bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic glucokinase activator treatment at clinically translatable exposures gives durable glucose lowering in two animal models of type 2 diabetes
Authors: Baker D J , Wilkinson G P , Atkinson A M , Jones H B , Coghlan M , Charles A D , Leighton B
Published: November 2013

Background and Purpose

Pharmacological activation of glucokinase (GK) lowers blood glucose in animal models and humans, confirming proof of concept for this mechanism. However, recent clinical evidence from chronic studies suggests that the glucose‐lowering effects mediated by glucokinase activators (GKAs) are not maintained in patients with type 2 diabetes (T2D). Existing preclinical data with GKAs do not explain this loss of sustained glucose‐lowering efficacy in patients. Here, we have assessed the effects of chronic (up to 11 months) treatment with two different GKAs in two models of T2D.

Experimental Approach

Two validated animal models of T2D, insulin‐resistant obese Zucker rats and hyperglycaemic gkwt/del mice, were treated with two different GKAs for 1 or 11 months respectively at exposures that translate to clinical exposures in humans. Blood glucose, cholesterol, triglycerides and insulin were measured. GKA pharmacokinetics were also determined.

Key Results

Treatment with either GKA provided sustained lowering of blood glucose for up to 1 month in the Zucker rat and up to 11 months in hyperglycaemic gkwt/del mice, with maintained compound exposures. This efficacy was achieved without increases in plasma or hepatic triglycerides, accumulation of hepatic glycogen or impairment of glucose‐stimulated insulin secretion.

Conclusions and Implications

Chronic treatment with two GKAs in two animal models of diabetes provided sustained lowering of blood glucose, in marked contrast to clinical findings. Therefore, either these animal models of T2D are not good predictors of responses in human T2D or we need a better understanding of the consequences of GK activation in humans.
Judgments and Reasoning About Parental Discipline Involving Induction and Psychological Control in China and Canada
Authors: Helwig Charles C. , To Sharon , Wang Qian , Liu Chunqiong , Yang Shaogang
Published: November 2013

This study examined judgments and reasoning about four parental discipline practices (induction or reasoning and three practices involving “psychological control”; Barber, 1996; two forms of shaming and love withdrawal) among children (7–14 years of age) from urban and rural China and Canada (N = 288) in response to a moral transgression. Children from all settings critically evaluated love withdrawal and preferred induction. Despite being perceived as more common in China than in Canada, with age, parental discipline based on shaming or love withdrawal was increasingly negatively evaluated and believed to have detrimental effects on children's feelings of self‐worth and psychological well‐being. Some cultural variations were found in evaluations of practices, perceptions of psychological harm, and attribution of parental goals.
Ex-vivo whole blood secretion of interferon (IFN)-γ and IFN-γ-inducible protein-10 measured by enzyme-linked immunosorbent assay are as sensitive as IFN-γ enzyme-linked immunospot for the detection of gluten-reactive T cells in human leucocyte antigen (HLA)-DQ2·5+-associated coeliac disease
Authors: Ontiveros N , Tye-Din J A , Hardy M Y , Anderson R P
Published: November 2013

T cell cytokine release assays are used to diagnose infectious diseases, but not autoimmune or allergic disease. Coeliac disease (CD) is a common T cell-mediated disease diagnosed by the presence of gluten-dependent intestinal inflammation and serology. Many patients cannot be diagnosed with CD because they reduce dietary gluten before medical workup. Oral gluten challenge in CD patients treated with gluten-free diet (GFD) mobilizes gluten-reactive T cells measurable by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) or major histocompatibility complex (MHC) class II tetramers. Immunodominant peptides are quite consistent in the 90% of patients who possess HLA-DQ2·5. We aimed to develop whole blood assays to detect gluten-specific T cells. Blood was collected before and after gluten challenge from GFD donors confirmed to have CD (n = 27, all HLA-DQ2·5+), GFD donors confirmed not to have CD (n = 6 HLA-DQ2·5+, 11 HLA-DQ2·5−) and donors with CD not following GFD (n = 4, all HLA-DQ2·5+). Plasma IFN-γ and IFN-γ inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) after whole blood incubation with peptides or gliadin, and correlated with IFN-γ ELISPOT. No T cell assay could distinguish between CD patients and controls prior to gluten challenge, but after gluten challenge the whole blood IFN-γ ELISA and the ELISPOT were both 85% sensitive and 100% specific for HLA-DQ2·5+ CD patients; the whole blood IP-10 ELISA was 94% sensitive and 100% specific. We conclude that whole blood cytokine release assays are sensitive and specific for detection of gluten-reactive T cells in CD; further clinical studies addressing the utility of these tests in patients with an uncertain diagnosis of CD is warranted.
Using the Assessment Framework to measure parental mood: an investigation of the reliability of the Adult Well‐Being Scale
Authors: Pepping Christopher A. , Dawe Sharon , Harnett Paul H.
Published: November 2013

The adoption of evidence‐based practice in social work has been widely promoted in recent years and with this, a growing emphasis on the evaluation of practice using well‐validated and reliable measurement processes. The Department of Health's ‘Framework for the Assessment of Children in Need and their Families’ in the UK includes quantitative measures that form part of a systematic assessment of the needs of children and their families that includes assessment of parenting capacity and parental emotional state. The measure selected to assess parental mood was originally known as the Irritability, Depression and Anxiety Scale, and has been renamed within the Assessment Framework as the Adult Well‐Being Scale. This instrument is designed to assess depression, anxiety, and inward and outward irritability. However, there has been relatively little contemporary evaluation of the reliability and validity of the measure, and the extent to which it measures the four constructs it is designed to assess. This research therefore conducted extensive analyses of the reliability, validity and underlying factor structure of the Adult Well‐Being Scale. The four subscales did not demonstrate sound psychometric properties. At best a total score may be used as an indicator of ‘overall psychological distress’.
From Invisibility to Protection — Children in Prison with their Parent in Finland
Authors: Enroos Rosi
Published: November 2013

This article explores the process through which children in prison with their imprisoned parent have become a target of social concern in Finland. It is asked how the new social problem of ‘children in prison’ has been constructed. The data consist of relevant parts of the legislation and official documents. Three phases of social problem construction are named: (i) Children in prison as a practical and private matter; (ii) intense debate, problem formulation and developing practices and (iii) a public institutionalised practice. The position of children changed from one of invisibility to the target of protection. On the basis of children's rights, children in prison became understood as a group of children who are in need of child protection services. This example demonstrates how the images of problems construct solutions for practices.
Body mass index and depressive symptoms in primary care settings: examining the moderating roles of smoking status, alcohol consumption and vigorous exercise
Authors: Hooker S. A. , MacGregor K. L. , Funderburk J. S. , Maisto S. A.
Published: November 2013

What is already known about this subject

Depressive symptoms and obesity are highly prevalent in primary care settings.

Depressive symptoms and obesity are positively related; as body weight increases, individuals are more likely to display depressive symptoms.

What this study adds

This study examines the moderating roles of health behaviours (alcohol use, smoking status and vigorous exercise) on the relationship between body mass index and depressive symptoms.

Exercise attenuates the relationship between depressive symptoms and obesity.

Primary care patients often report multiple health risk behaviours and symptoms, including obesity and depressive symptomatology. This study examined the relationship between body mass index (BMI) and depressive symptomatology among primary care patients and tested its moderation by health behaviours. Primary care patients (n = 497) completed self‐report questionnaires. Using three multilevel models, we tested the moderation of health behaviours on the BMI‐depressive symptoms relationship. After controlling for relevant covariates, BMI was positively related to depressive symptoms. Smokers reported more depressive symptoms (P < 0.01), whereas vigorous exercisers reported fewer (P < 0.001). Alcohol consumption was not related to depressive symptoms (P > 0.05). Only vigorous exercise significantly moderated the BMI‐depression relationship (P < 0.05). BMI is positively related to depressive symptoms among patients who do not participate in vigorous activity, suggesting that vigorous activity reduces the risk for depressive symptoms among patients with higher BMI.
Relations between Species Rarity, Vulnerability, and Range Contraction for a Beetle Group in a Densely Populated Region in the Mediterranean Biodiversity Hotspot
Authors: FATTORINI SIMONE
Published: November 2013

Rarity is often considered an indication of species extinction risk, and it is frequently used to obtain measures of species vulnerability. However, there is no strong evidence of a correlation between species vulnerability and threat. Moreover, there is no consensus about how rarity should be measured. I used a multidimensional characterization of species rarity to calculate a vulnerability index for tenebrionid beetles inhabiting an Italian region in the Mediterranean biodiversity hotspot. I used different metrics to examine 3 dimensions of rarity: species range, ecology, and population. Species with rarity values below the median were scored as rare for each dimension. I combined rarity scores into a vulnerability index. I then correlated species vulnerability with range trends (expanded vs. contracted). Different measures of the same rarity dimension were strongly correlated and produced similar vulnerability scores. This result indicates rarity‐based vulnerability estimates are slightly affected by the way a certain rarity dimension is measured. Vulnerability was correlated with range trends; species with the highest vulnerability had the strongest range contraction. However, a large number of common species also underwent range contraction in the last 50 years, and there was no clear relation between range contraction and their ecology. This indicates that in general human‐induced environmental changes affected species irrespective of their assumed vulnerability and that focusing only on rare species may severely bias perceptions of the extent of species decline.

Relaciones entre Rareza de Especies, Vulnerabilidad y Contracción de Distribución Geográfica para un Grupo de Escarabajos en una Región Densamente Poblada en el Hotspot de Biodiversidad del Mediterráneo
Design Strategy for a Smoking Cessation Trial of Survival
Authors: Shuster Jonathan J.
Published: November 2013

Despite unequivocal evidence that smoking cessation is beneficial in terms of survival, there is at present no firm evidence that smoking cessation programs save lives. While they do increase quit rates, the collective evidence from randomized trials is inconclusive with respect to long‐term survival. Withdrawal symptoms and the potential for harm when a subjects relapses after a prolonged period of cessation (e.g., 5+ years) might mitigate some or all of the benefits of the sustained quitters. This paper will review the key survival epidemiology and argue for a large randomized field trial of about 30,000 subjects, followed personally for 5 years and collectively for 15 years through the National Death Index. The intervention should be personalized, but reproducible through a treatment assignment algorithm. Personal coaching should be a major part of the intervention. Important short‐term data on healthcare utilization should also be collected. Strong financial motivation for quitting (or prevention of smoking in the first place) is also presented. This paper is intended to motivate a large collective effort amongst the US Clinical and Translational Science Awardees to design the intervention and bring together the interested players to conduct the study.
Early Detection of Left Ventricular Contractility Abnormalities by Two‐Dimensional Speckle Tracking Strain in Chagas' Disease
Authors: Barbosa Marcia M , Rocha Manoel O Costa , Vidigal Daniel Furtado , de Carvalho Bicalho Carneiro Renata , Araújo Rafaela Drumond , Palma Mariana Campos , de Barros Marcio Vinicius Lins , Nunes Maria Carmo P
Published: November 2013

Background

Chagas' disease is an important cause of heart failure, and early identification of cardiac involvement may help to identify patients at risk for disease progression. Two‐dimensional (2D) speckle tracking (ST) strain seems to be a useful tool to detect incipient ventricular dysfunction. This study aims to analyze if 2D strain can detect contractility abnormalities in asymptomatic patients with Chagas' disease.

Methods

Seventy‐eight asymptomatic Chagas' disease patients (46% male; age 44.7 ± 8.6 years) with normal cardiovascular exams and a control group of 38 healthy subjects (58% male; age 44.1 ± 9.2 years) were included in the study. Using 2D strain software, left ventricular (LV) end‐systolic longitudinal, radial, and circumferential strain were measured. Global right ventricular (RV) longitudinal strain was also assessed.

Results

Echocardiographic parameters of LV systolic and diastolic function were similar between patients and controls. 2D longitudinal strain in the basal inferior, and inferoseptal walls, as well as apical segment of the inferolateral wall were lower in patients compared with controls. 2D radial strain was reduced in several segments of the LV walls as well as the global radial strain. 2D circumferential strain at the basal segment of the anterior wall showed a lower value in patients compared with controls, whereas global circumferential strain was similar between patients and controls. 2D RV strain did not differ between groups.

Conclusion

In a subgroup of asymptomatic patients with Chagas' disease without evident cardiac involvement, 2D strain was reduced compared with healthy individuals, suggesting incipient LV dysfunction in these patients. 2D ST strain has the potential for detecting early myocardial impairment in the setting of Chagas' disease.
Fish oil improves anxiety‐like, depressive‐like and cognitive behaviors in olfactory bulbectomised rats
Authors: Pudell Claudia , Vicente Bianca A. , Delattre Ana M. , Carabelli Bruno , Mori Marco A. , Suchecki Deborah , Machado Ricardo B. , Zanata Sílvio M. , Visentainer Jesuí V. , de Oliveira Santos Oscar , Lima Marcelo M. S. , Ferraz Anete C.
Published: November 2013

Depression is increasingly present in the population, and its pathophysiology and treatment have been investigated with several animal models, including olfactory bulbectomy (Obx). Fish oil (FO) supplementation during the prenatal and postnatal periods decreases depression‐like and anxiety‐like behaviors. The present study evaluated the effect of FO supplementation on Obx‐induced depressive‐like behavior and cognitive impairment. Female rats received supplementation with FO during habituation, mating, gestation, and lactation, and their pups were subjected to Obx in adulthood; after the recovery period, the adult offspring were subjected to behavioral tests, and the hippocampal levels of brain‐derived neurotrophic factor (BDNF), serotonin (5‐HT) and the metabolite 5‐hydroxyindoleacetic (5‐HIAA) were determined. Obx led to increased anxiety‐like and depressive‐like behaviors, and impairment in the object location task. All behavioral changes were reversed by FO supplementation. Obx caused reductions in the levels of hippocampal BDNF and 5‐HT, whereas FO supplementation restored these levels to normal values. In control rats, FO increased the hippocampal level of 5‐HT and reduced that of 5‐HIAA, indicating low 5‐HT metabolism in this brain region. The present results indicate that FO supplementation during critical periods of brain development attenuated anxiety‐like and depressive‐like behaviors and cognitive dysfunction induced by Obx. These results may be explained by increased levels of hippocampal BDNF and 5‐HT, two major regulators of neuronal survival and long‐term plasticity in this brain structure.
The transcription factor CCAAT enhancer‐binding protein β protects rat cerebellar granule neurons from apoptosis through its transcription‐activating isoforms
Authors: Peña‐Altamira Emiliano , Polazzi Elisabetta , Moretto Edoardo , Lauriola Mattia , Monti Barbara
Published: November 2013

CCAAT enhancer‐binding protein β is a transcription factor that is involved in many brain processes, although its role in neuronal survival/death remains unclear. By using primary cultures of rat cerebellar granule neurons, we have shown here that CCAAT enhancer‐binding protein β is present as all of its isoforms: the transcriptional activators liver activator proteins 1 and 2, and the transcriptional inhibitor liver inhibitory protein. We have also shown that liver activator protein 1 undergoes post‐translational modifications, such as phosphorylation and sumoylation. These isoforms have different subcellular localizations, liver activator protein 2 being found in the cytosolic fraction only, liver inhibitory protein in the nucleus only, and liver activator protein 1 in both fractions. Through neuronal apoptosis induction by shifting mature cerebellar granule neurons to low‐potassium medium, we have demonstrated that nuclear liver activator protein 1 expression decreases and its phosphorylation disappears, whereas liver inhibitory protein levels increase in the nuclear fraction, suggesting a pro‐survival role for liver activator protein transcriptional activation and a pro‐apoptotic role for liver inhibitory protein transcriptional inhibition. To confirm this, we transfected cerebellar granule neurons with plasmids expressing liver activator protein 1, liver activator protein 2, or liver inhibitory protein respectively, and observed that both liver activator proteins, which increase CCAAT‐dependent transcription, but not liver inhibitory protein, counteracted apoptosis, thus demonstrating the pro‐survival role of liver activator proteins. These data significantly improve our current understanding of the role of CCAAT enhancer‐binding protein β in neuronal survival/apoptosis.
Developing intentionality and researching multilingually: An ecological and methodological perspective
Authors: Stelma Juup , Fay Richard , Zhou Xiaowei
Published: November 2013

This paper uses an ecological perspective to understand a researcher's developing intentionalityvis‐à‐visher multilingual engagement with research processes, namely, ‘researching multilingually’. The paper discusses ecological thinking inAppliedLinguistics, ecological themes present in the literature addressing aspects of researching multilingually, and the particular understanding of intentionality we have employed. The potential of intentionality as an heuristic for understanding researching multilingually is explored with reference to a recent research experience of one of the authors –XiaoweiZhou. This includes analyses ofXiaowei's developing awareness of linguistic possibilities, associated research‐relevant affordances, and her articulation of the intentionality of researching multilingually. We suggest that the combination of an ecological perspective and a focus on intentionality provides a unique methodological understanding of researching multilingually.
Alginate coatings containing grapefruit essential oil or grapefruit seed extract for grapes preservation
Authors: Aloui Hajer , Khwaldia Khaoula , Sánchez‐González Laura , Muneret Laurence , Jeandel Carole , Hamdi Moktar , Desobry Stéphane
Published: November 2013

Biodegradable coatings based on 1% and 2% sodium alginate (NaAlg) with and without grapefruit seed extract (GSE) or grapefruit essential oil (GEO) were applied to table grapes to preserve their quality. Changes in weight loss, firmness and antioxidant activity were assessed over 15 days of cold storage. The effectiveness of developed coatings to control postharvest decay of inoculated grape berries stored for 5 days at 20 °C was also investigated. Biodegradable coatings based on pure NaAlg and those containing GSE were efficient in reducing weight loss and maintaining firmness during storage. Coatings incorporating either GEO or GSE were able to preserve the antioxidant activity of treated grapes and to reduce decay incidence in inoculated fruits. Coatings formulated with 2% NaAlg‐1% GSE showed the greatest preservation of antioxidant activity and the highest antifungal effect, with an effective control of water and firmness losses. These coatings can be recommended for maintaining table grapes quality.
The role of intracavernosal injection therapy and the reasons of withdrawal from therapy in patients with erectile dysfunction in the era of PDE5 inhibitors
Authors: Sung H. H. , Ahn J. S. , Kim J. J. , Choo S. H. , Han D. H. , Lee S. W.
Published: November 2013

There has been little data regarding the role of intracavernosal injection (ICI) treatment, its discontinuation rate and the reasons of withdrawal in patients with erectile dysfunction (ED) in the era of phosphodiesterase type 5 (PDE5) inhibitors. The aim of this study was to investigate the rate of withdrawal and its associated reasons in patients undergoing ICI therapy. Patients who were prescribed with ICI treatment two times or more were included since the introduction of sildenafil in Korea in 1999. Telephone surveys were performed to evaluate intercourse rates, withdrawal rates and their associated reasons, adverse events and the patients' satisfaction with their sex lives after the ICI treatments. Two hundred and ninety‐four men were contacted by telephone. The mean age was 61.8 ± 7.9 years with a follow‐up duration of 25.6 ± 32.1 months. At the last follow‐up, 79.9% had discontinued the treatment. Most patients had previously failed PDE5 inhibitor treatment prior to the ICI therapy, and more than half had two or more risk factors of ED. Adequate penile rigidity after ICI therapy was restored in 60.2% of patients. The reasons for discontinuation of ICI were poor response (43.1%), inconvenience of use (18.3%), switch to other treatments (10.7%), loss of libido (6.7%), adverse events (5.5%) and return of spontaneous erection (2.8%). Pain was the most common adverse event in the withdrawal group, whereas prolonged erection was most common in the continuing group. Following ICI treatment, PDE5 inhibitors were the most common therapeutic option (63.1%). The overall satisfaction rate regarding sex life was significantly high in the treatment‐continuing group. In conclusion, patients on ICI treatment had severe ED and high withdrawal rates in the era of PDE5 inhibitors. The most common reason for treatment discontinuation was poor response. Before initiating ICI treatments, sufficient counselling is necessary.
Real‐Time Contact Force Sensing for Pulmonary Vein Isolation in the Setting of Paroxysmal Atrial Fibrillation: Procedural and 1‐Year Results
Authors: MARIJON ELOI , FAZAA SAMIA , NARAYANAN KUMAR , GUY‐MOYAT BENOIT , BOUZEMAN ABDESLAM , PROVIDENCIA RUI , TREGUER FREDERIC , COMBES NICOLAS , BORTONE AGUSTIN , BOVEDA SERGE , COMBES STEPHANE , ALBENQUE JEAN‐PAUL
Published: November 2013

Real‐Time Contact Force Sensing for Pulmonary Vein Isolation

Introduction

The additional benefit of contact force (CF) technology during pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (AF) to improve mid‐term clinical outcome is unclear.

Methods and Results

Eligible patients with symptomatic paroxysmal AF were enrolled in this prospective trial, comparing circular antral catheter ablation (guided by Carto 3 System, Biosense Webster) using either a new open‐irrigated CF catheter (SmartTouch Thermocool, Biosense Webster) (CF group) or a non‐CF open‐irrigated catheter (EZ Steer Thermocool, Biosense Webster) (control group). Overall, 30 patients were enrolled in each group, with a standardized 12‐month follow‐up, free of antiarrhythmic therapy. Demographic, cardiovascular and anatomic characteristics were similar in both groups. Though complete PVI was eventually achieved in all cases in both groups, success using an exclusive anatomic approach was 80.0% in CF group versus 36.7% in control group (P < 0.0001). CF use was associated with significant reductions in fluoroscopy exposure (P < 0.01) and radiofrequency time (P = 0.01). The incidence rates of AF recurrence were 10.5% (95% CI, 1.38–22.4) in the CF group, and 35.9% (95% CI, 12.4–59.4) in the control group (log rank test, P = 0.04). After adjustment on potential confounders, the use of CF catheter was found to be associated with a lower AF recurrence (OR 0.18, 95% CI 0.04–0.94, P = 0.04).

Conclusion

Our findings suggest a potential benefit of real‐time CF sensing technology, in reducing AF recurrence during the first year after PVI.
Diapause termination of Rhagoletis cerasi pupae is regulated by local adaptation and phenotypic plasticity: escape in time through bet‐hedging strategies
Authors: Moraiti C. A. , Nakas C. T. , Papadopoulos N. T.
Published: November 2013

Persistence and thriving of univoltine, herbivore insect species of the temperate zone rely on obligate diapause response that ensures winter survival and synchronization with host phenology. We used a stenophagous fruit fly (Rhagoletis cerasi) with obligate pupae diapause to determine genetic and environmental effects on diapause intensity of geographically isolated populations with habitat heterogeneity. Pupae from two Greek and one German populations with various gene flow rates were exposed at five constant chilling temperatures (0–12 °C) for different durations and then incubated at a high temperature until all adults have emerged. Pupae diapause intensity differs among Greek and German populations, suggesting an adaptive response to habitat heterogeneity (mostly differences in phenology patterns of local host cultivars). Moderately warm winter temperatures, such as 8 °C, promote diapause termination in all three populations. Insufficient chilling (short duration or warmer temperatures) regulates the expression of prolonged dormancy. Interestingly, extended chilling (longer than required for terminating diapause) ‘return’ pupae to another (facultative) cycle of dormancy enabling adults to emerge during the next appropriate ‘window of time’; a strategy first time reported for univoltine insects. Consequently, diapause duration of R. cerasi is determined both by i) the adaptive response to local climatic conditions (annual dormancy) and ii) the plastic responses to interannual climatic variability resulting in two types of long life cycles within populations, prolonged and facultative dormancy as response to insufficient chilling and extended exposure to chilling, respectively. Long life cycles are expressed as a part of dormancy bet‐hedging strategies of R. cerasi populations.
EFA6A, a guanine nucleotide exchange factor for Arf6, interacts with sorting nexin‐1 and regulates neurite outgrowth
Authors: Fukaya Masahiro , Fukushima Daisuke , Hara Yoshinobu , Sakagami Hiroyuki
Published: November 2013

The membrane trafficking and actin cytoskeleton remodeling mediated by ADP ribosylation factor 6 (Arf6) are functionally linked to various neuronal processes including neurite formation and maintenance, neurotransmitter release, and receptor internalization. EFA6A is an Arf6‐specific guanine nucleotide exchange factor that is abundantly expressed in the brain. In this study, we identified sorting nexin‐1 (SNX1), a retromer component that is implicated in endosomal sorting and trafficking, as a novel interacting partner for EFA6A by yeast two‐hybrid screening. The interaction was mediated by the C‐terminal region of EFA6A and a BAR domain of SNX1, and further confirmed by pull‐down assay and immunoprecipitation from mouse brain lysates. In situ hybridization analysis demonstrated the widespread expression of SNX1 in the mouse brain, which overlapped with the expression of EFA6A in the forebrain. Immunofluorescent analysis revealed the partial colocalization of EFA6A and SNX1 in the dendritic fields of the hippocampus. Immunoelectron microscopic analysis revealed the overlapping subcellular localization of EFA6A and SNX1 at the post‐synaptic density and endosomes in dendritic spines. In Neuro‐2a neuroblastoma cells, expression of either EFA6A or SNX1 induced neurite outgrowth, which was further enhanced by co‐expression of EFA6A and SNX1. The present findings suggest a novel mechanism by which EFA6A regulates Arf6‐mediated neurite formation through the interaction with SNX1.

image

We identified sorting nexin‐1 (SNX1) as a novel binding partner for EFA6A, and demonstrated overlapping ultrastructural localization of EFA6A and SNX1 in spines and dendrites of hippocampal neurons. Furthermore, we showed that this interaction enhanced neurite outgrowth of Neuro‐2a cells. The present findings suggest the importance of the interaction between EFA6A and SNX1 in Arf6‐mediated neuronal functions in dendritic spines.
Effects of Cognitive Strategy Interventions and Cognitive Moderators on Word Problem Solving in Children at Risk for Problem Solving Difficulties
Authors: Swanson H. Lee , Lussier Cathy , Orosco Michael
Published: November 2013

This study investigated the role of strategy instruction and cognitive abilities on word problem solving accuracy in children with math difficulties (MD). Elementary school children (N = 120) with and without MD were randomly assigned to 1 of 4 conditions: general‐heuristic (e.g., underline question sentence), visual‐schematic presentation (diagrams), general‐heuristic + visual‐schematic, and an untreated control. When compared to the control condition that included children with MD, an advantage at posttest was found for children with MD for the visual‐schematic‐alone condition on measures of problem solving and calculation accuracy, whereas all strategy conditions facilitated posttest performance in correctly identifying problem solving components. The results also suggested that strategy conditions drew upon different cognitive resources. The General‐heuristic condition drew primarily upon the executive component of working memory (WM), Visual‐schematic condition drew upon the visual component of WM and the combined strategies condition drew upon number processing skills.
A gene with major phenotypic effects as a target for selection vs. homogenizing gene flow
Authors: Raeymaekers Joost A. M. , Konijnendijk Nellie , Larmuseau Maarten H. D. , Hellemans Bart , De Meester Luc , Volckaert Filip A. M.
Published: November 2013

Genes with major phenotypic effects facilitate quantifying the contribution of genetic vs. plastic effects to adaptive divergence. A classical example is Ectodysplasin (Eda), the major gene controlling lateral plate phenotype in three‐spined stickleback. Completely plated marine stickleback populations evolved repeatedly towards low‐plated freshwater populations, representing a prime example of parallel evolution by natural selection. However, many populations remain polymorphic for lateral plate number. Possible explanations for this polymorphism include relaxation of selection, disruptive selection or a balance between divergent selection and gene flow. We investigated 15 polymorphic stickleback populations from brackish and freshwater habitats in coastal North‐western Europe. At each site, we tracked changes in allele frequency at theEdagene between subadults in fall, adults in spring and juveniles in summer.Edagenotypes were also compared for body size and reproductive investment. We observed a fitness advantage for theEdaallele for the low morph in freshwater and for the allele for the complete morph in brackish water. Despite these results, the differentiation at theEdagene was poorly correlated with habitat characteristics. Neutral population structure was the best predictor of spatial variation in lateral plate number, suggestive of a substantial effect of gene flow. A meta‐analysis revealed that the signature of selection atEdawas weak compared to similar studies in stickleback. We conclude that a balance between divergent selection and gene flow can maintain stickleback populations polymorphic for lateral plate number and that ecologically relevant genes may not always contribute much to local adaptation, even when targeted by selection.
Interplay of the fungal sumoylation network for control of multicellular development
Authors: Harting Rebekka , Bayram Özgür , Laubinger Karen , Valerius Oliver , Braus Gerhard H.
Published: November 2013

The role of the complex network of the ubiquitin‐like modifier SumO in fungal development was analysed. SumO is not only required for sexual development but also for accurate induction and light stimulation of asexual development. The Aspergillus nidulans COMPASS complex including its subunits CclA and the methyltransferase SetA connects the SumO network to histone modification. SetA is required for correct positioning of aerial hyphae for conidiophore and asexual spore formation. Multicellular fungal development requires sumoylation and desumoylation. This includes the SumO processing enzyme UlpB, the E1 SumO activating enzyme AosA/UbaB, the E2 conjugation enzyme UbcN and UlpA as major SumO isopeptidase. Genetic suppression analysis suggests a connection between the genes for the Nedd8 isopeptidase DenA and the SumO isopeptidase UlpA and therefore a developmental interplay between neddylation and sumoylation in fungi. Biochemical evidence suggests an additional connection of the fungal SumO network with ubiquitination. Members of the cellular SumO network include histone modifiers, components of the transcription, RNA maturation and stress response machinery, or metabolic enzymes. Our data suggest that the SumO network controls specific temporal and spatial steps in fungal differentiation.
The haustorial transcriptomes of Uromyces appendiculatus and Phakopsora pachyrhizi and their candidate effector families
Authors: Link Tobias I. , Lang Patrick , Scheffler Brian E. , Duke Mary V. , Graham Michelle A. , Cooper Bret , Tucker Mark L. , van de Mortel Martijn , Voegele Ralf T. , Mendgen Kurt , Baum Thomas J. , Whitham Steven A.
Published: November 2013

Haustoria of biotrophic rust fungi are responsible for the uptake of nutrients from their hosts and for the production of secreted proteins, known as effectors, which modulate the host immune system. The identification of the transcriptome of haustoria and an understanding of the functions of expressed genes therefore hold essential keys for the elucidation of fungus–plant interactions and the development of novel fungal control strategies. Here, we purified haustoria from infected leaves and used 454 sequencing to examine the haustorial transcriptomes of Phakopsora pachyrhizi and Uromyces appendiculatus, the causal agents of soybean rust and common bean rust, respectively. These pathogens cause extensive yield losses in their respective legume crop hosts. A series of analyses were used to annotate expressed sequences, including transposable elements and viruses, to predict secreted proteins from the assembled sequences and to identify families of candidate effectors. This work provides a foundation for the comparative analysis of haustorial gene expression with further insights into physiology and effector evolution.
Ectoparasites in urban stray cats in Jerusalem, Israel: differences in infestation patterns of fleas, ticks and permanent ectoparasites
Authors: SALANT H. , MUMCUOGLU K. Y. , BANETH G.
Published: November 2013

In a period cross‐sectional study performed to examine ectoparasites on 340 stray cats in Jerusalem, Israel, 186 (54.7%) were infested with the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae), 49 (14.4%) with the cat louse, Felicola subrostratus (Phthiraptera: Trichodectidae), 41 (12.0%) with the ear mite, Otodectes cynotis (Astigmata: Psoroptidae), three (0.9%) with the fur mite, Cheyletiella blakei (Trobidiformes: Cheyletidae), two (0.6%) with the itch mite Notoedres cati (Astigmata: Sarcoptidae), and 25 (7.3%) with ticks of the species Rhipicephalus sanguineus sensu lato (Ixodida: Ixodidae), Rhipicephalus turanicus or Haemaphysalis adleri (Ixodida: Ixodidae). A higher number of flea infestations was observed in apparently sick cats (P < 0.05) and in cats aged < 6 months (P < 0.05). The proportion of flea‐infested cats (P < 0.01), as well as the number of fleas per infested cat (P < 0.01), was higher in autumn than in other seasons. By contrast with findings in cats with flea infestations, rates of infestation with ticks were higher amongst cats with clinical signs (P < 0.01) and cats aged ≥ 6 months (P < 0.05). The high rates of ectoparasite infestation in the cats studied constitute a risk for the spread of vector‐borne infections of zoonotic and veterinary importance.
TO LEARN OR TO CHANGE: OPTIMAL R&D INVESTMENTS UNDER UNCERTAINTY IN THE CASE OF CLIMATE CHANGE
Authors: MIAO RUIQING , HENNESSY DAVID A.
Published: November 2013

When studying R&D investments in technologies that address potential damage from climate change (termed as “research to change” or RTC), current literature overlooks the effects of purchased learning (i.e., learn through scientific research, termed as “research to learn” or RTL) about climate change. We investigate interactions between optimal R&D investments in RTC and RTL under uncertainty in climate change and research outcomes, while accounting for the positive impact that successful RTL may have on RTC outcome. We find that simultaneously investing in both RTL and RTC may be optimal when the probability that climate change imposes a specific level of damage is either moderate or very high and when RTL cost is relatively low. Whenever RTL and RTC are conducted simultaneously, then they substitute. However, when it is not optimal to conduct RTC and RTL simultaneously, then an increase in RTC cost decreases, at least weakly, RTL investment (i.e., RTL and RTC complement). When the probability that climate change imposes damage increases, then the optimal RTL investment may first decrease and then increase. Moreover, we identify conditions under which either the precautionary principle or the learn‐then‐act principle should be followed regarding R&D investments.
Organ‐specific phosphorus‐allocation patterns and transcript profiles linked to phosphorus efficiency in two contrasting wheat genotypes
Authors: AZIZ TARIQ , FINNEGAN PATRICK M. , LAMBERS HANS , JOST RICARDA
Published: November 2013

Recent studies have identified genotypic variation in phosphorus (P) efficiency, but rarely have the underlying mechanisms been described at the molecular level. We demonstrate that the highly P‐efficient wheat (Triticum aestivum L.) cultivar Chinese 80‐55 maintains higher inorganic phosphate (Pi) concentrations in all organs upon Pi withdrawal in combination with higher Pi acquisition in the presence of Pi when compared with the less‐efficient cultivar Machete. These findings correlated with differential organ‐specific expression of Pi transporters TaPHT1;2, TaPHT1;5, TaPHT1;8, TaPHT2;1 and H+‐ATPase TaHa1. Observed transcript level differences between the cultivars suggest that higher de novo phospholipid biosynthetic activities in Pi‐limited elongating basal leaf sections are another crucial adaptation in Chinese 80‐55 for sustaining growth upon Pi withdrawal. These activities may be supported through enhanced breakdown of starch in Chinese 80‐55 stems as suggested by higher TaGPho1 transcript levels. Chinese 80‐55 fine roots on the other hand show strong suppression of transcripts involved in glycolysis, transcriptional regulation and ribosomal activities. Our work reveals major differences in the way the two contrasting cultivars allocate Pi and organic P compounds between source and sink tissues and in the acclimation of their metabolism to changes in Pi availability.
Desiccation tolerance of Sphagnum revisited: a puzzle resolved
Authors: Hájek T. , Vicherová E.
Published: November 2013

As ecosystem engineers, Sphagnum mosses control their surroundings through water retention, acidification and peat accumulation. Because water retention avoids desiccation, sphagna are generally intolerant to drought; however, the literature on Sphagnum desiccation tolerance (DT) provides puzzling results, indicating the inducible nature of their DT. To test this, various Sphagnum species and other mesic bryophytes were hardened to drought by (i) slow drying; (ii) ABA application and (iii) chilling or frost. DT tolerance was assessed as recovery of chlorophyll fluorescence parameters after severe desiccation. We monitored the seasonal course of DT in bog bryophytes. Under laboratory conditions, following initial de‐hardening, untreated Sphagnum shoots lacked DT; however, DT was induced by all hardening treatments except chilling, notably by slow drying, and in Sphagnum species of the section Cuspidata. In the field, sphagna in hollows and lawns developed DT several times during the growing season, responding to reduced precipitation and a lowered water table. Hummock and aquatic species developed DT only in late autumn, probably as a response to frost. Sphagnum protonemata failed to develop DT; hence, desiccation may limit Sphagnum establishment in drier habitats with suitable substrate chemistry. Desiccation avoiders among sphagna form compact hummocks or live submerged; thus, they do not develop DT in the field, lacking the initial desiccation experience, which is frequent in hollow and lawn habitats. We confirmed the morpho‐physiological trade‐off: in contrast to typical hollow sphagna, hummock species invest more resources in water retention (desiccation avoidance), while they have a lower ability to develop physiological DT.
Disentangling the Influence of Value Predispositions and Risk/Benefit Perceptions on Support for Nanotechnology Among the American Public
Authors: Kim Jiyoun , Yeo Sara K. , Brossard Dominique , Scheufele Dietram A. , Xenos Michael A.
Published: November 2013

Using nanotechnology as a case study, this article explores (1) how people's perceptions of benefits and risks are related to their approval of nanotechnology, (2) which information‐processing factors contribute to public risk/benefit perceptions, and (3) whether individuals’ predispositions (i.e., deference to scientific authority and ideology) may moderate the relationship between cognitive processing and risk perceptions of the technology. Results indicate that benefit perceptions positively affect public support for nanotechnology; perceptions of risk tend to be more influenced by systematic processing than by heuristic cues, whereas both heuristic and systematic processing influence benefit perceptions. People who are more liberal‐minded tend to be more affected by systematic processing when thinking about the benefits of nanotechnology than those who are more conservative. Compared to less deferent individuals, those who are more deferent to scientific authority tend to be less influenced by systematic processing when making judgments about the benefits and risks of nanotechnology. Implications are discussed.
Advice to Risk Assessors Modeling Viral Health Risk Associated with Household Graywater
Authors: O'Toole Joanne , Sinclair M. , Fiona Barker S. , Leder Karin
Published: November 2013

Quantitative microbial risk assessment (QMRA) is a valuable tool that can be used to predict the risk associated with human exposure to specific microbial contaminants in water sources. The transparency inherent in the QMRA process benefits discussions between multidisciplinary teams because members of such teams have different expertise and their confidence in the risk assessment output will depend upon whether they regard the selected input data and assumptions as being suitable and/or plausible. Selection of input data requires knowledge of the availability of appropriate data sets, the limitations of using a particular data set, and the logic of using alternative approaches. In performing QMRA modeling and in the absence of directly relevant data, compromises must be made. One such compromise made is to use available Escherichia coli data and apply a ratio of enteric viruses to indicator E. coli in wastewater obtained from prior studies to estimate the concentration of enteric viruses in other wastewater types/sources. In this article, we have provided an argument for why we do not recommend the use of a pathogen to E. coli ratio to estimate virus concentrations in single household graywater and additionally suggested circumstances in which use of such a ratio may be justified.
Emulating a Gravity Model to Infer the Spatiotemporal Dynamics of an Infectious Disease
Authors: Jandarov Roman , Haran Murali , Bjørnstad Ottar , Grenfell Bryan
Published: November 2013

Probabilistic models for infectious disease dynamics are useful for understanding the mechanism underlying the spread of infection. When the likelihood function for these models is expensive to evaluate, traditional likelihood-based inference may be computationally intractable. Furthermore, traditional inference may lead to poor parameter estimates and the fitted model may not capture important biological characteristics of the observed data. We propose a novel approach for resolving these issues that is inspired by recent work in emulation and calibration for complex computer models. Our motivating example is the gravity time series susceptible–infected–recovered model. Our approach focuses on the characteristics of the process that are of scientific interest. We find a Gaussian process approximation to the gravity model by using key summary statistics obtained from model simulations. We demonstrate via simulated examples that the new approach is computationally expedient, provides accurate parameter inference and results in a good model fit. We apply our method to analyse measles outbreaks in England and Wales in two periods: the prevaccination period from 1944 to 1965 and the vaccination period from 1966 to 1994. On the basis of our results, we can obtain important scientific insights about the transmission of measles. In general, our method is applicable to problems where traditional likelihood-based inference is computationally intractable or produces a poor model fit. It is also an alternative to approximate Bayesian computation when simulations from the model are expensive.
Species richness estimates of Blattodea s.s. (Insecta: Dictyoptera) from northern Guyana vary depending upon methods of species delimitation
Authors: EVANGELISTA DOMINIC A. , BOURNE GODFREY , WARE JESSICA L.
Published: November 2013

Cockroaches (Order: Blattodea) comprise a taxon that, although very abundant in tropical forests, remains largely unstudied. Making sense of the diversity of species is a challenging task hindered by the large numbers of species and the abundance of cryptic or polymorphic forms. Here, we estimated species richness of cockroaches (s.s.) from northern Guyana while applying a method to deal with these confounding factors. We utilized two interpretations of abundance data, the first using only morphological information, and the second using both morphological and genetic barcode information. The two methods of species delimitation greatly influenced the resulting estimates of species richness. When incorporating genetic barcodes, our total species richness estimate decreased by 26%. Our results emphasize the importance of using independent datasets to delimit species boundaries and expert identification of specimens when possible.