properties, nanoparticles have been used. As antibiotics are commonly thought to be homogeneously dispersed through the blood, therefore, non-Newtonian fluid of Casson micropolar blood flow in the heart valve for two dimensional with variable properties is used. The heat transfer with induced magnetic field translational attraction under the influence of slip is considered for the resemblance of the heart valve prosthesis. The numeral results have been obtained by using the Chebyshev pseudospectral method.

Findings
It is proven that vascular resistance decreases for increasing blood velocity. It is noted that when the magnetic field will be induced from the heart valve prosthesis then it may cause a decrease in vascular resistance. The unbounded molecules and antibiotic concentration that are able to penetrate the bacteria are increased by increasing values of vascular resistance. The bacterial growth density cultivates for upswing values of magnetic permeability and magnetic parameters.

Originality/value
To the best of the authors’ knowledge, this is the first study to investigate a mathematical model with numerical simulation for bacterial growth in the heart valve.
The association of analysts’ cash flow forecasts with stock recommendation profitability
Authors: Pan Shanshan , Xu Zhaohui Randall 
Published: March 2020

Purpose
The purpose of this paper is to examine whether analysts’ cash flow forecasts improve the profitability of their stock recommendations and whether the positive effect of cash flow forecasts on analysts’ stock recommendation performance varies with firms’ earnings quality.

Design/methodology/approach
To test the authors’ predictions, they identify a sample of 161,673 stock recommendations with contemporaneous earnings forecasts and/or cash flow forecasts and regress market-adjusted stock returns on a binary variable that proxies for the issuance of cash flow forecasts while controlling for contemporaneous earnings forecast accuracy, earnings quality, analysts’ forecast experience and capability and certain firm characteristics. The authors’ test results are robust to alternative measures of recommendation profitability, earnings quality and the use of recommendation revisions instead of recommendation levels.

Findings
The authors find that when analysts issue cash flow forecasts concurrently with earnings forecasts, their stock recommendations lead to higher profitability than when they only issue earnings forecasts, after controlling for analysts’ forecast capability. Moreover, the authors document that the contemporaneous positive relationship between cash flow forecasts and recommendations profitability is stronger for firms with low earnings quality than for firms with high earnings quality. The findings suggest that cash flow forecasts issued by analysts in response to market demand likely play a more important role in firm valuation than cash flow forecasts issued by analysts mainly because of supply-side considerations.

Research limitations/implications
Future research could build on these findings to conduct further investigation on the alternative incentives for analysts’ forecasts of sales growth and long-term growth rates.

Practical implications
These findings may also help investors to better assess the quality of analysts’ research outputs and to identify superior stock recommendations.

Originality/value
This study provides insight into the role of cash flow forecasts in firm valuation and adds fresh evidence to the debate on the usefulness of cash flow forecasts. It extends the stream of research on the characteristics of analyst forecasts and increases our knowledge about the role of analysts in the financial market.
Evaluation of gaps in early warning mechanisms and evacuation procedures for coastal communities in Sri Lanka
Authors: Perera Chamal , Jayasooriya Darshana , Jayasiri Gimhan , Randil Chameera , Bandara Chaminda , Siriwardana Chandana , Dissanayake Ranjith , Hippola Sameera , Sylva Kamani , Kamalrathne Thushara , Kulatunga Asela 
Published: March 2020

Purpose
Even though Sri Lanka has established Early Warning (EW) mechanisms and Evacuation Procedures (EP) for the communities affected by the coastal disasters, there are several gaps, which hinder effective mechanisms in operation of disaster management practices. These gaps affect both the vulnerable communities and relevant authorities involved in the Disaster Management sector. This paper aims to identify and evaluate those gaps while providing adequate solutions.

Design/methodology/approach
For that, questionnaire surveys were carried out with a sample size of 217 via an online survey (117) among the urban level and interviews and telephone interviews (100) with the village level coastal communities. Data analysis was carried out using statistical analysis of questionnaire surveys and grounded theory was used for in-depth qualitative study.

Findings
Primary and secondary data obtained from the surveys were categorized under five themes, namely, response to early warning systems, evacuation routes, shelters, drills and training, effect of having a family vehicle, relatives and domestic animals, evacuation of people with special needs and cooperation with local government units. This paper analyses these themes in detail.

Originality/value
While critically evaluating the gaps in existing early warning mechanisms and evacuation procedures, this paper identifies correlations between some of the gaps and recommendations as well. Input from the international academics were also obtained at different forums and have strengthen the findings to overcome the barriers, which hinder successful mechanisms.