bluuebunny/crossref_metadata_2025 huggingface dataset:
Political business cycles and economic growth in Africa
Authors: Iddrisu Abdul Ganiyu , Bokpin Godfred A.
Published: July 2018

Purpose

The purpose of this paper is to understand both the incidence and the impact of the African political business cycle (PBC) in the light of a literature which has argued that, with major extensions of democracy since the 1990s, the cycle has both become more intense and has made African political systems more fragile. It answers two very important macroeconomic questions crucial to the validity of the opportunistic model. It, first, answers the question of whether election cycles contribute to money growth in the light of government expenditure, and second, whether election cycles have an effect on economic growth in the light of money supply.

Design/methodology/approach

The study employs data from 39 African countries from 1990 to 2014 to address these important empirical questions using panel regression techniques.

Findings

The paper found PBC to be present in Africa. It also found that such cycles do not translate to economic performance in African countries. The paper therefore indicates the need for African policy makers to take measures to eliminate or lessen the scale of PBCs.

Social implications

There are many ways in which today’s political choices affect future well-being. Recently, economists have concluded that we pass on the inflationary (or deflationary) consequences of current policies to the future generation.

Originality/value

This paper is unique in its approach to investigate the objectives.
A random effects multinomial logit model for the determinants of exit modes
Authors: Irfan Mohd , Saha Sarani , Singh Sanjay Kumar
Published: July 2018

Purpose

The purpose of this paper is to examine the factors associated with three modes of firms’ exit (voluntary liquidation, involuntary liquidation and acquisition) in a mutually exclusive environment. In particular, three modes of exit are treated as independent events given that different causes and consequences exist for each exit mode. The data set is a panel of 4,408 US manufacturing firms spanning over the period 1976–1995.

Design/methodology/approach

The discrete choice model is used to establish a relationship between modes of exit and a set of explanatory variables, which are specific to the firm, industry and macroeconomic conditions. Use of panel data encourages us to estimate a random effects multinomial logistic regression model, which allows exit modes as mutually exclusive events and at the same time controls the firm-specific unobserved heterogeneity in the sample.

Findings

The analysis suggests that the determinants of voluntary liquidation are age, size, profitability, technology intensity and inflation level. The determinants of involuntary liquidation are size, leverage, profitability and inflation level. For acquisition, determinants are age, size, advertising intensity, Tobin’sq, GDP growth, inflation level and interest rate. The findings suggest that exit modes have a different set of determinants and the scale of effects of some common determinants such as age, size and profitability differs between exit modes.

Research limitations/implications

The analysis presented in this study relies on data from US manufacturing firms only. Thus, there is a need to explore the determinants of exit modes in other countries as well using the proposed econometric model.

Practical implications

The findings presented in this paper are useful for managers and policymakers to design strategies/actions for avoiding particular mode of exit.

Originality/value

This study provides empirical evidence on the differences in factors associated with exit modes and confirms the existence of mutually exclusive nature of exit modes. Findings suggest that for future empirical studies on firm exit, the exit modes must be treated as a heterogeneous event.
Is exit tax a good idea for the taxman?
Authors: Dai Darong
Published: July 2018

Purpose

The purpose of this paper is to study whether it is a rational choice for a tax authority to impose an exit tax on capitalists.

Design/methodology/approach

The tax authority chooses a lump-sum exit tax to maximize a weighted objective of expected tax revenue and expected tax horizon. The tax revene consists of capital income taxes and exit taxes. Capitalists are motivated by sustainable capital accumulation and hence maximize the terminal capital stock.

Findings

The author finds that the objective function of the tax authority is strictly increasing in the exit tax, which holds for extensions with sales tax, labor income tax or proportional exit tax, and hence equilibrium exit tax is equal to an exogenous upper bound.

Originality/value

To the author’s knowledge, no existing literature investigates this issue theoretically, and hence the current paper represents the first attempt. The author hopes this theoretical analysis can trigger related empirical studies.
Stimulating broadband adoption: state-owned companies versus tax exemptions – the Brazilian case
Authors: Baigorri Carlos M. , Maldonado Wilfredo L.
Published: July 2018

Purpose

The purpose of this paper is to propose a new methodology to assess the economic and social impacts of policies to promote mass access to the internet in fixed broadband. The authors apply the methodology to the Brazilian broadband market.

Design/methodology/approach

For this purpose, municipal information concerning the provision of EILD is used, and then a stylized model of definition of service penetration based on information regarding the price, the distribution of income and the number of households served is proposed.

Findings

The results indicate that cost reduction policies are more effective than measures to promote competition through the introduction of state-owned enterprises in the telecommunication market for broadband service. On the other hand, the results also indicate that the federal and state governments face a dilemma between broadband policy and tax policy.

Originality/value

This is a new and original methodology to model the broadband market demand, which is useful to assess the impact of regulation policies in the sector as well as structural changes in that market.
Competencies expected of graduate quantity surveyors working in developing countries
Authors: Yogeshwaran Gayathri , Perera B.A.K.S. , Ariyachandra M.R. Mahendrini Fernando
Published: July 2018

Purpose

Quantity surveying education in Sri Lanka (SL) presently does not appear to be catering to the industry needs indicating that it may not be up to the expected standard. Hence, the purpose of this study is to identify the gap between the competencies of graduate quantity surveyors (QSs) and the competencies that industry in SL expects from them.

Design/methodology/approach

A hybrid approach was used, consisting of desk reviews, expert interviews and a questionnaire survey. A comparative analysis identifying differences between two competency levels was carried out.

Findings

Analysis reveals that competencies of graduate QSs in areas of cost planning, strategic planning, risk management, value management, life cycle cost analysis, sustainability, surveying and levelling, research and development, building surveying and business management are at levels higher than industry needs. However, majority of competencies are at levels lower than industry expectations.

Research limitations/implications

This research was focused only on competencies of QSs who have successfully completed a quantity surveying degree programme accredited by Institute of QSs SL, Royal Institution of Chartered Surveyors, Australian Institute of QSs and Pacific Association of QSs. It excluded non-graduates’ competencies as they gain competencies only through work experience.

Practical implications

This study revealed the need for designing quantity surveying degree programmes to cater to industry needs to ensure that graduates from these programmes are acceptable to the industry.

Originality/value

This study made an original contribution to knowledge by identifying the gap that currently exists between industry needs and programme outcomes of quantity surveying degree programmes, which could be invaluable when improving quantity surveying education in SL.
Role of culture in low carbon supply chain capabilities
Authors: Ambekar Sudhir , Prakash Anand , Patyal Vishal Singh
Published: July 2018

Purpose

The purpose of this paper is to propose a low carbon culture (LCC) adoption model for gaining the right carbon capabilities by integrating the dimensions of flexibility or control and external or internal of competing values framework (CVF) with that of level of carbon emission (LCE).

Design/methodology/approach

This study reviewed literature related to low carbon supply chain, CVF and carbon capabilities to synthesize currently available frameworks for assessing culture and carbon-related insights. Based on these insights, this study proposes the carbon culture adoption model and presents some research propositions.

Findings

This study has extended categorization of culture suggested in CVF from four categories to eight distinct categories by adding “LCE” as a third dimension. The new categories of carbon culture are: “Red,” “Antagonist,” “Obligatory,” “Early Adopter,” “Follower,” “Transitive,” “Pragmatist” and “Green.” This categorization of organizations would help in selecting appropriate low carbon practices (LCPs).

Research limitations/implications

This study presents purely conceptual framework with some research propositions which needs to be empirically tested.

Practical implications

Organizations can formulate right policies for low carbon capabilities based on the LCC of their supply chain.

Originality/value

With increasing awareness about environment across stakeholders, organizations around the world are under pressure to reduce their carbon footprints. The extent of reduction in carbon footprints depends on the right capabilities across the supply chain which in turn depends on selection of the right combination of LCPs based on the supply chain culture.
Business value of enterprise resource planning spending and scope
Authors: Ghobakhloo Morteza , Azar Adel , Tang Sai Hong
Published: July 2018

Purpose

The purpose of this study is to contribute to the existing knowledge about the value of post-implementation Enterprise Resource Planning (ERP) system at the firm level.

Design/methodology/approach

A questionnaire-based survey was conducted to collect data from 217 Malaysian firms that successfully implemented ERP system. Data analysis was conducted with partial least squares-structural equation modeling and partial least squares multi-group analysis techniques.

Findings

Higher ERP spending and greater ERP scope in the post-implementation stage were associated with higher performance gains.

Research limitations/implications

Among other limitations, relying on a small sample size and cross-sectional data of this study and lack of generalizability of findings tend to have certain limitations. An interesting direction for future research would be to extend this study by conducting a multi-level analysis to understand how ERP spending and scope would affect the micro-level performance.

Practical implications

Non-financial performance gain is another valuable outcome of ERP implementation. The choice between in-house and off-the-shelf ERP systems will have dramatic impacts on the future profitability of firms. ERP risk management team and related practices during implementation phase result in a significantly higher financial gain in the post-implementation phase.

Originality/value

This study assesses the business value of ERP at the post-implementation phase while accounting for key contextual and managerial issues, a topic that has received little attention to date.
The application of biochar to screen printing liquid waste polluted land, its effect in soil, mustard greens to heavy metals (Fe, Cr)
Authors: Sujana I. Putu
Published: July 2018

Purpose

The purpose of this paper is to analyse the screen printing liquid waste polluted soil physical, chemical and biological characteristics, with the unpolluted soil, and to analyse the application of some types of biochar towards the growth of mustard greens plants and the concentration of heavy metals Fe, Cr on the screen printing liquid waste polluted soil.

Design/methodology/approach

This research was conducted in a green house by using fully randomized design, split plot design pattern, with three replications. The main plot is the type of biochar, and the subplot is the dosage of biochar. The biochar consists of four types (B1 = chicken manure biochar, B2 = coconut shell biochar, B3 = rice hulls biochar and B4 = mahogany woods biochar). The dosage of biochar consists of four levels (D0 = control, D1 = 5 ton/hectare, D2 = 10 ton/hectare and D3 = 15 ton/hectare). The tested variable is being analysed by using analysis of variance (ANOVA).

Findings

The screen printing liquid waste polluted soil physical, chemical and biological characteristics analysis shows that the soil pH is neutral, a low C organic, a low N total, a high P, CEC and base saturation, while the texture is soft. The analysis results of rice hulls biochar physical, chemical and biological characteristics are quantitatively better in comparison with chicken manure biochar, coconut shell biochar and mahogany biochar. The quantitative application of rice hulls biochar15 ton/hectare dosage can increase the growth of mustard greens, and also, it recovers the soil characteristics by heavy metals total rate of 14.11 ppm Fe and 0.95 ppm Cr from the plant, while 209.05 ppm Fe and 4.12 ppm Cr were found in the soil.

Originality/value

This is one of few studies the biochar to screen printing liquid waste polluted lands. Currently, numerous kinds of chemical substances have been applied in a form of fertilizer and pesticide into the soil. Other activities like transporting the crop residues, and the contamination of irrigation water that is caused by screen printing liquid waste, have also affected the soil. It becomes degraded where the soil becomes compact and losses its nutrients, and it is containing heavy metals material that is toxic for plants. Biochar is applied into the polluted soil to improve the soil, which is hard to decompose and is long-lasting in the soil. These days, both the raw or ready food products are exposed to the heavy metals with a large and concerning number, especially in big cities which most of the soil is polluted.
Dref-3 yarn structure with plied staple fibrous core
Authors: Bhowmick Manik , Rakshit Arup Kumar , Chattopadhyay Sajal Kumar
Published: July 2018

Purpose

Dref-3 friction spun core yarns produced using staple fibre yarn as the core, e.g. Jute core yarn wrapped with cotton fibre, have poorer mechanical properties compared to the core yarn itself. The purpose of this study was to understand the structure of such yarns, that will lead to the optimization of fibre, machine and process variables for production of better quality yarn from the Dref-3/3000 machines.

Design/methodology/approach

The Dref spinning trials were conducted following a full factorial design with six variables, all with two operative levels. The Dref-3 friction spun yarn, in which the core is a plied, twisted ring yarn composed of cotton singles and the sheath, formed from the same cotton fibres making the singles, has been examined. The structures have also been studied by using the tracer fibre technique.

Findings

It was observed that rather than depending on the plied core yarn, the tensile properties of the Dref-3 yarn are significantly determined by the parameters those affect the constituent single yarn tensile properties, i.e. the amount of twist and its twist direction, yarn linear density and the sheath fibre proportion used during the Dref spinning in making the final yarn. Further, when the twist direction of single yarn, double yarn and the Dref spinning false twisting are in the same direction, the produced core-sheath yarn exhibits better tensile properties.

Practical implications

The understanding of the yarn structure will lead to optimized production of all staple fibre core Dref spun yarns.

Social implications

The research work may lead to utilization of coarse and harsh untapped natural fibres to the production of value-added textile products.

Originality/value

Though an earlier research has reported the effects of sheath fibre fineness and length on the tensile and bending properties of Dref-3 friction yarn, the present study is the first documented attempt using the tracer fibre technique to understand Dref-3 yarn structure with plied staple fibrous core.
Physiological and pathophysiological role of reactive oxygen species and reactive nitrogen species in the kidney
Authors: Ishimoto Yu , Tanaka Tetsuhiro , Yoshida Yoko , Inagi Reiko
Published: July 2018

End‐stage renal disease is a leading cause of morbidity and mortality worldwide. The prevalence of the disease and the number of patients who receive renal replacement therapy are expected to increase in the next decade. Accumulating evidence suggests that chronic hypoxia in the tubulointerstitium represents the final common pathway to end‐stage renal failure, and that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the key players in kidney injury. However, ROS and RNS that exceed the physiological levels associated with the pathophysiology of most kidney diseases. The molecules that comprise ROS and RNS play an important role in regulating solute and water reabsorption in the kidney, which is vital for maintaining electrolyte homeostasis and the volume of extracellular fluid. This article reviews the physiological and pathophysiological role of ROS and RNS in normal kidney function and in various kidney diseases.
The microbiomes of a XVIII century mummy from the castle of Krásna Hôrka (Slovakia) and its surrounding environment
Authors: Kraková Lucia , Šoltys Katarína , Puškárová Andrea , Bučková Mária , Jeszeová Lenka , Kucharík Marcel , Budiš Jaroslav , Orovčík L´ubomír , Szemes Tomáš , Pangallo Domenico
Published: July 2018

This microbiological survey was performed to determine the conservation state of a mummy in the Slovak castle of Krásna Hôrka and its surrounding environment. Culture‐dependent identification was coupled with biodegradation assays on keratin, gelatin and cellulose. Next Generation Sequencing (NGS) using Illumina platform was used for a deeper microbial investigation. Three environmental samples were collected: from the glass of the sarcophagus, from the air inside it, and from the air of the chapel where the mummy is located. Seven different samples were taken from mummy's surface: from the left ear, left‐hand palm, left‐hand nail, left instep, right hand, abdomen and mineral crystals embedded within the skin. Three internal organ samples, from the lung, pleura and stomach, were also included in this study. Together, the culture‐dependent and culture‐independent analyses revealed that the bacterial communities present had fewer taxa than the fungal ones. The mycobiome showed the largest variability and included Epicoccum nigrum, Penicillium spp., Alternaria spp., Aspergillus spp., Cladosporium spp. and Aureobasidium pullulans; many other Ascomycota and Basidiomycota genera were detected by NGS. The most interesting results came from the skin mineral crystals and the internal organs. The hydrolytic assays revealed those microorganisms which might be considered dangerous ‘mummy pathogens’. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd
Novel phage–host interactions and evolution as revealed by a cyanomyovirus isolated from an estuarine environment
Authors: Xu Yongle , Zhang Rui , Wang Nannan , Cai Lanlan , Tong Yigang , Sun Qiang , Chen Feng , Jiao Nianzhi
Published: July 2018

Cyanophages are thought to affect the community structure, population dynamics, metabolic activity and evolution of picocyanobacteria and to impact the biogeochemical cycling in aquatic ecosystems. Here, we report an estuarine Synechococcus phage, S‐CBWM1, which represents a novel viral lineage and exhibits interesting genetic features related to phage–host interactions and evolution. S‐CBWM1 encapsidates four virion‐associated proteins related to cellular metabolic regulation. Several novel auxiliary metabolic genes related to multidrug efflux, cell wall and capsule synthesis or modifications were also identified. In addition, the presence of the largest number of tRNA genes hitherto found in a phage genome may contribute to the translation efficiency of unique genes. These genomic and proteomic features of S‐CBWM1 suggested phage–host interactions involved in adaptation to eutrophic estuarine environments. Phylogenetic and metagenomic analysis of the polγ gene in the S‐CBWM1 genome provided new insights into the evolutionary path of mitochondrial DNA polymerase gamma. The S‐CBWM1 psbA contains two group I introns, representing the first instance of multiple introns within psbA from phage. The isolation of S‐CBWM1 reveals that estuarine ecosystems contain evolutionarily novel cyanophages that drive unique phage–host interactions.
Failure mode and effects analysis in a paperless radiotherapy department
Authors: Frewen Helen , Brown Elizabeth , Jenkins Michael , O'Donovan Anita
Published: July 2018

Introduction

The international move towards digital healthcare record keeping has seen an increase in the number of radiotherapy departments moving towards a paperless framework. With the recent transition to a paperless radiation oncology framework at the Princess Alexandra Hospital Brisbane, it was crucial to perform a prospective risk assessment to quantify the most significant sources of risk in the electronic environment.

Methods

A failure mode and effects analysis (FMEA) was performed using a web‐based three‐round Delphi technique. Participants included Radiation Therapists and Radiation Oncologists. A detailed process map was created of all process steps and their sub‐processes from patient booking to treatment. The first round was an open qualitative round to identify failure modes. The subsequent rounds were used to score all failure modes using the risk priority number (RPN) scoring method, based on the product of occurrence, severity and detectability scoring. The final round was also used to identify risk mitigation strategies.

Results

The process map consisted of 60 process steps and 141 sub‐processes. A list of 83 failure modes was identified and consensus was achieved regarding the risk scoring for a prioritised list of 20. Four of the top five failure modes were related to communication errors. Eighteen feasible solutions were recommended for incorporating into clinical practice to increase patient safety.

Conclusion

The FMEA proved a valuable systematic method of prospectively identifying vulnerabilities in a paperless radiotherapy department. In particular, this FMEA identified numerous failure modes concerning communication and documentation, highlighting the need for sustained vigilance when performing all electronic processes.
Bayesian Inference of Hub Nodes Across Multiple Networks
Authors: Kim Junghi , Do Kim-Anh , Ha Min Jin , Peterson Christine B.
Published: July 2018

Hub nodes within biological networks play a pivotal role in determining phenotypes and disease outcomes. In the multiple network setting, we are interested in understanding network similarities and differences across different experimental conditions or subtypes of disease. The majority of proposed approaches for joint modeling of multiple networks focus on the sharing of edges across graphs. Rather than assuming the network similarities are driven by individual edges, we instead focus on the presence of common hub nodes, which are more likely to be preserved across settings. Specifically, we formulate a Bayesian approach to the problem of multiple network inference which allows direct inference on shared and differential hub nodes. The proposed method not only allows a more intuitive interpretation of the resulting networks and clearer guidance on potential targets for treatment, but also improves power for identifying the edges of highly connected nodes. Through simulations, we demonstrate the utility of our method and compare its performance to current popular methods that do not borrow information regarding hub nodes across networks. We illustrate the applicability of our method to inference of co-expression networks from The Cancer Genome Atlas ovarian carcinoma dataset.
Information Content of Cluster–Period Cells in Stepped Wedge Trials
Authors: Kasza Jessica , Forbes Andrew B.
Published: July 2018

Stepped wedge and other multiple-period cluster randomized trials, which collect data from multiple clusters across multiple time periods, are being conducted with increasing frequency; statistical research into these designs has not kept apace. In particular, some stepped wedge designs with missing cluster–period “cells” have been proposed without any formal justification. Indeed there are no general guidelines regarding which cells of a stepped wedge design contribute the least information toward estimation of the treatment effect, and correspondingly which may be preferentially omitted. In this article, we define a metric of the information content of cluster–period cells, entire treatment sequences, and entire periods of the standard stepped wedge design as the increase in variance of the estimator of the treatment effect when that cell, sequence, or period is omitted. We show that the most information-rich cells are those that occur immediately before or after treatment switches, but also that there are additional cells that contribute almost as much to the estimation of the treatment effect. However, the information content patterns depend on the assumed correlation structure for the repeated measurements within a cluster.
Lysosomal cathepsin D is upregulated in Alzheimer's disease neocortex and may be a marker for neurofibrillary degeneration
Authors: Chai Yuek Ling , Chong Joyce R. , Weng Jiaju , Howlett David , Halsey Andrea , Lee Jasinda H. , Attems Johannes , Aarsland Dag , Francis Paul T. , Chen Christopher P. , Lai Mitchell K.P.
Published: July 2018

Alzheimer's disease (AD) is characterized by accumulation of β‐amyloid plaques (AP) and neurofibrillary tangles (NFT) in the cortex, together with synaptic loss and amyloid angiopathy. Perturbations in the brain lysosomal system, including the cathepsin family of proteases, have been implicated in AD where they may be involved in proteolytic clearance of misfolded and abnormally aggregated peptides. However, the status of cathepsin D (catD) is unclear in Lewy body dementia, the second most common form of neurodegenerative dementia after AD, and characterized by Lewy bodies (LB) containing aggregated α‐synuclein. Furthermore, earlier reports of catD changes in AD have not been entirely consistent. We measured CatD immunoreactivities in the temporal (Brodmann area BA21) and parietal (BA40) cortices of well characterized AD brains as well as two clinical subtypes of Lewy body dementia, namely Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB), known to show varying degrees of concomitant AD pathology. Increased catD immunoreactivities in AD were found for both neocortical regions measured, where they also correlated with neuropathological NFT scores and phosphorylated pSer396 tau burden, and appeared to co‐localize at least partly to NFT‐containing neurons. In contrast, catD was increased only in BA40 in DLB and not at all in PDD, did not correlate with LB scores, and did not appreciably co‐localize with α‐synuclein inclusions. Our study suggests that catD upregulation may be an adaptive response to AD‐related processes leading to neurofibrillary degeneration, but may not be directly associated with formation of α‐synuclein inclusions in Lewy body dementia.
Stable isotope‐labelled morphine to study in vivo central and peripheral morphine glucuronidation and brain transport in tolerant mice
Authors: Weinsanto Ivan , Laux‐Biehlmann Alexis , Mouheiche Jinane , Maduna Tando , Delalande François , Chavant Virginie , Gabel Florian , Darbon Pascal , Charlet Alexandre , Poisbeau Pierrick , Lamshöft Marc , Van Dorsselaer Alain , Cianferani Sarah , Parat Marie‐Odile , Goumon Yannick
Published: July 2018

Background and Purpose

Chronic administration of medication can significantly affect metabolic enzymes leading to physiological adaptations. Morphine metabolism in the liver has been extensively studied following acute morphine treatment, but such metabolic processes in the CNS are poorly characterized. Long‐term morphine treatment is limited by the development of tolerance, resulting in a decrease of its analgesic effect. Whether or not morphine analgesic tolerance affects in vivo brain morphine metabolism and blood–brain barrier (BBB) permeability remains a major question. Here, we have attempted to characterize the in vivo metabolism and BBB permeability of morphine after long‐term treatment, at both central and peripheral levels.

Experimental Approach

Male C57BL/6 mice were injected with morphine or saline solution for eight consecutive days in order to induce morphine analgesic tolerance. On the ninth day, both groups received a final injection of morphine (85%) and d3‐morphine (morphine bearing three 2H; 15%, w/w). Mice were then killed and blood, urine, brain and liver samples were collected. LC–MS/MS was used to quantify morphine, its metabolite morphine‐3‐glucuronide (M3G) and their respective d3‐labelled forms.

Key Results

We found no significant differences in morphine CNS uptake and metabolism between control and tolerant mice. Interestingly, d3‐morphine metabolism was decreased compared to morphine without any interference with our study.

Conclusions and Implications

Our data suggests that tolerance to the analgesic effects of morphine is not linked to increased glucuronidation to M3G or to altered global BBB permeability of morphine.
17β‐Estradiol reduces mitochondrial cAMP content and cytochrome oxidase activity in a phosphodiesterase 2‐dependent manner
Authors: Pozdniakova Sofya , Guitart‐Mampel Mariona , Garrabou Gloria , Di Benedetto Giulietta , Ladilov Yury , Regitz‐Zagrosek Vera
Published: July 2018

Background and Purpose

Mitochondria possess their own source of cAMP, that is, soluble adenylyl cyclase (sAC). Activation or expression of mitochondrial sAC promotes mitochondrial function. Oestrogen receptor signalling plays an essential role in the regulation of mitochondrial function. Here we aimed to determine whether 17β‐estradiol may affect mitochondrial cAMP signalling.

Experimental Approach

Expression of the intra‐mitochondrial proteins (Western blot), mitochondrial cAMP content (FRET‐based live imaging and MS assay), mitochondrial membrane potential and cytochrome oxidase activity were analysed in H9C2 and C2C12 cells.

Key Results

A 24 h treatment with 17β‐estradiol significantly reduced the basal level of mitochondrial cAMP, without affecting the intra‐mitochondrial content of sAC, phosphodiesterase 2 (PDE2) or PKA and the activity of the intra‐mitochondrial sAC. The effect of 17β‐estradiol on mitochondrial cAMP was prevented by inhibition of a cGMP‐activated PDE2 or soluble guanylyl cyclase (sGC), suggesting a role of NO signalling. Indeed, 17β‐estradiol raised cellular levels of cGMP and the intra‐mitochondrial expression of the catalytic subunit β of sGC was found. The 17β‐estradiol‐induced reduction of the mitochondrial cAMP level was accompanied by decreased cytochrome oxidase activity and mitochondrial membrane potential in a PDE2‐dependent manner.

Conclusions and Implications

17β‐estradiol reduced the basal level of mitochondrial cAMP content and cytochrome oxidase activity in a sAC‐independent but in a PDE2‐dependent manner. The results suggest a role of 17β‐estradiol‐induced activation of NO signalling in the regulation of mitochondrial cAMP content. Our study adds a new aspect to the complex action of oestrogens on mitochondrial biology, that is relevant to hormone replacement therapy.
Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1‐dependent mitochondrial oxidative damage
Authors: Wu Bing , Feng Jian‐yu , Yu Li‐ming , Wang Yan‐chun , Chen Yong‐qing , Wei Yan , Han Jin‐song , Feng Xiao , Zhang Yu , Di Shou‐yin , Ma Zhi‐qiang , Fan Chong‐xi , Ha Xiao‐qin
Published: July 2018

Background and Purpose

Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin‐1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin‐1.

Experimental Approach

I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin‐1 (sirtinol and SIRT1 siRNA).

Key Results

In vivo and in vitro, icariin given before I/R significantly improved post‐I/R heart contraction and limited the infarct size and leakage of creatine kinase‐MB and LDH from the damaged myocardium. Icariin also attenuated I/R‐induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn‐superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin‐1 was significantly up‐regulated in hearts treated with icariin, whereas Ac‐FOXO1 was simultaneously down‐regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin‐induced cardioprotection or disrupted icariin‐mediated mitochondrial homeostasis.

Conclusions and Implications

Pretreatment with icariin protected cardiomyocytes from I/R‐induced oxidative stress through activation of sirtuin‐1 /FOXO1 signalling.
Combined effect of cabozantinib and gefitinib in crizotinib‐resistant lung tumors harboring ROS1 fusions
Authors: Kato Yuka , Ninomiya Kiichiro , Ohashi Kadoaki , Tomida Shuta , Makimoto Go , Watanabe Hiromi , Kudo Kenichiro , Matsumoto Shingo , Umemura Shigeki , Goto Koichi , Ichihara Eiki , Ninomiya Takashi , Kubo Toshio , Sato Akiko , Hotta Katsuyuki , Tabata Masahiro , Toyooka Shinichi , Maeda Yoshinobu , Kiura Katsuyuki
Published: July 2018

The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non‐small cell lung cancer (NSCLC) harboring ROS1 fusion genes. However, patients inevitably develop resistance to this agent. Therefore, a new treatment strategy is required for lung tumors with ROS1 fusion genes. In the present study, lung cancer cell lines, HCC78 harboring SLC34A2‐ROS1 and ABC‐20 harboring CD74‐ROS1, were used as cell line‐based resistance models. Crizotinib‐resistant HCC78R cells were established from HCC78. We comprehensively screened the resistant cells using a phosphor‐receptor tyrosine kinase array and RNA sequence analysis by next‐generation sequencing. HCC78R cells showed upregulation of HB‐EGF and activation of epidermal growth factor receptor (EGFR) phosphorylation and the EGFR signaling pathway. Recombinant HB‐EGF or EGF rendered HCC78 cells or ABC‐20 cells resistant to crizotinib. RNA sequence analysis by next‐generation sequencing revealed the upregulation of AXL in HCC78R cells. HCC78R cells showed marked sensitivity to EGFR‐TKI or anti‐EGFR antibody treatment in vitro. Combinations of an AXL inhibitor, cabozantinib or gilteritinib, and an EGFR‐TKI were more effective against HCC78R cells than monotherapy with an EGFR‐TKI or AXL inhibitor. The combination of cabozantinib and gefitinib effectively inhibited the growth of HCC78R tumors in an in vivo xenograft model of NOG mice. The results of this study indicated that HB‐EGF/EGFR and AXL play roles in crizotinib resistance in lung cancers harboring ROS1 fusions. The combination of cabozantinib and EGFR‐TKI may represent a useful alternative treatment strategy for patients with advanced NSCLC harboring ROS1 fusion genes.
Do short implants have similar survival rates compared to standard implants in posterior single crown?: A systematic review and meta‐analysis
Authors: Tolentino da Rosa de Souza Patricia , Binhame Albini Martini Milena , Reis Azevedo‐Alanis Luciana
Published: July 2018

Background

Short implants have been presented as an option for posterior rehabilitation in cases of poor bone height.

Purpose

To compare the survival rate of short implants and standard implants when used in posterior single crowns, in addition to reporting marginal bone loss, prosthetic failures, and surgical complications.

Materials and methods

Electronic search (PubMed, LILACS, Cochrane Library, Scopus, and Web of Science) and hand search were performed to identify all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that evaluated both short and standard implants in posterior single crowns.

Results

Out of 345 articles identified by both electronic and hand search, four studies were selected (one CCT and three RCTs). The meta‐analysis for the survival rate showed that there was no significant difference between the short implants and the standard ones (P = 1.00; RR:1.00; CI:0.97‐1.03) performed with three RCTs for a one‐year follow‐up. The mean marginal bone loss ranged from 0.1 mm to 0.54 mm. Only one study reported the presence of prosthetic failures and surgical complications.

Conclusions

The survival rate of short implants was similar to the standard ones in posterior single crowns, for the one‐year follow‐up period. They also presented low surgical complications, prosthetic failures and marginal bone loss, being a predictable treatment for single rehabilitation in posterior tooth loss.
Modeling the effect of osseointegration on dental implant pullout and torque removal tests
Authors: Rittel Daniel , Dorogoy Avraham , Shemtov‐Yona Keren
Published: July 2018

Background

Osseointegration of dental implants is a key factor for their success. It can be assessed either by destructive (eg, pullout or torque extraction), or nondestructive methods (eg, resonant frequency analysis). However, as of today there is a scarcity of models that can relate the outcome of destructive tests to the level of osseointegration.

Purpose

To study various percentages of bone to implant bonding (tie) using finite element simulations. While evolutions of the bone mechanical properties are not explicitly taken into account, emphasis is put on the 3‐dimensional variable extent of the bone‐implant bonding, its statistical distribution, and its influence on the measurable extraction and torque loads, seeking to obtain a quantitative relationship.

Materials and Methods

We performed numerical simulations of randomly tied implants and calculated the evolution of the pullout force as well as that of the extraction torque.

Conclusion

Within simplifying assumptions for the osseointegration represented by a tie (as opposed to frictional) constraint, the results of this work indicate that the torque test is more discriminant than the extraction one, while both cannot really discriminate osseointegration levels below a relative variation of 20%.
Immediate prophylactic vs endoscopic or symptomatic‐driven azathioprine treatment to prevent surgical recurrence after intestinal resection for Crohn's disease
Authors: Guo Z. , Cai X. , Liu R. , Gong J. , Li Y. , Cao L. , Wang Z. , Zhu W.
Published: July 2018

Aim

Azathioprine can prevent postoperative recurrences in Crohn's disease. We compared the efficacy of azathioprine in preventing surgical recurrence to explore whether immediate prophylaxis after surgery is better than azathioprine started after endoscopic or clinical recurrence.

Method

Data of patients with intestinal resection and ileocolic anastomosis for Crohn's disease between 2006 and 2015 were retrieved from a prospectively maintained database. Patients were grouped according to the strategies of postoperative therapy with azathioprine. Univariate and multivariate proportional hazard Cox regression analyses were conducted to identify independent predictive factors for surgical recurrence.

Results

Only age equal to or less than 16 years at diagnosis was an independent risk factor for surgical recurrence in all 166 patients (P = 0.005). In patients with high risk of recurrence (27 in the symptom‐driven group, 39 in the endoscopy‐driven group and 69 in the immediate prophylaxis group), both immediate and endoscopy‐driven azathioprine delayed and reduced surgical recurrence compared with symptom‐driven azathioprine (P = 0.035, 0.019). Their efficacy in reducing surgical recurrence was confirmed by Cox regression analyses (hazard ratio 0.465, P = 0.045; hazard ratio 0.352, P = 0.028). Surgical recurrence was similar between the immediate and endoscopy‐driven groups. In addition, age ≤ 16 at diagnosis was still an independent risk factor for surgical recurrence in this subgroup.

Conclusions

In patients with high risk of recurrence, both immediate prophylactic azathioprine after surgery and azathioprine started after endoscopic recurrence can delay and reduce surgical recurrence compared with azathioprine started after clinical recurrence. In addition, azathioprine started immediately after surgery was not superior to azathioprine started after discovery of endoscopic recurrence.
Universal Principles of Human Communication: Preliminary Evidence From a Cross‐cultural Communication Game
Authors: Fay Nicolas , Walker Bradley , Swoboda Nik , Umata Ichiro , Fukaya Takugo , Katagiri Yasuhiro , Garrod Simon
Published: July 2018

The present study points to several potentially universal principles of human communication. Pairs of participants, sampled from culturally and linguistically distinct societies (Western and Japanese, N = 108: 16 Western–Western, 15 Japanese–Japanese and 23 Western–Japanese dyads), played a dyadic communication game in which they tried to communicate a range of experimenter‐specified items to a partner by drawing, but without speaking or using letters or numbers. This paradigm forced participants to create a novel communication system. A range of similar communication behaviors were observed among the within‐culture groups (Western–Western and Japanese–Japanese) and the across‐culture group (Western–Japanese): They (a) used iconic signs to bootstrap successful communication, (b) addressed breakdowns in communication using other‐initiated repairs, (c) simplified their communication behavior over repeated social interactions, and (d) aligned their communication behavior over repeated social interactions. While the across‐culture Western–Japanese dyads found the task more challenging, and cultural differences in communication behavior were observed, the same basic findings applied across all groups. Our findings, which rely on two distinct cultural and linguistic groups, offer preliminary evidence for several universal principles of human communication.
The underlying mechanisms of neurobehavioral risks in sex chromosome trisomies
Authors: van Rijn Sophie
Published: July 2018

This commentary is on the original article by Wilson and Bishop on pages 1132–1139 of this issue.
Barriers and facilitators to “moving on” from early intervention in psychosis services
Authors: Woodward Sarah , Bucci Sandra , Edge Dawn , Berry Katherine
Published: July 2018

Aim

Transition from early intervention in psychosis services (EIPS) to ongoing care can be challenging for staff and service users. This study aims to explore staff views of the barriers and facilitators to transition from EIPS.

Methods

Eighteen EIPS staff were interviewed about their experiences of discharge processes and interviews were analysed thematically.

Results

Four themes were identified: (1) “nowhere to go”: illustrated how service users remained in EIPS because other teams lacked capacity to take them; (2) “collaboration between agencies” highlights the challenges of working across boundaries; (3) “therapeutic relationships”: reflects the loss service users and staff experienced at discharge; (4) “advanced planning” relates to the necessity for advanced planning and service user empowerment to facilitate the discharge process.

Conclusions

This is the first in‐depth exploration of EIPS staff views on discharge processes. To ensure seamless transitions throughout care pathways, services need better inter‐agency collaboration and more adequate preparation for transition.
Structural plasticity of the HHD2 domain of whirlin
Authors: Delhommel Florent , Cordier Florence , Saul Frederick , Chataigner Lucas , Haouz Ahmed , Wolff Nicolas
Published: July 2018

Whirlin is a protein essential to sensory neurons. Its defects are responsible for nonsyndromic deafness or for the Usher syndrome, a condition associating congenital deafness and progressive blindness. This large multidomain scaffolding protein is expressed in three isoforms with different functions and localizations in stereocilia bundles of hearing hair cells or in the connecting cilia of photoreceptor cells. The HHD2 domain of whirlin is the only domain shared by all isoforms, but its function remains unknown. In this article, we report its crystal structure in two distinct conformations, a monomeric five‐helix bundle, similar to the known structure of other HHD domains, and a three‐helix bundle organized as a swapped dimer. Most of the hydrophobic contacts and electrostatic interactions that maintain the globular monomeric form are conserved at the protomer interface of the dimer. NMR experiments revealed that the five‐helix conformation is predominant in solution, but exhibits increased dynamics on one face encompassing the hinge loops. Using NMR and SAXS, we also show that HHD2 does not interact with its preceding domains. Our findings suggest that structural plasticity might play a role in the function of the HHD2 domain.
Impaired GAD1 expression in schizophrenia‐related WISKET rat model with sex‐dependent aggressive behavior and motivational deficit
Authors: Büki A. , Horvath G. , Benedek G. , Ducza E. , Kekesi G.
Published: July 2018

After peri‐adolescence isolation rearing (IS) and subchronic ketamine (KET) treatment, adult, selectively bred Wistar rats (named WISKET) mimic abnormal behaviors reminiscent of human schizophrenia, including reduced prepulse‐inhibition of startle reflex, disturbances in cognition, locomotor activity and thermoregulation, decreased pain sensitivity and electrophysiological alterations. To further validate our WISKET rat line, regarding its translational utility in schizophrenia research, we examined their social behavior and introduced a short and simple holeboard (HB)‐like test to investigate their motivational deficit that predicts the cognitive disturbance. Sex‐dependent alterations in schizophrenia may yield important insights into its etiology; thus, male and female WISKET rats were also investigated and compared with their naive Wistar counterparts. Considering the contribution of the hippocampal and cortical GABAergic inhibitory circuitry in these behavioral alterations, molecular‐biology studies were also performed regarding the GAD1 gene products. Impaired social activity with increased aggression, stress‐related behavior, active social withdrawal, motivation deficit and decreased exploration were observed, especially in male WISKET rats, compared with Wistar ones and their corresponding females. These alterations were accompanied by sex‐dependent alterations regarding GAD67 mRNA and protein expression in the prefrontal cortex and hippocampus. In conclusion, the WISKET animals are valuable tools for animal‐based preclinical drug discovery studies for predictive screening of novel compounds improving negative symptoms with potential antipsychotic efficacy.