bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple aspects of plasticity in clutch size vary among populations of a globally distributed songbird
Authors: Westneat David F. , Bókony Veronika , Burke Terry , Chastel Olivier , Jensen Henrik , Kvalnes Thomas , Lendvai Ádám Z. , Liker András , Mock Douglas , Schroeder Julia , Schwagmeyer P. L. , Sorci Gabriele , Stewart Ian R. K.
Published: November 2013

Plasticity in life‐history characteristics can influence many ecological and evolutionary phenomena, including how invading organisms cope with novel conditions in new locations or how environmental change affects organisms in native locations. Variation in reaction norm attributes is a critical element to understanding plasticity in life history, yet we know relatively little about the ways in which reaction norms vary within and among populations.

We amassed data on clutch size from marked females in eight populations of house sparrows (Passer domesticus) fromNorthAmerica andEurope. We exploited repeated measures of clutch size to assess both the extent of within‐individual phenotypic plasticity and among‐individual variation and to test alternative hypotheses about the underlying causes of reaction norm shape, particularly the decline in clutch size with date.

Across all populations, females of this multibrooded species altered their clutch size with respect to date, attempt order, and the interaction of date and order, producing a reaction norm in multidimensional environmental space. The reaction norm fits that predicted by a model in which optimal clutch size is driven by a decline with date hatched in the ability of offspring to recruit. Our results do not fit those predicted for other proposed causes of a seasonal decline in clutch size.

We also found significant differences between populations in response to date and the date by attempt order interaction. We tested the prediction that the relationship with date should be increasingly negative as breeding season becomes shorter but found steeper declines in clutch size with date in populations with longer seasons, contrary to the prediction. Populations also differed in the level of among‐individual variation in reaction norm intercept, but we found no evidence of among‐individual variation in reaction norm slope.

We show that complex reaction norms in life‐history characters exhibit within‐ and among‐population variance. The nature of this variance is only partially consistent with current life‐history theory and stimulates expansions of such theory to accommodate complexities in adaptive life history.
EDITOR'S CHOICE: Application of genetic diversity–ecosystem function research to ecological restoration
Authors: Kettenring Karin M. , Mercer Kristin L. , Reinhardt Adams Carrie , Hines Jes
Published: November 2013

Three common goals for restoration are (i) rapid plant establishment, (ii) long‐term plant persistence and (iii) restoration of functioning ecosystems. Restoration practitioners often use cultivars optimized for rapid plant establishment under highly disturbed conditions to achieve the first goal; locally adapted genotypes are championed for the second because they can be well suited for local environmental conditions. Restoring functioning ecosystems is considered a loftier goal that practitioners struggle to achieve because we lack proven techniques.

Similar to the demonstrated benefits of species, functional and phylogenetic diversity for ecosystem functions (EFs), recent genetic diversity (GD)–ecosystem function (EF) experiments have shown that increases in plantGDcan positively influence many differentEFs. Would the introduction of diverse plant genotypes of a given species into a restoration enhance ecosystem functioning and the evolutionary potential of restored populations?

In this review, we first examine three propagule‐sourcing approaches: cultivar, local adaptation andGD. Next, we raise questions that if addressed, could help practitioners implement aGDapproach in restoration: (i) How might the selection, relatedness and arrangement of genotypes be optimized to restore functioning ecosystems, (ii) How do traits that affect anEFrelate to neutral or adaptive diversity, more common measures ofGDand (iii) at which spatial and temporal scales doesGDinfluenceEFs in restorations?

Synthesis and applications. Although each propagule‐sourcing approach may be best suited for a particular restoration goal, each approach may simultaneously benefit other goals. Yet cultivars and locally adapted populations that have experienced artificial and/or natural selection may not possess the levels of diversity that will confer expected benefits to different ecosystem functions. Future research should determine the relative value of each approach (or a combination of approaches) for simultaneously achieving multiple restoration goals. Restoration experiments, where plant genetic diversity (GD) is manipulated and monitored over scales relevant to restoration, could reveal the true promise of aGDapproach to restoration.
Protest Camps: An Emerging Field of Social Movement Research
Authors: Frenzel Fabian , Feigenbaum Anna , McCurdy Patrick
Published: November 2013

Recently protest camps have emerged around the world as a highly visible form of protest. Part and parcel of new social movement activism for over 40 years, they are important sites and catalysts for identity creation, expression, political contention and incubators for social change. While research has punctually addressed individual camps, there is lack of comparative and comprehensive research that links historic and contemporary protest camps as a unique area of interdisciplinary study. Research on the phenomenon to date has remained punctual and case based. This paper proposes to study protest camps as a distinct new field of research in social movement studies. Existing literature is critically reviewed and framed in three thematic clusters of spatiality, affect and autonomy. On the basis of this review the paper develops a research approach based on the analysis of infrastructures used to make protest camps. We contest that an infrastructural analysis highlights protest camps as a unique organizational form and transcends the limits of case-based research while respecting the varying contexts and trajectories of protest camps.
Ethopolitics and the Financial Citizen
Authors: Pathak Pathik
Published: November 2013

While personal debt has been the subject of intense research activity over the past decade, in particular from think tanks and government bodies, it remains relatively undertheorized and neglected in general by the social sciences. This article offers a novel theoretical frame for the analysis of personal debt – and personal overindebtedness in particular – by highlighting the construction of deviance from financial behavioural normativities. Using Nikolas Rose's concept of ‘ethopolitics’ to describe the relocation of government from questions of rational administration to those of everyday morality and ethics, this article presents two characterizations of deviance from an ethopolitical imaginary of financial citizenship: irresponsibility and incapability. From this framework, the article explores the nature of the state sponsored normalization of indebtedness and the stigmatization of overindebtedness as a corollary of ‘delinquent’ dispositions and dependencies. This article suggests that UK government policy concerning financial responsibility has been shaped by an ethopolitical imaginary of financial citizenship which is based upon a skewed understanding of structure and agency which has its parallel in the attribution of unemployment to ‘worklessness’.
SLIT3 is Increased in Supracervical Human Foetal Membranes and in Labouring Myometrium and Regulates Pro‐Inflammatory Mediators
Authors: Lim Ratana , Barker Gillian , Lappas Martha
Published: November 2013

Problem

Inflammation is associated with preterm birth, a worldwide healthcare issue. SLIT3 has a role in inflammation, and thus, the purpose of this study was to determine the effect of SLIT3 on labour mediators in human gestational tissues.

Method of study

SLIT3 protein expression was performed using immunohistochemistry in foetal membranes and myometrium with no labour and after labour. Foetal membranes were also obtained from a distal site (DS) and supracervical site (overlying the cervix; SCS). SLIT3 gene silencing was achieved using siRNA in primary amnion and myometrial cells. Pro‐inflammatory and pro‐labour mediators were evaluated by qRT‐PCR, ELISA and gelatin zymography.

Results

SLIT3 expression was greater in foetal membranes from the SCS compared with DS and in myometrium after term spontaneous labour onset. SLIT3 siRNA in primary amnion and myometrial cells decreased IL‐1β‐induced pro‐inflammatory cytokine gene expression and release (IL‐6 and IL‐8) and MMP‐9 gene expression and release. In amnion cells, SLIT3 siRNA knockdown decreased IL‐1β‐induced COX‐2 expression and prostaglandin PGE2 release. There was no effect of SLIT3 siRNA on IL‐1β‐induced NF‐κB transcriptional activity.

Conclusion

Our results demonstrate that SLIT3 is increased with labour, and both our amnion and our myometrial studies describe a pro‐inflammatory effect of SLIT3 in these tissues.
Randomized controlled trial of laparoscopic anterior 180° partial versus posterior 270° partial fundoplication
Authors: Daud Wan Najmi Wan , Thompson Sarah K. , Jamieson Glyn G. , Devitt Peter G. , Martin Ian J. G. , Watson David I.
Published: November 2013

Background

Previous trials show good outcomes following anterior and posterior partial versus Nissen fundoplication for gastro‐oesophageal reflux. However, it is unclear which partial fundoplication performs best. This study compared anterior 180° versus posterior 270° fundoplication.

Methods

At three hospitals, patients were randomized to anterior 180° versus posterior 270° partial fundoplication, and clinical outcomes were determined using a structured questionnaire at 3, 6 and 12 months. Heartburn, dysphagia and satisfaction were assessed using 0–10 analoue scales, and adverse outcomes and side effects were determined. Endoscopy, manometry and pH monitoring were performed 6 months after surgery.

Results

Forty‐seven patients were randomized to anterior (n = 23) versus posterior (n = 24) fundoplication. Clinical outcomes for 93–98% of patients were available at each follow‐up point. At 12 months, the mean heartburn score was higher following anterior fundoplication (2.7 versus 0.8, P = 0.045), although differences were not significant at earlier follow‐up. Conversely, following posterior fundoplication, patients were less able to belch at 3 (56% versus 16%, P = 0.013) and 6 months (43% versus 9%, P = 0.017). No significant differences were demonstrated for dysphagia. Both groups had high rates of satisfaction with the outcome – 85% versus 86% satisfied at 12 months follow‐up.

Conclusion

Both partial fundoplications are effective treatments for gastro‐oesophageal reflux. Posterior partial fundoplication is associated with less reflux symptoms offset by more side effects.
Akt pathway protein expression in gastrointestinal Kaposi sarcomas: relevance for tumor biology
Authors: Badescu Alina , Couvelard Anne , Handra‐Luca Adriana
Published: November 2013

Gastrointestinal Kaposi sarcoma (KS) is classical, but rare. The AKT signaling pathway plays a central role in G protein‐coupled receptor, key protein of KS histogenesis, encoded by KSHV/HHV8. There is increasing evidence that rapamycin, acting on AKT pathway, may be useful in the treatment of KS, including in HIV patients. We aimed to study the expression pattern of AKT pathway proteins in gastrointestinal KS. Expression of AKT, 4EBP1, PTEN, mTOR was assessed in 19 gastrointestinal KS biopsies by immunohistochemistry (17 patients). Protein expression in tumor spindle cells and in intratumor stromal vascular endothelial cells was analyzed with regard to clinicomorphological features. Tumor AKT related to lack of marked extravasated erythrocytes, tumor PTEN to presence of intratumor hemosiderin (p = 0.04 for both comparisons). Presence of both extravasated erythrocytes and hemosiderin related directly to endothelial stromal vascular nuclear PTEN and to low endothelial mTOR (p = 0.4 and 0.03, respectively). High tumor 4EBP1 related to a high slit‐type abnormal vascular component (p = 0.04). The results of our study suggest pro‐permeability or pro‐angiogenic roles for 4EBP1 and PTEN and, opposite roles for AKT and mTOR in KS. Our hypotheses warrant further studies to obtain more generally applicable results.
Application of consensus theory to formalize expert evaluations of plant species distribution models
Authors: van Zonneveld Maarten , Castañeda Nora , Scheldeman Xavier , van Etten Jacob , Van Damme Patrick
Published: November 2013

Aim

Application of environmental envelope modelling (EEM) for conservation planning requires careful validation. Opinions of experts who have worked with species of interest in the field can be a valuable and independent information source to validate EEM because of their first‐hand experience with species occurrence and absence. However, their use in model validation is limited because of the subjectivity of their feedback. In this study, we present a method on the basis of cultural consensus theory to formalize expert model evaluations.

Methods

We developed, for five tree species, distribution models with nine different variable combinations and Maxent EEM software. Species specialists validated the generated distribution maps through an online Google Earth interface with the scores from Invalid to Excellent. Experts were also asked about the commission and omission errors of the distribution models they evaluated. We weighted expert scores according to consensus theory. These values were used to obtain a final average expert score for each of the produced distribution models. The consensus‐weighted expert scores were compared with un‐weighted scores and correlated to four conventional model performance parameters after cross‐validation with test data: Area Under Curve (AUC), maximum Kappa, commission error and omission error.

Results

The median consensus‐weighted expert score of all species–variable combinations was close to Fair. In general, experts that reached more consensus with peers were more positive about the EEM outcomes, compared to those that had more opposite judgements. Both consensus‐weighted and un‐weighted scores were significantly correlated to corresponding AUC, maximum Kappa and commission error values, but not to omission errors. More than half of the experts indicated that the distribution model they considered best included areas where the species is known to be absent. One third also indicated areas of species presence that were omitted by the model.

Conclusions

Our results indicate that experts are fairly positive about EEM outcomes. This is encouraging, but EEM application for conservation actions remains limited according to them. Methods to formalize expert knowledge allow a wider use of this information in model validation and improvement, and they complement conventional validation methods of presence‐only modelling. Online GIS and survey applications facilitate the consultation of experts.
Clinical implementation of genetic testing in medicine: a US regulatory science perspective
Authors: Lesko Lawrence J. , Schmidt Stephan
Published: November 2013

Heterogeneity of treatment effects in unselected patient populations has stimulated various strategic approaches to reduce variability and uncertainty and improve individualization of drug selection and dosing. The rapid growth of DNA sequencing and related technologies has ramped up progress in interpreting germline and somatic mutations and has begun to reshape medicine, especially in oncology. Over the past decade, regulatory agencies realized that they needed to be proactive and not reactive if personalized medicine was to become a reality. The US Food and Drug Administration, in particular, took steps to nurture the field through peer‐reviewed publications, co‐sponsoring public workshops and issuing guidance for industry. The following two major approaches to personalized medicine were taken: (i) encouragement of de novo co‐development of drug–genetic test combinations by industry; and (ii) retrospective assessment of legacy genetic data for the purpose of updating drug labels. The former strategy has been more successful in getting new targeted therapies to the marketplace with successful adoption, while the latter, as evidenced by the low adoption rate of pharmacogenetic testing, has been less successful. This reflection piece makes clear that several important things need to happen to make personalized medicine diffuse in more geographical areas and among more therapeutic specialties. The debate over clinical utility of genetic tests needs to be resolved with consensus on evidentiary standards. Physicians, as gatekeepers of prescription medicines, need to increase their knowledge of genetics and the application of the information to patient care. An infrastructure needs to be developed to make access to genetic tests and decision‐support tools available to primary practitioners and specialists outside major medical centres and metropolitan areas.
Two Faces of Inflammation: An Immunopharmacological View
Authors: Moilanen Eeva
Published: November 2013

Inflammation is a protective response intended to eliminate pathogens and other offending agents which have potential to cause cell injury, as well as malignant and necrotic cells. However, if the inflammatory response is dysregulated or inappropriately focused, it has considerable potential to cause harm and can lead to development of inflammatory diseases such as allergic and autoimmune diseases. Despite the recent success in cytokine‐targeted therapies, for example by the use of specific biological drugs, there are still considerable unmet needs in the treatment of inflammatory diseases. Further, recent discoveries in many diseases in addition to the classical inflammatory diseases have revealed inflammation to be a major factor participating in the underlying pathophysiological processes, either through activation of inflammatory cells or through triggering of inflammatory signalling mechanisms in the tissue cells. Examples of such diseases and conditions are many cardiovascular, metabolic and degenerative diseases, as well as cancer, obesity and pain. This brings the immunopharmacological approach into a new perspective in the drug development in very wide therapeutic areas. Immunopharmacology investigates mechanisms of inflammation and potential molecules and targets to treat inflammatory diseases. The current issue of Basic and Clinical Pharmacology and Toxicology focuses on some of the novel inflammatory mechanisms with potential in anti‐inflammatory drug development, including kinase pathways, TRP ion channels, eicosanoid system, obesity‐related adipokines, autoantibodies against citrullinated proteins, eosinophils, platelets and pathways connecting nervous and immune systems. The MiniReviews are based on lectures given at the symposium “Novel Drugs and Drug Targets to Treat Inflammation” in Ylläs, Finland, in March 2013.
Relationship between clinical features and inflammation‐related monocyte gene expression in bipolar disorder – towards a better understanding of psychoimmunological interactions
Authors: Haarman Bartholomeus (Benno) CM , Riemersma‐Van der Lek Rixt F , Burger Huibert , Netkova Mina , Drexhage Roosmarijn C , Bootsman Florian , Mesman Esther , Hillegers Manon HJ , Spijker Anne T , Hoencamp Erik , Drexhage Hemmo A , Nolen Willem A
Published: November 2013

Objectives

Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro‐inflammatory gene expression in patients with bipolar disorder (BD). We hypothesized a priori that increased monocyte pro‐inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms.

Methods

Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro‐inflammatory gene expression and clinical features, from which feature‐expression heat maps were drawn.

Results

No associations were found between pro‐inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti‐epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression.

Conclusions

Our hypothesis that lifetime psychotic features would be associated with pro‐inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro‐inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood‐regulating medications.
Therapeutic potential of midkine in cardiovascular disease
Authors: Kadomatsu Kenji , Bencsik Péter , Görbe Anikó , Csonka Csaba , Sakamoto Kazuma , Kishida Satoshi , Ferdinandy Péter
Published: November 2013

Ischaemic heart disease, stroke and their pathological consequences are life‐threatening conditions that account for about half of deaths in developed countries. Pathology of these diseases includes cell death due to ischaemia/reperfusion injury, vascular stenosis and cardiac remodelling. The growth factor midkine plays a pivotal role in these events. Midkine shows an acute cytoprotective effect in ischaemia/reperfusion injury at least in part via its anti‐apoptotic effect. Moreover, while midkine promotes endothelial cell proliferation, it also recruits inflammatory cells to lesions. These activities eventually enhance angiogenesis, thereby preventing cardiac tissue remodelling. However, midkine's activity in recruiting inflammatory cells into the vascular wall also triggers neointima formation, and consequently, vascular stenosis. Moreover, midkine is induced in cancer tissues where it enhances angiogenesis. Therefore, midkine may promote tumour formation through its angiogenic and anti‐apoptotic activity. This review focuses on the roles of midkine in ischaemic cardiovascular disease and their pathological consequences, that is angiogenesis, vascular stenosis, and cardiac remodelling, and discusses the possible therapeutic potential of modulation of midkine in these diseases.

Linked Articles

This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐4
Transient receptor potential (TRP) channels in the airway: role in airway disease
Authors: Grace M S , Baxter M , Dubuis E , Birrell M A , Belvisi M G
Published: November 2013

Over the last few decades, there has been an explosion of scientific publications reporting the many and varied roles of transient receptor potential (TRP) ion channels in physiological and pathological systems throughout the body. The aim of this review is to summarize the existing literature on the role of TRP channels in the lungs and discuss what is known about their function under normal and diseased conditions. The review will focus mainly on the pathogenesis and symptoms of asthma and chronic obstructive pulmonary disease and the role of four members of the TRP family: TRPA1, TRPV1, TRPV4 and TRPM8. We hope that the article will help the reader understand the role of TRP channels in the normal airway and how their function may be changed in the context of respiratory disease.

Linked Articles

This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
Role of the A2B receptor–adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats
Authors: Antonioli L , Fornai M , Awwad O , Giustarini G , Pellegrini C , Tuccori M , Caputi V , Qesari M , Castagliuolo I , Brun P , Giron M C , Scarpignato C , Blandizzi C , Colucci R
Published: November 2013

Background and Purpose

Adenosine A2B receptors regulate several physiological enteric functions. However, their role in the pathophysiology of intestinal dysmotility associated with inflammation has not been elucidated. Hence, we investigated the expression of A2B receptors in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation.

Experimental Approach

Colitis was induced by 2,4‐dinitrobenzenesulfonic acid (DNBS). Colonic A2B receptor expression and localization were examined by RT‐PCR and immunofluorescence. The interaction between A2B receptors and adenosine deaminase was assayed by immunoprecipitation. The role of A2B receptors in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs).

Key Results

A2B receptor mRNA was present in colon from both normal and DNBS‐treated rats but levels were increased in the latter. A2B receptors were predominantly located in the neuromuscular layer, but, in the presence of colitis, were increased mainly in longitudinal muscle. Functionally, the A2B receptor antagonist MRS 1754 enhanced both electrically‐evoked and carbachol‐induced cholinergic contractions in normal LMPs, but was less effective in inflamed tissues. The A2B receptor agonist NECA decreased colonic cholinergic motility, with increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A2B receptors and adenosine deaminase, which colocalize in the neuromuscular compartment.

Conclusions and Implications

Under normal conditions, endogenous adenosine modulates colonic motility via A2B receptors located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired due to a link between A2B receptors and adenosine deaminase, which catabolizes adenosine, thus preventing A2B receptor activation.
The effect of smoking cessation on airway inflammation in young asthma patients
Authors: Westergaard C. G. , Porsbjerg C. , Backer V.
Published: November 2013

Background

Smoking has been shown to have several detrimental effects on asthma, including poor symptom control, attenuated treatment response and accelerated decline in lung function. In spite of this, smoking is at least as common among asthma patients as in the rest of the population. The aggravations of smoking on asthma may be caused by effects on airway inflammation, which has been found to be changed in asthmatic smokers. It is not known whether these smoking‐induced airway inflammation changes are reversible after smoking cessation.

Objective

The aim of this study was to assess airway changes in asthmatic smokers before and during smoking cessation.

Methods

Forty‐six smokers with asthma, all steroid‐free (age range: 19–40), were recruited. All participants attempted smoking cessation over a period of 3 months. Visits were performed at weeks 0, 6 and 12 and included induced sputum, FeNO, methacholine challenge, lung function, Asthma Control Questionnaire (ACQ6) and exhaled CO.

Results

Twenty‐six of 46 patients succeeded in quitting smoking. In the quitters, improvements in methacholine AHR (77% before and 52% after smoking cessation, respectively, P = 0.016) and ACQ6 score (1.7–0.7, P = 0.034) and FeNO (8.7–14.8 p.p.b., P = 0.002) were observed, whereas no significant changes were found regarding eosinophils or lung function. A small but significant decrease in neutrophils (54.1–52%, P = 0.003) was present in quitters compared with the non‐quitters. Non‐quitters experienced no changes in any parameters.

Conclusion

Smoking cessation improved asthma control, but the changes were not related to change in eosinophilic inflammation, and the reduction in neutrophils was small. Thus, airway inflammation with eosinophils and neutrophils may be less important drivers of asthma control in smokers than other factors.

Clinical Relevance

Smoking cessation may improve clinically important disease parameters such as AHR and symptom score, but likely unrelated to changes in airway inflammation.
Imaging of immune cell behavior and function in multiple sclerosis and experimental autoimmune encephalomyelitis
Authors: Pesic Marija , Kawakami Naoto , Bartholomäus Ingo , Kyratsous Nikolaos I.
Published: November 2013

To visualize the entire process of encephalitogenic T cell infiltration into the target organ, we performed intravital imaging by using two‐photon microscopy in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. Intravital imaging documented that T cells first appear in the leptomeningeal blood vessels where they crawl in an integrin‐dependent manner and scan the intraluminal surface for extravasation sites. After diapedesis, the T cells continue to crawl on the abluminal surface, where they meet local antigen presenting cells (APC) that can provide stimuli to the T cells for the subsequent infiltration into the central nervous system (CNS) parenchyma. Although flow cytometric analysis documented that the infiltrated T cells upregulated their activation markers in the CNS meninges, it was unclear at which scanning step the activation occurred. We recently introduced two genetically encoded fluorescent T cell activation sensors for intravital imaging. The first is a fluorescent resonance energy transfer‐based Ca2+ sensor for the quantification of the intracellular Ca2+ concentration, a major step in T cell receptor signaling. The second sensor is a truncated nuclear factor of activated T cells fused to green fluorescent protein, which subcellular localization corresponds to the T cell activation state. Introducing these sensors into the lymphocytes enables the visualization of the interactions of encephalitogenic T cells with different blood–brain barrier structures, and allows us to assess the functional aspect of these interactions directly in vivo. This model system can be further used to evaluate therapeutic compounds and to better understand the activities of T cells in vivo.
Design, evaluation, and screening methods for efficient targeted mutagenesis with transcription activator‐like effector nucleases in medaka
Authors: Ansai Satoshi , Inohaya Keiji , Yoshiura Yasutoshi , Schartl Manfred , Uemura Norihito , Takahashi Ryosuke , Kinoshita Masato
Published: November 2013

Genome editing using engineered nucleases such as transcription activator‐like effector nucleases (TALENs) has become a powerful technology for reverse genetics. In this study, we have described efficient detection methods for TALEN‐induced mutations at endogenous loci and presented guidelines of TALEN design for efficient targeted mutagenesis in medaka, Oryzias latipes. We performed a heteroduplex mobility assay (HMA) using an automated microchip electrophoresis system, which is a simple and high‐throughput method for evaluation of in vivo activity of TALENs and for genotyping mutant fish of F1 or later generations. We found that a specific pattern of mutations is dominant for TALENs harboring several base pairs of homologous sequences in target sequence. Furthermore, we found that a 5′ T, upstream of each TALEN‐binding sequence, is not essential for genomic DNA cleavage. Our findings provide information that expands the potential of TALENs and other engineered nucleases as tools for targeted genome editing in a wide range of organisms, including medaka.
Parvovirus B19 at the culprit coronary stenosis predicts outcome after stenting
Authors: Niccoli Giampaolo , Severino Anna , Pieroni Maurizio , Cosentino Nicola , Ventrone Maria A. , Conte Micaela , Roberto Marco , Gallinella Giorgio , Liuzzo Giovanna , Leone Antonio M. , Porto Italo , Burzotta Francesco , Trani Carlo , Crea Filippo
Published: November 2013

Background

Parvovirus (PV) B19 DNA is detected in endothelial cells and may cause endothelial dysfunction, which is involved in in‐stent restenosis. We aimed at performing an exploratory analysis that evaluated if PVB19 DNA at the culprit coronary stenosis would be associated with an increased rate of major adverse cardiac events (MACE) after coronary stenting.

Materials and methods

Consecutive patients undergoing stent implantation for stable or unstable coronary artery disease were enroled. Serology for PVB19 infection and presence of DNA for PVB19 on balloons used for predilatation were assessed in all patients. MACE rate, as a composite of cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularization (TLR) was obtained at 24 month follow‐up. Adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for variables associated with MACE.

Results

One hundred and nine patients [age 66 ± 10, male sex 89 (82%)] were enroled. At 24‐month follow‐up, 18 patients experienced a MACE. Two patients (2%) experienced MI, while 16 patients (15%) experienced clinically driven TLR. At multiple Cox regression analysis, the presence of PVB19 DNA on the balloon and the use of bare‐metal stents were independent predictors of MACE [HR 3·30, 95% CI (1·12–10·08), P = 0·03 and HR 4·19, 95% CI (1·60–10·94), P = 0·003].

Conclusions

PVB19 DNA detected on the balloon used for dilatation of coronary stenosis before stent implantation is associated with MACE rate at follow‐up, mainly due to clinically driven TLR. The results of this exploratory analysis should be confirmed in a larger population.
Reducing whiteflies on cucumber using intercropping with less preferred vegetables
Authors: Zhao Qing , Zhu Junwei J. , Qin Yuchuan , Pan Pengliang , Tu Hongtao , Du Wenxiao , Zhou Wangfang , Baxendale Frederick P.
Published: November 2013

The effectiveness of four less preferred vegetables – celery, asparagus lettuce, Malabar spinach, and edible amaranth – were investigated for suppression of two biotypes of sweet potato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) on cucumber, Cucumis sativus L. (Cucurbitaceae). Intercropping celery and Malabar spinach with cucumber significantly reduced whitefly numbers on cucumber. Y‐tube olfactometer behavioral assays revealed that whiteflies were strongly repelled from the aqueous extracts of the less preferred vegetables. The level of whitefly repellency varied with combinations of intercropped vegetables, and also differed between the two whitefly biotypes. For whitefly biotype B, the greatest repellency was observed with asparagus lettuce extract, whereas celery and Malabar spinach extracts were more repellent to whitefly biotype Q. Two major volatile constituent compounds were identified, D‐limonene from celery and geranyl nitrile from Malabar spinach. Sprayable 1% formulations of these compounds significantly reduced whitefly colonization on cucumber under field conditions.
Adverse effects of fluorescent dust marking on the behavior of western black widow spiderlings
Authors: Still Meghan B. , Miles Lindsay S. , Gburek Theresa M. , Johnson J. Chadwick
Published: November 2013

Fluorescent dust marking is commonly employed to identify and track small arthropods for studies of ecology, demography, and behavior. Despite its widespread use, no study to date has empirically tested the suitability of dust marking for studies of spider behavior. Here, we test the effects of fluorescent dust marking on proximity of cohabitation, sibling cannibalism, and non‐cannibalistic mortality of western black widow spiderlings, Latrodectus hesperus Chamberlin & Ivie (Araneae: Theridiidae). Results indicate that dust‐marked spiderlings cohabitated at closer proximities and died sooner than undusted spiderlings due to a greater incidence of cannibalism in the dust‐marked group. Thus, we conclude that fluorescent dust marking significantly affected the cohabitation and cannibalistic behavior of L. hesperus spiderlings. Although few studies have reported adverse effects of dust marking on arthropods, our results should serve as a warning to future studies that normal behavior may be disrupted by the use of these fluorescent dust markers. Therefore, preliminary testing should be routine when determining the suitability of any marking technique for not only new species, but also new life stages and behaviors.
Host removal as a potential control method for Phytophthora cinnamomi on severely impacted black gravel sites in the jarrah forest
Authors: Crone M. , McComb J. A. , O'Brien P. A. , Hardy G. E. St J.
Published: November 2013

Removal of living plants from an area of Eucalyptus marginata (jarrah) forest on black gravel sites infested with Phytophthora cinnamomi significantly reduced subsequent pathogen recovery. Vegetation, including trees and annual and herbaceous perennial plants, was killed on the sites by herbicide application. To determine whether this treatment efficiently eliminated P. cinnamomi, soil samples were seasonally collected and baited to test for the presence of the pathogen. There were no recoveries on treated sites in autumn, 28 months after removal of all vegetation by herbicide application. To test whether this was the result of the complete elimination of the pathogen or whether inoculum remained, regrowth on sites was not controlled after this period leading to the re‐establishment of annual and herbaceous perennial species, some of which are hosts of P. cinnamomi. Recovery of P. cinnamomi after plant regrowth on the formerly treated sites indicated that for complete pathogen removal, sites need to remain free of vegetation for longer than 28 months. Overall, however, this study confirms that the pathogen is a weak saprophyte, and withdrawal of host material for a period of time may make eventual rehabilitation of these sites possible.
Adolescent family perceptions in the At‐Risk Mental State for psychosis
Authors: Welsh Patrick , Tiffin Paul A.
Published: November 2013

Aim

There is a long‐standing interest in the relationship between patients affected by psychosis and their families. Previous research also suggests that perceived family dysfunction is a factor commonly associated with psychological problems in adolescence. The current study examined the role of self‐reported family perceptions in the context of adolescents with an At‐Risk Mental State (ARMS) for psychosis.

Methods

Family perceptions were obtained using the Family Perceptions Scale (FPS) and compared across three groups; an ARMS for psychosis group (n = 44), a first‐episode affective/non‐affective psychosis group (n = 26) and a control group (n = 140) drawn from a community population.

Results

Scores on the FPS Expressed Emotion subscale were significantly higher in the psychosis and ARMS groups, compared to controls (P = 0.039 and P = 0.041, respectively). In contrast, participants in the ARMS group reported poorer perceived problem solving and lower levels of nurturing behaviour in their families compared to controls (P = 0.032 and P = 0.027). Overall, family perceptions were not related to symptom severity in both the ARMS and psychosis groups (except for manic symptomatology and Expressed Emotion).

Conclusions

These findings highlight that ARMS patients are likely to report higher levels of perceived family dysfunction compared to a community sample of young people. However, the mechanisms by which family perceptions may contribute to the development of distressing psychotic symptoms remain unclear and require further study. Family work, with a focus upon improving perceived expressed emotion, nurturing behaviours and hostility may at this stage represent a feasible adjunct therapy for those with ARMS.
Determinants of Entrepreneurial Intent: A Meta–Analytic Test and Integration of Competing Models
Authors: Schlaegel Christopher , Koenig Michael
Published: November 2013

Increasing interest in the development of entrepreneurial intentions has elevated the importance of theories that predict and explain individuals’ propensity to start a firm. The purpose of this study is to meta–analytically test and integrate the theory of planned behavior and the entrepreneurial event model. We summarize the findings of 98 studies (123 samples, n = 114,007) and utilize meta–analytic structural equation modeling to examine the empirical fit of the competing theories and the integrated model. Our results demonstrate support for the competing theories and indicate the moderating role of contextual boundary conditions in the development of entrepreneurial intent. Furthermore, our findings suggest that the integrated model provides additional explanatory power and a fuller understanding of the process through which entrepreneurial intent develops.
An Effectual Approach to International Entrepreneurship: Overlaps, Challenges, and Provocative Possibilities
Authors: Sarasvathy Saras , Kumar K. , York Jeffrey G. , Bhagavatula Suresh
Published: November 2013

In this paper, we outline several interesting observations about international entrepreneurship (IE) research through the theoretical lens of effectuation. In doing so, we show how an effectual approach can help resolve four central conflicts and knowledge gaps identified in two recent comprehensive reviews of IE. We then present an illustrative case study from India that provides an intriguing comparison with the most recent modification of the Uppsala model to integrate with effectuation theory. Finally, we offer four provocative possibilities for future research at the intersection of IE and effectuation research.
High–Potential Concepts, Phenomena, and Theories for the Advancement of International Entrepreneurship Research
Authors: McDougall–Covin Patricia , Jones Marian V. , Serapio Manuel G.
Published: November 2013

The purpose of this special issue on international entrepreneurship (IE) is to explore concepts, phenomena, and theories with high potential to advance the field. Rather than identify concepts from the extant IE literature, we took the more novel approach of challenging leading researchers to write about IE–relevant issues through the perceptual lenses of their own, or other scholarly domains. Through this process of cross–fertilization, our intention was to generate new topics and fresh insights, alternative arguments, and constructs. The issue's seven articles enrich concepts and theories for IE; advance complementary, or competing arguments that underpin IE thinking; and open the IE dialogue to issues of current global significance.
Critical evaluation of root canal transportation by instrumentation
Authors: Bürklein Sebastian , Schäfer Edgar
Published: November 2013

Proper chemomechanical disinfection of the entire root canal system is required for a successful treatment outcome. Various techniques of mechanical root canal preparation have been introduced and described. Preservation of the integrity of the root canal anatomy and especially of the location of the apical foramen is important during mechanical root canal preparation. Despite the introduction of flexible nickel–titanium instruments and torque‐limited devices, root canal preparation of severely curved canals is still challenging and canals may be transported and/or other procedural errors may occur during preparation procedures. There are several aspects that influence the performance of root canal instruments with respect to their shaping ability. This article elucidates different parameters having an impact on canal transportation and discusses the impact of canal transportation on treatment outcomes.
Ultrasonics in endodontics
Authors: Park Ellen
Published: November 2013

The power of ultrasonic vibrations has been harnessed in the field of dentistry—evolving in its use and purpose—for just over 60 years. The first section of this review describes the evolution and various applications of ultrasound in dentistry, and examines in detail the ultrasonic tools that have been developed for endodontic purposes. The second section of this review describes the use of ultrasonics during specific endodontic procedures, from access to obturation, incorporating as much as possible the most recent and relevant research available to date.
Retracted: MicroRNA‐183 suppresses retinoblastoma cell growth, invasion and migration by targeting LRP6
Authors: Wang Jianwen , Wang Xiaochun , Li Zhongji , Liu Hongtao , Teng Yan
Published: November 2013

Our study demonstrates the downregulation of microRNA‐183 (miR‐183) in retinoblastoma (RB) tissues and RB cell lines compared with normal retinal tissues. The ectopic expression of miR‐183 in the RB cell lines Y79, SO‐RB50 and WERI‐RB1 suppresses cell viability, migration and invasion. Furthermore, the Wnt co‐receptor low‐density lipoprotein receptor‐related protein 6 (LRP6) was identified as a new target of miR‐183, and restoration of the expression of LRP6 rescues the effects induced by miR‐183 in RB cells. These results indicate that miR‐183 targets and downregulates LRP6 in the growth, migration and invasion of RB cells.
Platelet‐activating factor downregulates the expression of liver X receptor‐α and its target genes in human neutrophils
Authors: Reyes‐Quiroz María E. , Alba Gonzalo , Santa‐María Consuelo , Saenz Javier , Geniz Isabel , Jiménez Juan , Ramírez Remedios , Martín‐Nieto José , Pintado Elizabeth , Sobrino Francisco
Published: November 2013

Liver X receptors (LXRs) are ligand‐activated members of the nuclear receptor superfamily that regulate the expression of genes involved in lipid metabolism and inflammation, although their role in inflammation and immunity is less well known. It has been reported that oxysterols/LXRs may act as anti‐inflammatory molecules, although opposite actions have also been reported. In this study, we investigated the effect of platelet‐activating factor (PAF), a proinflammatory molecule, on LXRα signalling in human neutrophils. We found that PAF exerted an inhibitory effect on mRNA expression of TO901317‐induced LXRα, ATP‐binding cassette transporter A1, ATP‐binding cassette transporter G1, and sterol response element binding protein 1c. This negative action was mediated by the PAF receptor, and was dependent on the release of reactive oxygen species elicited by PAF, as it was enhanced by pro‐oxidant treatment and reversed by antioxidants. Current data also support the idea that PAF induces phosphorylation of the LXRα molecule in an extracellular signal‐regulated kinase 1/2‐mediated fashion. These results suggest that a possible mechanism by which PAF exerts its proinflammatory effect is through the downregulation of LXRα and its related genes, which supports the notion that LXRα ligands exert a modulatory role in the neutrophil‐mediated inflammatory response.
Single‐molecule enzymology à la Michaelis–Menten
Authors: Grima Ramon , Walter Nils G. , Schnell Santiago
Published: November 2013

Over the past 100 years, deterministic rate equations have been successfully used to infer enzyme‐catalysed reaction mechanisms and to estimate rate constants from reaction kinetics experiments conducted in vitro. In recent years, sophisticated experimental techniques have been developed that begin to allow the measurement of enzyme‐catalysed and other biopolymer‐mediated reactions inside single cells at the single‐molecule level. Time‐course data obtained using these methods are considerably noisy because molecule numbers within cells are typically quite small. As a consequence, the interpretation and analysis of single‐cell data requires stochastic methods, rather than deterministic rate equations. Here, we concisely review both experimental and theoretical techniques that enable single‐molecule analysis, with particular emphasis on the major developments in the field of theoretical stochastic enzyme kinetics, from its inception in the mid‐20th century to its modern‐day status. We discuss the differences between stochastic and deterministic rate equation models, how these depend on enzyme molecule numbers and substrate inflow into the reaction compartment, and how estimation of rate constants from single‐cell data is possible using recently developed stochastic approaches.