bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localised Dynactin protects growing microtubules to deliveroskarmRNA to the posterior cortex of theDrosophilaoocyte
Authors: Nieuwburg Ross , Nashchekin Dmitry , Jakobs Maximilian , Carter Andrew , Trong Philipp Khuc , Goldstein Raymond E. , Johnston Daniel St 
Published: March 2017

AbstractThe localisation ofoskarmRNA to the posterior of theDrosophilaoocyte defines where the abdomen and germ cells form in the embryo. Kinesin 1 transportsoskarmRNA to the oocyte posterior along a polarised microtubule cytoskeleton that grows from non-centrosomal microtubule organising centres (ncMTOCs) along the anterior/lateral cortex. Here we show that the formation of this polarised microtubule network also requires the posterior regulation of microtubule growth. A mutation in the Dynactin Arp1 subunit causes mostoskarmRNA to localise in the posterior cytoplasm rather than cortically.oskarmRNA transport and anchoring are normal in this mutant, but the microtubules fail to reach the posterior pole. Thus, Dynactin acts as an anti-catastrophe factor that extends microtubule growth posteriorly. Kinesin 1 transports Dynactin to the oocyte posterior, creating a positive feedback loop that increases the length and persistence of the posterior microtubules that deliveroskarmRNA to the cortex.
Histologically resolved spatial multi-omics of human oral squamous cell carcinoma
Authors: Chen Tao , Cao Chen , Zhang Jianyun , Streets Aaron , Huang Yanyi , Li Tiejun 
Published: March 2017

AbstractBoth the composition of cell types and their spatial distribution in a tissue play a critical role in cellular function, organ development, and disease progression. For example, intratumor heterogeneity and the distribution of transcriptional and genetic events in single cells drive the genesis and development of cancer. However, it can be challenging to fully characterize the molecular profile of cells in a tissue with high spatial resolution because microscopy has limited ability to extract comprehensive genomic information, and the spatial resolution of genomic techniques tends to be limited by dissection. There is a growing need for tools that can be used to explore the relationship between histological features, gene expression patterns, and spatially correlated genomic alterations in healthy and diseased tissue samples. Here, we present a technique that combines label-free histology with spatially resolved multi-omics in un-fixed and unstained tissue sections. This approach leverages stimulated Raman scattering microscopy to provide chemical contrast that reveals histological tissue architecture, allowing for high-resolutionin situlaser micro-dissection of regions of interests. These micro-tissue samples are then processed for DNA and RNA sequencing to identify unique genetic profiles that correspond to distinct anatomical regions. We demonstrate the capabilities of this technique by mapping gene expression and copy number alterations to histologically defined regions in human squamous cell carcinoma (OSCC). Our approach provides complementary insights in tumorigenesis and offers an integrative tool for macroscale cancer tissues with spatial multi-omics assessments.
Predicting the impact of pneumococcal conjugate vaccine programme options in Vietnam: a dynamic transmission model
Authors: Le Polain De Waroux Olivier , Edmunds W. John , Takahashi Kensuke , Ariyoshi Koya , Mulholland E. Kim , Goldblatt David , Choi Yoon Hong , Dang Duc-Anh , Yoshida Lay Myint , Flasche Stefan 
Published: March 2017

ABSTRACTBackgroundCatch-up campaigns (CCs) at the introduction of the pneumococcal conjugate vaccines (PCVs) may accelerate the impact of PCVs. However, limited vaccine supplies may delay vaccine introduction if additional doses are needed for such campaigns. We studied the relative impact of introducing PCV13 with and without catch-up campaign, and the implications of potential introduction delays.MethodsWe used a dynamic transmission model applied to the population of Nha Trang in Sout central Vietnam. Four strategies were considered: routine vaccination (RV) only, and RV alongside catch-up campaigns among <1y olds (CC1), <2y olds (CC2) and <5y olds (CC5). The model was parameterised with local data on human social contact rates, and was fitted to local carriage data. Post-PCV predictions were based on best estimates of parameters governing post-PCV dynamics, including serotype competition, vaccine efficacy and duration of protection.ResultsOur model predicts elimination of vaccine-type (VT) carriage across all age groups within 10 years of introduction in all scenarios with near-complete replacement by non-VT. Most of the benefit of CCs is predicted to occur within the first 3 years after introduction, with the highest impact in the first year, when IPD incidence is predicted to be 11% (95%CrI 9 – 14%) lower than RV with CC1, 25% (21 – 30 %) lower with CC2 and 38% (32 – 46%) lower with CC5.However, CCs would only prevent more cases of IPD insofar such campaigns do not delay introduction by more than 31 (95%CrI 30 – 32) weeks with CC1, 58 (53 – 63) weeks with CC2 and 89 (78 – 101) weeks for CC5.ConclusionCCs are predicted to offer a substantial additional reduction in pneumococcal disease burden over RV alone, if their implementation does not result in much introduction delay. Those findings are important to help guide vaccine introduction in countries that have not yet introduced PCV, particularly in Asia.
Interaction of N-3-oxododecanoyl homoserine lactone with transcriptional regulator LasR ofPseudomonas aeruginosa: Insights from molecular docking and dynamics simulations
Authors: Grabski Hovakim , Hunanyan Lernik , Tiratsuyan Susanna , Vardapetyan Hrachik 
Published: March 2017

ABSTRACTBackgroundIn 2017 World Health Organization announced the list of the most dangerous superbugs and among them isPseudomonas aeruginosa,which is an antibiotic resistant opportunistic human pathogen as well as one of the ‘SKAPE’ pathogens. The central problem is that it affects patients suffering from AIDS, cystic fibrosis, cancer, burn victims etc.P. aeruginosacreates and inhabits surface-associated biofilms. Biofilms increase resistance to antibiotics and host immune responses, because of those current treatments are not effective. It is imperative to find new antibacterial treatment strategies againstP. aeruginosa,but detailed molecular properties of the LasR protein are not clearly known to date. In the present study, we tried to analyse the molecular properties of the LasR protein as well as the mode of its interactions with autoinducer (AI) the N-3-oxododecanoyl homoserine lactone (3-0-C12-HSL).ResultsWe performed docking and molecular dynamics (MD) simulations of the LasR protein ofP. aeruginosawith the 3-0-C12-HSL ligand. We assessed the conformational changes of the interaction and analysed the molecular details of the binding of the 3-0-C12-HSL with LasR. A new interaction site of the 3-0-C12-HSL with LasR protein was found, which involves interaction with conservative residues from ligand binding domain (LBD), beta turns in the short linker region (SLR) and DNA binding domain (DBD). It will be referenced as the LBD-SLR-DBD bridge interaction or “the bridge”. We have also performed LasR monomer protein docking and found a new form of dimerization.ConclusionsThis study may offer new insights for future experimental studies to detect the interaction of the autoinducer with “the bridge” of LasR protein and a new interaction site for drug design.
Modelling firing regularity in the ventral cochlear nucleus: mechanisms, and effects of stimulus level and synaptopathy
Authors: Goodman Dan F. M. , Winter Ian M. , Léger Agnès C. , de Cheveigné Alain , Lorenzi Christian 
Published: March 2017

AbstractThe auditory system processes temporal information at multiple scales, and disruptions to this temporal processing may lead to deficits in auditory tasks such as detecting and discriminating sounds in a noisy environment. Here, a modelling approach is used to study the temporal regularity of firing by chopper cells in the ventral cochlear nucleus, in both the normal and impaired auditory system. Chopper cells, which have a strikingly regular firing response, divide into two classes, sustained and transient, based on the time course of this regularity. Several hypotheses have been proposed to explain the behaviour of chopper cells, and the difference between sustained and transient cells in particular. However, there is no conclusive evidence so far. Here, a reduced mathematical model is developed and used to compare and test a wide range of hypotheses with a limited number of parameters. Simulation results show a continuum of cell types and behaviours: chopper-like behaviour arises for a wide range of parameters, suggesting that multiple mechanisms may underlie this behaviour. The model accounts for systematic trends in regularity as a function of stimulus level that have previously only been reported anecdotally. Finally, the model is used to predict the effects of a reduction in the number of auditory nerve fibres (deafferentation due to, for example, cochlear synaptopathy). An interactive version of this paper in which all the model parameters can be changed is available online.HighlightsA low parameter model reproduces chopper cell firing regularityMultiple factors can account for sustained vs transient chopper cell responseThe model explains stimulus level dependence of firing regularityThe model predicts chopper cells fire more irregularly after deafferentationAn interactive version of the paper allows readers to change parameters
The perforated borders of labour migration and the formal state
Authors: Portes Virginio Francis Vinicius , Garvey Brian , Stewart Paul 
Published: March 2017

PurposeThe purpose of this paper is to explore the variation in migrant labour market regimes and what these reveal about variant patterns of state and extra state regulation in two contemporary political economies.Design/methodology/approachResearch based upon a participatory action research agenda in Mexico and the north of Ireland. Migrant workers and their families where involved in the project and its development. This included participation in the research design, its focus and purpose.FindingsMigrant workers experiences of labour market subordination are part of wider processes of subordination and exclusion involving both the state, but also wider, often meta- and para-state, agents. In different locations, states and contexts, the precarity experienced by migrant workers and their families highlights the porosity of the formal rational legal state and moreover, in the current economic context, the compatibility of illegality and state sponsored neoliberal economic policies.Research limitations/implicationsIt is important to extend this study to other geographic and political economy spaces.Practical implicationsThe study challenges the limits of state agency suggesting the need for extra state, i.e. civil society, participation to support and defend migrant workers.Originality/valueNotwithstanding the two very different socio-economic contexts, the paper reveals that the interaction, dependence and restructuring of migrant labour markets can be understood within the context of meta- and para-state activities that link neoliberal employment insecurities. Migrants’ experiences illustrate the extent to which even formal legal employment relations can also be sustained by para- and meta- (illegal and alegal) actions and institutions.
All precarious? Institutional change and turning points in labour market trajectories in Spain
Authors: López Andreu Martí 
Published: March 2017

Purpose
The purpose of this paper is to explore the effects of changes in employment regulation in Spain on individual labour market trajectories. It is well known that the Spanish labour market has been strongly hit by the 2007 recession. Furthermore, after 2010 and in the benchmark of “austerity”, several reforms were implemented to further flexibilise employment regulation. At the same time, public sector budgets suffered severe cutbacks, that impacted working conditions and prospects of public sector workers. These reforms were implemented by different governments and substantially changed previous existing patterns of employment. This paper explains how these reforms have reinforced previous existing trends towards greater flexibility and weaker employment protection and how they lead to a shift in the position of work in society.

Design/methodology/approach
The emerging patterns that these changes provoked are illustrated thorough data from narrative biographies of workers affected by a job loss or a downgrading of working conditions. The workers of the sample had relatively stable positions and careers and were affected by changes that substantially modified their paths.

Findings
The paper shows how reforms have expanded work and employment insecurities and have broken career paths. It demonstrates how the reforms have weakened the position of work and organised labour in society and how, when institutional supports are jeopardised, the capacity to plan and act is harassed by the traditional social inequalities.

Originality/value
The paper enhances the knowledge about the impact of institutional changes by analysing their effects in individual working lives by means of narrative biographies.
Re-evaluating work-based learning pedagogy
Authors: Nottingham Paula McIver 
Published: March 2017

Purpose
The purpose of this paper is to examine work-based learning (WBL) pedagogy within higher education (HE) related to the use of the “field of study” concept.

Design/methodology/approach
This paper reviews WBL literature to discuss the original context of the concept and relates this to current pedagogic approaches through qualitative interviews and written explanations.

Findings
WBL pedagogy continues to use the concepts from field of study WBL but the study also indicates that academic practitioners are developing pedagogy to meet the needs of current workplace and educational policy.

Research limitations/implications
This paper is limited in its scope due to the small number of respondents but there are potential implications about emerging directions for this pedagogic range.

Practical implications
The paper argues that field of study WBL is still relevant to existing practice but further engagement and research surrounding WBL pedagogy is needed to examine this range of HE.

Originality/value
The added value is the evidence of evolving WBL pedagogy that can inform issues of flexibility within HE provision.
Leaving fingerprints: principals’ considerations while implementing education reforms
Authors: Schechter Chen , Shaked Haim 
Published: March 2017

PurposeTurning an education reform program into school reality greatly depends on the principal. In certain cases, principals choose to implement reform instructions only partially. The purpose of this paper is to explore school principals’ considerations leading to their decisions not to fulfill a national reform’s guidelines in a full and complete way.Design/methodology/approachThis qualitative study is based on interviews with 59 school principals. Generating themes was an inductive process, grounded in the various perspectives articulated by principals.FindingsData analysis yielded three major considerations: adjusting to school reality; caring for teachers; and using discretion.Research limitations/implicationsLongitudinal studies in order to explore how principals’ considerations and mediation strategies evolve and unfold throughout the reform implementation would be useful. The authors suggest complementing principals’ verbally expressed perceptions with more objective measures such as direct observations (recorded on video and then reflected upon), to evaluate their considerations and mediating strategies.Practical implicationsProviding prospective and in-service principals with leadership education programs in order to develop an upgraded understanding of their role as mediating agents between the inner and outer spheres of school-life.Originality/valueAs principals serve as mid-level policymakers who leave their “fingerprints” on policies received from the authorities, exploring these considerations may contribute to both the scholarship and the practice of the leadership role in times of education reforms.
Concentration and financial stability in the property-liability insurance sector: global evidence
Authors: Altuntas Muhammed , Rauch Jannes 
Published: March 2017

Purpose
This paper aims to examine the effect of concentration in the insurance sector on insurer stability for a large set of developed and developing countries. In particular, the authors test whether concentration reduces financial fragility in the insurance sector (“concentration-stability view”) or decreases stability in the insurance sector (“concentration-fragility view”).

Design/methodology/approach
The authors use a data set of 14,402 firm-year observations of property-liability insurers who appear in A.M. Best’s Statement File Global database during the period 2004-2012. They use regression analyses to examine the effect of concentration on the stability of insurance firms and apply different measures of concentration.

Findings
The results provide empirical support for the “concentration- fragility view”; that is, higher levels of concentration are associated with decreases in the insurance sector’s financial stability.

Research limitations/implications
The results have important policy implications, given that a primary purpose of insurance regulation is to protect policyholders against insurance firm defaults.

Originality/value
No previous research analyzes how recent trends in competition and consolidation, which have led to changes in insurance market concentration, affect the stability of insurance firms around the world. This research is the first paper that provides evidence on the relation between concentration and stability in the insurance sector.
Five years investigation of female and male genotypes in périgord black truffle (Tuber melanosporum Vittad.) revealed contrasted reproduction strategies
Authors: De la Varga Herminia , Le Tacon François , Lagoguet Mélanie , Todesco Flora , Varga Torda , Miquel Igor , Barry‐Etienne Dominique , Robin Christophe , Halkett Fabien , Martin Francis , Murat Claude 
Published: March 2017

SummaryThe Périgord black truffle (Tuber melanosporum Vittad.) is a heterothallic ascomycete that establishes ectomycorrhizal symbiosis with trees and shrubs. Small‐scale genetic structures of female genotypes in truffle orchards are known, but it has not yet been studied in male genotypes. In this study, our aim was to characterize the small‐scale genetic structure of both male and female genotypes over five years in an orchard to better understand the T. melanosporum sexual reproduction strategy, male genotype dynamics, and origins. Two‐hundred forty‐one ascocarps, 475 ectomycorrhizas, and 20 soil cores were harvested and genotyped using microsatellites and mating type genes. Isolation by distance analysis revealed pronounced small‐scale genetic structures for both female and male genotypes. The genotypic diversity was higher for male than female genotypes with numerous small size genotypes suggesting an important turnover due to ascospore recruitment. Larger and perennial female and male genotypes were also detected. Only three genotypes (1.5%) were found as both female and male genotypes (hermaphrodites) while most were detected only as female or male genotype (dioecy). Our results suggest that germinating ascospores act as male genotypes, but we also proposed that soil mycelium could be a reservoir of male genotypes.
Gregarious cyanobacteria
Authors: Stal Lucas J. 
Published: March 2017

SummaryHuber and collaborators reported in this issue of Environmental Microbiology about freshwater picocyanobacteria that showed phenotypic plasticity in the sense that they appeared as single cells as well as in aggregates. The authors suggested that aggregation might be an inducible defense as a response to the presence of grazers. This has been described for eukaryotic phytoplankton and for the cyanobacterium Microcystis but thus far not for picocyanobacteria. Although inducible defense as an explanation is an attractive possibility, it is also problematic. Aggregation is common among cyanobacteria and it offers many advantages as compared with a free‐living lifestyle. Here these advantages are highlighted and the possibility of inducible defense is critically assessed.
A Longitudinal Assessment of the Effect of Resident‐Centered Care on Quality in Veterans Health Administration Community Living Centers
Authors: Sullivan Jennifer L. , Shwartz Michael , Stolzmann Kelly , Afable Melissa K. , Burgess James F. 
Published: March 2017

ObjectiveTo examine whether changes in resident‐centered care (RCC) over time were associated with changes in quality.Data Sources/Study SettingData sources were the Minimum Dataset quality indicators (which consist of measures of both prevalence and incidence of adverse events) and the Artifacts of Culture Change Tool (which measures RCC; FYs 2009–2012) from 130 Veterans Health Administration community living centers.Study DesignA retrospective longitudinal study.Data Collection/Extraction MethodsData were from VA secondary data sources.Principal FindingsThe overall relationship between RCC and quality was not statistically significant (p = .22), although there was a weakly significant negative relationship (i.e., increased RCC was associated with poorer quality) in the seven quarters after implementation of an automated version of the Artifacts Tool (p = .08). In facility‐specific analyses, there were 15 facilities with a weakly significant (p < .10) positive relationship between RCC and quality and 21 with a weakly significant negative relationship. Adjusted cost per patient day was over 50 percent higher in the 21 facilities with a negative relationship than in the 15 facilities with a positive relationship (p < .05).ConclusionsThe Artifacts score is a formal performance metric in the VA, and thus, facilities were explicitly incentivized to increase RCC. Using qualitative methods to identify characteristics that distinguished those facilities able to increase both RCC and quality from those that suffered declines in quality as RCC was improved is an important follow‐up to this study.