bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of theLegionellaDot/Icm type IV secretion systemin situby electron cryotomography
Authors: Ghosal Debnath , Chang Yi-Wei , Jeong Kwangcheol C. , Vogel Joseph P. , Jensen Grant J.
Published: November 2016

Type IV secretion systems (T4SSs) are large macromolecular machines that translocate protein and DNA and are involved in the pathogenesis of multiple human diseases. Here, using electron cryotomography (ECT), we report thein situstructure of the Dot/Icm type IVB secretion system (T4BSS) utilized by the human pathogenLegionella pneumophila. This is the first structure of a type IVB secretion system, and also the first structure of any T4SSin situ. While the Dot/Icm system shares almost no sequence homology with type IVA secretion systems (T4ASSs), its overall structure shows remarkable similarities to two previously imaged T4ASSs, suggesting shared aspects of mechanism. However, compared to one of these, the negative-stain reconstruction of the purified T4ASS from the R388 plasmid, it is approximately twice as long and wide and exhibits several additional large densities, reflecting type-specific elaborations and potentially better structural preservationin situ.
A Large Scale Joint Analysis of Flowering Time Reveals Independent Temperate Adaptations in Maize
Authors: Swarts Kelly , Bauer Eva , Glaubitz Jeffrey C. , Ho Tiffany , Johnson Lynn , Li Yongxiang , Li Yu , Miller Zachary , Romay Cinta , Schöen Chris-Carolin , Wang Tianyu , Zhang Zhiwu , Buckler Edward S. , Bradbury Peter
Published: November 2016

Modulating days to flowering is a key mechanism in plants for adapting to new environments, and variation in days to flowering drives population structure by limiting mating. To elucidate the genetic architecture of flowering across maize, a quantitative trait, we mapped flowering in five global populations, a diversity panel (Ames) and four half-sib mapping designs, Chinese (CNNAM), US (USNAM), and European Dent (EUNAM-Dent) and Flint (EUNAM-Flint). Using whole-genome projected SNPs, we tested for joint association using GWAS, resampling GWAS and two regional approaches; Regional Heritability Mapping (RHM) (1,2) and a novel method, Boosted Regional Heritability Mapping (BRHM). Direct overlap in significant regions detected between populations and flowering candidate genes was limited, but whole-genome cross-population predictive abilities were ≤0.78. Poor predictive ability correlated with increased population differentiation (r = 0.41), unless the parents were broadly sampled from across the North American temperate-tropical germplasm gradient; uncorrected GWAS results from populations with broadly sampled parents were well predicted by temperate-tropical FSTs in machine learning. Machine learning between GWAS results also suggested shared architecture between the American panels and, more distantly, the European panels, but not the Chinese panel. Machine learning approaches can reconcile non-linear relationships, but the combined predictive ability of all of the populations did not significantly enhance prediction of physiological candidates. While the North American-European temperate adaption is well studied, this study suggest independent temperate adaptation evolved in the Chinese panel, most likely in China after 1500, a finding supported by differential gene ontology term enrichment between populations.
L-DOPA Reduces Model-Free Control of Behavior by Attenuating the Transfer of Value to Action
Authors: Kroemer Nils B. , Lee Ying , Pooseh Shakoor , Eppinger Ben , Goschke Thomas , Smolka Michael N.
Published: November 2016

Dopamine is a key neurotransmitter in reinforcement learning and action control. Recent findings suggest that these components are inherently entangled. Here, we tested if increases in dopamine tone by administration of L-DOPA upregulate deliberative “model-based” control of behavior or reflexive “model-free” control as predicted by dual-control reinforcement-learning models. Alternatively, L-DOPA may impair learning as suggested by “value” or “thrift” theories of dopamine. To this end, we employed a two-stage Markov decision-task to investigate the effect of L-DOPA (randomized cross-over) on behavioral control while brain activation was measured using fMRI. L-DOPA led to attenuated model-free control of behavior as indicated by the reduced impact of reward on choice and increased stochasticity of model-free choices. Correspondingly, in the brain, L-DOPA decreased the effect of reward while prediction-error signals were unaffected. Taken together, our results suggest that L-DOPA reduces model-free control of behavior by attenuating the transfer of value to action.
Incomplete Dominance of Deleterious Alleles Contributes Substantially to Trait Variation and Heterosis in Maize
Authors: Yang Jinliang , Mezmouk Sofiane , Baumgarten Andy , Buckler Edward S. , Guill Katherine E. , McMullen Michael D. , Mumm Rita H. , Ross-Ibarra Jeffrey
Published: November 2016

Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring by crossing two inbred parents. We test these ideas using evolutionary measures of sequence conservation to ask whether incorporating information about putatively deleterious alleles can inform genomic selection (GS) models and improve phenotypic prediction. We measured a number of agronomic traits in both the inbred parents and hybrids of an elite maize partial diallel population and re-sequenced the parents of the population. Inbred elite maize lines vary for more than 350,000 putatively deleterious sites, but show a lower burden of such sites than a comparable set of traditional landraces. Our modeling reveals widespread evidence for incomplete dominance at these loci, and supports theoretical models that more damaging variants are usually more recessive. We identify haplotype blocks using an identity-by-decent (IBD) analysis and perform genomic prediction analyses in which we weigh blocks on the basis of segregating putatively deleterious variants. Cross-validation results show that incorporating sequence conservation in genomic selection improves prediction accuracy for grain yield and other fitness-related traits as well as heterosis for those traits. Our results provide empirical support for an important role for incomplete dominance of deleterious alleles in explaining heterosis and demonstrate the utility of incorporating functional annotation in phenotypic prediction and plant breeding.

Author Summary

A key long-term goal of biology is understanding the genetic basis of phenotypic variation. Although most new mutations are likely disadvantageous, their prevalence and importance in explaining patterns of phenotypic variation is controversial and not well understood. In this study we combine whole genome-sequencing and field evaluation of a maize mapping population to investigate the contribution of deleterious mutations to phenotype. We show thata prioriprediction of deleterious alleles correlates well with effect sizes for grain yield and that variants predicted to be more damaging are on average more recessive. We develop a simple model allowing for variation in the heterozygous effects of deleterious mutations and demonstrate its improved ability to predict both phenotypes and hybrid vigor. Our results help reconcile alternative explanations for hybrid vigor and highlight the use of leveraging evolutionary history to facilitate breeding for crop improvement.
Flowtrace: simple visualization of coherent structures in biological fluid flows
Authors: Gilpin William , Prakash Vivek N. , Prakash Manu
Published: November 2016

1

We present a simple, intuitive algorithm for visualizing time-varying flow fields that can reveal complex flow structures with minimal user intervention. We apply this technique to a variety of biological systems, including the swimming currents of invertebrates and the collective motion of swarms of insects. We compare our results to more experimentally-diffcult and mathematically-sophisticated techniques for identifying patterns in fluid flows, and suggest that our tool represents an essential “middle ground” allowing experimentalists to easily determine whether a system exhibits interesting flow patterns and coherent structures without the need to resort to more intensive techniques. In addition to being informative, the visualizations generated by our tool are often striking and elegant, illustrating coherent structures directly from videos without the need for computational overlays. Our tool is available as fully-documented open-source code available for MATLAB, Python, or ImageJ atwww.flowtrace.org.
Evolutionary forces affecting synonymous variations in plant genomes
Authors: Clément Yves , Sarah Gautier , Holtz Yan , Homa Felix , Pointet Stéphanie , Contreras Sandy , Nabholz Benoit , Sabot François , Sauné Laure , Ardisson Morgane , Bacilieri Roberto , Besnard Guillaume , Berger Angélique , Cardi Céline , De Bellis Fabien , Fouet Olivier , Jourda Cyril , Khadari Bouchaib , Lanaud Claire , Leroy Thierry , Pot David , Sauvage Christopher , Scarcelli Nora , Tregear James , Vigouroux Yves , Yahiaoui Nabila , Ruiz Manuel , Santoni Sylvain , Labouisse Jean-Pierre , Pham Jean-Louis , David Jacques , Glémin Sylvain
Published: November 2016

Base composition is highly variable among and within plant genomes, especially at third codon positions, ranging from GC-poor and homogeneous species to GC-rich and highly heterogeneous ones (particularly Monocots). Consequently, synonymous codon usage is biased in most species, even when base composition is relatively homogeneous. The causes of these variations are still under debate, with three main forces being possibly involved: mutational bias, selection and GC-biased gene conversion (gBGC). So far, both selection and gBGC have been detected in some species but how their relative strength varies among and within species remains unclear. Population genetics approaches allow to jointly estimating the intensity of selection, gBGC and mutational bias. We extended a recently developed method and applied it to a large population genomic datasets based on transcriptome sequencing of 11 angiosperm species spread across the phylogeny. We found that base composition is far from mutation-drift equilibrium in most genomes and that gBGC is a widespread and stronger process than selection. gBGC could strongly contribute to base composition variation among plant species, implying that it should be taken into account in plant genome analyses, especially for GC-rich ones.
Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells
Authors: Lev Shapira , Maya Ralph , Enosh Tomer , Shai Cohen , Oren Kobiler
Published: November 2016

Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1) fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s). Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA), Suberohydroxamic Acid (SBX), Valporic Acid (VPA) and Suberoylanilide Hydoxamic Acid (SAHA). We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the infection. Different cell types (HFF, Vero and U2OS), which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX), which may down regulate the number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in differences in the number of genomes that initiate expression.
Bridging microscopic and macroscopic mechanisms of p53-MDM2 binding using molecular simulations and kinetic network models
Authors: Zhou Guangfeng , Pantelopulos George A. , Mukherjee Sudipto , Voelz Vincent A.
Published: November 2016

Under normal cellular conditions, the tumor suppressor protein p53 is kept at a low levels in part due to ubiquitination by MDM2, a process initiated by binding of MDM2 to the intrinsically disordered transactivation domain (TAD) of p53. Although many experimental and simulation studies suggest that disordered domains such as p53 TAD bind their targets nonspecifically before folding to a tightly-associated conformation, the molecular details are unclear. Toward a detailed prediction of binding mechanism, pathways and rates, we have performed large-scale unbiased all-atom simulations of p53-MDM2 binding. Markov State Models (MSMs) constructed from the trajectory data predict p53 TAD peptide binding pathways and on-rates in good agreement with experiment. The MSM reveals that two key bound intermediates, each with a non-native arrangement of hydrophobic residues in the MDM2 binding cleft, control the overall on-rate. Using microscopic rate information from the MSM, we parameterize a simple four-state kinetic model to (1) determine that induced-fit pathways dominate the binding flux over a large range of concentrations, and (2) predict how modulation of residual p53 helicity affects binding, in good agreement with experiment. These results suggest new ways in which microscopic models of bound-state ensembles can be used to understand biological function on a macroscopic scale.

AUTHOR SUMMARY

Many cell signaling pathways involve protein-protein interactions in which an intrinsically disordered peptide folds upon binding its target. Determining the molecular mechanisms that control these binding rates is important for understanding how such systems are regulated. In this paper, we show how extensive all-atom simulations combined with kinetic network models provide a detailed mechanistic understanding of how tumor suppressor protein p53 binds to MDM2, an important target of new cancer therapeutics. A simple four-state model parameterized from the simulations shows a binding-then-folding mechanism, and recapitulates experiments in which residual helicity boosts binding. This work goes beyond previous simulations of small-molecule binding, to achieve pathways and binding rates for a large peptide, in good agreement with experiment.
Odorant cues linked to social immunity induce lateralized antenna stimulation in honey bees (Apis mellifera L.)
Authors: McAfee Alison , Collins Troy F. , Madilao Lufiani L. , Foster Leonard J.
Published: November 2016

Hygienic behaviour (HB) is a social immunity trait in honey bees (Apis mellifera L.) whereby workers detect, uncap and remove unhealthy brood, improving disease resistance in the colony. This is clearly economically valuable; however, the molecular mechanism behind it is not well understood. The freeze-killed brood (FKB) assay is the conventional method of HB selection, so we compared odour profiles of FKB and live brood. Surprisingly, we found that significantly more brood pheromone (β-ocimene) was released from FKB. β-ocimene abundance also positively correlated with HB, suggesting there could be a brood effect contributing to overall hygiene. We found that β ocimene stimulated worker antennae in a dose-dependent manner, with the left antennae responding significantly stronger than right antennae in hygienic bees, but not in non-hygienic bees. This suggests that HB depends not only on odour detection, but also lateralization of sensitivity. We also compared odour profiles of Varroa-infested brood to healthy brood and found an overall interactive effect between developmental stage and infestation, but specific odours did not drive these differences. Overall, the data we present here is an important foundation on which to build our understanding the molecular mechanism behind this complex behaviour.
Crystal structures ofp-substituted derivatives of 2,6-dimethylbromobenzene with ½ ≤Z′ ≤ 4
Authors: Navarrete Guitérrez Angélica , Aguirre Hernández Gerardo , Bernès Sylvain
Published: November 2016

The crystal structures of four bromoarenes based on 2,6-dimethylbromobenzene are reported, which are differentiated according the functional groupXplacedparato the Br atom:X= CN (4-bromo-3,5-dimethylbenzonitrile, C9H8BrN), (1),X= NO2(2-bromo-1,3-dimethyl-5-nitrobenzene, C8H8BrNO2), (2),X= NH2(4-bromo-3,5-dimethylaniline, C8H10BrN), (3) andX= OH (4-bromo-3,5-dimethylphenol, C8H9BrO), (4). The content of the asymmetric unit is different in each crystal,Z′ = ½ (X= CN),Z′ = 1 (X= NO2),Z′ = 2 (X= NH2), andZ′ = 4 (X= OH), and is related to the molecular symmetry and the propensity ofXto be involved in hydrogen bonding. In none of the studied compounds does the crystal structure feature other non-covalent interactions, such as π–π, C—H...π or C—Br...Br contacts.
Gender bias in household education expenditure: the case of West Bengal
Authors: Majumder Amita , Mitra Chayanika
Published: November 2016

Purpose

This paper aims to detect gender bias in education expenditure on “students”, who are children and young adults, in a household in the rural and the urban sectors of West Bengal. Outlay equivalent ratios have been calculated using the Engel curve approach, where the budget share function is log quadratic in income, to identify items relating exclusively to education of school/college going students. Heckman’s (1979) two-step procedure is used for estimation to address selection bias The 68th round (July 2011 to June 2012) household level consumption expenditure survey data of the National Sample Survey Organisation have been used for the analysis.

Design/methodology/approach

Engel curve approach is used to capture parental preference for student’s welfare and to find the existence of male student favouritism in the field of education. In case of exclusive adult goods, the addition of a student will reduce the resource allocated for adult goods leading to negative income effect. If a household favours males over females, then that household is likely to sacrifice more for a male student’s education than that for a female student. To address selection bias, Heckman’s two-step procedure has been used.

Findings

The authors find that not all education items relate exclusively to students of a household. Expenditure on books is not exclusively for students, whereas other educational items, such as stationary and photocopy charges, tuition fees and private coaching fees, are found to be students’ items only. Transport cost is found to be an adult good. Further, we find evidence of pro male bias in expenditure on educational items, and the extent of gender bias is more in the urban sectors compared to the rural sectors in West Bengal.

Originality/value

The objective of this paper is to identify the educational items exclusively for “students” and to test the difference in the allocation of resources in education, with respect to these items, between a male student and a female student for both sectors in West Bengal, using the outlay equivalent ratios.
A generalized stochastic production frontier analysis of technical efficiency of rice farming
Authors: Bhattacharyya Aditi , Mandal Raju
Published: November 2016

Purpose

This paper aims to analyze farm-level technical inefficiency of rice farming in Assam, India, using a multiple-output generalized stochastic frontier framework.

Design/methodology/approach

Primary data for this study were collected in 2009-2010 from 310 farm-households in four non-contiguous districts of Dhubri, Morigaon, Dibrugarh and Cachar that are located in different agro-climatic regions of Assam. Based on a Cobb–Douglas production function for multiple rice varieties, the paper simultaneously estimates the generalized stochastic production frontier and examines effects of exogenous factors on farm-level technical inefficiency.

Findings

Results of this study show that the average technical inefficiency of farms is 8.5 per cent in the sample. Further, inefficiency is lower in the frequently flood prone areas, and availability of government support helps reduce such inefficiency as well. However, technical efficiency is higher for the Muslim farm-households, and it decreases with greater land fragmentation. The study also finds that the use of primitive technology like bullock reduces technical efficiency of rice farming.

Originality/value

This paper is based on a novel data set that has specially been collected to examine productivity and efficiency of rice cultivation in the flood plains of Assam that has not been studied before. Further, to the best of the authors’ knowledge, this paper is the first one to model rice production as a multiple-output stochastic production frontier and analyze technical efficiency of rice production accordingly.
Electricity supply, industrialization and economic growth: evidence from Nigeria
Authors: Alley Ibrahim , Egbetunde Tajudeen , Oligbi Blessing
Published: November 2016

Purpose

Most studies on electricity-economic growth nexus in the literature are preoccupied with causality, with little attention paid to the transmission mechanisms. The orientation of most of these studies is obviously predicated on their assumption that electricity enters the production function in a Hicks-neutral fashion. Based on the assumption that productivity of capital is affected by electricity supply, this study estimates a production function in which electricity enters the model in capital-augmenting style. The study aims to examine the transmission channels in the electricity-economic growth nexus.

Design/methodology/approach

Using monthly data on Nigeria from 1980 to 2013, the study uses the three-stage least square regression technique, which not only controls for possible endogeneity in the model but also allows for tracing the transmission linkages to estimate the relationship between electricity and economic growth in Nigeria.

Findings

This study establishes that electricity positively affected economic growth in Nigeria however through its positive effects on industrial output. The direct effect of electricity on economic growth was insignificant. This study thus concluded that the transmission mechanism in electricity-economic growth nexus is the electricity-induced industrial growth.

Practical implications

Nigeria should increase her electricity supply (for increased electricity consumption) because this would significantly stimulate her industrialization and economic growth.

Originality/value

This study differs from earlier studies in that it did not primarily focus on causality; it examined the transmission channels in the electricity-economic growth nexus. Moreover, it differs from them on the implicit assumptions made by earlier studies that electricity enters the production function in a Hicks-neutral fashion. It rather estimated a model in which electricity enters the production function in capital-augmenting fashion because the study assumed that productivity of capital is affected by electricity supply.
Examining why developers encourage foreign investment in local residential real estate in India
Authors: Tiwari Alok , Aljoufie Mohammed
Published: November 2016

Purpose

The study aims to explore the role of non-resident Indian (NRI) investors into staggering local housing market and the efforts of developers and regulators to lure such investors.

Design/methodology/approach

Primary data for this exploratory study were assembled through a Google form-based questionnaire circulated over internet among NRIs residing in Kingdom of Saudi Arabia, USA, Singapore and United Arab Emirates, whereas the secondary data sources include the Government of India policy documents, World Bank data, Reserve Bank of India archives and reports published in reputed financial and others print media sources.

Findings

Indian housing market is confronted with a demand and supply mismatch at present. While a massive demand lingers at affordable housing segment, on the contrary, millions of housing inventories are also piling up. Consequently, property developers are attempting to lure the large population of NRIs residing at global cities. Study observes that sentimental attachment to the homeland, higher rate of returns, anticipated rental incomes are the major decisive elements. Additionally, growth in infrastructure, world-class amenities offered by developers, conformity to sustainability and political stability is the other critical reasons.

Research limitations/implications

On first hand, the study outlines a novel kind of foreign investment in Indian local residential real estate that is via NRI channel. Second, non-resident investors might surprise to the property developers and government through a realistic strategic approach.

Originality/value

Probably, the study is first of its type gazing at NRI investors, as a foreign investor, in the local residential real estate.
Behavior of land markets and restrictions on housing access in Buenos Aires between 2003 and 2013
Authors: Baer Luis , Kauw Mark
Published: November 2016

Purpose

This paper aims to understand the paradoxal development in Buenos Aires, Argentina, where economic growth was not accompanied by improved housing access. The period between the years 2003 and 2013 was characterized by a sustained economic growth with social inclusion and a great expansion of both social and private housing supply in the cities of Argentina. However, this growth was not accompanied by an improvement in the overall access to land and housing. On the contrary, the habitation problems in terms of access to formal, environmentally safe and well-located land with decent facilities have worsened. The City of Buenos Aires is one of the places where this paradox is most manifested.

Design/methodology/approach

The functioning of the land markets and the real estate development in Buenos Aires will be analyzed in the period 2003-2013 in relation to the macroeconomic context, the monetary effort for the acquisition and rent of a formal dwelling and certain logics of urban development.

Findings

The rhythm of urban land valorization continuously surpassed that of other commodities and services. The expansion of residential production did not improve the access to formal housing. On the contrary, habitation issues have worsened and conflicts concerning access to land, housing and the city have rapidly increased since 2003.

Originality/value

In a Latin American context, this paper is the first to establish a conceptual relationship based on empirical data between land price dynamics and real estate development. The paper is also original in its identification of a change in valorization rhythm and pattern of real estate development in the past decade (2003-2013).
Rental rate as an alternative pricing for Islamic home financing
Authors: Mohd Yusof Rosylin , Bahlous Mejda , Haniffa Roszaini
Published: November 2016

Purpose

This paper aims to contribute to the banking and housing market literature by proposing an alternative measure of rate of return for Islamic banks that is based on the rental rate of the property. This alternative Islamic mortgage pricing mechanism could be adopted by Islamic banks as a replacement for mortgage rates if it is found to be independent from any form of interest rates as required by Islamic law.

Design/methodology/approach

By investigating the short run and long run dynamics between rental price index (RPI) and the proposed Islamic Rental Rate (RR-I) and, three selected macroeconomic indicators in the UK via autoregressive distributed lag model, the authors examine the link between RPI, RR-I and the real economy.

Findings

The findings provide evidence that while RPI in the UK is significantly related to three leading macroeconomic variables, namely, gross domestic product (GDP), real effective exchange rate and interest rates measures, while RR-I is only impacted by changes in GDP. More importantly, the authors show that there is no short or long run dynamics between the rental rate and any form of interest rates.

Research limitations/implications

This paper did not attempt to investigate the impact of the physical attributes of the rental property to formalize the model describing the relationship between RPI and RR-I. Also, other macroeconomic factors like household income growth, risk, house value growth rate and taxation could be included in future models.

Practical implications

As Rental Rate is not linked to the macroeconomic determinants, it is therefore more stable, resilient and sustainable and, at the same time, making the financing less risky for both parties, as they are less susceptible to economic vulnerabilities.

Social implications

Some calculations incorporating the proposed RR-I can also be extended to the pricing of products based on other contracts such as Tawarruq, Bai Bithaman Ajil or even Murabahah for a fairer and just pricing to both the banks and customers.

Originality/value

The results suggest that Islamic banks should consider incorporating the proposed rental rate (RR-I) when pricing their home financing products, as this will lead to less dependence on interest rates for benchmarking. In addition, using the proposed rental rate (RR-I) reduces the exposure to the subjective evaluation by property valuators and speculative macroeconomic elements.
Competition and efficiency in the non-life insurance market in South Africa
Authors: Alhassan Abdul Latif , Biekpe Nicholas
Published: November 2016

Purpose

The purpose of this paper is to examine the empirical effect of competition on cost and profit efficiency in the South African non-life insurance market in a three-stage analysis.

Design/methodology/approach

Using annual firm level data on 80 non-life insurance companies from 2007 to 2012, the authors first employ the stochastic frontier analysis (SFA) to estimate cost and profit efficiency scores. In the second stage, the authors measure insurance market competition using the Panzar-Rosse (P-R)H-statistics. In the final stage, the authors estimate a fixed-effects panel regression model which controls for heteroskedasticity to examine the effect of competition on the estimated efficiency scores. Firm size, diversification, age, risk, reinsurance and leverage are employed as control variables.

Findings

From the SFA, the authors find average cost and profit efficiency of 80.08 and 45.71 per cent, respectively. This suggests that non-life insurers have high levels of efficiency in cost and low efficiency in profit. The annual estimates of the P-RH-statistics also suggest that firms in the market earn revenues under conditions of monopolistic competition. The authors find a positive effect of competition on cost and profit efficiency to validate the “quiet-life” hypothesis which posits that competition improves efficiency.

Practical implications

Regulatory policies should be directed towards enhancing competition to improve on the low profit earning potential of firms in the non-life market.

Originality/value

To the best of the authors’ knowledge, this study presents the first application of a non-structural measure of competition to examine the empirical relationship between competition and efficiency in insurance markets.
Brazil: monetary policy and the neutral interest rate
Authors: da Silva Cleomar Gomes , de Araújo Rafael Cavalcanti
Published: November 2016

Purpose

The purpose of this paper is to analyze the conduct of monetary policy in Brazil and estimate the country’s neutral real interest rate.

Design/methodology/approach

The authors make use of a state-space macroeconomic model representation.

Findings

The period of analysis goes from 2003 up to the end of 2013 and the results show that the country’s natural rate of interest was around 4.2 percent in December 2013.

Originality/value

One of the main differences of this work is the inclusion of variables such as the real exchange rate and world interest rate. This is important because these variables play an important role in the definition of the interest rate and, consequently, in the definition of the neutral interest rate.
Expanding the Online Political Demos but Maintaining the Status Quo? Internet and Social Media Use by Finnish Voters Prior to Elections, 2003–15
Authors: Strandberg Kim , Carlson Tom
Published: November 2016

Though reinforcement/mobilisation theories regarding the impact of the Internet on citizens’ political engagement are predictive, there are few longitudinal studies on how the profile of the citizens using the Internet for political purposes has changed and how this relates to such theoretical perspectives. Using survey data from four Finnish parliamentary elections, 2003–15, this longitudinal study examines the evolution of the predictors of belonging to the segment of citizens who extensively engage in searching for political information online during the elections. Additionally, the research longitudinally studies the evolution of the drivers of citizens deeming online sources as important for informing their voting decisions. In light of demographic and resource‐based traits, a mobilisation trend is detected across time in the analyses. As to factors concerning attitudes and orientation to politics, however, a more evident reinforcement trend has emerged. These patterns are also evident when examining social media engagement through searching for political information during campaigns. Although the Internet and social media are becoming important for a demographically increasingly diverse group of citizens, especially the young, it is those already predisposed for doing so who have, over time, engaged politically to an increasing degree through these channels.
Why do lactobacilli dominate the human vaginal microbiota?
Authors: Witkin SS , Linhares IM
Published: November 2016

Lactobacilli are the most abundant vaginal bacteria in women. They inhibit binding of other bacteria to epithelial cells and produce lactic acid that kills or inhibits the growth of many other bacteria. Lactic acid blocks histone deacetylases, thereby enhancing gene transcription and DNA repair. Lactic acid induces autophagy in epithelial cells to degrade intracellular microorganisms and promote homeostasis. Lactobacilli are tolerated by vaginal epithelial cells and inhibit induction of pro‐inflammatory cytokines. Emotional stress may reduce lactobacilli abundance in the vaginal microbiota and enhance inflammation. The ability of lactobacilli to inhibit infection without inducing inflammation may maximise fecundity and successful pregnancy outcome in women.

Tweetable abstract

Lactobacilli prevent infection without inducing inflammation to maximise fertility and pregnancy outcome.
Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high‐fat and high‐fructose diets
Authors: Huang Jiung‐Pang , Cheng Mei‐Ling , Hung Cheng‐Yu , Wang Chao‐Hung , Hsieh Po‐Shiuan , Shiao Ming‐Shi , Chen Jan‐Kan , Li Dai‐Er , Hung Li‐Man
Published: November 2016

Background

The aim of the present study was to compare insulin resistance and metabolic changes using a global lipidomic approach.

Methods

Rats were fed a high‐fat diet (HFD) or a high‐fructose diet (HFrD) for 12 weeks to induce insulin resistance (IR) syndrome. After 12 weeks feeding, physiological and biochemical parameters were examined. Insulin sensitivity and plasma metabolites were evaluated using a euglycemic–hyperinsulinemic clamp and mass spectrometry, respectively. Pearson's correlation coefficient was used to investigate the strength of correlations.

Results

Rats on both diets developed IR syndrome, characterized by hypertension, hyperlipidemia, hyperinsulinemia, impaired fasting glucose, and IR. Compared with HFrD‐fed rats, non‐esterified fatty acids were lower and body weight and plasma insulin levels were markedly higher in HFD‐fed rats. Adiposity and plasma leptin levels were increased in both groups. However, the size of adipocytes was greater in HFD‐ than HFrD‐fed rats. Notably, the lipidomic heat map revealed metabolites exhibiting greater differences in HFD‐ and HFrD‐fed rats compared with controls. Plasma adrenic acid levels were higher in HFD‐ than HFrD‐fed rats. Nevertheless, linoleic and arachidonic acid levels decreased in HFrD‐fed rats compared with controls. Plasma concentrations of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were significantly reduced after feeding of both diets, particularly the HFrD. There was a strong positive correlation between these two fatty acids and the insulin sensitivity index.

Conclusions

The systemic lipidomic analysis indicated that a reduction in DHA and DPA was strongly correlated with IR in rats under long‐term overnutrition. These results provide a potential therapeutic target for IR and metabolic syndrome.
Searching for clarity in muddy water: future considerations for classifying compulsive sexual behavior as an addiction
Authors: Kraus Shane W. , Voon Valerie , Kor Ariel , Potenza Marc N.
Published: November 2016

Commentary to: Should compulsive sexual behavior be considered an addiction?
Minimally Invasive Implantation of HeartWare Assist Device and Simultaneous Tricuspid Valve Reconstruction Through Partial Upper Sternotomy
Authors: Hillebrand Julia , Hoffmeier Andreas , Djie Tiong Tjan Tonny , Sindermann Juergen R. , Schmidt Christoph , Martens Sven , Scherer Mirela
Published: November 2016

Left ventricular assist device (LVAD) implantation is a well‐established therapy to support patients with end‐stage heart failure. However, the operative procedure is associated with severe trauma. Third generation LVADs like the HeartWare assist device (HeartWare, Inc., Framingham, MA, USA) are characterized by enhanced technology despite smaller size. These devices offer new minimally invasive surgical options. Tricuspid regurgitation requiring valve repair is frequent in patients with the need for mechanical circulatory support as it is strongly associated with ischemic and nonischemic cardiomyopathy. We report on HeartWare LVAD implantation and simultaneous tricuspid valve reconstruction through minimally invasive access by partial upper sternotomy to the fifth left intercostal space. Four male patients (mean age 51.72 ± 11.95 years) suffering from chronic heart failure due to dilative (three patients) and ischemic (one patient) cardiomyopathy and also exhibiting concomitant tricuspid valve insufficiency due to annular dilation underwent VAD implantation and tricuspid valve annuloplasty. Extracorporeal circulation was established via the ascending aorta, superior vena cava, and right atrium. In all four cases the LVAD implantation and tricuspid valve repair via partial median sternotomy was successful. During the operative procedure, no conversion to full sternotomy was necessary. One patient needed postoperative re‐exploration because of pericardial effusion. No postoperative focal neurologic injury was observed. New generation VADs are advantageous because of the possibility of minimally invasive implantation procedure which can therefore minimize surgical trauma. Concomitant tricuspid valve reconstruction can also be performed simultaneously through partial upper sternotomy. Nevertheless, minimally invasive LVAD implantation is a challenging operative technique.
Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy
Authors: Colombel J.‐F. , Jharap B. , Sandborn W. J. , Feagan B. , Peyrin‐Biroulet L. , Eichner S. F. , Robinson A. M. , Mostafa N. M. , Zhou Q. , Thakkar R. B.
Published: November 2016

Background

Adalimumab is approved for use in patients with moderate to severe Crohn's disease (CD) or ulcerative colitis (UC) who have not achieved disease control with conventional therapies including corticosteroids and/or immunomodulators (IMM).

Aim

To analyse six studies that examined efficacy, pharmacokinetics and safety of combination IMM/adalimumab therapy, compared with adalimumab monotherapy in patients with inadequate disease control on conventional therapy.

Methods

Patients with moderate to severe CD or UC from randomised, double‐blind, placebo‐controlled trials were analysed. Adalimumab was added to background therapy; patients were categorised as receiving adalimumab monotherapy (CD induction, n = 245, maintenance, n = 185; UC induction, n = 213, maintenance, n = 157) or combination therapy (CD induction, n = 139, maintenance, n = 139; UC induction, n = 140, maintenance, n = 100) according to baseline immunomodulator use. Efficacy was reported for the intent‐to‐treat populations from each study, with remission defined as CD activity index <150 for CD and Mayo score ≤2 with no subscore >1 for UC. Safety was assessed via adverse events.

Results

The proportions of patients achieving remission were similar for adalimumab monotherapy and immunomodulator combination therapy in all studies. Median adalimumab concentrations at week 4 or 8 were numerically but not significantly higher with adalimumab combination therapy vs. monotherapy in the CD and UC studies respectively. Incidence and rate of adverse events was similar for adalimumab monotherapy and combination therapy.

Conclusions

Post hoc analysis of six randomised, controlled trials demonstrated no efficacy benefits with immunomodulator/adalimumab combination therapy, compared with adalimumab monotherapy in CD and UC patients with inadequate disease control on conventional therapy; the safety of the two treatment approaches was comparable.
Is it important to palpate lymph nodes in open surgery for colorectal cancer?
Authors: Yamaoka Yusuke , Kinugasa Yusuke , Shiomi Akio , Yamaguchi Tomohiro , Kagawa Hiroyasu , Yamakawa Yushi , Furutani Akinobu , Numata Masakatsu
Published: November 2016

Introduction

In laparoscopic or robotic surgery, surgeons cannot directly palpate lymph nodes (LN), which could be considered a shortcoming in that procedure. This study was performed to evaluate the importance of palpation diagnosis of LN metastasis in colorectal cancer surgery.

Methods

This study enrolled 408 patients who underwent curative resection for primary colorectal cancer in our department in 2014. The diameter of each manually dissected LN was measured, and the LN was then examined by palpation to determine whether it was metastatic based on its consistency. The palpation and pathological diagnoses of each LN were compared. Sensitivities, specificities, positive predictive values, negative predictive values, and accuracies were calculated for palpation diagnosis of LN metastasis in a node‐by‐node analysis, according to LN size.

Results

Of the 13 750 dissected LN, 444 LN (3.2%) were metastatic. Overall, palpation diagnosis of LN metastasis revealed node‐by‐node sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 50%, 98%, 52%, 98%, and 97%, respectively. The sensitivity for LN 3 mm and smaller and for LN 15 mm and larger was 3% and 90%, respectively.

Conclusion

Palpation diagnosis of LN metastasis in colorectal cancer surgery was unreliable. Although poor haptics is considered to be a disadvantage in laparoscopic and robotic surgery, they are not inferior to open surgery in terms of LN dissection.
Dynamic population pharmacokinetic–pharmacodynamic modelling and simulation supports similar efficacy in glycosylated haemoglobin response with once or twice‐daily dosing of canagliflozin
Authors: de Winter Willem , Dunne Adrian , de Trixhe Xavier Woot , Devineni Damayanthi , Hsu Chyi‐Hung , Pinheiro Jose , Polidori David
Published: November 2016

Aim

Canagliflozin is an SGLT2 inhibitor approved for the treatment of type‐2 diabetes. A dynamic population pharmacokinetic–pharmacodynamic (PK/PD) model relating 24‐h canagliflozin exposure profiles to effects on glycosylated haemoglobin was developed to compare the efficacy of once‐daily and twice‐daily dosing.

Methods

Data from two clinical studies, one with once‐daily, and the other with twice‐daily dosing of canagliflozin as add‐on to metformin were used (n = 1347). An established population PK model was used to predict full 24‐h profiles from measured trough concentrations and/or baseline covariates. The dynamic PK/PD model incorporated an Emax relationship between 24‐h canagliflozin exposure and HbA1c‐lowering with baseline HbA1c affecting the efficacy.

Results

Internal and external model validation demonstrated that the model adequately predicted HbA1c‐lowering for canagliflozin once‐daily and twice‐daily dosing regimens. The differences in HbA1c reduction between the twice‐daily and daily mean profiles were minimal (at most 0.023% for 100 mg total daily dose [TDD] and 0.011% for 300 mg TDD, up to week 26, increasing with time and decreasing with TDD) and not considered clinically meaningful.

Conclusions

Simulations using this model demonstrated the absence of clinically meaningful between‐regimen differences in efficacy, supported the regulatory approval of a canagliflozin‐metformin immediate release fixed‐dose combination tablet and alleviated the need for an additional clinical study.
Caffeic acid phenethyl ester (CAPE) revisited: Covalent modulation of XPO1/CRM1 activities and implication for its mechanism of action
Authors: Wu Sijin , Zhang Keren , Qin Hongqiang , Niu Mingshan , Zhao Weijie , Ye Mingliang , Zou Hanfa , Yang Yongliang
Published: November 2016

Caffeic acid phenethyl ester (CAPE) is the bioactive constituent of propolis from honeybee hives and is well known for its anti‐inflammatory, anticarcinogenic, antioxidant, and immunomodulatory properties. Herein, we revisited the cellular mechanism underlying the diverse biological effects of CAPE. We demonstrated that XPO1/CRM1, a major nuclear export receptor, is a cellular target of CAPE. Through nuclear export functional assay, we observed a clear shift of XPO1 cargo proteins from a cytoplasmic localization to nucleus when treated with CAPE. In particular, we showed that CAPE could specifically target the non‐catalytic and conserved Cys528 of XPO1 through the means of mass spectrometric analysis. In addition, we demonstrated that the mutation of Cys528 residue in XPO1 could rescue the nuclear export defects caused by CAPE. Furthermore, we performed position‐restraint molecular dynamics simulation to show that the Michael acceptor moiety of CAPE is the warhead to enable covalent binding with Cys528 residue of XPO1. The covalent modulation of nuclear export by CAPE may explain its diverse biological effects. Our findings may have general implications for further investigation of CAPE and its structural analogs.