bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of index signals to avoid the cost of dishonesty
Authors: Biernaskie Jay M. , Grafen Alan , Perry Jennifer C.
Published: July 2014

Animals often convey useful information, despite a conflict of interest between the signaller and receiver. There are two major explanations for such ‘honest’ signalling, particularly when the size or intensity of signals reliably indicates the underlying quality of the signaller. Costly signalling theory (including the handicap principle) predicts that dishonest signals are too costly to fake, whereas the index hypothesis predicts that dishonest signals cannot be faked. Recent evidence of a highly conserved causal link between individual quality and signal growth appears to bolster the index hypothesis. However, it is not clear that this also diminishes costly signalling theory, as is often suggested. Here, by incorporating a mechanism of signal growth into costly signalling theory, we show that index signals can actually be favoured owing to the cost of dishonesty. We conclude that costly signalling theory provides the ultimate, adaptive rationale for honest signalling, whereas the index hypothesis describes one proximate (and potentially very general) mechanism for achieving honesty.
Effects of deception in social networks
Authors: Iñiguez Gerardo , Govezensky Tzipe , Dunbar Robin , Kaski Kimmo , Barrio Rafael A.
Published: July 2014

Honesty plays a crucial role in any situation where organisms exchange information or resources. Dishonesty can thus be expected to have damaging effects on social coherence if agents cannot trust the information or goods they receive. However, a distinction is often drawn between prosocial lies (‘white’ lies) and antisocial lying (i.e. deception for personal gain), with the former being considered much less destructive than the latter. We use an agent-based model to show that antisocial lying causes social networks to become increasingly fragmented. Antisocial dishonesty thus places strong constraints on the size and cohesion of social communities, providing a major hurdle that organisms have to overcome (e.g. by evolving counter-deception strategies) in order to evolve large, socially cohesive communities. In contrast, white lies can prove to be beneficial in smoothing the flow of interactions and facilitating a larger, more integrated network. Our results demonstrate that these group-level effects can arise as emergent properties of interactions at the dyadic level. The balance between prosocial and antisocial lies may set constraints on the structure of social networks, and hence the shape of society as a whole.
An experimental analysis of the heritability of variation in glucocorticoid concentrations in a wild avian population
Authors: Jenkins Brittany R. , Vitousek Maren N. , Hubbard Joanna K. , Safran Rebecca J.
Published: July 2014

Glucocorticoid hormones (CORT) are predicted to promote adaptation to variable environments, yet little is known about the potential for CORT secretion patterns to respond to selection in free-living populations. We assessed the heritable variation underlying differences in hormonal phenotypes using a cross-foster experimental design with nestling North American barn swallows (
Hirundo rustica erythrogaster
). Using a bivariate animal model, we partitioned variance in baseline and stress-induced CORT concentrations into their additive genetic and rearing environment components and estimated their genetic correlation. Both baseline and stress-induced CORT were heritable with heritability of 0.152 and 0.343, respectively. We found that the variation in baseline CORT was best explained by rearing environment, whereas the variation in stress-induced CORT was contributed to by a combination of genetic and environmental factors. Further, we did not detect a genetic correlation between these two hormonal traits. Although rearing environment appears to play an important role in the secretion of both types of CORT, our results suggest that stress-induced CORT levels are underlain by greater additive genetic variance compared with baseline CORT levels. Accordingly, we infer that the glucocorticoid response to stress has a greater potential for evolutionary change in response to selection compared with baseline glucocorticoid secretion patterns.
Macrolide- and tetracycline-resistance determinants of colonizing group B streptococcus in women in Egypt
Authors: Shabayek Sarah , Abdalla Salah
Published: July 2014

Group B streptococcus (GBS) is a commensal bacterium of the human gastrointestinal and genital tracts. It is a leading cause of neonatal sepsis and meningitis, and has also been recognized as an important pathogen in pregnant women and the elderly. We investigated mechanisms of macrolide and tetracycline resistance in GBS colonizing women in Egypt. A total of 100 isolates were screened using standard antibiotic susceptibility tests. A multiplex PCR assay was used to detect macrolide- and tetracycline-resistance determinants. All isolates were uniformly susceptible to penicillin G, ampicillin, cefotaxime, vancomycin and levofloxacin. The resistance rates to erythromycin, clindamycin, azithromycin, tetracycline and chloramphenicol were 17, 14, 16, 98 and 1 %, respectively. Among the erythromycin-resistant isolates, 82.4 % had constitutive macrolide–lincosamide–streptogramin B (cMLSB) resistance, 5.9 % had inducible MLSB (iMLSB) resistance and 11.8 % had M phenotype resistance. Among the cMLSB phenotypes, 64.3 % of isolates harboured the ermB gene and 35.7 % of isolates harboured none of the investigated macrolide-resistance genes. The single strain expressing the iMLSB phenotype possessed the ermA gene. Of the two strains with the M phenotype, only one possessed the mefA/E gene. Conversely, seven macrolide-sensitive strains (MIC <0.03 µg ml−1) were ermB positive and one macrolide-sensitive strain (MIC <0.03 µg ml−1) harboured mefA/E. Tetracycline resistance was predominantly due to tetM, which was detected alone (83.7 %) or in association with tetL (12.2 %), tetK (1 %) or tetO (1 %). One strain carried tetM associated with both tetL and tetK, and another strain carried tetO alone. The tetO strains were positive for the mefA/E gene, and the tetL and tetK carrier strains harboured the ermB gene. Susceptible strains harbouring but not expressing an antibiotic-resistance gene should be regarded as potentially resistant. These results emphasize the need to monitor the epidemiology of GBS antibiotic resistance in Egypt.
Molecular epidemiology of enterovirus 71 strains isolated from children in Yamagata, Japan, between 1990 and 2013
Authors: Mizuta Katsumi , Aoki Yoko , Matoba Yohei , Yahagi Kazue , Itagaki Tsutomu , Katsushima Fumio , Katsushima Yuriko , Ito Sueshi , Hongo Seiji , Matsuzaki Yoko
Published: July 2014

Enterovirus 71 infections have become a major public issue in the Asia-Pacific region due to the large number of fatal cases. To clarify the longitudinal molecular epidemiology of enterovirus 71 (EV71) in a community, we isolated 240 strains from children, mainly with hand-foot-and-mouth diseases, between 1990 and 2013 in Yamagata, Japan. We carried out a sequence analysis of the VP1 region (891 bp) using 223 isolates and identified six subgenogroups (B2, B4, B5, C1, C2 and C4) during the study period. Subgenogroups C1 and B2 were found only between 1990 and 1993 and have not reappeared since. In contrast, strains in subgenogroups C2, C4 and B5 appeared repeatedly with genomic variations. Recent reports from several local communities in Japan have suggested that identical predominant subgenogroup strains, which have also been found in the Asia-Pacific region, have been circulating in a wide area in Japan. However, it is likely that there is a discrepancy between the major subgenogroups circulating in the Asia-Pacific region and those in Europe. It is necessary to continue the analysis of the longitudinal epidemiology of EV71 in local communities, as well as on regional and global levels, to develop strategies against severe EV71 infections.
Endocannabinoid CB1 antagonists inhibit hepatitis C virus production, providing a novel class of antiviral host-targeting agents
Authors: Shahidi Mahsa , Tay Enoch S. E. , Read Scott A. , Ramezani-Moghadam Mehdi , Chayama Kazuaki , George Jacob , Douglas Mark W.
Published: July 2014

Direct-acting antivirals have significantly improved treatment outcomes in chronic hepatitis C (CHC), but side effects, drug resistance and cost mean that better treatments are still needed. Lipid metabolism is closely linked with hepatitis C virus (HCV) replication, and endocannabinoids are major regulators of lipid homeostasis. The cannabinoid 1 (CB1) receptor mediates these effects in the liver. We have previously shown upregulation of CB1 receptors in the livers of patients with CHC, and in a HCV cell-culture model. Here, we investigated whether CB1 blockade inhibited HCV replication. The antiviral effect of a CB1 antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), was examined in HCV strain JFH1 cell-culture and subgenomic replicon models. The effects on the expression of genes involved in lipid metabolism were also measured. CB1 short hairpin RNA (shRNA) was used to confirm that the effects were specific for the cannabinoid receptor. Treatment with AM251 strongly inhibited HCV RNA (~70 %), viral protein (~80 %), the production of new virus particles (~70 %) and virus infectivity (~90 %). As expected, AM251 reduced the expression of pro-lipogenic genes (SREBP-1c, FASN, SCD1 and ACC1) and stimulated genes promoting lipid oxidation (CPT1 and PPARα). This effect was mediated by AMP-activated protein kinase (AMPK). Stable CB1 knockdown of cells infected with HCV showed reduced levels of HCV RNA compared with controls. Thus, reduced CB1 signalling inhibits HCV replication using either pharmacological inhibitors or CB1 shRNA. This may be due, at least in part, to reduced lipogenesis, mediated by AMPK activation. We suggest that CB1 antagonists may represent an entirely new class of drug with activity against HCV.
Modelling of human herpesvirus infections in humanized mice
Authors: Berges Bradford K. , Tanner Anne
Published: July 2014

The human herpesviruses (HHVs) are remarkably successful human pathogens, with some members of the family successfully establishing infection in the vast majority of humans worldwide. Although many HHV infections result in asymptomatic infection or mild disease, there are rare cases of severe disease and death found with nearly every HHV. Many of the pathogenic mechanisms of these viruses are poorly understood, and in many cases, effective antiviral drugs are lacking. Only a single vaccine exists for the HHVs and researchers have been unable to develop treatments to cure the persistent infections associated with HHVs. A major hindrance to HHV research has been the lack of suitable animal models, with the notable exception of the herpes simplex viruses. One promising area for HHV research is the use of humanized mouse models, in which human cells or tissues are transplanted into immunodeficient mice. Current humanized mouse models mostly transplant human haematopoietic stem cells (HSCs), resulting in the production of a variety of human immune cells. Although all HHVs are thought to infect human immune cells, the beta- and gammaherpesviruses extensively infect and establish latency in these cells. Thus, mice humanized with HSCs hold great promise to study these herpesviruses. In this review, we provide a historical perspective on the use of both older and newer humanized mouse models to study HHV infections. The focus is on current developments in using humanized mice to study mechanisms of HHV-induced pathogenesis, human immune responses to HHVs and effectiveness of antiviral drugs.
Arabidopsis MSL10 Has a Regulated Cell Death Signaling Activity That Is Separable from Its Mechanosensitive Ion Channel Activity
Authors: Veley Kira M. , Maksaev Grigory , Frick Elizabeth M. , January Emma , Kloepper Sarah C. , Haswell Elizabeth S.
Published: July 2014

Members of the MscS superfamily of mechanosensitive ion channels function as osmotic safety valves, releasing osmolytes under increased membrane tension. MscS homologs exhibit diverse topology and domain structure, and it has been proposed that the more complex members of the family might have novel regulatory mechanisms or molecular functions. Here, we present a study of MscS-Like (MSL)10 from Arabidopsis thaliana that supports these ideas. High-level expression of MSL10-GFP in Arabidopsis induced small stature, hydrogen peroxide accumulation, ectopic cell death, and reactive oxygen species- and cell death-associated gene expression. Phosphomimetic mutations in the MSL10 N-terminal domain prevented these phenotypes. The phosphorylation state of MSL10 also regulated its ability to induce cell death when transiently expressed in Nicotiana benthamiana leaves but did not affect subcellular localization, assembly, or channel behavior. Finally, the N-terminal domain of MSL10 was sufficient to induce cell death in tobacco, independent of phosphorylation state. We conclude that the plant-specific N-terminal domain of MSL10 is capable of inducing cell death, this activity is regulated by phosphorylation, and MSL10 has two separable activities—one as an ion channel and one as an inducer of cell death. These findings further our understanding of the evolution and significance of mechanosensitive ion channels.
Board structure in listed firms: evidence from an emerging economy
Authors: Oba Beyza , Tigrel Elvin , Sener Pinar
Published: July 2014

Purpose

– This paper aims to understand the determinants of board structure of listed firms at institutional, industry and firm levels within an emerging economy. At the institutional level, the paper explores laws, managerial culture and the role of state in instituting and endorsing corporate governance practices. At the firm level, ownership patterns (family and non-family), experience in the capital markets, age and size of the firms are studied to find out the relation between these variables and the board structure.

Design/methodology/approach

– The research domain of the study is listed firms operating on the Istanbul Stock Exchange. The data for the study are collected at two phases; at the first phase, compliance reports, annual reports, articles of association and annual shareholders’ meeting reports of each firm in the sample are analyzed. At the second stage, secondary data are used for understanding the dynamics of Turkish institutional context.

Findings

– The results of this study reveal that boards of directors of listed Turkish firms comply with the governance practices instituted by state agencies, except on issues as independent members and committees that will influence the majority owners’ control domain and private benefits.

Originality/value

– This paper draws attention on institutional context and argues that “good governance” instruments developed for Anglo-Saxon stock market-controlled business systems provide limited explanation for an emerging economy that is characterized by close cooperation between the state, family-owned businesses and financial markets. The study offers insight to policy makers at a national level, interested in developing corporate governance principles regarding boards of directors of listed firms.
‘You shall not pass!’: quantifying barrier permeability and proximity avoidance by animals
Authors: Beyer Hawthorne L. , Gurarie Eliezer , Börger Luca , Panzacchi Manuela , Basille Mathieu , Herfindal Ivar , Van Moorter Bram , R. Lele Subhash , Matthiopoulos Jason
Published: July 2014

Impediments to animal movement are ubiquitous and vary widely in both scale and permeability. It is essential to understand how impediments alter ecological dynamics via their influence on animal behavioural strategies governing space use and, for anthropogenic features such as roads and fences, how to mitigate these effects to effectively manage species and landscapes.

Here, we focused primarily on barriers to movement, which we define as features that cannot be circumnavigated but may be crossed. Responses to barriers will be influenced by the movement capabilities of the animal, its proximity to the barriers, and habitat preference. We developed a mechanistic modelling framework for simultaneously quantifying the permeability and proximity effects of barriers on habitat preference and movement.

We used simulations based on our model to demonstrate how parameters on movement, habitat preference and barrier permeability can be estimated statistically. We then applied the model to a case study of road effects on wild mountain reindeer summer movements.

This framework provided unbiased and precise parameter estimates across a range of strengths of preferences and barrier permeabilities. The quality of permeability estimates, however, was correlated with the number of times the barrier is crossed and the number of locations in proximity to barriers. In the case study we found that reindeer avoided areas near roads and that roads are semi‐permeable barriers to movement. There was strong avoidance of roads extending up to c. 1 km for four of five animals, and having to cross roads reduced the probability of movement by 68·6% (range 3·5–99·5%).

Human infrastructure has embedded within it the idea of networks: nodes connected by linear features such as roads, rail tracks, pipelines, fences and cables, many of which divide the landscape and limit animal movement. The unintended but potentially profound consequences of infrastructure on animals remain poorly understood. The rigorous framework for simultaneously quantifying movement, habitat preference and barrier permeability developed here begins to address this knowledge gap.
Evidence for weak genetic recombination at the PTP2 locus of Nosema ceranae
Authors: Gómez‐Moracho Tamara , Bartolomé Carolina , Martín‐Hernández Raquel , Higes Mariano , Maside Xulio
Published: July 2014

The microsporidian Nosema ceranae is an emergent pathogen that threatens the health of honeybees and other pollinators all over the world. Its recent rapid spread across a wide variety of host species and environments demonstrated an enhanced ability of adaptation, which seems to contradict the lack of evidence for genetic recombination and the absence of a sexual stage in its life cycle. Here we retrieved fresh data of the patterns of genetic variation at the PTP2 locus in naturally infected Apis mellifera colonies, by means of single genome amplification. This technique, designed to prevent the formation of chimeric haplotypes during polymerase chain reaction (PCR), provides more reliable estimates of the diversity levels and haplotype structure than standard PCR‐cloning methods. Our results are consistent with low but significant rates of recombination in the history of the haplotypes detected: estimates of the population recombination rate are of the order of 30 and support recent evidence for unexpectedly high levels of variation of the parasites within honeybee colonies. These observations suggest the existence of a diploid stage at some point in the life cycle of this parasite and are relevant for our understanding of the dynamics of its expanding population.
Resource effects on denitrification are mediated by community composition in tidal freshwater wetlands soils
Authors: Morrissey Ember M. , Franklin Rima B.
Published: July 2014

Accurate prediction of denitrification rates remains difficult, potentially owing to complex uncharacterized interactions between resource conditions and denitrifier communities. To better understand how the availability of organic matter (OM) and nitrate (NO3–), two of the resources most fundamental to denitrifiers, affect these populations and their activity, we performed an in situ resource manipulation in tidal freshwater wetland soils. Soils were augmented with OM to double ambient concentrations, using either compost or plant litter, and fertilized with KNO3 at two levels (low: ∼ 5 mg l–1 NO3––N and high: ∼ 50 mg l–1 NO3––N) in a full factorial design. Community composition of nirS‐denitrifers (assessed using terminal restriction fragment length polymorphism) was interactively regulated by both NO3– concentration and OM type, and the associated shifts in community composition were relatively consistent across sampling dates (6, 9 and 12 months of incubation). Denitrification potential (pDNF) rates were also strongly affected by NO3– fertilization and increased by ∼ 10–100‐fold. Path analysis revealed that the influence of resource availability on pDNF rates was largely mediated through changes in nirS‐denitrifier community composition. These results suggest that a greater understanding of denitrifier community ecology may enable more accurate prediction of denitrification rates.
Numeracy of Africans, Asians, and Europeans during the early modern period: new evidence from Cape Colony court registers
Authors: Baten Jörg , Fourie Johan
Published: July 2014

The lack of accurate measures of human capital formation often constrains investigations into the long‐run determinants of growth and comparative economic development, especially in the developing world. Using the reported ages of criminals in the Court of Justice records in the Cape Archives, this article documents for the first time numeracy levels and trends for inhabitants of the Cape Colony born between the late seventeenth and early nineteenth century: the native Khoesan, European settlers, and imported slaves from other African regions and Asia. This variety of origins allows us to compare contemporaneous levels of early modern development across three continents. By isolating those slaves born at the Cape, we also provide a glimpse into the dynamics of human capital transfer in a colonial setting. The Colony's relatively high level of human capital overall had implications for what was later to be the richest country on African soil, but the very unequal attainment of numeracy also foreshadowed extreme income inequality.
Lightning Deaths: A Retrospective Review of New Mexico's Cases, 1977–2009
Authors: Pincus Jennifer L. , Lathrop Sarah L. , Briones Alice J. , Andrews Sam W. , Aurelius Michelle B.
Published: July 2014

To better understand lightning deaths, a retrospective review of electronic records from New Mexico's Office of the Medical Investigator database was performed between 1977 and 2009 to update and assess current risk factors. Information on demographics, circumstances, autopsy, and death certificates were collected and analyzed. Fifty‐four decedents were identified, ages 2–71 years old (mean 34 years old), 42 males and 12 females. Common racial/ethnic groups were non‐Hispanic Whites and American Indians (together comprising 72% of all cases). Physical findings were often related to the heat carried by the electrical current including clothing alterations (29.6%) and burning of skin (53.7%). Most deaths occurred on weekend afternoons in summer months, associated with recreational activities or agricultural work, and rural locations (77.8%). Utilizing the demographic information, clustered events, and associated outdoor activities will assist in creating public awareness and provide a framework to support targeted warnings in an attempt to prevent future deaths.
Demographic Change, Differential Ageing, and Public Policy in Rural and Regional Australia: A Three‐State Case Study
Authors: SMAILES PETER , GRIFFIN TREVOR , ARGENT NEIL
Published: July 2014

This paper takes a differential demographic change in six rural settlement categories within rural and regional Australia as the starting point for the measurement of differential ageing using a Relative Ageing Index which compares ageing in sub‐populations with the national norm. The spatial units employed are 412 rural communities, approximated by social catchments each consisting of a country town and its surrounding dispersed population. The study covers the period from 1981 to 2006 and includes the rural areas of New South Wales, Victoria, and South Australia, excluding major cities, peri‐urban areas, and the remote rangelands. It examines demographic change and differential ageing in a selection of the rural settlement categories recommended for further analysis in the report of the ‘Demographic Change and Liveability Panel’, one of three advisory panels established in 2010 by the then Commonwealth Government seeking to develop a sustainable population strategy for Australia. Ageing profiles are produced for the whole study area, for the individual rural settlement categories, and for the urban and rural components within each category separately. Results show that differential ageing is least advanced in the ‘regional cities’, most advanced in the ‘sea change’, but of most concern in the agriculture‐based rural settlement categories where it exacerbates the effects of overall population decline. In all categories, ageing in the dispersed rural population element exceeded that of the urban component. Results emphasise the vital role of the ‘regional cities’ category in future public policy development supported by ameliorative and collaborative measures for their surrounding agriculture‐based communities.
Unconventional Gas Development: Why a Regional Community Said No
Authors: LUKE HANABETH , LLOYD DAVID , BOYD WILLIAM , den EXTER KRISTIN
Published: July 2014

Public concern resulting from unconventional coal seam gas (CSG) exploration and production has become a contentious planning issue in regional Australia, with public concern drawing attention to government planning obligations. To assist Lismore City Council (Northern New South Wales) in its deliberations on the topic, a referendum‐style poll on the issue of CSG industry development was held in conjunction with the local government elections of September 2012. The poll question, ‘Do you support CSG exploration and production in the Lismore City Council area?’, elicited a poll response rate of 97% of eligible voters, of which 87% voted ‘no’. This paper reports the results of an exit poll survey using the Theory of Planned Behaviour to frame motivations behind the poll result, and examines the role of the poll and exit poll survey in providing a process of deliberative democracy in the context of the CSG debate. Key details highlighted by the results were that non‐supporters of CSG exploration were primarily concerned about water quality, while supporters saw the primary benefit being regional employment. Emerging themes of this study are the need for more independent research on potential risks and benefits of CSG developments, increase in institutional transparency, and the development of renewable alternatives. The study concludes that the principles of deliberative democracy involved in the Lismore City Council poll and subsequent exit poll survey have provided an opportunity for a more open discussion and genuine discourse within the CSG debate.
The Effect of Ezetimibe on Androgen Production in Hypercholesterolemic Women with Polycystic Ovary Syndrome
Authors: Krysiak Robert , Zmuda Witold , Okopien Boguslaw
Published: July 2014

Aims

Statin therapy was found to reduce circulating androgen levels in patients with polycystic ovary syndrome (PCOS). No similar data are available for ezetimibe.

Methods

The study included 14 women with PCOS and hypercholesterolemia, intolerant to statins or having contraindications to this treatment, who were treated with ezetimibe (10 mg daily). They were compared with 14 matched women with both of these disorders receiving simvastatin (40 mg daily). Plasma lipids, glucose homeostasis markers, and serum levels of androgens, sex hormone‐binding globulin, and gonadotropins were assessed at baseline and after 3 months of treatment.

Results

Both simvastatin and ezetimibe decreased plasma levels of total and LDL cholesterol. Ezetimibe, but not simvastatin, slightly reduced insulin resistance. Simvastatin decreased serum levels of total testosterone (−23%, P < 0.001), free testosterone (−32%, P < 0.001), androstendione (−20%, P < 0.01), and dehydroepiandrosterone sulfate (−17%, P < 0.05), as well as tended to reduce the luteinizing hormone/follicle‐stimulating hormone ratio (−23%, P = 0.095). Ezetimibe only insignificantly reduced serum levels of free testosterone (−14%, P = 0.098). There were no differences in the effects of simvastatin on circulating hormone levels between insulin‐resistant and insulin‐sensitive subjects. In turn, the effect of ezetimibe on free testosterone levels was stronger in insulin‐resistant patients.

Conclusions

Although ezetimibe and simvastatin are equipotent in lowering lipid levels in hypercholesterolemic patients with coexisting PCOS, simvastatin exhibits a more pronounced effect on circulating androgen levels in this group of patients.
The Cardinal Sins of European Energy Policy: Nongovernance in an Uncertain Global Landscape
Authors: Szulecki Kacper , Westphal Kirsten
Published: July 2014

Recent years have seen some fundamental changes in the way the global energy sector and its governance function. All of these changes have a significant impact on the energy policy choices that are available for EU policy makers and should be incorporated in a proactive European strategy for the future. Instead, however, we witness a general stalemate in the energy policy debate within the EU, and internal problems seem to impede any meaningful and coherent external policy. In this article, building on a wide literature review, we sketch the changing global energy landscape, explaining the current state of ‘unprecedented uncertainty’ around a set of major issues. Then we describe what we see as the five ‘cardinal sins’ of European energy policy and governance, which preclude effective common responses and external action. We conclude by outlining possible ways of overcoming the challenges that face European energy policy and governance.
Surgical results of resectable small cell lung cancer
Authors: Kawano Daigo , Okamoto Tatsuro , Fujishita Takatoshi , Suzuki Yuzo , Kitahara Hirokazu , Shimamatsu Shinichiro , Maehara Yoshihiko
Published: July 2014

Background

The standard of care for patients with small cell lung cancer (SCLC) is chemotherapy and radiotherapy, even for patients with limited disease. To define the role of surgical resection in patients with limited SCLC, we investigated the outcomes of patients diagnosed with limited‐stage disease (LD) SCLC.

Methods

The records of 57 LD SCLC patients who underwent surgical resection from April 1974 to March 2012 were retrospectively analyzed.

Results

There were six women and 51 men, with a median age of 63.5 years. The overall five‐year survival rate was 28.6% (median, 18.2 months). The p‐stage II and III patients had a significantly worse survival than the p‐stage I patients (13.4% vs. 43.4%, P = 0.0036). However, the c‐stage was not found to correlate with survival. Patients who underwent pneumonectomy had a significantly worse outcome than those who underwent other surgical procedures (0.0% vs. 32.0%, P = 0.0002). In a multivariate Cox proportional hazards analysis, p‐stage II or III (hazard ratio [HR] 3.040 P = 0.0017) and pneumonectomy (HR 6.177, P = 0.00159) were significant independent predictors of an adverse survival outcome.

Conclusions

Surgical treatment can be considered in SCLC patients with pathologically proven N0 status, although pneumonectomy should be avoided.
A simple numerical tool to infer whether a species is extinct
Authors: Lee Tamsin E.
Published: July 2014

Including uncertain sightings when inferring extinction of a species is relatively new and has proven to be significant. However, including uncertain sightings leads to non‐trivial mathematical problems which are inaccessible to many ecologists.

I use the Pohnpei Mountain Starling Aplonis pelzelni to describe an Excel spreadsheet which infers extinction from a sighting record. The spreadsheet implements a Bayesian model which includes uncertainty around the prior, uncertain sightings and survey effort.

Survey effort has not been included in extinction models before, but clearly plays a significant role in extinction estimates, which the Pohnpei Mountain Starling example demonstrates.

The spreadsheet (included as supplementary material) is user‐friendly, fast and accessible on Windows.
Considering species richness and rarity when selecting optimal survey traps: comparisons of semiochemical baited flight intercept traps for Cerambycidae in eastern North America
Authors: Dodds Kevin J. , Allison Jeremy D. , Miller Daniel R. , Hanavan Ryan P. , Sweeney Jon
Published: July 2014

We compared standard multiple‐funnel, modified multiple‐funnel, intercept panel and canopy malaise (SLAM) traps with top and bottom collecting cups for their effectiveness (species richness, rarity, abundance) at capturing Cerambycidae in eastern North America.

Experiments were conducted in New York, Louisiana, Massachusetts and Georgia in 2011 and 2012. A combination of pheromones and host volatiles chosen to match local forest types were used as lures.

Species richness tended to be higher in SLAM and modified funnel traps than standard funnel and intercept panel traps. SLAM traps also captured the highest number of species, unique species, rare (species accounting for ≤ 1% of total cerambycids at a site) and singleton species at each site.

Individual‐based rarefaction and sample‐based species accumulation curves suggested that SLAM traps are more effective for capturing cerambycid species. For many estimates, modified funnel and funnel traps were lower than SLAM traps but greater than intercept panel traps for describing cerambycid communities.

Modified funnel and SLAM traps generally captured the highest abundance of cerambycids but the response of the individual subfamily and species varied by trap type.

SLAM traps should be considered as a strong tool to describe cerambycid communities when used in conjunction with pheromones and host volatiles.
The use of pictograms improves symptom evaluation by patients with functional dyspepsia
Authors: Tack J. , Carbone F. , Holvoet L. , Vanheel H. , Vanuytsel T. , Vandenberghe A.
Published: July 2014

Background

No validated patient‐reported outcome (PRO) measure exists for functional dyspepsia (FD) assessment. Verbal descriptions of different upper abdominal symptoms may be poorly distinguishable to patients.

Aim

To investigate whether understanding of FD symptoms is enhanced by pictograms symbolising the nature of the symptoms, besides verbal descriptors.

Methods

Consecutive FD patients were randomised to fill out a questionnaire assessing nineupper gastrointestinal symptoms (post‐prandial fullness, early satiation, epigastric pain, epigastric burning, bloating centred in the upper abdomen, nausea, vomiting, heartburn, regurgitation) with or without accompanying pictograms. Symptoms were rated for frequency and severity (0–5), and patients also identified the most bothersome symptom. Subsequently, in‐depth history was taken by an expert clinician, who filled out the same symptom ratings. Concordance between patient and clinician ratings was quantified using chi‐square and kappa statistics.

Results

Content validity of pictograms was first confirmed by 15 FD patients. Next, 76 patients (52 women, age 42.2 ± 1.9) were randomised to questionnaires with or without pictograms. The concordance with clinician's assessment as gold standard rose from 36 without to 48% for questions with pictograms (P < 0.0001). Considering the Rome III subdivision, benefit in concordance with pictograms was present for post‐prandial distress, epigastric pain syndrome and reflux symptoms. Kappa statistics confirmed these gains (weighted kappa values for concordance of symptom frequency ratings rose from 0.214 to 0.446 with pictograms), and also showed better concordance of the most bothersome symptom with pictograms.

Conclusion

Pictograms accompanying verbal descriptors significantly improve concordance of functional dyspepsia symptom ratings by patients with evaluation by their physicians.
Upper limit of cancer extent on biopsy defining very low‐risk prostate cancer
Authors: Bratt Ola , Folkvaljon Yasin , Loeb Stacy , Klotz Laurence , Egevad Lars , Stattin Pär
Published: July 2014

Objective

To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low‐risk prostate cancer.

Patients and Methods

We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern ≤3 only, prostate‐specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4–5 in the RP specimen was analysed with logistic regression.

Results

In all, 438 (34%) of the 1286 men had Gleason pattern 4–5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and <8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1–2 or 3–4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01).

Conclusions

Men aged <70 years with stage T1c prostate cancer and 3–4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4–5 cancer than men with 1–2 cores with cancer, provided that the total biopsy cancer length is <8 mm. We propose that the definition of very low‐risk prostate cancer is widened accordingly.
Role of nuclear Lamin A/C in cardiomyocyte functions
Authors: Carmosino Monica , Torretta Silvia , Procino Giuseppe , Gerbino Andrea , Forleo Cinzia , Favale Stefano , Svelto Maria
Published: July 2014

Lamin A/C is a structural protein of the nuclear envelope (NE) and cardiac involvement in Lamin A/C mutations was one of the first phenotypes to be reported in humans, suggesting a crucial role of this protein in the cardiomyocytes function. Mutations in LMNA gene cause a class of pathologies generically named ‘Lamanopathies’ mainly involving heart and skeletal muscles. Moreover, the well‐known disease called Hutchinson–Gilford Progeria Syndrome due to extensive mutations in LMNA gene, in addition to the systemic phenotype of premature aging, is characterised by the death of patients at around 13 typically for a heart attack or stroke, suggesting again the heart as the main site sensitive to Lamin A/C disfunction. Indeed, the identification of the roles of the Lamin A/C in cardiomyocytes function is a key area of exploration. One of the primary biological roles recently conferred to Lamin A/C is to affect contractile cells lineage determination and senescence. Then, in differentiated adult cardiomyocytes both the ‘structural’ and ‘gene expression hypothesis’ could explain the role of Lamin A in the function of cardiomyocytes. In fact, recent advances in the field propose that the structural weakness/stiffness of the NE, regulated by Lamin A/C amount in NE, can ‘consequently’ alter gene expression.
δ‐Opioid receptors up‐regulate excitatory amino acid transporters in mouse astrocytes
Authors: Liang Jianfeng , Chao Dongman , Sandhu Harleen K , Yu Yanbing , Zhang Li , Balboni Gianfranco , Kim Dong H , Xia Ying
Published: July 2014

Background and Purpose

Astrocytic excitatory amino acid transporters (EAATs) regulate extracellular glutamate concentrations and play a role in preventing neuroexcitotoxicity. As the δ‐opioid receptor (DOP receptor) is neuroprotective against excitotoxic injury, we determined whether DOP receptor activation up‐regulates EAAT expression and function.

Experimental Approach

We measured mRNA and protein expression of EAAT1, EAAT2 and EAAT3 in cultured mouse astrocytes exposed to a specific DOP receptor agonist (UFP‐512) with or without a DOP receptor antagonist, DOP receptor siRNA or inhibitors of PKC, PKA, PI3K, p38, MAPK, MEK and ERK, and evaluated the function of EAATs by measuring glutamate uptake.

Key Results

Astrocytic DOP receptor mRNA and protein were suppressed by DOP receptor siRNA knockdown. DOP receptor activation increased mRNA and protein expression of EAAT1 and EAAT2, but not EAAT3, thereby enhancing glutamate uptake of astrocytes. DOP receptor‐induced EAAT1 and EAAT2 expression was largely reversed by DOP receptor antagonist naltrindole or by DOP receptor siRNA knockdown, and suppressed by inhibitors of MEK, ERK and p38. DOP receptor‐accelerated glutamate uptake was inhibited by EAAT blockers, DOP receptor siRNA knockdown or inhibitors of MEK, ERK or p38. In contrast, inhibitors of PKA, PKC or PI3K had no significant effect on DOP receptor‐induced EAAT expression.

Conclusions and Implications

DOP receptor activation up‐regulates astrocytic EAATs via MEK‐ERK‐p38 signalling, suggesting a critical role for DOP receptors in the regulation of astrocytic EAATs and protection against neuroexcitotoxicity. As decreased EAAT expression contributes to pathophysiology in many neurological diseases, including amyotrophic lateral sclerosis, our findings present a new platform for potential treatments of these diseases.
Feleucin‐BO1: A Novel Antimicrobial Non‐Apeptide Amide from the Skin Secretion of the Toad, Bombina orientalis, and Design of a Potent Broad‐Spectrum Synthetic Analogue, Feleucin‐K3
Authors: Hou Xiaojuan , Du Qiang , Li Renjie , Zhou Mei , Wang Hui , Wang Lei , Guo Can , Chen Tianbao , Shaw Chris
Published: July 2014

Feleucins‐BV1 and ‐BV2 are recently described prototypes of a novel antimicrobial non‐apeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin‐BO1 (FLGLLGSLLamide) which is co‐encoded with a different novel bombinin, named feleucin precursor‐associated bombinin (FPA‐bombinin‐BO), from the skin secretion of Bombina orientalis. Synthetic feleucin‐BO1 displayed activity against a reference Gram‐positive bacterium. Staphylococcus aureus (MIC 34 μm) but was inactive (> 250 μm) against the Gram‐negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity‐enhanced analogue, feleucin‐K3 (F‐K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin‐BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly enhanced potency and spectrum of activity. The MICs of F‐K3 against the reference micro‐organisms were 7 μm (S. aureus), 14 μm (E. coli) and 7 μm (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.
Are urinary levels of high mobility group box 1 markers of active nephritis in anti-neutrophil cytoplasmic antibody-associated vasculitis?
Authors: de Souza A W S , Abdulahad W H , Sosicka P , Bijzet J , Limburg P C , Stegeman C A , Bijl M , Westra J , Kallenberg C G M
Published: July 2014

The objective of this study is to evaluate urinary high mobility group box 1 (HMGB1) levels as markers for active nephritis in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in comparison with urinary CD4+ effector memory T cells and urinary monocyte chemoattractant protein-1 (MCP-1). Twenty-four AAV patients with active nephritis and 12 healthy controls (HC) were evaluated. In nine patients, samples were also obtained during remission. Urinary levels of HMGB1 were measured by Western blot. CD4+T cells and CD4+ effector memory T cells (CD4+CD45RO+CCR7-) were determined in urine and whole blood by flow cytometry. Measurement of urinary levels of MCP-1 and serum HMGB1 levels were performed by enzyme-linked immunosorbent assay (ELISA). AAV patients with active nephritis had higher median intensity of HMGB1 in urine than HC [10·3 (7·05–18·50) versus 5·8 (4·48–7·01); P = 0·004]. Both urinary HMGB1 and MCP-1 levels decreased significantly from active nephritis to remission. The urinary MCP-1/creatinine ratio correlated with Birmingham Vasculitis Activity Score (BVAS) (P = 0·042). No correlation was found between the HMGB1/creatinine ratio and 24-h proteinuria, estimated glomerular filtration rate (eGFR), MCP-1/creatinine ratio, BVAS and serum HMGB1. A positive correlation was found between urinary HMGB1/creatinine ratio and CD4+T cells/creatinine ratio (P = 0·028) and effector memory T cells/creatinine ratio (P = 0·039) in urine. Urinary HMGB1 levels are increased in AAV patients with active nephritis when compared with HC and patients in remission, and urinary HMGB1 levels are associated with CD4+T cells and CD4+ effector memory T cells in urine. Measurement of urinary HMGB1 may be of additional value in identifying active glomerulonephritis in AAV patients.
Impaired decision‐making and selective cortical frontal thinning in Cushing's syndrome
Authors: Crespo Iris , Esther Granell‐Moreno , Santos Alicia , Valassi Elena , Yolanda Vives‐Gilabert , De Juan‐Delago Manel , Webb Susan M. , Gómez‐Ansón Beatriz , Resmini Eugenia
Published: July 2014

Context and objective

Cushing's syndrome (CS) is caused by a glucocorticoid excess. This hypercortisolism can damage the prefrontal cortex, known to be important in decision‐making. Our aim was to evaluate decision‐making in CS and to explore cortical thickness.

Subjects and methods

Thirty‐five patients with CS (27 cured, eight medically treated) and thirty‐five matched controls were evaluated using Iowa gambling task (IGT) and 3 Tesla magnetic resonance imaging (MRI) to assess cortical thickness. The IGT evaluates decision‐making, including strategy and learning during the test. Cortical thickness was determined on MRI using freesurfer software tools, including a whole‐brain analysis.

Results

There were no differences between medically treated and cured CS patients. They presented an altered decision‐making strategy compared to controls, choosing a lower number of the safer cards (P < 0·05). They showed more difficulties than controls to learn the correct profiles of wins and losses for each card group (P < 0·05). In whole‐brain analysis, patients with CS showed decreased cortical thickness in the left superior frontal cortex, left precentral cortex, left insular cortex, left and right rostral anterior cingulate cortex, and right caudal middle frontal cortex compared to controls (P < 0·001).

Conclusions

Patients with CS failed to learn advantageous strategies and their behaviour was driven by short‐term reward and long‐term punishment, indicating learning problems because they did not use previous experience as a feedback factor to regulate their choices. These alterations in decision‐making and the decreased cortical thickness in frontal areas suggest that chronic hypercortisolism promotes brain changes which are not completely reversible after endocrine remission.