bluuebunny/crossref_metadata_2025 huggingface dataset:
Ayurveda and Panchakarma: Measuring the Effects of a Holistic Health Intervention
Authors: Conboy L. A. , Edshteyn Ingrid , Garivaltis Hilary
Published: May 2009

Ayurveda, the traditional medical system of India, is understudied in western contexts. Using data gathered from an Ayurvedic treatment program, this study examined the role of psychosocial factors in the process of behavior change and the salutogenic process. This observational study examined associations with participation in the 5-day Ayurvedic cleansing retreat program, Panchakarma. Quality of life, psychosocial, and behavior change measurements were measured longitudinally on 20 female participants. Measurements were taken before the start of the program, immediately after the program, and 3 months postprogram. The program did not significantly improve quality of life. Significant improvements were found in self-efficacy towards using Ayurveda to improve health and reported positive health behaviors. In addition, perceived social support and depression showed significant improvements 3 months postprogram after the subjects had returned to their home context. As a program of behavior change, our preliminary results suggest that the complex intervention Panchakarma may be effective in assisting one's expected and reported adherence to new and healthier behavior patterns.
Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells
Authors: Schofer Markus D. , Fuchs-Winkelmann S. , Wack C. , Rudisile M. , Dersch R. , Leifeld I. , Wendorff J. , Greiner A. , Paletta J. R. J. , Boudriot U.
Published: May 2009

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.
SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay
Authors: Yamashita Akio , Izumi Natsuko , Kashima Isao , Ohnishi Tetsuo , Saari Bonnie , Katsuhata Yukiko , Muramatsu Reiko , Morita Tomoko , Iwamatsu Akihiro , Hachiya Takahisa , Kurata Rie , Hirano Hisashi , Anderson Philip , Ohno Shigeo
Published: May 2009

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs containing premature translation termination codons (PTCs). SMG-1 and Upf1 transiently form a surveillance complex termed “SURF” that includes eRF1 and eRF3 on post-spliced mRNAs during recognition of PTC. If an exon junction complex (EJC) exists downstream from the SURF complex, SMG-1 phosphorylates Upf1, the step that is a rate-limiting for NMD. We provide evidence of an association between the SURF complex and the ribosome in association with mRNPs, and we suggest that the SURF complex functions as a translation termination complex during NMD. We identified SMG-8 and SMG-9 as novel subunits of the SMG-1 complex. SMG-8 and SMG-9 suppress SMG-1 kinase activity in the isolated SMG-1 complex and are involved in NMD in both mammals and nematodes. SMG-8 recruits SMG-1 to the mRNA surveillance complex, and inactivation of SMG-8 induces accumulation of a ribosome:Upf1:eRF1:eRF3:EJC complex on mRNP, which physically bridges the ribosome and EJC through eRF1, eRF3, and Upf1. These results not only reveal the regulatory mechanism of SMG-1 kinase but also reveal the sequential remodeling of the ribosome:SURF complex to the predicted DECID (DECay InDucing) complex, a ribosome:SURF:EJC complex, as a mechanism of in vivo PTC discrimination.
Too many ends: aberrant transposition: Figure 1.
Authors: Weil Clifford F.
Published: May 2009

A recent study by Zhang and colleagues published in the March 15, 2009, issue of Genes & Development (pp. 755–765) demonstrates that maize Ac/Ds transposons mediate translocations and other rearrangements through aberrant execution of the normal transposition process. Ac transposase uses one end from each of two neighboring elements in these events, which may happen more commonly than previously thought. In genomes where there can be many transposon ends scattered across all the chromosomes, such mistakes can have important consequences.
Global Positive Expectancies of the Self and Adolescents' Substance Use Avoidance: Testing a Social Influence Mediational Model
Authors: Carvajal Scott C . , Evans Richard I . , Nash Susan G . , Getz J. Greg
Published: May 2009

ABSTRACT
Grounded in theories of global positive expectancies and social influences of behavior, this investigation posited a model in which global positive expectancies are related to substance use as mediated by attitudes, subjective norms, self‐efficacy, and intentions. Using a cohort sample (
n = 525), structural equation modeling was employed to test the hypothesized predictions of future substance use. The findings suggest that, relative to adolescents with lower global positive expectancies, adolescents with higher global positive expectancies use substances less frequently over time because of their protective attitudinal and control‐oriented perceptions towards that behavior. Additionally, results from the current investigation also extend prior findings on the factor structure of global positive expectancies, suggesting these expectancies can be viewed as a second‐order factor representing optimism and two components of hope—agency and pathways.
Late Cenozoic structural and stratigraphic evolution of the northern Chinese Tian Shan foreland
Authors: Lu Honghua , Burbank Douglas W. , Li Youli , Liu Yunming
Published: May 2009

Three successive zones of fault‐related folds disrupt the proximal part of the northern Tian Shan foreland in NW China. A new magnetostratigraphy of the Taxi He section on the north limb of the Tugulu anticline in the middle deformed zone clarifies the chronology of both tectonic deformation and depositional evolution of this collisional mountain belt. Our ∼1200‐m‐thick section encompasses the upper Cenozoic terrigenous sequence within which ∼300 sampling horizons yield an age span of ∼8–2 Ma. Although the basal age in the Taxi He section of the Xiyu conglomerate (often cited as an indicator of initial deformation) is ∼2.1 Ma, much earlier growth of the Tugulu anticline is inferred from growth strata dated at ∼6.0 Ma. Folding of Neogene strata and angular unconformities in anticlines in the more proximal and distal deformed zones indicate deformation during Miocene and Early Pleistocene times, respectively. In the Taxi He area, sediment‐accumulation rates significantly accelerate at ∼4 Ma, apparently in response to encroaching thrust loads. Together, growth strata, angular unconformities, and sediment‐accumulation rates document the northward migration of tectonic deformation into the northern Tian Shan foreland basin during the late Cenozoic. A progradational alluvial–lacustrine system associated with this northward progression is subdivided into two facies associations at Tugulu: a shallow lacustrine environment before ∼5.9 Ma and an alluvial fan environment subsequently. The lithofacies progradation encompasses the time‐transgressive Xiyu conglomerate deposits, which should only be recognized as a lithostratigraphic unit. Along the length of the foreland, the locus of maximum shortening shifts between the medial and proximal zones of folding, whereas the total shortening across the foreland remains quite homogeneous along strike, suggesting spatially steady tectonic forcing since late Miocene times.
The use of gastrointestinal intubation studies for controlled release development
Authors: Sutton Steven C.
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Regional gastrointestinal absorption and toleration studies to support controlled release (CR) development have been limited to naso‐intubation and telemetric capsule methods.

• The use of intubation for this purpose has been individually reported for single CR candidates; viz rivastigmine, and UK‐338,003.

• Nyberg et al. have recently published a report on 13 Phase I studies using a telemetric capsule.

WHAT THIS STUDY ADDS

• When the highest ethical standards were employed in the recruitment, treatment, compensation and follow‐up care given to all participants, subjects were easily recruited, and clinical intubation studies were uncomplicated to complete.

• From the eight Phase I studies, improved methods are proposed for unequivocal interpretation of the results.

• When required, clinical intubation studies are uniquely designed to aid in the CR development of drug candidates.

AIMS

This review describes clinical results of gastrointestinal intubation studies of eight controlled release (CR) candidates under development during the 1990s and offers suggestions for determining why, when and how to conduct human intubation studies.

METHODS

Experience with the administration of the following eight compounds to various regions of the gastrointestinal tract is described: CJ‐13,610, CP‐195,543, CP‐331,684, CP‐409,092, CP‐424,391, azithromycin, sertraline, and trovafloxacin. Also included are human pharmacokinetic studies with prototype CR dosage forms for CJ‐13,610 and CP‐424,391.

RESULTS

Intubation studies, while appearing invasive, are safe and not unpleasant procedures that have been found to be valuable in the development of CR formulations.

CONCLUSIONS

The following recommendations are made regarding intubation studies: (i) no intubation study is recommended for compounds with high permeability, since these compounds are likely to be well absorbed from the colon; (ii) compounds with moderate permeability may require an intubation study if the dog colon and in silico models predict a marginally acceptable CR concentration–time profile; (iii) use a dose that approximates 1 h of the intended CR delivery rate; (iv) use the smallest volume possible; (v) define and record tubing placement; (vi) use a thermodynamically stable solution or/and suspension.
Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review
Authors: Staahl Camilla , Olesen Anne Estrup , Andresen Trine , Arendt‐Nielsen Lars , Drewes Asbjørn Mohr
Published: May 2009

AIM

Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non‐opioid analgesics have been assessed in human volunteers using experimental pain models.

METHODS

A literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non‐opioid analgesics.

RESULTS

Nonsteroidal anti‐inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods like evoked brain potentials. The N‐methyl‐D‐aspartate antagonists exemplified by ketamine generally needed strong, long‐lasting or repeated pain in the skin for detectable analgesia, whereas pain in muscle and viscera generally was more easily attenuated. Gabapentin worked well in several models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in modulation of experimental pain. Imipramine attenuated pain in most experimental models, whereas amitriptyline had weaker effects. Delta‐9‐tetrahydrocannabinol attenuated pain in only a few models.

CONCLUSIONS

Pain induction and assessment are very important for the sensitivity of the pain models. Generally, experimental pain models need to be designed with careful consideration of the pharmacological mechanisms and pharmacokinetics of analgesics. The drawback with the different study designs is also discussed. This knowledge can aid the decisions that need to be taken when designing experimental pain studies for compounds entering Phase I and II trials.
Gefitinib–phenytoin interaction is not correlated with the14C‐erythromycin breath test in healthy male volunteers
Authors: Chhun Stephanie , Verstuyft Celine , Rizzo‐Padoin Nathalie , Simoneau Guy , Becquemont Laurent , Peretti Ilana , Swaisland Alan , Wortelboer Robert , Bergmann Jean Francois , Mouly Stephane
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The response to gefitinib is variable and could be explained partly by the interindividual variability in gefitinib exposure.

• Gefitinib is mainly metabolized by CYP3A4 and CYP2D6, and is to a lesser extent a P‐glycoprotein (P‐gp) substrate.

• Patients with cancer are at high risk of drug–drug interactions, such as with phenytoin, a potent CYP3A4 inducer.

WHAT THIS STUDY ADDS

• The reduced systemic exposure of gefitinib with multiple‐dose phenytoin treatment.

• An effect attributed to the possible induction of intestinal CYP3A4 because of the lack of correlation between changes in gefitinib disposition and the erythromycin breath test and the lack of association between allelic variant in the ABCB1 gene and baseline and induced oral gefitinib clearance.

• The CYP2D6 extensive metabolizer seems to be less sensitive to the interaction with phenytoin, as the magnitude of induction of gefitinib clearance was greater in CYP2D6 poor metabolizers than in CYP2D6 extensive metabolizers.

AIMS

We aimed to describe the pharmacokinetic interaction between phenytoin, a potent CYP3A4 and P‐glycoprotein (P‐gp) (ABCB1) inducer, and gefitinib, a CYP3A4, CYP2D6 and P‐gp substrate.

METHODS

An open‐label, randomized, two‐phase crossover study was conducted. Eighteen healthy male volunteers (nine homozygous CC and nine homozygous TT as determined by theirABCB1C3435T polymorphism in exon 26) received a single oral dose of 250 mg gefitinib alone or after 5 days treatment with phenytoin (5 mg kg−1daily). Gefitinib plasma concentrations were determined by high‐performance liquid chromatography. Hepatic CYP3A4 activity was evaluated by the14C‐erythromycin breath test (ERMBT) and theABCB1andCYP2D6genetic polymorphisms were determined by the TaqMan allelic discrimination assay and long polymerase chain reaction, respectively.

RESULTS

Following treatment with phenytoin, mean gefitinibCmaxand AUC0–∞decreased by 26 ± 44% [95% confidence interval (CI) for the difference 5–48%,P= 0.005] and 47 ± 26% (95% CI for the difference 34–60%,P= 0.001), respectively, and apparent oral clearance increased by 126 ± 93% (95% CI for the difference 80–172%,P= 0.004). Concomitantly, phenytoin increased the mean ERMBT by 91 ± 44% (95% CI 75–105%,P< 0.001) from baseline, but the extent of liver CYP3A4 induction was not correlated to the extent of interaction. Furthermore, this interaction was independent ofABCB1genetic polymorphism. TheCYP2D6genotype was slightly but significantly related to gefitinib clearance (P= 0.04) during the control phase.

CONCLUSIONS

The significant interaction between gefitinib and phenytoin was not correlated with the erythromycin breath test and was independent ofABCB1polymorphism, but may involve presystemic CYP3A‐mediated intestinal first‐pass.
Effects ofGinkgo bilobaextract on the pharmacokinetics of bupropion in healthy volunteers
Authors: Lei He‐Ping , Ji Wei , Lin Jian , Chen Hao , Tan Zhi‐Rong , Hu Dong‐Li , Liu Li‐Juan , Zhou Hong‐Hao
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Bupropion, an antidepressant and smoking cessation drug, is metabolized to its active metabolite hydroxybupropion almost exclusively by CYP2B6.

• Ginkgo bilobais among the most commonly used herbal extract in the general population, and is likely to be used by depressed patients receiving bupropion.

• Studies have reported thatG. bilobaadministration to rats markedly increased the CYP content and CYP2B mRNA in the liver, and intake ofG. bilobaalso induced various hepatic CYP enzymes, especially CYP2B‐type enzymes.

• There may be drug interactions betweenG. bilobaextract and bupropion (CYP2B6 substrate).

WHAT THIS STUDY ADDS

• Fourteen‐day oral administration ofG. bilobaextract had no statistically significant effect on the pharmacokinetics of bupropion or its active metabolite hydroxybupropion, as measured by AUC, which suggestsG. bilobadoes not significantly affect the metabolism of bupropion following a single oral dose in healthy Chinese men.

AIMS

To assess the effects ofGinkgo bilobaextract on the pharmacokinetics of bupropion in healthy volunteers.

METHODS

Fourteen healthy male volunteers (age range 19–25 years) received orally administered bupropion (150 mg) alone and during treatment withG. biloba240 mg day−1(two 60‐mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6‐catalysed metabolite, hydroxybupropion.

RESULTS

Ginkgo bilobaextract administration resulted in no significant effects on the AUC0–∞of bupropion and hydroxybupropion. Bupropion mean AUC0–∞value was 1.4 µg·h ml−1[95% confidence interval (CI) 1.2, 1.6] prior toG. bilobatreatment and 1.2 µg·h ml−1(95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC0–∞value was 8.2 µg·h ml−1(95% CI 6.5, 10.4) beforeG. bilobaadministration and 8.7 µg·h ml−1(95% CI 7.1, 10.6) after treatment. TheCmaxof hydroxybupropion increased from 221.8 ng ml−1(95% CI 176.6, 278.6) to 272.7 ng ml−1(95% CI 215.0, 345.8) (P = 0.038) and thet1/2of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000).

CONCLUSIONS

Ginkgo bilobaextract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. AlthoughG. bilobaextract treatment appears to reduce significantly thet1/2and increase theCmaxof hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally withG. bilobaextract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion.
Frequency and nature of drug–drug interactions in a Dutch university hospital
Authors: Zwart‐van Rijkom Jeannette E. F. , Uijtendaal Esther V. , Ten Berg Maarten J. , Van Solinge Wouter W. , Egberts Antoine C. G.
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Drug–drug interactions (DDIs) may lead to often preventable adverse drug events and health damage.

• In Dutch community pharmacies approximately 6% of all prescriptions generate a DDI alert.

• Hospitalized patients may be especially at risk, as they are more severely ill and multiple medications may be prescribed simultaneously; however, only limited data are available on the frequency and nature of DDIs during hospitalization.

WHAT THIS STUDY ADDS

• In a Dutch university hospital 10% of all prescriptions generated a DDI alert; overall 25% of patients encountered at least one potential DDI.

• Besides the risk of decreased effectiveness (25% of the DDIs), the most frequently occurring potential clinical consequence of the DDIs was an increased risk of side‐effects, such as an increased bleeding risk (22% of DDIs), hypotension (15%) and nephrotoxicity (13%).

• Almost half of the DDIs could be managed by monitoring laboratory values.

AIM

Drug–drug interactions (DDIs) may lead to often preventable adverse drug events and health damage. Especially within hospitals, this might be an important factor, as patients are severely ill and multiple medications may be prescribed simultaneously. The objective of this study was to measure the frequency and nature of DDI alerts in a Dutch university hospital.

METHODS

All patients hospitalized in the University Medical Centre Utrecht in 2006 who were prescribed at least one medication were included. The frequency of DDIs was calculated as: (i) the percentage of patients experiencing at least one DDI, and (ii) the percentage of prescriptions generating a DDI alert. Based on the national professional guideline, DDIs were classified into categories of potential clinical outcome, management advice, clinical relevance (A–F) and available evidence (0–4).

RESULTS

Of the 21 277 admissions included, 5909 (27.8%) encountered at least one DDI. Overall, the prescribing physician received a DDI alert in 9.6% of all prescriptions. The most frequently occurring potential clinical consequence of the DDIs was an increased risk of side‐effects such as increased bleeding risk (22.0%), hypotension (14.9%), nephrotoxicity (12.6%) and electrolyte disturbances (10.5%). Almost half (48.6%) of the DDIs could be managed by monitoring laboratory values.

CONCLUSIONS

Computerized DDI alerts may be a useful tool to prevent adverse drug events within hospitals, but they may also result in ‘alert fatigue’. The specificity of alerts could significantly improve by the use of more sophisticated clinical decision support systems taking into account, for example, laboratory values.
Timed feeding of mice modulates light‐entrained circadian rhythms of reticulated platelet abundance and plasma thrombopoietin and affects gene expression in megakaryocytes
Authors: Hartley Paul S. , Sheward John , Scholefield Emma , French Karen , Horn Jacqueline M. , Holmes Megan C. , Harmar Anthony J.
Published: May 2009

Circadian (c. 24 h) rhythms of physiology are entrained to either the environmental light‐dark cycle or the timing of food intake. In the current work the hypothesis that rhythms of platelet turnover in mammals are circadian and entrained by food intake was explored in mice. Mice were entrained to 12 h light‐dark cycles and given either ad libitum (AL) or restricted access (RF) to food during the light phase. Blood and megakaryocytes were then collected from mice every 4 h for 24 h. It was found that total and reticulated platelet numbers, plasma thrombopoietin (TPO) concentration and the mean size of mature megakaryocytes were circadian but not entrained by food intake. In contrast, a circadian rhythm in the expression of Arnt1 in megakaryocytes was entrained by food. Although not circadian, the expression in megakaryocytes of Nfe2, Gata1, Itga2b and Tubb1 expression was downregulated by RF, whereas Ccnd1 was not significantly affected by the feeding protocol. It is concluded that circadian rhythms of total platelet number, reticulated platelet number and plasma TPO concentration are entrained by the light‐dark cycle rather than the timing of food intake. These findings imply that circadian clock gene expression regulates platelet turnover in mammals.
Quantification of seminal germ cells in azoospermia: correlations with testicular histology and TESE outcome
Authors: Yeung C. H. , Beiglböck‐Karau L. , Luetjens C. M. , Wunsch A. , Nieschlag E.
Published: May 2009

In the treatment of male infertility by intra‐cytoplasmic injection of spermatozoa (ICSI) extracted from testicular tissue (TESE), the high incidence of negative TESE outcome calls for non‐invasive prognostic methods. Literature suggests that seminal haploid germ cell detection could be one. For this purpose, a multi‐parametric stringent flow cytometric method was applied to 50 TESE patients for the quantification of ejaculated germ cells. Cells from 50 ejaculates were identified and quantified as spermatozoa (HC, highly condensed), round spermatids (1N), primary spermatocytes (SPC) (4N) or diploid cells (2N, including somatic and non‐testicular cells) by their DNA and mitochondria staining and laser scatter characteristics, and compared with testicular biopsy histology and TESE outcome. Whereas 96% of patients displayed a diploid peak in the distribution histograms, the HC, 1N and 4N peaks were absent from the majority of samples. In 13 ejaculates, either a HC or 1N or 4N peak, or a combination of these, was discernible. Although seminal germ cell numbers bore no overall association with elongated spermatids (ES) in histology or spermatozoa retrieval in TESE outcome, 4N cells per ejaculate were correlated with the percentage of tubule sections showing SPC as the most advanced germ cells. The incidence of HC peaks was higher in patients showing some ES in histology or sperm retrieval than in the sperm‐negative groups. In groups with suspected obstruction showing nearly full spermatogenesis and maximal sperm retrieval, there was no incidence of a HC peak. Germ cell peaks were associated with germ cell degeneration noted in testicular histology. In conclusion, seminal germ cells cannot provide good prognosis for TESE, although their presence could indicate the spermatogenic activity in the testis.
Intimate partner abuse factors associated with women’s health: a general population study
Authors: Svavarsdottir Erla Kolbrun , Orlygsdottir Brynja
Published: May 2009

Title.  Intimate partner abuse factors associated with women’s health: a general population study.

Aim.  This paper is a report of a study to investigate the correlates of physical and psychological health in a general population‐based sample of Icelandic women who experienced abuse in close relationships.

Background.  Most studies examining the health concerns associated with intimate partner abuse have been based on clinical populations; however, their findings may not be representative of the general population of women experiencing intimate partner abuse.

Method.  A cross‐sectional correlational study was conducted. The Women’s Response to Battering Model was used to guide the choice of variables. Questionnaires were mailed to 7523 randomly‐selected Icelandic women. Data collection started in December 2005 and ended a year later. A total of 1974 married and 772 cohabiting women answered the questionnaires (n = 2746). Independent t‐tests and stepwise regression were used to analyse the data.

Findings.  Health risk behaviours (e.g. alcohol misuse, smoking), chronic health conditions/illnesses (e.g. sleep disturbance, depression, eating disorders) and currently being victim of intimate partner violence predicted the women’s physical and psychological health.

Conclusion.  Interventions designed to decrease health risk behaviours, treat chronic health conditions/illnesses and offer best practice first response to women who are victims of intimate partner violence can be offered to reduce the short‐ and long‐term effects of violence on their physical and psychological health. Public health policy needs to focus specifically on intimate partner violence against women and the role that public health nurses can have in early identification and offering appropriate interventions within primary healthcare settings.
The lack of mitochondrial AtFtsH4 protease alters Arabidopsis leaf morphology at the late stage of rosette development under short‐day photoperiod
Authors: Gibala Marta , Kicia Marta , Sakamoto Wataru , Gola Edyta M. , Kubrakiewicz Janusz , Smakowska Elwira , Janska Hanna
Published: May 2009

AtFtsH4 is one of four inner membrane‐bound mitochondrial ATP‐dependent metalloproteases in Arabidopsis thaliana, called AAA proteases, whose catalytic site is exposed to the intermembrane space. In the present study, we used a reverse‐genetic approach to investigate the physiological role of the AtFtsH4 protease. We found that loss of AtFtsH4 did not significantly affect Arabidopsis growth under optimal conditions (long days); however, severe morphological and developmental abnormalities in late rosette development occurred under short‐day conditions. The asymmetric shape and irregular serration of expanding leaf blades were the most striking features of the ftsh4 mutant phenotype. The severe abnormal morphology of the leaf blades was accompanied by ultrastructural changes in mitochondria and chloroplasts. These abnormalities correlated with elevated levels of reactive oxygen species and carbonylated mitochondrial proteins. We found that two classes of molecular chaperones, Hsp70 and prohibitins, were over‐expressed in ftsh4 mutants during late vegetative growth under both short‐ and long‐day conditions. Taken together, our data indicate that lack of AtFtsH4 results in impairment of organelle development and Arabidopsis leaf morphology under short‐day conditions.
The relative importance of birds and bees in the pollination ofMetrosideros excelsa(Myrtaceae)
Authors: SCHMIDT‐ADAM GABRIELE , MURRAY BRIAN G. , YOUNG ANDREW G.
Published: May 2009

Exclusion experiments were used to assess the effect of different pollinator groups on outcrossing and seed production inMetrosideros excelsa. The main study site was Little Barrier Island, New Zealand where indigenous bird and native solitary bees are the main flower visitors. Our results showed that native birds were more important pollinators ofM. excelsathan native bees. Seed production was much higher in open pollination than in two exclusion experiments where either birds were excluded and native bees only had access to flowers, or where all pollinators had been excluded. The number of fertile seeds per capsule was 45% higher after open pollination than in treatments with bee visitation only and 28% higher than in treatments where all flower visitors were excluded. Estimated outcrossing rates were significantly higher (tm = 0.71) for open pollination in the upper canopy (>4 m above‐ground level) where bird visitation is presumed to be more frequent than for a treatment with native bee access only (tm = 0.40). Our results also suggest that a large proportion of seeds (66%) arise from autonomous self‐pollination when all pollinators are excluded. In four trees of a modified mainland population with predominantly introduced birds and a mixture of introduced and native bees there was no decrease in seed production for the treatment allowing bee access only, indicating that – in contrast to native bees – honeybees may be more efficient pollinators ofM. excelsa. Observation of the foraging behaviour of both groups of bees showed that native bees contact the stigma of flowers less frequently than honeybees. This is likely to be a consequence of their smaller body size relative to honeybees.
The ecological value of Eryngium horridum in maintaining biodiversity in subtropical grasslands
Authors: FIDELIS ALESSANDRA , OVERBECK GERHARD E. , PILLAR VALÉRIO D. , PFADENHAUER JÖRG
Published: May 2009

The role of facilitation in the structuring of plant communities has been often demonstrated in environments under high abiotic stress, especially in semi‐arid and arid ecosystems and high elevations. Few studies, however, analysed facilitation in systems that are highly productive and rich in species, which are thought to be theoretically unlikely to demonstrate strong effects of facilitation. Here, we investigate the importance of Eryngium horridum, a rosette species, on the maintenance of plant diversity in subtropical grasslands in southern Brazil. We evaluated facilitation in areas under two different types of management: abandonment and grazing. Plots were established in areas with and without individuals of E. horridum and all species were identified and had their cover estimated. The Relative Neighbour Effect index was calculated in order to verify the presence of competition or facilitation. Our results indicated facilitation in both abandoned and in grazed grasslands, but apparently through different mechanisms. In the first case, the plant's architecture opens the canopy and allows more light to reach small forbs in the grass matrix. In the second case, E. horridum appears to protect more palatable species from herbivores. Otherwise considered an obnoxious species, E. horridum plays an important ecological role in subtropical grasslands in southern Brazil by facilitating other species and consequently, increasing local richness. Areas with this rosette species are important sources of diaspores, which are able to colonize new open sites and thus, maintain biodiversity.
SUCCESS, TRUTH, AND MODERNISM IN HOLOCAUST HISTORIOGRAPHY: READING SAUL FRIEDLÄNDER THIRTY‐FIVE YEARS AFTER THE PUBLICATION OF METAHISTORY1
Authors: KANSTEINER WULF
Published: May 2009

This essay provides a close reading of Saul Friedländer's exceptionally successful comprehensive history of the Holocaust from the theoretical perspective of Hayden White's philosophy of history. Friedländer's The Years of Extermination has been celebrated as the first synthetic history of the “Final Solution” that acknowledges the experiences of the victims of Nazi genocide. But Friedländer has not simply added the voices of the victims to a conventional historical account of the Holocaust. Instead, by displacing linear notions of time and space and subtly deconstructing conventional concepts of causality, he has invented a new type of historical prose that performs rather than analyzes the victims' point of view. Friedländer's innovation has particularly radical consequences for the construction of historical explanations. On the one hand, Friedländer explicitly argues that anti‐Semitism was the single most important cause of the Holocaust. On the other hand, his transnational, multifaceted history of the “Final Solution” provides a wealth of data that escapes the conceptual grasp of his explicit model of causation. Friedländer chooses this radically self‐reflexive strategy of historical representation to impress on the reader the existential sense of disbelief with which the victims experienced Nazi persecution. To Friedländer, that sense of disbelief constitutes the most appropriate ethical response to the Holocaust. Thus the narratological analysis of The Years of Extermination reveals that the exceptional quality of the book, as well as presumably its success, is the result of an extraordinarily creative act of narrative imagination. Or, put into terms developed by White, who shares Friedländer's appreciation of modernist forms of writing, The Years of Extermination is the first modernist history of the Holocaust that captures, through literary figuration, an important and long neglected reality of the “Final Solution.”
DIGITALIZING HISTORICAL CONSCIOUSNESS
Authors: FOGU CLAUDIO
Published: May 2009

What is a “historical” video game, let alone a successful one? It is difficult to answer this question because all our definitions of history have been constructed in a linear‐narrative cultural context that is currently being challenged and in large part displaced by digital media, especially video games. I therefore consider this question from the point of view of historical semantics and in relation to the impact of digital technology on all aspects of the historiographical operation, from the establishment of digital archives, to the production of e‐texts, to the digital remediation of visual modes of historical representation. Seen from this dual perspective, video games appear to participate in a process of spatialization and virtualization of historical semantics. In the first place, video games have begun to detach the notion of history from its double reference to the past and to the real—“what essentially happened”—that it had acquired at the end of the eighteenth century. Second, they also challenge the semiotic production of “historic events” that has characterized the construction of modern historical consciousness. Historical video games, in other words, replace representation with simulation and presence with virtuality, thereby marginalizing the oscillation of the modern historical imagination between historical facts and historic events, transcendence and immanence, representation and presence. Although digital reworkings of historical semantics have not produced any grammatical transformation of the signifier, history—nor does this essay propose one—I do argue that the impact of video games on our contemporary historic(al) culture is of paradigmatic proportions similar to those described by Reinhart Koselleck for the dawn of the modern age. Focusing on one of the most successful contemporary video games, Sid Meier's Civilization, I show how the remediation of cinematic genres by video games is pushing the processes of de‐temporalization and de‐referentialization of history toward the formation of a new notion of the historical that may be conceptualized as the inversion of the classic Aristotelian paradigm: history has replaced poetry and philosophy as the realm of the possible.
An International Actor Under Pressure: The Impact of the War on Terror and the Fifth Enlargement on EU Voting Cohesion at the UN General Assembly 2000–05*
Authors: JAKOBSSON ULF
Published: May 2009

This article examines empirically whether Iraq and the fifth enlargement affected EU voting cohesion at the UN General Assembly 2000–05. It poses the question of whether the entrants' willingness to co‐operate might have ameliorated the expected adverse effects of Iraq and an increase in the number of new members.
Momentum and Impediments: Why Europe Won't Emerge as a Full Political Actor on the World Stage Soon*
Authors: KROTZ ULRICH
Published: May 2009

Is Europe about to rise as a full political actor on the world stage? Conventional wisdom had it that European integration in foreign policy, security and defence was unlikely to amount to much very quickly. More recently, however, a diverse group of scholars has argued that pan‐European political actorhood had gained considerable substance. Surveying the recent literature, pertinent related writings and relevant primary materials on the matter, this article identifies and systematizes the many different factors affecting European high‐politics actorhood in the early 21st century. A fully grown international actor Europe, it finds, remains a longer‐term project rather than an imminent prospect.
Dominant role of lipid rafts L‐type calcium channel in activity‐dependent potentiation of large dense‐core vesicle exocytosis
Authors: Park Yongsoo , Kim Kyong‐Tai
Published: May 2009

Calcium influx triggers exocytosis by promoting vesicle fusion with the plasma membrane. However, different subtypes of voltage‐gated calcium channel (VGCC) have distinct roles in exocytosis. We previously reported that repetitive stimulation induces activity‐dependent potentiation (ADP) which represents the increase of neurotransmitter release. Here, we show that L‐type VGCC have a dominant role in ADP of large dense‐core vesicle (LDCV) exocytosis. Repetitive stimulation activating VGCC can induce ADP, whereas activation of bradykinin (BK) G protein‐coupled receptors or purinergic P2X cation channels can not. L‐type VGCC has the dominant role in ADP of LDCV exocytosis by regulating Protein Kinase C (PKC)‐epsilon translocation and phosphorylation of myristoylated alanine‐rich C kinase substrate (MARCKS), a target molecule of PKC‐epsilon. We provide evidence that L‐type VGCC, PKC‐epsilon, and MARCKS, but not Q‐type VGCC, are selectively located in lipid rafts. Also, PKC‐epsilon translocation induced by L‐type VGCC activation occurs in lipid rafts. Disruption of lipid rafts abolishes ADP of LDCV exocytosis and changes the fusion pore kinetics without affecting the first stimulation‐induced exocytosis, showing that lipid rafts are involved in the potentiation process. Taken together, we suggest that L‐type VGCC in lipid rafts selectively mediates ADP of LDCV exocytosis by regulating PKC‐epsilon translocation and MARCKS phosphorylation.
Do Very High Tax Rates Induce Bunching? Implications for the Design of Income Contingent Loan Schemes*
Authors: CHAPMAN BRUCE , LEIGH ANDREW
Published: May 2009

Under the Higher Education Contribution Scheme graduates face a sharp discontinuity in their taxable incomes. At the first repayment threshold, they are required to pay a percentage of their entire income to reduce their debts. This results in an extremely high effective marginal tax rate. Using a sample of taxpayer returns we investigate whether taxpayers bunch below the repayment threshold. We find a statistically significant degree of bunching below the threshold, but the effect is economically small. The result has important implications for the design of income contingent university loan schemes.
β1‐ and β2‐Adrenoceptor polymorphisms and cardiovascular diseases
Authors: Leineweber Kirsten , Heusch Gerd
Published: May 2009

β1‐ and β2‐Adrenoceptors (AR) play a pivotal role in the regulation of cardiovascular function. Both β‐AR subtypes are polymorphic: two single nucleotide polymorphisms (SNPs) have been described for the β1‐ (Ser49Gly, Arg389Gly) and four for the β2‐AR (Arg‐19Cys, Arg16Gly, Gln27Glu, Thr164Ile), and they are possibly of functional relevance. In recombinant cell systems, Gly49‐β1‐AR are more susceptible to agonist‐promoted down‐regulation than Ser49‐β1‐AR, whereas Arg389‐β1‐AR are three to four times more responsive to agonist‐evoked stimulation than Gly389‐β1‐AR. With respect to β2‐AR, the Cys‐19 variant is associated with greater β2‐AR expression than the Arg‐19 variant; Gly16‐β2‐AR are more susceptible, whereas Glu27‐β2‐AR are almost resistant to agonist‐promoted down‐regulation; Thr164‐β2‐AR are three to four times more responsive to agonist‐evoked stimulation than Ile164‐β2‐AR. Several studies addressed potential phenotypic consequences of these SNPsin vivoby influencing and/or contributing to the pathophysiology of cardiovascular/pulmonary diseases such as hypertension, congestive heart failure, arrhythmias or asthma. At present, it appears that these β‐AR SNPs are very likely not disease‐causing genes but possibly predictive for the responsiveness to agonists and antagonists. Patients carrying one or two alleles of the Gly389‐β1‐AR are poor or non‐responders to agonists and antagonists, whereas patients homozygous for the Arg389‐β1‐AR are good responders. Subjects carrying the Ile164‐β2‐AR exhibit blunted responses to β2‐AR stimulation. Asthma patients carrying the Arg16‐Gln27‐Thr164‐β2‐AR haplotype who receive regularly short‐ or long‐acting β2‐AR agonists are rather susceptible to agonist‐induced desensitization and in consequence exhibit reduced bronchodilating and ‐protective effects and/or increased asthma exacerbations. The clinical relevance of these findings is still under debate.
Companies on the Scale
Authors: Wiedmann Thomas O. , Lenzen Manfred , Barrett John R.
Published: May 2009

A determination of the sustainability performance of a company ought to fulfill certain requirements. It has to take into account the direct impacts from on‐site processes as well as indirect impacts embodied in the supply chains of a company. This life cycle thinking is the common theme of popular footprint analyses, such as carbon, ecological, or water footprinting. All these indicators can be incorporated into one common and consistent accounting and reporting scheme based on economic input−output analysis, extended with data from all three dimensions of sustainability. We introduce such a triple‐bottom‐line accounting framework and software tool and apply it in a case study of a small company in the United Kingdom. Results include absolute impacts and relative intensities of indicators and are put into perspective by a benchmark comparison with the economic sector to which the company belongs. Production layer decomposition and structural path analysis provide further valuable detail, identifying the amount and location of triple‐bottom‐line impacts in individual upstream supply chains. The concept of shared responsibility has been applied to avoid double‐counting and noncomparability of results. Although in this work we employ a single‐region model for the sake of illustration, we discuss how to extend our ideas to international supply chains. We discuss the limitations of the approach and the implications for corporate sustainability.
Protein Kinase D‐Dependent Trafficking of the Large Herpes simplex Virus Type 1 Capsids from the TGN to Plasma Membrane
Authors: Rémillard‐Labrosse Gaudeline , Mihai Constantina , Duron Johanne , Guay Ginette , Lippé Roger
Published: May 2009

The biosynthetic pathway carries cargos from the endoplasmic reticulum (ER) to the trans Golgi network (TGN) via a typical passage through the Golgi. Interestingly, large particles such as procollagen, chylomicrons and some viruses all reach the TGN by atypical routes. Given this dichotomy, we anticipated that such cargos might rely on non‐classical machineries downstream of the TGN. Using Herpes simplex virus type 1 (HSV‐1) as a model and a synchronized infection protocol that focuses on TGN to plasma membrane transport, the present study revealed the surprising implication of the cellular serine‐threonine protein kinase D in HSV‐1 egress. These findings, confirmed by a variety of complementary means [pharmacological inhibitors, dominant negative mutant, RNA interference and electron microscopy (EM)], identify one of possibly several cellular factors that modulate the egress of viruses transiting at the TGN. Moreover, the involvement of this kinase, previously known to regulate the transport of small basolateral cargos, highlights the trafficking of both small and exceptionally large entities by a common machinery downstream of the TGN, in sharp contrast to earlier steps of transport. Conceptually, this indicates the TGN is not only a sorting station from which cargos can depart towards different destinations but also a meeting point where conventional and unconventional routes can meet along the biosynthetic pathway. Lastly, given the apical release of HSV‐1 in neurons, it opens up the possibility that this kinase might regulate some apical sorting.