bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow
Authors: Slogotskaya Liudmila , Bogorodskaya Elena , Ivanova Diana , Sevostyanova Tatiana 
Published: June 2018

AbstractBackground. A group of Russian scientists has developed Diaskintest, which comprises Mycobacterium tuberculosis-specific recombinant proteins CFP10-ESAT6, for skin testing (0.2 µg/0.1 ml).Study purpose: to evaluate the comparative sensitivity of TST with 2 TU PPD-L and a skin test with tuberculous recombinant allergen (Diaskintest) containing the ESAT6-CFP10 protein in children and adolescents with newly diagnosed respiratory tuberculosis during mass screening in the primary medical service in Moscow, 2013–2016.Materials and methods. The trial was a comprehensive retrospective group study of children and adolescents diagnosed in Moscow with respiratory tuberculosis in 2013–2016, aged 0 to 17 years inclusive. From 441 patients selected for analysis 408 patients had both tests (TST with 2 TU PPD-L and Diaskintest) performed, in 193 patients both tests were given simultaneously, of them 162 patients were BCG-vaccinated.Results. Comparative results of both tests in 408 patients with tuberculosis: at cut-off 5 mm, both tests has similar sensitivity: Diaskintest 98.3 % (95 % CI 97.0–99.6 %), TST 98.0 % (95 % CI 96.7–99.4 %), at cut-off 10 mm, the sensitivity decreases for both tests: Diaskintest 90.0 % (95 % CI 87.0–93.0 %), TST 88.7 % (95 % CI 85.6–91.9 %), but at cut-off 15 mm, the decrease in sensitivity is statistically significant: for Diaskintest 61.5 % (95 % CI 56.7–66.3 %), and for TST 46.3 % (95 % CI 41.4–51.3 %), p <0.0001.The results of simultaneous setting of tests on different hands in 193 people (including 162 BCG-vaccinated), do not differ from the results for 408 people.The correlation between the results of Diaskintest and TST was significant in all groups.Conclusion. In children and adolescents with respiratory tuberculosis, Diaskintest of 0.2 µg/ml and the Mantoux test with 2 TU PPD-L have high sensitivity (98%) at a cut-off of 5 mm; however, at cut-off 15 mm sensitivity is significantly reduced, and the decrease is more pronounced in the Mantoux test. The advantage of Diaskintest is that, unlike the Mantoux test, it has high specificity under the conditions of mass BCG vaccination. The test is cost-effective, simple to carry out, and can be used in mass screening.
Secretion of an Argonaute protein by a parasitic nematode and the evolution of its siRNA guides
Authors: Chow FWN , Koutsovoulos G , Ovando-Vázquez C , Neophytou K , Bermúdez-Barrientos JR , Laetsch DR , Robertson E , Kumar S , Claycomb JM , Blaxter M , Abreu-Goodger C , Buck AH 
Published: June 2018

AbstractExtracellular RNA has been proposed to mediate communication between cells and organisms however relatively little is understood regarding how specific sequences are selected for export. Here we describe a specific Argonaute protein (exWAGO) that is secreted in extracellular vesicles (EVs) released by the gastrointestinal nematodeHeligmosomoides bakeri, at multiple copies per EV. Phylogenetic and gene expression analyses demonstrate exWAGO orthologues are highly conserved and abundantly expressed in related parasites but highly diverged in free-living genusCaenorhabditis. We show that the most abundant small RNAs released from the nematode parasite are not microRNAs as previously thought, but rather secondary small interfering RNAs (siRNAs) that are produced by RNA-dependent RNA Polymerases. The siRNAs that are released in EVs have distinct evolutionary properties compared to those resident in free-living or parasitic nematodes. Immunoprecipitation of exWAGO demonstrates that it specifically associates with siRNAs from transposons and newly evolved repetitive elements that are packaged in EVs and released into the host environment. Together this work demonstrates molecular and evolutionary selectivity in the small RNA sequences that are released in EVs into the host environment and identifies a novel Argonaute protein as the mediator of this.
Systematic discovery of uncharacterized transcription factors inEscherichia coliK-12 MG1655
Authors: Gao Ye , Yurkovich James T. , Seo Sang Woo , Kabimoldayev Ilyas , Dräger Andreas , Chen Ke , Sastry Anand V. , Fang Xin , Mih Nathan , Yang Laurence , Eichner Johannes , Cho Byung-Kwan , Kim Donghyuk , Palsson Bernhard O. 
Published: June 2018

ABSTRACTTranscriptional regulation enables cells to respond to environmental changes. Yet, among the estimated 304 candidate transcription factors (TFs) inEscherichia coliK-12 MG1655, 185 have been experimentally identified and only a few tens of them have been fully characterized by ChIP methods. Understanding the remaining TFs is key to improving our knowledge of theE. colitranscriptional regulatory network (TRN). Here, we developed an integrated workflow for the computational prediction and comprehensive experimental validation of TFs using a suite of genome-wide experiments. We applied this workflow to: 1) identify 16 candidate TFs from over a hundred candidate uncharacterized genes; 2) capture a total of 255 DNA binding peaks for 10 candidate TFs resulting in six high-confidence binding motifs; 3) reconstruct the regulons of these 10 TFs by determining gene expression changes upon deletion of each TF; and 4) determine the regulatory roles of three TFs (YiaJ, YdcI, and YeiE) as regulators of L-ascorbate utilization, proton transfer and acetate metabolism, and iron homeostasis under iron limited condition, respectively. Together, these results demonstrate how this workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs in parallel.
Identification and characterization of genes encoding the nuclear envelope LINC complex in the monocot speciesZea mays
Authors: Gumber Hardeep K. , McKenna Joseph F. , Estrada Amado L. , Tolmie Andrea F. , Graumann Katja , Bass Hank W. 
Published: June 2018

ABSTRACTThe LINC (Linker of Nucleoskeleton to Cytoskeleton) complex is an essential multi-protein structure spanning the nuclear envelope. It connects the cytoplasm to the nucleoplasm, functions to maintain nuclear shape and architecture, and regulates chromosome dynamics during cell division. Knowledge of LINC complex composition and function in the plant kingdom is primarily limited to Arabidopsis, but critically missing from the evolutionarily distant monocots which include grasses, the most important agronomic crops worldwide. To fill this knowledge gap, we identified and characterized 22 maize genes, including a new grass-specific KASH gene family. Using bioinformatic, biochemical, and cell biological approaches, we provide evidence that representative KASH candidates localize to the nuclear periphery and interact with ZmSUN2in vivo. FRAP experiments using domain-deletion constructs verified that this SUN-KASH interaction was dependent on the SUN but not the coiled-coil domain of ZmSUN2. A summary working model is proposed for the entire maize LINC complex encoded by conserved and divergent gene families. These findings expand our knowledge of the plant nuclear envelope in a model grass species, with implications for both basic and applied cellular research.SUMMARY STATEMENTGenes encoding maize candidates for the core LINC and associated complex proteins have been comprehensively identified with functional validation by one or more assays for several of the KASH genes.
Optimizing sequential decisions in the drift-diffusion model
Authors: Nguyen Khanh P. , Josić Krešimir , Kilpatrick Zachary P. 
Published: June 2018

AbstractTo make decisions organisms often accumulate information across multiple timescales. However, most experimental and modeling studies of decision-making focus on sequences of independent trials. On the other hand, natural environments are characterized by long temporal correlations, and evidence used to make a present choice is often relevant to future decisions. To understand decision-making under these conditions we analyze how a model ideal observer accumulates evidence to freely make choices across a sequence of correlated trials. We use principles of probabilistic inference to show that an ideal observer incorporates information obtained on one trial as an initial bias on the next. This bias decreases the time, but not the accuracy of the next decision. Furthermore, in finite sequences of trials the rate of reward is maximized when the observer deliberates longer for early decisions, but responds more quickly towards the end of the sequence. Our model also explains experimentally observed patterns in decision times and choices, thus providing a mathematically principled foundation for evidence-accumulation models of sequential decisions.
Enterococcus faecalisV583 LuxS/AI-2 system is devoid of role in intra-species quorum-sensing but contributes to virulence in aDrosophilahost model
Authors: Gaspar Frederic , Teixeira Neuza , Montero Natalia , Aleksandrzak-Piekarczyk Tamara , Matos Renata , Gonzalez-Zorn Bruno , Jacinto António , Barreto Crespo Maria Teresa , Silva Lopes Maria de Fátima 
Published: June 2018

AbstractThe AI-2 i nterspecies quorum-sensing molecule is produced by the LuxS enzyme and has been ascribed a role in virulence in several bacteria. The nosocomial pathogenEnterococcus faecalisinhabits several different environments where multispecies communities are established. However, despite the presence of aluxSgene in this pathogen, its role inE. faecalispathogenesis has never been assessed. In the present work, we deleted theluxSgene from the vancomycin-resistant clinical isolateE. faecalisV583 and demonstrated the lack of AI-2 production by the mutant strain. Using microarrays and externally added (S)-4,5-dihydroxy-2,3-pentanedione we showed that AI-2 is not sensed byE. faecalisas a canonical quorum-sensing molecule and that theluxSmutation caused pleiotropic effects in gene expression, which could not be complemented by extracellularly added AI-2. These global differences in gene expression affected several gene functional roles, mainly those enrolled in metabolism and transport. Metabolic phenotypi ng of theluxSmutant, using Biolog plates, showed differences in utilization of galactose. AI-2 production by LuxS was shown to be irrelevant for some phenotypes related to the pathogenic potential ofE. faecalisnamely biofilm formation, adhesion to Caco-2 cells, resistance to oxidative stress and survival inside J-774 macrophages. However, theluxSmutant was attenuated when tested in theDrosophilaseptic injury model, as its deletion led to delayed fly death. Overall our findings show that differential gene expression related to theluxSmutation cannot be ascribed to quorum-sensing. Moreover, the role of LuxS appears to be limited to metabolism.
Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits
Authors: Lopez-Rodriguez Ana Belen , Hennessy Edel , Murray Carol , Lewis Anouchka , Barra Niamh de , Fagan Steven , Rooney Michael , Nazmi Arshed , Cunningham Colm 
Published: June 2018

AbstractAlzheimer’s disease (AD) causes devastating cognitive decline and has no disease-modifying therapies. Neuroinflammation is a significant contributor to disease progression but its precise contribution remains unclear. An emerging literature indicates that secondary inflammatory insults including acute trauma and infection alter the trajectory of chronic neurodegenerative diseases and the roles of microglia and astrocytes require elucidation. The current study, using the APP/PS1 mouse model of AD, demonstrates that microglia are primed by β-amyloid pathology to induce exaggerated IL-1β responses to acute stimulation with LPS or IL-1β. Despite disease-associated NLRP3 inflammasome activation, evidenced by ASC speck formation, APP/PS1 microglial cells show neither IL-1β induction nor NFκB p65 nuclear localisation. Upon secondary stimulation with LPS or IL-1β, NFκB-p65 nuclear localisation and exaggerated pro-IL-1 induction occur. Microglial priming was also unmasked by secondary stimulation with systemic LPS leading to significant cognitive impairment in APP/PS1 mice compared to WT LPS-treated mice. Astrocytes have also recently emerged as displaying significant phenotypic heterogeneity. Here, by-passing microglial priming, and acutely challenging mice with intra-hippocampal IL-1β we demonstrate that astrocytes proximal to Aβ-plaques are also primed to produce exaggerated CCL2, CXCL1 and CXCL10 responses. Many astrocytosis-associated genes in APP/PS1 mice share these exaggerated responses to IL-1β, while others are equally induced in both strains. Collectively the data show that the amyloid-laden brain shows multiple vulnerabilities to secondary inflammatory challenge: both microglia and astrocytes are primed to produce exaggerated secondary inflammation and systemic LPS is sufficient to cause cognitive impairments relevant to delirium, selectively in animals with prior amyloid pathology.
Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons
Authors: Deneault Eric , White Sean H. , Rodrigues Deivid C. , Ross P. Joel , Faheem Muhammad , Zaslavsky Kirill , Wang Zhuozhi , Alexandrova Roumiana , Pellecchia Giovanna , Wei Wei , Piekna Alina , Kaur Gaganjot , Howe Jennifer L. , Kwan Vickie , Thiruvahindrapuram Bhooma , Walker Susan , Pasceri Peter , Merico Daniele , Yuen Ryan K.C. , Singh Karun K. , Ellis James , Scherer Stephen W. 
Published: June 2018

SummaryAutism Spectrum Disorder is phenotypically and genetically heterogeneous, but genomic analyses have identified candidate susceptibility genes. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of 10 ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NEUROG2)-directed differentiation of iPSCs allowed production of cortical excitatory neurons, and mutant proteins were not detectable. RNAseq revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory post-synaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2- and SCN2A-null neurons. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.
Epicatechin modulates stress-resistance in C. elegans via Insulin/IGF-1 signaling pathway
Authors: Ayuda-Durán Begoña , González-Manzano Susana , Miranda-Vizuete Antonio , Dueñas Montserrat , Santos-Buelga Celestino , González-Paramás Ana M. 
Published: June 2018

AbstractThe nematode Caenorhabditis elegans has been used to examine the influence of epicatechin (EC), an abundant flavonoid in the human diet, in some stress biomarkers (ROS production, lipid peroxidation and protein carbonylation). Furthermore, the ability of EC to modulate the expression of some key genes in the insulin/IGF-1 signaling pathway (IIS), involved in longevity and oxidative or heat shock stress response, has also been explored. The final aim was to contribute to the elucidation of the mechanisms involved in the biological effects of flavonoids. The results showed that EC-treated wild-type C. elegans exhibited increased survival and reduced oxidative damage of biomolecules when submitted to thermal stress. EC treatment led to a moderate elevation in ROS levels, which might activate endogenous mechanisms of defense protecting against oxidative insult. The enhanced stress resistance induced by EC was found to be mediated through the IIS pathway, since assays in daf-2, age-1, akt-1, akt-2, sgk-1, daf-16, skn-1 and hsf-1 loss of function mutant strains failed to show any heat-resistant phenotype against thermal stress when treated with EC. Consistently, EC treatment upregulated the expression of some stress resistance associated genes, such as gst-4, hsp-16.2 and hsp-70, which are downstream regulated by the IIS pathway.
Open government data (OGD) in six Middle East countries: an evaluation of the national open data portals
Authors: Saxena Stuti 
Published: June 2018

Purpose
The purpose of this study is to do provide an overview of open government data (OGD) frameworks in six Middle East countries (Cyprus, Turkey, Egypt, Iran, Lebanon and Jordan) and to underscore the barriers in using the open data sets.

Design/methodology/approach
OGD framework offered by Sieber and Johnson (2015) is deployed for the present purpose. Primarily, documentary analysis is being used for substantiating the study and the national portals of the six countries are investigated.

Findings
In line with the frameworks chosen for this study, OGD initiatives across the six Middle East countries are at an emerging phase. All the six countries qualify for the “data over the wall” model as advanced by Sieber and Johnson (2015), wherein there are basic provisions of “data aggregation.” Furthermore, the data are incomplete and outdated, which serve as barriers in using these data sets for analysis and interpretation. Therefore, there are a number of barriers in using the open data sets. However, there are many prospects for using these data sets which would improve public accountability and transparency in the long run.

Practical implications
Besides helping in improved decision-making, the governments may be in a better position to appreciate the relevance of adopting a robust OGD initiative in facilitating the economic growth of their country.

Social implications
This study is relevant for ensuring that citizen engagement is promoted and there is co-creation of public value.

Originality/value
Hitherto, OGD has been investigated in the six Gulf Cooperation Council (GCC) countries (Bahrain, Oman, Qatar, Kuwait, Saudi Arabia and the United Arab Emirates) but the other countries in Middle East have not been investigated. This study selects six countries outside the GCC ambit and investigates the nature and scope of OGD initiatives in each of them apart from underlining the barriers in using the open data sets.
Visioning “smart city” across the Gulf Cooperation Council (GCC) countries
Authors: Saxena Stuti , Al-Tamimi Tariq Ali Said Mansour 
Published: June 2018

Purpose
The study aims to underscore the initiatives taken by the Gulf Cooperation Council (GCC) countries in spearheading their drive towards creating “smart” cities.

Design/methodology/approach
The study uses a qualitative approach by invoking documentary analysis supplemented by responses provided by 13 interviewees from public and private sector.

Findings
All the six GCC countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and United Arab Emirates) are keen on building upon their infrastructure to push their “smart city” agenda which would go a long way in furthering the economic diversification objective of their region besides improving the quality of public services.

Originality/value
Hitherto, research has been focused on appreciating the “smart city” initiatives of developed countries; this study seeks to build upon the literature on “smart cities” by contextualizing the research setting in the developing countries. Second, the study shows that with the ongoing oil prices crisis in the GCC, the “smart city” initiatives of the countries are conceived as possible avenues of economic diversification and competitiveness.
Much discussed, little conceptualized: supply chain volatility
Authors: Nitsche Benjamin , Durach Christian F. 
Published: June 2018

PurposeA conceptual framework of supply chain volatility (SCV) is developed to help researchers and practitioners converge their discussions and understandings on this vital phenomenon. Sources, dimensions and moderators of SCV are investigated and a conceptual framework is proposed. The paper aims to discuss these issues.Design/methodology/approachData triangulation was performed through reviewing 2,789 peer-reviewed articles and conducting a group exercise with 23 practitioners. Consequently, 364 sources were identified. Through a structured synthesis process that built on the Q-methodology with multiple academics, a framework of meta-level sources, dimensions and moderators of SCV was developed. An additional on-site meeting with 17 practitioners was conducted aiming at delineating the dimensions by their effect on SCV.FindingsThe authors propose 20 meta-level sources that contribute to five distinct dimensions of SCV, proposing behavior of customers and decision makers as contextual moderating variables. A classification scheme consisting of three descriptive SCV-affecting characteristics is proposed to delineate the dimension’s effect on SCV: relative deviating impact, repetitiveness and influenceability. Results are summarized in 15 propositions.Research limitations/implicationsThe paper extends knowledge on SCV and provides a coherent conceptualization of the phenomenon for future research. The proposed framework demands quantitative testing to derive more reliable conclusions.Practical implicationsThe framework aims at reducing the gap between research and practice. It helps managers to understand researchers’ discussions and how to derive expedient implications from them.Originality/valueIt is the first study that systematically synthesizes widely spread literature in this field to derive a conceptual framework that seeks to explain SCV in a holistic way.
The art of building initial trust in medical services
Authors: Terres Mellina da Silva , Basso Kenny 
Published: June 2018

Purpose
The purpose of this study is to investigate the antecedents of the patient’s initial trust in the doctor. In this sense, it is proposed that trust in the hospital plays a mediating role in the relationship between the physical evidence in the service environment and the patient’s initial trust in the doctor.

Design/methodology/approach
Two experimental studies with factorial between-subjects design with random assignment were used. The data were analyzed through an analysis of variance.

Findings
The results show that design and social factors affect the patient’s initial trust in the doctor through his trust in the hospital. The results also showed that reputation and recommendation affect the initial trust.

Originality/value
This is the first study to consider antecedents of patient’s initial trust in the doctor. Most of the studies about trust focuses on investigating trust in situations where there is a prior relationship; however, this study arises some evidences that trust starts to be constructing even before the patient properly meets the doctor. These findings are valuable because they highlight the importance of physical evidences, reputation and positive word-of-mouth for building initial trust.