bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous edaravone plus therapeutic hypothermia offers limited neuroprotection in the hypoxic-ischaemic newborn piglet
Authors: Yamato Satoshi (Hamano) , Nakamura Shinji , Htun Yinmon , Nakamura Makoto , Jinnai Wataru , Nakao Yasuhiro , Mitsuie Tsutomu , Koyano Kosuke , Wakabayashi Takayuki , Morimoto Aya (Hashimoto) , Sugino Masashiro , Iwase Takashi , Kondo Sonoko (Ijichi) , Yasuda Saneyuki , Ueno Masaki , Miki Takanori , Kusaka Takashi 
Published: February 2020

AbstractTherapeutic hypothermia is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one). To compare the neuroprotective effects of edaravone plus therapeutic hypothermia with those of therapeutic hypothermia alone after a hypoxic-ischaemic insult in the newborn piglet, anaesthetized piglets were subjected to 40 min of hypoxia (3–5% inspired oxygen) and cerebral ischaemia was assessed by cerebral blood volume. Body temperature was maintained at 38.5 °C in the normothermia group (NT, n = 8) and at 34 °C (24 h after the insult) in the therapeutic hypothermia (TH, n = 7) and therapeutic hypothermia plus edaravone (3 mg intravenous every 12 h for 3 days after the insult; TH+EV, n = 6) groups under mechanical ventilation. Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (p= 0.025 vs. NT) and 15.0 (3.9) in the TH+EV group. The histopathological score of the TH+EV group showed no significant improvement compared with that of the other groups. In conclusion, edaravone plus therapeutic hypothermia had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.
Analyzing Presymptomatic Tissue to Gain Insights into the Molecular and Mechanistic Origins of Late-Onset Degenerative Trinucleotide Repeat Disease
Authors: Chu Yongjun , Hu Jiaxin , Liang Hanquan , Kanchwala Mohammed , Xing Chao , Beebe Walter , Bowman Charles B. , Gong Xin , Corey David R. , Mootha V. Vinod 
Published: February 2020

ABSTRACTHow genetic defects trigger the molecular changes that cause late-onset disease is important for understanding disease progression and therapeutic development. Fuchs’ endothelial corneal dystrophy (FECD) is an RNA-mediated disease caused by a trinucleotide CUG expansion in an intron within theTCF4gene. The mutant intronic CUG RNA is present at 1-2 copies per cell, posing a challenge to understand how a rare RNA can cause disease. Late-onset FECD is a uniquely advantageous model for studying how RNA triggers disease because; 1) Affected tissue is routinely removed during surgery; 2) The expanded CUG mutation is one of the most prevalent disease-causing mutations, making it possible to obtain pre-symptomatic tissue from eye bank donors to probe how gene expression changes precede disease; and 3) The affected tissue is a homogeneous single cell monolayer, facilitating accurate transcriptome analysis. Here we use RNA sequencing (RNAseq) to compare tissue from individuals who are pre-symptomatic (Pre_S) to tissue from patients with late stage FECD (FECD_REP). The abundance of mutant repeat intronic RNA in Pre_S and FECD_REP tissue is elevated due to increased half-life in a corneal cell-specific manner. In Pre_S tissue, changes in splicing and extracellular matrix gene expression foreshadow the changes observed in advanced disease and predict the activation of the fibrosis pathway and immune system seen in late-stage patients. The absolute magnitude of splicing changes is similar in presymptomatic and late stage tissue. Our data identify gene candidates for early drivers of disease and biomarkers that may represent diagnostic and therapeutic targets for FECD. We conclude that changes in alternative splicing and gene expression are observable decades prior to the diagnosis of late-onset trinucleotide repeat disease.
Seasonal variation in physiology and shell condition of the pteropodLimacina retroversain the Gulf of Maine relative to life cycle and carbonate chemistry
Authors: Maas Amy E. , Lawson Gareth L. , Bergan Alexander J. , Wang Zhaohui A. , Tarrant Ann M. 
Published: February 2020

AbstractNatural cycles in the seawater partial pressure of carbon dioxide (CO2) in the Gulf of Maine, which vary from ∼250-550 µatm seasonally, provide an opportunity to observe how the life cycle and phenology of the shelled pteropodLimacina retroversaresponds to changing food, temperature and carbonate chemistry conditions. Distributional, hydrographic, and physiological sampling suggest that pteropod populations are located in the upper portion of the water column (0-150 m) with a maximum abundance above 50 m, allowing them to generally avoid aragonite undersaturation. Gene expression and shell condition measurements show, however, that the population already experiences biomineralization stress in the winter months even when aragonite is slightly oversaturated, reinforcing the usefulness of this organism as a bio-indicator for pelagic ecosystem response to ocean acidification. There appear to be two reproductive events per year with one pulse timed to coincide with the spring bloom, the period with highest respiration rate, fluorescence, and pH, and a second more extended pulse in the late summer and fall. During the fall there is evidence of lipid storage for overwintering, allowing the second generation to survive the period of low food and aragonite saturation state. Based on these observations we predict that in the future pteropods will likely be most vulnerable to changing CO2regionally during the fall reproductive event when CO2concentration already naturally rises and there is the added stress of generating lipid stores.
A regulatory protein that represses sporulation inClostridioides difficile
Authors: Martins Diogo , Mendes Aristides L. , Antunes Jessica , Henriques Adriano O. , Serrano Mónica 
Published: February 2020

AbstractBacteria that reside in the gastrointestinal tract of healthy humans are essential for our health, sustenance and well-being. About 50 to 60% of those bacteria have the ability to produce resilient spores, important for the life cycle in the gut and for host-to-host transmission. A genomic signature for sporulation in the human intestine was recently described, which spans both commensals and pathogens such asClostridioides difficile, and contains several genes of unknown function. We report on the characterization of a signature gene,csiA, which, as we show, is involved in the control of sporulation initiation inC. difficile. Spo0A is the main regulatory protein controlling entry into sporulation and we show that an in-frame deletion ofcsiAresults in increased sporulation, and increased expression ofspo0Aper cell. Spo0A also drives transcription of thespoIIAandspoIIGoperons, coding for the first forespore-(σF) and mother cell-specific (σE) RNA polymerase sigma factors. Strikingly, deletion ofcsiAincreases expression of thespoIIGoperon, but not that of thespoIIAoperon. Increased expression ofspoIIGresults in increased production and proteolytic activation of pro-σE, suggesting that normally, the levels of active σEare limiting for sporulation. While other regulatory proteins affect both sporulation and several processes during the transition phase of growth, including toxin production or motility, deletion of thecsiAgene does not alter the expression of the genes coding for the TcdA and TcdB cytotoxins or the genes involved in motility. Thus, our results establish that CsiA acts to modulate sporulation by reducing expression of thespo0Agene.
Regulation of NF-kappa B and cell death by bacterial gingipains
Authors: Urnowey Sonya , Ansai Toshihiro , Bitko Vira , Barik Sailen 
Published: February 2020

AbstractThe role of non-caspase proteases in the regulation of programmed cell death is relatively under-studied. In this short communication, we report that infection of human gingival fibroblast (HGF) cellsex vivobyPorphyromonas gingivalisrapidly activated NF-kappa B, an antiapoptotic player; PI3 kinase was also induced, and together, they inhibited apoptosis. Later, pro-apoptotic cellular genes, including caspases, were induced. Apoptosis was evidenced by the degradation of nuclear DNA and activation of caspases. Unexpectedly, aP. gingivalismutant that lacked all three major gingipain proteases was defective in promoting apoptosis, which was consistent with the cleavage of procaspase-3 to the active form by the culture supernatant of wild typeP. gingivalis, but not that of the triple protease mutant. These results suggest that cellular death in theP. gingivalis-infected gum may be orchestrated by gingipain-regulated apoptotic factors.
Identification of novel RNA Polymerase II CTD interaction sites on the mRNA Capping Enzyme
Authors: Bage Marcus G. , Almohammed Rajaei , Cowling Victoria H. , Pisliakov Andrei V. 
Published: February 2020

1AbstractRecruitment of the mRNA Capping Enzyme (CE/RNGTT) to the site of transcription is essential for the formation of the 5’ mRNA cap, which in turn ensures efficient transcription, splicing, polyadenylation, nuclear export and translation of mRNA in eukaryotic cells. The CE is recruited and activated by the Serine-5 phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II. Through the use of molecular dynamics simulations and enhanced sampling techniques, we provide a systematic and detailed characterisation of the human CE-CTD interface, describing the effect of the CTD phosphorylation state, length and orientation on this interaction. Our computational analyses identify novel CTD interaction sites on the human CE surface and quantify their relative contributions to CTD binding. We also identify differences in the CTD binding conformation when phosphorylated at either the Serine-2 or Serine-5 positions, thus providing insights into how the CE reads the CTD code. The computational findings are then validated by binding and activity assays. These novel CTD interaction sites are compared with cocrystal structures of the CE-CTD complex in different eukaryotic taxa, leading to the conclusion that this interface is considerably more conserved than previous structures have indicated.
A non-canonical histone acetyltransferase targets intragenic enhancers and regulates plant architecture
Authors: Yang Xueyong , Yan Jianbin , Zhang Zhen , Lin Tao , Xin Tongxu , Wang Bowen , Wang Shenhao , Zhao Jicheng , Zhang Zhonghua , Lucas William J. , Li Guohong , Huang Sanwen 
Published: February 2020

AbstractAxillary meristem development determines both plant architecture and crop yield; this critical process is regulated by the TCP transcription factor (TF) family, including the maizeTB1and ArabidopsisBRC1. Studies have shown that both TB1 and AtBRC1 can target the gene body regions of some target genes and activate their expression; however, the regulatory mechanisms remain largely unknown. Here, we show that a cucumberCYC/TB1homologue,TEN, controls the identity and mobility of tendrils. Through its C-terminus, TEN binds at intragenic enhancers of target genes; its N-terminal domain functions as a novel, non-canonical histone acetyltransferase (HAT) to preferentially act on lysine 56 and 122, of the histone H3 globular domain. This HAT activity is responsible for chromatin loosening and host gene activation. The N-termini of all tested CYC/TB1-like proteins contain an intrinsically disordered region (IDR), and despite their sequence divergence, they have conserved HAT activity. This study discovered a non-canonical class of HATs, and as well, provides a mechanism by which modification at the H3 globular domain is integrated with the transcription process.
High-Throughput CRISPR/Cas9 Mutagenesis Streamlines Trait Gene Identification in Maize
Authors: Liu Hai-Jun , Jian Liumei , Xu Jieting , Zhang Qinghua , Zhang Maolin , Jin Minliang , Peng Yong , Yan Jiali , Han Baozhu , Liu Jie , Gao Fan , Liu Xiangguo , Huang Lei , Wei Wenjie , Ding Yunxiu , Yang Xiaofeng , Li Zhenxian , Zhang Mingliang , Sun Jiamin , Bai Minji , Song Wenhao , Chen Hanmo , Sun Xi’ang , Li Wenqiang , Lu Yuming , Liu Ya , Zhao Jiuran , Qian Yangwen , Jackson David , Fernie Alisdair R. , Yan Jianbing 
Published: February 2020

Abstract
Maize (Zea mays) is one of the most important crops in the world. However, few agronomically important maize genes have been cloned and used for trait improvement, due to its complex genome and genetic architecture. Here, we integrated multiplexed CRISPR/Cas9-based high-throughput targeted mutagenesis with genetic mapping and genomic approaches to successfully target 743 candidate genes corresponding to traits relevant for agronomy and nutrition. After low-cost barcode-based deep sequencing, 412 edited sequences covering 118 genes were precisely identified from individuals showing clear phenotypic changes. The profiles of the associated gene-editing events were similar to those identified in human cell lines and consequently are predictable using an existing algorithm originally designed for human studies. We observed unexpected but frequent homology-directed repair through endogenous templates that was likely caused by spatial contact between distinct chromosomes. Based on the characterization and interpretation of gene function from several examples, we demonstrate that the integration of forward and reverse genetics via a targeted mutagenesis library promises rapid validation of important agronomic genes for crops with complex genomes. Beyond specific findings, this study also guides further optimization of high-throughput CRISPR experiments in plants.
ALEPH: a network-oriented approach for the generation of fragment-based libraries and for structure interpretation
Authors: Medina Ana , Triviño Josep , Borges Rafael J. , Millán Claudia , Usón Isabel , Sammito Massimo D. 
Published: February 2020

The analysis of large structural databases reveals general features and relationships among proteins, providing useful insight. A different approach is required to characterize ubiquitous secondary-structure elements, where flexibility is essential in order to capture small local differences. TheALEPHsoftware is optimized for the analysis and the extraction of small protein folds by relying on their geometry rather than on their sequence. The annotation of the structural variability of a given fold provides valuable information for fragment-based molecular-replacement methods, in which testing alternative model hypotheses can succeed in solving difficult structures when no homology models are available or are successful.ARCIMBOLDO_BORGEScombines the use of composite secondary-structure elements as a search model with density modification and tracing to reveal the rest of the structure when both steps are successful. This phasing method relies on general fold libraries describing variations around a given pattern of β-sheets and helices extracted usingALEPH. The program introduces characteristic vectors defined from the main-chain atoms as a way to describe the geometrical properties of the structure.ALEPHencodes structural properties in a graph network, the exploration of which allows secondary-structure annotation, decomposition of a structure into small compact folds, generation of libraries of models representing a variation of a given fold and finally superposition of these folds onto a target structure. These functions are available through a graphical interface designed to interactively show the results of structure manipulation, annotation, fold decomposition, clustering and library generation.ALEPHcan produce pictures of the graphs, structures and folds for publication purposes.
Safe RPAS integration in non-segregated airspace
Authors: Pérez-Castán Javier A. , Gómez Comendador Fernando , Rodríguez-Sanz Álvaro , Arnaldo Valdés Rosa M. , Alonso-Alarcon Jose Felix 
Published: February 2020

Purpose
This paper aims to assess the implications in safety levels by the integration of remotely piloted aircraft system (RPAS). The goal is to calculate the number of RPAS that can jointly operate with conventional aircraft regarding conflict risk, without exceeding current safety levels.

Design/methodology/approach
This approach benchmarks a calculated level of safety (CLS) with a target level of safety (TLS). Monte Carlo (MC) simulations quantify the TLS based on the current operation of conventional aircraft. Then, different experiments calculate the CLS associated with combinations of conventional aircraft and RPAS. MC simulations are performed based on probabilistic distributions of aircraft performances, entry times and geographical distribution. The safety levels are based on a conflict risk model because the safety metrics are the average number of conflicts and average conflict duration.

Findings
The results provide restrictions to the number of RPAS that can jointly operate with conventional aircraft. The TLS is quantified for four conventional aircraft. MC simulations confirm that the integration of RPAS demands a reduction in the total number of aircraft. The same number of RPAS than conventional aircraft shows an increase over 90% average number of conflicts and 300% average conflict time.

Research limitations/implications
The methodology is applied to one flight level of en-route airspace without considering climbing or descending aircraft.

Originality/value
This paper is one of the most advanced investigations performed to quantify the number of RPAS that can be safely integrated into non-segregated airspace, which is one of the challenges for the forthcoming integration of RPAS. Particularly, Europe draws to allow operating RPAS and conventional aircraft in non-segregated airspace by 2025, but this demanding perspective entails a thorough analysis of operational and safety aspects involved.
Exploring the effectiveness of maintenance and quality management strategies in Indian manufacturing enterprises
Authors: Sahoo Saumyaranjan 
Published: February 2020

PurposeThe purpose of the paper is to examine the impact of human-related support practices, total productive maintenance (TPM) practices, and total quality management (TQM) practices on manufacturing performance parameters and their inter-relationship.Design/methodology/approachA research project was carried out in 94 Indian manufacturing companies, using the questionnaire method. The survey data was drawn from 169 respondents working in these companies. In this paper, the impact of TPM and TQM practices on manufacturing performance parameters and especially the role of support practices is investigated empirically using various structural equation models.FindingsTwo factors namely top management and leadership and human resource development categorized as support practices were found to positively influence the adoption of technical practices, i.e., TPM and TQM practices. Hence support practices were found to indirectly affect the manufacturing performance parameters via the technical factors. Also analyzing various structural equation models (SEM), shop floor implementation of TPM practices were found to be influenced (or guided) by the philosophy of TQM practices. In other words, through the proper adoption of TQM practices, the effectiveness of TPM practices gets increased.Research limitations/implicationsBecause of the chosen research approach, the research results may lack generalizability. Therefore, researchers are encouraged to test the proposed propositions further using a case study approach.Practical implicationsThe present study provides useful insights to practicing managers. The result of the study explaining the interrelationship between support practices (behavioral aspect) and technical practices can be used by practicing managers to develop a better understanding of the contribution of support and technical practices towards the realization of organizational objectives of growth and sustainability. In practice, TQM plays a great role in the adoption of TPM practices, which in turn helps to achieve quality in processes and therefore in products.Originality/valuePrevious research has often either concentrated on technical practices as one dimension without studying the effects of support practices on improving the adoption of technical practices. The results of the study take one step further by investigating the relationship between multiple aspects (support and technical aspects) of manufacturing practices and their impact on manufacturing performance.
Project management for social good
Authors: Goel Ashish , Ganesh L.S. , Kaur Arshinder 
Published: February 2020

PurposeRecent research on construction project management (CPM) envisions addressing wider social good while delivering value to the funding organizations. It is complemented by a growing body of knowledge on social sustainability in construction projects. These two literature streams are currently scattered and there is a lack of holistic guidance on integrating social sustainability with CPM. The current study addresses this knowledge gap through a critical review of these two bodies of literature and thereby proposing a conceptual framework for socially sustainable CPM.Design/methodology/approachA conceptual modelling approach, involving sequential steps of knowledge acquisition, and knowledge abstraction and representation, has been used. Knowledge acquisition was based on a systematic search and short-listing of research articles and knowledge abstraction was performed through thematic analysis of the 81 shortlisted articles. The categories abstracted through thematic analysis were integrated and presented as the framework.FindingsA framework for socially sustainable CPM, consisting of four social sustainability characteristics and six areas of social sustainability integration in CPM (SSI-CPM), has been proposed. It presents possibilities of integrating social concerns in CPM processes at various levels – ranging from permanent firms that provide resources to the temporary (project) organization that delivers value.Originality/valueThis study seeks to bridge the gap between theory and practice of realizing social good through construction projects. To this end, a conceptual framework has been proposed along with an agenda for future research encompassing social sustainability and CPM.
Financial access, governance and insurance sector development in sub-Saharan Africa
Authors: Asongu Simplice , Odhiambo Nicholas M. 
Published: February 2020

PurposeThis study investigates the role of financial access in moderating the effect of governance on insurance consumption in 42 sub-Saharan African countries using data for the period 2004–2014.Design/methodology/approachTwo life insurance indicators are used, notably: life insurance and non-life insurance. Six governance measurements are also used, namely: political stability, ‘voice and accountability’, government effectiveness, regulation quality, corruption-control and the rule of law. The empirical evidence is based on the Generalised Method of Moments (GMM) and Least Squares Dummy Variable Corrected (LSDVC) estimators.FindingsEstimations from the LSDVC are not significant while the following main findings are established from the GMM. First, financial access promotes life insurance through channels of political stability, ‘voice and accountability’, government effectiveness, the rule of law and corruption-control. Second, financial access also stimulates non-life insurance via governance mechanisms of political stability, ‘voice and accountability’, government effectiveness, regulation quality, the rule of law and corruption-control.Originality/valueThis research complements the sparse literature on insurance promotion in Africa by engaging the hitherto unexplored role of financial access through governance channels.