bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the dynamic mechanisms of thePseudomonas aeruginosaquorum sensing and virulence networks using Boolean modelling
Authors: Banzhaf Manuel , Resendis-Antonio Osbaldo , Zepeda-Mendoza M. Lisandra 
Published: September 2019

AbstractIntroductionPseudomonas aeruginosais an opportunistic pathogen with an extraordinary metabolic adaptability and a large repertoire of virulence factors that allow it to cause acute and chronic infections. Treatment ofP. aeruginosainfections often fail due to its antibiotic resistance mechanisms, thus novel strategies aim at targeting virulence factors instead of growth-related features. However, there is currently not a clear understanding of the dynamic nature inherent to the wiring of its virulence networks.ResultsIn this study, we manually reconstructed the signalling and transcriptional regulatory networks of 12 acute (incl. pyocin and elastase) and 8 chronic virulence factors (incl. biofilm), and the 4 quorum sensing (QS) systems ofP. aeruginosa.Using Boolean modelling (BM), we unveiled the important roles that stochasticity and node connectivity play in the networks’ inherent dynamicity and robustness. We showed that both the static interactions, as well as the time when the interactions take place, are important features in the QS network. In addition, we found that the virulence factors of the acute networks are under strict repression, or under an activation that is non-strict or oscillatory, while the chronic networks favour the repression of the virulence factor, with only moderate activation under certain conditions.ConclusionIn conclusion, ourin silico-modelling framework provided us with a system-level view of theP. aeruginosavirulence and QS networks to gain new insights into the various mechanisms that support its pathogenicity and response to stressors targeting these networks. Thus, we suggest that BM provides an invaluable tool to guide the design of new treatments againstP. aeruginosa.
Rapid phylogenetic analysis of African swine fever virus from metagenomic sequences
Authors: Xiong Dongyan , Zhang Xiaoxu , Yu Junping , Wei Hongping 
Published: September 2019

AbstractAfrican swine fever virus (ASFV) has devastating impacts on swine health and the world economy. Rapid and accurate phylogenetic analysis of ASFV causing outbreaks is important to reveal diversity and evolutionary of ASFV. Because it is time-consuming and needs biosafety laboratories to isolate ASFV, here we present a new way to perform rapid genome-wide phylogenetic analysis of ASFV using an allele calling based on gene by gene approach directly from genome drafts assembled from metagenomic sequences. Using open-accessed chewBBACA software, 41 publicly available ASFV genomes were analyzed to optimize the parameters and find the alleles. Alleles as many as 94 were found for building the phylogenetic trees, which covered more than 56% of the whole genome. Based on the alleles, current ASFV isolates could be divided into two major clades and a few subclades. Then the method is used to analyze two ASFV genome drafts assembled from two metagenomic sequences of a swine whole blood and a swine spleen tissue collected in Wuhan, China. It shows that the two ASFV genomes showed highest similarity to that of Pig/HLJ/2018 strain and DB/LN/2018 strain, which isolated recently in China. This proved that the ASFV in Wuhan originate from the same source causing the earlier outbreaks in Helongjiang and Liaoning province of China. This method makes it possible to analyze phylogenetic analysis of ASFV draft genomes flexibly without the need of ASFV isolation. Furthermore, because it is based on Allele calling, the ASFV-specific genetic markers found could be translated into clinical diagnostics or can be used broadly to identify conserved putative therapeutic candidates.
Resolving sub-clonal heterogeneity within cell-line growths by single cell sequencing genomic DNA
Authors: Velazquez-Villarreal Enrique I. , Maheshwari Shamoni , Sorenson Jon , Fiddes Ian T. , Kumar Vijay , Yin Yifeng , Webb Michelle , Catalanotti Claudia , Grigorova Mira , Edwards Paul A. , Carpten John D. , Craig David W. 
Published: September 2019

ABSTRACTWe performed shallow single-cell sequencing of genomic DNA across 1,475 cells from a well-studied cell-line, COLO829, to resolve overall tumor complexity and clonality. This melanoma tumor-line has been previously characterized by multiple technologies and provides a benchmark for evaluating somatic alterations, though has exhibited conflicting and indeterminate copy number states. We identified at least four major sub-clones by discriminant analysis of principal components (DAPC) of single cell copy number data. Break-point and loss of heterozygosity (LOH) analysis of aggregated data from sub-clones revealed a complex rearrangement of chromosomes 1, 10 and 18 that was maintained in all but two sub-clones. Likewise, two of the sub-clones were distinguished by loss of 1 copy of chromosome 8. Re-analysis of previous spectral karyotyping data and bulk sequencing data recapitulated these sub-clone hallmark features and explains why the original bulk sequencing experiments generated conflicting copy number results. Overall, our results demonstrate how shallow copy number profiling together with clustering analysis of single cell sequencing can uncover significant hidden insights even in well studied cell-lines.
Target Gene Notebook: Connecting genetics and drug discovery
Authors: Reeve Mary Pat , Kirby Andrew , Wierzbowski Jamey , Daly Mark , Hutz Janna 
Published: September 2019

AbstractTarget Gene Notebook was developed to enable more efficient linking of genetic associations to functional biological information. This process is essential to translating genetic insights into therapeutic hypotheses and, eventually, drug discovery. Although many public databases provide access to unfiltered genome annotations and genetic results, there was no existing tool to maintain group curation and integration with proprietary experimental data. We provide Target Gene Notebook freely via the MIT open-source license for the purposes of assisting therapeutic target evaluation and the creation of durable institutional and public knowledge bases. Implemented as a Java backend serving mainly Javascript content derived from gene-specific SQLite databases, Target Gene Notebook enables automated access to the most widely used sources of genetic association, expression and protein QTL data, provides intuitive interfaces to credible set and colocalization information, and enables comprehensive literature review and annotation by multiple users simultaneously to create a consistent target knowledgebase within an organization or across a consortium. TargetGeneNotebook is freely available from GitHub https://github.com/targetgenenotebook/tgn.git under the MIT open-source end-user license agreement and a live version of the interface is provided at http://tgn.broadinstitute.org/.
The nasopalatine ducts of the mouse conserve a functional role in pheromone signaling
Authors: Levy Dana Rubi , Sofer Yizhak , Brumfeld Vlad , Zilkha Noga , Kimchi Tali 
Published: September 2019

AbstractSocial communication in most mammals is mediated by chemosignals, collected by active sniffing and detected mainly by the vomeronasal organ (VNO). In reptiles, however, chemosignals are delivered to the VNO through the oral cavity via the nasopalatine ducts (NPDs) – two direct passageways connecting the nasal and the oral cavities. While the structure of the NPDs is highly conserved across terrestrial vertebrate, it is unclear whether they retain any functional role in mammalian chemosignaling. Here we assess the role of the mouse NPDs in VNO function and associated behavioral responses. By reconstructing the 3D morphological architecture of the mouse snout using micro CT, we identify a net of micro-tunnels forming a direct passageway connecting the NPDs to the nasal cavity and the vomeronasal organ. We further demonstrate that physical obstruction of the NPDs destructs VNO clearance, and reduces chemosignaling-evoked neuronal activation in the medial amygdala. Obstruction of the NPDs also impaired the innate male preference for female chemosignals as well as social approach behavior, indicating the crucial role of the murine nasopalatine ducts in pheromone sensing.
Localized calcium accumulations prime synapses for phagocyte removal in cortical neuroinflammation
Authors: Jafari Mehrnoosh , Schumacher Adrian-Minh , Snaidero Nicolas , Neziraj Tradite , Ullrich Gavilanes Emily M. , Jürgens Tanja , Flórez Weidinger Juan Daniel , Schmidt Stephanie S. , Beltrán Eduardo , Hagan Nellwyn , Woodworth Lisa , Ofengeim Dimitry , Gans Joseph , Wolf Fred , Kreutzfeldt Mario , Portugues Ruben , Merkler Doron , Misgeld Thomas , Kerschensteiner Martin 
Published: September 2019

SUMMARYCortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. Here we use functional and structuralin vivoimaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread but transient loss of dendritic spines. Spines destined for removal show a local calcium accumulation and are subsequently removed by invading macrophages and activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy.HIGHLIGHTSWidespread, but transient loss of synapses in inflammatory lesions and beyondReversible impairment of neuronal firing and circuit function in the inflamed cortexCalcium dyshomeostasis of single spines precedes swift synapse lossPhagocyte-mediated spine pruning as targetable mechanism of synapse loss
Hierarchical structure is employed by humans during visual motion perception
Authors: Bill Johannes , Pailian Hrag , Gershman Samuel J , Drugowitsch Jan 
Published: September 2019

AbstractIn the real world, complex dynamic scenes often arise from the composition of simpler parts. The visual system exploits this structure by hierarchically decomposing dynamic scenes: when we see a person walking on a train or an animal running in a herd, we recognize the individual’s movement as nested within a reference frame that is itself moving. Despite its ubiquity, surprisingly little is understood about the computations underlying hierarchical motion perception. To address this gap, we developed a novel class of stimuli that grant tight control over statistical relations among object velocities in dynamic scenes. We first demonstrate that structured motion stimuli benefit human multiple object tracking performance. Computational analysis revealed that the performance gain is best explained by human participants making use of motion relations during tracking. A second experiment, using a motion prediction task, reinforced this conclusion and provided fine-grained information about how the visual system flexibly exploits motion structure.
The ALBA RNA-binding proteins function redundantly to promote growth and flowering in Arabidopsis
Authors: Wang Naiqi , Jalajakumari Meachery , Miller Thomas , Asadi Mohsen , Millar Anthony A 
Published: September 2019

AbstractRNA-binding proteins (RBPs) are critical regulators of gene expression, but have been poorly studied relative to other classes of gene regulators. Recently, mRNA-interactome capture identified many Arabidopsis RBPs of unknown function, including a family of ALBA domain containing proteins. Arabidopsis has three short-form ALBA homologues (ALBA1-3) and three long-form ALBA homologues (ALBA4-6), both of which are conserved throughout the plant kingdom. Despite this ancient origin, ALBA-GUS translational fusions of ALBA1, ALBA2, ALBA4, and ALBA5 had indistinguishable expression patterns, all being preferentially expressed in young, rapidly dividing tissues. Likewise, all four ALBA proteins had indistinguishable ALBA-GFP subcellular localizations in roots, all being preferentially located to the cytoplasm, consistent with being mRNA-binding. Genetic analysis demonstrated redundancy within the long-form ALBA family members; in contrast to single alba mutants that all appeared wild-type, a triple alba456 mutant had slower rosette growth and a strong delay in flowering-time. RNA-sequencing found most differentially expressed genes in alba456 were related to metabolism, not development. Additionally, changes to the alba456 transcriptome were subtle, suggesting ALBA4-6 participates in a process that does not strongly affect transcriptome composition. Together, our findings demonstrate that ALBA protein function is highly redundant, and is essential for proper growth and flowering in Arabidopsis.HighlightThe RNA-binding ALBA proteins have indistinguishable expression patterns and subcellular localizations in Arabidopsis, acting redundantly to promote growth and flowering via a mechanism that does not strongly affect transcriptome composition.
Employment exclusion in Spain: a territorial approach
Authors: Lafuente-Lechuga Matilde , Faura-Martínez Ursula , García-Luque Olga 
Published: September 2019

PurposeThis paper studies social inequality in the vital field of employment in Spain during the crisis period 2009-2014.Design/methodology/approachFactor analysis is used to build a synthetic index of employment exclusion. The starting information matrix collects data from a wide set of employment variables for all 17 Spanish autonomous communities and the autonomous cities of Ceuta and Melilla. Based on this information, four factors are extracted which explain employment exclusion in different situations of vulnerability, such as unemployment, temporality, poverty or low pay.FindingsIn the territorial ranking, Madrid, Basque Country, Aragon and Catalonia show the lowest risk of employment exclusion, whereas Ceuta, Andalusia, Extremadura and Canary Islands show the highest ones.Originality/valueThe main value of this research is that it confirms the need for coordination of public policies in order to foster social and territorial cohesion in Spain.
In flight again with wings that were once broken; effects of post-traumatic growth and personal resources on burnout recovery
Authors: Semeijn Judith , Van Ruysseveldt Joris , Vonk Greet , van Vuuren Tinka 
Published: September 2019

PurposeAdequate recovery from burnout is important to understand. The purpose of this paper is to investigate whether post-traumatic growth (PTG) contributes to higher engagement and reduced symptoms of burnout and whether this process is mediated by personal resources.Design/methodology/approachIn a cross-sectional survey, 166 Dutch workers who had fully recovered from burnout were questioned on their level of PTG, their personal resources (optimism, resilience and self-efficacy), and their levels of engagement and burnout.FindingsFully recovered workers scored somewhat higher on current burnout level, but did not differ from norm group workers in their engagement level. Moreover, PTG appeared to positively affect both higher engagement and lower burnout levels, which is fully mediated by personal resources.Research limitations/implicationsPost-traumatic growth (PTG) impacts on engagement and burnout levels amongst workers who have recovered from burnout by enhancing personal resources. The role of personal resources and the impact of PTG on engagement and burnout complaints following (recovery from) burnout deserve further investigation.Practical implicationsManagement can support workers who have (recovered from a) burnout, by being aware of their (higher) engagement, and facilitate the enhancement of PTG and personal resources.Originality/valueThis study is one of the first to study the role of PTG after (recovery from) burnout and reveals valuable findings for both research and practice.
Skills and knowledge management in higher education: how service learning can contribute to social entrepreneurial competence development
Authors: Halberstadt Jantje , Timm Jana-Michaela , Kraus Sascha , Gundolf Katherine 
Published: September 2019

Purpose
The purpose of this paper is to elaborate on how service learning approaches are able to foster social entrepreneurship competences. The aim of the paper is to formulate a framework of key competences for social entrepreneurship and to give first insights in how service learning actually has an impact on change in students’ set of competences.

Design/methodology/approach
This paper uses a mixed-methods approach combining qualitative data collectionmethods of learning diaries of the students and semi-structured interviews, including 40 master’s students studying at a German university in interdisciplinary learning settings and five instructors from the same universities. Analysis was carried out by means of qualitative content analysis.

Findings
This paper provides empirical insights about the competences that are being fostered by service learning. From these, a framework for social entrepreneurship competences is being derived.

Research limitations/implications
The set of competences should be further investigated, as it was derived out of a small data set. Therefore, researchers are encouraged to use the set of competences for social entrepreneurship as a basis for future research and on a longer-term perspective, which lead to substantial implications for educational practice.

Practical implications
This paper includes implications for new perspectives on service learning in the light of the development of a relevant framework for social entrepreneurship competence, having significant implications for educational practice in social entrepreneurship education.

Originality/value
With this paper, the authors fulfill the need of a framework of social entrepreneurship competences that serves as a foundation for educational practice and further research in the context of service learning and beyond.
Mean reversion in corporate leverage: evidence from India
Authors: Chauhan Gaurav S. , Banerjee Pradip 
Published: September 2019

Purpose
Recent papers on target capital structure show that debt ratio seems to vary widely in space and time, implying that the functional specifications of target debt ratios are of little empirical use. Further, target behavior cannot be adjudged correctly using debt ratios, as they could revert due to mechanical reasons. The purpose of this paper is to develop an alternative testing strategy to test the target capital structure.

Design/methodology/approach
The authors make use of a major “shock” to the debt ratios as an event and think of a subsequent reversion as a movement toward a mean or target debt ratio. By doing this, the authors no longer need to identify target debt ratios as a function of firm-specific variables or any other rigid functional form.

Findings
Similar to the broad empirical evidence in developed economies, there is no perceptible and systematic mean reversion by Indian firms. However, unlike developed countries, proportionate usage of debt to finance firms’ marginal financing deficits is extensive; equity is used rather sparingly.

Research limitations/implications
The trade-off theory could be convincingly refuted at least for the emerging market of India. The paper here stimulated further research on finding reasons for specific financing behavior of emerging market firms.

Practical implications
The results show that the firms’ financing choices are not only depending on their own firm’s specific variables but also on the financial markets in which they operate.

Originality/value
This study attempts to assess mean reversion in debt ratios in a unique but reassuring manner. The results are confirmed by extensive calibration of the testing strategy using simulated data sets.
Occupational contact dermatitis in a manicurist
Authors: Nakagawa Michiyo , Hanada Miho , Amano Hiroo 
Published: September 2019

AbstractWe report a case of a manicurist who developed an allergic skin reaction to acrylates, manifested by itchy erythema, papules, vesicles and fissures on her hands, fingertips, forearm and eyelids. Patch tests showed positive reactions to three nail products used: ethylene glycol dimethacrylate, 2‐hydroxyethyl methacrylate, ethyl acrylate and 2‐hydroxyethyl acrylate in (meth)acrylate series. By using gel nail products, our patient became sensitized to 2‐hydroxyethyl methacrylate. We assume that this had been the trigger, leading to the occurrence of cross‐reactions between numerous acrylates including ethylene glycol dimethacrylate, ethyl acrylate and 2‐hydroxyethyl acrylate. When handling nail products, it is necessary to prevent airway sensitization, contact sensitization and cross‐reaction between various acrylates.
Association of rs3783641 single‐nucleotide polymorphism in GTP cyclohydrolase 1 gene with post‐herpetic neuralgia
Authors: Zheng Na‐Na , Zhang Ruo‐Chen , Yang Xiao‐Xiao , Zhong Lian‐Sheng 
Published: September 2019

AbstractPost‐herpetic neuralgia (PHN) is a well‐established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate‐limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single‐nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high‐resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.