bluuebunny/crossref_metadata_2025 huggingface dataset:
Arl1p regulates spatial membrane organization at the
trans
-Golgi network through interaction with Arf-GEF Gea2p and flippase Drs2p
Authors: Tsai Pei-Chin , Hsu Jia-Wei , Liu Ya-Wen , Chen Kuan-Yu , Lee Fang-Jen S.
Published: January 2013

Significance

Membrane asymmetry, curvature, and dynamics have major roles in cellular processes, including vesicle transport. The GTPase ADP ribosylation factor (Arf) and a lipid translocase (flippase) are critical for membrane reorganization during vesicle formation. Direct evidence that Arf and flippase work in concert on membrane transformation/architecture is, however, lacking. We demonstrate that activated Arf-like protein Arl1 interacts with the Arf-activating guanine nucleotide-exchange factor Gea2 and flippase Drs2, forming a ternary complex that is required for lipid asymmetry and Arl1 function at the Golgi. These findings represent a previously missing piece of the puzzle that is our understanding of Arf-mediated membrane remodeling.
Contribution of Thy1+NK cells to protective IFN-γ production duringSalmonellaTyphimurium infections
Authors: Kupz Andreas , Scott Timothy A. , Belz Gabrielle T. , Andrews Daniel M. , Greyer Marie , Lew Andrew M. , Brooks Andrew G. , Smyth Mark J. , Curtiss Roy , Bedoui Sammy , Strugnell Richard A.
Published: January 2013

IFN-γ is critical for immunity against infections with intracellular pathogens, such asSalmonella enterica. However, which of the many cell types capable of producing IFN-γ controlsSalmonellainfections remains unclear. Using a mouse model of systemicSalmonellainfection, we observed that only a lack of all lymphocytes or CD90 (Thy1)+cells, but not the absence of T cells, Retinoic acid-related orphan receptor (ROR)-γt–dependent lymphocytes, (NK)1.1+cells, natural killer T (NKT), and/or B cells alone, replicated the highly susceptible phenotype of IFN-γ–deficient mice toSalmonellainfection. A combination of antibody depletions and adoptive transfer experiments revealed that early protective IFN-γ was provided by Thy1-expressing natural killer (NK) cells and that these cells improved antibacterial immunity through the provision of IFN-γ. Further analysis of NK cells producing IFN-γ in response toSalmonellaindicated that less mature NK cells were more efficient at mediating antibacterial effector function than terminally differentiated NK cells. Inspired by recent reports of Thy1+NK cells contributing to immune memory, we analyzed their role in secondary protection against otherwise lethal WTSalmonellainfections. Notably, we observed that a newly generatedSalmonellavaccine strain not only conferred superior protection compared with conventional regimens but that this enhanced efficiency of recall immunity was afforded by incorporating CD4−CD8−Thy1+cells into the secondary response. Taken together, these findings demonstrate that Thy1-expressing NK cells play an important role in antibacterial immunity.
Pattern and synchrony of gene expression among sympatric marine microbial populations
Authors: Ottesen Elizabeth A. , Young Curtis R. , Eppley John M. , Ryan John P. , Chavez Francisco P. , Scholin Christopher A. , DeLong Edward F.
Published: January 2013

Significance

Microbial communities regulate the cycling of energy and matter in the environment, yet how they respond to environmental change is not well-known. We describe here a day in the life of wild planktonic microbial species using robotic sampling coupled with genome-wide gene expression analysis. Our results showed that closely related populations, as well as very different bacterial and archaeal species, displayed remarkably similar time-variable synchronous patterns of gene expression over 2 d. Our results suggest that specific environmental cues may elicit cross-species coordination of gene expression among diverse microbial groups, potentially enabling multispecies coupling of metabolic activity.
Role of 53BP1 oligomerization in regulating double-strand break repair
Authors: Lottersberger Francisca , Bothmer Anne , Robbiani Davide F. , Nussenzweig Michel C. , de Lange Titia
Published: January 2013

Tumor suppressor p53-binding protein 1 (53BP1) regulates the repair of dysfunctional telomeres lacking the shelterin protein TRF2 by promoting their mobility, their nonhomologous end-joining (NHEJ), and, as we show here, by blocking 5′ resection by CtIP. We report that these functions of 53BP1 required its N-terminal ATM/ATR target sites and its association with H4K20diMe, but not the BRCT domain, the GAR domain, or the binding of 53BP1 to dynein. A mutant lacking the oligomerization domain (53BP1
oligo
) was only modestly impaired in promoting NHEJ of dysfunctional telomeres and showed no defect with regard to the repression of CtIP. This 53BP1
oligo
allele was previously found to be unable to support class switch recombination or to promote radial chromosome formation in PARP1 inhibitor-treated Brca1-deficient cells. The data therefore support two conclusions. First, the requirements for 53BP1 in mediating NHEJ at dysfunctional telomeres and in class switch recombination are not identical. Second, 53BP1-dependent repression of CtIP at double-strand breaks (DSBs) is unlikely to be sufficient for the generation of radial chromosomes in PARP1 inhibitor-treated Brca1-deficient cells.
Analysis of turnover dynamics of the submembranous actin cortex
Authors: Fritzsche Marco , Lewalle Alexandre , Duke Tom , Kruse Karsten , Charras Guillaume
Published: January 2013

The cell cortex is a thin network of actin, myosin motors, and associated proteins that underlies the plasma membrane in most eukaryotic cells. It enables cells to resist extracellular stresses, perform mechanical work, and change shape. Cortical structural and mechanical properties depend strongly on the relative turnover rates of its constituents, but quantitative data on these rates remain elusive. Using photobleaching experiments, we analyzed the dynamics of three classes of proteins within the cortex of living cells: a scaffold protein (actin), a cross-linker (α-actinin), and a motor (myosin). We found that two filament subpopulations with very different turnover rates composed the actin cortex: one with fast turnover dynamics and polymerization resulting from addition of monomers to free barbed ends, and one with slow turnover dynamics with polymerization resulting from formin-mediated filament growth. Our data suggest that filaments in the second subpopulation are on average longer than those in the first and that cofilin-mediated severing of formin-capped filaments contributes to replenishing the filament subpopulation with free barbed ends. Furthermore, α-actinin and myosin minifilaments turned over significantly faster than F-actin. Surprisingly, only one-fourth of α-actinin dimers were bound to two actin filaments. Taken together, our results provide a quantitative characterization of essential mechanisms under­lying actin cortex homeostasis.
Mge1, a nucleotide exchange factor of Hsp70, acts as an oxidative sensor to regulate mitochondrial Hsp70 function
Authors: Marada Adinarayana , Allu Praveen Kumar , Murari Anjaneyulu , PullaReddy BhoomiReddy , Tammineni Prasad , Thiriveedi Venkata Ramana , Danduprolu Jayasree , Sepuri Naresh Babu V.
Published: January 2013

Despite the growing evidence of the role of oxidative stress in disease, its molecular mechanism of action remains poorly understood. The yeast Saccharomyces cerevisiae provides a valuable model system in which to elucidate the effects of oxidative stress on mitochondria in higher eukaryotes. Dimeric yeast Mge1, the cochaperone of heat shock protein 70 (Hsp70), is essential for exchanging ATP for ADP on Hsp70 and thus for recycling of Hsp70 for mitochondrial protein import and folding. Here we show an oxidative stress–dependent decrease in Mge1 dimer formation accompanied by a concomitant decrease in Mge1–Hsp70 complex formation in vitro. The Mge1-M155L substitution mutant stabilizes both Mge1 dimer and Mge1–Hsp70 complex formation. Most important, the Mge1-M155L mutant rescues the slow-growth phenomenon associated with the wild-type Mge1 strain in the presence of H2O2 in vivo, stimulation of the ATPase activity of Hsp70, and the protein import defect during oxidative stress in vitro. Furthermore, cross-linking studies reveal that Mge1–Hsp70 complex formation in mitochondria isolated from wild-type Mge1 cells is more susceptible to reactive oxygen species compared with mitochondria from Mge1-M155L cells. This novel oxidative sensor capability of yeast Mge1 might represent an evolutionarily conserved function, given that human recombinant dimeric Mge1 is also sensitive to H2O2.
Energy metabolism regulates clathrin adaptors at thetrans-Golgi network and endosomes
Authors: Aoh Quyen L. , Hung Chao-wei , Duncan Mara C.
Published: January 2013

Glucose is a master regulator of cell behavior in the yeast Saccharomyces cerevisiae. It acts as both a metabolic substrate and a potent regulator of intracellular signaling cascades. Glucose starvation induces the transient delocalization and then partial relocalization of clathrin adaptors at the trans-Golgi network and endosomes. Although these localization responses are known to depend on the protein kinase A (PKA) signaling pathway, the molecular mechanism of this regulation is unknown. Here we demonstrate that PKA and the AMP-regulated kinase regulate adaptor localization through changes in energy metabolism. We show that genetic and chemical manipulation of intracellular ATP levels cause corresponding changes in adaptor localization. In permeabilized cells, exogenous ATP is sufficient to induce adaptor localization. Furthermore, we reveal distinct energy-dependent steps in adaptor localization: a step that requires the ADP-ribosylation factor ARF, an ATP-dependent step that requires the phosphatidyl-inositol-4 kinase Pik1, and third ATP-dependent step for which we provide evidence but for which the mechanism is unknown. We propose that these energy-dependent mechanisms precisely synchronize membrane traffic with overall proliferation rates and contribute a crucial aspect of energy conservation during acute glucose starvation.
A Real-Time PCR Assay for Early Detection of Eastern Filbert Blight
Authors: Molnar Thomas J. , Walsh Emily , Capik John M. , Sathuvalli Vidyasagar , Mehlenbacher Shawn A. , Rossman Amy Y. , Zhang Ning
Published: January 2013

Eastern filbert blight (EFB) is a devastating disease of European hazelnut, Corylus avellana, which causes economic losses in Oregon, where 99% of the U.S. crop is produced. The causal fungus, Anisogramma anomala, is native to eastern North America, where it is found associated with the American hazelnut (C. americana). Although C. americana is tolerant, EFB causes cankers, branch dieback, and death of C. avellana. Detection and identification of A. anomala is time consuming using conventional methods because the fungus can only be cultured from sporulating perithecia and the disease symptoms and signs only show 12 to 16 months after infection. In this study, a TaqMan real-time polymerase chain reaction (PCR) assay based on a ribosomal DNA internal transcribed spacer was developed for A. anomala. The assay was validated with multiple isolates of A. anomala, closely related species, common environmental microorganisms, and over 100 C. avellana samples. The real-time PCR assay detected as low as 0.12 pg of A. anomala genomic DNA, and positively diagnosed EFB on 82% of asymptomatic plants as early as 15 weeks from infection. The real-time PCR assay is more sensitive and faster than traditional diagnostic methods. It can facilitate hazelnut breeding and disease management by early and accurate diagnosis of EFB.
Major histocompatibility complex peptide ligands as olfactory cues in human body odour assessment
Authors: Milinski Manfred , Croy Ilona , Hummel Thomas , Boehm Thomas
Published: January 2013

In many animal species, social communication and mate choice are influenced by cues encoded by the major histocompatibility complex (MHC). The mechanism by which the MHC influences sexual selection is a matter of intense debate. In mice, peptide ligands of MHC molecules activate subsets of vomeronasal and olfactory sensory neurons and influence social memory formation; in sticklebacks, such peptides predictably modify the outcome of mate choice. Here, we examine whether this evolutionarily conserved mechanism of interindividual communication extends to humans. In psychometric tests, volunteers recognized the supplementation of their body odour by MHC peptides and preferred ‘self’ to ‘non-self’ ligands when asked to decide whether the modified odour smelled ‘like themselves’ or ‘like their favourite perfume’. Functional magnetic resonance imaging indicated that ‘self’-peptides specifically activated a region in the right middle frontal cortex. Our results suggest that despite the absence of a vomeronasal organ, humans have the ability to detect and evaluate MHC peptides in body odour. This may provide a basis for the sensory evaluation of potential partners during human mate choice.
Analysis of structure characteristics of a flying probe tester
Authors: Chen Chuji , Shi Hongyan , Song Fumin
Published: January 2013

Purpose

The purpose of this paper is to present a method for evaluating the structural dynamic characteristics of a flying probe tester.

Design/methodology/approach

The dynamic characteristics of a flying probe tester framework were analyzed based on a finite element analysis method. First, modal analysis was carried out to characterize the modal parameters of the structure. Second, the harmonic response was analyzed according to the modal analysis and the response curve of the structural system was studied. Finally, transient analysis was conducted to obtain the transient response of the structures at the beginning of the vibration.

Findings

The natural frequency and the response frequency of a natural granite structure was the highest and the transient vibration displacement amplitude was the smallest compared with cast iron and artificial stone structures.

Originality/value

A comprehensive understanding of the dynamic characteristics of the framework of a flying probe tester with three different materials has been achieved. The results of the analyses provide a reference for the framework design of a flying probe tester.
BS 11000 for health commissioning
Authors: Quayle Adrian , Ashworth David , Gillies Alan
Published: January 2013

Purpose

The purpose of this paper is to consider how BS 11000 may be usefully deployed within a commissioning situation in the light of the Department of Health's suggestion that it represents “best practice”.

Design/methodology/approach

The study uses case studies from other sectors (criminal justice) and IT outsourcing to consider the nature of the commissioning relationship at the heart of the English NHS post‐2013. It looks at how BS 11000 is intended to support business relationships and how this can address potential problems identified in the case studies.

Findings

The study finds that business relationships are often regarded in a reductionist manner based on a simple contractual relationship. The case studies suggest that a richer more collaborative business relationship is required for effective provision of services. The authors suggest that BS 11000 can help organisations put in place the foundations of such relationships.

Research limitations/implications

The Clinical Commissioning Groups are still being formed, and the marketplace for service providers in the NHS is expanding dramatically. This means that there are limited opportunities for studying this issue in situ, and therefore it is necessary to use case studies from other domains.

Practical implications

This study suggests that the commissioning relationship is more complex than a simple contractual relationship, and a genuine partnership is needed between the new Clinical Commissioning Groups and their providers.

Social implications

From 2013, the NHS is intended to be a commissioner of services rather than a provider. Effective health and social care will depend upon an effective commissioning relationship.

Originality/value

The study provides insights from related fields into an area that cannot yet be studied itself, as it is still being formed. It has access to unpublished data from an ESRC funded study to provide new insights from a related public‐sector context.
A lifecycle perspective on buyer‐supplier collaboration in process development projects
Authors: Rönnberg‐Sjödin David
Published: January 2013

Purpose

Development and implementation of new process equipment within the process industries frequently necessitate strong collaboration between process firms and their equipment suppliers in joint process development projects. However, collaboration in this setting entails significant challenges over the lifecycle of these projects. Accordingly, the purpose of this article is to explore the problems and opportunities faced by equipment suppliers during collaboration with process firms, throughout the various lifecycle stages of process development projects.

Design/methodology/approach

The article synthesizes results from 22 interviews in a multiple case study of eight equipment suppliers in the process industries and a comprehensive review of relevant literature to identify critical problems of opportunities during the lifecycle. In total, data were gathered from firms in six different countries.

Findings

A deficient pre‐study may create problems due to miscommunication during development when close interaction is required. Purchasing discussions can be done simultaneously to development when a supplier has been selected, although uncertainty is a problem. It is important to get end‐user feedback and commitment during development and later stages. During assembly and installation and start‐up, a variety of actors are working simultaneously which requires coordination and planning from an early stage. Close interaction and education with end‐user is critical for the technology transfer in the start‐up stage. Sharing of experiences enhances operational performance during production.

Research limitations/implications

This study contributes by employing information rich case study data to describe the problem and opportunities faced over the full lifecycle in joint process development projects in the process industry. In particular, key issues over the lifecycle have been identified and described (e.g. purchasing, start‐up, education). Moreover, the adoption of a lifecycle perspective has indicated how activities, issues, and managerial challenges in specific stages are interconnected and affect the joint work in the following stages.

Practical implications

The findings of this article serves as guidelines to managers in equipment supplier firms and their customers by highlighting the problems and opportunities for improvement that occur during the interconnected stages of process development projects.

Originality/value

By focusing on the collaborative activities in different stages, this study higlights the critical problems and opportunities in the lifecycle of process equipment. In addition this article outlines how joint process development activities can facilitate enhanced operational performance, by means of collaborative design, installation and operation of new process equipment – i.e. “open operation”.
Integrated manufacturing strategy for deployment of CADCAM methodology in a SMME
Authors: Esan Adedeji O. , Khan Mohammed K. , Qi Hong S. , Naylor Craig
Published: January 2013

Purpose

Cost reduction through the use of technology has become the competitive strength of companies. The benefits of technology integration are quite credible and have been effective in business competition. The purpose of this paper is to describe an integrated manufacturing strategy for the deployment of a CAD/CAM system in a small, medium manufacturing enterprise (SMME).

Design/methodology/approach

A case study of a SMME is utilised in deploying an integrated CAD/CAM system for practical application of manufacturing technology for achieving sustainable growth through lean systems design (LSD). The paper presents a techno‐economic and technology change management framework, with an application of a holistic set of lean deployment tools that include establishing a strategic and operational plan for implementing CAD/CAM systems as a means to achieving world‐class performance.

Findings

The paper shows that the CAD/CAM integration within the case company increased knowledge of CAD/CAM technology, productivity, and flexibility whilst reducing throughput times. Based on the literature review and the current case study, a framework for ideal CAD/CAM implementation has been proposed. The paper also shows that management and organisational structures are key inhibitors for successful implementation of technology integration.

Research limitations/implications

The paper uses a single case study to validate deployment of the integrated manufacturing strategy in SMMEs. Hence there is a limitation to its generality.

Practical implications

The paper provides an opportunity to further understand CAD/CAM system implementation protocols within a well structured framework and its configuration within SMMEs.

Social implications

The CAD/CAM implementation framework will allow the SMMEs to achieve Lean manufacturing (thereby minimising wastes) leading to improved growth and employment rates.

Originality/value

The presentation of conceptualisation, development and implementation of an integrated CAD/CAM system in support of organisational wide Lean manufacturing initiative in SMMEs is an originality of this paper.
Image, place and nostalgia in hospitality branding and marketing
Authors: Hunt Louise , Johns Nick
Published: January 2013

Purpose

The purpose of this paper is to examine the nature of nostalgia, especially nostalgia associated with place, and its potential in the development of branding and advertising images for the hospitality industry.

Design/methodology/approach

The paper achieves its aims by reviewing the relevant literature and illustrating the extant theory with the results of a small pilot study.

Findings

Nostalgia is an effective tool for developing brand and advertising images for the hospitality industry. It is relevant especially to place and place‐related aspects such as terroir and it communicates with consumers of all ages. As well as evoking a direct response, nostalgic images also bring to mind many related sounds, odours and objects, which may also be linked with expectation. However, nostalgic images must be chosen with care, since some individuals may be negatively affected by them.

Practical implications

Hospitality organizations can make greater use of their links with place, culture and food by incorporating nostalgic imagery in their branding and advertising. The effects of nostalgia are felt by more age groups than is generally recognized.

Original/value

There has been little, if any, attention to nostalgia as a marketing tool in the hospitality industry. This article, which addresses this shortfall, will appeal to hospitality managers and entrepreneurs who seek to improve the effectiveness of their branding and advertising.
The effects of different types of trust on consumer perceptions of food safety
Authors: Chen Weiping
Published: January 2013

Purpose

The aim of this research is to empirically investigate how different types of trust relate to consumer perceptions of food safety.

Design/methodology/approach

After a review of trust literature this study classifies trust into three distinct types: supplier‐level specific trust, industry‐level specific trust and general trust. The direct and indirect relationships between three types of trust and consumer perceptions of food safety were studied through a survey of 1165 consumers from Beijing municipality, China using structural equation model as an analytical tool.

Findings

The results indicate that trust in manufacturers and trust in retailers are directly positively related to food safety perceptions. Trust in farmers is not directly related to food safety perceptions. Industry‐level specific trust is not related to food safety perceptions directly, but it is positively related to supplier‐level specific trust, which in turn is positively related to food safety perceptions. Finally, general trust has only a weak indirect positive effect through its effect on trust in food manufacturers.

Practical implications

The results imply that consumer perceived safety of food products might be enhanced by improving consumer trust in manufacturers and trust in retailers. The results also suggest that food suppliers are more difficult to build consumer trust when industry‐level specific trust is low and declining. In addition, food suppliers also get potential benefits through influencing and improving industry‐level specific trust. At last, the results suggest that some concerns about food safety are related to individuals' world reviews and maybe beyond the control of the food system.

Originality/value

This study is the first to investigate the relationship between different types of specific trust in the context of food safety. Accordingly, it complements existing trust models and helps predict and explain how trust relates to food safety perceptions directly and indirectly through interactions between different types of trust.
Facilitating Remote Laboratory Deployments Using a Relay Gateway Server Architecture
Authors: Melkonyan Arsen , Gampe Andreas , Pontual Murillo , Huang Grant , Akopian David
Published: January 2013

Hands-on experiments prepare students to deal with real-world problems and help to efficiently digest theoretical concepts and relate those to practical tasks. However, shortage of equipment, high costs, and the lack of human resources for laboratory maintenance and assistance decrease the implementation capacity of the hands-on training laboratories. At the same time, the Internet has become a common networking medium and is increasingly used to enhance education and training. In addition, experimental equipment at many sites is typically underutilized. Thus, remote laboratories accessible through the Internet can resolve cost and access constraints as they can be used at flexible times and from various locations. While many solutions have been proposed so far, this paper addresses an important issue of facilitating remote lab deployments by providing remote connectivity services to lab providers using a Relay Gateway Server architecture. A proof-of-concept solution is described which also includes other previously reported useful features. The system has been tested in engineering labs and student assessment is provided.
Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine
Authors: Veenendaal MVE , Painter RC , de Rooij SR , Bossuyt PMM , van der Post JAM , Gluckman PD , Hanson MA , Roseboom TJ
Published: January 2013

Objective

We previously showed that maternal under‐nutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. Also, we found increased neonatal adiposity among the grandchildren of women who had been undernourished during pregnancy. In the present study we investigated whether these transgenerational effects have led to altered body composition and poorer health in adulthood in the grandchildren.

Design

Historical cohort study.

Setting

Web‐based questionnaire.

Population

The adult offspring (F2) of a cohort of men and women (F1) born around the time of the 1944–45 Dutch famine.

Methods

We approached the F2 adults through their parents. Participating F2 adults (n = 360, mean age 37 years) completed an online questionnaire.

Main outcome measures

Weight, body mass index (BMI), and health in F2 adults, according to F1 prenatal famine exposure.

Results

Adult offspring (F2) of prenatally exposed F1 fathers had higher weights and BMIs than offspring of prenatally unexposed F1 fathers (+4.9 kg, P = 0.03; +1.6 kg/m², P = 0.006). No such effect was found for the F2 offspring of prenatally exposed F1 mothers. We observed no differences in adult health between the F2 generation groups.

Conclusions

Offspring of prenatally undernourished fathers, but not mothers, were heavier and more obese than offspring of fathers and mothers who had not been undernourished prenatally. We found no evidence of transgenerational effects of grandmaternal under‐nutrition during gestation on the health of this relatively young group, but the increased adiposity in the offspring of prenatally undernourished fathers may lead to increased chronic disease rates in the future.
BRIC Agricultural Policies Through a WTO Lens
Authors: Brink Lars , Orden David , Datz Giselle
Published: January 2013

This article examines the agricultural policies of Brazil, Russia, India and China (BRIC) through the prism of the disciplines on agricultural domestic support in the World Trade Organization (WTO). Although the BRIC are often grouped collectively as an emerging force in the world economy, divergent agricultural interests are reflected in different approaches towards agricultural policy both through international dispute settlement and notification of their own support. We examine the support notified to the WTO for verification of compliance with their legal commitments, which under the complex WTO rules often differs significantly from measurement of support in economic terms. We note the resulting difficulties of these disciplines in establishing limits on trade‐distorting support. Implications of a Doha agreement are examined. Although the prospect of adoption of new Doha disciplines has become remote, the negotiated provisions are informative about the future policy space the BRIC sought to maintain. Russia’s domestic support commitments under its 2012 WTO accession extend the international disciplines but share the complexity of the other cases.
The economics of network neutrality
Authors: Economides Nicholas , Hermalin Benjamin E.
Published: January 2013

Under the current regime for Internet access, “network neutrality,” parties are billed only by the Internet service provider (ISP) through which they connect to the Internet; pricing is not contingent on the content being transmitted. Recently, ISPs have proposed that content and applications providers pay them additional fees for accessing the ISPs’ residential clients, as well as fees to prioritize certain content. We analyze the private and social implications of such fees when the network is congested and more traffic implies greater delays. We derive conditions under which network neutrality would be welfare superior to any feasible scheme for prioritizing service.
Endogenous asymmetry in a dynamic procurement auction
Authors: Saini Viplav
Published: January 2013

We show how to numerically solve for a Markov‐perfect equilibrium of a dynamic auction game where a procurer repeatedly purchases construction services from capacity‐constrained firms. We find that the procurer is best off scheduling frequent auctions for small project sizes. Otherwise, firm capacity utilization rates become larger and more asymmetric, which softens competition and increases procurement costs. We also find that forward‐looking bidding dampens the competition‐softening effects of asymmetry: farsighted firms compete more intensely than myopic ones. This can undermine the goal of a bid‐preference‐style affirmative action program: more farsighted firms respond less to the asymmetry induced via bid preferences.
Replication of Established Common Genetic Variants for Adult BMI and Childhood Obesity in Greek Adolescents: The TEENAGE Study
Authors: Ntalla Ioanna , Panoutsopoulou Kalliope , Vlachou Panagiota , Southam Lorraine , William Rayner Nigel , Zeggini Eleftheria , Dedoussis George V.
Published: January 2013

Multiple genetic loci have been associated with body mass index (BMI) and obesity. The aim of this study was to investigate the effects of established adult BMI and childhood obesity loci in a Greek adolescent cohort. For this purpose, 34 variants were selected for investigation in 707 (55.9% females) adolescents of Greek origin aged 13.42 ± 0.88 years. Cumulative effects of variants were assessed by calculating a genetic risk score (GRS‐34) for each subject. Variants at the FTO, TMEM18, FAIM2, RBJ, ZNF608 and QPCTL loci yielded nominal evidence for association with BMI and/or overweight risk (p < 0.05). Variants at TFAP2B and NEGR1 loci showed nominal association (p < 0.05) with BMI and/or overweight risk in males and females respectively. Even though we did not detect any genome‐wide significant associations, 27 out of 34 variants yielded directionally consistent effects with those reported by large‐scale meta‐analyses (binomial sign p = 0.0008). The GRS‐34 was associated with both BMI (beta = 0.17 kg/m2/allele; p < 0.001) and overweight risk (OR = 1.09/allele; 95% CI: 1.04–1.16; p = 0.001). In conclusion, we replicate associations of established BMI and childhood obesity variants in a Greek adolescent cohort and confirm directionally consistent effects for most of them.
The impact of child sexual abuse on the course of bipolar disorder: a systematic review
Authors: Maniglio Roberto
Published: January 2013

Maniglio R. The impact of child sexual abuse on the course of bipolar disorder: a systematic review.  Bipolar Disord 2013: 15: 341–358. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Objectives:  The aim of this review was to elucidate the impact of child sexual abuse on all clinical phenomena that occur after the onset of bipolar disorder, including associated clinical features that are not part of the diagnostic criteria for the disorder.

Methods:  Five databases were searched and supplemented with a hand search of reference lists from retrieved papers. Study quality was assessed using a validated quality assessment tool. Blind assessments of study eligibility and quality were conducted by two independent researchers to reduce bias, minimize errors, and enhance the reliability of findings. Disagreements were resolved by consensus.

Results:   Eighteen studies that included a total of 2996 adults and youths with bipolar disorder and met the minimum quality criteria necessary to ensure objectivity and not invalidate results were analyzed. Across studies, child sexual abuse was strongly (and perhaps directly) associated with posttraumatic stress disorder; whereas it was less strongly (and perhaps indirectly) related to suicide attempts, alcohol and/or drug abuse or dependence, psychotic symptoms, and an early age of illness onset. In regard to the association between child sexual abuse and other clinical variables concerning the course of bipolar disorder, evidence was scant or conflicting.

Conclusions:  Child sexual abuse is associated (either directly or indirectly) with some clinical phenomena that represent a more severe form of bipolar disorder. Although such a traumatic experience may directly affect the development of posttraumatic stress disorder, the effects of early sexual abuse on later suicidal behavior, substance abuse, and psychotic symptoms may operate through the mediating influences of certain psychopathological or neurobiological variables.
Design and pharmacological characterization of VUF14480, a covalent partial agonist that interacts with cysteine 983.36 of the human histamine H4 receptor
Authors: Nijmeijer S , Engelhardt H , Schultes S , van de Stolpe A C , Lusink V , de Graaf C , Wijtmans M , Haaksma E E J , de Esch I J P , Stachurski K , Vischer H F , Leurs R
Published: January 2013

Background and Purpose

The recently proposed binding mode of 2‐aminopyrimidines to the human (h) histamine H4 receptor suggests that the 2‐amino group of these ligands interacts with glutamic acid residue E1825.46 in the transmembrane (TM) helix 5 of this receptor. Interestingly, substituents at the 2‐position of this pyrimidine are also in close proximity to the cysteine residue C983.36 in TM3. We hypothesized that an ethenyl group at this position will form a covalent bond with C983.36 by functioning as a Michael acceptor. A covalent pyrimidine analogue will not only prove this proposed binding mode, but will also provide a valuable tool for H4 receptor research.

Experimental Approach

We designed and synthesized VUF14480, and pharmacologically characterized this compound in hH4 receptor radioligand binding, G protein activation and β‐arrestin2 recruitment experiments. The ability of VUF14480 to act as a covalent binder was assessed both chemically and pharmacologically.

Key Results

VUF14480 was shown to be a partial agonist of hH4 receptor‐mediated G protein signalling and β‐arrestin2 recruitment. VUF14480 bound covalently to the hH4 receptor with submicromolar affinity. Serine substitution of C983.36 prevented this covalent interaction.

Conclusion and Implications

VUF14480 is thought to bind covalently to the hH4 receptor‐C983.36 residue and partially induce hH4 receptor‐mediated G protein activation and β‐arrestin2 recruitment. Moreover, these observations confirm our previously proposed binding mode of 2‐aminopyrimidines. VUF14480 will be a useful tool to stabilize the receptor into an active confirmation and further investigate the structure of the active hH4 receptor.

Linked Articles

This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Effect of an Increase in Left Ventricular Pressure Overload on Left Atrial‐Left Ventricular Coupling in Patients with Hypertension: A Two‐Dimensional Speckle Tracking Echocardiographic Study
Authors: Miyoshi Hirokazu , Oishi Yoshifumi , Mizuguchi Yukio , Iuchi Arata , Nagase Norio , Ara Nusrat , Oki Takashi
Published: January 2013

Background

Two‐dimensional speckle tracking echocardiography (2DSTE) has recently been applied to evaluate left atrial (LA) function in addition to left ventricular (LV) function. However, whether 2DSTE can provide insight into LA‐LV interaction related to an increase in LV pressure overload remains unknown.

Methods

One hundred five asymptomatic patients with hypertension were studied by conventional, pulsed and tissue Doppler, and 2DSTE. Hypertensive patients were classified into 2 groups according to the ratio of early diastolic to atrial systolic velocity (E/A) of transmitral flow: E/A ≥ 1 (n = 37) and E/A < 1 (n = 68). We used (E/peak early diastolic mitral annular motion velocity [e′])/peak systolic LA strain (S‐LAs) and E/e′, as parameters of LA stiffness during ventricular systole and LV diastolic stiffness, respectively.

Results

The peak early diastolic LV longitudinal strain rate, and peak early diastolic LA strain and strain rate were lower in the E/A < 1 group than in the E/A ≥ 1 group. The E/e′/S‐LAs and E/e′ were greater in the E/A < 1 group. In the E/A < 1 group, systolic blood pressure (SBP) correlated with LV wall thickness parameters, A, e′, E/e′, peak early diastolic LV longitudinal strain rate, and E/e′/S‐LAs. Multivariate regression analysis indicated that A, E/e′, and E/e′/S‐LAs were defined as strong predictors related to SBP.

Conclusion

In patients with hypertension, an elevation in SBP leads to increased LA stiffness during ventricular systole and LV diastolic stiffness, in association with continued and further advanced LV diastolic dysfunction. 2DSTE is considered a sensitive tool for detecting abnormal LA‐LV coupling related to an increased LV pressure overload.
A Novel Echocardiographic Method for the Detection of Subclinical Atherosclerosis in Newly Diagnosed, Untreated Type 2 Diabetes
Authors: Simsek Hakki , Sahin Musa , Gunes Yilmaz , Dogan Adnan , Gumrukcuoglu Hasan Ali , Tuncer Mustafa
Published: January 2013

Background

Diabetes accelerates the natural process of atherosclerosis and is a predictor for progression of atherosclerotic lesions. To improve clinical outcomes, noninvasive imaging modalities have been proposed to measure and monitor atherosclerosis. Recently, it has been shown that the color M‐mode–derived propagation velocity of the descending thoracic aorta (aortic velocity propagation [AVP]) was associated with coronary and carotid atherosclerosis.

Methods

Carotid intima‐media thickness (CIMT) and AVP were measured in 72 patients with newly diagnosed type 2 diabetes and 44 healthy people. Individuals who had previously used oral hypoglycemic agents or insulin treatment or had a history of hyperlipidemia, cigarette smoking, hypertension, and cardiovascular disease were excluded from this study.

Results

Compared with control group, patients with type 2 diabetes had significantly lower AVP (39.9 ± 6.5 vs. 58.4 ± 6.7 cm/sec, P < 0.001) and higher CIMT (1.1 ± 0.1 vs. 0.95 ± 0.12 mm, P < 0.001) measurements. There were significant correlations between AVP and CIMT (r = −0.835, P < 0.001), AVP and fasting plasma glucose (r = −0.796, P < 0.001)), AVP and HbA1 c (r = −0918 P < 0.001).

Conclusions

Diabetes mellitus may be associated with subclinical atherosclerosis assessed by measurement of AVP and CIMT. These simple methods might improve patient selection for primary prevention atherosclerotic progression.
Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: a study on patients with panic disorder, generalized anxiety disorder and obsessive–compulsive disorder
Authors: Dell'Osso Bernardo , Camuri Giulia , Benatti Beatrice , Buoli Massimiliano , Altamura A. Carlo
Published: January 2013

Aim

The latency to first pharmacological treatment (duration of untreated illness or ‘DUI’) is supposed to play a major role in terms of outcome in psychotic conditions. Interest in the field of affective disorders and, in particular, of duration of untreated anxiety, has been recently registered as well. However, a preliminary epidemiologic investigation of the phenomenon is necessary. The present study was aimed to investigate and compare age at onset, age at first pharmacological treatment and DUI in a sample of patients affected by different anxiety disorders. DUI was defined as the interval between the onset of the specific anxiety disorder and the administration of the first adequate pharmacological treatment in compliant subjects.

Methods

Study sample included 350 patients, of both sexes, with a DSM‐IV‐TR diagnosis of panic disorder (n = 138), generalized anxiety disorder (n = 127) and obsessive–compulsive disorder (n = 85).

Results

Panic disorder was associated with the shortest DUI (39.5 months), whereas obsessive–compulsive disorder was associated with the longest latency to treatment (94.5 months) (F = 13.333; P < 0.0001). Patients with generalized anxiety disorder showed a mean DUI of 81.6 months.

Conclusion

Present results indicate that patients with different anxiety disorders may wait for years (from 3 up to 8) before receiving a first adequate pharmacological treatment. Differences in terms of age at onset, age at the first pharmacological treatment and, ultimately, in DUI in specific anxiety disorders may depend on multiple clinical and environmental factors. Latency to non‐pharmacological interventions (e.g. psychoeducation and different forms of psychotherapy) needs to be addressed and correlated with DUI in future studies.
Pilot programme of modular symptom‐specific group cognitive behaviour therapy in a ‘Real World’ early intervention in psychosis service
Authors: Raune David , Law Suzanne
Published: January 2013

Aim

A modular symptom‐specific (MSS) programme of early intervention group cognitive behaviour therapy for psychosis might confer additional therapeutic benefits and clinical and financial efficiency, but the approach is empirically untested. Therefore, we devised a novel MSS programme to test – in a culturally diverse ‘Real World’ early intervention service – its relevancy, feasibility, acceptability and safety.

Method

The MSS programme comprised six different groups across 33 sessions: Psycho‐Education (3), Mood‐Management (5), Delusions (8), Auditory Hallucinations (8), Past Auditory Hallucinations (3) and Negative Symptoms (6). All patients were eligible for psycho‐education, but other groups required a specific symptom.

Results

Patients (n = 166, 37% White) showed wide heterogeneity in the activity, type and number of symptoms, and group‐relevant symptoms were common. Eighteen groups have run so far, each type of group at least once, 58/166 (35%) of patients attended across 281/412 (68%) group sessions, 46/58 (79%) of patients re‐attended, and the 58 patients attended groups a mean of 4.8 times. Patients were significantly (P < 0.05) more likely to attend the programme if they had a schizophrenia diagnosis, a longer psychotic illness length or one active group‐relevant (psychotic/mood) symptom. Diagnostically uncertain psychosis patients were almost significantly (P = 0.05) less likely to attend the programme. duration of untreated psychosis and ethnicity were unrelated to attendance/re‐attendance. No group‐related risk incidents occurred.

Conclusion

A MSS programme approach is highly relevant to early intervention symptom heterogeneity and is feasible, culturally acceptable and safe; it also appears particularly efficient. Future research should now test its clinical efficacy.
Poor outcome associated with symptomatic deterioration among help‐seeking individuals at risk for psychosis: a naturalistic follow‐up study
Authors: Morita Keiko , Kobayashi Hiroyuki , Takeshi Kiyoaki , Tsujino Naohisa , Nemoto Takahiro , Mizuno Masafumi
Published: January 2013

Aims

It remains debatable whether early intervention for psychosis is capable of meeting the needs of at‐risk subjects. The aims of this study were to describe the actual impact of interventions on subjective difficulties and to explore the factors that may be associated with a poor outcome.

Methods

Participants were help‐seeking outpatients at a university hospital who met the Criteria of Prodromal Syndromes. Changes in the symptoms, subjective experience and current insight were assessed using the Scales of Prodromal Symptoms, the Subjective Well‐being under Neuroleptics, and the Scale to Assess Unawareness of Mental Disorder, respectively. Global functioning, social functioning and subjective quality of life were evaluated using the Global Assessment of Functioning Scale, the Social Functioning Scale, and the WHO‐Quality of Life 26, respectively. These measures were assessed both at baseline and after 1 year.

Results

Forty‐six patients agreed to participate. Of the 27 patients who completed the reassessment at the follow‐up point, 13 patients (48%) showed little improvement in their positive/negative symptoms, subjective well‐being or awareness of their symptoms. Additionally, less severe negative symptoms, more severe general symptoms and lower subjective well‐being at baseline significantly predicted a deterioration of positive/negative symptoms after 1 year.

Conclusion

Our findings suggest that the current strategy for reducing psychosis risk based on positive symptoms should be reappraised.