bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and quantification of blood apoptotic bodies in neurological patients
Authors: Serrano-Heras Gemma , Díaz-Maroto Inmaculada , Carrión Blanca , Perona-Moratalla Ana B. , Gracia Julia , Arteaga Sandra , Hernández-Fernández Francisco , García-García Jorge , Castro-Robles Beatriz , Ayo-Martín Oscar , Segura Tomás 
Published: September 2019

AbstractDysregulation of apoptosis may contribute to the etiology and/or progression of several prevalent diseases, including stroke and neurodegenerative pathologies. So, detection of the apoptotic processes in patients would be useful in daily clinical practice, However, thein vivoanalysis of apoptosis that occurs in tissue has limitations. We therefore propose to use circulating apoptotic bodies as biomarkers for measuring apoptotic death in patients. Since there is no scientific literature establishing the most appropriate method for measuring apoptotic bodies from human blood samples, we here describe a reproducible centrifugation-based method combined with electron microscopy, dynamic light scattering and flow cytometry studies to isolate, characterize and quantify plasma apoptotic bodies of patients with ischemic stroke, multiple sclerosis and Parkinson’s disease. The analysis revealed that our isolation protocol achieves notable recovery rates of highly-purified intact apoptotic bodies. This easy and rapid procedure would help physicians to implement the use of plasma apoptotic bodies analysis as a non-invasive tool to monitor apoptotic death in neurological patients for prognostic purposes and for following disease activity and assessing drug effectiveness.
PINK1-dependent phosphorylation of Serine111 within the SF3 motif of Rab GTPases impairs effector interactions and LRRK2 mediated phosphorylation at Threonine72
Authors: Vieweg Sophie , Mulholland Katie , Bräuning Bastian , Kachariya Nitin , Lai Yu-Chiang , Toth Rachel , Sattler Michael , Groll Michael , Itzen Aymelt , Muqit Miratul M. K. 
Published: September 2019

AbstractLoss of function mutations in the PINK1 kinase are causal for autosomal recessive Parkinson disease (PD) whilst gain of function mutations in the LRRK2 kinase cause autosomal dominant PD. PINK1 indirectly regulates the phosphorylation of a subset of Rab GTPases at a conserved Serine111 (Ser111) residue within the SF3 motif. Using genetic code expansion technologies we have produced stoichiometric Ser111-phosphorylated Rab8A revealing impaired interactions with its cognate guanine nucleotide exchange factor (GEF) and GTPase activating protein (GAP). In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2. Strikingly we demonstrate that Ser111 phosphorylation negatively regulates the ability of LRRK2 but not MST3 or TAK1 to phosphorylate Thr72 in vitro and demonstrate an interplay of PINK1- and LRRK2-mediated phosphorylation of Rab8A in cells. Finally, we present the crystal structure of Ser111-phosphorylated Rab8A and NMR structure of Ser111-phosphorylated Rab1B that does not demonstrate any major changes suggesting that the phosphorylated SF3 motif may disrupt effector-Switch II interactions. Overall, we demonstrate antagonistic regulation between PINK1-dependent Ser111 phosphorylation and LRRK2-mediated Thr72 phosphorylation of Rab8A suggesting that small molecule activators of PINK1 may have therapeutic potential in patients harbouring LRRK2 mutations.
Dynamic rewiring of the human interactome by interferon signalling
Authors: Kerr Craig H. , Skinnider Michael A. , Madero Angel M. , Andrews Daniel D.T. , Stacey R. Greg , Chan Queenie W.T. , Stoynov Nikolay , Jan Eric , Foster Leonard J. 
Published: September 2019

ABSTRACTBackgroundThe type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes (ISGs). Transcriptomic and biochemical approaches have established comprehensive catalogues of ISGs across species and cell types, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to delineate the effects of IFN signalling on the human proteome, culminating in the use of protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network.ResultsWe identified >27,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer ISG protein synthesis.ConclusionsOur map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing ISGs in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.
Spatial control of nucleoporin assembly by Fragile X-related proteins
Authors: Agote-Arán Arantxa , Schmucker Stephane , Jerabkova Katerina , Boyer Inès Jmel , Berto Alessandro , Pacini Laura , Ronchi Paolo , Kleiss Charlotte , Guerard Laurent , Schwab Yannick , Moine Hervé , Mandel Jean-Louis , Jacquemont Sebastien , Bagni Claudia , Sumara Izabela 
Published: September 2019

SummaryNucleoporins (Nups) build highly organized Nuclear Pore Complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs to regulate nucleocytoplasmic exchange. In the cytoplasm, a large excess of soluble Nups has been reported, but how their assembly is restricted to the NE is currently unknown. Here we show that Fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule and dynein-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and Fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup protein condensates. Likewise, several models of Fragile X syndrome (FXS), characterized by a loss of FMRP, also accumulate cytoplasmic Nup aggregates. These aggregate-containing cells display aberrant nuclear morphology and a delay in G1 cell cycle progression. Our results reveal an unexpected role for the FXR protein family and dynein in the spatial regulation of nucleoporin assembly.HighlightsCytoplasmic nucleoporins are assembled by Fragile X-related (FXR) proteins and dyneinFXR-Dynein pathway downregulation induces aberrant cytoplasmic aggregation of nucleoporinsCellular models of Fragile X syndrome accumulate aberrant cytoplasmic nucleoporin aggregates.FXR-Dynein pathway regulates nuclear morphology and G1 cell cycle progressioneTOC BlurbNucleoporins (Nups) form Nuclear Pore Complexes (NPCs) at the nuclear envelope. Agote-Arán at al. show how cells inhibit aberrant assembly of Nups in the cytoplasm and identify Fragile X-related (FXR) proteins and dynein that facilitate localization of Nups to the nuclear envelope and control G1 cell cycle progression.Graphical abstract
GRASP: a Bayesian network structure learning method using adaptive sequential Monte Carlo
Authors: Yu Kaixian , Cui Zihan , Qiu Xing , Zhang Jinfeng 
Published: September 2019

AbstractBayesian networks (BNs) provide a probabilistic, graphical framework for modeling high-dimensional joint distributions with complex dependence structures. BNs can be used to infer complex biological networks using heterogeneous data from different sources with missing values. Despite extensive studies in the past, network structure learning from data is still a challenging open question in BN research. In this study, we present a sequential Monte Carlo (SMC) based three-stage approach, GRowth-based Approach with Staged Pruning (GRASP). A double filtering strategy was first used for discovering the overall skeleton of the target BN. To search for the optimal network structures we designed an adaptive SMC (adSMC) algorithm to increase the diversity of sampled networks which were further improved by a new stage to reclaim edges missed in the skeleton discovery step. GRASP gave very satisfactory results when tested on benchmark networks. Finally, BN structure learning using multiple types of genomics data illustrates GRASP’s potential in discovering novel biological relationships in integrative genomic studies.
Further investigation of the potential anti-neoplastic, anti-inflammatory and immunomodulatory actions of phenoxybenzamine using the Broad Institute CLUE platform
Authors: Inchiosa Mario A. 
Published: September 2019

AbstractPrevious clinical studies with the FDA-approved alpha-adrenergic antagonist, phenoxybenzamine, showed apparent efficacy to reverse the symptoms and disabilities of the neuropathic condition, Complex Regional Pain Syndrome; also, the anatomic spread and intensity of this syndrome has a proliferative character and it was proposed that phenoxybenzamine may have an anti-inflammatory, immunomodulatory mode of action. A previous study gave evidence that phenoxybenzamine had anti-proliferative activity in suppression of growth in several human tumor cell cultures. The same report demonstrated that the drug possessed significant histone deacetylase inhibitory activity. Utilizing the Harvard/Massachusetts Institute of Technology Broad Institute genomic database, CLUE, the present study suggests that the gene expression signature of phenoxybenzamine in malignant cell lines is consistent with anti-inflammatory/immunomodulatory activity and suppression of tumor expansion by several possible mechanisms of action. Of particular note, phenoxybenzamine demonstrated signatures that were highly similar to those with glucocorticoid agonist activity. Also, gene expression signatures of phenoxbenzamine were consistent with several agents in each case that were known to suppress tumor proliferation, notably, protein kinase C inhibitors, Heat Shock Protein inhibitors, epidermal growth factor receptor inhibitors, and glycogen synthase kinase inhibitors. Searches in CLUE also confirmed the earlier observations of strong similarities between gene expression signatures of phenoxybenzamine and several histone deacetylase inhibitors.
Correction of z-motion artefacts to allow population imaging of synaptic activity in awake behaving mice
Authors: Ryan Thomas , Hinojosa Antonio , Vroman Rozan , Papasavvas Christoforos , Lagnado Leon 
Published: September 2019

AbstractFunctional imaging of head-fixed, awake, behaving mice using two-photon imaging of fluorescent activity reporters has become a powerful tool in the studying the function of the brain. Motion artefacts are an inevitable problem during such experiments and are routinely corrected for in x and y dimensions. However, axial (z) shifts of several microns can also occur, leading to intensity fluctuations in structures such as synapses that are small compared to the axial point-spread function of the microscope. Here we present a simple strategy to correct z-motion artefacts arising over the course of a time-series experiment in a single optical plane. Displacement in z was calculated using dye-filled blood vessels as an anatomical marker, providing high contrast images and accuracy to within ∼0.1 µm. The axial profiles of ROIs corresponding to synapses were described using a Moffat function and this “ROI-spread function” used to correct activity traces on an ROI-by-ROI basis. We demonstrate the accuracy and utility of the procedures in simulation experiments using fluorescent beads and then apply them to correcting measurements of synaptic activity in populations of vasoactive-intestinal peptide (VIP) interneurons expressing the synaptic reporter SyGCaMP6f. Correction of z-motion artefacts had a substantial impact on the apparent correlation between synaptic activity and running speed, demonstrating the importance of correcting for these artefacts for the interpretation of in vivo imaging experiments in awake mice.Summary of Key PointsMotion artefacts associated with motor behaviour are an inevitable problem of multiphoton imaging in awake behaving animals, particularly imaging synapses.Correction of axial motion usually requires volumetric imaging resulting in slower rates of acquisition.We describe a method that is easy to implement to correct z-motion artefacts that allows population imaging of synaptic activity while scanning a single plane in a standard multiphoton microscope.The method uses a reference volume acquired in two colour channels – an activity reporter and an anatomical marker of blood vessels. The procedure estimates the z-displacement in every frame and applies an intensity correction in which the z point-spread function for each synapse is modelled as a Moffat function.We demonstrate that the method allows synaptic calcium activity signals to be collected from populations of synaptic boutons in mouse primary visual cortex during locomotion.
AFF3 and BACH2 are master regulators of metabolic inflexibility, β/α-cell transition, and dedifferentiation in type 2 diabetes
Authors: Son Jinsook , Ding Hongxu , Accii Domenico , Califano Andrea 
Published: September 2019

ABSTRACTType 2 Diabetes is associated with defective insulin secretion, reduced β-cell mass, and increased glucagon production. Cell lineage-tracing in rodents and human autopsy surveys support the notion of β-cell dedifferentiation as a unifying mechanism for these abnormalities. Yet, mechanistic determinants of human β-cell failure remain elusive. Using regulatory-network-based single-cell analysis of human islets, we identify aberrant, diabetes-enriched transitional states characterized by metabolic inflexibility, α/β-transition, and endocrine progenitor/stem cell features. A coordinated transcription factor hierarchy mediating cell state transition emerged and was validated using barcoded guide-based, single-cell gene transfer and calcium flux measures in primary human islet cells. Specifically, two master regulators and associated epigenetic drivers emerged, one (AFF3) controlling β- to α-like-cell reprogramming, the other (BACH2) transition to a dedifferentiated endocrine progenitor-like cell. The findings provide mechanistic insight into diabetic islet cell dysfunction and suggest actionable pathways for pharmacological intervention.
Development of the duodenal, ileal, jejunal and caecal microbiota in chickens
Authors: Glendinning Laura , Watson Kellie A , Watson Mick 
Published: September 2019

AbstractBackgroundThe chicken intestinal microbiota plays a large role in chicken health and productivity and a greater understanding of its development may lead to interventions to improve chicken nutrition, disease resistance and welfare.ResultsIn this study we examine the duodenal, jejunal, ileal and caecal microbiota of chickens from day of hatch to 5 weeks of age (day 1, 3, 7, 14 and week 5). DNA was extracted from intestinal content samples and the V4 region of the 16S rRNA gene was amplified and sequenced. We identify significant differences in microbial community composition, diversity and richness between samples taken from different locations within the chicken intestinal tract. We also characterise the development of the microbiota at each intestinal site over time.ConclusionsOur study builds upon existing literature to further characterise the development of the chicken intestinal microbiota.
Understanding the impacts of Chinese business activity in Kenya from the perspective of locals
Authors: Okumu Charles Onjumi , Fee Anthony 
Published: September 2019

Purpose
The authors report a field study examining the perceptions of Kenyan host-country stakeholders toward activities of Chinese businesses in their country, and the consequences of this on the legitimacy that they bestow on pertinent entities.

Design/methodology/approach
Interviews and observations across an eight-week period of field research revealed generally negative attitudes toward Chinese businesses, with issues pertinent to moral legitimacy prominent, notably, perceptions of corrupt practices, environmental neglect and profit expatriation.

Findings
The authors also find evidence that these negative attitudes spilled over to contaminate Kenyans’ perceptions of their own government, which respondents associated closely with the activities of Chinese entities.

Originality/value
The authors extend understanding of legitimacy theory and the implications of foreign business activity by highlighting that businesses may be mistaken to believe that their international business activities are politically neutral, and while host governments may believe that the economic benefits arising from attracting foreign business activity can buttress their legitimacy, the perceived activities of these businesses, in the absence of supporting institutional frameworks, may render this counterproductive.
Evaluation and improvement of the credit transfer models in the student exchange process
Authors: Nizam Ali 
Published: September 2019

Purpose
Increasing flexibility and student mobility are among the most important objectives of today’s universities. The purpose of this paper is to discuss the effects of student exchange process (SEP) on a campus management system (CMS), compare different models and recommend an improvement handling transfer process.

Design/methodology/approach
A comprehensive literature review of how credit transfer is handled in today’s CMS was conducted to understand the information management methods used in the student transfer process. On this basis, a flexible task-based system design is recommended to facilitate the transfer of educational gains between universities. For evaluating the effectiveness of different system designs in the SEP, the duration of information processing process steps was measured quantitatively via on-site observations and user interview in a university’s horizontal, vertical and the Erasmus student exchange (SE) data.

Findings
Building a flexible system design based on a loosely coupled mapping between curriculum and educational activities, and increasing the self-management capabilities of a student will facilitate managing SE data in an integrated environment and reduce the university staff’s workload considerably.

Originality/value
To the author’s knowledge, this is the first study making quantitatively measurement and comparison of different credit transfer methods of CMSs. Based on this result, the authors have recommended a new flexible method that supports increasing a student’s self-administration capabilities, reducing the workload of university staff, and contributes academic mobility.
Automation, job characteristics and job insecurity
Authors: Coupe Tom 
Published: September 2019

Purpose
The purpose of this paper is to analyze whether specific jobs characteristics, which experts have identified as being more automation proof, are associated with reduced job insecurity.

Design/methodology/approach
Data come from a recent survey providing information on sources of job insecurity as well as on detailed job characteristics. The analysis is based on various regression models.

Findings
People who have jobs that involve lots of personal interaction are less likely to be concerned about losing their job because of automation, or because of other reasons, and are more likely to think their job will exist 50 years from now. Having a creative job does not change these concerns. The share of respondents who fear losing their job to automation is fairly small, and those who do, typically fear other sources of job insecurity as much or even more.

Practical implications
Developing interpersonal skills is more likely to be an effective strategy for reducing job insecurity than developing creative skills. The findings further suggest that policies aimed at automation are unlikely to suffice for the elimination of worry over job loss, as many workers who fear automation at the same time feel there are other reasons that might lead to the loss of their job.

Originality/value
There are very few studies that link fear of losing one’s job to automation to a job’s characteristics. The survey used here is unique in the level of detail provided on job characteristics.
Citizen feedback and executives
Authors: Havaeji Hossein , Albadvi Amir 
Published: September 2019

PurposeThe purpose of this paper is to design a model in order that government hears citizen voices and welcomes people’s suggestions to improve its performance, it may be regarded as Management By People’s Suggestions.Design/methodology/approachAfter designing a conceptual model, collected data through the responses of 451 questionnaires from nine areas of Iran Territory Development Plan were analyzed using the structural equation model and an ANOVA.FindingsThe results indicate three directions are initiatives for the action of using citizens’ opinions to improve government performance. The directions are as follows: the direction of government strategies moving toward citizens’ needs; the direction of developing a seamless, integrated, coordinated, relationship between citizens and authorities; and the direction of centralizing citizens’ suggestions and criticisms.Practical implicationsThis study suggests an approach using citizen feedback to improve government performance in Iran where it appears to be signs of a gap between people and government.Originality/valueThis paper reveals that, before any effort for citizen relationship management, investigations into effective directions which affect citizen–government relationship seems essential.
From green to good supply chains:
Authors: Carbone Valentina , Moatti Valérie , Schoenherr Tobias , Gavirneni Srinagesh 
Published: September 2019

PurposeThe purpose of this paper is to investigate to what extent dynamic capabilities (DCs) developed in the field of green supply chain management can foster social supply chain performance. In addition, the role of both human and stakeholder capital in enhancing this relationship is investigated.Design/methodology/approachRelying on the theoretical framework of the resource-based view, complemented with the DCs perspective, the authors hypothesize about the benefits of a firm’s environmental management capability for its social supply chain performance, as well as the moderating role of both human and stakeholder capital. Our contentions are tested through a multi-year database of socially responsible investments covering 1,177 multinational corporations.FindingsThe findings show that companies can sustain positive and superior social performance in their supply chain by leveraging DCs developed in the environmental field. This impact is further shown to be elevated in the presence of both human and stakeholder capital.Research limitations/implicationsThis study represents a snapshot of the transformation process from environmentally to socially responsible supply chains. While the secondary data employed offers unique advantages, secondary data also have limitations.Social implicationsDeveloping environmental capabilities not only enhances companies’ profitability, but can also lead to better supply chains through improved labor conditions and well-being.Originality/valueThe authors’ shift from a company-centric to a sustainability-centric conceptualization of DCs can open up new opportunities to engage research, potentially leading to high-impact results in the field of sustainable supply chain management. In addition, the authors leverage a secondary data source not frequently utilized in prior work.