bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards the molecular architecture of the peroxisomal receptor docking complex
Authors: Lill Pascal , Hansen Tobias , Wendscheck Daniel , Klink Bjoern Udo , Jeziorek Tomasz , Miehling Jonas , Bender Julian , Drepper Friedel , Girzalsky Wolfgang , Warscheid Bettina , Erdmann Ralf , Gatsogiannis Christos 
Published: November 2019

AbstractImport of yeast peroxisomal matrix proteins is initiated by cytosolic receptors, which specifically recognize and bind the respective cargo proteins. At the peroxisomal membrane, the cargo-loaded receptor interacts with the docking protein Pex14p that is tightly associated with Pex17p. Previous data suggest that this interaction triggers the formation of an import pore for further translocation of the cargo. The mechanistic principles are however unclear, mainly because structures of higher order assemblies are still lacking. Here, using an integrative approach, we provide the first structural characterization of the major components of the peroxisomal docking complex Pex14p/Pex17p, in a native bilayer environment and reveal its subunit organization. Our data show that three copies of Pex14p and a single copy of Pex17p assemble to form a 20 nm rod-like particle. The different subunits are arranged in a parallel manner, showing interactions along their complete sequences and providing receptor binding-sites on both membrane sides. The long rod facing the cytosol is mainly formed by the predicted coiled-coil domains of Pex14p and Pex17p, possibly providing the necessary structural support for the formation of the import pore. Further implications of Pex14p/Pex17p for formation of the peroxisomal translocon are discussed.
SIRT2-knockdown Rescues GARS-induced Charcot-Marie-Tooth Neuropathy
Authors: Shen Chao , Qi Qian , Qin Yicai , Zhou Dejian , Chen Xinyuan , Qi Yun , Yan Zhiqiang , Lin Xinhua , Lin Jinzhong , Yu Wei 
Published: November 2019

AbstractCharcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. Mutations in GARS (GARSCMT2D) show partial loss-of-function features, suggesting that tRNA-charging deficits play a role in disease pathogenesis, but the underlying mechanisms are not fully understood. In this study we report that wild-type GARS tightly binds the NAD+-dependent deacetylase SIRT2 and inhibits its deacetylation activity, resulting in the hyperacetylated α-tubulin, the major substrate of SIRT2. Previous studies showed that acetylation of α-tubulin protects microtubules from mechanical breakage and keep axonal transportation. However, CMT2D mutations in GARS can not inhibit SIRT2 deacetylation, which leads to decrease acetylated α-tubulin and severe axonal transport deficits. Genetic reduction of SIRT2 in the Drosophila model rescues the GARS–induced axonal CMT neuropathy and extends the life span. Our findings demonstrate the pathogenic role of SIRT2-dependent α-tubulin deacetylation in mutant GARS-induced neuropathies and provide new perspectives for targeting SIRT2 as a potential therapy against hereditary axonopathies.
Neonatal endotoxin stimulation was associated with long- term innate immune markers and an anti-allergic response in bronchiolar epithelium in spite of allergen challenge
Authors: García Luciana N , Leimgruber Carolina , Nicola Juan P. , Quintar Amado A , Maldonado Cristina A 
Published: November 2019

ABSTRACTAsthma is a heterogeneous disease underlying different medical processes, being the allergic asthma, with an early-onset in childhood, the most common type. In this phenotype, the continuous exposure to allergens produces a Th2-driven airway remodeling process that leads to symptoms and pathophysiological changes in asthma. Strategies as the avoidance of aeroallergen exposure in early life have been tested to prevent asthma, without a clear success. Alongside, several mouse models of aeroallergen challenge have dissected potential homeostatic responses by which environmental microbial stimulation reduces the subsequent allergic inflammation in the offspring. This suggests the onset of underlying preventive mechanisms in the beginning of asthma that have not been fully recognized. In this study, we aimed to evaluate if neonatal LPS-induced stimulus in epithelial host defenses could contribute to the prevent asthma in adult Balb/c mice. For this purpose, we studied the response of bronchiolar club cells (CC) that are situated in the crossroads of the host defense and allergic inflammation, and express specific pro and antiallergic proteins. LPS stimulus in the neonatal life intensified the production of TLR-4, TNFα, and natural anti-allergic products (CCSP and SPD), changes that contributed to prevent asthma triggering in adulthood. At epithelial level, CC skipped the mucous metaplasia, declining the overproduction of mucin via the EGFR pathway and the mice expressed normal breathing patterns in front of OVA challenge. Furthermore, the overexpression of TSLP, an epithelial pro-Th2 cytokine was blunted and normal TSLP and IL-4 levels were found in bronchoalveolar lavage (BAL). Complementing this shift, we also detected lower eosinophilia in BAL while an increase in phagocytes as well as in regulatory cells (CD4+CD25+FOXP3+ and CD4+IL-10+) was seen, whit an elevation in IL-12 and TNFα secretion. Summarizing, our study pointed to stable asthma-preventive effects promoted by neonatal LPS-stimulation; the main finding was the increase of several anti-Th2 specific proteins at epithelial level, together with an important diminution of pro-Th2 TSLP, conditions that promoted changes in the local immune response with Treg. We thus evidenced several anti-allergic dynamic mechanisms overlying in the epithelium that could be favored in an adequate epidemiological environment
TCF7L2 plays a complex role in human adipose progenitor biology which may contribute to genetic susceptibility to type 2 diabetes
Authors: Verma Manu , Loh Nellie Y. , Vasan Senthil K. , van Dam Andrea D. , Todorčević Marijana , Neville Matt J. , Karpe Fredrik , Christodoulides Constantinos 
Published: November 2019

ABSTRACTNon-coding genetic variation at TCF7L2 is the strongest genetic determinant of type 2 diabetes (T2D) risk in humans. TCF7L2 encodes a transcription factor mediating the nuclear effects of WNT signalling in adipose tissue (AT). Here we mapped the expression of TCF7L2 in human AT and investigated its role in adipose progenitor (AP) biology. APs exhibited the highest TCF7L2 mRNA abundance compared to mature adipocytes and adipose-derived endothelial cells. Obesity was associated with reduced TCF7L2 transcript levels in subcutaneous abdominal AT but increased expression in APs. In functional studies, TCF7L2 knockdown (KD) in APs led to dose-dependent activation of WNT/β-catenin signaling, impaired proliferation and dose-dependent effects on adipogenesis. Whilst partial KD enhanced adipocyte differentiation, complete KD impaired lipid accumulation and adipogenic gene expression. Overexpression of TCF7L2 accelerated adipogenesis. Transcriptome-wide profiling revealed that TCF7L2 can modulate multiple aspects of AP biology including extracellular matrix secretion, immune signalling and apoptosis. The T2D-risk allele at rs7903146 was associated with reduced AP TCF7L2 expression and enhanced AT insulin sensitivity. Our study highlights a complex role for TCF7L2 in AP biology and suggests that in addition to regulating pancreatic insulin secretion, genetic variation at TCF7L2 may also influence T2D risk by modulating AP function.
Reactomics: using mass spectrometry as a reaction detector
Authors: Yu Miao , Petrick Lauren 
Published: November 2019

AbstractUntargeted metabolomics analysis captures chemical reactions among small molecules. Common mass spectrometry-based metabolomics workflows first identify the small molecules significantly associated with the outcome of interest, then begin exploring their biochemical relationships to understand biological fate (environmental studies) or biological impact (physiological response). We suggest an alternative by which biochemical relationships can be directly retrieved through untargeted high-resolution paired mass distance (PMD) analysis without a priori knowledge of the identities of participating compounds. Retrieval is done using high resolution mass spectrometry as a chemical reaction detector, where PMDs calculated from the mass spectrometry data are linked to biochemical reactions obtained via data mining of small molecule and reaction databases, i.e. ‘Reactomics’. We demonstrate applications of reactomics including PMD network analysis, source appointment of unknown compounds, and biomarker reaction discovery as a complement to compound discovery analyses used in traditional untargeted workflows. An R implementation of reactomics analysis and the reaction/PMD databases is available as the pmd package (https://yufree.github.io/pmd/).
dNEMO: a tool for quantification of mRNA and punctate structures in time-lapse images of single cells
Authors: Kowalczyk Gabriel J. , Cruz J. Agustin , Guo Yue , Zhang Qiuhong , Sauerwald Natalie , Lee Robin E. C. 
Published: November 2019

ABSTRACTMany biological processes are regulated by single molecules and molecular assemblies within cells that are visible by microscopy as punctate features, often diffraction limited. Here we present detecting-NEMO (dNEMO), a computational tool optimized for accurate and rapid measurement of fluorescent puncta in fixed-cell and time-lapse images. The spot detection algorithm uses the à trous wavelet transform, a computationally inexpensive method that is robust to imaging noise. By combining automated with manual spot curation in the user interface, fluorescent puncta can be carefully selected and measured against their local background to extract high quality single-cell data. Integrated into the workflow are segmentation and spot-inspection tools that enable almost real-time interaction with images without time consuming pre-processing steps. Although the software is agnostic to the type of puncta imaged, we demonstrate dNEMO using smFISH to measure transcript numbers in single cells in addition to the transient formation of IKK/NEMO puncta from time-lapse images of cells exposed to inflammatory stimuli.
Host cholesterol dependent activation of VapC12 toxin enriches persister population duringMycobacterium tuberculosisinfection
Authors: Talwar Sakshi , Pandey Manitosh , Sharma Chandresh , Kutum Rintu , Lum Josephine , Carbajo Daniel , Goel Renu , Poidinger Michael , Dash Debasis , Singhal Amit , Pandey Amit Kumar 
Published: November 2019

AbstractA worldwide increase in the frequency of multidrug-resistant and extensively drug-resistant cases of tuberculosis is mainly due to therapeutic noncompliance associated with a lengthy treatment regimen. Depending on the drug susceptibility profile, the treatment duration can extend from 6 months to 2 years. This protracted regimen is attributed to a supposedly non-replicating and metabolically inert subset of theMycobacterium tuberculosis(Mtb) population, called ‘persisters’. The mechanism underlying stochastic generation and enrichment of persisters is not fully known. We have previously reported that the utilization of host cholesterol is essential for mycobacterial persistence. In this study, we have demonstrated that cholesterol-induced activation of a ribonuclease toxin (VapC12) inhibits translation by targeting proT tRNA in Mtb. This results in cholesterol-specific growth modulation that increases the frequency of the generation of persisters in a heterogeneous Mtb population. Also, a null mutant strain of this toxin (ΔvapC12) failed to persist and demonstrated an enhanced growth phenotype in a guinea pig model of Mtb infection. Thus, we have identified a novel strategy through which cholesterol-specific activation of a toxin–antitoxin (TA) module in Mtb enhances persister formation during infection. In addition to identifying the mechanism, the study provides opportunity for targeting persisters, a new paradigm facilitating tuberculosis drug development.
“Saying yes to everything”: Slung Low’s mission in a time of rapid change
Authors: Perry Rachel 
Published: November 2019

PurposeThis study explores what it means to be a mission-driven arts organisation (MDAO) in the UK. Drawing on literature relating to artistic risk and rupture, mission and vision, and arts participation, the purpose of this paper is to shed light on how Slung Low, a theatre organisation with a core staff of five, creates large and complex initiatives and seeks to make a difference to its local community.Design/methodology/approachUsing a case study approach, this interpretive study makes use of qualitative data to offer context-specific knowledge about how MDAOs create new initiatives including: interviews with members of the Slung Low team; attendance at company meetings; analysis of internal organisational documents, company website and artistic director’s blog; and articles about Slung Low from the local, national and theatre industry press. Data was gathered through a research collaboration with Slung Low which is supported by Paul Hamlyn Foundation.FindingsThe results offer fresh insight into how MDAOs take a positive approach to rupture and rapid change. The study finds that by embracing risk and committing to an ambitious and provocative mission, small-scale arts organisations can achieve artistic, cultural and social objectives which far exceed their size.Research limitations/implicationsThis paper offers an organisational perspective on the research questions and so participants were not interviewed on this occasion. However, the participant view will be the subject of further research with Slung Low.Originality/valueThis research paper provides insight into one of the UK’s most innovative theatre companies during a period of monumental change, and advances knowledge on mission-driven organisations by offering reflections on what it means to be an arts organisation which places rupture, risk and usefulness at the heart of its mission.
Study on the corrosion resistance performance of PbO2-ZrO2 nanocomposite electrode in NaCl electrolyte solution
Authors: Teng Ganggang , Wei Feng , Yao Yingwu 
Published: November 2019

Purpose
This paper aims to improve the corrosion resistance performance and stability of PbO2 electrodes in chloride wastewater.

Design/methodology/approach
The morphology of PbO2-ZrO2 nanocomposite electrodes was observed by scanning electron microscopy (SEM). The open circuit potential (OCP) curves, anodic polarization curves, electrochemical impedance spectra, accelerated life tests, weight-loss tests and reusability tests were used to study the corrosion resistance properties and stability of PbO2-ZrO2 nanocomposite electrodes in NaCl solution.

Findings
SEM showed that the surface morphology of PbO2-ZrO2 nanocomposite electrodes became compacted and smooth. Electrochemical tests showed that ZrO2 nanoparticles could increase the OCP, corrosion potential and charge transfer resistance, and decrease the corrosion current density in 3.5 Wt. per cent NaCl electrolyte solution. Besides, PbO2-ZrO2 nanocomposite electrodes showed high reusability for acetamiprid degradation, the accelerated service life could reach 146 h, which was almost 3.3 times longer than that of PbO2 electrodes (44 h), weight-loss tests showed that the corrosion resistance for PbO2-ZrO2 nanocomposite electrodes was 2.3 times as compared to PbO2 electrodes.

Originality/value
By the codeposition of ZrO2 nanoparticles, the corrosion resistance performance and stability of PbO2 electrodes in NaCl electrolyte were improved.
Enhancing cognitive and entrepreneurship competencies through EBL
Authors: Kholilah  , Wafaretta Vega , Syariati Dian 
Published: November 2019

Purpose
Entrepreneurship-based learning (EBL) is one of the student-center learningmethods that can answer learning challenges in the era of industrial revolution 4.0. EBL is expected to improve students’ competencies and make students more adaptable to the changes in the world of work in the future. The paper aims to discuss this issue.

Design/methodology/approach
This study uses quasi-experiments and divides classes into project class and control class. The project consists of making business proposals, conducting business, liquidating the partnership, and recording business transaction using the Xero platform. The Wilcoxon Signed Ranks Test, Mann–Whitney Test and independent t-test were carried out to test whether there are differences of cognitive abilities and entrepreneurial (general, social and functional) competencies between the project class and control class.

Findings
The results of the study shows there are differences of understanding of partnership accounting and the achievement of social and functional entrepreneurial competencies between the project class and control class.

Research limitations/implications
This study implies in using EBL to improve entrepreneurial skills for students beyond cognitive abilities.

Originality/value
The novelty of this research is the implementation of EBL in partnership accounting topics.
Rhetorical strategies and emotions in political marketing management
Authors: Ortigueira-Sánchez Luis Camilo , Cárdenas-Egúsquiza Ana Lucía 
Published: November 2019

Purpose
The purpose of this paper is to analyze how political marketing management in terms of communication practices influence the voters’ emotional responses as they observe and listen to the discourse of a political leader.

Design/methodology/approach
An experiment was conducted, in which participants watched the last debate of the campaign leading up the Peruvian presidential elections held in June 2016. During the experiment, the Emotient FACET technology codifies the facial micro-expressions of participants.

Findings
The results reveal that a voter’s political tendencies influence the intensity of their positive emotions, when the political leader communicated a challenging message. Rhetorical strategies and non-verbal behaviors accompany this type of message in order to emphasize the discourse and persuade the audience.

Practical implications
The findings suggest that the gender gap in attitudes toward female politicians exists and could change the relationship found, influencing negative emotions instead of positive emotions. The implications of the findings for achieving political success are discussed.

Originality/value
The study makes a methodological contribution, employing an experimental protocol based on Emotient FACET technology in a political context, thereby enabling more direct and objective measurement of voters’ emotional responses.
Investigation of process and product parameters for physico-chemical properties of low Glycemic Index water chestnut and barley flour-based extruded snacks
Authors: Beigh Mushtaq , Hussain Syed Zameer , Qadri Tahiya , Naseer Bazila , Raja Tariq , Naik Haroon 
Published: November 2019

Purpose
Keeping in view the diabetes status that has affected about 415 million people globally and is the leading cause of death in many countries along with therising demand for low Glycemic Index (GI) foods, the purpose of this paper is to optimize the extrusion process for the development of low GI snacks from underutilized crops like water chestnut and barley.

Design/methodology/approach
The extrusion parameters (screw speed and barrel temperature), feed moisture and water chestnut flour, barley flour proportion, were varied and their effects on system and product responses (specific mechanical energy, water absorption index, water solubility index, bulk density, expansion ratio and breaking strength) were studied.

Findings
All the system and product responses were significantly affected by independent variables. Response surface and regression models were established to determine the responses as function of process variables. Models obtained were highly significant with high coefficient of determination (R2=0.88). The optimum processing conditions obtained by numerical optimization for the development of snacks were 90°C barrel temperature, 300 rpm screw speed, 14 per cent feed moisture and WCF-to-BF ratio as 90:10. Shelf life studies confirmed that the developed snacks can be safely stored in HDPE bags for a period of six months under ambient conditions.

Originality/value
Water chestnut and barley flour did not blend till date for extrusion cooking. Such snacks shall be a viable food option for diabetic people and can act as laxative due to high fibre and β-glucan content from barley.
Agile business process management
Authors: Badakhshan Peyman , Conboy Kieran , Grisold Thomas , vom Brocke Jan 
Published: November 2019

Purpose
Business Process Management (BPM) is key for successful organisational management. However, BPM techniques are often criticized for their inability to deal with continuous and significant change and uncertainty. Following recent calls to make BPM more agile and flexible towards change, this study presents the results of a systematic literature review (SLR) of agile concepts in BPM. Analysing and synthesising previous works and drawing on agility research in the field of IS, this paper introduces a framework for agile BPM. Integrating different components that define agility in the context of BPM, this framework offers a number of important implications. On the theoretical side, the authors argue that the concept of agile BPM departs in some important ways from traditional BPM research. This, in turn, points to various opportunities for future research. On the practical side, the authors suggest that emerging technologies, such as process mining, embody important features that help organisations to be more responsive to change. The paper aims to discuss these issues.

Design/methodology/approach
To assess the state of the art of agility in the BPM research, the authors conducted an SLR. More specifically, the authors drew on the approach of vom Brocke et al. (2009, 2015), which consists of five steps: defining the scope of the review; conceptualising the topic; searching for literature; analysing and synthesising literature; and developing a research agenda.

Findings
This study presents the results of a systematic review of agile concepts in BPM. This study then proposes a resulting research framework that can be used to strengthen the concept of agile BPM and provides an agenda for research in this rapidly growing and increasingly necessary area of BPM.

Originality/value
In this paper, the authors establish a shared understanding of agile BPM and develop an agile BPM framework that represents the current state as well as implications for research and practice in agile BPM.