bluuebunny/crossref_metadata_2025 huggingface dataset:
The tandem‐repeat polymorphism of the DC‐SIGNR gene in HCV infection
Authors: Nattermann J. , Ahlenstiel G. , Berg T. , Feldmann G. , Nischalke H. D. , Müller T. , Rockstroh J. , Woitas R. , Sauerbruch T. , Spengler U.
Published: October 2005

Summary.  The C‐type lectin DC‐SIGNR has been shown to bind hepatitis C virus (HCV). Here, we analysed the tandem‐repeat polymorphism of the DC‐SIGNR gene with respect to intraindividual HCV replication. In a cross‐sectional comparison HCV‐infected patients (n = 430) and healthy subjects (n = 100) were genotyped for the DC‐SIGNR polymorphism using PCR. The distribution of DC‐SIGNR alleles did not differ significantly between the two groups. However, HCV‐infected patients with 5‐, 6‐, and 7‐repeat alleles had higher HCV‐RNA levels when compared with carriers of 4‐ and 9‐repeat alleles (P < 0.05). Thus, the DC‐SIGNR polymorphism might affect HCV loads supporting the concept that DC‐SIGNR contributes to HCV replication efficacy.
Interannual genetic heterogeneity of pollen pools accepted by Quercus salicina individuals
Authors: NAKANISHI A. , TOMARU N. , YOSHIMARU H. , MANABE T. , YAMAMOTO S.
Published: October 2005

Since flowering often varies among years in wind‐pollinated woody species, the genetic composition of pollen pools accepted by seed parents can differ between years. The interannual heterogeneity of pollen flow may be important for maintaining genetic diversity within populations because it can increase genetic variation within populations and the effective sizes of the populations. In this study we examined heterogeneity, using paternity analysis and analysis of molecular variance, in the genetic composition of pollen pools among different reproductive years for six Quercus salicina seed parents in an 11.56‐ha plot in a temperate old‐growth evergreen broadleaved forest. The genotypes at seven microsatellite loci were determined for 111 adult trees and 777 offspring of the six seed parents in 2–5 reproductive years. Genetic differentiation of pollen pools among different reproductive years for each seed parent was significant over all seed parents and for each of four seed parents that were analysed for more than 2 years, but not for either of the other two seed parents (analysed for 2 years). For both the pollen pools originating from inside the plot and those originating from outside it, genetic differentiation among different reproductive years for each seed parent was significant over all seed parents. However, among‐year genetic differentiation in the pollen pools originating from within the plot was detected for all four of the seed parents that were analysed for more than 2 years, but for only one of the four in the pools originating from outside the plot. Genetic diversity (estimated as allelic richness and gene diversity) was higher for pollen pools over all reproductive years than for pollen pools in single years. These results indicate that the year‐to‐year genetic variation of pollen pools increases genetic diversity in offspring and is strongly affected by the variation in pollen parents within the plot because of their high pollination contributions. The high year‐to‐year variation in pollen parents within the plot and overall supports the hypothesis that the offspring produced across years represent a larger genetic neighbourhood.
Comparison of leaf structure and photosynthetic characteristics of C3 and C4Alloteropsis semialata subspecies
Authors: UENO O. , SENTOKU N.
Published: October 2005

Alloteropsis semialata (R. Br.) Hitchcock includes both C3 and C4 subspecies: the C3 subspecies eckloniana and the C4 subspecies semialata. We examined the leaf structural and photosynthetic characteristics of these plants. A. semialata ssp. semialata showed high activities of photosynthetic enzymes involved in phosphoenolpyruvate carboxykinase‐type C4 photosynthesis and an anomalous Kranz anatomy. Phosphoenolpyruvate carboxylase; pyruvate, Pi dikinase and glycine decarboxylase (GDC) were compartmentalized between the mesophyll (M) and inner bundle sheath cells, whereas ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco) occurred in both cells. A. semialata ssp. eckloniana also showed an anomalous non‐Kranz anatomy, in which the mestome sheath cells included abundant chloroplasts and mitochondria. Rubisco and GDC accumulated densely in the M and mestome sheath cells, whereas the levels of C4 enzymes were low. The activity levels of photorespiratory enzymes in both subspecies were intermediate between those in typical C3 and C4 plants. The values of CO2 compensation points in A. semialata ssp. semialata were within the C4 range, whereas those in A. semialata ssp. eckloniana were somewhat lower than the C3 range. These data suggest that the plants are C3‐like and C4‐like but not typical C3 and C4, and when integrated with previous findings, point to important variability in the expression of C4 physiology in this species complex. A. semialata is therefore an intriguing grass species with which to study the evolutionary linkage between C3 and C4 plants.
Total skin electron irradiation therapy in mycosis fungoides using high‐dose rate mode: A preliminary experience
Authors: Parida Dillip K. , Verma Kaushal K. , Chander Subhash , Joshi R. C. , Rath Goura K.
Published: October 2005

Introduction  Total skin electron irradiation (TSEI) therapy is the treatment of choice for mycosis fungoides. However, conventional TSEI therapy is time consuming as well as patient unfriendly. Therefore we used high‐dose rate (HDR) mode TSEI in these patients. High‐dose rate mode of TSEI is a technological innovation attached to a Linear Accelerator (Philips, SL‐20, Netherlands), which can deliver an electron beam of 30 Gy/min at the iso‐center. The iso‐center faces the patient, 100 cm away from the target of the linear accelerator. The patient is treated at a distance of 10 feet from the iso‐center of the linear accelerator. The dose delivered to the skin was 1.13 Gy/min, making the treatment execution much easier and patient compliance much better.

Methods  Seven male patients between 40 and 64 years in age having mycosis fungoides for 9–18 months were treated by TSEI using high‐dose rate mode between 1998 and 2000. The TSEI was performed according to the Stanford technique, delivering a total dose of 36 Gy. Each patient received a dose of 1.2 Gy/field/day. There were six fields, i.e. anterior, posterior, left and right anterior obliques, and left and right posterior obliques in both the upper and lower parts of the body. The eyes and nails were shielded at each session of radiotherapy. The times taken at each session of the therapy and radiation‐associated side‐effects were determined in each patient. The patients were followed up to 26 months (median 9 months) to look for any relapse.

Results  Three patients had early stage disease (IB) whereas four patients had advanced disease (IIB). Six patients out of these had complete remission following TSEI while one patient died as a result of progression of the disease during treatment. The treatment time taken at each treatment session in each individual patient was approximately 15 min. Radiation‐associated morbidity was seen in all patients. Cutaneous lesions relapsed in two patients after 4 and 10 months, respectively, while four patients were alive without the disease at the end of 2 years.

Conclusions  Total skin electron irradiation using high‐dose rate mode delivery of electrons is an easy, better, compliant and effective therapeutic modality for treatment of mycosis fungoides with an acceptable range of toxicities.
Long‐term follow‐up study of 142 patients with vitiligo vulgaris treated by autologous, non‐cultured melanocyte–keratinocyte cell transplantation
Authors: Mulekar Sanjeev V.
Published: October 2005

Background  Vitiligo vulgaris patients are difficult to treat surgically owing to large area involvement. Larger areas can be treated with the help of in vitro cultured melanocytes. These techniques are complex. In most of the studies published to date the number of patients reported is low and follow‐up period short.

Objective  To evaluate long‐term efficacy and safety of melanocyte–keratinocyte cell transplantation in large number of vitiligo vulgaris patients.

Methods  A simpler and modified method based on that of Olsson and Juhlin has been used. It uses shave biopsy skin sample up to 1/10th the size of recipient area. Skin sample is incubated, cells mechanically separated using trypsin–EDTA solution, and then centrifuged to prepare a suspension. Cell suspension is then applied to a dermabraded de‐pigmented skin area and collagen dressing given to keep it in place.

Results  One hundred and forty‐two patients with vitiligo vulgaris were treated and observed for a period up to 6 years. Eighty (56%) patients showed excellent, 15 (11%) showed good, 13 (9%) showed fair and 34 (24%) showed poor repigmentation, which was retained till the end of the respective follow‐up period.
Mycosis fungoides associated with intestinal mucosa‐associated lymphoid tissue lymphoma
Authors: Ohmatsu Hanako , Saeki Hidehisa , Fujita Hideki , Toyoma Keiko , Sugaya Makoto , Asahina Akihiko , Masuda Shigeo , Hirai Hisamaru , Watanabe Toshiaki , Nagawa Hirokazu , Tamaki Kunihiko
Published: October 2005

Coexistence of cutaneous T‐cell lymphoma (CTCL) and a B‐cell malignancy is rare. We report a case of mycosis fungoides (MF) associated with intestinal mucosa‐associated lymphoid tissue (MALT) lymphoma, which is a low‐grade B‐cell lymphoma of marginal cell origin. To the best of our knowledge, there have been only two cases of coexistent CTCL and MALT lymphoma, and this is the first case with typical MF and intestinal MALT lymphoma. The coexistence in our case might be coincidental, but genetic predisposition and the immunoregulatory capacity of neoplastic T lymphocytes may be factors contributing to this association.
Induction of IL‐6 in co‐culture of bronchial epithelial cells and eosinophils is regulated by p38 MAPK and NF‐κB
Authors: Wang C. B. , Wong C. K. , Ip W. K. , Li M. L. Y. , Tian Y. P. , Lam C. W. K.
Published: October 2005

Background:  Prominent infiltration of eosinophils into the airway mucosa and release of inflammatory mediators upon their adhesion onto airway epithelial cells are the immunopathogical mechanisms of allergic asthma.

Objective:  We investigated the effect of normal and paraformaldyhyde‐fixed human eosinophils on BEAS‐2B cells, a human bronchial epithelial cell line, for the release of inflammatory cytokine interleukin (IL)‐6.

Methods:  Interleukin‐6 in cell culture supernatant, protein amount of p38 mitogen‐activated protein kinase (MAPK), and nuclear factor‐κB (NF‐κB) activity in BEAS‐2B cells were analyzed by Western blot and enzyme‐linked immunosorbent assay (ELISA). IL‐6 gene expression was assessed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), and p38 MAPK activity and inhibitor (I)κB‐α induction were evaluated by Western blot.

Results:  Co‐culture of BEAS‐2B cells and eosinophils induced a significant elevation of IL‐6 expression in BEAS‐2B cells. Interaction of eosinophils and BEAS‐2B cells led to a marked induction in phospho‐p38 MAPK, phospho‐IκB‐α and activity of NF‐κB in BEAS‐2B cells. NF‐κB inhibitor BAY 11‐7082 and p38 MAPK inhibitor SB 203580 significantly decreased IL‐6 release in a co‐culture of BEAS‐2B cells and eosinophils. Fixed human eosinophils were able to maintain their ability to induce IL‐6 release in co‐culture, activate p38 MAPK and NK‐κB, and up‐regulate IL‐6 gene expression in BEAS‐2B cells.

Conclusions:  These data indicate that the interaction of eosinophils and bronchial epithelial cells plays an important role in airway inflammation, at least partly, via IL‐6 induction.
Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen
Authors: López‐Torrejón G. , Ibáñez M. D. , Ahrazem O. , Sánchez‐Monge R. , Sastre J. , Lombardero M. , Barber D. , Salcedo G.
Published: October 2005

Background:  Orange is among the most widely consumed fruits, and among the plant food sources causing allergic reactions according to popular perception. However, its relevant allergenic components are virtually unknown. Profilin is a well‐defined minor plant panallergen, showing prevalences around 30% in fruits and vegetables.

Methods:  Twenty‐three orange‐allergic patients were studied. Natural orange profilin, named Cit s 2, was purified by affinity chromatography and characterized by N‐terminal amino acid sequencing, matrix‐assisted laser desorption/ionization mass spectrometry analysis and isolation of its coding cDNA. Reactivity to Cit s 2 was analyzed in vivo by skin prick tests (SPT) and in vitro by IgE immunodetection, specific IgE determination in individual sera and enzyme‐linked immunosorbent assay‐inhibition assays.

Results:  The N‐terminal amino acid sequence and molecular mass of natural Cit s 2, both fully in agreement with the complete amino acid sequence deduced from its coding cDNA, demonstrated its profilin nature. An unexpectedly high reactivity to Cit s 2 was found in vivo (78% of positive SPT responses) and in vitro (87% of sera from orange allergic patients had specific IgE to Cit s 2). The purified allergen inhibited around 50% of the IgE binding to an orange pulp extract.

Conclusion:  Orange profilin Cit s 2, unlike other plant food profilins, is a major and highly prevalent allergen.
On hidden heterogeneity in directional asymmetry – can systematic bias be avoided?ET AL.
Authors: Stige L. C. , David B. , Alibert P.
Published: October 2005

Directional asymmetry (DA) biases the analysis of fluctuating asymmetry (FA) mainly because among-individual differences in the predisposition for DA are difficult to detect. However, we argue that systematic bias mainly results from predictable associations between signed right–left asymmetry and other factors, i.e. from systematic variation in DA. We here demonstrate methods to test and correct for this, by analysing bilateral asymmetry in size and shape of an irregular sea urchin. Notably, in this model system, DA depended significantly on body length and geographic origin, although mean signed asymmetry (mean DA) was not significant in the sample as a whole. In contrast to the systematic variation in DA, undetectable, random variability in the underlying DA mainly leads to reduced statistical power. Using computer simulations, we show that this loss of power is probably slight in most circumstances. We recommend future studies on FA to routinely test and correct for not only as yet for mean DA, but also for systematic variation in DA.
In search of clinal variation in the period and clock timing genes in Australian Drosophila melanogaster populations
Authors: Weeks A. R. , Mckechnie S. W. , Hoffmann A. A.
Published: October 2005

Clinal variation for repeat number in the Thr-Gly region of the period circadian timing gene in Drosophila melanogaster was described in Europe and has subsequently been used as evidence of thermal selection on period alleles. To test for clinal variation in this gene along the east coast of Australia, the period polymorphism was scored on flies from multiple samples collected repeatedly over a 5-year interval, along with variation at another circadian rhythm locus, clock. For period, there was no consistent evidence of clinal variation in the 17 and/or 20 repeat alleles, although when average allele length was examined a weak consistent clinal pattern was detected. For clock there was no evidence of clinal variation in the two most common alleles or in average repeat size. These data are inconsistent with the reported patterns in Europe and suggest that clinal variation in timing genes needs to be re-examined in this region.
The linkage between the stem rust resistance gene Sr2 and pseudo‐black chaff in wheat can be broken
Authors: Mishra A. N. , Kaushal K. , Yadav S. R. , Shirsekar G. S. , Pandey H. N.
Published: October 2005

Recessively inherited gene Sr2 has provided the basis of durable resistance to stem rust (caused by Puccinia graminis tritici) in wheat (Triticum aestivum L.) worldwide. The associated earhead and stem melanism or ‘pseudo‐black chaff’ is generally used as a marker for this gene. Sr2 has been postulated in many wheat cultivars of India including ‘Lok 1’, based on associated pseudo‐black chaff in adult plants, and leaf chlorosis in seedlings. However, dominant inheritance of the resistance factor operating in ‘Lok 1’, and a 13 : 3 (resistant : susceptible) F2 segregation in the ‘Sr2‐line’ (‘Chinese Spring’6 × ‘Hope’ 3B) × ‘Lok 1’ cross confirmed that Sr2 was absent in ‘Lok 1’. Susceptible plants with a pseudo‐black chaff phenotype were observed in F2 populations of ‘Agra Local’ (susceptible) × ‘Lok 1’, and the ‘Sr2‐line’ × ‘Lok 1’ crosses. Most of the F3 families derived from the susceptible F2 segregants with pseudo‐black chaff phenotypes were true breeding for the expression of pseudo‐black chaff with susceptibility to stem rust. Thus, linkage of pseudo‐black chaff with Sr2 in wheat can be broken, and hence, caution may be exercised in using pseudo‐black chaff as a marker for selecting Sr2 in breeding programmes.
A new gene located on chromosome 2 causing hybrid sterility in a remote cross of rice
Authors: Zhu S. , Wang C. , Zheng T. , Zhao Z. , Ikehashi H. , Wan J.
Published: October 2005

‘Ketan Nangka’, the donor of the wide compatibility gene (WCG) showed typical hybrid sterility when crossed to a landrace, ‘Bai Mi Fen’, of Yunnan province in China. A genome‐wide analysis was performed for a backcrossed population of ‘Ketan Nangka’/‘Bai Mi Fen’//‘Ketan Nangka’ using a total of 143 simple sequence repeat markers and an expressed sequence tagged marker to cover the entire rice linkage map. As a result, two independent loci were found to cause hybrid sterility via female gamete abortion. The locus on chromosome 4 may correspond to S9, but the other, on chromosome 2, was different from all the previously reported hybrid sterility loci and was designated as S29(t) following the hybrid sterility nomenclature. On the basis of allelic interaction which causes female gamete abortion, two alleles were found: S29kn(t) in ‘Ketan Nangka’ and S29bi(t) in ‘Bai Mi Fen’. In the heterozygote, S29kn(t)/S29bi(t), which was semi‐sterile, female gametes carrying S29bi(t) were aborted. An Aus variety from the Indian subcontinent, ‘Dular’, was found to have a neutral allele, S29n(t). Two molecular markers, RM185 and RM425, linked to S9 and S29(t), respectively, will be useful for marker‐aided transfer of WCGs in hybrid rice breeding.
Introgression from wild Cicer reticulatum to cultivated chickpea for productivity and disease resistance
Authors: Singh S. , Gumber R. K. , Joshi N. , Singh K.
Published: October 2005

Interspecific hybridization is known to improve productivity and resistance to diseases in many crops. Therefore, an attempt was made to introgress productivity and disease resistance into chickpea from wild Cicer species. The true F1 hybrids of cultivated chickpea genotypes ‘L550’ and ‘FGK45’ with C. reticulatum were backcrossed twice to their cultivated female parents to minimize the linkage drag of undesirable wild traits. The pedigree method was followed to advance the segregating populations from straight crosses (without backcross) and BC1/BC2 generations to F5–F7. The interspecific derivatives recorded up to a 16.9% increase over the check cultivars and a 25.2% increase over the female parent in a preliminary yield evaluation trial. Of the 22 interspecific derivatives thus derived, four desi and two kabuli lines were further evaluated for seed yield in replicated trials at three diverse locations. These lines possess a high degree of resistance to wilt, foot rot and root rot diseases, and recorded a 6.1–17.0% seed yield increase over the best check cultivars.
Morphology, inheritance and mapping of a compressed lamina mutant of carrot
Authors: Nothnagel T. , Ahne R. , Straka P.
Published: October 2005

A compressed lamina mutant at a locus named COLA was selected in an inbred population of the cultivated carrot Daucus carota sativus Hoffm. Whereas segregation analyses of F2 progenies, as well as corresponding F3 families, indicated a monogenic recessive inheritance, detailed morphological and histological analyses revealed pleiotropic effects of the COLA gene. The mutant plants exhibited a semi‐dwarf phenotype, shortened epidermal and leaf parenchyma cells and significantly reduced lamina dimensions. Furthermore, the mutant developed stipules and hypogynous flowers, contrary to the stipule‐less leaves and epigynous flowers of the wild type. Using bulked segregant analyses, thirty‐nine marker candidates were detected using 180 RAPD primer and 56 AFLP primer pairs. Twelve primers were linked to the COLA locus and mapped in a linkage group with a total length of 44.2 cM. Potential application of the compressed lamina mutant in carrot research is discussed.
NMDA and dopamine interactions in the nucleus accumbens modulate cortical acetylcholine release
Authors: Zmarowski Amy , Sarter Martin , Bruno John P.
Published: October 2005

The nucleus accumbens (NAC) plays a key role in directing appropriate motor output following the presentation of behaviorally relevant stimuli. As such, we postulate that accumbens efferents also participate in the modulation of neuronal circuits regulating attentional processes directed toward the identification and selection of these stimuli. In this study, N‐methyl‐d‐aspartate (NMDA) and D1 ligands were perfused into the shell region of the NAC of awake rats. Cortical cholinergic transmission, a mediator of attentional processes, was measured via microdialysis probes inserted into the prefrontal cortex (PFC). NMDA perfusions (150 or 250 µm) into NAC resulted in significant increases in acetylcholine (ACh) efflux in PFC (150–200% above baseline levels). Co‐administration of the D1 antagonist SCH‐23390 (150 µm) markedly attenuated (by approx. 70%) ACh efflux following perfusions of 150 µm NMDA but not following 250 µm NMDA, suggesting that D1 receptor activity contributes to the ability of the lower but not the higher concentration of NMDA to increase cortical ACh release. Collectively, these data reveal a positive modulation of NMDA receptors by D1 receptors in NAC that is expressed trans‐synaptically at the level of cortical transmission. This modulation may underlie the coordinated linking of attentional processes and motor output following exposure to salient and behaviorally relevant stimuli.
Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine‐induced locomotor activity, reward and CREB phosphorylation
Authors: Karasinska Joanna M. , George Susan R. , Cheng Regina , O'Dowd Brian F.
Published: October 2005

Co‐localization of dopamine D1 and D3 receptors in striatal neurons suggests that these two receptors interact at a cellular level in mediating dopaminergic function including psychostimulant‐induced behaviour. To study D1 and D3 receptor interactions in cocaine‐mediated effects, cocaine‐induced locomotion and reward in mice lacking either D1, D3 or both receptors were analysed. Spontaneous locomotor activity was increased in D1–/–and D1–/–D3–/–mice and D1–/–D3–/–mice did not exhibit habituation of spontaneous rearing activity. Cocaine (20 mg/kg) increased locomotor activity in wild‐type and D3–/–mice, failed to stimulate activity in D1–/–mice and reduced activity in D1–/–D3–/–mice. In the conditioned place preference, all groups exhibited reward at 5, 10 and 20 mg/kg of cocaine. D1–/–D3–/–mice did not demonstrate preference at 2.5 mg/kg of cocaine although preference was observed in wild‐type, D1–/–and D3–/–mice. The transcription factor cAMP‐responsive element binding protein (CREB) is activated by phosphorylation in striatal regions following dopamine receptor activation. Striatal pCREB levels following acute cocaine were increased in wild‐type and D3–/–mice and decreased in D1–/–and D1–/–D3–/–mice. After repeated administration of 2.5 mg/kg of cocaine, D1–/–mice had lower pCREB levels in caudate–putamen and nucleus accumbens. Our findings suggest that, although spontaneous and cocaine‐induced horizontal activity depended mainly on the presence of the D1 receptor, there may be crosstalk between D1 and D3 receptors in rearing habituation and the perception of cocaine reward at low doses of the drug. Furthermore, alterations in pCREB levels were associated with changes in cocaine‐induced locomotor activity but not reward.
Role of imidazoline receptors in the anti‐aversive properties of clonidine during opiate withdrawal in rats
Authors: Georges F. , Caillé S. , Vouillac C. , Le Moine C. , Stinus L.
Published: October 2005

Clonidine is used as a treatment for heroin addiction. Previous studies have reported that clonidine attenuated conditioned place aversion (CPA) to naloxone‐precipitated opiate withdrawal by acting on α2 adrenoceptors (α2R). However, clonidine acts as a partial agonist both at α2R and at imidazoline‐1 receptors (I1Rs). The current study was designed to determine the role of I1R in the induction of naloxone‐induced CPA in morphine‐dependent rats. Morphine dependence was induced by subcutaneous implantation of morphine pellets. Morphine‐dependent rats were tested in a three‐chamber place‐aversion apparatus. A range of agonists were chosen on the basis of their differential selectivity for α2R and I1R. As expected, pretreatment with clonidine prevented naloxone‐induced CPA. By contrast, pretreatment with a selective α2R agonist (UK14304) failed to prevent the CPA. We then tested whether the high affinity of clonidine for I1R was responsible for the difference between these two α2R agonists. Rilmenidine (a mixed α2R/I1R agonist) attenuated aversion to opiate withdrawal in a dose‐dependent manner. The action of clonidine on I1R was studied by co‐administering clonidine with RX821002, a specific α2R antagonist. Co‐treatment with RX821002 and clonidine blocked naloxone‐induced CPA. These results indicate that the pharmacologically protective effects of clonidine on naloxone‐induced CPA are related to actions on I1RS as well as α2Rs.
Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor‐dependent behavioural response
Authors: Bilang‐Bleuel Alicia , Ulbricht Sabine , Chandramohan Yalini , De Carli Sonja , Droste Susanne K. , Reul Johannes M. H. M.
Published: October 2005

Chromatin remodelling associated with transcriptional activation of silent genes involves phosphorylation at Serine‐10 and acetylation at Lysine‐14 in the N‐terminal tails of the nucleosomal protein histone H3. We have identified neurons predominantly in the dentate gyrus showing a speckled nuclear immunoreactivity pattern for phosphorylated histone H3 [i.e. P(Ser10)‐H3] and phospho‐acetylated histone H3 [i.e. P(Ser10)‐Ac(Lys14)‐H3]. Forced swimming increased the number of P(Ser10)‐H3‐positive [P(Ser10)‐H3+] neurons in the rat and mouse dentate gyrus. Exposure of mice to a predator had a similar effect, but exposing rats to ether vapour or a cold environment evoked no change in the number of P(Ser10)‐H3+ dentate neurons, indicating that the effect of stress on histone H3 phosphorylation is stressor‐specific. The forced swimming‐induced increase in dentate P(Ser10)‐H3+ neurons peaked at 8–24 h, was restricted to NeuN+ (i.e. mature) neurons, and occurred mainly in the middle and superficial aspects of the granular cell layer. Moreover, this increase showed stimulus strength dependency (i.e. swimming at 19 °C produced a larger increase than swimming at 25 °C) and could be blocked by the glucocorticoid receptor (GR) antagonists RU 38486 and ORG 34517. Under these experimental conditions, when the forced swimming‐induced behavioural immobility response was determined in a re‐test 24 h after the initial forced swim test, striking correlations were observed between the phosphorylation of histone H3 in dentate gyrus granule neurons and the acquired immobility response. Our data indicate that stressful events with a strong psychological component such as forced swimming evoke distinct GR‐dependent histone modifications in mature dentate gyrus granule neurons that may participate in the behavioural adaptation of the organism to this event.
Different function of pedunculopontine GABA and glutamate receptors in nucleus accumbens dopamine, pedunculopontine glutamate and operant discriminative behavior
Authors: Steiniger‐Brach Björn , Kretschmer Beate D.
Published: October 2005

The nucleus accumbens, as the main input structure of the ventral basal ganglia loop, is described as a limbic–motor interface. Dopamine input to nucleus accumbens modulates processing of concurrent glutamate input from limbic structures carrying motor and motivational information. There is evidence that these dopamine/glutamate interactions are fundamentally involved in response selection processes. However, the pedunculopontine tegmental nucleus (PPTg) in the brainstem is connected with limbic structures as well as dopaminergic midbrain areas, which also project to the nucleus accumbens. Furthermore, behavioral studies implicate the PPTg in complex, motivated behavior. Thus, the PPTg might be involved in motivated behavior by influencing response selection processes in the nucleus accumbens. In this study we used in vivo microdialysis in freely moving rats in order to inhibit (100, 200, 300 and 400 µm baclofen) or stimulate [5, 12.5, 25 or 50 µmα‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionic acid (AMPA)] the PPTg in animals that are performing an operant discrimination task for food reward. The behavioral consequences were correlated with dopamine and glutamate levels in nucleus accumbens and PPTg, respectively. PPTg inhibition by local GABAB receptors impaired the response rate and accuracy of performance in the operant discrimination task. PPTg stimulation by local AMPA receptors exclusively impaired the response rate. Both treatments blocked the performance‐driven dopamine signal in nucleus accumbens, whereas glutamate in PPTg was enhanced after AMPA administration only. The data indicate that the PPTg functionally participates in a network of subcortical and cortical structures, which is responsible for the execution of motivated behavior and response selection processes.
Co‐induction of activity‐dependent genes in songbirds
Authors: Velho Tarciso A. F. , Pinaud Raphael , Rodrigues Paulo V. , Mello Claudio V.
Published: October 2005

Song behavior in songbirds induces the expression of activity‐dependent genes in brain areas involved in perceptual processing, production and learning of song. This genomic response is thought to represent a link between neuronal activation and long‐term changes in song‐processing circuits of the songbird brain. Here we demonstrate that Arc, an activity‐regulated gene whose product has dendritic localization and is associated with synaptic plasticity, is rapidly induced by song in the brain of zebra finches. We show that, in the context of song auditory stimulation, Arc expression is induced in several telencephalic auditory areas, most prominently the caudomedial nidopallium and mesopallium, whereas in the context of singing, Arc is also induced in song control areas, namely nucleus HVC, used as a proper name, the robust nucleus of the arcopallium and the interface nucleus of the nidopallium. We also show that song‐induced Arc expression co‐localizes at the cellular level with those of the transcriptional regulators zenk and c‐fos, and that the song induction of these three genes is dependent on activation of the mitogen‐activated protein kinase signaling pathway. These findings provide evidence for an involvement of Arc in the brain's response to birdsong. They also demonstrate that genes representing distinct genomic and cellular regulatory programs, namely early effectors and transcription factors, are co‐activated in the same neuronal cells by a naturally learned stimulus.
Contribution of Primary Care to Health Systems and Health
Authors: STARFIELD BARBARA , SHI LEIYU , MACINKO JAMES
Published: October 2005

Evidence of the health‐promoting influence of primary care has been accumulating ever since researchers have been able to distinguish primary care from other aspects of the health services delivery system. This evidence shows that primary care helps prevent illness and death, regardless of whether the care is characterized by supply of primary care physicians, a relationship with a source of primary care, or the receipt of important features of primary care. The evidence also shows that primary care (in contrast to specialty care) is associated with a more equitable distribution of health in populations, a finding that holds in both cross‐national and within‐national studies. The means by which primary care improves health have been identified, thus suggesting ways to improve overall health and reduce differences in health across major population subgroups.
Annotation: Pathways to care for children with mental health problems
Authors: Sayal Kapil
Published: October 2005

Background:  Although many children with mental health problems are in contact with primary health care services, few receive appropriate help.

Methods:  Using a pathways to care model, this paper systematically reviews the literature relating to access to services. It separates out the various stages of help‐seeking: parental perception of problems, use of primary care services, recognition within primary care, and referral to or use of specialist health services.

Results:  Following parental awareness of child symptoms, parental perception of problems is the key initial step in the help‐seeking process. Although children with mental health problems or disorders are regular attenders within primary care and most parents acknowledge that it is appropriate to discuss concerns about psychosocial issues in this setting, few children are presented with mental health symptoms even if their parents have such concerns. Subsequently, less than half of children with disorders are recognised in primary care. Amongst recognised children, about half are referred to specialist services. Overall, up to one‐third of children with disorders receive services for mental health problems. Factors such as the type and severity of disorder, parental perceptions, child age and gender, and family and social background factors determine which affected children access services.

Conclusions:  As there are inequities in patterns of service use, a greater emphasis on developing resources at population and primary care levels is required. Barriers involving parental perceptions and expression of concerns within consultations should be minimised at these levels. This requires both public education approaches and improved training and specialist support for primary care services to enhance their ability to provide for these children.
Rearranging Receptors
Authors: Brooks‐Kayal Amy R.
Published: October 2005

Summary: The immature brain is highly susceptible to seizures. The heightened susceptibility to seizures appears to be due, at least in part, to developmental changes that skew the balance between excitatory and inhibitory neurotransmitter systems in the brain in favor of a state of excitation. Multiple factors, including changes in GABAergic and glutaminergic receptor composition, number, and distribution, all contribute to produce the characteristic limbic hyperexcitability seen during the early postnatal period. Infants and young children who experience prolonged or repetitive seizures have an increased risk of subsequently developing epilepsy. Evidence to date suggests that status epilepticus produces permanent changes in the molecular and cellular structure of limbic circuitry that, in turn, result in a long‐lasting increase in hippocampal excitability and lower seizure thresholds in later life.
Design and Analysis of Genetic Association Studies to Finely Map a Locus Identified by Linkage Analysis: Sample Size and Power Calculations
Authors: Hanson R. L. , Looker H. C. , Ma L. , Muller Y. L. , Baier L. J. , Knowler W. C.
Published: October 2005

Association (e.g. case‐control) studies are often used to finely map loci identified by linkage analysis. We investigated the influence of various parameters on power and sample size requirements for such a study. Calculations were performed for various values of a high‐risk functional allele (fA), frequency of a marker allele associated with the high risk allele (f1), degree of linkage disquilibrium between functional and marker alleles (D′) and trait heritability attributable to the functional locus (h2). The calculations show that if cases and controls are selected from equal but opposite extreme quantiles of a quantitative trait, the primary determinants of power are h2 and the specific quantiles selected. For a dichotomous trait, power also depends on population prevalence. Power is optimal if functional alleles are studied (fA= f1 and D′= 1.0) and can decrease substantially as D′ diverges from 1.0 or as f1 diverges from fA. These analyses suggest that association studies to finely map loci are most powerful if potential functional polymorphisms are identified a priori or if markers are typed to maximize haplotypic diversity. In the absence of such information, expected minimum power at a given location for a given sample size can be calculated by specifying a range of potential frequencies for fA (e.g. 0.1‐0.9) and determining power for all markers within the region with specification of the expected D′ between the markers and the functional locus. This method is illustrated for a fine‐mapping project with 662 single nucleotide polymorphisms in 24 Mb. Regions differed by marker density and allele frequencies. Thus, in some, power was near its theoretical maximum and little additional information is expected from additional markers, while in others, additional markers appear to be necessary. These methods may be useful in the analysis and interpretation of fine‐mapping studies.
Validation of a French version of the Child‐OIDP index
Authors: Tubert‐Jeannin Stéphanie , Pegon‐Machat Estelle , Gremeau‐Richard Christelle , Lecuyer Marie‐Maxence , Tsakos Georgios
Published: October 2005

The Child‐OIDP index is an indicator of oral health‐related quality of life, which has been validated among 12‐yr‐old children in Thailand. The aim of this study was to assess the reliability, validity, and applicability of this questionnaire among French children. After translation and cultural adaptation, the Child‐OIDP was tested on 414 10‐yr‐old children in France. The children completed the Child‐OIDP in face‐to‐face interviews, were clinically examined, and answered questions evaluating their global self‐rated oral health. Parents filled in a questionnaire concerning their socio‐demographic background. An oral impact on daily life was reported by 73% of the children. The mean Child‐OIDP score was 6.32 [standard deviation (SD) 8.22] and the median was 3.33. The internal reliability was confirmed with a Cronbach's alpha of 0.57. The retest procedure (n = 62) showed a satisfactory reproducibility (r = 0.81, κ = 0.75). The index was shown to be a valid instrument. Construct validity was satisfactory as the Child‐OIDP score increased when the children's perceived oral health decreased. The Child‐OIDP score was able to discriminate between different socio‐demographic groupings and varied according to dental status. This study showed that the Child‐OIDP is applicable for use among children in France. It has promising psychometric properties but further research is required to evaluate its sensitivity to change.
Effectiveness of clinical practice guideline implementation on lower third molar management in improving clinical decision‐making: a randomized controlled trial
Authors: Van Der Sanden Wil J. M. , Mettes Dirk G. , Plasschaert Alphons J. M. , Grol Richard P. T. M. , Mulder Jan , Verdonschot Emiel H.
Published: October 2005

The objective of this study was twofold, namely to evaluate the effectiveness of a dental clinical practice guideline on the management of asymptomatic impacted lower third molars (i) on referral rates and (ii) on dentists' change in knowledge. A two‐arm cluster randomized controlled trial, with pre‐ and post‐test assessments, was conducted. A guideline was implemented by multifaceted interventions (i.e. feedback, reminders, and an interactive meeting). The effect was evaluated after 1 yr by repeating the baseline questionnaire and by monitoring the number of patients who were referred for removal of their asymptomatic impacted mandibular third molars. Instruments were questionnaires for detecting changes in knowledge, patient records, and panoramic radiographs. The knowledge of dentists regarding asymptomatic mandibular third molar management was found to increase significantly in the intervention group as compared to the control group. There was no statistically significant difference between the groups in guideline‐consistent patient referral rates at the post‐test assessment. It was concluded that the methodology employed for dissemination and implementation of a clinical practice guideline on asymptomatic mandibular third molar management improves dentists' knowledge on this topic and is effective in improving decision‐making in simulated cases; however, no clinical effect was demonstrated.
Coenzyme A affects firefly luciferase luminescence because it acts as a substrate and not as an allosteric effector
Authors: Fraga Hugo , Fernandes Diogo , Fontes Rui , Esteves da Silva Joaquim C. G.
Published: October 2005

The effect of CoA on the characteristic light decay of the firefly luciferase catalysed bioluminescence reaction was studied. At least part of the light decay is due to the luciferase catalysed formation of dehydroluciferyl‐adenylate (L‐AMP), a by‐product that results from oxidation of luciferyl‐adenylate (LH2‐AMP), and is a powerful inhibitor of the bioluminescence reaction (IC50 = 6 nm). We have shown that the CoA induced stabilization of light emission does not result from an allosteric effect but is due to the thiolytic reaction between CoA and L‐AMP, which gives rise to dehydroluciferyl‐CoA (L‐CoA), a much less powerful inhibitor (IC50 = 5 µm). Moreover, the Vmax for L‐CoA formation was determined as 160 min−1, which is one order of magnitude higher than the Vmax of the bioluminescence reaction. Results obtained with CoA analogues also support the thiolytic reaction mechanism: CoA analogues without the thiol group (dethio‐CoA and acetyl‐CoA) do not react with L‐AMP and do not antagonize its inhibitor effect; CoA and dephospho‐CoA have free thiol groups, both react with L‐AMP and both antagonize its effect. In the case of dephospho‐CoA, it was shown that it reacts with L‐AMP forming dehydroluciferyl‐dephospho‐CoA. Its slower reactivity towards L‐AMP explains its lower potency as antagonist of the inhibitory effect of L‐AMP on the light reaction. Moreover, our results support the conjecture that, in the bioluminescence reaction, the fraction of LH2‐AMP that is oxidized into L‐AMP, relative to other inhibitory products or intermediates, increases when the concentrations of the substrates ATP and luciferin increases.
The concepts of bias, precision and accuracy, and their use in testing the performance of species richness estimators, with a literature review of estimator performance
Authors: Walther Bruno A. , Moore Joslin L.
Published: October 2005

The purpose of this review is to clarify the concepts of bias, precision and accuracy as they are commonly defined in the biostatistical literature, with our focus on the use of these concepts in quantitatively testing the performance of point estimators (specifically species richness estimators). We first describe the general concepts underlying bias, precision and accuracy, and then describe a number of commonly used unscaled and scaled performance measures of bias, precision and accuracy (e.g. mean error, variance, standard deviation, mean square error, root mean square error, mean absolute error, and all their scaled counterparts) which may be used to evaluate estimator performance. We also provide mathematical formulas and a worked example for most performance measures. Since every measure of estimator performance should be viewed as suggestive, not prescriptive, we also mention several other performance measures that have been used by biostatisticians or ecologists. We then outline several guidelines of how to test the performance of species richness estimators: the detailed description of data simulation models and resampling schemes, the use of real and simulated data sets on as many different estimators as possible, mathematical expressions for all estimators and performance measures, and the presentation of results for each scaled performance measure in numerical tables with increasing levels of sampling effort. We finish with a literature review of promising new research related to species richness estimation, and summarize the results of 14 studies that compared estimator performance, which confirm that with most data sets, non‐parametric estimators (mostly the Chao and jackknife estimators) perform better than other estimators, e.g. curve models or fitting species‐abundance distributions.
Removal of chemical–mechanical polishing-induced damage layer in single crystal La3Ga5SiO14 by inductively coupled plasma etching
Authors: Cho Hyun , Pearton S. J.
Published: October 2005

Practical and controllable etch rates are obtained for chemical–mechanical polishing (CMP)-processed single crystalline langasite (La3Ga5SiO14) wafers in Cl2∕Ar inductively coupled plasmas. The effects of plasma composition, ion flux, and ion energy on the etch rate and surface morphology are examined. A maximum etch rate ∼1600Å∕min was achieved either at relatively high source power (∼1000W) or high Cl2 content conditions and the etched surfaces are found to retain smooth surface morphology under a wide range of plasma conditions. The CMP-induced subsurface layer formed in the langasite wafer was successfully removed in Cl2∕Ar inductively coupled plasmas and the electrical conductivity was restored to the initial value (∼1×10−4Ω−1cm−1) measured before being CMP processed at an etch depth of ∼700Å.
Real-time material quality prediction, fault detection, and contamination control in AlGaN∕GaN high electron mobility transistor metalorganic chemical vapor deposition process using in situ chemical sensing
Authors: Cho Soon , Rubloff Gary W. , Aumer Michael E. , Thomson Darren B. , Partlow Deborah P.
Published: October 2005

Gallium nitride and its alloys promise to be key materials for future heterojunction semiconductor devices aimed at high frequency, high power electronic applications. However, manufacturing for such high performance products is challenged by reproducibility and material quality constraints that are notably higher than those required for optoelectronic applications. To meet this challenge, in situ mass spectrometry was implemented in AlGaN∕GaN∕AlN metalorganic chemical vapor deposition processes as a real-time process and wafer state metrology tool. In particular, the various pregrowth gas phase impurity levels within the reactor, measured by mass spectrometry in real time, were correlated to photoluminescence band-edge and deep-level properties measured postprocess. Band-edge intensities increased and deep-level intensities decreased with lower oxygen-containing impurity levels in the pregrowth environment. These real-time indications of oxygen impurity incorporation were used for fault detection and to optimize preprocess reactor conditioning involving degassing of the wafer susceptor and furnace liner elements. Because this in situ sensing provides a control on contaminants to assure high material quality and a fault detection capability as well, it is now implemented routinely for both purposes. These real-time contamination control and fault detection strategies complement an overall advanced process control program for GaN-based semiconductor manufacturing, offering a systematic methodology to improve the product quality of GaN-based electronic devices.