bluuebunny/crossref_metadata_2025 huggingface dataset:
A single amino acid defines cross‐species reactivity of tree shrew (Tupaia belangeri) CD1d to human invariant natural killer T (iNKT) cells
Authors: Zhang Ping , Li Demin , Stewart‐Jones Guillaume , Shao Xiaoli , Zhang Yuanxu , Chen Qiongyu , Li Yijiang , He You‐Wen , Xu Xiao‐Ning , Zhang Hua‐Tang
Published: June 2009

The non‐classical major histocompatibility complex (MHC) class I molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells, which are an important part of the innate immune system. CD1d/iNKT systems are highly conserved in evolution, and cross‐species reactivity has been suggested to be a common feature of different animals based on research in humans and mice. However, we found that CD1d from the tree shrew (Tupaia belangeri), a close evolutionary relative of primates, failed to stimulate human iNKT cells, despite being more homologous to human CD1d than that of mouse. Sequence comparison and molecular modelling showed that two of the key amino acid residues in human CD1d proposed to be in direct contact with T‐cell receptors were mutated in tree shrew CD1d. Substitution of one of the residues, but not the other, with the human residue enabled tree shrew CD1d to regain the ability to present lipid antigen to human iNKT cells. These results indicate that CD1d/iNKT recognition is species‐specific, and that cross‐species reactivity may be less common than currently proposed. Also, a naturally occurring CD1d mutation(s) that confers inability to stimulate iNKT cell function may have implications for future studies on CD1d/iNKT‐associated diseases.
Conservation value of cacao agroforestry for amphibians and reptiles in South‐East Asia: combining correlative models with follow‐up field experiments
Authors: Wanger Thomas C. , Saro Akbar , Iskandar Djoko T. , Brook Barry W. , Sodhi Navjot S. , Clough Yann , Tscharntke Teja
Published: June 2009

1. Although agricultural expansion is a primary threat to tropical biodiversity, experimental studies evaluating the conservation value of tropical agricultural habitats are scarce. In particular, little is known about the sensitivity of amphibians and reptiles to habitat disturbance in areas of very high diversity such as South‐East Asia.

2. We used a two‐step approach to determine the relationship between habitat complexity and conservation value of cacao agroforestry for herpetological diversity in Sulawesi (Indonesia). Indonesia is the third largest cacao‐exporting country globally and forest conversion to cacao plantations is a major threat to its biodiversity. We first sampled 43 cacao plantations six times to determine the environmental variables that best explained herpetofaunal diversity patterns using a Bayesian model selection approach. Based on these results, we experimentally manipulated leaf litter thickness (LLT), number of branch piles (LOGS) and LLT + LOGS combinations in the cacao plots. The experimental data were analysed using Bayesian hierarchical regression.

3. The best supported correlative models incorporated LLT, LOGS, air temperature and the ratio between leaf litter and shrub cover, showing the importance of habitat heterogeneity and suggesting climate change sensitivity. The subsequent structural manipulation of these attributes changed amphibian and reptile species richness, and reptile abundance, but only addition of leaf litter did so in a biologically meaningful way, providing microhabitat resources. However, the main beneficiaries were common disturbance‐tolerant reptiles.

4. 
Synthesis and applications. The different results from the correlative model and the independent manipulative experiments showed how important such a combined approach is to derive adequate conservation management recommendations. Increasing leaf litter in cacao agroforestry will work best if implemented on a landscape scale to incorporate sufficient environmental variation and species life histories. This will mainly enhance the richness and abundance of disturbance‐tolerant species, which still may maintain ecosystem functions such as pest removal. Particularly for rare species, native forests remain critical for herpetological richness. The direct temperature sensitivity suggests that future climate change impacts may be severe for herpetological diversity in plantation habitats and, hence, demand further research.
Mental health and creating safety: the participation of relatives in psychiatric treatment and its significance
Authors: Piippo Jukka , Aaltonen Jukka
Published: June 2009

Aims and objectives.  We aimed to discover the significance of the participation of relatives in the treatment process using the principles of the Need‐Adapted Approach. The study is based on joint interviews with 10 psychiatric patients, their relatives and a multiprofessional treatment team.

Background.  The Need‐Adapted Approach was developed in Finland for difficult psychiatric problems in public sector psychiatry. The central feature of the approach is the active participation of patients and their relatives in planning the treatment and in the treatment process. It emphasises horizontal expertise and open discussions between the patient, relatives and professionals.

Design.  A qualitative method based on the grounded theory approach was used.

Method.  The main focus in the analysis was on how the informants experienced the significance of the participation of their relatives in the treatment process.

Results.  Seven categories and one core category were identified. Primary categories which increased safety were: (1) shared understanding, (2) a new kind of relationship opens up and (3) being able to cope with life. Secondary categories were: (4) exclusion and (5) need for a one‐to‐one relationship. Ambivalent categories were: (6) whom or what one can believe and (7) keeping the illness secret. One core category, safety, was identified among the categories. A theoretical model was created for clinical purposes.

Conclusions.  When practiced correctly, the Need‐Adapted Approach makes it possible to create circumstances in psychiatric treatment where the patient and his/her relatives can experience increased safety in spite of the anxiety connected to the psychiatric difficulties.

Relevance to clinical practice.  Clinical workers and nursing personnel can use our findings in their practical work with psychiatric patients and their relatives. Our findings support further theoretical considerations concerning safety and can be used as guidelines for nursing personnel in their work.
Nursing home care for older people in Taiwan: a process of forced choice
Authors: Wu Shu‐Chen , White Alan , Cash Keith , Foster Sally
Published: June 2009

Aim.  To generate a substantive theory for understanding the phenomenon of nursing home care for older people in Taiwan.

Background.  Taiwanese culture shows great respect for older people and older people are traditionally cared for at home by their families. However, the older population in Taiwan is rapidly increasing and this demographic shift, together with various socio‐economic changes, has resulted in nursing homes becoming a new and significant care option.

Design.  A grounded theory approach was used to study the residents and relatives from three nursing homes in Taiwan.

Methods.  Formal and informal interviews and participant observation data were collected over two months in each nursing home. Forty nursing home residents and 20 of their relatives were recruited. The data were analysed using the constant comparative method and involved the use of theoretical memos and theoretical sampling procedures.

Results.  The study found that nursing home care for older people in Taiwan is understood to be a process of forced choice, involving three stages; namely, ‘becoming a problem’, ‘making a forced choice’ and ‘coping with the forced choice’.

Conclusion.  Taiwan is in a state of conflict with regard to providing care for older people, a situation in which the influence of traditional cultural and that of industrialisation exist side by side. The consequence of having to relocate older people into nursing homes means that both parties are the victims of this choice.

Relevance to clinical practice.  This conceptual explanation helps us to understand how the Taiwanese respond to the issue of care for older people and how they resolve their main concerns related to it. Subsequently, it is hoped that this will help health care practitioners to provide care more effectively to meet the needs of the Taiwanese with the aim of enhancing the standards of care for older people.
A discourse analysis of difficult clinical situations in relation to nutrition and hydration during end of life care
Authors: Van Der Riet Pamela , Higgins Isabel , Good Phillip , Sneesby Ludmilla
Published: June 2009

Aim and objectives.  The following discussion builds upon a previous publication that reported on the perceptions and discourses of palliative care nurses and doctors in relation to nutrition and hydration at the end of life. The aim of this paper is to report the discourses of nurses and doctors in relation to the challenges they faced when managing the care of patients with severe brain injury vs. the clearer cut situations when caring for terminally ill patients with cancer. The objectives of the study were to:

explore the tensions in the discourses during end of life care,

explore the challenges regarding nutrition and hydration at the end of life.

Background.  The decision to withdraw life support seems to be made more readily than the decision to withdraw nutrition and hydration at the end of life. The abatement of nutrition and hydration during the terminal phase of life is a controversial issue for a range reasons. Indeed, whilst it is accepted practice in the palliative care setting, nurses and doctors often struggle with the idea.

Design.  The design for this study used discourse analysis framed by a post structural framework.

Method.  Focus groups were conducted with nurses working in palliative care units. Single interviews were conducted with doctors from a tertiary palliative care unit.

Results.  The findings revealed contesting discourses involving quality of life and the prolongation of life.

Conclusions.  The provision of food and fluid has profound emotional and social meanings for patients and families. The study reported here examined these issues with health professionals. The findings point to the challenges and tensions faced by health professionals in relation to decision making and medical hydration during end of life care. The concern is that tensions arise when decisions need to be made and how best to make these. The contesting discourses for nurses and doctors when nutrition and hydration is ceased involve maintaining quality of life vs. the prolongation of life.

Relevance to clinical practice.  Medical and nursing staff have different attitudes and beliefs towards end of life care. Tensions arise when decisions need to be made based on quality of life or prolongation of life. The successful merging of curative and palliative care is not without challenges. There has been little exploration of this situation.
Frequency of nurses’ smoking cessation interventions: report from a national survey
Authors: Sarna Linda , Bialous Stella A , Wells Marjorie , Kotlerman Jenny , Wewers Mary E , Froelicher Erika S
Published: June 2009

Aims and objectives.  To describe the frequency of nurses’ delivery of tobacco cessation interventions (‘Five A’s’: Ask, Advise, Assess, Assist, Arrange) and to determine the relationship of interventions to nurses’ awareness of the Tobacco Free Nurses initiative.

Background.  Tobacco cessation interventions can be effectively provided by nurses. The delivery of smoking cessation interventions by healthcare providers is mandated by several organisations in the USA and around the world. Lack of education and resources about tobacco cessation may contribute to the minimal level of interventions. The Tobacco Free Nurses initiative was developed to provide nurses with easy access to web‐based resources about tobacco control.

Design.  Cross‐sectional survey of nurses (n = 3482) working in 35 Magnet‐designated hospitals in the USA (21% response rate).

Method.  A valid and reliable questionnaire used in previous studies to assess the frequency of the nurse’s delivery of smoking cessation interventions (‘Five A’s’) was adapted for use on the web.

Results.  The majority of nurses asked (73%) and assisted (73%) with cessation. However, only 24% recommended pharmacotherapy. Only 22% referred to community resources and only 10% recommended use of the quitline. Nurses familiar with TFN (15%) were significantly more likely to report delivery of all aspects of interventions, including assisting with cessation (OR = 1·55, 95% CI 1·27, 1·90) and recommending medications (OR = 1·81, 95% CI 1·45, 2·24).

Conclusions.  Nurses’ delivery of comprehensive smoking cessation interventions was suboptimal. Awareness of Tobacco Free Nurses was associated with increased interventions.

Relevance to clinical practice.  Further efforts are needed to ensure that nurses incorporate evidence‐based interventions into clinical practice to help smokers quit. These findings support the value of Tobacco Free Nurses in providing nurses with information to support patients’ quit attempts.
Impact of segmental chromosomal duplications on leaf size in the grandifolia‐D mutants of Arabidopsis thaliana
Authors: Horiguchi Gorou , Gonzalez Nathalie , Beemster Gerrit T.S. , Inzé Dirk , Tsukaya Hirokazu
Published: June 2009

The number of cells in an organ is a major factor that specifies its size. However, the genetic basis of cell number determination is not well understood. To obtain insight into this genetic basis, three grandifolia‐D (gra‐D) mutants of Arabidopsis thaliana were characterized that developed huge leaves with two to three times more cells than the wild‐type. Genetic and microarray analyses showed that a large segmental duplication had occurred in all the gra‐D mutants, consisting of the lower part of chromosome 4. In the duplications, genes were found that encode AINTEGUMENTA (ANT), a factor that extends the duration of cell proliferation, and CYCD3;1, a G1/S cyclin. The expression levels of both genes increased and the duration of cell proliferation in the leaf primordia was extended in the gra‐D mutants. Data obtained by RNAi‐mediated knockdown of ANT expression suggested that ANT contributed to the huge‐leaf phenotype, but that it was not the sole factor. Introduction of an extra genomic copy of CYCD3;1 into the wild‐type partially mimicked the gra‐D phenotype. Furthermore, combined elevated expression of ANT and CYCD3;1 enhanced cell proliferation in a cumulative fashion. These results indicate that the duration of cell proliferation in leaves is determined in part by the interaction of ANT and CYCD3;1, and also demonstrate the potential usefulness of duplication mutants in the elucidation of genetic relationships that are difficult to uncover by standard single‐gene mutations or gain‐of‐function analysis. We also discuss the potential effect of chromosomal duplication on evolution of organ size.
Risk factors for SARS infection among hospital healthcare workers in Beijing: a case control study
Authors: Liu Wei , Tang Fang , Fang Li‐Qun , De Vlas Sake J. , Ma Huai‐Jian , Zhou Jie‐Ping , Looman Caspar W. N. , Richardus Jan Hendrik , Cao Wu‐Chun
Published: June 2009

Objective  To evaluate possible severe acute respiratory syndrome (SARS) infection associated risk factors in a SARS affected hospital in Beijing by means of a case control study.

Methods  Fifty‐one infected and 426 uninfected staff members were asked about risk behaviours and protective measures when attending to SARS patients. Univariate and multivariate logistic regression analyses were performed to identify the major risk and protective factors.

Results  Multivariate analysis confirmed the strong role of performing chest compression (or intubation, which is highly correlated), contact with respiratory secretion, and emergency care experience as risk factors to acquire SARS infection. For the studied protective measures, wearing 16‐layer cotton surgical mask, wearing 12‐layer cotton surgical mask, wearing multiple layers of mask, taking prophylactic medicine, taking training and nose washing turned out to be protective against infection.

Conclusions  This study highlighted activities associated with increased and decreased risk for SARS infection during close contact with SARS patients. These findings may help to guide recommendations for the protection of high‐risk occupational groups.
Post‐zygotic isolation in cactophilicDrosophila: larval viability and adult life‐history traits ofD. mojavensis/D. arizonaehybrids
Authors: BONO J. M. , MARKOW T. A.
Published: June 2009

Drosophila mojavensisandDrosophila arizonaeare cactophilic flies that have been used extensively in speciation studies. Incomplete premating isolation, evidence of reinforcement, and a lack of recent introgression between these species point to a potentially important role for post‐zygotic isolating barriers in this system. Other than hybrid male sterility, however, post‐zygotic isolation betweenD. mojavensisandD. arizonaehas received little attention. In this study, we examined viability and life‐history traits ofD. mojavensis/D. arizonaeF1hybrids from sympatric crosses. Specifically, we reared hybrids and purebreds on the natural host cacti of each parental species and compared viability, development time, thorax length, and desiccation resistance between hybrids and purebreds. Interestingly, hybrid females from both crosses performed similarly or even better than purebred females. In contrast, hybrid sons ofD. arizonaemothers, in addition to being sterile, had shorter average thorax length than males of both parental species, and hybrid males from both crosses had substantially lower desiccation resistance thanD. mojavensismales. The probable cost to hybridization forD. mojavensisfemales resulting from reduced desiccation resistance of hybrid sons may have been an important selective factor in the history of reinforcement for crosses involving these females.
The seven deadly sins of comparative analysis
Authors: FRECKLETON R. P.
Published: June 2009

Phylogenetic comparative methods are extremely commonly used in evolutionary biology. In this paper, I highlight some of the problems that are frequently encountered in comparative analyses and review how they can be fixed. In broad terms, the problems boil down to a lack of appreciation of the underlying assumptions of comparative methods, as well as problems with implementing methods in a manner akin to more familiar statistical approaches. I highlight that the advent of more flexible computing environments should improve matters and allow researchers greater scope to explore methods and data.
Genetic variation in the hypothalamic pathways and its role on obesity
Authors: Van Vliet‐Ostaptchouk J. V. , Hofker M. H. , Van Der Schouw Y. T. , Wijmenga C. , Onland‐Moret N. C.
Published: June 2009

Over recent decades, the prevalence of obesity has increased dramatically worldwide. Although this epidemic is mainly attributable to modern (western) lifestyle, multiple twin and adoption studies indicate the significant role of genes in the individual's predisposition to becoming obese. As the hypothalamus plays a central role in controlling body weight, its regulatory circuits may represent a crucial system in the pathogenesis of the disorder. Genetic variations in genes in the hypothalamic pathways may therefore contribute to the susceptibility for obesity in humans and animals.

We summarize current knowledge on the physiological role of the hypothalamus in body‐weight regulation and review genetic studies on the hypothalamic candidate genes in relation to obesity. Together, data from functional and genetic studies as well as the new, common, obesity loci identified in genome‐wide association scans support an important role for the hypothalamic genes in predisposing to obesity. However, findings are still inconclusive for many candidate genes. To improve our understanding of the genetic architecture of common obesity, we suggest that specific obesity phenotypes should be considered and different analytical approaches used. Such studies should consider multiple genes from the same physiological pathways, together with environmental risk factors.
Teachers making connections: Online communities as a source of professional learning
Authors: Duncan‐Howell Jennifer
Published: June 2009

The impact of the Internet on our lives has been pervasive. People are increasingly turning to the social interaction available on the Internet to satisfy their needs, whether these are professional or personal. The Internet offers users fast access to social contacts such as online chat groups and discussion lists, helping us to make connections with others. Online communities are being increasingly used by teachers for professional support, guidance and inspiration. These are often organised around subject areas and offer teachers opportunities to develop both personally and professionally. Online communities may present as a source of continuous professional development for teachers as they are able to deliver authentic and personalised opportunities for learning. This paper will present the findings of a study that was conducted on three online communities for teachers. It will explore the nature of online community membership and offer some conclusions regarding their potential as a source of professional learning for teachers.
Towards a material ethnography of linguistic landscape: Multilingualism, mobility and space in a South African township1
Authors: Stroud Christopher , Mpendukana Sibonile
Published: June 2009

The study of multilingual landscapes promises to introduce a new perspective into theories and policies of multilingualism, and to provide essential data for a politics of language. However, the theorization of space and language underlying the notion of linguistic landscape is not able to capture the manifold complexities of (transnational) multilingual mobility that is characteristic of many late‐modern multilingual societies. Basing our argument on signage data from a contemporary South Africa in a dynamic phase of social transformation, we argue that more refined notions of space coupled to a material ethnography of multilingualism could provide a theoretically more relevant and methodologically refocused notion of (multilingual) linguistic landscape. Specifically, we take an approach to landscapes as semiotic moments in the social circulation of discourses (in multiple languages), and view signs as re‐semiotized, socially invested distributions of multilingual resources, the material, symbolic and interactional artifacts of a sociolinguistics of mobility.
Improving predictions of the location and use of warrens in sensitive rabbit populations
Authors: Barrio I. C. , Bueno C. G. , Tortosa F. S.
Published: June 2009

The location and use of warrens is a key factor in the population dynamics of the European rabbitOryctolagus cuniculusL., which can influence stability and persistence in the long term. Within the species' original distribution range, its numbers have declined sharply in recent decades, which is a serious problem for the conservation of Mediterranean ecosystems. Artificial warrens are commonly used to bolster rabbit populations and the characterization of natural warrens in those areas might improve their efficiency. In this study, we use binomial generalized linear models to identify the factors associated with the location and use of warrens in a low‐density area and we evaluate the effect of including the spatial structure of the data in the model. In addition, we generate a map that predicts the most suitable areas for artificial warrens. Contrary to what was expected, habitat variables are only secondary factors, and the location and use of warrens is influenced mainly by spatial factors, such as proximity to nearby warrens. Furthermore, the aggregated spatial pattern of warrens suggests that, at the local scale, for example, the hunting estate, intra‐specific interactions might be playing a primary role in these low‐density populations. To identify the most suitable sites for artificial warrens and, thereby, improve the efficiency of artificial warren building for conservation purposes, information about spatial structures should be included in models predicting natural warrens of European rabbits.
Can a large metropolis sustain complex herpetofauna communities? An analysis of the suitability of green space fragments in Rome
Authors: Vignoli L. , Mocaer I. , Luiselli L. , Bologna M. A.
Published: June 2009

Urban areas are primary causes of species' range fragmentation and reduction. However, relatively few studies have attempted to describe the habitat variables influencing the diversity and conservation of amphibians and reptiles, particularly in Mediterranean Europe and in large metropolitan areas. We explored this broad conservation ecology problem by studying the richness and diversity patterns in relation to a suite of six independent habitat variables in Rome, one of the most ancient cities of the world. We considered all the green remnant areas (n=62) of Rome, ranging 1 to >1000 ha in size, which are interspersed within a sea of urbanized matrix. A total of 10 amphibian and 15 reptile species were studied. Their presence/absence patterns were assessed and the effects of the various habitat variables on each species were predicted by a logistic regression model. A total of 1261 presence records (404 amphibians and 857 reptiles) were analysed. Fragment size and wood size within each fragment did correlate significantly with the species richness of both amphibians and reptiles, and there was a clear threshold effect after 50 ha of wooded surface. The presence of water bodies positively affected the species distribution. One amphibian and three reptiles inhabited exclusively fragments >50 ha. The distance from the centre did not affect fragment species richness. The presence of most species of both amphibians and reptiles was positively influenced by the irregular versus circular shape of the wooded area. The legal protection of a given area did not influence the observed patterns but the total number of sheltered species. Overall, our study suggests that, in order to maintain the current diversity and population viability, it is necessary, in addition to water bodies' maintenance, to (1) preserve the wooded landscapes over 50 ha; (2) promote irregularly shaped increases in the wood surface; (3) maintain ecotonal boundaries.
Parent–child hostility and child ADHD symptoms: a genetically sensitive and longitudinal analysis
Authors: Lifford Kate J. , Harold Gordon T. , Thapar Anita
Published: June 2009

Background:  Families of children with attention‐deficit/hyperactivity disorder (ADHD) report higher rates of conflict within the family and more negative parent–child relationships. This study aimed to test whether negative parent–child relationships have a risk effect on ADHD symptoms using two complementary designs.

Method:  The first sample included 886 twin pairs, aged 11–17 years, derived from a population‐based twin study. The second sample was derived from a longitudinal community study and included 282 parents and their children, aged 11–14 years. Questionnaires were used to assess ADHD symptoms and hostility in the mother–child and father–child relationship. Bivariate genetic analysis was used to test the contribution of genetic and environmental factors to the association between parent–child hostility and ADHD symptoms in the twin sample. Cross‐lagged and reciprocal effects models were used to test for a bidirectional relationship between parent–child hostility and ADHD symptoms over time in the longitudinal study.

Results:  For boys, both genetic and environmental factors contributed to the link between mother–son hostility and ADHD symptoms, but genetic factors alone explained the association between father–son hostility and ADHD symptoms. For girls, the association between ADHD symptoms and mother–daughter hostility as well as father–child hostility was attributed to genetic factors alone. The longitudinal study provided evidence of boys’ ADHD symptoms impacting upon mother–son hostility both within and across time. There were no effects in the opposite direction.

Conclusions:  A causal hypothesis of family relations influencing ADHD symptoms was not supported. Boys’ ADHD symptoms appear to have an environmentally mediated impact upon mother–son hostility.
Positive illusions about a partner's physical attractiveness and relationship quality
Authors: BARELDS DICK P. H. , DIJKSTRA PIETERNEL
Published: June 2009

The present research examined the existence of positive illusions about a partner's physical attractiveness and its relations to relationship quality. Positive illusions were assumed to exist when individuals rated their partner as more attractive than their partner rated him or herself. In two Dutch community samples of 117 and 203 married or cohabiting heterosexual couples, both partners rated their own and their partner's facial and bodily attractiveness. In Study 2, both partners completed three measures of relationship quality. Both studies found evidence for the existence of positive illusions about a partner's physical attractiveness. Moreover, Study 2 found clear positive illusion actor effects for relationship quality. This association differed by age of couples.
Demand‐withdraw patterns in marital conflict in the home
Authors: PAPP LAUREN M. , KOUROS CHRYSTYNA D. , CUMMINGS E. MARK
Published: June 2009

The present study extended laboratory‐based findings of demand‐withdraw communication into marital conflict in the home and further explored its linkages with spousal depression. U.S. couples (N = 116) provided diary reports of marital conflict and rated depressive symptoms. Hierarchical linear modeling results indicated that husband demand‐wife withdraw and wife demand‐husband withdraw occurred in the home at equal frequency, and both were more likely to occur when discussing topics that concerned the marital relationship. For both patterns, conflict initiator was positively linked to the demander role. Accounting for marital satisfaction, both demand‐withdraw patterns predicted negative emotions and tactics during marital interactions and lower levels of conflict resolution. Spousal depression was linked to increased likelihood of husband demand‐wife withdraw.
Triggering neurotrophic factor actions through adenosine A2A receptor activation: implications for neuroprotection
Authors: Sebastião Ana M , Ribeiro Joaquim A
Published: June 2009

G protein coupled receptors and tropomyosin‐related kinase (Trk) receptors have distinct structure and transducing mechanisms; therefore, cross‐talk among them was unexpected. Evidence has, however, accumulated showing that tonic adenosine A2A receptor activity is a required step to allow synaptic actions of neurotrophic factors, namely upon synaptic transmission at both pre‐ and post‐synaptic level as well as upon synaptic plasticity. An enhancement of A2A receptor tonus upon ageing may partially compensate the loss of TrkB receptors, rescuing to certain degree the facilitatory action of brain derived neurotrophic factor in aged animals, which might prove particularly relevant in the prevention of neurodegeneration upon ageing. A2A receptors also trigger synaptic actions of other neurotrophic factors, such as glial derived neurotrophic factor at dopaminergic striatal nerve endings. The growing evidence that tonic adenosine A2A receptor activity is a crucial step to allow actions of neurotrophic factors in neurones will be reviewed and discussed in the light of therapeutic strategies for neurodegenerative diseases.
The ‘sweet’ and ‘bitter’ involvement of glycosaminoglycans in lung diseases: pharmacotherapeutic relevance
Authors: Papakonstantinou Eleni , Karakiulakis George
Published: June 2009

The extracellular matrix (ECM) plays a significant role in the structure and function of the lung. The ECM is a three‐dimensional fibre mesh, comprised of various interconnected and intercalated macromolecules, among which are the glycosaminoglycans (GAG). GAG are long, linear and highly charged, heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units (macromolecular sugars) and most of them, as their name implies, have a sweet taste. In the lung, GAG support the structure of the interstitium, the subepithelial tissue and the bronchial walls, and are secreted in the airway secretions. Besides maintaining lung tissue structure, GAG also play an important role in lung function as they regulate hydration and water homeostasis, modulate the inflammatory response and influence lung tissue repair and remodelling. However, depending on their size and/or degree of sulphation, and their immobilization or solubilization in the ECM, specific GAG in the lung either live up to their sweet taste/name, supporting normal lung physiology, or they are associated to ‘bitter’ effects, related to lung pathology. The present review discusses the biological role of GAG in the lung as well as the involvement of these molecules in various respiratory diseases. Given the great structural diversity of GAG, understanding the changes in GAG expression that occur in lung diseases may lead to novel targets for pharmacological intervention in order to prevent and/or to treat a range of lung diseases.
Inhibiting glycogen synthase kinase‐3 reduces endotoxaemic acute renal failure by down‐regulating inflammation and renal cell apoptosis
Authors: Wang Y , Huang WC , Wang CY , Tsai CC , Chen CL , Chang YT , Kai JI , Lin CF
Published: June 2009

Background and purpose:  Excessive inflammation and apoptosis are pathological features of endotoxaemic acute renal failure. Activation of glycogen synthase kinase‐3 (GSK‐3) is involved in inflammation and apoptosis. We investigated the effects of inhibiting GSK‐3 on lipopolysaccharide (LPS)‐induced acute renal failure, nuclear factor‐κB (NF‐κB), inflammation and apoptosis.

Experimental approach:  The effects of inhibiting GSK‐3 with inhibitors, including lithium chloride (LiCl) and 6‐bromo‐indirubin‐3′‐oxime (BIO), on LPS‐treated (15 mg·kg−1) C3H/HeN mice (LiCl, 40 mg·kg−1 and BIO, 2 mg·kg−1) and LPS‐treated (1 µg·mL−1) renal epithelial cells (LiCl, 20 mM and BIO, 5 µM) were studied. Mouse survival was monitored and renal function was analysed by histological and serological examination. Cytokine and chemokine production, and cell apoptosis were measured by enzyme‐linked immunosorbent assay and terminal deoxynucleotidyl transferase‐mediated dUTP–biotin nick‐end labelling staining, respectively. Activation of NF‐κB and GSK‐3 was determined by immunostaining and Western blotting, respectively.

Key results:  Mice treated with GSK‐3 inhibitors showed decreased mortality, renal tubular dilatation, vacuolization and sloughing, blood urea nitrogen, creatinine and renal cell apoptosis in response to endotoxaemia. Inhibiting GSK‐3 reduced LPS‐induced tumour necrosis factor‐α (TNF‐α) and CCL5/RANTES (released upon activation of normal T‐cells) in vivo in mice and in vitro in murine kidney cortical collecting duct epithelial M1 cells. Inhibiting GSK‐3 did not block TNF‐α‐induced cytotoxicity in rat kidney proximal tubular epithelial NRK52E or in M1 cells.

Conclusions and implications:  These results suggest that GSK‐3 inhibition protects against endotoxaemic acute renal failure mainly by down‐regulating pro‐inflammatory TNF‐α and RANTES.
Oncolytic gene therapy for canine cancers: teaching old dog viruses new tricks
Authors: Arendt M. , Nasir L. , Morgan I. M.
Published: June 2009

The use of viruses to treat cancer has been studied for decades. With the advancement of molecular biology, viruses have been modified and genetically engineered to optimize their ability to target cancer cells. Canine viruses, such as distemper virus and adenovirus, are being exploited for the treatment of canine cancer as the dog has proven to be a good comparative model for human cancer research and proof of concept investigations. In this review, we introduce the concept of oncolytic viruses and describe some of the preliminary attempts to use oncolytic viruses for the treatment of canine cancer.
The Accurate Control of Ultrafiltration
Authors: Flendrig J. Guus , Carpay Wim M. , Dekkers Wil T.
Published: June 2009

An apparatus has been constructed to regulate ultra‐filtration accurately during dialysis. The principle of the apparatus is that, per unit of time, exactly the same amount of dialysate is introduced into the dialyzer as is discharged from it. The apparatus consists of two isovolumetric pumps connected in line. The four compartments of the two pumps must change their functions at every pump stroke. This is accomplished by a switching system. There is a continuously closed dialysate circuit. The fluid extracted from this circuit will be replenished from the blood compartment of the dialyzer. Ultrafiltration is regulated by a simple peristaltic pump, which sucks the fluid out of the closed dialysate circuit. The isovolumetric pumps and the switching system are driven by the elevated pressure of the dialysate (0.5–1.0 atm). The apparatus can be used in single pass dialysis. Dialysis in accordance with the Bergström principle can be simply performed.

In over 5,000 dialyses with several types of dialyzers, ultrafiltration was always accurate within the measuring limits. Considerable improvement was noticed in the well‐being of the patients; hypotension, nausea, vomiting and muscle cramps were not seen.
Hemodiafiltration: A New Alternative To Hemofiltration And Conventional Hemodialysis*
Authors: Leber Heinrich‐Wolfgang , Wizemann Volker , Goubeaud G. , Rawer Peter , Schütterle Georg
Published: June 2009

A new dialysis method, termed hemodiafiltration, is proposed. The procedure consists of the combination of hemofiltration and conventional hemodialysis using high flux membranes with a transmembrane pressure (TMP) of 300–500 mmHg and a dialysate flow of 900 ml/min. Due to the combination of convective mass transfer and diffusion, the clearance values of both small and larger molecules are significantly higher than during hemofiltration or hemodialysis alone with the same membranes. The removal of excess water is better tolerated than during hemodialysis. With this new method, six patients have been successfully treated for six months (three times per week, three hours per treatment) without side effects. Thus, hemodiafiltration appears to be the method of choice to shorten dialysis time.
Surface Chemistry Characteristics of Human Umbilical Vein used as Chronic Canine Arteriovenous Fistulas
Authors: Shapiro Raphael I. , Cerra Frank B. , Hoffman Jeffrey K. , Baier Robert E.
Published: June 2009

Six bilateral loop arteriovenous fistulas from the femoral artery to the femoral vein were constructed in dogs using Dacron‐mesh‐coated human umbilical vein. Each graft was punctured twice weekly with a 16 gauge needle for up to 36 weeks, and biopsies were done every four to eight weeks. The long‐term patency was 83% at 24 weeks. There was no thrombosis from the needle puncture. Serial histologic examination revealed progressive transmural fibrous cell ingrowth and progressive neointimal cell formation. Scanning electron microscopy demonstrated areas of disrupted basement membrane covered with laminar fibrin meshes, probably representing sites of needle puncture. With multiple attenuated internal reflection spectroscopy of the graft lumens, minimal to moderate lipid deposition was observed to a depth of 1 μm at 32–36 weeks. No abnormal amounts of minerals were found within the graft walls with energy‐dispersive x‐ray analysis. Critical surface tensions remained within the biocompatible range of 20–30 dynes/cm. Human umbilical vein possesses many of the surface chemistry qualities of an ideal vascular prosthesis, has excellent long term patency, and is suitable for use where angioaccess with repeated needle puncture is needed.
The Green Design Apprenticeship
Authors: Matthews Deanna H. , Hawkins Troy R. , Jaramillo Paulina , Marriott Joe , Sharrard Aurora L.
Published: June 2009

In order to convey the results of our industrial ecology research to broader audiences, the Green Design Institute research group at Carnegie Mellon University offers the Green Design Apprenticeship for local high school students. The Green Design Apprenticeship introduces participants to industrial ecology concepts and how they intersect with engineering. The content of the program has evolved to include the topics of life cycle assessment, energy and water resources, transportation, and the built environment. The program has resulted in exposing a new generation of scholars to industrial ecology and has also benefited the research of graduate students involved with the program. The process of developing the instructional materials for younger, novice students based on complex industrial ecology research was a challenging task requiring thoughtful and iterative planning. Through the development and delivery of the program, we have experienced awareness of where our own research fits into the larger industrial ecology scope, have improved our communication of complex industrial ecology concepts into simple terms, and have gained valuable insight for engaging students in our teaching.
Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia
Authors: Pal Arnab , Srivastava Tapasya , Sharma Manish K , Mehndiratta Mohit , Das Prerna , Sinha Subrata , Chattopadhyay Parthaprasad
Published: June 2009

Hypoxia is an integral part of tumorigenesis and contributes extensively to the neoplastic phenotype including drug resistance and genomic instability. It has also been reported that hypoxia results in global demethylation. Because a majority of the cytosine‐phosphate‐guanine (CpG) islands are found within the repeat elements of DNA, and are usually methylated under normoxic conditions, we suggested that retrotransposable Alu or short interspersed nuclear elements (SINEs) which show altered methylation and associated changes of gene expression during hypoxia, could be associated with genomic instability. U87MG glioblastoma cells were cultured in 0.1% O2 for 6 weeks and compared with cells cultured in 21% O2 for the same duration. Real‐time PCR analysis showed a significant increase in SINE and reverse transcriptase coding long interspersed nuclear element (LINE) transcripts during hypoxia. Sequencing of bisulphite treated DNA as well as the Combined Bisulfite Restriction Analysis (COBRA) assay showed that the SINE loci studied underwent significant hypomethylation though there was patchy hypermethylation at a few sites. The inter‐alu PCR profile of DNA from cells cultured under 6‐week hypoxia, its 4‐week revert back to normoxia and 6‐week normoxia showed several changes in the band pattern indicating increased alu mediated genomic alteration. Our results show that aberrant methylation leading to increased transcription of SINE and reverse transcriptase associated LINE elements could lead to increased genomic instability in hypoxia. This might be a cause of genetic heterogeneity in tumours especially in variegated hypoxic environment and lead to a development of foci of more aggressive tumour cells.
Inhibition of IGF‐IR tyrosine kinase induces apoptosis and cell cycle arrest in imatinib‐resistant chronic myeloid leukaemia cells
Authors: Shi Ping , Chandra Joya , Sun Xiaoping , Gergely Mate , Cortes Jorge E. , Garcia‐Manero Guillermo , Arlinghaus Ralph B. , Lai Raymond , Amin Hesham M.
Published: June 2009

Although signalling through the type I insulin‐like growth factor receptor (IGF‐IR) maintains the survival of haematopoietic cells, a specific role of IGF‐IR in haematological neoplasms remains largely unknown. Chronic myeloid leukaemia (CML) is the most common subtype of chronic myeloproliferative diseases. Typically, CML evolves as a chronic phase (CP) disease that progresses into accelerated (AP) and blast phase (BP) stages. In this study, we show that IGF‐IR is universally expressed in four CML cell lines. IGF‐IR was expressed in only 30% and 25% of CP and AP patients, respectively, but its frequency of expression increased to 73% of BP patients. Increased expression levels of IGF‐IR with CML progression was supported by quantitative real‐time PCR that demonstrated significantly higher levels of IGF‐IR mRNA in BP patients. Inhibition of IGF‐IR decreased the viability and proliferation of CML cell lines and abrogated their growth in soft agar. Importantly, inhibition of IGF‐IR decreased the viability of cells resistant to imatinib mesylate including BaF3 cells transfected with p210 BCR‐ABL mutants, CML cell lines and primary neoplastic cells from patients. The negative effects of inhibition of IGF‐IR were attributable to apoptosis and cell cycle arrest due to alterations of downstream target proteins. Our findings suggest that IGF‐IR could represent a potential molecular target particularly for advanced stage or imatinib‐resistant cases.
INTERTEMPORAL CHOICE AND DEVELOPMENT POLICY: NEW EVIDENCE ON TIME‐VARYING DISCOUNT RATES FROM VIETNAM AND RUSSIA
Authors: ANDERSON C. Leigh , GUGERTY Mary Kay
Published: June 2009

Assuming that individual discount rates are constant over time has important implications for policies and programs that involve intertemporal decision making. Using original data from Vietnam and Russia, we find evidence that discount rates do change over time for many individuals, implying that preferences for savings and credit might not be intertemporally consistent. We find that commonly held beliefs about gender and age influences do not hold once having children and location are controlled for. Within countries, however, residency does matter. Rural Vietnamese populations have higher discount rates, and living in a Russian trading town is associated with significantly higher discount rates and present bias than living in a government town. We argue that these behaviors are particularly likely to influence resource allocation in developing economies because there are fewer formal institutions and competitive markets to temper their effects.
EXPLORING THE IMPORTANCE OF EXCESS FEMALE MORTALITY AND DISCRIMINATION IN “NATALITY” IN EXPLAINING THE “LOWNESS” OF THE SEX RATIO IN INDIA
Authors: JAYARAJ D.
Published: June 2009

The beginning of the present century has been marked by a shift in attention from “excess” female mortality to discrimination in natality in explaining the “lowness” of the sex ratio or proportion of women in India's population. Such a shift in focus seemingly suggests that discrimination in intra‐family allocation of resources has reduced substantially in India. In this context, an attempt has been made to decompose the observed lowness of the sex ratio in India vis‐à‐vis that of the stable population into that attributable to: (1) age structure difference, (2) excess female mortality, and (3) abnormalities in sex ratios at birth in India. Estimated contributions by each factor suggest that, as late as 2001, excess female mortality or the lowness of the relative survival advantage of women is the single most important determinant of “missing” women in India. The results also point to the importance of age structure difference, which accounts for a little more than 17% of the lowness of the sex ratio in India in 2001.
Functional meals: technological, practical and consumer perspectives
Authors: Rodgers Svetlana
Published: June 2009

Serving functional (health‐improving) meals in restaurants is a novel concept that requires complex product development to optimise taste and texture and minimise the impact of preparation on nutritional functionality. This can be facilitated through the latest technological advances such as the wide range of novel ingredients, equipment and preparation techniques including developments in molecular gastronomy. From a business perspective, functional meals present an opportunity for differentiation; from a consumer perspective, it offers an alternative to highly processed industrial functional foods such as those found on supermarket shelves. Technological complexity and legislative requirements are the main obstacles for future developments.