bluuebunny/crossref_metadata_2025 huggingface dataset:
Defense styles in depressed suicide attempters
Authors: CORRUBLE EMMANUELLE , BRONNEC MARIE , FALISSARD BRUNO , HARDY PATRICK
Published: May 2004

Abstract  Defense styles may discriminate between depressed patients with or without recent suicide attempts. The aim of the present study was to identify which defense mechanisms are associated with recent suicide attempts in depression. The Defense Style Questionnaire (DSQ) was rated at admission by 156 depressed inpatients with (n = 60) or without (n = 96) recent suicide attempt. Depression intensity was correlated negatively with mature style, humor and sublimation and positively with projection. Although it was not significantly different in terms of sociodemographic and depression variables, recent suicide attempters had higher scores on immature style, especially acting out, passive agression, autistic fantasy and projection. Prospective assessment of defense styles and suicide attempts should be carried out to determine whether these differences are a cause of imminent suicide attempts in depression. If so, the DSQ may be used in clinical practice to help discriminate depressed patients with high risk of imminent suicide attempt.
Relation between cortical dopamine D2 receptor occupancy and suppression of conditioned avoidance response in non‐human primate
Authors: TAKANO AKIHIRO , SUHARA TETSUYA , MAEDA JUN , ANDO KIYOSHI , OKAUCHI TAKASHI , OBAYASHI SHIGERU , NAKAYAMA TAKASHI , KAPUR SHITIJ
Published: May 2004

Abstract  Suppression of the conditioned avoidance response (CAR), a useful test for screening for antipsychotic effects, has been discussed in relation to the blockade of dopaminergic transmission. The purpose of the present paper was to investigate the relationship between cortical dopamine D2 receptor occupancy and the suppression of CAR by haloperidol in non‐human primate. The avoidance rate was measured for four different doses of haloperidol treatment in a rhesus monkey, and the cortical D2 receptor occupancy was measured in a parallel session using positron emission tomography with [11C]FLB 457. The successful avoidance response rate was decreased for doses of 10 and 30 µg/kg of haloperidol, and this decrement was associated with 65–77% of D2 receptor occupancy. It is suggested that the threshold level of cortical dopamine D2 receptor occupancy for the suppression of CAR is demonstrated in the present study.
Patterns of floristic richness in vegetation communities of California: regional scale analysis with multi‐temporal NDVI
Authors: Fairbanks Dean H. K. , McGwire Kenneth C.
Published: May 2004

Aim  Applying water‐energy dynamics and heterogeneity theory to explain species richness via remote sensing could allow for the regional characterization and monitoring of vegetation community assemblages and their environment. We assess the relationship of multi‐temporal normalized difference vegetation index (NDVI) to plant species richness in vegetation communities.

Location  California, USA.

Methods  Sub‐regions containing species inventories for chaparral, coastal sage scrub, foothill woodland, and yellow pine forest communities were intersected with a vegetation community map and an AVHRR NDVI time series for 1990, 1991, 1992, 1995 and 1996. Principal components analysis reduced the AVHRR data to three variables representing the sum and temporal trajectories of NDVI within each community. A fourth variable representing heterogeneity was tested using the standard deviation of the first component. Quadratic forms of these variables were also tested. Species richness was analysed by stepwise regression.

Results  Chaparral, coastal sage scrub, and yellow pine forest had the best relationships between species richness and NDVI. Richness of chaparral was related to NDVI heterogeneity and spring greenness (r2 varied between 0.26 and 0.62 depending on year of NDVI data). Richness of coastal sage scrub was nonlinearly related to annual NDVI and heterogeneity (r2 0.63–0.81), with peak richness at intermediate values. Foothill woodland richness was related to heterogeneity in a monotonic curvilinear fashion (r2 0.28–0.35). Yellow pine forest richness was negatively related to spring greenness and positively related to heterogeneity (r2 0.40–0.46).

Main Conclusions  While NDVI's relationship to species richness varied, the selection of NDVI variables was generally consistent across years and indicated that spatial variability in NDVI may reflect important patterns in water‐energy use that affect plant species richness. The principal component axis that should correspond closely with annual mean NPP showed a less prominent role. We conclude that plant species richness for coarse vegetation associations can be characterized and monitored at a regional scale and over long periods of time using relatively coarse resolution NDVI data.
How fast and far might tree species migrate in the eastern United States due to climate change?
Authors: Iverson Louis R. , Schwartz M. W. , Prasad Anantha M.
Published: May 2004

Aim We describe and use a model, SHIFT, to estimate potential migration due to climate change over the next 100 years.

Location Eastern United States.

Methods Five species, currently confined to the eastern half of the United States and not extending into Canada, were used to assess migration potential:Diospyros virginiana(persimmon),Liquidambar styraciflua(sweetgum),Oxydendrum arboreum(sourwood),Pinus taeda(loblolly pine), andQuercus falcatavar.falcata(southern red oak). SHIFT is a matrix simulation model using simple inverse power functions to provide a distance decay of seed dispersal and is driven primarily by the abundance of the species near the boundary, the forest density within and beyond the boundary, and the distance between cells. For each cell outside the current boundary, the model creates an estimate of the probability that each unoccupied cell will become colonized over a period of 100 years. SHIFT is a ‘fat‐tailed’ migration model that allows rare very long distance dispersal events and colonization could occur up to 500 km beyond the current distribution boundary. Model outputs were analysed using transects through sections showing relatively low and high colonization probabilities as a result of low and high densities of target trees (high source strength) as well as high densities of forest (high sink strength). We also assess migration potential for species by concentric rings around the current boundary.

Results Model outputs show the generally limited nature of migration for all five species over 100 years. There is a relatively high probability of colonization within a zone of 10–20 km (depending on habitat quality and species abundance) from the current boundary, but a small probability of colonization where the distance from the current boundary exceeds about 20 km. Whether biologically plausible or not, rare very long distance migration events are not sufficient to rescue migration. Species abundance (the source strength of migration) near the range boundary carried relatively more influence than percentage forest cover (sink strength) in determining migration rates.

Main conclusion The transect evaluation revealed the importance of abundance of the species near the boundary, indicating that rare species may have much more difficulty in unassisted northward migration due to climate change. The concentric rings analysis of the model outputs showed that only the first 10–20 km of area would have a reasonably high probability of colonization. Rare, long‐distance events permit colonization of remote outliers, but much more needs to be understood about the likelihood of these rare events to predict the frequency of outlier establishment.
Sensitivity of macroecological patterns of South American parrots to differences in data sources
Authors: Mathias Pablo V. C. , Mendonça Cláudio V. , Rangel Thiago F. L. V. B. , Diniz‐Filho José A. F.
Published: May 2004

A criticism of macroecological studies has been their extensive use of secondary data sources. In this note we evaluate how different data sources affect macroecological patterns for the parrots of South America. We mapped extents of parrot occurrence based on four sources of range maps. We compared basic statistics for geographical range size distribution (mean, variance and skew) and calculated correlations between geographical range size estimates and grid cell species richness estimates. Finally, results from multiple regression analyses of species richness against six environmental variables were also compared. We found that patterns were very robust to the data source, with only relatively slight quantitative differences. Our results reinforce the notion that patterns emerging from macroecological analyses are robust to variations in data sources and cannot be merely artefacts resulting from low data quality, notably poorly defined mapping and conflicting taxonomy.
Difference Equations for the Higher‐Order Moments and Cumulants of the INAR(1) Model
Authors: Eduarda Da Silva Maria , Oliveira Vera Lúcia
Published: May 2004

Recently, as a result of the growing interest in modelling stationary processes with discrete marginal distributions, several models for integer value time series have been proposed in the literature. One of these models is the INteger‐AutoRegressive (INAR) model. Here we consider the higher‐order moments and cumulants of the INAR(1) process and show that they satisfy a set of Yule–Walker type difference equations. We also obtain the spectral and bispectral density functions, thus characterizing the INAR(1) process in the frequency domain. We use a frequency domain approach, namely the Whittle criterion, to estimate the parameters of the model. The estimation theory and associated asymptotic theory of this estimation method are illustrated numerically.
The adjustment of prediction intervals to account for errors in parameter estimation
Authors: Kabaila Paul , He Zhisong
Published: May 2004

Abstract.  Standard approximate 1 − α prediction intervals (PIs) need to be adjusted to take account of the error in estimating the parameters. This adjustment may be aimed at setting the (unconditional) probability that the PI includes the value being predicted equal to 1 − α. Alternatively, this adjustment may be aimed at setting the probability that the PI includes the value being predicted equal to 1 − α, conditional on an appropriate statistic T. For an autoregressive process of order p, it has been suggested that T consist of the last p observations. We provide a new criterion by which both forms of adjustment can be compared on an equal footing. This new criterion of performance is the closeness of the coverage probability, conditional on all of the data, of the adjusted PI and 1 − α. In this paper, we measure this closeness by the mean square of the difference between this conditional coverage probability and 1 − α. We illustrate the application of this new criterion to a Gaussian zero‐mean autoregressive process of order 1 and one‐step‐ahead prediction. For this example, this comparison shows that the adjustment which is aimed at setting the coverage probability equal to 1 − α conditional on the last observation is the better of the two adjustments.
Some Results on Cointegration with Random Coefficients in the Error Correction Form: Estimation and Testing
Authors: Fong P. W. , Li W. K.
Published: May 2004

Abstract.  This study considers a time‐series model with random coefficients in cointegration. The estimation problem can be solved by maximizing the log‐likelihood. Asymptotic distributions of the least squares and maximum likelihood estimates are considered. The randomness of the cointegration vector is checked by a score‐based test approach. The test statistic converges asymptotically to a functional of Brownian processes. An empirical application to two cointegrated series, federal fund rate and 90‐day treasury bill rate is considered.
Inclusive learning disability research: the (nondisabled) researcher's role
Authors: Walmsley Jan
Published: May 2004

In this paper, the role of the nondisabled researcher who supports inclusive research in learning disability is explored. The author argues for more transparency about the role in order to highlight the challenges of working inclusively on research projects, the real contribution of people with learning difficulties to research, and the training/support implications of working inclusively.
To be labelled, or not to be labelled: that is the question
Authors: Ho Anita
Published: May 2004

• ‘Learning disability’ label establishes accommodation eligibility and civil rights protection but provides an excuse for school officials and legislators to adopt a medical model of learning disabilities and ignore other problems in the educational and social systems.

• A commitment to inclusion and equality requires an acknowledgement of various categorization problems, and a realization that various contexts may contribute to people's different learning patterns.

• Pathologizing learning difference may be unnecessary or even counterproductive if we presume that all children learn in their unique ways. It is more productive to design flexible curricula that can accommodate learning diversity.
Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ‐synuclein, α‐synuclein and double α/γ‐synuclein null mutant mice
Authors: Robertson Darren C. , Schmidt Oliver , Ninkina Natalia , Jones Paul A. , Sharkey John , Buchman Vladimir L.
Published: May 2004

The growing body of evidence suggests that intermediate products of α‐synuclein aggregation cause death of sensitive populations of neurones, particularly dopaminergic neurones, which is a critical event in the development of Parkinson's disease and other synucleinopathies. The role of two other members of the family, β‐synuclein and γ‐synuclein, in neurodegeneration is less understood. We studied the effect of inactivation of γ‐synuclein gene on mouse midbrain dopaminergic neurones. Reduced number of dopaminergic neurones was found in substantia nigra pars compacta (SNpc) but not in ventral tegmental area (VTA) of early post‐natal and adult γ‐synuclein null mutant mice. Similar reductions were revealed in α‐synuclein and double α‐synuclein/γ‐synuclein null mutant animals. However, in none of these mutants did this lead to significant changes of striatal dopamine or dopamine metabolite levels and motor dysfunction. In all three studied types of null mutants, dopaminergic neurones of SNpc were resistant to methyl‐phenyl‐tetrahydropyridine (MPTP) toxicity. We propose that both synucleins are important for effective survival of SNpc neurones during critical period of development but, in the absence of these proteins, permanent activation of compensatory mechanisms allow many neurones to survive and become resistant to certain toxic insults.
TorsinB – perinuclear location and association with torsinA
Authors: Hewett Jeffrey W. , Kamm Christoph , Boston Heather , Beauchamp Roberta , Naismith Teri , Ozelius Laurie , Hanson Phyllis I. , Breakefield Xandra O. , Ramesh Vijaya
Published: May 2004

The torsins comprise a four‐member family of AAA+ chaperone proteins, including torsinA, torsinB, torp2A and torp3A in humans. Mutations in torsinA underlie early onset torsion dystonia, an autosomal dominant, neurologically based movement disorder. TorsinB is highly homologous to torsinA with its gene adjacent to that for torsinA on human chromosome 9q34. Antibodies have been generated which can distinguish torsinA and torsinB from each other, and from the torps in human and rodent cells. TorsinB (∼ MW 38 kDa), like torsinA (∼ MW 37 kDa), is an N‐glycosylated protein and both reside primarily in the endoplasmic reticulum (ER) and nuclear envelope in cultured cells. Immunoprecipitation studies in cultured cells and human brain tissue indicate that torsinA and torsinB are associated with each other in cells. Overexpression of both wild‐type torsinB and mutant torsinA lead to enrichment of the protein in the nuclear envelope and formation of large cytoplasmic inclusions. We conclude that torsinB and torsinA are localized in overlapping cell compartments within the same protein complex, and thus may carry out related functions in vivo.
Choline availability modulates human neuroblastoma cell proliferation and alters the methylation of the promoter region of the cyclin‐dependent kinase inhibitor 3 gene
Authors: Niculescu Mihai D. , Yamamuro Yutaka , Zeisel Steven H.
Published: May 2004

Choline is an important methyl donor and a component of membrane phospholipids. In this study, we tested the hypothesis that choline availability can modulate cell proliferation and the methylation of genes that regulate cell cycling. In several other model systems, hypomethylation of cytosine bases that are followed by a guanosine (CpG) sites in the promoter region of a gene is associated with increased gene expression. We found that in choline‐deficient IMR‐32 neuroblastoma cells, the promoter of the cyclin‐dependent kinase inhibitor 3 gene (CDKN3) was hypomethylated. This change was associated with increased expression of CDKN3 and increased levels of its gene product, kinase‐associated phosphatase (KAP), which inhibits the G1/S transition of the cell cycle by dephosphorylating cyclin‐dependent kinases. Choline deficiency also reduced global DNA methylation. The percentage of cells that accumulated bromodeoxyuridine (proportional to cell proliferation) was 1.8 times lower in the choline‐deficient cells than in the control cells. Phosphorylated retinoblastoma (p110) levels were 3 times lower in the choline‐deficient cells than in control cells. These findings suggest that the mechanism whereby choline deficiency inhibits cell proliferation involves hypomethylation of key genes regulating cell cycling. This may be a mechanism for our previously reported observation that stem cell proliferation in hippocampus neuroepithelium is decreased in choline‐deficient rat and mouse fetuses.
Neuroprotective properties of Bcl‐w in Alzheimer disease
Authors: Zhu Xiongwei , Wang Yang , Ogawa Osamu , Lee Hyoung‐gon , Raina Arun K. , Siedlak Sandra L. , Harris Peggy L. R. , Fujioka Hisashi , Shimohama Shun , Tabaton Massimo , Atwood Craig S. , Petersen Robert B. , Perry George , Smith Mark A.
Published: May 2004

While there is a host of pro‐apoptotic stimuli that target neurons in Alzheimer disease (AD), given the chronicity of the disease and the survival of many neurons, those neurons must either avoid or, at minimum, delay apoptotic death signaling. In this study, we investigated Bcl‐w, a novel member of the Bcl‐2 family that promotes cell survival. In AD, we found increased levels of Bcl‐w associated with neurofibrillary pathology and punctate intracytoplasmic structures whereas, in marked contrast, there are only low diffuse levels of Bcl‐w in the neuronal cytoplasm of age‐matched control cases. Immunoblot analysis confirmed that Bcl‐w levels were significantly increased in AD. By electron microscopy, we determined that the increased Bcl‐w expression in AD was ultrastructurally localized to mitochondria and neurofibrillary pathology. To investigate the cause and consequence of Bcl‐w up‐regulation in neurons, we found that fibrillized amyloid‐β led to increased Bcl‐w protein levels in M17 human neuroblastoma cells, and that overexpression of Bcl‐w significantly protected neurons against staurosporine‐ and amyloid‐β‐induced apoptosis. Taken together, these series of results suggest that Bcl‐w may play an important protective role in neurons in the diseased brain and that this aspect could be therapeutically harnessed to afford neuroprotection.
S100A1 codistributes with synapsin I in discrete brain areas and inhibits the F‐actin‐bundling activity of synapsin I
Authors: Benfenati Fabio , Ferrari Rosaria , Onofri Franco , Arcuri Cataldo , Giambanco Ileana , Donato Rosario
Published: May 2004

The Ca2+‐sensor protein S100A1 was recently shown to bind in vitro to synapsins, a family of synaptic vesicle phosphoproteins involved in the regulation of neurotransmitter release. In this paper, we analyzed the distribution of S100A1 and synapsin I in the CNS and investigated the effects of the S100A1/synapsin binding on the synapsin functional properties. Subcellular fractionation of rat brain homogenate revealed that S100A1 is present in the soluble fraction of isolated nerve endings. Confocal laser scanning microscopy and immunogold immunocytochemistry demonstrated that S100A1 and synapsin codistribute in a subpopulation (5–20%) of nerve terminals in the mouse cerebral and cerebellar cortices. By forming heterocomplexes with either dephosphorylated or phosphorylated synapsin I, S100A1 caused a dose‐ and Ca2+‐dependent inhibition of synapsin‐induced F‐actin bundling and abolished synapsin dimerization, without affecting the binding of synapsin to F‐actin, G‐actin or synaptic vesicles. These data indicate that: (i) synapsins and S100A1 can interact in the nerve terminals where they are coexpresssed; (ii) S100A1 is unable to bind to SV‐associated synapsin I and may function as a cytoplasmic store of monomeric synapsin I; and (iii) synapsin dimerization and interaction with S100A1 are mutually exclusive, suggesting an involvement of S100A1 in the Ca2+‐dependent regulation of synaptic vesicle trafficking.
Enhanced anandamide degradation is associated with neuronal apoptosis induced by the HIV‐1 coat glycoprotein gp120 in the rat neocortex
Authors: Maccarrone Mauro , Piccirilli Silvia , Battista Natalia , Del Duca Claudio , Nappi Giuseppe , Corasaniti M. Tiziana , Finazzi‐Agrò Alessandro , Bagetta Giacinto
Published: May 2004

Human immunodeficiency virus type‐1 coat glycoprotein gp120 causes delayed apoptosis in rat brain neocortex. Here, we investigated the possible role of the endocannabinoid system in this process. It is shown that gp120 causes a time‐dependent increase in the activity and immunoreactivity of the anandamide (AEA)‐hydrolyzing enzyme fatty acid amide hydrolase (FAAH), paralleled by increased activity of the AEA membrane transporter and decreased endogenous levels of AEA. The AEA‐synthesizing phospholipase D and the AEA‐binding receptors were not affected by gp120. None of the changes induced by gp120 in the cortex were induced by bovine serum albumin, nor were they observed in the hippocampus of the same animals. Also, the activity of 5‐lipoxygenase, which generates AEA derivatives able to inhibit FAAH, decreased down to approximately 25% of the control activity upon gp120 treatment, due to reduced protein level (∼45%). In addition, the FAAH inhibitor methyl‐arachidonoyl fluorophosphonate significantly reduced gp120‐induced apoptosis in rat brain neocortex, whereas selective blockers of AEA membrane transporter or of AEA‐binding receptors were ineffective. Taken together, these results suggest that gp120, by activating FAAH, decreases endogenous levels of AEA, and the latter effect seems instrumental in the execution of delayed neuronal apoptosis in the brain neocortex of rats.
Resistance to cerebral ischemic injury in UCP2 knockout mice: evidence for a role of UCP2 as a regulator of mitochondrial glutathione levels
Authors: De Bilbao Fabienne , Arsenijevic Denis , Vallet Philippe , Hjelle Ole Petter , Ottersen Ole Petter , Bouras Constantin , Raffin Yvette , Abou Karin , Langhans Wolfgang , Collins Sheila , Plamondon Julie , Alves‐Guerra Marie‐Clotilde , Haguenauer Anne , Garcia Irene , Richard Denis , Ricquier Daniel , Giannakopoulos Panteleimon
Published: May 2004

Uncoupling protein 2 (UCP2) is suggested to be a regulator of reactive oxygen species production in mitochondria. We performed a detailed study of brain injury, including regional and cellular distribution of UCP2 mRNA, as well as measures of oxidative stress markers following permanent middle cerebral artery occlusion in UCP2 knockout (KO) and wild‐type (WT) mice. Three days post ischemia, there was a massive induction of UCP2 mRNA confined to microglia in the peri‐infarct area of WT mice. KO mice were less sensitive to ischemia as assessed by reduced brain infarct size, decreased densities of deoxyuridine triphosphate nick end‐labelling (TUNEL)‐labelled cells in the peri‐infact area and lower levels of lipid peroxidation compared with WT mice. This resistance may be related to the substantial increase of basal manganese superoxide dismutase levels in neurons of KO mice. Importantly, we found a specific decrease of mitochondrial glutathione (GSH) levels in UCP2 expressing microglia of WT, but not in KO mice after ischemia. This specific association between UCP2 and mitochondrial GSH levels regulation was further confirmed using lipopolysaccharide models of peripheral inflammation, and in purified peritoneal macrophages. Moreover, our data imply that UCP2 is not directly involved in the regulation of ROS production but acts by regulating mitochondrial GSH levels in microglia.
Entrepreneurial Management and Governance in Family Firms: An Introduction
Authors: Steier Lloyd P. , Chrisman James J. , Chua Jess H.
Published: May 2004

Many organizations, ranging from small entrepreneurial start–ups to large, multi–business and multi–national enterprises, exhibit a family dimension. Although there is much evidence that this familial dimension is pervasive in organizing economic activities, it remains understudied. The articles in this special issue further our understanding of family businesses and how they might be usefully managed and organized at operational and policy levels. They examine important topics—management succession, agency costs in family versus non–family firms, the effects of culture, and family elites in rent–seeking societies—and improve our understanding of the role of family in entrepreneurial wealth creation at both firm and societal levels. Importantly, these papers further our understanding of the contingencies and contexts wherein family based approaches to organizing enterprise might yield advantages or disadvantages.
Photodynamic therapy of interdigital mycoses of the feet with topical application of 5‐aminolevulinic acid
Authors: Calzavara‐Pinton P. G. , Venturini M. , Capezzera R. , Sala R. , Zane C.
Published: May 2004

Background: Findings of in vitro studies have demonstrated that dermatophytes and yeasts can be effectively photosensitized after topical delivery of 5‐aminolevulinic acid (ALA). This procedure, called photodynamic therapy (PDT), seems to lack mutagenic activity and hazard of selection of drug‐resistant strains.

Methods: Twenty percent ALA preparation in Eucerin cream was applied under an occlusive dressing to skin lesions of nine patients with clinical and microbiological evidence of interdigital mycosis of the feet. After 4 h, lesions were irradiated with 75 J/cm2 of broad‐band red light. Interdigital lesions of the other foot served as control (treated with only light or only ALA). After 7 days from the first treatment, no further treatment was delivered if lesions were not clinically evident and direct microscopic examination was negative. Otherwise, three additional weekly treatments were delivered. Four weeks after the last treatment, patientshad a final follow‐up clinical and laboratory examination.

Results: Clinical and microbiological recovery was seen in six out of nine patients after one (four cases) or four (two cases) treatments. However, after 4 weeks, recurrences were seen in four patients. Overall tolerability was always good.

Conclusion: Under the conditions employed in the present study, ALA‐PDT had good therapeutic effects on interdigital mycosis of the feet. However, recurrences were quick. In vivo environmental conditions, i.e. temperature, humidity and pH of the interdigital skin, could induce a poor cell uptake of ALA and a deficient biosynthesis of photosensitizing protoporphyrin IX. In addition, the irregular tridimensional shape of this peculiar anatomical area could lead to a non‐uniform delivery of light and/or ALA cream. However, the present results can stimulate further studies on the PDT of superficial skin mycoses.
Gene expression profiling of in vivo UVB‐irradiated human epidermis
Authors: Enk Claes D. , Shahar Iris , Amariglio Ninette , Rechavi Gideon , Kaminski Naftali , Hochberg Malka
Published: May 2004

Background: Several recent studies have employed microarray profiling to study UVB‐regulated gene expression in human skin. These studies are all based on UV‐irradiated cultured cells that differ substantially from the intact tissues they are supposed to imitate. The purpose of the present study was to analyze the differential expression of UVB‐regulated genes in intact human epidermis following in vivo UV irradiation.

Methods: The forearms of human volunteers were exposed to 4 MED of UVB in vivo, followed by removal of epidermal samples from exposed and non‐exposed areas after 24 h. RNA samples were analyzed using oligonucleotide microarray (Affymetrix) technology analyzing 12 500 genes simultaneously. Verification of selected genes was performed by semi‐quantitative reverse transcriptase polymerase chain reaction.

Results: Gene expression patterns clearly distinguished UV‐exposed epidermis from unexposed skin. Classification of these genes into functional categories revealed that several biological processes are globally affected by UVB. Significant changes were seen in more than 800 genes.

Conclusion: Human intact epidermis responds to a single low dose of in vivo UVB irradiation by differential regulation of numerous genes. Our results illustrate the power of global gene expression analysis of human epidermis to identify molecular pathways involved in UV‐induced photodamage.
Physical activity as a preventive measure for coronary heart disease risk factors in early childhood
Authors: Sääkslahti Arja , Numminen Pirkko , Varstala Väinö , Helenius Hans , Tammi Anne , Viikari Jorma , Välimäki Ilkka
Published: May 2004

Physical activity causes acute physiological and long‐term adaptive responses in the body. It is a protective factor for coronary heart disease (CHD) in adults. It has been assumed that children younger than 8 years of age may be in general active enough and there would be hardly any relationships between physical activity and CHD risk factors in early childhood. One hundred and fifty‐five children (age 4–7 years) participated in this physical activity study during three consecutive years. Physical activity was examined twice a year with a special‐purpose physical activity diary. CHD risk factors were measured during annual health care visits in the Specific Turku Coronary Risk‐Factor Intervention Project (STRIP). We found that physical activity was related to CHD risk factors in early childhood. Among the girls, low‐activity playing was related to a higher BMI. At the mean age of 6 years, high‐activity playing was negatively related to serum total cholesterol (r=−0.32*) and positively to the high‐density lipoprotein (HDL)/total cholesterol ratio (r=0.37**). The negative relationship between high‐activity playing and triglycerides was highest (r=−0.32*) at the mean age of six. Among 4‐year‐old boys, playing outdoors correlated positively with serum HDL cholesterol concentration (r=0.29*) and the HDL/total ratio (r=0.35**). At the age of 5 years, physically active playing correlated positively with systolic blood pressure (r=0.25*). Playing outdoors and high‐activity playing already have important health‐maintaining effects in 4–7‐year‐old children. These positive effects differ between genders. (*P<0.05 **P<0.01)
Secular trends in physical fitness and obesity in Danish 9‐year‐old girls and boys: Odense School Child Study and Danish substudy of the European Youth Heart Study
Authors: Wedderkopp N. , Froberg K. , Hansen H. S. , Andersen L. B.
Published: May 2004

Introduction:  Low physical fitness and obesity have been shown to be associated with cardiovascular disease (CVD) risk. Obesity is on the increase in many countries, but little is known about physical fitness trends. Monitoring of changes in fitness and obesity in the population is important for preventive strategies, and the aim of this study was to analyse the secular trends in fitness and body composition in Danish children.

Materials and methods:  Two representative population studies were conducted 12 years apart on 9‐year‐old children in the same location: the Odense School Child Study in 1985–86 and the European Youth Heart Study in 1997–98. In both studies, physical fitness was determined by a maximal cycle ergometer test, and obesity was assessed by skinfolds.

Results:  Boys had a lower physical fitness and were fatter in 1997–98 than in 1985–86. In addition, an increased polarization is emerging, with the difference between the fit and the unfit and the difference between the lean and the fat being greater in 1997–98 than in 1985–86. In girls, a similar polarization was found, but no overall change in fitness or obesity.

Conclusion:  The negative trend and increased polarization for physical fitness and obesity in Danish children suggest a future generation with a higher degree of CVD risk.
The Law: Must the Senate Take a Floor Vote on a Presidential Judicial Nominee?
Authors: Sollenberger Mitchel A.
Published: May 2004

President George W. Bush has frequently urged the Senate to fulfill its constitutional duty and vote on his nominations to the federal courts. The administration argues that the Senate must hold up‐or‐down floor votes on all judicial nominees. Senate Democrats counter that the president is trying to short‐circuit the procedural steps of the confirmation process. Currently, both sides are waging an ideological and institutional battle over the judicial confirmation process. This article analyzes the claim that the Senate must vote on all of the president's judicial nominees, and concludes that there is no basis for requiring that the Senate must hold mandatory confirmation votes for lower‐court nominees. By tradition, the Senate generally takes floor votes for nominations to the Supreme Court.
Cellular and Gene Therapy for Major Histocompatibility Complex Class II Deficiency
Authors: Matheux Franck , Villard Jean
Published: May 2004

Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model of this disease. In addition, by a direct genetic correction approach, a diagnostic test to determine which of the four MHC II genes is defective in new MHC II-deficiency patients has been optimized.
Use of Recombinant Congenic Strains in Mapping Disease-Modifying Genes
Authors: Müllerová Jana , Hozák Pavel
Published: May 2004

Previous research studies have established much information about single-gene diseases. However, other genes also influencing the outcome of a disease and genes involved in complex disease remain largely unknown. Here we report on recombinant congenic strains of mice, a powerful tool for genetic dissection of a complex trait.
“Vision” in Single-Celled Algae
Authors: Kateriya Suneel , Nagel Georg , Bamberg Ernst , Hegemann Peter
Published: May 2004

Photosynthetic unicellular algae have a unique visual system. In Chlamydomonas reinhardtii, the pigmented eye comprises the optical system and at least five different rhodopsin photoreceptors. Two of them, the channelrhodopsins, are rhodopsin-ion channel hybrids switched between closed and open states by photoisomerization of the attached retinal chromophore. They promise to become a useful tool for noninvasive control of membrane potential and intracellular ion concentrations.
Concomitant Administration of Lumiracoxib and a Triphasic Oral Contraceptive Does Not Affect Contraceptive Activity or Pharmacokinetic Profile
Authors: Kalbag Jyoti , Elder Cheryl , Scott Graham , Wang Yibin , Milosavljev Slavica , Leese Philipp , Caldwell Jacque , Rordorf Christiane
Published: May 2004

This study evaluated the effect of lumiracoxib on the pharmacokinetics and pharmacodynamics of ethinyl estradiol (EE) and levonorgestrel (LN) in Triphasil®‐28 (a triphasic oral contraceptive). Females stabilized on Triphasil®‐28 continued on Triphasil®‐28 alone for another month (Treatment Period 1), then also received lumiracoxib (400 mg daily) or placebo for 28 days each (Periods 2 and 3) in a double‐blind crossover design. Plasma pharmacokinetic profiles were assessed on Day 21 of Periods 2 and 3. Progesterone and plasma sex hormone binding globulin (SHBG) concentrations were measured before and 2 hours after Triphasil®‐28 administration on Day 21 of all three treatment periods. Lumiracoxib had no significant effect on EE or LN pharmacokinetics or on progesterone or SHBG concentrations, indicating that anovulation and Triphasil®‐28 effectiveness was maintained. Adverse events were similar for lumiracoxib and placebo. Therefore, no clinically important consequences are anticipated if lumiracoxib is coadministered with oral contraceptives containing EE or LN.
Influence of Omeprazole on Bioavailability of Bismuth following Administration of a Triple Capsule of Bismuth Biskalcitrate, Metronidazole, and Tetracycline
Authors: Spénard Jean , Aumais Christian , Massicotte Julie , Tremblay Claude , Lefebvre Marc
Published: May 2004

The objective of this study was to determine the impact of omeprazole on bismuth (Bi) bioavailability when given in a three‐in‐one capsule containing bismuth biskalcitrate, metronidazole, and tetracycline. Thirty‐four healthy volunteers were randomly assigned to receive three capsules (each containing bismuth biskalcitrate 140mg+ metronidazole 125 mg+ tetracycline 125 mg) qid alone × 6 days or the same treatment + omeprazole (OM) 20 mg bid. Blood was drawn at intervals for 24 hours after the last dose. After the last dose, mean (CV) Cmin for plasma bismuth was 2882 pg/mL (36%) and 1195 pg/mL (23%) (p < 0.001), with and without OM, respectively. Mean (CV)Cmax was 25,493 pg/mL (69%) and 8061 pg/mL (28%) (p < 0.001) with and without OM, respectively. AUC0‐24 increased by 2.9 in presence of OM (p < 0.001). Adverse events in both groups were usually mild and of a gastrointestinal nature, and all had resolved by the end of the trial. This study confirms an interaction between Bi biskalcitrate and OM. Risk of Bi toxicity, seen after long‐term use of Bi compounds, is minimal here because plasma levels of Bi remained well below the toxic levels of 50 μg/L, and the treatment period with this triple capsule + OM is only 10 days, a substantially lower number of days compared to that which might produce Bi toxicity.
Omeprazole as a CYP2C19 Marker in Chinese Subjects: Assessment of Its Gene‐Dose Effect and Intrasubject Variability
Authors: Yin Ophelia Q. P. , Tomlinson Brian , Chow Albert H. L. , Waye Mary M. Y. , Chow Moses S. S.
Published: May 2004

The objective of this study was to determine the reliability of omeprazole as a marker for CYP2C19 activity in Chinese subjects. In 27 healthy male Chinese subjects, the CYP2C19 phenotype was first determined with the standard mephenytoin hydroxylation index (HI) method. Subsequently, the subjects were randomized in a three‐way crossover manner to receive an oral 40‐mg dose from each of three omeprazole formulations (as part of a bioequivalence study). Multiple blood samples were obtained over 12 hours, and plasma concentrations of omeprazole, 5‐hydroxyomeprazole, and omeprazole sulfone were determined by a high‐performance liquid chromatography (HPLC) method. Individual CYP2C19 genotype was determined by the polymerase chain reaction/restriction fragment length polymorphism method. To assess the specificity for CYP2C19 activity, the hydroxylation metabolic ratio (MR) of omeprazole (AUComeprazole/AUC5‐hydroxyomeprazole) was compared to mephenytoin HI and related to CYP2C19 genotype status. The inter‐ and intrasubject variabilities of MR were also calculated, and their magnitudes were compared. The intersubject MR varied more than 20 fold. Among the subjects, there was a gene‐dose effect, and the mean MR was 1.76, 3.45, and 33.08, respectively, in the homozygous extensive metabolizers (wt/wt, n = 9), heterozygous extensive metabolizers (wt/m1 or wt/m2, n = 10), and poor metabolizers (m1/m1 or m1/m2, n = 7). However, the coefficients of variation for intrasubject MR only ranged from 4.5% to 33.7% over the three periods with the three formulations. The phenotype based on MR was concordant with HI. In view of the clear gene‐dose effect, concordance with mephenytoin HI, and low intrasubject variability, omeprazole MR following a 40‐mg oral dose can be considered as a specific and sensitive marker for CYP2C19 activity in Chinese subjects
Complete cycles of bloodstream trypanosome RNA editing in vitro
Authors: HALBIG KARI , DE NOVA-OCAMPO MONICA , CRUZ-REYES JORGE
Published: May 2004

RNA editing in kinetoplastid protists is required for the maturation of mitochondrial pre-mRNAs and occurs by protein-catalyzed cycles of uridylate insertion and deletion. During the complex life cycle of Trypanosoma brucei this process is differentially regulated in the mammalian bloodstream and insect procyclic stages. Complementary guide RNAs (gRNAs) direct editing, but the abundance of these transcripts is not developmentally controlled. The establishment of in vitro systems that recreate efficient RNA editing in bloodstream T. brucei would be valuable for mechanistic studies of regulation. Here we describe a robust in vitro system that reconstitutes full cycles of both U insertion and U deletion in bloodstream trypanosomes, and the first direct comparisons of the in vitro systems for strains of mammalian and insect stages.
The structure of a ribosomal protein S8/spc operon mRNA complex
Authors: MERIANOS HELEN J. , WANG JIMIN , MOORE PETER B.
Published: May 2004

In bacteria, translation of all the ribosomal protein cistrons in the spc operon mRNA is repressed by the binding of the product of one of them, S8, to an internal sequence at the 5′ end of the L5 cistron. The way in which the first two genes of the spc operon are regulated, retroregulation, is mechanistically distinct from translational repression by S8 of the genes from L5 onward. A 2.8 Å resolution crystal structure has been obtained of Escherichia coli S8 bound to this site. Despite sequence differences, the structure of this complex is almost identical to that of the S8/helix 21 complex seen in the small ribosomal subunit, consistent with the hypothesis that autogenous regulation of ribosomal protein synthesis results from conformational similarities between mRNAs and rRNAs. S8 binding must repress the translation of its own mRNA by inhibiting the formation of a ribosomal initiation complex at the start of the L5 cistron.
A general method for rapid and nondenaturing purification of RNAs
Authors: KIEFT JEFFREY S. , BATEY ROBERT T.
Published: May 2004

A key bottleneck in RNA structural studies is preparing milligram quantities of RNA, and current techniques have changed little in over a decade. To address this, we have developed an affinity tag-based purification method of RNA oligonucleotides. The tag is attached to the 3′-end of almost any desired RNA sequence, allowing for the rapid and specific removal of the RNA of interest directly from in vitro transcription reactions using an affinity column to which a specific RNA-binding protein has been attached. Following a wash, the RNA of interest is eluted by the addition of imidazole to the column, activating a mutant HδV ribozyme incorporated into the tag. The affinity column can then be rapidly regenerated using conditions that release the protein–RNA tag interaction without denaturing the protein. To demonstrate that this method rapidly generates high-quality RNA, we have transcribed, purified, and generated diffraction-quality crystals of a mutant form of the Tetrahymena thermophila P4–P6 domain in a 48-h time period.
Measuring Global Brand Equity Using Cross-National Survey Data
Authors: Hsieh Ming-Huei
Published: May 2004

This article presents a newly developed survey-based method for the measurement of customer-based brand equity in a cross-national context. The proposed national brand equity (NBE) model decomposes customer-based brand equity into two components: measured and unmeasured brand equity. Whereas the measured component of brand equity identifies the effectiveness of individual benefit associations across the globe, the unmeasured component captures the value that is attached to the brand but not measured by the commonly elicited associations. The author applies the NBE model to 18 brands across 16 worldwide automobile markets, which provides opportunities for assessing the applicability of the proposed model. Furthermore, in response to the trend of increasing brand globalization, the author develops a model of global brand equity to assess a brand's value relative to that of its global competitors. Based on the NBE model, the global brand equity model incorporates national weighting factors in the aggregation of NBE across countries. The resultant aggregation yields a global brand equity index, which provides practical applications for benchmarking against the best brand and serves as a good indicator of a brand's relative value in the global market.
Assessing National Identity in Russia between Generations using the National Identity Scale
Authors: Thelen Shawn T. , Honeycutt Earl D.
Published: May 2004

This research examines the structure of the national identity (NATID) scale in Russia. On the basis of confirmatory factor analysis results, the authors recommend modifications to strengthen the construct's application. By employing multigroup analysis, the authors assess the relationships between each NATID scale component (national heritage, cultural homogeneity, belief system, and consumer ethnocentrism) and overall national identity for invariance across two different Russian age cohorts: Soviet Russians and contemporary Russians. Soviet Russians reached their “age of socialization” when the Soviet Union was intact, whereas contemporary Russians achieved their age of socialization during the Gorbachev and Yeltsin eras. The results indicate a lack of invariance across age cohorts in the relationship between all the subconstructs, with the exception of national heritage, and overall national identity. As a result, researchers should consider that the relationship between components of the NATID scale and overall national identity is likely to vary in strength across groups in the same country. This insight is significant for firms that conduct market research, introduce products, and develop marketing strategies for selected markets.
Self‐Harmful Behaviors in a Population‐Based Sample of Young Adults
Authors: Nada‐Raja Shyamala , Skegg Keren , Langley John , Morrison Dianne , Sowerby Paula
Published: May 2004

A birth cohort of 472 women and 494 men aged 26 years was interviewed about a range of self‐harmful behaviors first and then asked about suicidal intent.‐Lifetime prevalence of self‐harm using traditional methods of suicide (ICD [International Classification of Diseases] self‐harm) was 13%, with 9% of the sample describing at least one such episode as “attempted suicide.” Other self‐harmful behaviors were common; 14% of women and 33% of men reported self‐battery. ICD self‐harm over the past year was reported by 3%, mostly without suicidal intent. ICD self‐harm and even lesser behaviors were associated with high odds of reporting suicidal ideation. The findings suggest that studies of self‐harm should include behaviors not necessarily associated with suicidal intent.