bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Cognitive Behaviour Therapies Validate Cognitive Models of Mood Disorders? A Review of the Empirical Evidence
Authors: Oei Tian P. S. , Free Michael L.
Published: September 2007

The efficacy of Cognitive Behaviour Therapy (CBT) in the treatment of depression is now established. However, explanations for the efficacy of CBT are mixed. The evidence needed to support the explanation advanced by cognitive theory is lacking. This paper critically reviews the available empirical evidence. Forty‐four outcome or process studies of therapy with depression are reviewed and 21 of these are subjected to a meta‐analysis to investigate the relationship between change in cognitions and change in level of depression during different kinds of therapy. Our analysis shows that: (1) change in cognitive style occurs in all four categories of treatment: CBT, Drug Therapy, Other‐Psychological Therapy, and Waiting List; (2) there was a significant difference between Waiting List and all the active treatments in change in cognitions, but not between active treatments; (3) the degree of change in cognitive style is significantly related to change in depression as measured by the Beck Depression Inventory (BDI), but not the Hamilton Rating Scale for Depression (HRS‐D); and (4) the relationship between cognitive change and depression is not unique to CBT. Our findings show that CBT does provide some support for the cognitive models of depression but the relationship between cognitive change and recovery from depression is not unique to CBT.
The Research Environment in Developing Countries: Contributions to the National Development of the Discipline
Authors: Adair John G.
Published: September 2007

Resources and the intellectual climate for research are important for quality scholarly work. Within the context of a national discipline, these factors play important roles in both facilitating and impeding its development. Peer review and feedback and productive role models shape new investigators, and thereby the course of the discipline. A strong national association and quality journal editing set standards for the discipline. The availability of journals and other resources, academic accountability, and a system to reward research contribute to an environment that encourages identification with the science and a commitment to research. In contrast, the absence of these factors promotes a diminished commitment that contaminates the intellectual climate and has serious consequences for the entire discipline. Consideration of the intellectual climate and the strategies to foster its development must give special consideration to the collectivistic nature of some cultures.
Factors Facilitating and Impeding Growth of Psychology in South Asia with Special Reference to India
Authors: Sinha Jai B.P.
Published: September 2007

The growth of psychology in South Asian countries has been impeded by the lack of intellectual climate, scarcity of resources, and poor professional support. These proximate factors are embedded in a socio‐cultural milieu of pervasive poverty, collectivism, and centralized control of resources. The cultural factors get a free hand because of the inappropriate nature of Western psychology, which is being transplanted as a greenhouse plant. Psychologists can come out of this greenhouse and develop an appropriate science by addressing societal problems from indigenous perspectives. If they do so, the same cultural factors would either facilitate the growth of psychology or be contained to a great extent.
Antecedents of Children's Performance on Class Inclusion Tasks: Some Zimbabwean Evidence
Authors: Mpofu Elias
Published: September 2007

An analysis of covariance hierarchical regression procedure was used to examine children's performance on verbally presented classification tasks in relation to the children's socio‐cultural background, age, level of schooling, and sex. Task perception and motivation were entered as covariates. A total of 296 black and white Zimbabwean children took part in the study. Social class membership, age, level of schooling, and sex explained a significant proportion of the variance in performance on the classification tasks, whereas cultural group membership did not. Implications for multicultural perspectives on children's cognitive development are discussed and suggestions made for further research.
The Perception of Ideal Best Friends by Chinese Adolescents
Authors: Cheng Cecilia , Bond Michael Harris , Chan Siu Ching
Published: September 2007

This study examines the characteristics of ideal best friends endorsed by Chinese adolescents. A comprehensive measure of person perception was used in order to assess those dimensions of personality where gender, similarity, and complementarity might be related to the rating of ideal best friends. Results indicated that ideal female best friends were rated higher on the communal dimension of Helpfulness; ideal male best friends were rated higher on the agentic dimensions of Extroversion, Assertiveness, and Application. Similarity effects were found for Openness to Experience, Extroversion, and Emotional Stability; complementarity effects for Assertiveness. These results were explained in terms of Chinese gender stereotypes and the requirements for harmonious dyadic interaction.
CREx: inferring genomic rearrangements based on common intervals
Authors: Bernt Matthias , Merkle Daniel , Ramsch Kai , Fritzsch Guido , Perseke Marleen , Bernhard Detlef , Schlegel Martin , Stadler Peter F. , Middendorf Martin
Published: September 2007

Summary: We present the web-based program CREx for heuristically determining pairwise rearrangement events in unichromosomal genomes. CREx considers transpositions, reverse transpositions, reversals and tandem-duplication-random-loss (TDRL) events. It supports the user in finding parsimonious rearrangement scenarios given a phylogenetic hypothesis. CREx is based on common intervals, which reflect genes that appear consecutively in several of the input gene orders.

Availability: CREx is freely available at http://pacosy.informatik.uni-leipzig.de/crex

Contact:  merkle@informatik.uni-leipzig.de
Activation of the ciliary neurotrophic factor (CNTF) signalling pathway in cortical neurons of multiple sclerosis patients
Authors: Dutta Ranjan , McDonough Jennifer , Chang Ansi , Swamy Lakshman , Siu Alan , Kidd Grahame J. , Rudick Richard , Mirnics Karoly , Trapp Bruce D.
Published: September 2007

Neuronal and axonal degeneration results in irreversible neurological disability in multiple sclerosis (MS) patients. A number of adaptive or neuroprotective mechanisms are thought to repress neurodegeneration and neurological disability in MS patients. To investigate possible neuroprotective pathways in the cerebral cortex of MS patients, we compared gene transcripts in cortices of six control and six MS patients. Out of 67 transcripts increased in MS cortex nine were related to the signalling mediated by the neurotrophin ciliary neurotrophic factor (CNTF). Therefore, we quantified and localized transcriptional (RT-PCR, in situ hybridization) and translational (western, immunohistochemistry) products of CNTF-related genes. CNTF-receptor complex members, CNTFRα, LIFRβ and GP130, were increased in MS cortical neurons. CNTF was increased and also expressed by neurons. Phosphorylated STAT3 and the anti-apoptotic molecule, Bcl2, known down stream products of CNTF signalling were also increased in MS cortical neurons. We hypothesize that in response to the chronic insults or stress of the pathogenesis of multiple sclerosis, cortical neurons up regulate a CNTF-mediated neuroprotective signalling pathway. Induction of CNTF signalling and the anti-apoptotic molecule, Bcl2, thus represents a compensatory response to disease pathogenesis and a potential therapeutic target in MS patients.
Isothermic surfaces in sphere geometries as Moutard nets
Authors: Bobenko Alexander I , Suris Yuri B
Published: September 2007

We give an elaborated treatment of discrete isothermic surfaces and their analogues in different geometries (projective, Möbius, Laguerre and Lie). We find the core of the theory to be a novel characterization of discrete isothermic nets as Moutard nets. The latter are characterized by the existence of representatives in the space of homogeneous coordinates satisfying the discrete Moutard equation. Moutard nets admit also a projective geometric characterization as nets with planar faces with a five-point property: a vertex and its four diagonal neighbours span a three-dimensional space.

Restricting the projective theory to quadrics, we obtain Moutard nets in sphere geometries. In particular, Moutard nets in Möbius geometry are shown to coincide with discrete isothermic nets. The five-point property, in this particular case, states that a vertex and its four diagonal neighbours lie on a common sphere, which is a novel characterization of discrete isothermic surfaces. Discrete Laguerre isothermic surfaces are defined through the corresponding five-plane property, which requires that a plane and its four diagonal neighbours share a common touching sphere. Equivalently, Laguerre isothermic surfaces are characterized by having an isothermic Gauss map. S-isothermic surfaces as an instance of Moutard nets in Lie geometry are also discussed.
Simultaneous inhibition of the mitogen‐activated protein kinase kinase and phosphatidylinositol 3′‐kinase pathways enhances sensitivity to paclitaxel in ovarian carcinoma
Authors: Kawaguchi Wakae , Itamochi Hiroaki , Kigawa Junzo , Kanamori Yasunobu , Oishi Tetsuro , Shimada Muneaki , Sato Sinya , Shimogai Ruri , Sato Seiya , Terakawa Naoki
Published: September 2007

Paclitaxel (PTX), one of the key drugs used to treat ovarian cancer, activates the Raf–mitogen‐activated protein kinase kinase (MEK) and phosphatidylinositol 3′‐kinase (PI3K) pathways, both considered to be proliferation and cell‐survival pathways. The present study aimed to clarify whether and how MEK and PI3K inhibitors affect sensitivity to PTX in ovarian cancer cells. We treated five ovarian cancer cell lines using PTX combined with MEK inhibitor (PD98059 [PD]) and PI3K inhibitor (LY294002 [LY]), then assessed cell viability, apoptosis, and expression of phosphorylated (p) MEK and pAkt. We also investigated the effect of combined treatment on survival in a xenograft model. The protein expression levels of MEK, pMEK, Akt, and pAkt were confirmed in all cell lines. pMEK levels increased after PTX treatment in all five ovarian cancer cell lines. Combining PTX with either PD or LY had an additive effect on cell‐growth inhibition. In contrast, we observed a synergistic effect when PTX was combined with both PD and LY. The number of apoptotic cells was significantly higher after treatment with PTX combined with PD and LY, compared with PTX alone or PTX with either PD or LY (P < 0.05). PD with PTX downregulated the protein expression level of pMEK and upregulated pAkt in all five cell lines. Treating nude mice with PTX and PD and LY prolonged survival in an ovarian cancer xenograft model (P < 0.005). These results indicate that further study is warranted for PTX combined with MEK inhibitor and PI3K inhibitor to treat ovarian carcinoma. (Cancer Sci 2007; 98: 2002–2008)
Upregulation of CC chemokine ligand 18 and downregulation of CX3C chemokine receptor 1 expression in human T‐cell leukemia virus type 1‐associated lymph node lesions: Results of chemokine and chemokine receptor DNA chip analysis
Authors: Shimizu Kei , Karube Kennosuke , Arakawa Fumiko , Nomura Yuko , Komatani Hideki , Yamamoto Kouhei , Yoshida Shiro , Aoki Ryosuke , Sugita Yasuo , Takeshita Morishige , Ohshima Koichi
Published: September 2007

Adult T‐cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T‐cell leukemia virus type 1 (HTLV‐1). The pathological features of the lymph nodes of ATLL change from those of lymphadenitis to Hodgkin's‐like features and those of lymphoma. Chemokines and their receptors are closely associated with T‐cell subgroups and immune responses. To clarify the relationship between chemokines and their receptor expression, as well as the development of ATLL, 17 cases with ATLL were analyzed using DNA chips of chemokines and their receptors. All cases showed a varied and mixed pattern of upregulated and downregulated gene expression of Th1, Th2, naïve, and cytotoxic cell‐associated chemokine genes. As CC chemokine ligand 18 (CCL18) accounted for the most upregulated gene and CX3C chemokine receptor 1 (CX3CR1) for the most downregulated gene, they were selected for immunohistochemical analysis. Immunohistochemical staining showed expression of the two genes in immunological cells, with a positive expression for reticulum cells, but not for ATLL cells. HTLV‐1‐associated lymphadenitis type (n = 13) and Hodgkin's‐like type (n = 12) cases showed significantly higher CCL18 expression than the non‐specific lymphadenitis cases (n = 10) (P < 0.05). However, all HTLV‐1‐associated cases showed significantly lower CX3CR1 expression than the non‐specific lymphadenitis cases (P < 0.05). These results suggest that upregulation of CCL18 expression and downregulation of CX3CR1 expression play a role in immune responses against the ATLL cells. (Cancer Sci 2007; 98: 1875–1880)
Ontogenetic changes in the association between antipredator responses and growth variables
Authors: WOHLFAHRT BIANCA , MIKOLAJEWSKI DIRK J. , JOOP GERRIT , VAMOSI STEVEN M.
Published: September 2007

Abstract 1. An organism’s growth parameters are expected to depend on environmental constraints, such as predation risk and food supply. However, antipredator responses, food intake, and thus growth of an animal may be mediated by behavioural traits, which are likely to differ among developmental stages. In this study, it was investigated how the relationship between growth and behavioural antipredator responses changes during ontogeny in the time‐constrained dragonfly species Libellula depressa, and which factors influenced specific behavioural decisions at different points in ontogeny.

2. The results revealed that behavioural strategies differed between larval developmental sages, depending on associations between larval growth, food supply, and predation risk. Early in ontogeny, faster development was correlated with high larval activity and high food supply. This resulted in high activity levels under high food conditions irrespectively of predator presence, and under low food supply in predator absence only. In the intermediate stage of development, all larvae displayed a high activity level, which was correlated in general with fast development. However, growth later in ontogeny was not only influenced by the activity level, but also by predator presence and food supply, with larvae reared under high food supply and/or in presence of predators attaining a higher final mass. Thus, not only the way in which larval growth parameters and behaviour are related changed during development, but also whether the factors influenced larval growth and behaviour. Once the larvae reached the ultimate stage of development, in which they overwinter, behavioural patterns observed were consistent with model predictions.

3. It is advocated that behavioural plasticity of prey organisms in different developmental stages should be analysed in the context of associated growth variables.
Context‐specific regulation of LINE‐1
Authors: Teneng Ivo , Stribinskis Vilius , Ramos Kenneth S.
Published: September 2007

The present study was conducted to evaluate the contextual specificity of long interspersed nuclear element‐1 (LINE‐1 or L1) activation by cellular stress and the role of the aryl hydrocarbon receptor (AHR) transcription factor and oxidative stress in the gene activation response. Activation of the AHR by the genotoxic carcinogen benzo(a)pyrene (BaP) increased L1 expression in human cervical carcinoma (HeLa) cells, human microvascular endothelial cells (HMEC), mouse vascular smooth muscle cells (mVSMC) and mouse embryonic kidney cells (mK4). In contrast, challenge with a different AHR ligand 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD), or UV irradiation (10–20 J/m2), induced L1 only in HeLa cells. Transactivation of the mouse L1Md‐A5 promoter was observed in all cell types challenged with BaP, while TCDD was without effect, and UV only activated L1 in HeLa cells. Genetic and pharmacological experiments implicated the AHR and oxidative stress as contextual determinants of L1 inducibility by cellular stress.
Sea‐level rise and drought interactions accelerate forest decline on the Gulf Coast of Florida, USA
Authors: DESANTIS LARISA R. G. , BHOTIKA SMRITI , WILLIAMS KIMBERLYN , PUTZ FRANCIS E.
Published: September 2007

Sea‐level rise threatens low‐lying coastal ecosystems globally. In Florida, USA, salinity stress due to increased tidal flooding contributes to the dramatic and well documented decline of species‐rich coastal forest areas along the Gulf of Mexico. Here, we present the results of a study of coastal forest stand dynamics in thirteen 400 m2 plots representing an elevation gradient of 0.58–1.1 m affected by tidal flooding and rising sea levels. We extended previously published data from 1992–2000 to 2005 to quantify the full magnitude of the 1998–2002 La Niña‐associated drought. Populations of the dominant tree species, Sabal palmetto (cabbage palm), declined more rapidly during 2000–2005 than predicted from linear regressions based on the 1992–2000 data. Dramatic increases in Juniperus virginiana (Southern red cedar) and S. palmetto mortality during 2000–2005 as compared with 1995–2000 are apparently due to the combined effects of a major drought and ongoing sea‐level rise. Additionally, coastal forest stands continued to decline in species richness with increased tidal flooding frequency and decreasing elevation. Stable isotope (H, O) analyses demonstrate that J. virginiana accesses fresher water sources more than S. palmetto. Carbon isotopes reveal increasing δ13C enrichment of S. palmetto and J. virginiana with increased tidal flooding and decreased elevation, demonstrating increasing water stress in both species. Coastal forests with frequent tidal flooding are unable to support species‐rich forests or support regeneration of the most salt‐tolerant tree species over time. Given that rates of sea‐level rise are predicted to increase and periodic droughts are expected to intensify in the future due to global climate change, coastal forest communities are in jeopardy if their inland retreat is restricted.
Impact of elevated carbon dioxide on the rhizosphere communities of Carex arenaria and Festuca rubra
Authors: DRIGO BARBARA , KOWALCHUK GEORGE A. , YERGEAU ETIENNE , BEZEMER T. MARTIJN , BOSCHKER HENRICUS T. S. , VAN VEEN JOHANNES A.
Published: September 2007

The increase in atmospheric carbon dioxide (CO2) levels is predicted to stimulate plant carbon (C) fixation, potentially influencing the size, structure and function of micro‐ and mesofaunal communities inhabiting the rhizosphere. To assess the effects of increased atmospheric CO2 on bacterial, fungal and nematode communities in the rhizosphere, Carex arenaria (a nonmycorrhizal plant species) and Festuca rubra (a mycorrhizal plant species) were grown in three dune soils under controlled soil temperature and moisture conditions, while subjecting the aboveground compartment to defined atmospheric conditions differing in CO2 concentrations (350 and 700 μL L−1). Real‐time polymerase chain reaction (PCR) and PCR‐denaturing gradient gel electrophoresis methods were used to examine effects on the size and structure of rhizosphere communities. Multivariate analysis of community profiles showed that bacteria were most affected by elevated CO2, and fungi and nematodes to a lesser extent. The influence of elevated CO2 was plant dependent, with the mycorrhizal plant (F. rubra) exerting a greater influence on bacterial and fungal communities. Biomarker data indicated that arbuscular mycorrhizal fungi (AMF) may play an important role in the observed soil community responses. Effects of elevated CO2 were also soil dependent, with greater influence observed in the more organic‐rich soils, which also supported higher levels of AMF colonization. These results indicate that responses of soil‐borne communities to elevated CO2 are different for bacteria, fungi and nematodes and dependent on the plant type and soil nutrient availability.
E‐business and organizational change: a structurational approach
Authors: Chu Catherine , Smithson Steve
Published: September 2007

Abstract. Although e‐business is a familiar part of the organizational landscape, its implementation remains a problem for large traditional organizations. This paper argues that the pervasiveness of e‐business calls for the adoption of an organizational change perspective to study its implementation. Using structuration theory, the paper analyzes a detailed case study of the implementation of a major e‐business initiative in a traditional automotive manufacturer. It shows how a combination of structural contradictions and unexpected consequences derailed the initiative.
Facilitation or Inhibition of the Oestradiol‐Induced Gonadotrophin Surge in the Immature Female Rat by Progesterone: Effects on Pituitary Responsiveness to Gonadotrophin‐Releasing Hormone (GnRH), GnRH Self‐Priming and Pituitary mRNAs for the Progesterone Receptor A and B Isoforms
Authors: Attardi B. , Scott R. , Pfaff D. , Fink G.
Published: September 2007

Progesterone can either facilitate or inhibit the oestradiol (E2)‐induced gonadotrophin surge. We have previously developed immature female rat models to characterise and investigate the mechanisms of progesterone inhibition or facilitation. The aim of the present study was to determine the role of pituitary responsiveness to gonadotrophin‐releasing hormone (GnRH) and GnRH self‐priming under conditions of progesterone‐facilitation and progesterone‐inhibition, and whether the underlying mechanisms reflect changes in mRNAs encoding the A and B isoforms of the progesterone receptor (PR) in the pituitary gland. Pituitary responsiveness to GnRH, determined by measuring the luteinising hormone (LH) response to one i.v. injection of GnRH, was decreased by 60–80% (P < 0.001) in the progesterone‐inhibition model. GnRH self‐priming, estimated as the increment in the LH response to the second of two injections of GnRH separated by 60 min, was also significantly reduced (P < 0.05) in this model. In the progesterone‐facilitation model, the LH response to GnRH injection was increased 2.5–3‐fold (P < 0.05), an effect suppressed by the progesterone receptor antagonist, mifepristone. Progesterone‐facilitation of LH release and increased pituitary responsiveness to GnRH were blocked by sheep anti‐GnRH serum injected i.v. immediately after insertion of progesterone implants. The PR‐B mRNA isoform, measured by solution hybridisation/RNase protection assay, was the predominant form in the pituitary of the immature female rat. PR‐B was increased by E2 and decreased by progesterone in both models. Thus, in immature female rats, progesterone‐inhibition of the E2‐induced LH surge is due to significant reduction in pituitary responsiveness to GnRH as well as in the magnitude of GnRH self‐priming. Progesterone‐facilitation of the E2‐induced LH surge is due to increased pituitary responsiveness to GnRH, which is mediated by PR, and depends on endogenous GnRH release. The differences between progesterone‐facilitation and progesterone‐inhibition are not due to differences in regulation of pituitary PR‐B mRNA.
Hyperglycaemic Hyperosmolar Nonketotic State as a Cause of Low Gonadotrophin Levels in Postmenopausal Diabetic Women: A Role for Severe Hypernatraemia
Authors: Lado‐Abeal J. , Lorenzo‐Solar M. , Lago‐Lestón R. , Palos‐Paz F. , Domingez‐Gerpe L.
Published: September 2007

Hypogonadotrophic hypogonadism is associated with uncontrolled diabetes mellitus. Hyperglycaemia is a unique metabolic abnormality of the hyperglycaemic hyperosmolar nonketotic state (HHNKS) and, as glucose availability regulates gonadotrophin release, we investigated whether gonadotrophin release is inhibited in diabetic women with HHNKS, and whether hyperglycaemia, hypernatraemia or both inhibit in vitro gonadotrophin‐releasing hormone (GnRH) expression in GT1‐7 neurones. Three groups of postmenopausal women were studied: nine diabetics with HHNKS, nine hospitalised ill nondiabetics and 15 healthy women. In addition, the effects of glucose (5.55, 33.3, 66.6 mmol/l) and sodium chloride (150 and 170 mmol/l) on GnRH expression were investigated using GT1‐7 neurones. Postmenopausal diabetics with HHNKS showed a decrease in serum levels of luteinising hormone (diabetic HHNKS 2.2 ± 0.9 IU/l versus ill nondiabetic 21.0 ± 2.3 IU/l and healthy controls 20.9 ± 2.8 IU/l, P < 0.01), follicle‐stimulating hormone (diabetic HHNKS 8.2 ± 2.1 IU/l versus ill nondiabetic 50.4 ± 9.1 IU/l and controls 60.2 ± 6.9 IU/l, P < 0.01) and free 3,5,3′‐triiodothyronine (diabetic HHNKS 1.48 ± 0.57 pmol/l versus ill nondiabetic 4.28 ± 0.26 pmol/l and controls 3.88 ± 0.11 pmol/l, P < 0.01). The plasma cortisol level was higher in both diabetic (985 ± 130 nmol/l) and ill nondiabetic (726 ± 52 nmol/l) women than in healthy women (512 ± 47 nmol/l), but no differences were observed in plasma oestradiol, thyroid‐stimulating hormone or free thyroxine. In vitro GT1‐7 neurones expressed three‐fold less GnRH at 170 mmol/l than at 150 mmol/l NaCl, whereas changing glucose concentrations in the culture medium did not affect GnRH expression. In conclusion, postmenopausal diabetic women with HHNKS show decreased serum gonadotrophin levels, and severe hypernatraemia may participate in the hypogonadotropism observed in HHNKS.
Paracrinicity: The Story of 30 Years of Cellular Pituitary Crosstalk
Authors: Denef C.
Published: September 2007

Living organisms represent, in essence, dynamic interactions of high complexity between membrane‐separated compartments that cannot exist on their own, but reach behaviour in co‐ordination. In multicellular organisms, there must be communication and co‐ordination between individual cells and cell groups to achieve appropriate behaviour of the system. Depending on the mode of signal transportation and the target, intercellular communication is neuronal, hormonal, paracrine or juxtacrine. Cell signalling can also be self‐targeting or autocrine. Although the notion of paracrine and autocrine signalling was already suggested more than 100 years ago, it is only during the last 30 years that these mechanisms have been characterised. In the anterior pituitary, paracrine communication and autocrine loops that operate during fetal and postnatal development in mammals and lower vertebrates have been shown in all hormonal cell types and in folliculo‐stellate cells. More than 100 compounds have been identified that have, or may have, paracrine or autocrine actions. They include the neurotransmitters acetylcholine and γ‐aminobutyric acid, peptides such as vasoactive intestinal peptide, galanin, endothelins, calcitonin, neuromedin B and melanocortins, growth factors of the epidermal growth factor, fibroblast growth factor, nerve growth factor and transforming growth factor‐β families, cytokines, tissue factors such as annexin‐1 and follistatin, hormones, nitric oxide, purines, retinoids and fatty acid derivatives. In addition, connective tissue cells, endothelial cells and vascular pericytes may influence paracrinicity by delivering growth factors, cytokines, heparan sulphate proteoglycans and proteases. Basement membranes may influence paracrine signalling through the binding of signalling molecules to heparan sulphate proteoglycans. Paracrine/autocrine actions are highly context‐dependent. They are turned on/off when hormonal outputs need to be adapted to changing demands of the organism, such as during reproduction, stress, inflammation, starvation and circadian rhythms. Specificity and selectivity in autocrine/paracrine interactions may rely on microanatomical specialisations, functional compartmentalisation in receptor–ligand distribution and the non‐equilibrium dynamics of the receptor–ligand interactions in the loops.
Chronic Central Administration of Apelin‐13 Over 10 Days Increases Food Intake, Body Weight, Locomotor Activity and Body Temperature in C57BL/6 Mice
Authors: Valle A. , Hoggard N. , Adams A. C. , Roca P. , Speakman J. R.
Published: September 2007

The peptide apelin has been located in a wide range of tissues, including the gastrointestinal tract, stomach and adipose tissue. Apelin and its receptor has also been detected in the arcuate and paraventricular nuclei of the hypothalamus, which are involved in the control of feeding behaviour and energy expenditure. This distribution suggests apelin may play a role in energy homeostasis, but previous attempts to discern the effects of apelin by acute injection into the brain have yielded conflicting results. We examined the effect of a chronic 10‐day intracerebroventricular (i.c.v.) infusion of apelin‐13 into the third ventricle on food intake, body temperature and locomotor activity in C57BL/6 mice. Apelin‐13 (1 µg/day) increased food intake significantly on days 3–7 of infusion; thereafter, food intake of treated and control individuals converged. This convergence was potentially because of progressive conversion of apelin‐13 to [Pyr1]apelin‐13 which has a four‐fold lower receptor binding affinity at the orphan G protein‐coupled receptor, APJ. Locomotor activity was also higher in the apelin‐treated mice, especially during the nocturnal peak, when most feeding occurs, and the first hours of the light phase. Body temperature was also elevated during this increased period of activity, but was otherwise unaffected. Apelin‐13‐infused animals gained more weight than the saline‐infused controls, suggesting the elevated locomotor activity did not offset the increased food intake. Elevated locomotion and the consequent increases in body temperature were probably secondary effects to the increased food intake. These results suggest that apelin‐13 may play a central role in the control of feeding behaviour and is one of only two peripheral ligands known to stimulate rather than inhibit intake. As apelin production is elevated during obesity, this may provide an important feed‐forward mechanism exacerbating the problem. Antagonists of the apelin receptor may therefore be useful pharmaceuticals in the treatment of obesity.
Increased expression of the MYB‐related transcription factor, PHR1, leads to enhanced phosphate uptake in Arabidopsis thaliana
Authors: NILSSON LENA , MÜLLER RENATE , NIELSEN TOM HAMBORG
Published: September 2007

Plants have evolved a number of adaptive strategies to cope with fluctuations in phosphorus (P) supply. The current knowledge of the transcriptional regulation of the P‐starvation response in plants is limited. However, one MYB‐related transcription factor, PHR1, is known to be involved in the P‐starvation response. In this paper, we characterize a T‐tagged phr1 knockout mutant and a series of transgenic plant lines which over‐express PHR1 in wild type (WT) and phr1 mutant background. The knockout mutant has an altered phosphate (Pi) allocation between root and shoot; accumulates less anthocyanins, sugars and starch than P‐starved WT; has a lower AGPase activity; and is impaired in induction of a subset of Pi starvation‐induced genes. Expression of PHR1 in the phr1 mutant rescues the responsiveness to P‐starvation and leads to WT levels of sugars and starch during Pi starvation conditions, confirming the involvement of PHR1 in adjusting carbon metabolism. Over‐expression of PHR1 further resulted in a dramatic increase in the microRNA miR399d, and this resulted in changes in the transcript level for the target gene PHO2. Furthermore, over‐expression of PHR1 in both WT and phr1 mutant results in strongly increased content of Pi irrespective of P regime. This shows that targeting a key regulatory element in the Pi starvation regulatory network represents a useful approach for molecular breeding of plants towards more efficient Pi uptake and assimilation.
The Arabidopsis her1 mutant implicates GABA in E‐2‐hexenal responsiveness
Authors: Mirabella Rossana , Rauwerda Han , Struys Eduard A. , Jakobs Cornelis , Triantaphylidès Christian , Haring Michel A. , Schuurink Robert C.
Published: September 2007

When wounded or attacked by herbivores or pathogens, plants produce a blend of six‐carbon alcohols, aldehydes and esters, known as C6‐volatiles. Undamaged plants, when exposed to C6‐volatiles, respond by inducing defense‐related genes and secondary metabolites, suggesting that C6‐volatiles can act as signaling molecules regulating plant defense responses. However, to date, the molecular mechanisms by which plants perceive and respond to these volatiles are unknown. To elucidate such mechanisms, we decided to isolate Arabidopsis thaliana mutants in which responses to C6‐volatiles were altered. We observed that treatment of Arabidopsis seedlings with the C6‐volatile E‐2‐hexenal inhibits root elongation. Among C6‐volatiles this response is specific to E‐2‐hexenal, and is not dependent on ethylene, jasmonic and salicylic acid. Using this bioassay, we isolated 18 E‐2‐hexenal‐response (her) mutants that showed sustained root growth after E‐2‐hexenal treatment. Here, we focused on the molecular characterization of one of these mutants, her1. Microarray and map‐based cloning revealed that her1 encodes a γ‐amino butyric acid transaminase (GABA‐TP), an enzyme that degrades GABA. As a consequence of the mutation, her1 plants accumulate high GABA levels in all their organs. Based on the observation that E‐2‐hexenal treatment induces GABA accumulation, and that high GABA levels confer resistance to E‐2‐hexenal, we propose a role for GABA in mediating E‐2‐hexenal responses.
The James Blundell Award Lecture 2006: transfusion and the treatment of haemorrhage: past, present and future
Authors: Dzik W. H.
Published: September 2007

summary In the early years of the 19th century, James Blundell reported in the Lancet the first clinical application of blood transfusion for the treatment of haemorrhage. Although these initial experiments may appear to us to have burst upon the medical world, Blundell had in fact done a decade of pre clinical research using animal models to establish principles to be brought to the clinic. His pivotal pre clinical experiments and the insights he gained are described in detail. Today, blood transfusion remains the cornerstone of treatment for serious bleeding – not only to restore oxygen carrying capacity but also to improve haemostasis, arrest and prevent bleeding. However, the indications for the use of blood components to treat bleeding remain ill‐defined. In particular, despite the enormous volumes of fresh frozen plasma (FFP) transfused worldwide, the evidence that commonly used coagulation tests are reliable guides to transfusion with FFP is scant. Recent laboratory and clinical studies provide insight into the weaknesses of current coagulation tests as a guide to blood management. In the future, the application of genomics to haemostasis will uncover genetic polymorphisms leading to improved diagnostics and more tailored medical therapeutics. Examples of the emerging use of clinical genomics are presented. Ultimately, the application of widescale genomics testing will refresh our understanding of human physiology and will reassert the importance of the individual in patient care.
Acquired cold urticaria symptoms can be safely prevented by ebastine
Authors: Magerl M. , Schmolke J. , Siebenhaar F. , Zuberbier T. , Metz M. , Maurer M.
Published: September 2007

Background:  Acquired cold urticaria (ACU) is a skin condition, in which exposure to cold results in wheals and itching and sometimes general systemic complications. It has a profound impact on patient quality of life. Second‐generation antihistamines are recommended as the first‐line treatment, but to date only a few have been scientifically tested for this condition.

Aim:  To assess the safety and efficacy of ebastine in preventing ACU symptoms.

Methods:  Twenty‐two adult ACU patients participated in a double‐blind crossover trial of 20 mg ebastine. The safety of ebastine was sensitively assessed with a psychometric battery testing cognitive performance and mood. After cold challenge, wheal and erythema were assessed by the investigator and the intensities of pruritus and burning were rated by the subject.

Results:  Ebastine had no negative impact on any of the parameters of cognitive performance or mood. It dramatically reduced the number of patients who experienced wheals, pruritus, and burning after challenge.

Conclusion:  Ebastine is safe and effective in preventing the symptoms of ACU.
A modified rapid monoclonal antibody‐specific immobilization of platelet antigen assay for the detection of human platelet antigen (HPA) antibodies: a multicentre evaluation
Authors: Campbell K. , Rishi K. , Howkins G. , Gilby D. , Mushens R. , Ghevaert C. , Metcalfe P. , Ouwehand W. H. , Lucas G.
Published: September 2007

Background  The monoclonal antibody‐specific immobilization of platelet antigens (MAIPA) assay is the cornerstone technique for the detection and identification of human platelet antigen (HPA) antibodies. However, the original technique described by Kiefel and colleagues requires approximately 8 h adding to diagnostic delay. Moreover, proficiency exercises indicate that there are substantial variations in the MAIPA protocol, and that these may account for interlaboratory differences in sensitivity and specificity.

Study Design and Methods  A review of current MAIPA assay protocols from six laboratories together with performance in quality‐assessment schemes identified several key variables potentially affecting the assay results. An optimized protocol was derived and assay time reduced to 5 h. The modified rapid MAIPA (MR‐MAIPA) assay was evaluated using 61 samples with a range of HPA antibodies typically encountered in cases of fetomaternal alloimmune thrombocytopenia (n = 22), post‐transfusion purpura (n = 8), platelet refractoriness (n = 7) and other platelet immune conditions (n = 24). The sensitivity of the assay was assessed using three international standards and the recombinant HPA‐1a antibody CamTran007. The results obtained were compared with the original findings obtained with the local MAIPA assays. In addition, four different glycoprotein IIb/IIIa capture monoclonal antibodies were evaluated for their effect on assay sensitivity.

Results  Complete concordance was found between the original MAIPA results and those obtained with the new assay when testing a selected panel of clinical samples. The modified assay had nanogram level sensitivity for the detection of HPA‐1a antibodies and titration of HPA‐1a and HPA‐5b antibody sensitivity standards yielded end‐points equal to or greater than the mean recorded in international workshops.

Conclusion  The MR‐MAIPA assay offers improved turnaround for the detection of HPA antibodies without loss of sensitivity.
The blood donation experience: self‐reported motives and obstacles for donating blood
Authors: Sojka B. Nilsson , Sojka P.
Published: September 2007

Background and Objectives  The aim of the study was to investigate motives for donating blood as well as difficulties and obstacles associated with blood donation as perceived by the donors themselves.

Materials and Methods  Six hundred consecutive blood donors (i.e. all blood donors with a history of at least one previous whole blood donation attending, during nine working days, the Blood Centre of Umeå University Hospital) received a self‐administered questionnaire that contained questions aimed at elucidating motives for donating blood (general motives for donating blood, specific motives for the first donation and motives for continuing to be an active blood donor). Questions concerning difficulties and obstacles that had to be overcome in order to continue being a blood donor were also included in the questionnaire.

Results  Altogether 531 whole blood donors filled in the questionnaire (88·5%; 322 men and 209 women). No statistically significant differences were found between male and female blood donors concerning general reasons and motives related to donating blood. The most frequently reported reasons for giving blood the first time were ‘influence from a friend’ (47·2% of donors) and ‘request via media’ (23·5% of donors). Among general reasons/motives with highest ranking of importance, the most commonly reported motive for donating blood were ‘general altruism’ (40·3%), ‘social responsibility/obligation’ (19·7%) and ‘influence from friends’ (17·9%). General altruism’ and ‘social responsibility/obligation’ were also the most frequent reasons for continuing to donate blood (68·4 and 16·0%, respectively). The most commonly reported obstacle to becoming a regular blood donor was ‘laziness’ (19·1%) followed by ‘fear of needles’ (10·5%).

Conclusions  Altruism was the most common general motive for donating blood and also for continuing to be an active blood donor. Yet, for the first blood donation, direct ‘influence from friends/relatives’, ‘media appeal’ and other types of recruitment were more commonly reported as reasons or motives for donating blood than altruism. The findings support the notion that different strategies should be used/adopted to get people to donate blood the first time (e.g. recruitment through other blood donors using, for example, the ‘bring a friend along’ method) and to retain these subjects as active blood donors (e.g. by information and by strengthening their sense of being a blood donor or their self‐efficacy etc.).
Long‐term changes and variability in diabetes risk factors prior to the development of impaired glucose homeostasis
Authors: Laspa E. , Christen A. , Efstathiadou Z. , Johnston D. G. , Godsland I. F.
Published: September 2007

Aims  To determine whether rate of change and variability in risk factors provides insight into the development of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or Type 2 diabetes (DM).

Methods  In a nested case‐control study, repeated risk factor measurements (mean number 4.3, duration 11.4 years) culminated in 59 men developing IFG (n = 37), IGT (n = 14) and/or DM (n = 11). For each case, two control subjects were matched for age and equivalence of follow‐up. Rates of change and variability in diabetes risk factors prior to diagnosis were quantified by regression analysis. Changes between penultimate and diagnostic visits were also analysed.

Results  The age‐related rise in body mass index (BMI) was attenuated prior to IFG compared with control subjects (+0.102 vs. +0.772 kg/m2/decade, P = 0.02). There was also some evidence for this prior to IGT and DM (IGT: –1.530 vs. +0.158 kg/m2/decade, P = 0.09; DM: –1.146 vs. +0.332 kg/m2/decade, non‐significant). Prior to onset, IGT cases were distinguished by higher inflammatory marker levels, a decline in insulinogenic index and greater variability in oral glucose tolerance test (OGTT) insulin, and DM cases by lower insulin sensitivity and higher liver enzyme activities. Fasting and OGTT glucose levels changed little during the mean 8.9 years prior to onset of IFG, IGT or DM. The transition to IGT or DM was accompanied by a fall in insulin sensitivity.

Conclusions  Except for BMI, change or variability in risk factor levels appears relatively unimportant in the development of clinically elevated glucose levels. Deterioration in glucose levels to IGT or DM occurs as a rapid, incremental increase accompanied by a decline in insulin sensitivity.
Serum angiotensin‐converting enzyme and frequency of severe hypoglycaemia in Type 1 diabetes: does a relationship exist?
Authors: Zammitt N. N. , Geddes J. , Warren R. E. , Marioni R. , Ashby J. P. , Frier B. M.
Published: September 2007

Aims  An association has been described between elevated serum angiotensin‐converting enzyme (ACE) and an increased risk of severe hypoglycaemia (SH). To ascertain whether this reported association could be replicated in a different country, it was re‐examined in 300 individuals with Type 1 diabetes.

Methods  People with Type 1 diabetes, none of whom was taking renin–angiotensin system blocking drugs, were recruited. Participants recorded the frequency with which they had experienced SH. Glycated haemoglobin (HbA1c) and serum ACE were measured. The difference in the incidence of SH between different quartiles of ACE activity and the relationship between serum ACE and SH were examined using non‐parametric statistical tests and a negative binomial model.

Results  Data were obtained from 300 patients [158 male; HbA1c median (range) 8.2% (5.2–12.8%), median age 36 years (16–88); duration of diabetes 14.5 years (2–49)]. The incidence of SH was 0.93 episodes per patient year. The mean incidence of SH in the top and bottom quartiles of ACE activity was 0.5 and 1.7 episodes per patient year, respectively, but this difference was not statistically significant (P = 0.075). Spearman's test showed a very weak, although statistically significant, association between serum ACE level and SH incidence (r = 0.115, P = 0.047). The binomial model also showed a statistically significant (P = 0.002), but clinically weak, relationship between serum ACE and SH.

Conclusions  The present survey showed a weak relationship between serum ACE and the frequency of SH, the clinical relevance of which is unclear. This limits the proposed role for serum ACE as an index of risk for SH.
Land Cover in a Managed Forest Ecosystem: Mexican Shade Coffee
Authors: Blackman Allen , Albers Heidi J. , ávalos-Sartorio Beatriz , Murphy Lisa Crooks
Published: September 2007

Managed forest ecosystems like shade coffee supply valuable ecological services. Yet little is known about the drivers and characteristics of clearing in such systems. We present a spatial econometric analysis of land cover in a shade coffee region in southern Mexico. We find that plots close to large cities are less likely to be cleared all other things being equal—the opposite of the pattern usually observed in natural forests. In addition, we find that membership in coffee‐marketing cooperatives, farm size, and certain soil types are associated with tree cover, while proximity to small town centers is associated with clearing.
Choosing Brands: Fresh Produce versus Other Products
Authors: Jin Yanhong H. , Zilberman David , Heiman Amir
Published: September 2007

Assuming that brands contribute to quality risk reduction, prestige, and design, we derive and test hypothesis on the willingness to pay (WTP) for brands across different product categories (electronics, clothing, packaged food, and fresh produce). Using the random effect tobit model on the stated point value of WTP and the ordered probit model on the stated range of WTP, we find that WTP for brands of fresh produce is least among the four product categories controlling for relevant demographic variations. Simulations show that fresh produce has a higher optimal price premium for brands but with a much smaller market share.
TAX COMPETITION IN THE PRESENCE OF INTERJURISDICTIONAL EXTERNALITIES: THE CASE OF CRIME PREVENTION*
Authors: Pinto Santiago M.
Published: September 2007

ABSTRACT The paper analyzes the effect of fiscal competition when local governments choose the level of public goods that generate spillover effects elsewhere. For instance, law enforcement activities affect both the crime level in the jurisdiction providing the good and in neighboring communities. The model shows that when local governments rely on capital taxation to finance these expenditures the spillover effects may not lead to an inefficient provision of public goods as predicted by the tax competition literature. In the model, capital is costlessly mobile and offenders relocate responding to differential criminal opportunities and differential local law enforcement efforts.