bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding experimentation as improvisation in arts research
Authors: Douglas Anne , Gulari Melehat Nil
Published: October 2015

Purpose

– The purpose of this paper is to address the following questions: in what sense does experimentation as improvisation lead to methodological innovation? What are the implications of artistic experimentation as improvisation for education and learning?

Design/methodology/approach

– The paper tracks the known concept within research of “experimentation” with a view to revealing how practice-led research in art works distinctively with experimentation. It proposes experimentation as improvisation drawing on a research project Sounding Drawing 2012 as an example. The paper situates art experimentation as improvisation in art (Cage, 1995) anthropology (Hallam and Ingold, 2007; Bateson, 1989) and the theoretical work of Arnheim (1986) on forms of cognition.

Findings

– Arts research as improvisation is participatory, relational and performative retaining the research subject in its life context. The artist as researcher starts with open-ended critical questions for which there are no known methods or immediate answer. By setting up boundary conditions from the outset and understanding the situatedness and contingencies of those conditions, the artist as improviser seeks ways of not only avoiding chaos and the arbitrary but also being trapped by what is already known.

Originality/value

– This approach is important within and beyond the arts because it consciously draws together different forms of cognition – intuition and relational knowledge and also sequential knowledge. It is also significant because it offers a different epistemology in which new knowledge emerges in the relationship between participants in the research taking form in co-creation. These qualities all position improvisation as a research paradigm and a counterpoint to positivism.
Co-designing non-hierarchical community arts research: the collaborative stories spiral
Authors: Gilchrist Paul , Holmes Claire , Lee Amelia , Moore Niamh , Ravenscroft Neil
Published: October 2015

Purpose

– The purpose of this paper is to examine the potential and durability of arts practice as research through developing a new approach to arts research that challenges the conventional association between dominant constructions of community and dominant modes of research.

Design/methodology/approach

– A co-design approach, situated in arts practice, has been used to generate a conceptual framework that offers potential to open up the workings of communities by examining them from the standpoint of those who have everyday experience of these communities.

Findings

– The paper argues that there can no longer be clearly demarcated boundaries between “academics” and “community partners” in a genuinely co-designed arts research process. Rather, there are “research partners” who share mutual recognition of skills and experiences that allow them to commit to a durable “new creative scholarship” that reflects their collective identities.

Social implications

– The conceptual framework celebrates the life stories of individuals at the expense of the grand metanarratives favoured by empirical sociology and mainstream humanities. The framework reflects the commitment of the authors to create accounts of communities that do justice to their collective wisdom, dynamism and connectivity, as well as their transience, their needs to transform and their responses to change, in ways that reflect the lives of those involved rather than the needs of externally imposed disciplinary regimes.

Originality/value

– The conceptual framework is a new approach to qualitative research; its value lies in putting the participants at the heart of the research process where they not only generate narrative, but also situate, mediate and remediate it in ways that extend conventional participative research practices.
Topical adenosine increases the proportion of thick hair in Caucasian men with androgenetic alopecia
Authors: Iwabuchi Tokuro , Ideta Ritsuro , Ehama Ritsuko , Yamanishi Haruyo , Iino Masato , Nakazawa Yosuke , Kobayashi Takashi , Ohyama Manabu , Kishimoto Jiro
Published: October 2015

Adenosine is an effective treatment for androgenetic alopecia (AGA) in Japanese men and women. Adenosine exerts its effects by significantly increasing the proportion of thick hair. In this study, we assessed the clinical outcome of adenosine treatment for 6 months in 38 Caucasian men. The change in proportion of thick hair (≥60 μm) compared with baseline in the adenosine group was significantly higher than that in the placebo group (P < 0.0001). The change in vellus hair proportion (<40 μm) was significantly lower in the adenosine group than that in the placebo group (P = 0.0154). The change in hair density compared with baseline of the adenosine group was also significantly higher compared with that of the placebo group (P = 0.0470). No adverse effects due to treatment were noted during this study by dermatological evaluation. Adenosine is effective in increasing the proportion of thick hair in Caucasian men with AGA as well as in Japanese men and women.
Too dry for lizards: short‐term rainfall influence on lizard microhabitat use in an experimental rainfall manipulation within a piñon‐juniper
Authors: Ryan Mason J. , Latella Ian M. , Giermakowski J. Tomasz , Snell Howard , Poe Steven , Pangle Robert E. , Gehres Nathan , Pockman William T. , McDowell Nate G.
Published: October 2015

Ectotherms such as lizards are expected to alter their behaviour and microhabitat use and experience population declines in response to rising temperatures. But the role of changing rainfall patterns on lizard behaviour and microhabitat use is not understood.

We used a 5‐year rainfall manipulation experiment in a piñon pine‐juniper woodland in central New Mexico to study how a lizard species' microhabitat use varies in four different rainfall treatments.

We examined ground temperatures in the sun and shade, and daily rainfall, within each treatment, during lizard activity periods, to address how lizards used sun or shade microhabitats on a daily basis. Our small‐scale rainfall and temperature measurements indicate that rainfall, not temperatures, predict lizard microhabitat use.

Lizards showed a strong preference for shaded microhabitats during dry periods and used sunny microhabitats following rainfall events, regardless of treatment type. Lizards remained active during dry periods, foraging in the shade of trees.

Our study shows that rainfall can influence lizard microhabitat use more than temperature in a piñon pine‐juniper woodland and the trees provide important refugia. The loss of piñon pine and juniper trees from prolonged drought threatens to limit the amount of shade available to lizards in the future.
Is basal metabolic rate associated with recruit production and survival in free‐living house sparrows?
Authors: Rønning Bernt , Broggi Juli , Bech Claus , Moe Børge , Ringsby Thor Harald , Pärn Henrik , Hagen Ingerid J. , Sæther Bernt‐Erik , Jensen Henrik
Published: October 2015

Life history theory predicts that available energy is limited and needs to be allocated among different processes such as growth, reproduction and self‐maintenance. Basal metabolic rate (BMR), a common measure of an animal's maintenance cost, is therefore believed to be a trait of ecological and evolutionary significance. However, althoughBMRis often assumed to be correlated with fitness, its association with individual variation in fitness in free‐living populations is virtually unknown.

We examined the relationship betweenBMRin late winter prior to the breeding season and recruit production (number of offspring recorded the subsequent year), as well as adult survival, in two populations of house sparrow (Passer domesticus) on the islands Leka and Vega in northern Norway.

Number of recruits tended to be negatively related toBMR. However, analysing the data for each sex within the two populations revealed that the negative effect ofBMRon recruit production was significant only for females in the Vega population.

Survival probability was associated withBMR, but the relationship differed both between sexes and populations. In the Leka population, we found evidence for stabilizing selection in the females and disruptive selection in the males. In contrast, there was no effect ofBMRon survival in the Vega population.

Body mass influenced adult survival, but not recruit production. Furthermore, the relationship betweenBMRand fitness in females remained significant after controlling for body mass. Thus, the selection onBMRin females was not driven by aBMR‐body mass correlation.

Basal metabolic rate was significantly related to fitness in both populations. However, the results in the present study show spatial variation as well as sex specific differences in the influence ofBMRon fitness in house sparrows.
A regionally informed abundance index for supporting integrative analyses across butterfly monitoring schemes
Authors: Schmucki Reto , Pe'er Guy , Roy David B. , Stefanescu Constantí , Van Swaay Chris A.M. , Oliver Tom H. , Kuussaari Mikko , Van Strien Arco J. , Ries Leslie , Settele Josef , Musche Martin , Carnicer Jofre , Schweiger Oliver , Brereton Tom M. , Harpke Alexander , Heliölä Janne , Kühn Elisabeth , Julliard Romain
Published: October 2015

The rapid expansion of systematic monitoring schemes necessitates robust methods to reliably assess species' status and trends. Insect monitoring poses a challenge where there are strong seasonal patterns, requiring repeated counts to reliably assess abundance. Butterfly monitoring schemes (BMSs) operate in an increasing number of countries with broadly the same methodology, yet they differ in their observation frequency and in the methods used to compute annual abundance indices.

Using simulated and observed data, we performed an extensive comparison of two approaches used to derive abundance indices from count data collected via BMS, under a range of sampling frequencies. Linear interpolation is most commonly used to estimate abundance indices from seasonal count series. A second method, hereafter the regional generalized additive model (GAM), fits a GAM to repeated counts within sites across a climatic region. For the two methods, we estimated bias in abundance indices and the statistical power for detecting trends, given different proportions of missing counts. We also compared the accuracy of trend estimates using systematically degraded observed counts of the Gatekeeper Pyronia tithonus (Linnaeus 1767).

The regional GAM method generally outperforms the linear interpolation method. When the proportion of missing counts increased beyond 50%, indices derived via the linear interpolation method showed substantially higher estimation error as well as clear biases, in comparison to the regional GAM method. The regional GAM method also showed higher power to detect trends when the proportion of missing counts was substantial.

Synthesis and applications. Monitoring offers invaluable data to support conservation policy and management, but requires robust analysis approaches and guidance for new and expanding schemes. Based on our findings, we recommend the regional generalized additive model approach when conducting integrative analyses across schemes, or when analysing scheme data with reduced sampling efforts. This method enables existing schemes to be expanded or new schemes to be developed with reduced within‐year sampling frequency, as well as affording options to adapt protocols to more efficiently assess species status and trends across large geographical scales.
Characterisation of the vegetable rennets used for ‘Torta del Casar’ cheesemaking by a protein profile method
Authors: Ordiales Elena , Martín Alberto , Benito Maria J , Ruiz‐Moyano Santiago , Gallardo Gustavo , Córdoba Maria de Guia
Published: October 2015

The purpose of this work was to develop a cheap, easy and fast procedure, based on protein analysis, that can be used in the characterisation of coagulants from thistle species, which can be used in Torta del Casar cheesemaking. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis showed high efficiency in the identification of Cynara cardunculus from other thistle species and in discriminating between the technological properties, milk‐clotting and casein degradation activities of the vegetable rennets used in this study. This technique allowed for the grouping of aqueous extracts from the flowers of C. cardunculus into five different groups, which exhibited variable ability to degrade milk caseins.
Catch 22: wetlands protection and fishing for survival
Authors: Gillespie Josephine
Published: October 2015

Environmental regulation of biodiversity hotspots, including wetlands, is of increasing importance in an era when species and habitat loss is common. A number of global environmental protection regimes attempt to set up processes that protect vulnerable species and their habitats. One such regulatory regime, the Ramsar Convention (Convention on Wetlands of International Importance, especially as Waterfowl Habitat), provides overarching protection for hundreds of wetlands around the world. In this paper, one Ramsar listed wetland, Southeast Asia's and Cambodia's largest freshwater lake, the Tonle Sap, is subject to a legal geographical analysis. A legal geography approach – one that puts front and centre an examination of both the environmental protection regulations for the wetlands and the people subject to them – enables the complexity of the legal‐human–environment dynamic in this unique wetlands to be revealed. Measuring the success, or otherwise, of environmental protection regulations requires an understanding of both the biophysical and social dynamics of the place subject to that protection. Geographers, particularly legal geographers, are well placed to document the human–environment dimensions of place and to expose fragilities or disconnections between regulations and place. Regulations that do not take adequate account of complex people–place dynamics are likely to fall short of expectations and run the risk of becoming self‐defeating, giving rise to a potential catch‐22 scenario.
Qualitative study of Queensland paramedics' perceived influences on their food and meal choices during shift work
Authors: Anstey Stephanie , Tweedie Judith , Lord Bill
Published: October 2015

Aim

This study aimed to explore the perceived influences on food and meal choices of Queensland paramedics during shift work.

Methods

A qualitative study using individual semi‐structured telephone interviews was conducted on a purposive sample of 15 paramedics working on a rotating shift roster in Queensland. Interviews explored the perceived influences on their food choices while working shifts. Interviews were audio recorded, transcribed verbatim and content analysed manually using open‐coding inductive thematic analysis.

Results

A conceptual model was developed that illustrated four major themes of influences on food choices that emerged from the data analysis. These themes were physiological influences, psychosocial influences, the physical environment and the organisational environment. Of significant influence on the participants' food choice unique to the nature of their shift work was the meal break structure and being ambulance based for the majority of their shift.

Conclusions

The specific influences affecting the food choice of paramedics are created by the environmental influences in which they work and result in extended periods of not eating or ‘opportunistic eating’. This has implications for their ability to make ‘healthy food choices’. Further investigation into strategies to enable paramedics to improve food choice within the context of the unpredictable nature of their workload and their work environment is warranted.
Amino Acid, Organic Acid, and Sugar Profiles of 3 Dry Bean (Phaseolus vulgaris L.) Varieties
Authors: John K.M. Maria , Luthria Devanand
Published: October 2015

In this study, we compared the amino acid, organic acid and sugar profiles of 3 different varieties of dry beans (black bean [BB], dark red bean [DRB], and cranberry bean [CB]). The efficiency of the 2 commonly used extraction solvents (water and methanol:chloroform:water [2.5:1:1, v/v/v/]) for cultivar differentiation based on their metabolic profile was also investigated. The results showed that the BB contained the highest concentration of amino acids followed by DRB and CB samples. Phenylalanine, a precursor for the biosynthesis of phenolic secondary metabolites was detected at low concentration in CB samples and correlated with the reduced anthocyanins content in CB extract as documented in the published literature. Comparing the extractability of 2 extraction solvents, methanol:chloroform:water (2.5:1:1, v/v/v/) showed higher recoveries of amino acids from 3 beans, whereas, sugars were extracted in higher concentration with water. Analytically, gas chromatography detected sugars (9), amino acids (11), and organic acids (3) in a single run after derivatization of the extracts. In comparison, ion chromatography detected only sugars in a single run without any derivatization step with the tested procedure. Bean samples are better differentiated by the sugar content extracted with water as compared to the aqueous organic solvent extracts using partial least‐square discriminant analysis.
Microbiological Quality of Raw Dried Pasta from the German Market, with Special Emphasis on Cronobacter Species
Authors: Akineden Ömer , Murata Kristina Johanna , Gross Madeleine , Usleber Ewald
Published: October 2015

The microbiological quality of 132 dried pasta products available on the German market, originating from 11 different countries, was studied. Sample materials included soft or durum wheat products, some of which produced with other ingredients such as eggs, spices, or vegetables. Parameters included hygiene indicators (aerobic plate count, mold count, the presence of Enterobacteriaceae) and pathogenic/toxinogenic bacterial species (Salmonella spp., Staphylococcus aureus, presumptive Bacillus cereus, and Cronobacter spp.). The overall results of hygiene parameters indicated a satisfactory quality. Salmonella was not found in any sample. Three samples were positive for S. aureus (102 to 104 colony forming unit (CFU)/g). Presumptive B. cereus at levels of 103 to 104 CFU/g were detected in 3 samples. Cronobacter spp. were isolated from 14 (10.6%) products. Of these, 9 isolates were identified as C. sakazakii, 2 each as C. turicensis and C. malonaticus, and 1 as C. muytjensii. The isolates were assigned to 9 multilocus sequence typing (MLST) sequence types and to 14 different PFGE profiles. Although pasta products are typically cooked before consumption, some consumers, and children in particular, may also eat raw pasta as nibbles. Raw pasta seems to be a relevant source of exposure to dietary Cronobacter spp., although health risks are probably restricted to vulnerable consumers. High numbers of presumptive B. cereus as found in some samples may be a risk after improper storage of cooked pasta products because toxinogenic strains are frequently found within this species.
Fluoroscopy‐assisted epidural catheter placement: an exploratory analysis of 303 pre‐operative epidurograms
Authors: Yeager M. P. , Bae E. E. , Parra M. C. , Barr P. A. , Bonham A. K. , Sites B. D.
Published: October 2015

Background

Epidural catheters that are placed for post‐operative analgesia have a significant failure rate in the first 24 hours. Beginning in 2011, we have used fluoroscopic guidance to place all non‐obstetrical epidural catheters. In this retrospective analysis, we hypothesized that the characteristics of dye distribution on an epidurogram obtained immediately after catheter placement would predict clinical catheter function after surgery.

Methods

The epidurograms and medical records of 303 consecutive patients who had epidural catheters placed for post‐operative analgesia were reviewed. We extracted data on epidural dye distribution on the epidurograms and compared these results to the clinical function of the epidural catheters assessed on post‐operative day 1 (POD1).

Results

The three‐dimensional pattern of epidural dye distribution (cephalad–caudad, right–left, anterior–posterior) had significant correlations with clinical function of an epidural catheter after surgery. Increased cephalad–caudad and anterior dye spread both correlated with decreased epidural solution infusion rates on POD1, whereas right‐ or left‐sided dye distribution correlated with unilateral sensory deficits. A higher catheter placement on the neuraxis correlated with lower pain scores after thoracic surgery.

Conclusions

An epidurogram obtained immediately after epidural catheter placement may have clinical utility for predicting clinical function of the catheter after surgery.
Capital structure of multinational and domestic corporations – a cross‐country comparison
Authors: Akhtar Shumi
Published: October 2015

This study investigates whether the determinants of capital structure between multinational corporations (MCs) and domestic corporations (DCs) vary across Australia, U.S., Japan, U.K. and Malaysia. Results show (i) the debt holding capacity and majority of the explanatory factors vary between DCs and MCs and also across countries; (ii) Australia, Japan, U.K. and Malaysian MCs hold significantly less long‐term debt relative to U.S. firms; (iii) DCs and MCs that operate under an imputation tax system hold significantly less short‐ and long‐term debt; and (iv) DCs and MCs operating under common law have significantly less short‐term debt and significantly higher long‐term debt.
Preaching to the Choir: Americans Prefer Communicating to Copartisan Elected Officials
Authors: Broockman David E. , Ryan Timothy J.
Published: October 2015

Past work suggests that partisan attachments isolate citizens from encountering elite messages contrary to their points of view. Here, we present evidence that partisan attachments not only serve to filter the information citizens receive from political elites; they also work in the other direction, isolating politicians from encountering potentially contrary perspectives from citizens. In particular, we hypothesized that Americans prefer expressing their opinions to politicians who share their party identification and avoid contacting outpartisan politicians. Three studies—drawing on a mixture of observational, field experimental, and natural experimental approaches—support this hypothesis: Citizens prefer to “preach to the choir,” contacting legislators of the same partisan stripe. In light of evidence that contact from citizens powerfully affects politicians’ stances and priorities, these findings suggest a feedback loop that might aggravate political polarization and help explain how politicians of different parties could develop different perceptions of the same constituencies.
Systematic review of randomized trials of the effect of iron supplementation on iron stores and oxygen carrying capacity in pregnancy
Authors: Daru Jahnavi , Cooper Natalie A.M. , Khan Khalid S.
Published: October 2015

Introduction

Anemia in pregnancy affects 25% of all pregnancies in Europe with iron deficiency affecting even more. Despite supplementation, iron deficiency persists. This review will assess the effect on serum ferritin (iron stores) and hemoglobin (oxygen‐carrying capacity) following iron supplementation in pregnant women with anemic and non‐anemic iron deficiency.

Material and methods

A systemic search of electronic databases and trial registers was conducted from inception to January 2014. Randomized controlled trials of iron supplementation that measured serum ferritin and hemoglobin levels before and after supplementation were selected. Two independent reviewers selected studies, extracted data and assessed quality. Descriptive analyses were carried out.

Results

The review included 23 randomized controlled trials (3525 women). In iron deficiency anemia, more studies described statistically significant increases in serum ferritin levels than in hemoglobin levels following intravenous iron supplementation. In non‐anemic iron deficiency there were more statistically significant increases in serum ferritin levels than in hemoglobin levels following oral supplementation. There were no studies reporting maternal quality of life outcomes.

Conclusions

Serum ferritin appears to change more than hemoglobin following iron supplementation. The clinical effects of this need further investigation.
Maybe “I Do,” Maybe I Don't: Respectability Politics in the Same‐Sex Marriage Ruling
Authors: Matsick Jes L. , Conley Terri D.
Published: October 2015

Frost and Gola (2015) offer empirical evidence that same‐sex and different‐sex relationship partners are similar in their experiences of intimacy and, as a result, the meaning of marriage will not fundamentally change with the legalization of same‐sex marriage. In this commentary, we offer another perspective: given the unique aspects of same‐sex relationships, we argue that the meaning of marriage may indeed change as same‐sex partners legally wed. We extend Frost and Gola (2015) by considering the limitations of respectability politics when advocating for same‐sex relationships and by shedding light on those who may seek to change the meaning of marriage.
Comparisons and Differences: A Commentary on Frost
Authors: Russell Glenda M.
Published: October 2015

This commentary on Frost's comparison of the meaning of intimacy in heterosexual and same‐sex couples explores how the concept of differences between advantaged and disadvantaged groups has often been used to further stigmatize the latter group. The commentary notes that feminist critiques have provided a way to avoid this trap, which is reflected in Frost's study. This research represents a creative mix of theories and methods that provides important, nuanced findings while avoiding reifying the traditional heterosexual/same‐sex hierarchy.
Stigma, Attachment, and Relationship Dissolution: Commentary on Meanings of Intimacy
Authors: Carnelley Katherine B. , Hepper Erica G.
Published: October 2015

The chief difference between Frost's same‐sex and heterosexual couples was that same‐sex couples experienced more stigma and discrimination. We discuss implications of these stressors for relationship outcomes and consider the role of attachment orientations. We also consider the imminent changes that might occur in these processes due to the legalization of same‐sex marriage in the United States. In particular, we hope that stigma and discrimination against LGB couples might decrease, and that attachment security might increase, together reducing their vulnerabilities for relationship dissolution. Legalization of same‐sex marriage should also provide new opportunities to investigate committed same‐sex relationships alongside committed heterosexual relationships.
Attachment Theory and Methods for Meanings of Couple Intimacy
Authors: Paetzold Ramona L. , Rholes W. Steven
Published: October 2015

We provide comments on “Meaning of Intimacy: A Comparison of Members of Heterosexual and Same‐Sex Couples,” noting that there are both content and methodological issues that should be addressed in the article. First, attachment theory, used by social psychologists as a major component of the study of relationships, is entirely omitted. Second, both qualitative and quantitative issues are raised by the ways in which intimacy categories are developed and participant stories assigned to them. Finally, none of the results are statistically significant. We address these issues in detail.
Prediction model for early biochemical recurrence after radical prostatectomy based on the Cancer of the Prostate Risk Assessment score and the presence of secondary circulating prostate cells
Authors: Murray Nigel P. , Aedo Socrates , Reyes Eduardo , Orellana Nelson , Fuentealba Cynthia , Jacob Omar
Published: October 2015

Objective

To establish a prediction model for early biochemical recurrence based on the Cancer of the Prostate Risk Assessment (CAPRA) score and the presence of secondary circulating prostate cells (CPCs).

Patients and Methods

We conducted a prospective single‐centre study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinicopathological findings were used to calculate the CAPRA score. At 90 days after surgery, blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs were identified using immunocytochemistry. A CPC was defined as a cell expressing prostate‐specific antigen (PSA) but not CD45. The CPC test results were defined as positive or negative. Patients were followed up for up to 5 years and biochemical recurrence was defined as a PSA level >0.2 ng/mL. The validity of the CAPRA score was calibrated using partial validation, and Cox proportional hazard regression to build three models: a CAPRA score model, a CPC model and a CAPRA/CPC combined model.

Results

A total of 321 men, with a mean age of 65.5 years, participated in the study. After 5 years of follow‐up the biochemical recurrence‐free survival rate was 98.55%. For the model that included CAPRA score there was a hazard ratio (HR) of 7.66, for the CPC model there was an HR of 34.52 and for the combined model there were HRs of 2.60 for CAPRA score and 22.5 for CPC. Using the combined model, 23% of men changed from the low‐risk to the high‐risk category, or vice versa.

Conclusion

The incorporation of CPC detection significantly improved the model's discriminative ability in establishing the probability of biochemical recurrence; patients in the high‐risk group according to CAPRA score who are negative for CPCs have a much better prognosis. The addition of CPC detection gives clinically significant information to aid the decision on who may be eligible for adjuvant therapy.
Honokiol sensitizes breast cancer cells to TNF‐α induction of apoptosis by inhibiting Nur77 expression
Authors: Xie Lei , Jiang Fuquan , Zhang Xindao , Alitongbieke Gulimiran , Shi Xinlei , Meng MinJun , Xu Yiming , Ren Anshi , Wang Jing , Cai Lijun , Zhou Yunxia , Xu Yang , Su Ying , Liu Jie , Zeng Zhiping , Wang Guanghui , Zhou Hu , Chen Quan Cheng , Zhang Xiao‐kun
Published: October 2015

Background and Purpose

The orphan nuclear receptor Nur77 is implicated in the survival and apoptosis of cancer cells. The purpose of this study was to determine whether and how Nur77 serves to mediate the effect of the inflammatory cytokine TNF‐α in cancer cells and to identify and characterize new agents targeting Nur77 for cancer therapy.

Experimental Approach

The effects of TNF‐α on the expression and function of Nur77 were studied using in vitro and in vivo models. Nur77 expression was evaluated in tumour tissues from breast cancer patients. The anticancer effects of honokiol and its mechanism of action were assessed by in vitro, cell‐based and animal studies.

Key Results

TNF‐α rapidly and potently induced the expression of Nur77 in breast cancer cells through activation of IκB kinase and JNK. Knocking down Nur77 resulted in TNF‐α‐dependent apoptosis, while ectopic Nur77 expression in MCF‐7 cells promoted their growth in animals. Levels of Nur77 were higher in tumour tissues than the corresponding tissues surrounding the tumour in about 50% breast cancer patients studied. Our in vitro and animal studies also identified honokiol as an effective sensitizer of TNF‐α‐induced apoptosis by inhibiting TNF‐α‐induced Nur77 mRNA expression, which could be attributed to its interference of TNFR1's interaction with receptor‐interacting protein 1 (RIPK1).

Conclusions and Implications

TNF‐α‐induced Nur77 serves as a survival factor to attenuate the death effect of TNF‐α in cancer cells. With its proven human safety profile, honokiol represents a promising agent that warrants further clinical development.
Blood–brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P‐glycoprotein on a novel verapamil influx carrier
Authors: Chapy Hélène , Saubaméa Bruno , Tournier Nicolas , Bourasset Fanchon , Behar‐Cohen Francine , Declèves Xavier , Scherrmann Jean‐Michel , Cisternino Salvatore
Published: October 2015

Background and Purpose

The respective impact and interplay between ABC (P‐glycoprotein/P‐gp/Abcb1a, BCRP/ABCG2, MRP/ABCC) and SLC transporter functions at the blood–brain barrier (BBB) and blood–retinal barriers (BRB) are incompletely understood.

Experimental Approach

We measured the initial cerebral and retinal distribution of selected ABC substrates by in situ carotid perfusion using P‐gp/Bcrp knockout mice and chemical ABC/SLC modulation strategies. P‐gp, Bcrp, Mrp1 and Mrp4 were studied by confocal retina imaging.

Key Results

Chemical or physical disruption of P‐gp increased [3H]‐verapamil transport by ~10‐fold at the BBB and ~1.5‐fold at the BRB. [3H]‐Verapamil transport involved influx‐mediated by an organic cation clonidine‐sensitive/diphenhydramine‐sensitive proton antiporter at both barriers; this effect was unmasked when P‐gp was partially or fully inhibited/disrupted at the BBB. Studies of [3H]‐mitoxantrone and [3H]‐zidovudine transport suggested, respectively, that Bcrp efflux was less involved at the BRB than BBB, whereas Mrps were significantly and similarly involved at both barriers. Confocal imaging showed that P‐gp and Bcrp were expressed in intra‐retinal vessels (inner BRB/iBRB) but absent from the blood/basal membrane of cells of the retinal pigment epithelium (outer BRB/oBRB/RPE) where, in contrast, Mrp1 and Mrp4 were localized.

Conclusions and Implications

P‐gp, Bcrp, Mrp1 and Mrp4 are differentially expressed at the outer and inner BRB, resulting in an altered ability to limit substrate distribution at the retina as compared with the BBB. [3H]‐Verapamil distribution is not P‐gp‐specific and involves a proton antiporter at both the BBB and BRB. However, this transport is concealed by P‐gp at the BBB, but not at the BRB, where P‐gp activity is reduced.
All‐trans retinoic acid protects against doxorubicin‐induced cardiotoxicity by activating the ERK2 signalling pathway
Authors: Yang Liang , Luo Cheng , Chen Cong , Wang Xun , Shi Wen , Liu Jiankang
Published: October 2015

Background and Purpose

Doxorubicin is a powerful antineoplastic agent for treating a wide range of cancers. However, doxorubicin cardiotoxicity of the heart has largely limited its clinical use. All‐trans retinoic acid (ATRA) plays an important role in many cardiac biological processes, but its protective effects on doxorubicin‐induced cardiotoxicity remain unknown. Here, we studied the effect of ATRA on doxorubicin cardiotoxicity and the underlying mechanisms.

Experimental Approaches

Cellular viability assays, Western blotting and mitochondrial respiration analyses were employed to evaluate the cellular response to ATRA in H9c2 cells and primary cardiomyocytes. Quantitative PCR and gene knockdown were performed to investigate the underlying molecular mechanisms of ATRA's effects on doxorubicin cardiotoxicity.

Key Results

ATRA significantly inhibited doxorubicin‐induced apoptosis in H9c2 cells and primary cardiomyocytes. ATRA was more effective against doxorubicin cardiotoxicity than resveratrol and dexrazoxane. ATRA also suppressed reactive oxygen species generation and restored expression levels of mRNA and proteins in the phase II detoxifying enzyme system: nuclear factor‐E2‐related factor 2, manganese superoxide dismutase, haem oxygenase‐1, and mitochondrial function (mitochondrial membrane integrity, mitochondrial DNA copy numbers and mitochondrial respiration capacity, biogenesis and dynamics). Both a ERK1/2 inhibitor (U0126) and ERK2 siRNA, but not ERK1 siRNA, abolished the protective effect of ATRA against doxorubicin‐induced toxicity in H9c2 cells. Remarkably, ATRA did not compromise the anticancer efficacy of doxorubicin in gastric carcinoma cells.

Conclusions and Implications

ATRA protected cardiomyocytes against doxorubicin‐induced toxicity, by activating the ERK2 pathway, without compromising its anticancer efficacy. Therefore, ATRA is a promising candidate as a cardioprotective agent against doxorubicin cardiotoxicity.
PPARγ agonists regulate bidirectional transport of amyloid‐β across the blood–brain barrier and hippocampus plasticity in db/db mice
Authors: Wang Hao , Chen Fang , Zhong Kai Long , Tang Su Su , Hu Mei , Long Yan , Miao Ming Xing , Liao Jian Min , Sun Hong Bing , Hong Hao
Published: October 2015

Background and Purpose

There is emerging evidence suggesting that abnormal transport of amyloid‐β (Aβ) across the blood–brain barrier (BBB) is involved in diabetes‐associated cognitive decline. We investigated whether PPARγ agonists restore Aβ transport across the BBB and hippocampal plasticity in db/db mice.

Experimental Approach

Efflux and influx of Aβ across the BBB were determined by stereotaxic intra‐cerebral or i.a. infusion of [125I]‐Aβ1–40 respectively. Receptor for advanced glycation end products (RAGE) and low‐density lipoprotein receptor‐related protein 1 (LRP1), which are involved in Aβ influx and efflux, PPARγ and NF‐κB p65 at the BBB, as well as hippocampal Aβ, caspase‐3, Bax and Bcl‐2 were assayed by Western blot, immunohistochemistry and RT‐PCR. In vivo, hippocampal LTP was recorded, and Morris water maze and Y‐maze tasks were performed.

Key Results

Treatment with PPARγ agonists, rosiglitazone (0.8 mg·kg−1) and pioglitazone (9.0 mg·kg−1), for 6 weeks significantly increased Aβ efflux and decreased Aβ influx across the BBB in db/db mice. Concomitantly, they decreased hippocampal Aβ1–40 and Aβ1–42, suppressed neuronal apoptosis, as indicated by decreased caspase‐3 activity and increased ratio of Bcl‐2/Bax, and increased hippocampal plasticity, characterized by an enhanced in vivo LTP and better performance in behavioural tests. Furthermore, the PPARγ agonists induced the expression of LRP1 gene by activation of PPARγ and suppressed RAGE gene expression by inactivation of NF‐κB signalling at the BBB of db/db mice.

Conclusions and Implications

PPARγ agonists modify abnormal Aβ transport across the BBB and this is accompanied by amelioration of β‐amyloidosis and an improvement in hippocampal plasticity in diabetic mice.
How Do Fruit Bat Seed Shadows Benefit Agroforestry? Insights from Local Perceptions in Kerala, India
Authors: Deshpande Kadambari , Kelkar Nachiket
Published: October 2015

Old‐world fruit bats are known to provide significant benefits to tropical agroforestry through seed dispersal services. However, the social pathways through which local people perceive and actually utilize these benefits are not well understood. Through interview surveys with plantation owners and farmers in the Western Ghats of Kerala (India), we documented local perceptions and knowledge about the socio‐ecological importance of fruit bat seed dispersal shadows. Respondents’ perceptions were highly positive, with greater benefits reported from seed dispersal, than costs from fruit damage by bats. Interestingly, seed aggregation of commercial fruit crops (cashew, areca) by fruit bats was perceived to reduce agricultural labour costs in plantations. Our study demonstrates that local perceptions can offer valuable insights toward understanding the contribution of bat‐generated ecosystem services for tropical agroforestry systems, and in turn may facilitate effective fruit bat conservation.
Quality, quantity and duration of lives
Authors: Duclos Jean‐Yves , Housseini Bouba
Published: October 2015

The evaluation of development processes and of public policies often involves comparisons of social states that differ in income distributions, population sizes and life longevity. This may require social evaluation principles to be sensitive to the quality, the quantity and the duration of lives. This paper: 1) reviews some of the normative issues at stake, 2) proposes and discusses some specific methods to address them in a generalized utilitarian framework and 3) briefly illustrates the application of some of these methods to the global distribution of incomes, population sizes and longevity over the last century. Depending on the approach taken, it is found inter alia that global social welfare in 2010 can be deemed to be between 1.8 and 407 times that of 1910, the role given to the quantity of lives being particularly important in that assessment.
Radiolabeled liposome imaging determines an indication for liposomal anticancer agent in ovarian cancer mouse xenograft models
Authors: Ito Ken , Hamamichi Shusei , Asano Makoto , Hori Yusaku , Matsui Junji , Iwata Masao , Funahashi Yasuhiro , Umeda Izumi O. , Fujii Hirofumi
Published: October 2015

Liposomal anticancer agents can effectively deliver drugs to tumor lesions, but their therapeutic effects are enhanced in only limited number of patients. Appropriate biomarkers to identify responder patients to these liposomal agents will improve their treatment efficacies. We carried out pharmacological and histopathological analyses of mouse xenograft models bearing human ovarian cancers (Caov‐3, SK‐OV‐3, KURAMOCHI, and TOV‐112D) to correlate the therapeutic effects of doxorubicin‐encapsulated liposome (Doxil®) and histological characteristics linked to the enhanced permeability and retention effect. We next generated 111In‐encapsulated liposomes to examine their capacities to determine indications for Doxil® treatment by single‐photon emission computed tomography (SPECT)/CT imaging. Antitumor activities of Doxil® were drastically enhanced in Caov‐3, moderately in SK‐OV‐3, and minimally in KURAMOCHI and TOV‐112D when compared to doxorubicin. Microvessel density and vascular perfusion were high in Caov‐3 and SK‐OV‐3, indicating a close relation with the enhanced antitumor effects. Next, 111In‐encapsulated liposomes were given i.v. to the animals. Their tumor accumulation and area under the curve values over 72 h were high in Caov‐3, relatively high in SK‐OV‐3, and low in two other tumors. Importantly, as both Doxil® effects and liposomal accumulation varied in the SK‐OV‐3 group, we individually obtained SPECT/CT images of SK‐OV‐3‐bearing mouse (n = 11) before Doxil® treatment. Clear correlation between liposomal tumor accumulation and effects of Doxil® was confirmed (R2 = 0.73). Taken together, our experiments definitely verified that enhanced therapeutic effects through liposomal formulations of anticancer agents depend on tumor accumulation of liposomes. Tumor accumulation of the radiolabeled liposomes evaluated by SPECT/CT imaging is applicable to appropriately determine indications for liposomal antitumor agents.
The Dimensionality of Language Ability in Young Children
Authors:   Language and Reading Research Consortium
Published: October 2015

The purpose of this study was to empirically examine the dimensionality of language ability for young children (4–8 years) from prekindergarten to third grade (n = 915), theorizing that measures of vocabulary and grammar ability will represent a unitary trait across these ages, and to determine whether discourse skills represent an additional source of variance in language ability. Results demonstrated emergent dimensionality of language across development with distinct factors of vocabulary, grammar, and discourse skills by third grade, confirming that discourse skills are an important source of variance in children's language ability and represent an important additional dimension to be accounted for in studying growth in language skills over the course of childhood.
Individual Differences in Statistical Learning Predict Children's Comprehension of Syntax
Authors: Kidd Evan , Arciuli Joanne
Published: October 2015

Variability in children's language acquisition is likely due to a number of cognitive and social variables. The current study investigated whether individual differences in statistical learning (SL), which has been implicated in language acquisition, independently predicted 6‐ to 8‐year‐old's comprehension of syntax. Sixty‐eight (N = 68) English‐speaking children completed a test of comprehension of four syntactic structures, a test of SL utilizing nonlinguistic visual stimuli, and several additional control measures. The results revealed that SL independently predicted comprehension of two syntactic structures that show considerable variability in this age range: passives and object relative clauses. These data suggest that individual differences in children's capacity for SL are associated with the acquisition of the syntax of natural languages.
Loss of asthma control and activation of coagulation and fibrinolysis
Authors: Sneeboer M. M. S. , Fens N. , van de Pol M. A. , Majoor C. J. , Meijers J. C.M. , Kamphuisen P. W. , Lutter R. , Sterk P. J. , Bel E. H.D.
Published: October 2015

Background

Epidemiologic studies have shown that patients with severe asthma have increased risk of pulmonary embolism, in particular patients with frequent asthma exacerbations. Therefore, we hypothesized that asthma exacerbations are associated with increased haemostatic activity.

Objective

To investigate whether induced loss of asthma control is associated with changes in coagulation and fibrinolytic parameters in peripheral blood.

Methods

We performed a prospective, inhaled steroid withdrawal study in 23 patients with moderate to moderately severe asthma, consisting of a baseline visit and a visit after loss of asthma control. During the visits, we measured asthma control questionnaire (ACQ), atopy, lung function, inflammatory markers (eosinophils and neutrophils), and haemostatic parameters in plasma.

Results

Complete cessation of inhaled corticosteroids led to a loss of asthma control in 22 of 23 patients. We found increased asthma symptoms (ACQ 0.9 vs. 2.9, P < 0.01), significantly reduced lung function (forced expiratory volume in 1 s (FEV1) 3.51L vs. 3.13L, P < 0.01) and increased levels of eosinophils in plasma (0.26 × 10E9/L vs. 0.16 × 10E9/L, P = 0.03) in patients after loss of asthma control. However, we observed no significant changes in the coagulation and fibrinolysis parameters.

Conclusion

Loss of asthma control after cessation of inhaled corticosteroids does not lead to increased haemostatic activation in patients with moderate to moderately severe asthma. This suggests that more severe inflammation or additional risk factors are required for activation of coagulation or reduction of fibrinolysis in asthma.
GLI3 mutations in syndromic and non‐syndromic polydactyly in two Indian families
Authors: Patel Rashmi , Singh Chandra Bhan , Bhattacharya Visweswar , Singh Subodh Kumar , Ali Akhtar
Published: October 2015

The GLI3 protein is a zinc finger transcription factor, expressed early in development. The GLI3 gene exhibits allelic heterogeneity as mutations in this gene are associated with several developmental syndromic and non‐syndromic polydactyly. The present study reports two cases: first, a familial case of Greig Cephalopolysyndactyly Syndrome (GCPS); the second is a sporadic case with both postaxial polydactyly (PAP) type A and B. Resequencing of GLI3 gene reveals a previously reported nonsense truncation mutation g.42007251G > A (p.R792X; rs121917714) in the GCPS family and a novel single nucleotide insertion g.42004239_42004240insA (p.E1478X) in the sporadic case of postaxial polydactyly (PAP). Both nonsense truncation mutations; p.R792X (GCPS) and p.E1478X (PAP) introduce a premature stop codon leading to loss of C‐terminal domains.
Correlation of external ear auricle formation with staging of human embryos
Authors: Ozeki‐Sato Maimi , Yamada Shigehito , Uwabe Chigako , Ishizu Koichi , Takakuwa Tetsuya
Published: October 2015

The formation of auricles in human embryos was evaluated between Carnegie stage (CS)19 and CS23, and the findings were correlated across the stages. The auricle was categorized into 11 steps according to Streeter's criteria with modifications. Mesenchyme cell condensation was observed at Step 7, and two layers of cartilage consisting of the auricle were recognized at Step11. The representative steps at each CS shifted from Step 3 to Step11 during CS16 and CS23, although several steps overlapped between adjacent CSs. These results indicate that observations of the auricle between CS19 and CS23 may be utilized for determining embryo staging as convincing supportive evidence of external features reflecting the internal histological structure, although other findings should also be taken into account.