bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Cortical Dendritic Membrane Potential and Spikes in Freely Behaving Rats
Authors: Moore Jason J. , Ravassard Pascal M. , Ho David , Acharya Lavanya , Kees Ashley L. , Vuong Cliff , Mehta Mayank R.
Published: December 2016

Neural activityin vivois primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which generate dendritic action potentials (DAP) and profoundly influence neural computation and plasticity. We measured neocortical sub- and supra-threshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and sub-millisecond temporal resolution. DAP firing rates were several fold larger than somatic rates. DAP rates were modulated by subthreshold DMP fluctuations which were far larger than DAP amplitude, indicting hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity.

One Sentence Summary

Measurement of cortical dendritic membrane potential for several days in freely behaving rats reveals disproportionate dendritic spiking and analog and digital coding.
Hnf4a mediates microbial control of intestinal gene expression and inflammation
Authors: Davison James M. , Lickwar Colin R. , Song Lingyun , Breton Ghislain , Crawford Gregory E. , Rawls John F.
Published: December 2016

Microbiota influence diverse aspects of intestinal epithelial physiology and disease in part by controlling tissue-specific transcription of host genes. However, host genomic mechanisms mediating microbial control of host gene expression are poorly understood. Using an unbiased screening strategy, we found that the zebrafish Hepatic nuclear factor 4 alpha (Hnf4a) transcription factor specifically binds and activates a microbiota-suppressed intestinal epithelial transcriptional enhancer. Genetic analysis disclosed that zebrafishhnf4aactivates nearly half of the genes that are suppressed by microbiota, suggesting microbiota negatively regulate Hnf4a. In support, analysis of genomic architecture in mouse intestinal epithelial cells revealed that microbiota colonization leads to activation or inactivation of hundreds of enhancers along with drastic genome-wide reduction of Hnf4a and Hnf4g occupancy. Interspecies meta-analysis suggests Hnf4a may mediate microbial contributions to inflammatory bowel disease pathogenesis. These results indicate Hnf4a plays a critical conserved role in maintaining intestinal homeostasis in response to microbiota and inflammation.
Bio.Ontology - Python tools for enrichment analysis and visualization of ontologies
Authors: Koziara Kamil , Herman-Izycka Julia , Wilczynski Bartek
Published: December 2016

Motivation

Functional annotation and enrichment analysis based on ontologies has become one of the standard methods of analysis of experimental results. Over the past decade, many methods have been proposed for statistical quantification of enrichment of different functional terms and many implementations of these methods are available. As the popularity of these methods grows, the need for tools facilitating their automation increases.

Results

We present a complete Python library for statistical enrichment analysis of gene sets and gene rankings compatible with most available biological ontologies. It allows the user to perform all necessary steps: reading the ontologies and gene annotations in multiple formats; performing enrichment analysis using various methods and visualizing the results as readable reports. Importantly, our library includes methods for correcting for multiple hypotheses testing including computation of False Discovery Rates.

Availability

The library is compatible with recent versions of python interpreter (≥ 2.6 or ≥ 3.3) and is available on github at:https://github.com/regulomics/biopythontogether with an API documentation and a tutorial. The sample galaxy installation can be found athttp://regulomics.mimuw.edu.pl/wp/GO/.

Contact

bartek@mimuw.edu.pl
DNA damage in 3D constricted migration or after lamin-A depletion in 2D: shared mechanisms of repair factor mis-localization under nuclear stress
Authors: Xia Yuntao , Irianto Jerome , Pfeifer Charlotte R. , Ji Jiazheng , Ivanovska Irena L. , Tewari Manu , Bennett Rachel R. , Harding Shane M. , Liu Andrea J. , Greenberg Roger A. , Discher Dennis E.
Published: December 2016

Cells that migrate through small, rigid pores and that have normal levels of the nuclear structure protein lamin-A exhibit an increase in DNA damage, which is also observed with lamin-A depletion in diseases such as cancer and with many lamin-A mutations. Here we show nuclear envelope rupture is a shared feature that increases in standard culture after lamin-A knockdown, which causes nuclear loss of multiple DNA repair factors and increased DNA damage. Some repair factors are merely mis-localized to cytoplasm whereas others are partially depleted unless rescued by lamin-A expression. Compared to standard cultures on rigid glass coverslips, the growth of lamin-A low cells on soft matrix relaxes cytoskeletal stress on the nucleus, suppresses the mis-localization of DNA repair factors, and minimizes DNA damage nearly to wildtype levels. Conversely, constricted migration of the lamin-A low cells causes abnormally high levels of DNA damage, consistent with sustained loss of repair factors. The findings add insight into why monogenic progeroid syndromes that often associate with increased DNA damage and predominantly impact cells in stiff tissues result from mutations only in lamin-A or DNA repair factors.
A Data Citation Roadmap for Scholarly Data Repositories
Authors: Fenner Martin , Crosas Mercè , Grethe Jeffrey , Kennedy David , Hermjakob Henning , Rocca-Serra Philippe , Durand Gustavo , Berjon Robin , Karcher Sebastian , Martone Maryann , Clark Timothy
Published: December 2016

This article presents a practical roadmap for scholarly data repositories to implement data citation in accordance with the Joint Declaration of Data Citation Principles, a synopsis and harmonization of the recommendations of major science policy bodies. The roadmap was developed by the Repositories Expert Group, as part of the Data Citation Implementation Pilot (DCIP) project, an initiative of FORCE11.org and the NIH BioCADDIE (https://biocaddie.org) program. The roadmap makes 11 specific recommendations, grouped into three phases of implementation: a) required steps needed to support the Joint Declaration of Data Citation Principles, b) recommended steps that facilitate article/data publication workflows, and c) optional steps that further improve data citation support provided by data repositories.
Identification of the maize Mediator CDK8 module, andDissociationinsertional mutagenesis ofZmMed12a
Authors: Núñez-Ríos Tania , Ahern Kevin R. , Alonso-Nieves Ana Laura , Lepe-Soltero Daniel , Martínez-Camacho Carol , García-Aguilar Marcelina , Brutnell Thomas P. , Gillmor C. Stewart , Sawers Ruairidh James Hay
Published: December 2016

Mediator is a conserved transcriptional co-activator that links transcription factors bound at enhancer elements to RNA Polymerase II. Mediator-RNA Polymerase II interactions can be sterically hindered by the Cyclin Dependent Kinase 8 (CDK8) module, a submodule of Mediator that acts to repress transcription in response to discrete cellular and environmental cues. The CDK8 module is conserved in all eukaryotes and consists of 4 proteins: CDK8, CYCLIN C (CYCC), MED12, and MED13. In this study, we have characterized the CDK8 module of Mediator in maize. The maize genome contains single copy genes forCdk8, CycC,andMed13,and two genes forMed12.Analysis of expression data for the CDK8 module demonstrated that all five genes are broadly expressed in maize tissues, withZmMed12a, ZmMed12b,andZmMed13exhibiting similar expression patterns. We performed aDissociation (Ds)insertional mutagenesis, recovering two independent insertions in theZmMed12agene. One of theseDsinsertions results in a truncation of theZmMed12atranscript. Our molecular characterization of the maize CDK8 module, as well as transposon tagging ofZmMed12a,establish the basis for molecular and functional studies of these important transcriptional regulators inZea mays.
Contesting China’s engagement with neoliberal urbanism
Authors: Li Lingyue , Chan Roger C.K.
Published: December 2016

Purpose

The purpose of this paper is to contribute to an in-depth understanding of China’s ongoing urban development by engaging with the theoretical dialogue of neoliberalism. It takes decentralization and marketization as the governance background to examine the evolving policy of land, housing and public service in China, with a particular focus on Chongqing. The mismatches experienced under the evolving policy are also discussed.

Design/methodology/approach

By reviewing and consulting related literature, archives, statistical yearbooks, government reports, local newspapers and urban planning documents, this paper offers an overview of urban policy in China. The authors have also taken two field trips and conducted interviews in Chongqing in Summer 2012 and Winter 2013.

Findings

This paper finds that urban China’s land, housing and public service markets have been re-regulated, with a rescaling of statehood, recalibration of central-local relations and reinvented urban governance in the post-reform era. These policies have evolved from the market-oriented principles of early reforms to a more hybrid approach for which the policies have matured and state intervention has been reintroduced. Mismatches have been generated by this evolution.

Originality/value

This paper provides an up-to-date examination of new initiatives for policy adjustment in urban China, with a closer look at Chongqing, one of the most dynamic contemporary metropolises in the country. It has important implications for the debate over China’s engagement with neoliberal urbanism. Also, it empirically reveals the mismatches created by the latest policy initiatives.
Foreword to the special edition, the return to Europe: a generation of re-inventing national identities
Authors: Brunet-Thornton Richard
Published: December 2016

Purpose

Readers from outside the region may not be familiar with the subject matter, therefore, the purpose of this paper is to serve as a foundation for the further reading and appreciation of the submitted manuscripts.

Design/methodology/approach

Based on a pertinent literature review, the foreword addresses the general subject matter of this special edition. The approach used was to introduce the reader to the contents as well as to complement and introduce the contributions.

Findings

The literature review substantiates the varied positions adopted and exposed by the contributing authors.

Originality/value

The contents are derived from original research. The value, as mentioned above, positions the reader to better understand the subject matter at hand.
Ideological shift and employees’ relationships: evidence from Ukraine
Authors: Bogodistov Yevgen , Lizneva Anzhela
Published: December 2016

Purpose

The purpose of this paper is to investigate the employees’ identities shift in Ukraine based on the relational model theory. The paper concentrates on the role which culture and history play in the use of relational models in firms on different organizational levels.

Design/methodology/approach

The proposed hypotheses were tested by multivariate analysis of variance and covariance tests with the data from 99 surveys of Ukrainian firms describing 219 intraorganizational relationships.

Findings

The results showed that culture and history play a significant role for the preference of a certain relational model. Position in the organization and gender influence the choice of the relational model.

Research limitations/implications

The sample of only Ukrainian employees restricts generalizability of the results. This study applies relational models theory in business domain and provides an alternative explanation of employees’ identities shift due to cultural differences and ideological past. Relational models are investigated on different organizational levels shedding light on models of relationships employees prefer in different settings.

Practical implications

Managers working in international settings should pay more attention to patterns of relationships in the target country since they are not freely chosen but partially predestined by the cultural background and the historical and ideological past. Relationships in firms are path dependent, whereby employees inherit models from their peers to apply them to their subordinates. Ukrainian female and male employees have different preferences concerning relational models.

Originality/value

This study is unique in that it applies an anthropological theory to relationships on different organizational levels and tests it in a business domain of a country in an ideological transition.
Responding to NAMAs and preparing for INDCs/NDCs
Authors: Lin Jui-Chu , Chen Wei-Ming , Chen Ding-Jang
Published: December 2016

Purpose

In this paper, the international progress of Nationally Appropriate Mitigation Actions (NAMAs), Intended Nationally Determined Contributions (INDCs), and Nationally Determined Contributions (NDCs) under the United Nations Framework Convention on Climate Change are reviewed. The content of Taiwan’s NAMAs and INDCs are also investigated, especially with reference to actions for the electricity sector. To better understand the greenhouse gas (GHG) reduction contribution from the electricity sector, this paper aims to examine challenges and solutions for implementing a carbon trading mechanism in Taiwan’s monopolistic electricity market under the newly passed Greenhouse Gases Emissions Reduction and Management Act (GHG ERMA).

Design/methodology/approach

Carbon reduction strategies for the electricity sector are discussed by examining and explaining Taiwan’s official documents and the law of GHG ERMA.

Findings

This study finds that market mechanisms should be utilized to allocate appropriate costs and incentives for GHG reductions to transform Taiwan into a low-carbon society.

Originality/value

This study identifies strategies for the electricity sector to reduce GHG emissions, especially the operation of a carbon-trading scheme under a non-liberalized electricity market.
Corporate governance reforms and shareholders’ confidence in emerging markets
Authors: Rahman Haseeb-Ur- , Ibrahim Mohd. Yussoff , Ahmad Ayoib Che
Published: December 2016

Purpose

The purpose of this paper is to investigate the relation of corporate governance (CG) attributes, such as separate leadership (SL) structure, independent chair (IC) of the board, and the proportion of independent directors on the board (Bind) recommended by the new Malaysian Code on Corporate Governance (2012), with firms’ market performance measured by share market price.

Design/methodology/approach

The paper uses a randomly selected sample of 150 non-financial Malaysian listed companies. To find the distinct impact of the code, the paper explicitly divides the sample into two-year pre-context (2010-2011) and two-year post-context (2013-2014) of the code. Besides descriptive statistics, the study also employs correlation and multiple regression estimators.

Findings

By comparing the pre-context and post-context of the code, the study found that SL and Bind have a significant positive relation while IC of the board has a significant negative relation with share market price after enactment of the code.

Research limitations/implications

The paper has a limitation of using only two years of data due to its non-availability particularly after enactment of the code. The findings show that the new code slightly improved compliance to the CG attributes investigated. Based on findings, the study also recommends further improvement in compliance to CG codes and other voluntary regulations in Malaysia.

Originality/value

Besides contributing to the limited and incongruent literature in pre-context and post-context of CG regulations, the paper also provides important insights for regulators and policy makers of the emerging markets like Malaysia.
Network size, structure and mutualism dependence affect the propensity for plant–pollinator extinction cascades
Authors: Vanbergen Adam J. , Woodcock Ben A. , Heard Matthew S. , Chapman Daniel S.
Published: December 2016

Pollinator network structure arising from the extent and strength of interspecific mutualistic interactions can promote species persistence and community robustness. However, environmental change may re‐organise network structure limiting capacity to absorb or resist shocks and increasing species extinctions.

We investigated if habitat disturbance and the level of mutualism dependence between species affected the robustness of insect–flower visitation networks Following a recently developed Stochastic Co‐extinction Model (SCM), we ran simulations to produce the number of extinction episodes (cascade degree), which we correlated with network structure in undisturbed and disturbed habitat. We also explicitly modelled whether a species’ intrinsic dependence on mutualism affected the propensity for extinction cascades in the network.

Habitat disturbance generated a gradient in network structure with those from disturbed sites being less connected, but more speciose and so larger. Controlling for network size (z‐score standardisation against the null model) revealed that disturbed networks had disproportionately low linkage density, high specialisation, fewer insect visitors per plant species (vulnerability) and lower nestedness (NODF).

This network structure gradient driven by disturbance increased and decreased different aspects of robustness to simulated plant extinction. Disturbance decreased the risk that an initial insect extinction would follow a plant species loss. Although, this effect disappeared when network size and connectance were standardised, suggesting the lower connectance of disturbed networks increased robustness to an initial secondary extinction.

However, if a secondary extinction occurred then networks from disturbed habitat were more prone to large co‐extinction cascades, likely resulting from a greater chance of extinction in these larger, speciose networks. Conversely, when species mutualism dependency was explicit in the SCM simulations the disturbed networks were disproportionately more robust to very large co‐extinction cascades, potentially caused by non‐random patterns of interaction between species differing in dependence on mutualism.

Our results showed disturbance altered the size and the distribution of interspecific interactions in the networks to affect their robustness to co‐extinction cascades. Controlling for effects due to network size and the interspecific variation in demographic dependence on mutualism can improve insight into properties conferring the structural robustness of networks to environmental changes.

A lay summary is available for this article.
Clinical value of MRI‐detected extramural venous invasion in rectal cancer
Authors: Tripathi Pratik , Rao Sheng Xiang , Zeng Meng Su
Published: December 2016

Extramural venous invasion (EMVI) is associated with a poor prognosis and a poor overall survival rate in rectal cancer. It can independently predict local and distant tumor recurrences. Preoperative EMVI detection in rectal cancer is useful for determining the treatment strategy. EMVI status is beneficial for the post‐treatment evaluation and analysis of rectal cancer. Magnetic resonance imaging (MRI) is a non‐invasive diagnostic modality with no radiation effects. High‐resolution MRI can detect EMVI with high accuracy. In addition, MRI results are equal to or even better than pathological results in the detection of medium to large EMVI in rectal cancer. MRI‐detected EMVI (mrEMVI) can be used as a potential biomarker that facilitates treatment methods. This review highlights the importance of MRI before and after rectal cancer treatment. In addition, we analyze the prognostic correlation between mrEMVI and circulating tumor cells (CTC) in rectal cancer. This article may help shed light on the significance of mrEMVI.
Coping with inevitable accidents in metabolism
Authors: Danchin Antoine
Published: December 2016

Genomic studies focus on key metabolites and pathways that, despite their obvious anthropocentric design, keep being ‘predicted’, while this is only finding again what is already known. As increasingly more genomes are sequenced, this lightpost effect may account at least in part for our failure to understand the function of a continuously growing number of genes. Core metabolism often goes astray, accidentally producing a variety of unexpected compounds. Catabolism of these forgotten metabolites makes an essential part of the functions coded in metagenomes. Here, I explore the fate of a limited number of those: compounds resulting from radical reactions and molecules derived from some reactive intermediates produced during normal metabolism. I try both to update investigators with the most recent literature and to uncover old articles that may open up new research avenues in the genome exploration of metabolism. This should allow us to foresee further developments in experimental genomics and genome annotation.
The Origin and Tectonic Setting of Precambrian Greywacke of Ribandar‐Chimbel, Goa, India: Petrological and Geochemical Evidence
Authors: FERNANDES Glancia Q , IYER Sridhar D. , KOTHA Mahender
Published: December 2016

The Precambrian greywacke of Ribandar‐Chimbel belonging to the Sanvordem Formation of the Goa Group, India, has been studied for petrography and analyzed for major trace elements. The greywacke is characterized by angular to sub‐round grains of quartz, feldspar, biotite, chlorite and clay minerals. The abundance of clay in the matrix seems to have influenced the Al2O3 content and the K2O/Al2O3 ratio. The variation diagrams indicate a decreasing trend of TiO2, Al2O3, Fe2O3 and MgO; whereas Na2O and CaO exhibit a scatter which could be a result of the variable presence of feldspar within the sediments. The immobile elements, vanadium (25 to 144 ppm), nickel (up to 107 ppm) and chromium (up to 184 ppm), reflect abundance of clay minerals. The greywacke shows strongly fractionated REE patterns with LaN/YbN = 8 to 26 and with higher total REE abundances (up to 245 ppm). The low REE enrichment and depletion in heavier REE with prominent negative Eu anomaly (Eu/Eu*= 0.54 to 0.79) suggest a derivation of the greywacke from an old upper continental crust composed chiefly of felsic components. Petrological evidence and geochemical data suggest that the deposition of the greywacke largely took place in a deep to shallow basin that progressively changed from that of a continental island arc to an active continental setting.
Reservoir Characteristics and Preservation Conditions of Longmaxi Shale in the Upper Yangtze Block, South China
Authors: RAN Bo , LIU Shugen , JANSA Luba , SUN Wei , YANG Di , WANG Shiyu , YE Yuehao , XIAO Christopher , ZHANHG Jian , ZHAI Cangbo , LUO Chao , ZHANG Changjun
Published: December 2016

The Upper Ordovician‐Lower Silurian Longmaxi Shale in the Upper Yangtze block represents one of the most important shale gas plays in China. The shale composition, porosity, organic thermal maturity, and methane sorption were investigated at the Qilongcun section in the Dingshan area, southeastern Sichuan Basin. The results show that the Upper Ordovician‐Lower Silurian Longmaxi Shale contains: (1) sapropelic I organic matter; (2) a 40‐m thick bedded sequence where total organic carbon (TOC) content is > 2%; (3) a 30m thick layer at the base of the Longmaxi Shale with a brittle mineral content higher than 50%; and (4) a mean methane adsorption capacity of 1.80 cm3/g (7 MPa pressure). A positive correlation between TOC and sorbed gas indicates that organic matter content exerts an important control on methane storage capacity. Based on the analysis of the shale reservoir characteristics, the lower member of the Longmaxi Shale can thus be considered a favorable stratum for shale gas exploration and exploitation. It has similar reservoir characteristics with the Longmaxi Shale in the Jiaoshiba area tested with a high‐yield industrial gas flow. However, based on tectonic analysis, differences in the level of industrial gas flow between the low‐yield study area and the high‐yield Jiaoshiba area may result from different tectonic preservation conditions. Evidence from these studies indicates the shale gas potential of the Longmaxi Shale is constrained by the reservoir and preservation conditions.
The impact of lions on the demography and ecology of endangered African wild dogs
Authors: Groom R. J. , Lannas K. , Jackson C. R.
Published: December 2016

It has long been recognized that superior carnivores can impact on the demography and ecology of smaller members of the guild, although exact mechanisms remain unclear. Here we use original data from a unique natural experiment to study some of the mechanisms by which African lions Panthera leo impact on African wild dogs Lycaon pictus. Using a study site where wild dogs outnumbered lions for several years prior to lion population recovery, we aimed to investigate whether or not, and by which means, wild dog populations are regulated and influenced by lions. We used 38 pack‐years of demographic and behavioural data across two 4‐year periods where lion density differed 20‐fold (pre‐lion era: 1996–1999 and lion era: 2010–2013) to assess how lions may affect wild dog pack size and age structure, litter size and pup survival (n = 329 pups), as well as den site selection (n = 46 dens). Pack size was significantly greater during the pre‐lion era. The pup to adult ratio was lower during the lion era and the change in pack composition was directly attributable to significantly greater lion‐induced pup mortality. We also demonstrate a behavioural shift, with locations selected for the vulnerable denning period being in more rugged terrain and in areas with lower prey densities during the lion era, as compared with the pre‐lion era. Lower adult recruitment into a population of an obligate cooperative breeder like the African wild dog can have complex consequences, including on feeding and defence of young, and mate finding.
The heterogeneous farm‐level impact of the 2005 CAP‐first pillar reform: A multivalued treatment effect estimation
Authors: Esposti Roberto
Published: December 2016

This article aims to evaluate the impact of the 2005 reform of the Common Agricultural Policy (CAP) on farm production choices as a treatment effect (TE). This impact is measured through alternative metrics of the short‐term changes of the output vector. The heterogeneity of the response to the reform is assessed by estimating both average and quantile TE. As this heterogeneous response may depend on the different farm‐level CAP support, a multivalued treatment approach is adopted and applied to treated units (i.e., supported farms). This approach is applied to a balanced panel of Italian FADN farms observed over years 2003–2007. Results show that the 2005 reform of the first pillar of the CAP actually had an impact in (re)orienting short‐term farm production choices but this response is largely heterogeneous and concentrated in the lower levels of support.
Disease‐Concordant Twins Empower Genetic Association Studies
Authors: Tan Qihua , Li Weilong , Vandin Fabio
Published: December 2016

Genome‐wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false‐positive results and lack of replication in independent studies. Related individuals, such as twin pairs concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease‐concordant twin design, which uses singletons from disease‐concordant twin pairs as cases and ordinary healthy samples as controls. We examined the power gain of the twin‐based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case‐control design with cases collected from the unrelated patient population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size of an ordinary case‐control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease‐concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease‐concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost.
Opisthorchis felineus negatively associates with skin test reactivity in Russia—EuroPrevall‐International Cooperation study
Authors: Fedorova O. S. , Janse J. J. , Ogorodova L. M. , Fedotova M. M. , Achterberg R. A. , Verweij J. J. , Fernández‐Rivas M. , Versteeg S. A. , Potts J. , Minelli C. , van Ree R. , Burney P. , Yazdanbakhsh M.
Published: December 2016

Background

Most studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish‐borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country.

Methods

Schoolchildren aged 7–11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples.

Results

Of the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms.

Conclusions

There is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country.
Prediction of progression to severe disease in women with late preterm hypertensive disorders of pregnancy
Authors: Zwertbroek Eva F. , Broekhuijsen Kim , Langenveld Josje , van Baaren Gert‐Jan , van den Berg Paul P. , Bremer Henk A. , Ganzevoort Wessel , van Loon Aren J. , Mol Ben W.J. , van Pampus Maria G. , Perquin Denise A.M. , Rijnders Robbert J.P. , Scheepers Hubertina C.J. , Sikkema Marko J. , Woiski Mallory D. , Groen Henk , Franssen Maureen T.M. ,   the HYPITAT‐II Study Group
Published: December 2016

Introduction

If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk.

Material and methods

We developed a prediction model using data from the HYPITAT‐II trail, which evaluated immediate delivery vs. expectant monitoring in women with non‐severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities.

Results

We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p = 0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73–0.81, p < 0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, <0.44 and >0.45, respectively).

Conclusion

In women with non‐severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice.
Multicompartment compliance aids in the community: the prevalence of potentially inappropriate medications
Authors: Counter David , Stewart Derek , MacLeod Joan , McLay James S.
Published: December 2016

Aims

To assess the prevalence of potentially inappropriate medications (PIMs) use in a population of community‐based multicompartment compliance aid (MCA) users in north‐east Scotland.

Methods

Data for MCAs dispensed by 48 of the 50 community pharmacies in Aberdeen City between 1st June to 31st October 2014, together with concurrently prescribed medications, patient demographics and Carstairs index of social deprivation were recorded. Drug‐specific quality indicators for PIMs from the Swedish National Board of Health and Welfare were applied and bivariate logistic regression analysis used to assess for associations with demographic variables.

Results

The median age was 82 years (range 12–105 years, 59% female). A total of 1977 PIMs were identified affecting 57.8% of patients. A quarter of patients were prescribed ≥10 medications and 43% had a prescription containing at least one clinically significant drug–drug interaction (DDI). Ten drug groups accounted for 76% of all DDIs. A significant increase in the risk for at least one PIM was associated with female sex (for all indicators of PIM use), age <80 years (three or more psychotropic medicines [OR 5.88, 2.96–11.70, P < 0.001]) and lower socioeconomic status (prescription of ≥10 medications [OR: 1.43, 95% CI: 1.16–1.78], prescription of a long‐acting benzodiazepine [OR: 1.84, CI: 1.14–2.98]).

Conclusions

MCA use is associated with a significant incidence of PIMs particularly affecting those younger than 80 years and those living in deprived areas. Our findings indicate the need for a more aggressive multidisciplinary approach to the review of the medications prescribed to MCA users.
Mass Spectrometry‐Based Tools to Characterize DNA–Protein Cross‐Linking by Bis‐Electrophiles
Authors: Groehler Arnold , Degner Amanda , Tretyakova Natalia Y.
Published: December 2016

DNA–protein cross‐links (DPCs) are unusually bulky DNA adducts that form in cells as a result of exposure to endogenous and exogenous agents including reactive oxygen species, ultraviolet light, ionizing radiation, environmental agents (e.g. transition metals, formaldehyde, 1,2‐dibromoethane, 1,3‐butadiene) and common chemotherapeutic agents. Covalent DPCs are cytotoxic and mutagenic due to their ability to interfere with faithful DNA replication and to prevent accurate gene expression. Key to our understanding of the biological significance of DPC formation is identifying the proteins most susceptible to forming these unusually bulky and complex lesions and quantifying the extent of DNA–protein cross‐linking in cells and tissues. Recent advances in bottom‐up mass spectrometry‐based proteomics have allowed for an unbiased assessment of the whole protein DPC adductome after in vitro and in vivo exposures to cross‐linking agents. This MiniReview summarizes current and emerging methods for DPC isolation and analysis by mass spectrometry‐based proteomics. We also highlight several examples of successful applications of these novel methodologies to studies of DPC lesions induced by bis‐electrophiles such as formaldehyde, 1,2,3,4‐diepoxybutane, nitrogen mustards and cisplatin.
The human genome as public: Justifications and implications
Authors: Bayefsky Michelle J.
Published: December 2016

Since the human genome was decoded, great emphasis has been placed on the unique, personal nature of the genome, along with the benefits that personalized medicine can bring to individuals and the importance of safeguarding genetic privacy. As a result, an equally important aspect of the human genome – its common nature – has been underappreciated and underrepresented in the ethics literature and policy dialogue surrounding genetics and genomics. This article will argue that, just as the personal nature of the genome has been used to reinforce individual rights and justify important privacy protections, so too the common nature of the genome can be employed to support protections of the genome at a population level and policies designed to promote the public's wellbeing.

In order for public health officials to have the authority to develop genetics policies for the sake of the public good, the genome must have not only a common, but also a public, dimension. This article contends that DNA carries a public dimension through the use of two conceptual frameworks: the common heritage (CH) framework and the common resource (CR) framework. Both frameworks establish a public interest in the human genome, but the CH framework can be used to justify policies aimed at preserving and protecting the genome, while the CR framework can be employed to justify policies for utilizing the genome for the public benefit. A variety of possible policy implications are discussed, with special attention paid to the use of large‐scale genomics databases for public health research.
Bithalamic gliomas may be molecularly distinct from their unilateral high‐grade counterparts
Authors: Broniscer Alberto , Hwang Scott N. , Chamdine Omar , Lin Tong , Pounds Stanley , Onar‐Thomas Arzu , Chi Lei , Shurtleff Sheila , Allen Sariah , Gajjar Amar , Northcott Paul , Orr Brent A.
Published: December 2016

Bithalamic gliomas are rare cancers diagnosed based on poorly defined radiologic criteria. Infiltrative astrocytomas account for most cases. While some previous studies reported dismal outcomes for patients with bithalamic gliomas irrespective of therapy and histologic grade, others described better prognoses even without anticancer therapy. Little is known about their molecular characteristics. We reviewed clinical, radiologic, and histologic features of patients with bithalamic gliomas treated at our institution over 15 years. Targeted sequencing of mutational hotspots in H3F3A, HIST1H3B, IDH1/2, and BRAF, and genome‐wide analysis of DNA methylation and copy number abnormalities was performed in available tumors. Eleven patients with bithalamic gliomas were identified. Their median age at diagnosis was 4.8 years (range: 1–15.7). Additional involvement of the brainstem, basal ganglia, and cerebral lobes occurred in 11, 9, and 3 cases, respectively. All patients presented with hydrocephalus. Two‐thirds of the patients had a histologic diagnosis of anaplastic astrocytoma. Despite aggressive therapy, our youngest patient, the only one diagnosed before 1 year of age, is the sole long‐term survivor. DNA methylation could be performed in seven tumors, all of which clustered with the RTK I ‘PDGFRA’ subgroup by unsupervised hierarchical analysis of methylation array against a previously published cohort of 59 pediatric high‐grade gliomas. Sequencing of hotspots mutations could be done in 10 tumors, none of which harbored H3F3A p.K27 and/or the respective DNA methylation signature, and any other hotspot mutations. Amplification of MDM4 (n = 2), PDGFRA (n = 2), and ID2 combined with MYCN (n = 1) were observed in 7 tumors available for analysis. In comparison with the previously published experience with unilateral high‐grade thalamic astrocytomas where H3F3A p.K27 was present in two‐thirds of cases, the absence of this molecular subgroup in bithalamic gliomas was striking. This finding suggests that unilateral and bithalamic high‐grade gliomas may represent two distinct molecular entities.
Pharmacological characterization of N‐[(2S)‐5‐(6‐fluoro‐3‐pyridinyl)‐2, 3‐dihydro‐1H‐inden‐2‐yl]‐2‐propanesulfonamide: a novel, clinical AMPA receptor positive allosteric modulator
Authors: Ward Simon E , Beswick Paul , Calcinaghi Novella , Dawson Lee A , Gartlon Jane , Graziani Francesca , Jones Declan N C , Lacroix Laurent , Selina Mok M H , Oliosi Beatrice , Pardoe Joanne , Starr Kathryn , Woolley Marie L , Harries Mark H
Published: December 2016

Background and Purpose

AMPA receptor positive allosteric modulators represent a potential therapeutic strategy to improve cognition in people with schizophrenia. These studies collectively constitute the preclinical pharmacology data package used to build confidence in the pharmacology of this molecule and enable a clinical trial application.

Experimental Approach

[N‐[(2S)‐5‐(6‐fluoro‐3‐pyridinyl)‐2,3‐dihydro 1H–inden‐2‐yl]‐2‐propanesulfonamide] (UoS12258) was profiled in a number of in vitro and in vivo studies to highlight its suitability as a novel therapeutic agent.

Key Results

We demonstrated that UoS12258 is a selective, positive allosteric modulator of the AMPA receptor. At rat native hetero‐oligomeric AMPA receptors, UoS12258 displayed a minimum effective concentration of approximately 10 nM in vitro and enhanced AMPA receptor‐mediated synaptic transmission at an estimated free brain concentration of approximately 15 nM in vivo. UoS12258 reversed a delay‐induced deficit in novel object recognition in rats after both acute and sub‐chronic dosing. Sub‐chronic dosing reduced the minimum effective dose from 0.3 to 0.03 mg·kg−1. UoS12258 was also effective at improving performance in two other cognition models, passive avoidance in scopolamine‐impaired rats and water maze learning and retention in aged rats. In side‐effect profiling studies, UoS12258 did not produce significant changes in the maximal electroshock threshold test at doses below 10 mg·kg−1.

Conclusion and Implications

We conclude that UoS12258 is a potent and selective AMPA receptor modulator exhibiting cognition enhancing properties in several rat behavioural models superior to other molecules that have previously entered clinical evaluation.
miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation
Authors: Ito Naomi , Sakai Atsushi , Miyake Noriko , Maruyama Motoyo , Iwasaki Hirotoshi , Miyake Koichi , Okada Takashi , Sakamoto Atsuhiro , Suzuki Hidenori
Published: December 2016

Background and Purpose

Although oxaliplatin is an effective anti‐cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non‐coding RNAs that negatively regulate gene expression in a sequence‐specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy‐induced neuropathic pain is unknown.

Experimental Approach

Oxaliplatin‐induced chronic neuropathic pain was induced in rats by i.p. injections of oxaliplatin (2 mg·kg−1) for five consecutive days. The expression levels of miR‐15b and β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1 also known as β‐secretase 1) were examined in the dorsal root ganglion (DRG). To examine the function of miR‐15b, an adeno‐associated viral vector encoding miR‐15b was injected into the DRG in vivo.

Key Results

Among the miRNAs examined in the DRG in the late phase of oxaliplatin‐induced neuropathic pain, miR‐15b was most robustly increased. Our in vitro assay results determined that BACE1 was a target of miR‐15b. BACE1 and miR‐15b were co‐expressed in putative myelinated and unmyelinated DRG neurons. Overexpression of miR‐15b in DRG neurons caused mechanical allodynia in association with reduced expression of BACE1. Consistent with these results, a BACE1 inhibitor dose‐dependently induced significant mechanical allodynia.

Conclusions and Implications

These findings suggest that miR‐15b contributes to oxaliplatin‐induced chronic neuropathic pain at least in part through the down‐regulation of BACE1.
Geological controls on the present temperature field of the western Sverdrup Basin, Canadian Arctic Archipelago
Authors: Chen Zhuoheng , Grasby Stephen E. , Dewing Keith , Osadetz Kirk G. , Brent Tom
Published: December 2016

Analysis of current temperature data in the Canadian Arctic Archipelago results in the recognition of two major thermal regimes. High temperature regions are observed where salt diapirs and salt cored anticlines are present. Low temperature fields are observed along the western and southern basin margins and around Cornwall‐Amund Ringnes islands, where regional Mesozoic aquifers are exposed to surface, connected to basin boundary faults, or regional unconformities. Meteoric and Holocene sub‐glacial water recharge are inferred to be responsible for the low geothermal regime and low formation water salinity. Neither exhumation associated with the Eocene “Eurekan” orogeny nor volcanic intrusion associated with opening of Amerasia Basin in late Jurassic‐early Cretaceous have been interpreted to be a significant influence on the present day temperature field, although thermal indicators show evidence of elevated thermal alteration of organic matter pointing to earlier, but now dissipated, thermal anomalies.
Getting help from abroad: The macroeconomics of foreign direct investment in infrastructure in low‐income countries
Authors: Germaschewski Yin
Published: December 2016

Infrastructure financing needs in most low‐income countries are substantial, but funding for such needs is only partly covered by national governments and aid donors. This paper introduces foreign direct investment (FDI) through public–private partnerships as a source of infrastructure financing in low‐income countries. A two‐sector open economy model is developed to assess the macroeconomic performance of FDI in infrastructure. With efficient foreign investment, an increase in revenue‐generating infrastructure investment boosts productivity and spurs private investment while stabilizing domestic prices. A direct comparison between infrastructure financed by domestic versus foreign investment shows that foreign investment creates higher output growth and welfare gains and is preferable to domestically sourced investment, irrespective of the underlying financing instrument the domestic economy is employing. FDI in non‐revenue‐generating infrastructure is also analyzed and discussed.