bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous opioids inhibit ischemia‐induced generation of immature hippocampal neurons via the µ‐opioid receptor
Authors: Kolodziej Angela , Stumm Ralf , Becker Axel , Höllt Volker
Published: March 2008

It is established that hippocampal neurogenesis is dynamically regulated by physiological and pathological stimuli including learning, environmental complexity, mental disorders and brain lesion. Little is known about factors regulating adaptive changes in neurogenesis. Using µ‐opioid receptor (MOP)‐knockout mice we addressed whether endogenous opioids influence ischemia‐induced enhancement of hippocampal neurogenesis. Permanent middle cerebral artery occlusion (MCAO) produced similar corticostriatal infarcts in MOP‐knockout and wildtype mice. Analyses of BrdU/doublecortin‐colabelled cells in the granule cell layer 14 days after MCAO showed that ischemic knockouts contained more immature neurons generated during days 9–11 than wildtypes. After 29 days, similar quantities of BrdU/NeuN‐labelled cells were found in ischemic knockout and wildtype mice, suggesting that granule cells that were formed in excess during days 9–11 in the knockouts were eliminated by day 29. Neurogenesis was similar in knockout and wildtype mice subjected to sham operation. In addition to a transient increase in neurogenesis, MCAO caused a transient up‐regulation of preprodynorphin and preproenkephalin mRNA expression in the granule cell layer. Our findings suggest that activated signalling via endogenous opioids and the MOP limits the enhanced generation of neuronal cells after ischemic corticostriatal lesions.
Pseudomonas aeruginosa strain RW41 mineralizes 4‐chlorobenzenesulfonate, the major polar by‐product from DDT manufacturing
Authors: Blasco Rafael , Ramos Juan‐Luis , Wittich Rolf‐Michael
Published: March 2008

Pseudomonas aeruginosa RW41 is the first bacterial strain, which could be isolated by virtue of its capability to mineralize 4‐chlorobenzenesulfonic acid (4CBSA), the major polar by‐product of the chemical synthesis of 1,1,1‐trichloro‐2,2‐bis‐(4‐chlorophenyl)ethane (DDT). This capability makes the isolate a promising candidate for the development of bioremediation technologies. The bacterial mineralization of 4CBSA proceeds under oxygenolytic desulfonation and transient accumulation of sulfite which then is oxidized to sulfate. High enzyme activities for the turnover of 4‐chlorocatechol were measured. The further catabolism proceeded through 3‐chloromuconate and, probably, the instable 4‐chloromuconolactone, which is directly hydrolyzed to maleylacetate. Detectable levels of maleylacetate reductase were only present when cells were grown with 4CBSA. When the ordinary catechol pathway was induced during growth on benzenesulfonate, catechol was ortho‐cleaved to cis,cis‐muconate and a partially purified muconate cycloisomerase transformed it to muconolactone in vitro. The same enzyme transformed 3‐chloro‐cis,cis‐muconate into cis‐dienelactone (76%) and the antibiotically active protoanemonin (24%). These observations are indicative for a not yet highly evolved catabolism for halogenated substrates by bacterial isolates from environmental samples which, on the other hand, are able to productively recycle sulfur and chloride ions from synthetic haloorganosulfonates.
Fluorescence in situ hybridization (FISH) analysis of the interactions between honeybee larvae and Paenibacillus larvae, the causative agent of American foulbrood of honeybees (Apis mellifera)
Authors: Yue Dominique , Nordhoff Marcel , Wieler Lothar H. , Genersch Elke
Published: March 2008

American foulbrood (AFB) is a bacterial disease of honeybee larvae caused by the spore‐forming bacterium Paenibacillus larvae. Although AFB and its aetiological agent are described now for more than a century, the general and molecular pathogenesis of this notifiable disease is poorly understood. We used fluorescence in situ hybridization (FISH) performed with P. larvae‐specific, 16S rRNA‐targeted oligonucleotide probes to analyse the early steps in the pathogenesis of American foulbrood. The following chain of events could be demonstrated: (i) the spores germinate in the midgut lumen, (ii) the vegetative bacteria massively proliferate within the midgut before, and (iii) they start to locally breach the epithelium and invade the haemocoel. The paracellular route was shown to be the main mechanism for invasion contrasting earlier hypotheses of phagocytosis of P. larvae. Invasion coincided with the death of the host implicating that the penetration of the midgut epithelium is a critical step determining the time of death.
The Meaning of Parental Control in Migrant, Sending, and Host Communities: Adaptation or Persistence?
Authors: Güngör Derya
Published: March 2008

The goal of the present study was to investigate whether migrant adolescents tend to adopt the host culture's view of parental control or whether they are inclined to reaffirm their heritage culture with regard to the meaning assigned to parental control. The hypotheses regarding the level and meaning of parental control were tested on 296 Turkish‐Belgian adolescents, 306 Turks in Turkey, and 304 Belgians in Belgium with median ages of 16, 17, and 16, respectively. Although migrants reported the highest level of parental control, their ratings of parental warmth, satisfaction with the relationships with their parents, and self‐esteem did not correlate with parental control as was the case among Belgians. The findings suggest that traditional parenting is accentuated in migrant families, and that there is continuity in the traditional meaning of parental control in migration. Findings are discussed with reference to contextual factors that may reinforce culture maintenance in migration.

Le but de cette recherche était d’étudier le sens que des adolescents immigrés assignaient au contrôle parental: adoptent‐ils la culture d’accueil ou ont‐ils plutôt tendance à réaffirmer leur héritage culturel? Des hypothèses tenant compte du niveau et de la signification du contrôle parental ont été testées auprès de 296 adolescents Turcs‐Belges, 306 Turcs de Turquie et 304 Belges de Belgique dont les âges médians étaient respectivement de 16, 17 et 16 ans. Bien que les immigrés présentent un plus haut niveau de contrôle parental, leurs résultats concernant la chaleur parentale, la satisfaction de leurs relations avec leurs parents, et l’estime de soi n’étaient pas corrélés avec le contrôle parental contrairement aux adolescents Belges. Ces résultats montrent que l’éducation traditionnelle est accentuée dans les familles immigrées, et que la signification traditionnelle accordée au contrôle parental persiste dans l’immigration. Ces résultats sont discutés en référence à des facteurs contextuels pouvant renforcer le maintien de la culture d’origine dans l’immigration.
Crossing the Tracks? Trends in the Training of Male and Female Workers in Great Britain
Authors: Jones Melanie K. , Latreille Paul L. , Sloane Peter J.
Published: March 2008

A small number of recent empirical studies report the intriguing finding that the ‘advantage’ in training incidence previously enjoyed by men has been reversed. The present article explores the sources of this gender differential using Labour Force Survey data, updating previous British studies and providing further insights into the above phenomenon. The results suggest that the greater part of the gender ‘gap’ derives from differences in characteristics, among the most important being occupation, industry and sector. However, the increased training incidence among females over time is not explained by changes in characteristics and suggests preferences for training may have changed.
Mothers’ representations of caregiving and their adult children's representations of attachment: Intergenerational concordance and relations to beliefs about mothering
Authors: BENGTSSON HANS , PSOUNI ELIA
Published: March 2008

Mothers (N= 35) and their adult children completed questionnaires and were interviewed in order to examine relationships between mothers’ caregiving representations and their adult children's attachment representations, and relationships between attachment/caregiving representations and beliefs about mothering. Mothers’ and their children's accounts of and present thinking about their past relationship were highly similar, indicating that the two parts develop concordant states of mind regarding their relationship. In contrast, there was no relationship between mothers’ and their adult children's beliefs about mothering, suggesting that such beliefs are not simply passed on from generation to generation within families. Attachment/caregiving classification interacted with generation in influencing a belief that biological facts determine maternal behavior, young adults with preoccupied attachment being particularly prone to reject this idea. Attachment/caregiving classification also had a significant effect on participants’ tendency to adhere to an idealized conception of mothering, this tendency being associated with a dismissive attachment/caregiving representation.
Free the animals? Investigating attitudes toward animal testing in Britain and the United States
Authors: SWAMI VIREN , FURNHAM ADRIAN , CHRISTOPHER ANDREW N.
Published: March 2008

In this study, 185 British and 143 American undergraduates completed a battery of tests that measured attitudes toward animal testing and various individual difference variables. Attitudes toward animal testing factored into two interpretable factors: general attitudes toward animal testing, and animal welfare and conditions of testing. Overall, there was support for animal testing under the right conditions, although there was also concern for the welfare of animals and the conditions under which testing takes place. There were small but significant national difference on both factors (with Americans more positive about testing and less positive about animal welfare), and a significant sex difference on the first factor (women were more negative about testing). Correlation and regression analyses showed that there were few significant individual difference predictors of both factors. These results are discussed in relation to past and future work on attitudes toward animal testing.
GOD AND NATURAL LAW: REFLECTIONS ON GENESIS 22
Authors: LEVERING MATTHEW
Published: March 2008

This essay first explores Immanuel Kant's reading of Genesis 22, which Kant identifies as a preeminent case of the irrationality of biblical religion. After comparing Kant's assurance about the norms of rationality with the postmodern work of John Thiel, which finds the world of disorder and death to be outside God's ordering and therefore unintelligible, the essay argues that one finds in Thomas Aquinas's and Duns Scotus's contrasting accounts of Genesis 22 the beginnings of the breakdown of the theocentric understanding of the natural law as a participation in God's wise ordering of created realities to their fulfillment. Modern and postmodern thinkers operate within the context of this anthropocentric shift.
ELECTION AND THE TRINITY: TWENTY‐FIVE THESES ON THE THEOLOGY OF KARL BARTH
Authors: HUNSINGER GEORGE
Published: March 2008

A new and “revisionist” reading would argue that the later Karl Barth saw the existence of the eternal Trinity not as the ground and presupposition, but as the consequence of God's pre‐temporal decision of election. A more “traditionalist” reading, on the other hand, as defended by this essay, denies that proposition. The texts adduced by the revisionists, it is argued, fail to make their case. More plausible, alternative readings are offered, counter‐evidence is marshaled, and the deleterious theological consequences of the revisionist alternative are spelled out. Barth could not have adopted it without contradicting his most basic convictions.
THE TOUCH OF HUMILITY: AN INVITATION TO CREATURELINESS
Authors: WIRZBA NORMAN
Published: March 2008

Humility has been much maligned and misunderstood in recent thought. An authentic sense of humility, however, is borne out of a deep appreciation for human creatureliness, and is concretely worked out in the grateful acceptance of our interdependent need. The phenomenological studies of Jean‐Louis Chrétien, particularly his analyses of touch and the “call‐response” structure to human life, are enlisted to show our true life as lived in humble reception and responsible engagement with the gifts of God. Far from being a debasement of humanity, humility—which finds its practical patterns in the divine life—is the core of our identity and vocation.
‘Fit Only for the Scrap Heap’: Rebuilding Returned Soldier Manhood in Australia after 1945
Authors: Garton Stephen
Published: March 2008

This paper examines the expert and popular discourses that sought to construct and disseminate the idea that Australia faced a masculinity crisis with the return of servicemen at the end of the Second World War. It explores how these discourses proposed a process of remasculinisation to ensure the successful reintegration of returning servicemen. These discourses were directed primarily at wives, mothers and fiancées, who were seen to bear the responsibility for rebuilding the manhood of returning men. Doctors played an important role in producing this prevailing discourse on the looming post‐war masculinity crisis, identifying its symptoms and proposing solutions. This crisis discourse filtered into popular culture through many means, predominantly, however, advice literature and romance fiction. While some of these expert and popular discourses constructed a backward looking ideal of domesticity for women, romance fiction in particular explored more modern possibilities of companionate marriage. The dissemination of a discourse about an impending masculinity crisis created different possibilities for the reconstruction of relations between men and women. The remasculinisation project could look both backwards (through ideals of women's subservience to damaged men) and forwards (through notions of marriage as a partnership) in imagining post war gender relations.
Missionary Masculinities, the Homoerotic Gaze and the Politics of Race: Gilbert White in Northern Australia, 1885–1915
Authors: O'Brien Anne
Published: March 2008

The considerable international literature on Christian missions and gender has rarely focused on missionary masculinity, or on the relationship between missionary homoeroticism and the defence of the rights of the colonised. This paper argues that homoeroticism played a part in the humanitarianism of Gilbert White who, from 1900 to 1915, was Anglican Bishop of Carpentaria in northern Australia, a heavily male frontier where inter‐racial tension and violence were common. White's attraction to the Aboriginal male body indirectly assisted all Aborigines by drawing attention to the ill effects of colonisation but his ambivalence to the female body left him uninterested in the plight of Aboriginal women, who suffered ‘extraordinary brutality’ on the frontier.
Manliness, Male Virtue and History Writing at the Seventeenth‐Century Ottoman Court
Authors: Baer Marc
Published: March 2008

When one compares Ottoman chronicles written in the wake of the failed Vienna campaign of 1683 to those composed prior to 1682 and finally to those completed in 1658 one finds, first, that gendered conceptions were central to the authors' depictions of the era and, second, that the model of manliness and male virtue that the authors conceived changed greatly. To authors writing during the first decade of Mehmed IV's reign (1648–58), male virtue was expressed in self‐mastery, the mastery of subordinates, particularly women, and the control of financial resources. Authors in the period between 1658 and 1682 imagined manliness in terms of bravery – manifested in hunting and waging war, labelled interchangeably ghaza or jihad – and Islamic zeal. After 1682, writers again returned to an understanding of male virtue and manliness centred on self‐control. This article explains the reasons for this change in conceptions of manliness and male virtue by relating it to the dynamic competition between courtly factions patronising literary production. The need to curry favour with these factions was reflected in the writers' choice of literary genre, which intervened discursively to offer different images of the sultan and valide sultan (queen mother).
Imagining the Beloved: Gender and Nation Building in Early Twentieth‐Century Hebrew Literature
Authors: Pinsker Shachar
Published: March 2008

This article traces the gender dimensions of Zionist nation building by examining literary texts written in the first three decades of the twentieth century. It offers a gender‐oriented analysis of a range of canonic and marginal literary texts and their historical contexts, and pays special attention to the ways in which literary production in general, and in Hebrew in particular, became an essential component in the effort to create an image of a ‘New Hebrew Man’. This highly gendered image was a central foundation of the Zionist project of nation building in Europe, and in the Jewish community in Palestine. Hebrew poems, stories and novels produced and sustained the symbolic economy of gender of the Zionist cultural project. At the same time, I argue that some Hebrew writers resisted the overt and implicit ideological demands of this project by calling attention to the internal contradictions inherent in the feminine figuration of the nation and the attempts to transform Jewish masculinity.
Clinicopathologic profile of normocomplementemic and hypocomplementemic urticarial vasculitis: a study from South India
Authors: Dincy CVP , George R , Jacob M , Mathai E , Pulimood S , Eapen EP
Published: March 2008

Background This study aims to study the clinical and histopathological characteristics of hypocomplementemic and normocomplementemic urticarial vasculitis (HUVS and NUV) among dermatology clinic attendees in a tertiary care hospital in South India.

Patients and methods A prospective study was conducted in the dermatology department from February 2003 to May 2004.

Seventy‐five patients met the inclusion criteria for UV. Sixty‐eight patients in whom complement levels were available were classified into either NUV or HUVS groups. Clinical features, laboratory parameters and histological features were compared, and the significance of differences was established using Pearson's Chi‐squared test.

Results There was a female preponderance among patients with HUVS. Wheals > 24 h were seen in 90% of patients, and in 54.4% of patients, the wheals were partially blanching or non‐blanching. Angioedema was more prevalent in patients with NUV than HUVS (44.4% vs. 21.4%). Systemic involvement was seen in 64.3% of patients with HUVS and 44.4% of patients with NUV. Fever, ANA positivity and systemic lupus erythematosus (SLE) were significantly associated with HUVS. In most cases of UV, a provoking factor could not be identified. Neutrophilic small vessel vasculitis was seen in 42.9% of patients with HUVS and 16.6% patients with NUV. Direct immunofluorescence test showing immunoreactants at the dermo‐epidermal junction were present in 60% of patients with HUVS and 33.3% patients with NUV.

Conclusion The clinical features of Indian patients with UV were similar to those reported from the West. Fever, ANA positivity and SLE were significantly associated with HUVS.
Quality of life in patients with facial steroid dermatitis before and after treatment
Authors: Liu Z‐H , Du X‐H
Published: March 2008

Background  Improper long‐term, even low‐dose, topical corticosteroids, especially application to the face, could induce steroid dermatitis, which was refractory and detrimental to the quality of life.

Objective  To evaluate the quality of life in patients with facial steroid dermatitis before and after the treatment of doxycycline and indomethacin plus support therapy.

Study design  A prospective study.

Setting  Outpatients of the Department of dermatology, the Third Hospital of Hangzhou, from August 2, 2004, to April 20, 2005.

Subjects  Fifty consecutive outpatients completed the treatment.

Intervention  The intervention is doxycycline 10 mg twice a day and indomethacin 25 mg twice a day for 4 weeks, cetirizine or loratadine 10 mg daily if pruritic, topical white petroleum if feeling dry and wet dressing if burning and oedema, plus psychological support and health education.

Main outcome measure  The efficacy of the treatment was quantified using a 24‐point steroid clinical score. The detriment of the quality of life was quantified using a 30‐point Dermatology Life Quality Index.

Results  The steroid dermatitis clinical score decreased significantly from 15.06 ± 4.61 at baseline to 4.52 ± 3.39 at 2 weeks after the end of treatment (week 6; P < 0.001). Twenty‐one patients underwent a rebound phenomenon and the steroid dermatitis clinical score increased significantly from 13.71 ± 4.33 at baseline (week 0) to 19.24 ± 3.40 at 1 week after treatment (week 1; P < 0.001). Quality of life score decreased significantly from 13.76 ± 7.68 at baseline to 3.44 ± 2.57 at 2 weeks after the end of treatment (week 6; P < 0.001).

Conclusions  The quality of life was profoundly affected by facial steroid dermatitis. Doxycycline and indomethacin plus support therapy might be effective in patients with facial steroid dermatitis.
Promoting child and adolescent mental health in the context of the HIV/AIDS pandemic with a focus on sub‐Saharan Africa
Authors: Earls Felton , Raviola Giuseppe J. , Carlson Mary
Published: March 2008

Background:  The pandemic of HIV/AIDS is actually a composite of many regional and national‐level epidemics. The progress made in many parts of the developed and developing world is tempered by the continued devastating consequences of HIV infection in sub‐Saharan Africa (SSA). This review focuses on the ways in which children and adolescents are impacted by the epidemic, giving particular attention to their mental health.

Methods:  A health promotion framework is adopted to guide analysis. Three issues are covered: prevention of HIV infection, care and treatment of children infected with HIV, and care of children whose caregivers are ill or have died of AIDS. Existing reviews and literature search engines were used to review the scientific literature, focusing on the past five years.

Results:  Preventive interventions continue to manifest limited benefits in behavioral changes. More complex causal models and improved behavioral measures are needed. In the African context, the time has come to view pediatric AIDS as a chronic disease in which the mental health of caregivers and children influences important aspects of disease prevention and management. Increasingly sophisticated studies support earlier findings that social and psychological functioning, educational achievement and economic well‐being of children who lose parents to AIDS are worse than that of other children.

Conclusions:  Important changes are taking place in SSA in increased access to HIV testing and antiretroviral therapies. To be effective in promoting mental health of children and adolescents, interventions require a more fundamental understanding of how to build HIV competence at personal and community levels. A key recommendation calls for the design and execution of population‐based studies that include both multilevel and longitudinal features. Such rigorous conceptual and empirical investigations that assess the capacities of children are required to mobilize children, families and communities in comprehensive actions plans for prevention, treatment and care in response to the enduring HIV/AIDS pandemic.
Multicultural assessment of child and adolescent psychopathology with ASEBA and SDQ instruments: research findings, applications, and future directions
Authors: Achenbach Thomas M. , Becker Andreas , Döpfner Manfred , Heiervang Einar , Roessner Veit , Steinhausen Hans‐Christoph , Rothenberger Aribert
Published: March 2008

Around the world, cultural blending and conflict pose challenges for assessment and understanding of psychopathology. Economical, evidence‐based, culturally robust assessment is needed for research, for answering public health questions, and for evaluating immigrant, refugee, and minority children. This article applies multicultural perspectives to behavioral, emotional, and social problems assessed on dimensions describing children's functioning, as rated by parents, teachers, children, and others. The development of Achenbach System of Empirically Based Assessment (ASEBA) and Strengths and Difficulties Questionnaire (SDQ) forms and their applications to multicultural research are presented. A primary aim of both questionnaires is to identify children at high risk of psychiatric disorders and who therefore warrant further assessment. The forms are self‐administered or administered by lay interviewers. ASEBA problem items are scored on 6 DSM‐oriented scales and 3 broader band scales, plus 8 syndromes derived statistically as taxonomic constructs and supported by uniform confirmatory factor analyses of samples from many populations. Comparisons of ASEBA scale scores, psychometrics, and correlates are available for diverse populations. SDQ forms are scored on one broad‐band scale and 5 a priori behavioral dimensions supported by data from various populations. For both instruments, factor analyses, psychometrics, and correlates are available for diverse populations. The willingness and ability of hundreds of thousands of respondents from diverse groups to complete ASEBA and SDQ forms support this approach to multicultural assessment. Although particular items and scales may have differential relevance among groups and additional assessment procedures are needed, comparable results are found in many populations. Scale scores vary more within than between populations, and distributions of scores overlap greatly among different populations. Ratings of children's problems thus indicate more heterogeneity within populations than distinctiveness between populations. Norms from multiple populations can be used to compare children's scores with relevant peer groups. Multicultural dimensional research can advance knowledge by diversifying normative data; by comparing immigrant children with nonimmigrant compatriots and with host country children; by identifying outlier findings for elucidation by emic research; and by fostering efforts to dimensionalize DSM‐V diagnostic criteria.
Oxytocin–ergometrine co‐administration does not reduce blood loss at caesarean delivery for labour arrest*
Authors: Balki M , Dhumne S , Kasodekar S , Kingdom J , Windrim R , Carvalho JCA
Published: March 2008

Objective  To determine if intravenous infusion of a combination of oxytocin and ergometrine maleate is better than oxytocin alone to decrease blood loss at caesarean delivery for labour arrest.

Design  Prospective, double‐blinded, randomised controlled trial.

Setting  Mount Sinai Hospital, Toronto, Canada.

Population  Women undergoing caesarean deliveries for labour arrest.

Methods  Forty‐eight women were randomised to receive infusion of either ergometrine maleate 0.25 mg + oxytocin 20 iu or oxytocin 20 iu alone, diluted in 1 l of lactated Ringer’s Solution, immediately after delivery of the infant. Unsatisfactory uterine contractions after delivery were treated with additional boluses of the study solution or rescue carboprost. Blood loss was estimated based on the haematocrit values before and 48 hours after delivery.

Main outcome measures  The primary outcome was the estimated blood loss, while the secondary outcomes included the use of additional uterotonics, need for blood transfusion and the incidence of adverse effects.

Results  The estimated blood loss was similar in the oxytocin–ergometrine and oxytocin‐only groups; 1218 ± 716 ml and 1299 ± 774 ml, respectively (P= 0.72). Significantly fewer women required additional boluses of the study drug in the oxytocin–ergometrine group (21 and 57%; P= 0.01). Nausea (42 and 9%; P= 0.01) and vomiting (25 and 4%; P= 0.05) were significantly more prevalent in the oxytocin–ergometrine group.

Conclusions  In women undergoing caesarean delivery for labour arrest, the co‐administration of ergometrine with oxytocin does not reduce intraoperative blood loss, despite apparently superior uterine contraction.
Is psychosocial stress in first ongoing pregnancies associated with pre‐eclampsia and gestational hypertension?
Authors: Vollebregt KC , Van Der Wal MF , Wolf H , Vrijkotte TGM , Boer K , Bonsel GJ
Published: March 2008

Objective  Investigating the association of pre‐eclampsia and gestational hypertension with psychosocial stress in the first half of pregnancy.

Design  Prospective community‐based cohort study.

Setting  Amsterdam, The Netherlands.

Population  Between January 2003 and March 2004, all pregnant Amsterdam women (n = 12 377) were invited to fill in a questionnaire with sociodemographic and psychosocial variables (response rate 67%). Only nulliparous women with a singleton pregnancy, who completed the questionnaire before 24 weeks, and delivered after 24 weeks, were included.

Methods  A postpartum questionnaire was used to gather information on hypertension or proteinuria. If this questionnaire was not available, the national obstetric register was used for pregnancy outcome. Medical files were examined for women with hypertension and/or proteinuria to confirm the diagnosis of pre‐eclampsia and gestational hypertension according to the International Society for the Study of Hypertension in Pregnancy guidelines. Psychosocial stress was defined as workstress (Work Experience and Appreciation Questionnaire partly based on the Job Content Instrument of Karasek et al.), anxiety (the State‐Trait Anxiety Inventory), depression (Center for Epidemiological Studies Depression Scale) and pregnancy‐related anxiety (PRAQ‐R). The association of psychosocial stress with the incidence of pre‐eclampsia and gestational hypertension was explored by multivariate analysis adjusted for sociodemographic and medical confounders.

Main outcome measures  Incidence of pre‐eclampsia and gestational hypertension.

Results  A total of 3679 women were included. The incidence of pre‐eclampsia and gestational hypertension was 3.5 and 4.4%, respectively. Workstress, anxiety, pregnancy‐related anxiety or depression had no effect on the incidence of pre‐eclampsia or gestational hypertension.

Conclusion  Psychosocial stress in the first half of pregnancy does not influence the incidence of pre‐eclampsia and gestational hypertension in nulliparous women.
The Debt‐Contracting Value of Accounting Information and Loan Syndicate Structure
Authors: BALL RYAN , BUSHMAN ROBERT M. , VASVARI FLORIN P.
Published: March 2008

We investigate how both the ownership structure and explicit contractual structure of syndicated loan deals are shaped by the debt‐contracting value (DCV) of borrowers' accounting information. DCV captures the inherent ability of firms' accounting numbers to capture credit quality deterioration in a timely fashion. We hypothesize and document that when a borrower's accounting information possesses higher DCV, information asymmetry between the lead arranger and other syndicate participants is lower, allowing lead arrangers to hold a smaller proportion of new loan deals. Further, we document that the influence of DCV on the proportion of the loan retained is conditional on the lead arranger's reputation, the existence of a credit rating, and the lead arranger's previous relationships with the same borrower. Finally, we find that when loans include performance pricing provisions, the likelihood that the single performance measure used is an accounting ratio, rather than a credit rating, is increasing in DCV.
20+ yr without leukemic or fibrotic transformation in essential thrombocythemia or polycythemia vera: predictors at diagnosis
Authors: Tefferi Ayalew , Gangat Naseema , Wolanskyj Alexandra P. , Schwager Susan , Pardanani Animesh , Lasho Terra L. , Mesa Ruben , McClure Rebecca F. , Li Chin‐Yang , Hanson Curtis A.
Published: March 2008

Objectives:  The current study identified patients with either essential thrombocythemia (ET) or polycythemia vera (PV) who have survived for at least 20 yr without the development of either acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) or myelofibrosis (MF) and compared their presenting features with those in whom these complications occurred in the first 10 yr of disease.

Methods:  The study patients were selected from an institutional database of 1061 patients with either ET (n = 603) or PV (n = 458). In both instances, three distinct groups were delineated and their presenting features compared; group A included patients who have remained AML/MDS/MF free after a minimum follow‐up of 20 yr; groups B and C included patients who developed either AML/MDS or MF, respectively, in the first decade of their disease.

Results:  The respective number of patients who fulfilled the above‐mentioned criteria for inclusion in groups A, B and C were 40, 12 and 8 for ET and 23, 18 and 12 for PV. In ET, compared with both groups B and C, group A displayed significantly fewer patients with less than normal hemoglobin level (P < 0.0001 and =0.02) or male sex (P = 0.005 and 0.05), respectively. On multivariable analysis, only anemia sustained its significance. A similar analysis in PV revealed an association between group B and leukocytosis using a leukocyte count threshold of either 10 or 15 × 109/L (P = 0.02).

Conclusion:  The current study identifies PV patients with leukocytosis and ET patients with anemia as the most likely to undergo leukemic or fibrotic transformation.
Detection of the STAT5B–RARA fusion transcript in acute promyelocytic leukemia with the normal chromosome 17 on G‐banding
Authors: Kusakabe Manabu , Suzukawa Kazumi , Nanmoku Toru , Obara Naoshi , Okoshi Yasushi , Mukai Harumi Y. , Hasegawa Yuichi , Kojima Hiroshi , Kawakami Yasushi , Ninomiya Haruhiko , Nagasawa Toshiro
Published: March 2008

Acute promyelocytic leukemia (APL) is characterized by chromosomal rearrangements of 17q21, leading to fusion of the gene‐encoding retinoic acid receptor alpha (RARA) with a number of alternative partner genes. Signal transducer and activator of transcription 5 beta (STAT5B) is one of the alternative partners. We report a rare case of APL with STAT5B–RARA fusion transcript and the normal chromosome 17 on G‐banding. Administration of all trans‐retinoic acid improved disseminated intravascular coagulation without decrease of the leukemia cells in his peripheral blood and bone marrow. The molecular mechanism of fusion between STAT5B and RARA by chromosomal rearrangement is discussed based on the data from genome database. Clinical characteristics of APL with STAT5B–RARA are also discussed.
Combined proteasome and Bcl‐2 inhibition stimulates apoptosis and inhibits growth in EBV‐transformed lymphocytes: a potential therapeutic approach to EBV‐associated lymphoproliferative diseases
Authors: Srimatkandada Pavani , Loomis Regina , Carbone Rocco , Srimatkandada Srinivasan , Lacy Jill
Published: March 2008

Objectives:  Epstein–Barr virus (EBV) transforms B‐cells into immortalized lymphoblastoid cells (LCLs) by triggering signaling pathways that lead to activation of multiple transcription factors and anti‐apoptotic proteins, including NF‐κB and Bcl‐2, respectively. Since proteasome inhibition suppresses NF‐κB activity, we sought to determine whether the proteasome inhibitor, bortezomib, alone or in combination with Bcl‐2 inhibition, has potential as a therapeutic strategy in EBV‐driven B‐cell neoplasms.

Methods:  We evaluated the effects of bortezomib in LCLs in vitro, in the presence and absence of the small molecular inhibitor of Bcl‐2, HA14‐1, on proliferation, apoptosis, caspase activation, and expression of Bcl‐2 family members, and in vivo in the severe combined immunodeficiency (SCID) model of EBV+ lymphoproliferative disease.

Results:  Bortezomib inhibited proliferation, stimulated apoptosis, and activated caspases‐3 and ‐9 in a dose‐dependent manner in LCLs. In vivo, bortezomib completely abrogated development of EBV+ lymphoproliferative disease in LCL‐bearing SCID mice. When HA14‐1 was added to bortezomib in vitro, we observed a synergistic anti‐proliferative effect and enhancement of apoptosis and caspase activation, including activation of caspase‐8, in LCLs. These events were associated with modulation of expression of Bcl‐2 family members towards a pro‐apoptotic profile with translocation of cytochrome C from mitochondria to cytoplasm.

Conclusions:  These studies demonstrated that bortezomib mediates anti‐tumor effects in EBV‐associated lymphoproliferations both in vitro and in vivo, and that its anti‐proliferative and apoptotic effects are synergistically enhanced in the presence of a Bcl‐2 inhibitor. These findings support further investigation of bortezomib in EBV+ lymphoproliferative diseases, and suggest that bortezomib in combination with Bcl‐2 antagonists represents a potential therapeutic strategy for EBV‐driven B‐cell neoplasms
The skin as a biofactory for systemic secretion of erythropoietin: potential of genetically modified keratinocytes and fibroblasts
Authors: Scheidemann Frank , Löser Maria , Niedermeier Andrea , Kromminga Arno , Therrien Jean‐Philippe , Vogel Jon , Pfützner Wolfgang
Published: March 2008

Background:  The skin is an interesting target tissue for gene therapy applications because of its ready accessibility. One possibility would be to utilize the genetically modified skin as a biofactory secreting a systemically needed product, such as erythropoietin (EPO).

Methods:  Keratinocytes (KC) and fibroblasts (FB) were transduced with a retroviral vector encoding human EPO. Gene transfer efficiency was assessed by real‐time PCR analysis and flow cytometry of transduced cells. In addition, EPO synthesis and secretion were analysed by quantifying the amount of RNA and secreted protein in both monolayer cultures and skin equivalents (SE).

Results:  When cultured as a monolayer, EPO‐KC synthesized significantly more EPO than EPO‐FB, as shown by quantitatively measuring the amount of secreted protein and RNA. This correlated with an increased EPO‐vector incorporation in KC compared with FB, demonstrated by determining both the percentage of transduced cells and the average transgene copy number per cell. In addition, in transduced cell cultures enriched to equally high percentages of EPO+ cells, KC showed a higher activity of EPO secretion than FB. Finally, when assembled in a SE, EPO‐KC secreted significantly higher amounts of EPO than EPO‐FB, although reduced secretory activity of EPO‐KC monolayers grown in high calcium concentrations suggested that in stratified epidermis differentiated KC secrete less EPO than non‐differentiated KC.

Conclusion:  In summary, while both transduced KC and FB are able to synthesize and secrete human EPO, KC show higher potential in serving as possible target cells for therapeutic substitution with EPO, probably because of improved transduction rates and increased secretory activity.
Smy2p Participates in COPII Vesicle Formation Through the Interaction with Sec23p/Sec24p Subcomplex
Authors: Higashio Hironori , Sato Ken , Nakano Akihiko
Published: March 2008

The coat protein complex II (COPII) is essential for vesicle formation from the endoplasmic reticulum (ER) and is composed of two heterodimeric subcomplexes, Sec23p/Sec24p and Sec13p/Sec31p, and the small guanosine triphosphatase Sar1p. In an effort to identify novel factors that may participate in COPII vesicle formation, we isolated SMY2, a yeast gene encoding a protein of unknown function, as a multicopy suppressor of the temperature‐sensitive sec24‐20 mutant. We found that even a low‐copy expression of SMY2 was sufficient for the suppression of the sec24‐20 phenotypes, and the chromosomal deletion of SMY2 led to a severe growth defect in the sec24‐20 background. In addition, SMY2 exhibited genetic interactions with several other genes involved in the ER‐to‐Golgi transport. Subcellular fractionation analysis showed that Smy2p was a peripheral membrane protein fractionating together with COPII components. However, Smy2p was not loaded onto COPII vesicles generated in vitro. Interestingly, coimmunoprecipitation between Smy2p and the Sec23p/Sec24p subcomplex was specifically observed in sec23‐1 and sec24‐20 backgrounds, suggesting that this interaction was a prerequisite for the suppression of the sec24‐20 phenotypes by overexpression of SMY2. We propose that Smy2p is located on the surface of the ER and facilitates COPII vesicle formation through the interaction with Sec23p/Sec24p subcomplex.
AP‐1 Membrane–Cytoplasm Recycling Regulated by μ1A‐Adaptin
Authors: Medigeshi Guruprasad R. , Krikunova Maria , Radhakrishnan Karthikeyan , Wenzel Dirk , Klingauf Jürgen , Schu Peter
Published: March 2008

The adaptor protein complex AP‐1 mediates vesicular protein sorting between the trans Golgi network and endosomes. AP‐1 recycles between membranes and the cytoplasm together with clathrin during transport vesicle formation and vesicle uncoating. AP‐1 recycles independent of clathrin, indicating binding to unproductive membrane domains and premature termination of vesicle budding. Membrane recruitment requires ADP ribosylation factor‐1‐GTP, a transmembrane protein containing an AP‐1‐binding motif and phosphatidyl‐inositol phosphate (PI‐4‐P). Little is known about the regulation of AP‐1 membrane–cytoplasm recycling. We identified the N‐terminal domain of μ1A‐adaptin as being involved in the regulation of AP‐1 membrane–cytoplasm recycling by constructing chimeras of μ1A and its homologue μ2. The AP‐1* complex containing this μ2–μ1A chimera had slowed down recycling kinetics, resulting in missorting of mannose 6‐phosphate receptors. The N‐terminal domain is only accessible from the cytoplasmic AP‐1 surface. None of the proteins known to influence AP‐1 membrane recycling bound to this μ1A domain, indicating the regulation of AP‐1 membrane–cytoplasm recycling by an yet unidentified cytoplasmic protein.
Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population‐based study
Authors: Arenz Stephan , Nennstiel‐Ratzel Uta , Wildner Manfred , Dörr Helmuth‐Günther , Von Kries Rüdiger
Published: March 2008

Aim: To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH).

Methods: Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population‐based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier‐bis sechsjahrige Kinder (MOT) 4–6.

Results: Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9–5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4–15) with a median dose of 12.0 μg/kg (range 7.2–17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid‐stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of ≤200 mU/L (p = 0.003). Children with CH had a significant increased risk for overweight (risk ratio [RR] 3.91, 95% confidence interval [CI] 1.22–11.75, p = 0.005) compared to the Bavarian reference children.

Conclusion: In this study, children with CH had an increased prevalence of overweight compared to reference data. Partially impaired motor skills could be shown, whereas the intellectual development was normal.
SUMOylation of the hepatoma‐derived growth factor negatively influences its binding to chromatin
Authors: Thakar Ketan , Niedenthal Rainer , Okaz Elwy , Franken Sebastian , Jakobs Astrid , Gupta Shivangi , Kelm Sørge , Dietz Frank
Published: March 2008

Hepatoma‐derived growth factor is a nuclear targeted mitogen containing a PWWP domain that mediates binding to DNA. To date, almost nothing is known about the molecular mechanisms of the functions of hepatoma‐derived growth factor, its routes of secretion and internalization or post‐translational modifications. In the present study, we show for the first time that hepatoma‐derived growth factor is modified by the covalent attachment of small ubiquitin‐related modifier 1 (SUMO‐1), a post‐translational modification with regulatory functions for an increasing number of proteins. Using a basal SUMOylation system in Escherichia coli followed by a MALDI‐TOF‐MS based peptide analysis, we identified the lysine residue SUMOylated located in the N‐terminal part of the protein adjacent to the PWWP domain. Surprisingly, this lysine residue is not part of the consensus motif described for SUMOylation. With a series of hepatoma‐derived growth factor mutants, we then confirmed that this unusual location is also used in mammalian cells and that SUMOylation of hepatoma‐derived growth factor takes place in the nucleus. Finally, we demonstrate that SUMOylated hepatoma‐derived growth factor is not binding to chromatin, in contrast to its unSUMOylated form. These observations potentially provide new perspectives for a better understanding of the functions of hepatoma‐derived growth factor.
hhLIM is a novel F‐actin binding protein involved in actin cytoskeleton remodeling
Authors: Zheng Bin , Wen Jin‐kun
Published: March 2008

Human heart LIM protein (hhLIM) is a newly cloned protein. In vitro analyses showed that green fluorescent protein (GFP)‐tagged hhLIM protein accumulated in the cytoplasm of C2C12 cells and colocalized with F‐actin, indicating that hhLIM is an actin‐binding protein in C2C12 cells. Overexpression of hhLIM–GFP in C2C12 cells significantly stabilized actin filaments and delayed depolymerization of the actin cytoskeleton induced by cytochalasin B treatment. Expression of hhLIM–GFP in C2C12 cells also induced significant changes in the organization of the actin cytoskeleton, specifically, fewer and thicker actin bundles than in control cells, suggesting that hhLIM functions as an actin‐bundling protein. This hypothesis was confirmed using low‐speed co‐sedimentation assays and direct observation of F‐actin bundles that formed in vitro in the presence of hhLIM. hhLIM has two LIM domains. To identify the essential regions and sites for association, a series of truncated mutants was constructed which showed that LIM domain 2 has the same activity as full‐length hhLIM. To further characterize the binding sites, the LIM domain was functionally destructed by replacing cysteine with serine in domain 2, and results showed that the second LIM domain plays a central role in bundling of F‐actin. Taken together, these data identify hhLIM as an actin‐binding protein that increases actin cytoskeleton stability by promoting bundling of actin filaments.
Epigenetics: application of virtual image restriction landmark genomic scanning (Vi‐RLGS)
Authors: Koike Kuniaki , Matsuyama Tomoki , Ebisuzaki Toshikazu
Published: March 2008

Restriction landmark genomic scanning (RLGS) is a powerful method for the systematic detection of genetic mutations in DNA length and epigenetic alteration due to DNA methylation. However, the identification of polymorphic spots is difficult because the resulting RLGS spots contain very little target DNA and many non‐labeled DNA fragments. To overcome this, we developed a virtual image restriction landmark genomic scanning (Vi‐RLGS) system to compare actual RLGS patterns with computer‐simulated RLGS patterns (virtual RLGS patterns). Here, we demonstrate in detail the contents of the simulation program (rlgssim), based on the linear relationship between the reciprocal of mobility plotted against DNA fragment length and Vi‐RLGS profiling of Arabidopsis thaliana.