bluuebunny/crossref_metadata_2025 huggingface dataset:
Streptococcus pneumoniaecapsule determines disease severity in experimental pneumococcal meningitis
Authors: Hathaway Lucy J. , Grandgirard Denis , Valente Luca G. , Täuber Martin G. , Leib Stephen L.
Published: March 2016

Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement.
Association between use of the progestin Depot Medroxyprogesterone Acetate and Cervicovaginal Lavage Proinflammatory Cytokines among HIV-1 and HSV-2 co-infected African women: a case control study
Authors: Walong Edwin , Gontier Christopher , Jaoko Walter , Bukusi Elizabeth
Published: March 2016

Background

Use of the progestin contraceptive Depot Medroxyprogesterone Acetate (DMPA) by HIV 1 infected women is associated with increased female to male transmission of HIV. Mucosal innate immune activation has been proposed as a likely mechanism. To establish the effect of DMPA upon mucosal immune activation, this study sought to evaluate the concentrations of 5 proinflammatory and the regulatory cytokine IL 10 in cervicovaginal lavage fluid.

Methods

This was a case control study, 70 participants were recruited, comprising of 35 asymptomatic ART naïve HIV positive women on DMPA recruited as cases and 35 age matched asymptomatic ART naive HIV positive women not on contraceptives recruited as controls. Peripheral blood CD4 and total lymphocyte counts, High vaginal swab microscopy, endocervical smears and cervical cytology were performed for each participant. Concentrations of six proinflammatory cytokines were measured on cervicovaginal lavage by multiplex cytometric bead array.

Results

The mean age of cases was 26.8 years and 30 years for controls. Total lymphocyte counts and CD4 cell counts were significantly higher among cases (p=0.02 and 0.004 respectively). HSV 2 prevalence as determined by ELISA was higher (p=0.034 among cases. The concentrations of the cytokines IL 1β, IL 6, IL 8, IL 12p70 and TNF α were lower among cases, with IL 1β being statistically significant (p=0.046). Concentrations of IL 10 was higher among cases (p=0.022). On multivariate analysis, reduction in IL 1β and IL 8 were associated with the duration of DMPA use (p=0.015 and 0.041 respectively). Inclusion of HSV 2 into the multivariate models showed elevation of all cytokines measured (p=<0.001).

Conclusion

DMPA use is associated with reduction of proinflammatory cytokines and elevation of the regulatory cytokine IL 10. This may explain increased female to male transmission of HIV infection by modulation of male genital tract mucosa in the absence of increased HIV 1 genital shedding.
An algebraic approach to parameter optimization in biomolecular bistable systems
Authors: Mardanlou Vahid , Franco Elisa
Published: March 2016

In a synthetic biological network it may often be desirable to maximize or minimize parameters such as reaction rates, fluxes and total concentrations of reagents, while preserving a given dynamic behavior. We consider the problem of parameter optimization in biomolecular bistable circuits. We show that, under some assumptions often satisfied by bistable biological networks, it is possible to derive algebraic conditions on the parameters that determine when bistability occurs. These (global) algebraic conditions can be included as nonlinear constraints in a parameter optimization problem. We derive bistability conditions using Sturm's theorem for Gardner and Collins toggle switch. Then we optimize its nominal parameters to improve switching speed and robustness to a subset of uncertain parameters.
fluff: exploratory analysis and visualization of high-throughput sequencing data
Authors: Georgiou Georgios , van Heeringen Simon J.
Published: March 2016

In this application note we describe fluff, a software package that allows for simple exploration, clustering and visualization of high-throughput sequencing data mapped to a reference genome. The package contains three command-line tools to generate publication-quality figures in an uncomplicated manner using sensible defaults. Genome-wide data can be aggregated, clustered and visualized in a heatmap, according to different clustering methods. This includes a predefined setting to identify dynamic clusters between different conditions or developmental stages. Alternatively, clustered data can be visualized in a bandplot. Finally, fluff includes a tool to generate genomic profiles. As command-line tools, the fluff programs can easily be integrated into standard analysis pipelines. The installation is straightforward and documentation is available at http://fluff.readthedocs.org.

Availability

fluff is implemented in Python and runs on Linux. The source code is freely available for download at http://github.com/simonvh/fluff.

Contact

s.vanheeringen@science.ru.nl
On the Origin and Evolutionary Consequences of Gene Body DNA Methylation
Authors: Bewick Adam J. , Ji Lexiang , Niederhuth Chad E. , Willing Eva-Maria , Hofmeister Brigitte T. , Shi Xiuling , Wang Li , Lu Zefu , Rohr Nicholas A. , Hartwig Benjamin , Kiefer Christiane , Deal Roger B. , Schmutz Jeremy , Grimwood Jane , Stroud Hume , Jacobsen Steven E. , Schneeberger Korbinian , Zhang Xiaoyu , Schmitz Robert J.
Published: March 2016

In plants, CG DNA methylation is prevalent in the transcribed regions of many constitutively expressed genes (“gene body methylation; gbM”), but the origin and function of gbM remain unknown. Here we report the discovery that Eutrema salsugineum has lost gbM from its genome, the first known instance for an angiosperm. Of all known DNA methyltransferases, only CHROMOMETHYLASE 3 (CMT3) is missing from E. salsugineum. Identification of an additional angiosperm, Conringia planisiliqua, which independently lost CMT3 and gbM supports that CMT3 is required for the establishment of gbM. Detailed analyses of gene expression, the histone variant H2A.Z and various histone modifications in E. salsugineum and in Arabidopsis thaliana epiRILs found no evidence in support of any role for gbM in regulating transcription or affecting the composition and modifications of chromatin over evolutionary time scales.
Empirical modelling of trait selection by partitioning selection into direct selection and selection that is mediated by interspecific interactions
Authors: Damgaard Christian
Published: March 2016

Trait selection has received considerable attention in the pursuit to understand niche-based community assembly processes and to generate ecological predictions. To further advance the study of trait selection, a conceptual statistical model is presented that outlines and discuss the possibilities of i) estimating the effect of interspecific interactions on traits rather than just testing weather selection has had an effect on the observed trait distributions, ii) discriminating between environmental filtering and niche partitioning processes and estimate the characteristic features and importance of both processes, and iii) predicting the effect of environmental changes and gradients on trait selection. To achieve these goals a number of necessary assumptions have to be specified and these assumptions are discussed and assessed. Simulated plant cover data from a simple uniform environment was successfully fitted to the model and the results indicates that it is possible to partition direct population growth and population growth that is mediated by interspecific interaction. The data requirements of the model are modest, i.e. time series data on plant species abundance and a species trait matrix. Consequently, the model concept may be used to model trait selection, including the effect of interspecific interactions, in many existing plant ecological datasets.
Relative contributions of conformational selection and induced fit
Authors: Michel Denis
Published: March 2016

A long standing debate in biochemistry is to determine whether the conformational changes observed during biomolecular interactions proceed through conformational selection (of preexisting isoforms) or induced fit (ligand-induced 3D reshaping). The latter mechanism had been invoked in certain circumstances, for example to explain the non-Michaelian activity of monomeric enzymes like glucokinase. But the relative importance of induced fit has been recently depreciated in favor of conformational selection, assumed to be always sufficient, predominant in general and in particular for glucokinase. The relative contributions of conformational selection and induced fit are reconsidered here in and out of equilibrium, in the light of earlier concepts such as the cyclic equilibrium rule and the turning wheel of Wyman, using single molecule state probability, one way fluxes and net fluxes. The conditions for a switch from conformational selection to induced fit at a given ligand concentration are explicitly determined. Out of equilibrium, the inspection of the enzyme states circuit shows that conformational selection alone would give a Michaelian reaction rate but not the established nonlinear behavior of glucokinase. Moreover, when induced fit and conformational selection coexist and allow kinetic cooperativity, the net flux emerging in the linkage cycle necessarily corresponds to the induced fit path.
Genotype-specific developmental plasticity shapes the timing and robustness of reproductive capacity inCaenorhabditis elegans
Authors: Alicea Bradly
Published: March 2016

The effects of environmental stress on developmental phenotypes allows us to observe the adaptive capacity of various genotypes. In single-genotype populations, this allows for observing the effects of standing variation on the process of developmental plasticity. Typically, such efforts do not allow us to distinguish the effect of genotype from the effects of environment. In the NematodeCaenorhabditis elegans, however, the L1 stage of development allows for precise and controlled imposition of starvation on a synchronized population of individuals. This allows for systematic comparisons within and between defined genotypes.

This study provides a number of innovations in the study of Nematode developmental plasticity. The first is to demonstrate systems-level mechanisms of adaptive response for various genetic mutant phenotypes to extended L1 arrest. The effects of developmental deprivation are quantifiable by applying statistical modeling techniques to reproductive time-series. This is characterized for both a wildtype strain (N2) and a host of genetic mutant strains. A further contribution is investigating the effects of starvation at multi-generational timescales. This includes both two generations post-starvation and multiple starvation experiences with selection for fecundity over 11 generations.

Statistical techniques such as Kernel Density Estimation (KDE), fold-change analysis, and Area Under the Curve (AUC) analysis reveal differences from baseline in the form of shifts in reproductive timing and kurtosis in peak reproductive capacity characterize adaptive responses that are semi-independent of environment. Extending these patterns of response toad hoccomparisons with multi-generational contexts reveals that different genotypes characterized by mutations of specific genetic loci lead to vastly different outcomes.
αE-catenin inhibits a Src–YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway
Authors: Li Peng , Silvis Mark R. , Honaker Yuchi , Lien Wen-Hui , Arron Sarah T. , Vasioukhin Valeri
Published: March 2016

Cell–cell adhesion protein αE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that αE-catenin inhibits β4 integrin-mediated activation of SRC tyrosine kinase. SRC is the first discovered oncogene, but the protein substrate critical for SRC-mediated transformation has not been identified. We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC–YAP1-mediated transformation. We uncovered a marked increase in this YAP1 phosphorylation in human and mouse SCC tumors with low/negative expression of αE-catenin. We demonstrate that the tumor suppressor function of αE-catenin involves negative regulation of the β4 integrin–SRC signaling pathway and that SRC-mediated phosphorylation and activation of YAP1 are an alternative to the canonical Hippo signaling pathway that directly connect oncogenic tyrosine kinase signaling with YAP1.
Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model
Authors: Chen Song , Wang Chenran , Yeo Syn , Liang Chun-Chi , Okamoto Takako , Sun Shaogang , Wen Jian , Guan Jun-Lin
Published: March 2016

Autophagy is an evolutionarily conserved cellular process controlled through a set of essential autophagy genes (Atgs). However, there is increasing evidence that most, if not all, Atgs also possess functions independent of their requirement in canonical autophagy, making it difficult to distinguish the contributions of autophagy-dependent or -independent functions of a particular Atg to various biological processes. To distinguish these functions for FIP200 (FAK family-interacting protein of 200 kDa), an Atg in autophagy induction, we examined FIP200 interaction with its autophagy partner, Atg13. We found that residues 582–585 (LQFL) in FIP200 are required for interaction with Atg13, and mutation of these residues to AAAA (designated the FIP200-4A mutant) abolished its canonical autophagy function in vitro. Furthermore, we created a FIP200-4A mutant knock-in mouse model and found that specifically blocking FIP200 interaction with Atg13 abolishes autophagy in vivo, providing direct support for the essential role of the ULK1/Atg13/FIP200/Atg101 complex in the process beyond previous studies relying on the complete knockout of individual components. Analysis of the new mouse model showed that nonautophagic functions of FIP200 are sufficient to fully support embryogenesis by maintaining a protective role in TNFα-induced apoptosis. However, FIP200-mediated canonical autophagy is required to support neonatal survival and tumor cell growth. These studies provide the first genetic evidence linking an Atg's autophagy and nonautophagic functions to different biological processes in vivo.
A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus
Authors: Takai Hiroyuki , Jenkinson Emma , Kabir Shaheen , Babul-Hirji Riyana , Najm-Tehrani Nasrin , Chitayat David A. , Crow Yanick J. , de Lange Titia
Published: March 2016

Coats plus (CP) can be caused by mutations in the CTC1 component of CST, which promotes polymerase α (polα)/primase-dependent fill-in throughout the genome and at telomeres. The cellular pathology relating to CP has not been established. We identified a homozygous POT1 S322L substitution (POT1CP) in two siblings with CP. POT1CP induced a proliferative arrest that could be bypassed by telomerase. POT1CP was expressed at normal levels, bound TPP1 and telomeres, and blocked ATR signaling. POT1CP was defective in regulating telomerase, leading to telomere elongation rather than the telomere shortening observed in other telomeropathies. POT1CP was also defective in the maintenance of the telomeric C strand, causing extended 3′ overhangs and stochastic telomere truncations that could be healed by telomerase. Consistent with shortening of the telomeric C strand, metaphase chromosomes showed loss of telomeres synthesized by leading strand DNA synthesis. We propose that CP is caused by a defect in POT1/CST-dependent telomere fill-in. We further propose that deficiency in the fill-in step generates truncated telomeres that halt proliferation in cells lacking telomerase, whereas, in tissues expressing telomerase (e.g., bone marrow), the truncations are healed. The proposed etiology can explain why CP presents with features distinct from those associated with telomerase defects (e.g., dyskeratosis congenita).
Early developmental pathways to autism spectrum disorder in tuberous sclerosis complex
Authors: Tye Charlotte , Varcin Kandice , Bolton Patrick , Jeste Shafali Spurling
Published: March 2016

Purpose

– Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD), yet no single genetic, neurological or neurophysiological risk marker is necessary or sufficient to increase risk for ASD. This paper aims to discuss the utility of adopting a developmental perspective.

Design/methodology/approach

– The increasing number of TSC infants presenting with abnormalities prenatally provides a unique opportunity to study risk pathways to ASD from birth. Here, the authors review findings to date that support the investigation of infants with TSC to further our understanding of typical and atypical development.

Findings

– Evidence has accumulated from studies of infants at familial risk for ASD (“baby siblings”) to suggest that early markers of ASD are present in the first year of life. The early waves of prospective studies of infants with TSC indicate dynamic changes in developmental trajectories to ASD and are likely to provide insight into cascading effects of brain “insult” early in development. Emerging evidence of phenotypic and biological homology between syndromic and idiopathic cases of ASD supports the notion of a convergence of risk factors on a final common pathway in ASD.

Originality/value

– The delineation of brain-based biomarkers of risk, prediction and treatment response in TSC will be critical in aiding the development of targeted intervention and prevention strategies for those infants at high risk of poorer developmental outcomes.
Divorce in the family business: unfolding the legal problems by learning from practice
Authors: Haag Kajsa , Sund Lars-Göran
Published: March 2016

Purpose

Our purpose is to explore the case of divorce in family business from a legal perspective and highlight the problems of applying family law in the family business context.

Design/methodology/approach

We rely on legal analysis and interviews with estate distribution executors to discuss problems with the legal rules and how they are practiced.

Findings

Our findings show that the law is ill fitted to the situation where there is a family business included in the division of marital property. In divorce, family law dictates the division of marital property and the family business is reduced to an asset to be divided like any other. Critical issues are identified and elaborated.

Research limitations/implications

Divorce and other disruptions to the family system should be considered in family business consultancy among other threats to the business. The legal perspective on divorce in the family business offered here primarily concerns ownership issues. The impact of divorce on management is equally in need of exploration, which is our suggestion for further studies.

Practical implications

Our paper illuminates in which ways the business is hampered from divorcing owners and discuss critical issues with applying family law in a family business context.

Originality/value

New light is shed on the practical problems of interpreting family law in a family business context advancing our understanding of family aspects in family business management.
An examination of the associations among cultural dimensions, relational silence and stress
Authors: Dedahanov Alisher Tohirovich , Lee Dohyung , Rhee Jaehoon , Yusupov Sardorbek
Published: March 2016

Purpose

– The purpose of this paper is to examine the relationship between power distance, collectivism and relational silence; the associations between relational silence and stress; and the mediating role of relational silence in the link between power distance, collectivism and stress.

Design/methodology/approach

– The authors conducted a survey among 1,153 highly skilled employees using a self-administered questionnaire. The authors received 813 responses from a total of 1,153 individuals. Among the 813 responses, the authors excluded 81 due to incomplete data, and thus analyzed a total of 732 responses. The overall response rate was 63.4 percent. Confirmatory factor analysis and structural equation modeling were utilized for the analyses.

Findings

– The findings suggest that power distance and collectivism induce relational silence; relational silence increases stress and mediates the associations between power distance, collectivism and stress.

Originality/value

– The present study is the first to provide empirical evidence of a link between power distance, collectivism and relational silence; the relationship between relational silence and stress; and the role of relational silence in mediating the associations between power distance, collectivism and stress.
How to make a knowledge-sharing group: a group social capital perspective
Authors: Wu Wei-Li , Lee Yi-Chih
Published: March 2016

Purpose

– Although the work group is the main context for knowledge exchange and combination in today’s organizations, few knowledge-sharing studies have been conducted at the group level. The purpose of this paper is to apply the concept of group social capital to determine how to promote knowledge sharing at the group level. The authors divided group social capital into two segments, conduits and resources, and argue that different group social capital conduits (i.e. work design in this study) lead to varied resources, which subsequently influence group knowledge sharing.

Design/methodology/approach

– In this study, group social capital conduits included social interaction and task interdependence, and group social capital resources included group trust and a supportive climate for knowledge sharing. The authors conducted a survey on work groups in the high-tech industry using a sample of 86 work groups.

Findings

– The results indicated that social interaction in a work group was positively related to group trust and that task interdependence was positively related to group trust and a supportive climate for knowledge sharing. Furthermore, group trust and a supportive climate for knowledge sharing were both found to have an influence on knowledge sharing.

Originality/value

– Applying the concept of group social capital, this paper is the first research to discuss how group social capital conduits and resources influence knowledge sharing. The results of this study lead us to a better understand the relationship between group social capital and knowledge sharing.
Current status of nanotechnology in Jordan
Authors: Alshamaileh Ehab , Al-Sulaibi Mazen , Al-Khawaldeh Ahmad , Almatarneh Mansour H. , El-Sabawi Dina , Al-Rawajfeh Aiman
Published: March 2016

Purpose

– The current status of nanotechnology research and development in Jordan is analyzed. In recent years, Jordanian institutions demonstrated considerable interest in the development and production of nanotechnology. Here the purpose of this paper is to provide detailed information about the status of nanotechnology in Jordan in terms of several factors that influence selectivity in nanotechnology and the number of published peer-reviewed research articles.

Design/methodology/approach

– Several factors that influence selectivity in nanotechnology and the number of published peer-reviewed research articles were analyzed. A detailed analysis of the collected data reveals that the number of publications, citations, and patents is highly dependent on the amount of research fund.

Findings

– The development in nanotechnology is associated with presence and accessibility of sensitive laboratory equipment. The nanotechnology research output in Jordan is still lower than it should be due to the lack of necessary laboratory infrastructure. This is due to the insufficient funds allocated to scientific research, the restrictive access to available instruments and the bureaucracy of some governmental departments. Compared to some developed countries, Jordan is noticeably behind in developing a nanotechnology system of research and industry. It will take time as well as technical and financial resources in order to achieve an advanced level in the field of nanotechnology in Jordan. Nevertheless, many Jordanian researchers are doing their best and are producing some good research articles.

Research limitations/implications

– The many applications to the same approach.

Practical implications

– Time and publications’ resources.

Social implications

– Peer cooperation.

Originality/value

– First comprehensive review ever. A base for researchers and decision makers.
Towards sustainable indicators of food and nutritional outcomes in India
Authors: Reddy A. Amarender , Rani Ch. Radhika , Cadman Timothy , Kumar Soora Naresh , Reddy Anugula N
Published: March 2016

Purpose

– The purpose of this paper is to measure performance of India in food and nutrition security relative to other Asian countries like Bangladesh, China, Africa and also developed countries from 1991 to 2016.

Design/methodology/approach

– The study is based on FAO food security indicators under four dimensions, namely, food availability, access, stability and utilization. These indicators are further categorized into determinants and outcome indicators of food security. A comprehensive fifteen indicators are examined in depth.

Findings

– Food availability in terms of dietary calories and protein per capita was less in India compared to even Africa and Bangladesh. However, food access indicators like road density is better, food prices remain low and stable, which improved food access and stability. However, in utilization indicators, access to water and sanitation remained low, anaemia among pregnant women and undernourishment was relatively higher when even compared to least developed countries like Africa and Bangladesh. Depth of food deficit (an indicator of severity of food deficit) was higher in India except Africa.

Research limitations/implications

– Future research should focus on policies for decreasing undernourishment and anaemia and severity in depth of food deficit with focus on India.

Practical implications

– The results highlight the severity of food deficit and anaemia among women, undernourishment and provide benchmark to monitor sustainable development goals in zero hunger goal.

Originality/value

– This study examined the relative performance of India in various food and nutrition security indicators in comparison to other countries.
Author‐suggested reviewers: gender differences and influences on the peer review process at an ecology journal
Authors: Fox Charles W. , Burns C. Sean , Muncy Anna D. , Meyer Jennifer A.
Published: March 2016

Peer review is the primary method by which journals evaluate the quality and importance of scientific papers. To help editors find suitable reviewers, many journals allow or require authors to suggest names of preferred and nonpreferred reviewers. Though authors should know best who is qualified to review their papers, they also have a strong incentive to suggest reviewers that they expect to review their paper positively.

In this study, we examine the reviewers that are suggested as preferred and nonpreferred by authors, the use of these author suggestions by editors, and the influence of author suggestions on the peer review process and outcomes at the journal Functional Ecology. In particular, we examined how gender of the participants (author, editor and reviewer) influences the role of preferred reviewers in the peer review process.

Even when not required by the journal, most authors suggest preferred reviewers, but few suggest nonpreferred reviewers. Most author‐preferred reviewers are male, but the proportion of women among author suggestions increased over the 11 years, from a low of 15% in 2004 to a high of 25% in 2014.

Male and female authors did not differ in how likely they were to suggest preferred reviewers, but the proportion of women among author suggestions was higher for female authors (~28%, averaged across years) than for male authors (~21%). Women that were suggested as author‐preferred reviewers were more likely to be selected by editors than were men suggested by authors.

There was no evidence that editor gender, seniority or length of service as an editor for Functional Ecology affected the probability that they used author suggestions. Of reviewers invited to review, those that were author‐suggested were more likely to respond to the editors' review invitations but were not more likely to agree to review.

Most strikingly, author‐preferred reviewers rated papers more positively than did editor‐selected reviewers, and papers reviewed by author‐preferred reviewers were much more likely to be invited for revision than were papers reviewed by editor‐selected reviewers. This difference was not influenced by the gender of the participants in the process.

Suggesting preferred reviewers benefits authors because preferred reviewers rate papers significantly more positively than do editor‐selected reviewers, improving the chances that a paper will be published. Journals and journal editors should recognize that preferred reviewers rate manuscripts differently than do editor‐selected reviewers, and be aware that this difference can have large effects on editor decisions.

A Lay Summary is available for this article.
Silencing of hypoxia inducible factor‐1α by RNA interference inhibits growth of SK‐NEP‐1 Wilms tumour cells in vitro, and suppresses tumourigenesis and angiogenesis in vivo
Authors: Shi Bo , Li Ying , Wang Xiuli , Yang Yi , Li Dan , Liu Xin , Yang Xianghong
Published: March 2016

Wilms tumour is the most common tumour of the pediatric kidney. Elevation of hypoxia‐inducible factor 1α (HIF‐1α) has been detected in 93% to 100% of human Wilms tumour specimens, suggesting a potential value of HIF‐1α as a therapeutic target for Wilms tumour. In the present study, a stable HIF‐1α‐silenced Wilms tumour cell strain was established by introducing HIF‐1α short‐hairpin RNA (shRNA) into SK‐NEP‐1 cells. Silencing of HIF‐1α significantly reduced single‐cell growth capacity, suppressed proliferation and arrested cell cycle of SK‐NEP‐1 cells. In addition, reduction of HIF‐1α expression induced apoptosis in SK‐NEP‐1 cells, which was accompanied by increased levels of cleaved caspase‐3, cleaved poly (ADP‐ribose) polymerase (PARP) and Bax as well as downregulation of Bcl‐2 in the cells. Furthermore, when inoculated subcutaneously in nude mice, HIF‐1α‐silenced SK‐NEP‐1 cells displayed retarded tumour growth and impaired tumour angiogenesis. In summary, the findings of this study suggest that HIF‐1α plays a critical role in the development of Wilms tumour, and it may serve as a candidate target of gene therapy for Wilms tumour.
A Long History of Faith‐Based Welfare in Australia: Origins and Impact
Authors: Swain Shurlee
Published: March 2016

In a nation where governments and churches have collaborated in the delivery of welfare services since 1788, such faith‐based welfare was seen as normative rather than problematic. Indeed most Australians would struggle to imagine a welfare system that was not built on such an arrangement. However, by the late twentieth century, the world views and ideologies of church leaders and politicians were no longer in alignment, creating tensions in the relationship. This article explores the origins and development of church–state collaboration in the delivery of welfare, and examines the impact this has had on both the shape of charity and the mission of the churches as faith‐based agencies are increasingly challenged in an environment in which government funding is tied to policies that potentially transgress the principles of the gospels, and victims of past welfare practices demand reparation.
The Critical Angle for Perforation versus Ricochet of a .38 CAL. LRN Bullet on a Windshield
Authors: Hirakawa Shunsuke , Saimoto Akihide , Ishimatsu Takakazu
Published: March 2016

From forensic point of view, it is important to clarify the condition whether ricochet or perforate for a bullet fired toward the automobile windshield. The purpose of this study was to specify the critical angle at which the ricochet of the fired bullet takes place. To estimate the result of firing, a rigid‐body dynamics simulation of the bullet together with the test‐firing using .38 CAL. LRN bullet was examined. It was found both from numerical simulation and firing test that when the incidence angle is <45°, a complete perforation of the windshield was observed, whereas the bullet ricocheted remaining a characteristic damage on the windshield when the incidence angle is >60°. To measure the static failure resistance of various windshields, static indentation test was also examined.
Optimal Reorganization of NASA Earth Science Data for Enhanced Accessibility and Usability for the Hydrology Community
Authors: Teng William , Rui Hualan , Strub Richard , Vollmer Bruce
Published: March 2016

A long‐standing “Digital Divide” in data representation exists between the preferred way of data access by the hydrology community and the common way of data archival by earth science data centers. Typically, in hydrology, earth surface features are expressed as discrete spatial objects (e.g., watersheds), and time‐varying data are contained in associated time series. Data in earth science archives, although stored as discrete values (of satellite swath pixels or geographical grids), represent continuous spatial fields, one file per time step. This Divide has been an obstacle, specifically, between the Consortium of Universities for the Advancement of Hydrologic Science, Inc. and NASA earth science data systems. In essence, the way data are archived is conceptually orthogonal to the desired method of access. Our recent work has shown an optimal method of bridging the Divide, by enabling operational access to long‐time series (e.g., 36 years of hourly data) of selected NASA datasets. These time series, which we have termed “data rods,” are pre‐generated or generated on‐the‐fly. This optimal solution was arrived at after extensive investigations of various approaches, including one based on “data curtains.” The on‐the‐fly generation of data rods uses “data cubes,” NASA Giovanni, and parallel processing. The optimal reorganization of NASA earth science data has significantly enhanced the access to and use of the data for the hydrology user community.
Optimizing ecological survey effort over space and time
Authors: Moore Alana L. , McCarthy Michael A.
Published: March 2016

Previous studies that optimize allocation of surveillance resources over space have assumed that detection rates are constant over time and that travel or survey costs are the same for all sites. Other recent research explicitly accounts for stochastically varying detection rates and distinct travel costs but restricts attention to the optimal number of visits to a single site. Here, we integrate these approaches to construct a model that optimizes the allocation of surveillance effort over both space and time.

The solution defines the budget that should be allocated to each site and the number of visits over which that search budget should be expended. We show that the solution has close affinities with that of Hauser and McCarthy (Ecology Letters, 12, 2009, 683), which ignored temporal variation in detection rates and travel costs. We illustrate our approach by finding the optimal allocation of survey effort over space and time that maximizes the expected number of detections of the cascade treefrog (Litoria pearsoniana) in a region.

In deriving our model, we also solve an alternative model to Moore et al. (PLoS One, 9, 2014) that considers the trade‐off between the number of visits and length of each visit when the detection rate at a site varies over time. We compare the predictions of the original model of Moore et al. (PLoS One, 9, 2014) and the new model using experimental data on detections of two species, showing the two models perform similarly well.

Interestingly, when variable detection rates and travel costs are considered using our model, the form of the resulting objective function is very similar to the case in which they are ignored; in both cases, the probability of failed detection at each site is a negative exponential function of effort. However, travel costs impose a discontinuity into the solution space making the decision variables semi‐continuous (i.e. the optimal surveillance effort at each site is either zero or a value greater than the travel cost). This discontinuity complicates the task of finding the optimal solution. We propose a straightforward algorithm that finds very good approximate solutions.
G Protein‐Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock‐Out Mice Show Enhanced Ethanol Reward
Authors: Tipps Megan E. , Raybuck Jonathan D. , Kozell Laura B. , Lattal K. Matthew , Buck Kari J.
Published: March 2016

Background

G protein‐gated inwardly rectifying potassium (GIRK) channels contribute to the effects of a number of drugs of abuse, including ethanol. However, the roles of individual subunits in the rewarding effects of ethanol are poorly understood.

Methods

We compare conditioned place preference (CPP) in GIRK3 subunit knock‐out (GIRK3−/−), heterozygote (GIRK3+/−), and wild‐type (WT) mice. In addition, the development of locomotor tolerance/sensitization and the effects of EtOH intoxication on associative learning (fear conditioning) are also assessed.

Results

Our data show significant EtOH CPP in GIRK3−/− and GIRK3+/− mice, but not in the WT littermates. In addition, we demonstrate that these effects are not due to differences in EtOH metabolism, the development of EtOH tolerance/sensitivity, or associative learning abilities. While there were no consistent genotype differences in the fear conditioning assay, our data do show a selective sensitization of the impairing effects of EtOH intoxication on contextual learning, but no effect on cued learning.

Conclusions

These findings suggest that GIRK3 plays a role in EtOH reward. Furthermore, the selectivity of this effect suggests that GIRK channels could be an effective therapeutic target for the prevention and/or treatment of alcoholism.
The Alcohol Sensitivity Questionnaire: Evidence for Construct Validity
Authors: Fleming Kimberly A. , Bartholow Bruce D. , Hilgard Joseph , McCarthy Denis M. , O'Neill Susan E. , Steinley Douglas , Sher Kenneth J.
Published: March 2016

Background

Variability in sensitivity to the acute effects of alcohol is an important risk factor for the development of alcohol use disorder (AUD). The most commonly used retrospective self‐report measure of sensitivity, the Self‐Rating of the Effects of Alcohol (SRE) form, queries a limited number of alcohol effects and relies on respondents’ ability to recall experiences that might have occurred in the distant past. Here, we investigated the construct validity of an alternative measure that queries a larger number of alcohol effects, the Alcohol Sensitivity Questionnaire (ASQ), and compared it to the SRE in predicting momentary subjective responses to an acute dose of alcohol.

Methods

Healthy young adults (N = 423) completed the SRE and the ASQ and then were randomly assigned to consume either alcohol or a placebo beverage (between‐subjects manipulation). Stimulation and sedation (Biphasic Alcohol Effects Scale) and subjective intoxication were measured multiple times after drinking.

Results

Hierarchical linear models showed that the ASQ reliably predicted each of these outcomes following alcohol but not placebo consumption, provided unique prediction beyond that associated with differences in recent alcohol involvement, and was preferred over the SRE (in terms of model fit) in direct model comparisons of stimulation and sedation.

Conclusions

The ASQ compared favorably with the better‐known SRE in predicting increased stimulation and reduced sedation following an acute alcohol challenge. The ASQ appears to be a valid self‐report measure of alcohol sensitivity and therefore holds promise for identifying individuals at‐risk for AUD and related problems.
Sex hormones and systemic inflammation are modulators of the obese‐asthma phenotype
Authors: Scott H. A. , Gibson P. G. , Garg M. L. , Upham J. W. , Wood L. G.
Published: March 2016

Background

Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese‐asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma.

Methods

Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive‐aged (<50 years old; n = 36) or older (>50 years old; n = 45). Thirteen (36.1%) reproductive‐aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers.

Results

Obese reproductive‐aged females had higher sputum %neutrophils than nonobese reproductive‐aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C‐reactive protein and IL‐6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive‐aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015).

Conclusions

This study suggests that sex hormones and systemic inflammation may be mediating the obese‐asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive‐aged females warrants further investigation.
Histopathology Image Analysis in Two Long‐Term Animal Experiments with Helical Flow Total Artificial Heart
Authors: Wotke Jiri , Homolka Pavel , Vasku Jaromír , Dobsak Petr , Palanova Petra , Mrkvicova Veronika , Konecny Petr , Soska Vladimir , Pohanka Michal , Novakova Marie , Yurimoto Terumi , Saito Itsuro , Inoue Yusuke , Isoyama Takashi , Abe Yusuke
Published: March 2016

Histopathological analysis can provide important information in long‐term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF‐TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF‐TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF‐TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 µm thick transverse sections were stained with hematoxylin‐eosin (HE). Additional staining was done for detection of connective tissue (Masson‐Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100× and 500× magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro‐particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro‐particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments.
From housing bust to credit crunch: Evidence from small business loans
Authors: Huang Haifang , Stephens Eric
Published: March 2016

This paper provides evidence that the 2007–2009 housing bust in the United States precipitated a “credit crunch” for small businesses. To remove demand‐driven correlations, we rely on within‐city comparisons. We ask whether banks whose mortgage portfolios were more heavily weighted in harder‐hit cities cut back lending to a greater extent in all cities where they make small business loans, relative to other banks in those cities. The evidence is consistent with a credit crunch. Large banks reacted with heavier cuts, but consistent evidence is also found among smaller banks. Quantitatively, the detected contribution to the overall decline in lending from the crunch appears modest.
Government policy under price uncertainty: A source of volatility in illegal immigration
Authors: Guzman Mark G. , Haslag Joseph H. , Orrenius Pia M.
Published: March 2016

This paper provides an alternative explanation for why illegal immigration can exhibit substantial volatility. We develop a model economy where migrants make decisions in the face of uncertain border enforcement and transfers from the host country. The uncertainty is extrinsic, a sunspot, and arises due to ambiguity regarding government policy; the sunspot manifests itself as uncertainty in the commodity price of money. Immigration volatility stems from both the trade‐off between the marginal benefits and costs (transfers and enforcement) to migrating and the existence of a sunspot. Finally, we examine the impact of changes in government policies on migration levels.
The evolution of financial intermediation: Evidence from 19th‐century Ontario microdata
Authors: Di Matteo Livio , Redish Angela
Published: March 2016

Microdata for Ontario decedents in 1892 and 1902 is analyzed to help explain the dramatic growth of the Canadian banking system in the late 19th century. Combining data from probate inventories with census data at the township level, we find that the expansion of deposit banking happened at the extensive rather than intensive margin and was correlated with the expansion of the branch network of the banking system, although we cannot assign causation. Wealth and urbanization help to explain the growth of deposit banking but the significance of a dummy variable for 1902 points to other time‐correlated factors such as innovations in transportation and financial innovations that lowered costs and facilitated access to banking services.