bluuebunny/crossref_metadata_2025 huggingface dataset:
Content, context and co-creation
Authors: Oliveira Eduardo , Panyik Emese
Published: July 2014

Content generated by tourists, travellers, professional travel bloggers and travel journalists who post, comment and share information on social media channels is arguably the greatest digital challenge of destination branding today. The tourist-/traveller-generated content is likely to generate brand value if integrated into the destination branding strategy. There is, however, a lack of theoretical awareness and empirical research into the role of social media content in shaping destination brands. By taking Portugal as a case study, this exploratory research is aimed to show how content analysis can be used to identify and understand the way tourists and travellers perceive the country as a tourist destination. The application of this methodology on online material could contribute to a refined destination branding initiative for Portugal by integrating user-generated and travel experts content into the strategy. It applies textual content analysis by using qualitative data analysis software (i.e. ATLAS.ti 7.0), within an interpretative paradigm, on tourism-oriented online publications in which the tourism potential of Portugal has been discussed. The findings highlight the tourist/traveller as an opinion maker with access to a plethora of information communication technologies to act as co-creators of brands. Therefore, it is wise to engage them and strategically integrate the content they generate into the whole destination branding effort.
The tools of the trade: The materiality of architecture in the patrimonialization of ‘Arab houses’ in Damascus
Authors: Copertino Domenico
Published: July 2014

The ethnographic study of architecture shows that building and restoring practices play an active part in the construction of the social groups that carry them out. ‘Proper’ practices and concepts of heritage distinguish ‘authentic’ from ‘inauthentic’ inhabitants of Damascus Old Town. Heritage development is therefore an act of culturally meaningful engagement through which an arena for confrontation and argument about the ‘production of the space’ is constituted. Focusing on the dynamic interrelationship of material, social and symbolic aspects of architecture, the author examines the agency and materiality of Arab houses as objects in a mutual relationship with people who build, restore, buy, sell and dwell in them. Getting involved in the material activities and engaging in relationships between the different social actors in this arena allows the intrusive ethnographic glance to grasp the cultural meaning of architecture, not simply as a symbolic representation of people who own, build and restore houses, but as a constitutive element of their sense of identity, belonging and distinction.
Resistance or friction: Understanding the significance of prisoners’ secondary adjustments
Authors: Rubin Ashley T
Published: July 2014

Scholars examining prisoners’ “secondary adjustments” have often emphasized prisoners’ “resistance” to the prison regime, particularly their agentic acts that frustrate the prison’s rules, goals, or functions. While these agency-centered accounts offer an important corrective to the understanding of prisons as totalizing institutions, they may go too far. I argue that scholars have overused (and misused) the term “resistance” to describe certain prisoner behaviors, creating both analytical and normative consequences. Instead, I suggest the concept of “friction” more accurately describes the reactive behaviors that occur when people find themselves in highly controlled environments.
Machiavelli and constituent power: The revolutionary foundation of modern political thought
Authors: Lucchese Filippo Del
Published: July 2014

This paper considers Niccolò Machiavelli’s contribution to a theory of constituent power. Modern authors who have analysed the concept of constituent power generally agree on its ambiguous, paradoxical and apparently contradictory essence. With few exceptions, Machiavelli is absent from both the historical reconstructions of and the theoretical debates on the origin of constituent power. My argument is built around two main theses: reintroducing Machiavelli to the debate on constituent power offers an original response to the theoretical fallacies and inconsistencies identified by modern scholars. In particular, Machiavelli’s philosophy contributes to the comprehension of constituent power as a living force within social order. My second thesis is that by tracing the source of constituent power back to Machiavelli, we can overcome the main theoretical problem implied by this concept, namely the problem of the priority of the factual or the juridical, by providing a vision that emphasises their immanent coexistence.
A Review of Teen Dating Violence Prevention Research
Authors: Malhotra Krithika , Gonzalez-Guarda Rosa M. , Mitchell Emma M.
Published: July 2014

The purpose of this article is to provide a critical review of the literature on evidence-based teen dating violence (TDV) prevention programs with a particular focus on highlighting gaps in the literature with regard to prevention efforts targeting Hispanic teens. The target populations, characteristics, designs, and results of TDV prevention studies reported in the scientific literature for the last 20 years were reviewed and analyzed according to cultural and contextual factors associated with TDV among Hispanic teens. To date, three studies have focused on a predominantly Hispanic population with only one study looking at the long-term effects of a TDV intervention. There is a growing need to develop and evaluate immediate and long-term effects of TDV prevention programs that address ethnic pride, acculturation and acculturative stress, familism, and gender norms within the context of Hispanic communities (e.g., machismo and marianismo). The authors discuss the implications for research, prevention practice, and policy regarding TDV prevention for Hispanic teens.
The use of technology in Prince Edward Island (Canada) high schools
Authors: Preston Jane P , Moffatt Lyndsay , Wiebe Sean , McAuley Alexander , Campbell Barbara , Gabriel Martha
Published: July 2014

The purpose of this paper is to document the perceptions of school leaders regarding the technological use, skills, and attitudes of high school teachers. Using a qualitative research approach, 11 educational leaders from Prince Edward Island (Canada) were individually interviewed. Participants represented the Department of Education, principals, vice-principals, and department heads. Analyzed through the concept of e-leadership, the findings indicated that participants used a growing array of technological tools and activities including Smartboards, flipped classrooms, Prezi, educational apps, YouTube, and teacher blogs. Participants identified lack of time as a possible reason why some teachers were not incorporating technology into student learning. Findings highlight the need for provincial and school district authorities to promote policies aimed at promoting e-leadership among teachers. We insert an appendix to provide descriptions of the technological terms included within the paper.
A reliability model of blade to avoid resonance considering multiple fuzziness
Authors: Zhang Meng , Lu Shan
Published: July 2014

The reliability of aero-engine blade to avoid resonance has a great impact on the safety of airplane. The resonance problem of blade is complex and includes not only randomness but also a lot of fuzziness. By describing the fuzziness of “blade resonance will not occur” through normal bathtub membership function and the inherent frequency through trapezoidal membership function, a Posfust reliability model of blade to avoid resonance, which considers the multiple fuzziness of state and inherent frequency, was proposed based on the probability theory and fuzzy cut-set theory in this article. Meanwhile, three limit forms of the model were analyzed and it was indicated that the Posbist model, Profust model and conventional random model were special cases of the Posfust reliability model in this article. Afterward, analyzing the deficiency of the previous cut-set distributions, a new cut-set distribution named modified truncated normal distribution was proposed to ensure the model has a good convergence in the three special cases. Furthermore, a numerical method was given to solve the Posfust reliability model, and the coefficient of variation of the numerical solution was calculated subsequently. Finally, the model and the numerical method were applied to evaluate the reliability of some blades. Simulations were carried out to explain how one can utilize the model and its numerical method obtained, verify the theoretical analysis results and study the influence of fuzzy degree on the reliability.
Unravelling India’s tobacco epidemic – priorities and recommendations for the second round of Global Adult Tobacco Survey (GATS)
Authors: Lal Pranay , Srinath Satyanarayana , Goel Sonu , Singh Rana J. , Sharma Deepak , Kumar Ravinder , Bera Om
Published: July 2014

The Global Adult Tobacco Survey, or GATS, has proved to be an invaluable tool for policymakers. In India, it highlighted the alarming rates of prevalence of use and risks both nationally and at state level. However, a rapid analysis of GATS-India shows that there are limitations in methods (sampling, questionnaire, measures undertaken to ensure data quality and management), which may impact the estimates of prevalence. This review discusses these potential weaknesses and recommends measures that can be adopted in the next round of surveys to overcome the limitations.
The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma
Authors: Spencer Andrew , Yoon Sung-Soo , Harrison Simon J. , Morris Shannon R. , Smith Deborah A. , Brigandi Richard A. , Gauvin Jennifer , Kumar Rakesh , Opalinska Joanna B. , Chen Christine
Published: July 2014

Key Points

Afuresertib has a favorable safety profile with manageable side effects and demonstrates single-agent activity against hematologic malignancies. Inhibition of AKT with afuresertib may provide a novel therapeutic strategy for hematologic malignancies, especially for multiple myeloma.
All-age relationship between arm span and height in different ethnic groups
Authors: Quanjer Philip H. , Capderou André , Mazicioglu Mumtaz M. , Aggarwal Ashutosh N. , Banik Sudip Datta , Popovic Stevo , Tayie Francis A.K. , Golshan Mohammad , Ip Mary S.M. , Zelter Marc
Published: July 2014

The objective of the present study was to establish multiethnic, all-age prediction equations for estimating stature from arm span in males and females.

The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5–99 years, from nine centres (in China, Europe, Ghana, India and Iran) was used to predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1503 patients were calculated using measured height and height calculated from arm span and age.

ASHR varied nonlinearly with age, was higher in males than in females and differed significantly between the nine sites. The data clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV1, FVC and FEV1/FVC using measured or predicted height did not differ, with standard deviations of 4.6% for FEV1, 5.0% for FVC and 0.3% for FEV1/FVC. The percentages of disparate findings for a low FEV1, FVC and FEV1/FVC in patients, calculated using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a restrictive pattern, there were 1.0% disparate findings.

Group- and sex-specific equations for estimating height from arm span and age to derive predicted values for spirometry are clinically useful.
Factors associated with low fitness in adolescents – A mixed methods study
Authors: Charlton Richard , Gravenor Michael B , Rees Anwen , Knox Gareth , Hill Rebecca , Rahman Muhammad A , Jones Kerina , Christian Danielle , Baker Julien S , Stratton Gareth , Brophy Sinead
Published: July 2014

Background

Fitness and physical activity are important for cardiovascular and mental health but activity and fitness levels are declining especially in adolescents and among girls. This study examines clustering of factors associated with low fitness in adolescents in order to best target public health interventions for young people.

Methods

1147 children were assessed for fitness, had blood samples, anthropometric measures and all data were linked with routine electronic data to examine educational achievement, deprivation and health service usage. Factors associated with fitness were examined using logistic regression, conditional trees and data mining cluster analysis. Focus groups were conducted with children in a deprived school to examine barriers and facilitators to activity for children in a deprived community.

Results

Unfit adolescents are more likely to be deprived, female, have obesity in the family and not achieve in education. There were 3 main clusters for risk of future heart disease/diabetes (high cholesterol/insulin); children at low risk (not obese, fit, achieving in education), children ‘visibly at risk’ (overweight, unfit, many hospital/GP visits) and ‘invisibly at risk’ (unfit but not overweight, failing in academic achievement). Qualitative findings show barriers to physical activity include cost, poor access to activity, lack of core physical literacy skills and limited family support.

Conclusions

Low fitness in the non-obese child can reveal a hidden group who have high risk factors for heart disease and diabetes but may not be identified as they are normal weight. In deprived communities low fitness is associated with non-achievement in education but in non-deprived communities low fitness is associated with female gender. Interventions need to target deprived families and schools in deprived areas with community wide campaigns.
Different pioneer plant species select specific rhizosphere bacterial communities in a high mountain environment
Authors: Ciccazzo Sonia , Esposito Alfonso , Rolli Eleonora , Zerbe Stefan , Daffonchio Daniele , Brusetti Lorenzo
Published: July 2014

The rhizobacterial communities of 29 pioneer plants belonging to 12 species were investigated in an alpine ecosystem to assess if plants from different species could select for specific rhizobacterial communities. Rhizospheres and unvegetated soils were collected from a floristic pioneer stage plot at 2,400 m a.s.l. in the forefield of Weisskugel Glacier (Matsch Valley, South Tyrol, Italy), after 160 years of glacier retreat. To allow for a culture-independent perspective, total environmental DNA was extracted from both rhizosphere and bare soil samples and analyzed by Automated Ribosomal Intergenic Spacer Analysis (ARISA) and Denaturing Gradient Gel Electrophoresis (DGGE). ARISA fingerprinting showed that rhizobacterial genetic structure was extremely different from bare soil bacterial communities while rhizobacterial communities clustered strictly together according to the plant species. Sequencing of DGGE bands showed that rhizobacterial communities were mainly composed of Acidobacteria and Proteobacteria whereas bare soil was colonized by Acidobacteria and Clostridia. UniFrac significance calculated on DGGE results confirmed the rhizosphere effect exerted by the 12 species and showed different bacterial communities (P < 0.05) associated with all the plant species. These results pointed out that specific rhizobacterial communities were selected by pioneer plants of different species in a high mountain ecosystem characterized by oligotrophic and harsh environmental conditions, during an early primary succession.
The Kardashian index: a measure of discrepant social media profile for scientists
Authors: Hall Neil
Published: July 2014

In the era of social media there are now many different ways that a scientist can build their public profile; the publication of high-quality scientific papers being just one. While social media is a valuable tool for outreach and the sharing of ideas, there is a danger that this form of communication is gaining too high a value and that we are losing sight of key metrics of scientific value, such as citation indices. To help quantify this, I propose the ‘Kardashian Index’, a measure of discrepancy between a scientist’s social media profile and publication record based on the direct comparison of numbers of citations and Twitter followers.
An RNA tertiary switch by modifying how helices are tethered
Authors: Ganser Laura R , Mustoe Anthony M , Al-Hashimi Hashim M
Published: July 2014

A viral tRNA-like structure has evolved a unique strategy to undergo a tertiary structure conformational switch that may help regulate viral regulation.
A systematic approach to identify novel cancer drug targets using machine learning, inhibitor design and high-throughput screening
Authors: Jeon Jouhyun , Nim Satra , Teyra Joan , Datti Alessandro , Wrana Jeffrey L , Sidhu Sachdev S , Moffat Jason , Kim Philip M
Published: July 2014

We present an integrated approach that predicts and validates novel anti-cancer drug targets. We first built a classifier that integrates a variety of genomic and systematic datasets to prioritize drug targets specific for breast, pancreatic and ovarian cancer. We then devised strategies to inhibit these anti-cancer drug targets and selected a set of targets that are amenable to inhibition by small molecules, antibodies and synthetic peptides. We validated the predicted drug targets by showing strong anti-proliferative effects of both synthetic peptide and small molecule inhibitors against our predicted targets.
Designing Therapeutic Clinical Trials for Older and Frail Adults With Cancer: U13 Conference Recommendations
Authors: Hurria Arti , Dale William , Mooney Margaret , Rowland Julia H. , Ballman Karla V. , Cohen Harvey J. , Muss Hyman B. , Schilsky Richard L. , Ferrell Betty , Extermann Martine , Schmader Kenneth E. , Mohile Supriya G.
Published: July 2014

A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer.
Refining the Chemotherapy Approach for Older Patients With Colon Cancer
Authors: McCleary Nadine J. , Dotan Efrat , Browner Ilene
Published: July 2014

Population studies support an increased incidence of most cancers among older adults. Colorectal cancer has high prevalence in the aging population, with a median age of 69 years at diagnosis and 74 years at death. The vast majority of patients with colon cancer (CC) will require chemotherapy treatments during their disease course, challenging oncologists with the task of tailoring therapy for older patients with CC in the face of limited evidence-based data to guide them. Factors such as comorbidity, performance status, cognitive function, and social support may affect decision making and complicate tolerance of any recommended therapy. In recent years, attention to the specific needs of the aging population with cancer has given rise to the field of geriatric oncology in general, and has generated an increasing fund of knowledge on which to base chemotherapy delivery for this specific population of patients with CC. This article will review the available data specifically for chemotherapy management of older patients with CC in the postoperative and metastatic settings.
Incorporating Biomarkers Into Cancer and Aging Research
Authors: Hubbard Joleen M. , Cohen Harvey J. , Muss Hyman B.
Published: July 2014

The challenge in treating the older adult with cancer is accurately accounting for and adapting management to the heterogeneity in health status of the individual patient. Many oncologists recognize that chronological age alone should not be the determinant when deciding on a treatment regimen. Easily measurable markers that provide an assessment of functional age would be ideal to assess frailty, which may predispose the patient to complications from cancer treatment, including increased toxicity, functional decline, decreased quality of life, and poorer survival. Several categories of potential markers, including chronic inflammatory markers, markers of cellular senescence, and imaging to assess muscle mass to detect sarcopenia, may provide insight into the likelihood of treatment-related complications. This article discusses candidate markers and strategies to evaluate these markers in cancer treatment trials, with the aim of developing a method to assess risk of oncologic outcomes and guide management decisions for both the physician and patient.
Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction
Authors: Davies Andrew R. , Gossage James A. , Zylstra Janine , Mattsson Fredrik , Lagergren Jesper , Maisey Nick , Smyth Elizabeth C. , Cunningham David , Allum William H. , Mason Robert C.
Published: July 2014

Purpose

Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable.

Methods

We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis.

Results

Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation.

Conclusion

The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.
MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells
Authors: Tsai Pai-Chi , Bake Shameena , Balaraman Sridevi , Rawlings Jeremy , Holgate Rhonda R. , Dubois Dustin , Miranda Rajesh C.
Published: July 2014

Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.
Deafness in occludin-deficient mice with dislocation of tricellulin and progressive apoptosis of the hair cells
Authors: Kitajiri Shin-ichiro , Katsuno Tatsuya , Sasaki Hiroyuki , Ito Juichi , Furuse Mikio , Tsukita Shoichiro
Published: July 2014

Occludin is the first identified protein in the tight junction (TJ), but its function has remained for the most part obscure. TJs have been demonstrated to play important roles in the inner ear function, and occludin is expressed in all the epithelial TJs in the inner ear. Thus, we examined the inner ears of occludin-deficient (Occ−/−) mice. Although inner ears initially developed normally in Occ−/− mice, apoptosis occurs in hair cells in the organ of Corti around day 12 after birth, and deafness develops. Since hair cell degeneration was not observed in cochlear explant cultures of Occ−/− mice, environmental changes were considered to be the trigger of cell death. As for the vestibular system, both the morphologies and functions are normal in Occ−/− mice. These phenotypes of Occ−/− mice are very similar with those of claudin-14 or claudin-9 deficient mice, leading us to speculate on the existence of imbalance induced by TJ abnormalities, such as localized ionic components. Moreover, the occludin deficiency led to dislocalization of tricellulin, a gene responsible for human deafness DFNB49. The deafness in Occ−/− mice may be due to this dislocalization of tricellulin.
The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis
Authors: Hale Michael A. , Swift Galvin H. , Hoang Chinh Q. , Deering Tye G. , Masui Toshi , Lee Youn-Kyoung , Xue Jumin , MacDonald Raymond J.
Published: July 2014

The orphan nuclear receptor NR5A2 is necessary for the stem-like properties of the epiblast of the pre-gastrulation embryo and for cellular and physiological homeostasis of endoderm-derived organs postnatally. Using conditional gene inactivation, we show that Nr5a2 also plays crucial regulatory roles during organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the expansion of the nascent pancreatic epithelium, for the subsequent formation of the multipotent progenitor cell (MPC) population that gives rise to pre-acinar cells and bipotent cells with ductal and islet endocrine potential, and for the formation and differentiation of acinar cells. At birth, the NR5A2-deficient pancreas has defects in all three epithelial tissues: a partial loss of endocrine cells, a disrupted ductal tree and a >90% deficit of acini. The acinar defects are due to a combination of fewer MPCs, deficient allocation of those MPCs to pre-acinar fate, disruption of acinar morphogenesis and incomplete acinar cell differentiation. NR5A2 controls these developmental processes directly as well as through regulatory interactions with other pancreatic transcriptional regulators, including PTF1A, MYC, GATA4, FOXA2, RBPJL and MIST1 (BHLHA15). In particular, Nr5a2 and Ptf1a establish mutually reinforcing regulatory interactions and collaborate to control developmentally regulated pancreatic genes by binding to shared transcriptional regulatory regions. At the final stage of acinar cell development, the absence of NR5A2 affects the expression of Ptf1a and its acinar specific partner Rbpjl, so that the few acinar cells that form do not complete differentiation. Nr5a2 controls several temporally distinct stages of pancreatic development that involve regulatory mechanisms relevant to pancreatic oncogenesis and the maintenance of the exocrine phenotype.
Potentiated Hsp104 variants suppress toxicity of diverse neurodegenerative disease-linked proteins
Authors: Jackrel Meredith E. , Shorter James
Published: July 2014

Protein misfolding is implicated in numerous lethal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD). There are no therapies that reverse these protein-misfolding events. We aim to apply Hsp104, a hexameric AAA+ protein from yeast, to target misfolded conformers for reactivation. Hsp104 solubilizes disordered aggregates and amyloid, but has limited activity against human neurodegenerative disease proteins. Thus, we have previously engineered potentiated Hsp104 variants that suppress aggregation, proteotoxicity and restore proper protein localization of ALS and PD proteins in Saccharomyces cerevisiae, and mitigate neurodegeneration in an animal PD model. Here, we establish that potentiated Hsp104 variants possess broad substrate specificity and, in yeast, suppress toxicity and aggregation induced by wild-type TDP-43, FUS and α-synuclein, as well as missense mutant versions of these proteins that cause neurodegenerative disease. Potentiated Hsp104 variants also rescue toxicity and aggregation of TAF15 but not EWSR1, two RNA-binding proteins with a prion-like domain that are connected with development of ALS and frontotemporal dementia. Thus, potentiated Hsp104 variants are not entirely non-specific. Indeed, they do not unfold just any natively folded protein. Rather, potentiated Hsp104 variants are finely tuned to unfold proteins bearing short unstructured tracts that are not recognized by wild-type Hsp104. Our studies establish the broad utility of potentiated Hsp104 variants.
Body size effects on the oxygen-sensitivity of dragonfly flight
Authors: Henry Joanna Randyl , Harrison Jon F.
Published: July 2014

One hypothesis for the small size of insects relative to vertebrates, and the existence of giant fossil insects, is that atmospheric oxygen levels constrain insect body sizes because oxygen delivery is more challenging in larger insects. This study tested this hypothesis in dragonflies by measuring the oxygen-sensitivity of flight metabolic rates and behavior during hovering for 11 species of dragonflies that ranged in mass by an order of magnitude. We measured flight times and flight metabolic rates in 7 oxygen concentrations ranging from 30% to 2.5% to assess the sensitivity of their flight to atmospheric oxygen. We also assessed the oxygen-sensitivity of flight in low-density air (nitrogen replaced with helium) in order to increase the metabolic demands of hovering flight. Lowered atmospheric densities did induce higher flight metabolic rates. Flight behavior was more sensitive to decreasing oxygen levels than flight metabolic rate. The oxygen-sensitivity of flight metabolic rates and behaviors were not correlated with body size, indicating that larger insects are able to maintain oxygen supply-to-demand even during flight.
Mitochondrial uncoupling as a regulator of life history trajectories in birds: An experimental study in the zebra finch
Authors: Stier Antoine , Bize Pierre , Roussel Damien , Schull Quentin , Massemin Sylvie , Criscuolo Francois
Published: July 2014

Mitochondria have a fundamental role in the transduction of energy from food into ATP. The coupling between food oxidation and ATP production is however never perfect but may nevertheless be of evolutionary significance. The 'uncoupling to survive' hypothesis suggests that 'mild' mitochondrial uncoupling evolved as a protective mechanism against the excessive production of damaging reactive oxygen species (ROS). Because resource allocation and ROS production are thought to shape animal life histories, alternative life history trajectories might be driven by individual variation in the degree of mitochondrial uncoupling. We tested this hypothesis in a small bird species, the zebra finch (Taeniopygia guttata), by treating adults with the artificial mitochondrial uncoupler 2,4-dinitrophenol (DNP) over a 32-months period. In agreement with our expectations, the uncoupling treatment increased metabolic rate. However, we found no evidence that treated birds enjoyed lower oxidative stress levels or greater survival rates, in contrast to previous results in other taxa. In vitro experiments revealed lower sensitivity of ROS production to DNP in mitochondria isolated from skeletal muscles of zebra finch than mouse. In addition, we found significant reductions in the number of eggs laid and in the inflammatory immune response in treated birds. Altogether, our data suggest that the 'uncoupling to survive' hypothesis may not be applicable for zebra finches, presumably due to lower effects of mitochondrial uncoupling on mitochondrial ROS production in birds than mammals. Mitochondrial uncoupling appeared nevertheless as a potential life-history regulator of traits such as fecundity and immunity at adulthood, even with food supplied ad-libitum.
Host orientation using volatiles in the phoretic nematode Caenorhabditis japonica
Authors: Okumura Etsuko , Yoshiga Toyoshi
Published: July 2014

Host orientation is the most important step in host-searching nematodes; however, information on direct cues from hosts to evoke this behavior is limited. Caenorhabditis japonica establishes a species-specific phoresy with Parastrachia japonensis. Dauer larvae (DL), the non-feeding and phoretic stage of C. japonica, are predominantly found on female phoretic hosts, but the mechanisms underlying the establishment of this phoresy remain unknown. To determine if C. japonica DL are able to recognize and orient themselves to a host using a volatile cue from the host, we developed a Y-tube olfactory assay system in which C. japonica DL were significantly attracted to the air from P. japonensis but not to the air from three other insects or to CO2. These results demonstrated that C. japonica DL utilize volatiles for host recognition and orientation and that the presence of a specific volatile kairomone released by the host attracts C. japonica DL.
A superfast muscle in the complex sonic apparatus of Ophidion rochei (Ophidiiformes): histological and physiological approaches
Authors: Kéver Loïc , Boyle Kelly S. , Dragičević Branko , Dulčić Jakov , Parmentier Eric
Published: July 2014

In teleosts, superfast muscles are generally associated with the swimbladder wall whose vibrations result in sound production. In Ophidion rochei, three pairs of muscles were named 'sonic' because their contractions affect swimbladder position: the dorsal sonic muscle (DSM), the intermediate sonic muscle (ISM), and the ventral sonic muscle (VSM). These muscles were investigated thanks to electron microscopy and electromyography in order to determine their function in sound production. Fibers of the VSM and DSM were much thinner than the fibers of the ISM and epaxial musculature. However, only VSM fibers had the typical ultrastructure of superfast muscles: low proportion of myofibrils, and high proportions of sarcoplasmic reticulum and mitochondria. In females, each sound onset was preceded by the onset of electrical activity in the VSM and the DSM (ISM was not tested). The electromyograms of the VSM were very similar to the waveforms of the sounds: means for the pulse period were 3.6±0.5 ms and 3.6±0.7 ms, respectively. This shows that the fast VSM (ca. 280 Hz) is responsible for the pulse period and fundamental frequency of female sounds. DSM electromyograms were generally characterized by one or two main peaks followed by periods of lower electrical activity which suggests a sustained contraction over the course of the sound. The fiber morphology of the ISM and its antagonistic position relative to the DSM are not indicative of a muscle capable of superfast contractions. Overall, this study experimentally shows the complexity of the sound production mechanism in the nocturnal fish O. rochei.
Parasitic and immune-modulation of flight activity in honey bees tracked with optical counters
Authors: Alaux Cédric , Crauser Didier , Pioz Maryline , Saulnier Cyril , Le Conte Yves
Published: July 2014

Host-parasite interactions are often characterized by changes in the host behaviour, which are either beneficial to the parasite or the host, or a non-adaptive byproduct of parasitism. Those interactions are further complicated in animal society since the individual fitness is associated with the group performance. However, a better understanding of host-parasite interaction in animal society first requires to identify individual host behavioural modification. Therefore, we challenged honey bee (Apis mellifera) workers with the parasite Nosema ceranae or an immune stimulation and tracked their flight activity over their lifetime with an optic counter. We found that bees responded differently to each stress: both Nosema-infected and immune-challenged bees performed a lower number of daily flights compared to control bees, but the duration of their flights increased and decreased over time, respectively. Overall, parasitized bees spent more time in the field each day than control bees and inversely for immune-challenged bees. Despite the stress due to immune challenge, bees had a survival similar to control bees likely due to their restricted activity. We discuss how those different behavioural modifications could be adaptive phenotypes. This study provides new insights into how biological stress can affect the behaviour of individuals living in society and how host responses evolved.
Scavenging ROS dramatically increases NMDA receptor whole cell currents in painted turtle cortical neurons
Authors: Dukoff David J. , Hogg David W. , Hawrsyh Peter J. , Buck Leslie T.
Published: July 2014

Oxygen deprivation triggers excitotoxic cell death in mammal neurons through excessive calcium loading via over-activation of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This does not occur in the western painted turtle which overwinters for months without oxygen. Neurological damage is avoided through anoxia-mediated decreases in NMDA and AMPA receptor currents that are dependent upon a modest rise in intracellular Ca2+ concentrations ([Ca2+]i) originating from mitochondria. Anoxia also blocks mitochondrial reactive oxygen species (ROS) generation which is another potential signaling mechanism to regulate glutamate receptors. To assess the effects of decreased intracellular [ROS] on NMDA and AMPA receptor currents we scavenged ROS with N-2-mercaptopropionylglycine (MPG) or N-acetylcysteine (NAC). Unlike anoxia, ROS scavengers increased NMDA receptor whole-cell currents by 100% while hydrogen peroxide decreased currents. AMPA receptor currents and [Ca2+]i concentrations were unaffected by ROS manipulation. Since decreases in [ROS] increased NMDA receptor currents we next asked if mitochondrial Ca2+ release prevents receptor potentiation during anoxia. Normoxic activation of mitochondrial ATP-sensitive potassium (mKATP) channels with diazoxide decreased NMDA receptor currents and was unaffected by subsequent ROS scavenging. Diazoxide application following ROS scavenging did not rescue scavenger-mediated increases in NMDA receptor currents. Fluorescent measurement of [Ca2+]i and ROS levels demonstrated that [Ca2+]i increases before ROS decreases. We conclude that decreases in ROS concentration are not linked to anoxia-mediated decreases in NMDA / AMPA receptor currents but are rather associated with an increase in NMDA receptor currents that is prevented during anoxia by mitochondrial Ca2+ release.
Cardiac responses to hypercapnia in larval zebrafish (Danio rerio): The links between CO2 chemoreception, catecholamines and carbonic anhydrase
Authors: Miller Scott , Pollack Jacob , Bradshaw Julia , Kumai Yusuke , Perry Steve F.
Published: July 2014

The ontogeny of carbon dioxide (CO2) sensing in zebrafish (Danio rerio) has not been examined. In this study, CO2-mediated increases in heart rate were used to gauge the capacity of zebrafish larvae to sense CO2. CO2 is thought to be detected via neuroepithelial cells (NECs), which are homologous to mammalian carotid body glomus cells. Larvae at 5 days post-fertilization (dpf) exhibited tachycardia when exposed for 30 min to 0.75% CO2 (~ 5.63 mm Hg); at 7 dpf, tachycardia was elicited by 0.5% CO2 (~ 3.75 mm Hg). Based on pharmacological evidence using β-adrenergic receptor (β1-AR) antagonists, and confirmed by β1-AR translational gene knockdown using morpholinos, the reflex tachycardia accompanying hypercapnia was likely mediated by the interaction of catecholamines with cardiac β1 receptors. Because the cardiac response to hypercapnia was abolished by the ganglionic blocker, hexamethonium, it is probable that the reflex cardio-acceleration was mediated by catecholamines derived from sympathetic adrenergic neurons. Owing to its likely role in facilitating intracellular acidification during exposure to hypercapnia, it was hypothesized that carbonic anhydrase (CA) is involved in CO2 sensing, and that inhibition of CA activity would blunt the downstream responses. Indeed, the cardiac response to hypercapnia (0.75% CO2) was reduced in fish at 5 dpf exposed to acetazolamide, a CA inhibitor, and in fish experiencing zCAc (CA2-like a) knockdown. Successful knockdown of zCAc was confirmed by CA activity measurements, western blotting and immunocytochemistry. Co-injection of embryos with zCAc morpholino and mRNA modified at the morpholino binding site, restored normal levels of CA activity and protein levels, and restored (rescued) the usual cardiac responses to hypercapnia. These data, combined with the finding that zCAc is expressed in NEC's located on the skin, suggest that the afferent limb of the CO2-induced cardiac reflex in zebrafish larvae is initiated by coetaneous CO2-sensing neuroepithelial cells.
Two inhibitors of the ubiquitin proteasome system enhance long-term memory formation upon olfactory conditioning in the honeybee (Apis mellifera)
Authors: Felsenberg Johannes , Dyck Yan , Kloß Alexander , Dahlmann Burkhardt , Klötzel Peter-Michael , Eisenhardt Dorothea
Published: July 2014

In honeybees (Apis mellifera) the proteasome inhibitor Z-Leu-Leu-Leu-CHO (MG132) enhances long-term memory (LTM) formation. Studies in vertebrates using different inhibitors of the proteasome demonstrate the opposite, namely an inhibition of memory formation. The reason for this contradiction remains unclear. MG132 is an inhibitor of the proteasome, but also blocks other proteases. Accordingly, one possible explanation might be that other proteases affected by MG132 are responsible for the enhancement of LTM formation. We test this hypothesis by comparing the effect of MG132 and the more specific proteasome inhibitor clasto-lactacystin beta-lactone (β-lactone). We show that these two inhibitors block the activity of the proteasome in honeybee brains to a similar extent, do not affect the animals’ survival but do enhance LTM retention upon olfactory conditioning. Thus, the enhancement of LTM formation is not due to MG132-specific side effects, but to inhibition of a protease targeted by MG132 and β-lactone, i.e. the proteasome.
Stronger Than the Sum of Its Parts? The Performance Implications of Peer Control Combinations in Teams
Authors: De Jong Bart A. , Bijlsma-Frankema Katinka M. , Cardinal Laura B.
Published: July 2014

Integrating theorizing on situational strength and complementarity with control theory, we investigate the mediating processes that transmit peer control combination effects to team performance. We argue that two critical peer control mechanisms—norm strength and peer pressure—complement each other such that their joint impact on team members becomes stronger than the sum of their parts. In a multiple mediator model, we identify effort and trust as two distinct mediating processes that explain the relationship between peer control combinations and team performance. Multisource, multiwave data from 41 self-managing healthcare teams largely support our model. The pattern of mediation was more complex than we anticipated, revealing an indirect effect of peer controls on effort via trust. Together, our findings offer insight into how controls complement each other and the processes through which they do so.
Quality of life data in older adults: self-assessment vs interview
Authors: Halvorsrud Liv , Kalfoss Mary
Published: July 2014

Background and purpose:

There are obstacles for older people when reporting quality of life (QoL) in a survey format. The aim of this study was to explore the quality of data obtained on self-assessed QoL among older people with respect to modes of administration.

Method and results:

Approximately half of the QoL items showed significantly higher mean values in the mail sample than in the interview sample. Data suggest that there may be more vulnerability towards offering socially desirable answers. Problems with reduced energy and loss of memory affect both modes of administration.

Conclusions:

This study demonstrates that investigating the mode of questionnaire administration among older people can be a valuable means by which to detect possible threats to data quality when interpreting QoL scores.