bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose-sensing mechanisms in pancreatic β-cells
Authors: MacDonald Patrick E , Joseph Jamie W , Rorsman Patrik
Published: November 2005

The appropriate secretion of insulin from pancreatic β-cells is critically important to the maintenance of energy homeostasis. The β-cells must sense and respond suitably to postprandial increases of blood glucose, and perturbation of glucose-sensing in these cells can lead to hypoglycaemia or hyperglycaemias and ultimately diabetes. Here, we review β-cell glucose-sensing with a particular focus on the regulation of cellular excitability and exocytosis. We examine in turn: (i) the generation of metabolic signalling molecules; (ii) the regulation of β-cell membrane potential; and (iii) insulin granule dynamics and exocytosis. We further discuss the role of well known and putative candidate metabolic signals as regulators of insulin secretion.
NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology
Authors: Cave Alison , Grieve David , Johar Sofian , Zhang Min , Shah Ajay M
Published: November 2005

Chronic heart failure, secondary to left ventricular hypertrophy or myocardial infarction, is a condition with increasing morbidity and mortality. Although the mechanisms underlying the development and progression of this condition remain a subject of intense interest, there is now growing evidence that redox-sensitive pathways play an important role. This article focuses on the involvement of reactive oxygen species derived from a family of superoxide-generating enzymes, termed NADPH oxidases (NOXs), in the pathophysiology of ventricular hypertrophy, the accompanying interstitial fibrosis and subsequent heart failure. In particular, the apparent ability of the different NADPH oxidase isoforms to define the response of a cell to a range of physiological and pathophysiological stimuli is reviewed. If confirmed, these data would suggest that independently targeting different members of the NOX family may hold the potential for therapeutic intervention in the treatment of cardiac disease.
A death round affecting a young compartmentalized mycelium precedes aerial mycelium dismantling in confluent surface cultures of Streptomyces antibioticus
Authors: Manteca Ángel , Fernández Marisol , Sánchez Jesús
Published: November 2005

Development-associated cell-death processes were investigated in detail during the growth and differentiation of Streptomyces antibioticus ATCC 11891 on confluent surface cultures, by using fluorescent viability probes, membrane and activity fluorescence indicators, and electron microscopy analysis. A previously unsuspected complexity was revealed, namely the presence of a very young compartmentalized mycelium that dies following an orderly pattern, leaving alternating live and dead segments in the same hypha. This death round is followed by the growth of a second mycelium which develops rapidly from the live segments of the first mycelium and dies massively in a second death round, which extends over the phases of aerial mycelium formation and sporulation.
Fluorescence assays for F-pili and their application
Authors: Daehnel Katrin , Harris Robin , Maddera Lucinda , Silverman Philip
Published: November 2005

Conjugative pili are extracellular filaments elaborated by Gram-negative bacteria expressing certain type IV secretion systems. They are required at the earliest stages of conjugal DNA transfer to establish specific and secure cell–cell contacts. Conjugative pili also serve as adsorption organelles for both RNA and DNA bacteriophages. Beyond these facts, the structure, formation and function of these filaments are poorly understood. This paper describes a rapid, quantitative assay for F-pili encoded by the F plasmid type IV secretion system. The assay is based on the specific lateral adsorption of icosahedral RNA bacteriophage R17 by F-pili. Bacteriophage particles conjugated with a fluorescent dye, Alexa 488, and bound to F-pili defined filaments visible by immunofluorescence microscopy. F-pili attached to F+cells and free F-pili were both visible by this method. For quantification, cell-bound bacteriophage were separated from free bacteriophage particles by sedimentation and released by suspending cell pellets in 0·1 % SDS. Fluorescence in cell-free supernatant fractions was measured by fluorometry. The authors present a characterization of this assay and its application to F-pilus formation by cells carrying mutations in the gene for the F-pilus subunit F-pilin. Each mutation introduced a cysteine, which F-pilin normally lacks, at a different position in its primary structure. Cysteine residues in the N-terminal domain I abolished filament formation as measured by fluorescent R17 binding. This was confirmed by measurements of DNA donor activity and filamentous DNA bacteriophage infection. With one exception (G53C), cysteines elsewhere in the F-pilin primary structure did not abolish filament formation, although some mutations differentially affected F-pilus functions.
Conjugative plasmid DNA transfer in Helicobacter pylori mediated by chromosomally encoded relaxase and TraG-like proteins
Authors: Backert Steffen , Kwok Terry , König Wolfgang
Published: November 2005

One of the striking characteristics ofHelicobacter pyloriis the extensive genetic diversity among clinical isolates. This diversity has been attributed to an elevated mutation rate, impaired DNA repair, DNA transfer and frequent recombination events. Plasmids have also been identified inH. pyloribut it remained unknown whether conjugation can contribute to DNA transfer between clinical isolates. To examine whetherH. pyloripossesses intrinsic capability for conjugative plasmid transfer, shuttle vectors were introduced intoH. pyloricontaining anoriTsequence of the conjugative IncPαplasmid RP4 but no mobilization (mob) genes. It was shown that these vectors could stably replicate and be mobilized among clinicalH. pyloristrains. It was also demonstrated thattraGand relaxase (rlx) homologues carried on theH. pylorichromosome were important for plasmid transfer. Primer extension studies and mutagenesis further confirmed that the relaxase homologuerlx1inH. pyloriencodes a functional enzyme capable of acting on the RP4oriT. Furthermore, the findings of this study indicate thattraGandrlx1act independently of the previously described type IV secretion systems, including that encoded by thecagpathogenicity island and thecomBtransformation apparatus, in mediating conjugative plasmid DNA transfer betweenH. pyloristrains.
The Drosophila nucleosome remodeling factor NURF is required for Ecdysteroid signaling and metamorphosis
Authors: Badenhorst Paul , Xiao Hua , Cherbas Lucy , Kwon So Yeon , Voas Matt , Rebay Ilaria , Cherbas Peter , Wu Carl
Published: November 2005

Drosophila NURF is an ISWI-containing ATP-dependent chromatin remodeling complex that regulates transcription by catalyzing nucleosome sliding. To determine in vivo gene targets of NURF, we performed whole genome expression analysis on mutants lacking the NURF-specific subunit NURF301. Strikingly, a large set of ecdysone-responsive targets is included among several hundred NURF-regulated genes. Null Nurf301 mutants do not undergo larval to pupal metamorphosis, and also enhance dominant-negative mutations in ecdysone receptor. Moreover, purified NURF binds EcR in an ecdysone-dependent manner, suggesting it is a direct effector of nuclear receptor activity. The conservation of NURF in mammals has broad implications for steroid signaling.
Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1
Authors: Wagner Nicole , Wagner Kay-Dietrich , Theres Heinz , Englert Christoph , Schedl Andreas , Scholz Holger
Published: November 2005

The formation of intramyocardial blood vessels is critical for normal heart development and tissue repair after infarction. We report here expression of the Wilms' tumor gene-1, Wt1, in coronary vessels, which could contribute to the defective cardiac vascularization in Wt1-/- mice. Furthermore, the high-affinity neurotrophin receptor TrkB, which is expressed in the epicardium and subepicardial blood vessels, was nearly absent from Wt1-deficient hearts. Activation of Wt1 in an inducible cell line significantly enhanced TrkB expression. The promoter of NTRK2, the gene encoding TrkB, was stimulated ∼10-fold by transient cotransfection of a Wt1 expression construct. The critical DNA-binding site for activation of the NTRK2 promoter by Wt1 was delineated by DNase I footprint analysis and electrophoretic mobility shift assay. Transgenic experiments revealed that the identified Wt1 consensus motif in the NTRK2 promoter was necessary to direct expression of a reporter gene to the epicardium and the developing vasculature of embryonic mouse hearts. Finally, mice with a disrupted Ntrk2 gene lacked a significant proportion of their intramyocardial blood vessels. These findings demonstrate that transcriptional activation of the TrkB neurotrophin receptor gene by the Wilms' tumor suppressor Wt1 is a crucial mechanism for normal vascularization of the developing heart.
High yield bacterial expression of active c‐Abl and c‐Src tyrosine kinases
Authors: Seeliger Markus A. , Young Matthew , Henderson M. Nidanie , Pellicena Patricia , King David S. , Falick Arnold M. , Kuriyan John
Published: November 2005

The Abl and Src tyrosine kinases are key signaling proteins that are of considerable interest as drug targets in cancer and many other diseases. The regulatory mechanisms that control the activity of these proteins are complex, and involve large‐scale conformational changes in response to phosphorylation and other modulatory signals. The success of the Abl inhibitor imatinib in the treatment of chronic myelogenous leukemia has shown the potential of kinase inhibitors, but the rise of drug resistance in patients has also shown that drugs with alternative modes of binding to the kinase are needed. The detailed understanding of mechanisms of protein–drug interaction and drug resistance through biophysical methods demands a method for the production of active protein on the milligram scale. We have developed a bacterial expression system for the kinase domains of c‐Abl and c‐Src, which allows for the quick expression and purification of active wild‐type and mutant kinase domains by coexpression with the YopH tyrosine phosphatase. This method makes practical the use of isotopic labeling of c‐Abl and c‐Src for NMR studies, and is also applicable for constructs containing the SH2 and SH3 domains of the kinases.
Solution structure of the Escherichia coli protein ydhR: A putative mono‐oxygenase
Authors: Revington Matthew , Semesi Anthony , Yee Adelinda , Shaw Gary S.
Published: November 2005

YdhR is a 101‐residue conserved protein from Escherichia coli. Sequence searches reveal that the protein has >50% identity to proteins found in a variety of other bacterial genomes. Using size exclusion chromatography and fluorescence spectroscopy, we determined that ydhR exists in a dimeric state with a dissociation constant of ∼40 nM. The three‐dimensional structure of dimeric ydhR was determined using NMR spectroscopy. A total of 3400 unambiguous NOEs, both manually and automatically assigned, were used for the structure calculation that was refined using an explicit hydration shell. A family of 20 structures was obtained with a backbone RMSD of 0.48 Å for elements of secondary structure. The structure reveals a dimeric α,β fold characteristic of the alpha+beta barrel superfamily of proteins. Bioinformatic approaches were used to show that ydhR likely belongs to a recently identified group of mono‐oxygenase proteins that includes ActVA‐Orf6 and YgiN and are involved in the oxygenation of polyaromatic ring compounds.
Risk of p53 gene mutation in esophageal squamous cell carcinoma and habit of betel quid chewing in Taiwanese
Authors: Goan Yih‐Gang , Chang Huang‐Chou , Hsu Hon‐Ki , Chou Yi‐Pin , Cheng Jiin‐Tsuey
Published: November 2005

A recent report suggested that BQ (BQ) chewing significantly correlated with the occurrence of esophageal squamous cell carcinoma (ESCC) in Taiwanese. BQ chewing was shown to be associated with p53 mutation in oral cancers. However, the relationship between BQ chewing and p53 mutation in ESCC is unclear. Seventy‐five primary ESCC patients were enrolled for mutational analysis of the p53 gene using polymerase chain amplification and direct sequencing of amplified product. Thirty‐seven mutations of the p53 gene were detected in 45.5% (34/75) of tumor specimens. These mutations significantly clustered in exon 5 (21/37) of the p53 gene. The incidence of p53 mutations did not associate with clinicopathological characteristics or the habits of cigarette smoking or alcohol consumption. However, BQ chewers exhibited significantly higher incidence of p53 gene mutations than non‐chewers (67.6% vs 32.4%, P = 0.007). After controlling the confounding factors of cigarette smoking and alcohol intake, BQ chewing still showed significant association with the incidence of p53 mutation in ESCCs (RR = 4.23; 95% CI, 1.317–13.60). The A:T to G:C transition (8/37, 21.6%) and G:C to T:A transversion (5/23, 13.5%) were the prevalent spectrum of p53 gene mutations. All A:T to G:C transitional mutations occurred in patients with the habits of BQ chewing and cigarette smoking. Noticeably, alcohol consumption could enhance this peculiar spectrum of p53 mutation in ESCC. Accordingly, p53 might be an important molecular target of BQ carcinogens in the development of ESCC in Taiwanese. (Cancer Sci 2005; 96: 758–765)
Leptosins isolated from marine fungus Leptoshaeria species inhibit DNA topoisomerases I and/or II and induce apoptosis by inactivation of Akt/protein kinase B
Authors: Yanagihara Miyako , Sasaki‐Takahashi Noriko , Sugahara Tetsuo , Yamamoto Seiko , Shinomi Masahito , Yamashita Izumi , Hayashida Masashi , Yamanoha Banri , Numata Atsushi , Yamori Takao , Andoh Toshiwo
Published: November 2005

DNA topoisomerases (topo) I and II are molecular targets of several potent anticancer agents. Thus, inhibitors of these enzymes are potential candidates or model compounds for anticancer drugs. Leptosins (Leps) F and C, indole derivatives, were isolated from a marine fungus, Leptoshaeria sp. as cytotoxic substances. In vitro cytotoxic effects of Lep were measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide‐based viability assay. Lep F inhibited the activity of topos I and II, whereas Lep C inhibited topo I in vitro. Interestingly both of the compounds were found to be catalytic inhibitors of topo I, as evidenced by the lack of stabilization of reaction intermediate cleavable complex (CC), as camptothecin (CPT) does stabilize. Furthermore, Lep C inhibited the CC stabilization induced by CPT in vitro. In vivo band depletion analysis demonstrated that Lep C likewise appeared not to stabilize CC, and inhibited CC formation by CPT, indicating that Lep C is also a catalytic inhibitor of topo I in vivo. Cell cycle analysis of Lep C‐treated cells showed that Lep C appeared to inhibit the progress of cells from G1 to S phase. Lep C induced apoptosis in RPMI8402 cells, as revealed by the accumulation of cells in sub‐G1 phase, activation of caspase‐3 and the nucleosomal degradation of chromosomal DNA. Furthermore, Leps F and C inhibited the Akt pathway, as demonstrated by dose‐dependent and time‐dependent dephosphorylation of Akt (Ser473). Our study shows that Leps are a group of anticancer chemotherapeutic agents with single or dual catalytic inhibitory activities against topos I and II. (Cancer Sci 2005; 96: 816–824)
Promotion of folate for the prevention of neural tube defects: who benefits?
Authors: Bower Carol , Miller Margaret , Payne Jan , Serna Peta
Published: November 2005

Since the publication of randomised trials showing firm evidence of prevention of neural tube defects with periconceptional folic acid, there have been population health promotion programmes to encourage women to take folic acid supplements, and the introduction of voluntary fortification of some foods with folic acid in Australia. In order to evaluate these two strategies, we collected data by self‐administered questionnaire from a random sample of recently pregnant women in Western Australia between September 1997 and March 2000. Response to health promotion was measured in three ways: (1) knowledge of the association between periconceptional folate and prevention of spina bifida (the ‘correct message’); (2) use of periconceptional vitamin supplements of folic acid daily in the periconceptional period; and (3) daily folate intake from fortified foods in the 6 months before pregnancy. We examined the relationship of maternal demographic and behavioural characteristics with these three measures.

Overall, 62.3% of women were aware of the correct message before pregnancy, 28.5% reported taking 200 µg or more of folic acid from supplements daily in the periconceptional period and 56.6% of women obtained 100 µg or more of folic acid from fortified foods. Women who first became aware of the correct message during pregnancy or who were unaware of the correct message before or during pregnancy were more likely than women aware before pregnancy to be younger, having their first pregnancy, be single or in a de facto relationship, have no tertiary education, and be a public patient. Similar associations were seen for women taking either no folic acid or < 200 µg of folic acid in supplements daily in the periconceptional period. There were no significant associations between these demographic variables and amount of folate obtained from fortified foods. Women who were unaware of the correct message and did not take folic acid supplements were more likely to have smoked, not to have engaged in exercise, and not to have planned their pregnancy, whereas there was no association with these behavioural characteristics and intake of folate from fortified foods.

These results indicate that health promotion strategies have not reached all segments of the target population equally, but there is no such disparity with folate‐fortified foods, and they suggest that mandatory fortification of a staple food is likely to reach all women regardless of demographic and behavioural characteristics, and hence provide improved opportunity for prevention of neural tube defects in Australia.
Accuracy of reporting maternal in‐hospital diagnoses and intrapartum procedures in Washington State linked birth records
Authors: Lydon‐Rochelle Mona T. , Holt Victoria L. , Nelson Jennifer C. , Cárdenas Vicky , Gardella Carolyn , Easterling Thomas R. , Callaghan William M.
Published: November 2005

While the impact of maternal morbidities and intrapartum procedures is a common topic in perinatal outcomes research, the accuracy of the reporting of these variables in the large administrative databases (birth certificates, hospital discharges) often utilised for such research is largely unknown. We conducted this study to compare maternal diagnoses and procedures listed on birth certificates, hospital discharge data, and birth certificate and hospital discharge data combined, with those documented in a stratified random sample of hospital medical records of 4541 women delivering liveborn infants in Washington State in 2000. We found that birth certificate and hospital discharge data combined had substantially higher true positive fractions (TPF, proportion of women with a positive medical record assessment who were positive using the administrative databases) than did birth certificate data alone for labour induction (86% vs. 52%), cephalopelvic disproportion (83% vs. 35%), abruptio placentae (85% vs. 68%), and forceps‐assisted delivery (89% vs. 55%). For procedures available only in hospital discharge data, TPFs were generally high: episiotomy (85%) and third and fourth degree vaginal lacerations (91%). Except for repeat caesarean section without labour (TPF, 81%), delivery procedures available only in birth certificate data had low TPFs, including augmentation (34%), repeat caesarean section with labour (61%), and vaginal birth after caesarean section (62%). Our data suggest that researchers conducting perinatal epidemiological studies should not rely solely on birth certificate data to detect maternal diagnoses and intrapartum procedures accurately.
Effects of low doses of inhaled fluticasone propionate on inflammation and remodelling in persistent‐mild asthma
Authors: Vignola A. M. , Riccobono L. , Profita M. , Foresi A. , Di Giorgi R. , Guerrera D. , Gjomarkaj M. , Di Blasi P. , Paggiaro P. L.
Published: November 2005

In asthma a dysregulation of eosinophil apoptosis and an imbalance of metalloproteinase‐9 (MMP‐9) and tissue inhibitor metalloproteinase‐1 (TIMP‐1) play an important role in airway inflammation and remodelling. We evaluated the effects of a low dose of inhaled fluticasone proprionate (FP) (100 μg bid by Diskus) for 4 weeks in 24 steroid naive patients with mild persistent asthma, symptomatic and with a sputum eosinophilia ≥3% on clinical outcomes and inflammatory markers such as the induced sputum eosinophils, the induced sputum apoptotic eosinophils, the levels of MMP‐9 and TIMP‐1 and their molar ratio in the induced sputum supernatants. After FP treatment forced expiratory volume (FEV1) and FEV1/forced vital capacity values, PEF (L/min), sputum apoptotic eosinophils, and MMP‐9/TIMP‐1 molar ratio in sputum supernatants of asthmatic subjects were significantly increased in comparison with baseline, while sputum eosinophils significantly decreased. Change (Δ) in FEV1 after treatment with FP negatively correlated with the Δ in sputum eosinophils, while the Δ in MMP‐9 values positively correlated with Δ in TIMP‐1 values. This study shows that the clinical improvement achieved by the use of low doses of FP in asthmatics is related, at least in part, to the resolution of eosinophilic inflammation and the downregulation of remodelling markers.
The effect of polymorphisms at the CD14 promoter and the TLR4 gene on asthma phenotypes in Turkish children with asthma
Authors: Saçkesen C. , Karaaslan C. , Keskin O. , Tokol N. , Tahan F. , Civelek E. , Soyer O. U. , Adalıoǧlu G. , Tuncer A. , Birben E. , Öner C. , Kalaycı O.
Published: November 2005

Background:  Endotoxin, with its potential to enhance type 1 immunity, is a significant player in the hygiene hypothesis. The combined effects of the genetic variants of various molecules in the endotoxin response pathway on asthma related phenotypes are largely unknown.

Objective:  To investigate the effects of the genetic variants of CD14 and TLR4 genes on asthma phenotypes in a large number of asthmatic children.

Methods:  613 asthmatic children were genotyped at the CD14‐C159T, TLR4‐A896G and TLR4‐C1196T loci. IgE, eosinophil numbers and FEV1 were compared in 327 children who were not on any controller medications and were symptom free. Multivariate logistic regression was used to determine the factors associated with total IgE.

Results:  Among children with atopic asthma, total IgE levels were significantly different among the three genotypes in the co‐dominant model [CC: 435 kU/l (interquartile range: 146–820); CT: 361 (140–710); TT 204 (98–435), P = 0.035]. TT genotype was significantly and independently associated with lower IgE levels (OR: 0.5 95%; CI = 0.28–0.90, P = 0.021). Both TLR4‐A896G and TLR4‐C1196T polymorphisms were more frequent in the mild asthma group with atopy (P = 0.032, 0.018, respectively). The combined effects of the genetic variants in CD14 and TLR4 genes did not improve the observed associations.

Conclusion:  Our study demonstrates that the CD14‐C159T promoter variant influences total IgE levels and also indicates that the T allele has a more profound effect on total IgE in children with atopic asthma. Polymorphisms in the TLR4 gene may be associated with milder forms of disease in atopic asthmatics in the population studied.
New cohorts of naive T cells exacerbate ongoing allergy but can be suppressed by regulatory T cells
Authors: Hauet‐Broere F. , Unger W. W. J. , van Berkel L. A. , Garssen J. , Hoijer M. A. , Kraal G. , Samsom J. N.
Published: November 2005

Although as pretreatment oral tolerance is a potent means to achieve systemic suppression, its application in ongoing disease is controversial. Here we propose that availability of naive T cells may critically determine whether immunological tolerance is achieved during ongoing antigenic reactivity. Infusion of naive antigen‐specific T cells into mice directly prior to eliciting a secondary Th2 response induces these naive cells to actively engage in the antigenic response despite presence of established memory. Naive antigen‐specific T‐cells divided faster, produced more interleukin (IL)‐2, IL‐4 and IL‐5 and enhanced immunoglobulin E (IgE) release during a secondary Th2 response, compared with naive T cells that were infused prior to a primary response. Despite such contribution by new cohorts of naive T cells co‐infusion of mucosal Tr together with naive T cells could suppress enhanced IgE release during a secondary Th2 response. We conclude that naive T cells contribute to a secondary Th2 response and although they can still be suppressed in the presence of sufficient numbers of mucosal Tr, they may interfere with potential therapeutic application of mucosal tolerance.
A cytoplasmic motif targets neuroligin‐1 exclusively to dendrites of cultured hippocampal neurons
Authors: Rosales Carlos R. , Osborne Kyle D. , Zuccarino Griselda V. , Scheiffele Peter , Silverman Michael A.
Published: November 2005

The formation of neuronal synapses is thought to depend on trans‐synaptic interactions between cell adhesion molecules (CAMs) on the surface of axons and dendrites. Synapses are highly asymmetric structures. Pre‐ and post‐synaptic domains might therefore be assembled around heterophilic CAMs which are polarized to axons vs. dendrites. We here investigated the targeting of neuroligin (NLG)‐1, a heterophilic CAM, which promotes synapse formation through interaction with its receptor β‐neurexin in axons. We demonstrate that NLG‐1 is highly polarized to the dendritic plasma membrane. Dendritic targeting relies on a cytoplasmic amino acid motif. By expressing chimeras of NLG‐1 and CD8, an unpolarized protein, we show that the cytoplasmic domain of NLG‐1 is necessary and sufficient for dendritic targeting. Furthermore, by truncation analysis we isolated a 32‐amino‐acid targeting motif. When appended to CD8 this cytoplasmic sequence is sufficient to direct exclusively dendritic localization of the protein. Analysis of yellow fluorescent protein‐tagged NLG‐1 revealed that vesicular structures containing NLG‐1 are excluded from the axon indicating that polarized distribution may be achieved by direct dendritic transport. We propose that the strict polarity of NLG‐1 contributes to the directional assembly of synapses during development of the central nervous system.
Neuronal expression of Nogo‐A mRNA and protein during neurite outgrowth in the developing rat olfactory system†
Authors: Richard Marion , Giannetti Nathalie , Saucier Diane , Sacquet Joëlle , Jourdan François , Pellier‐Monnin Véronique
Published: November 2005

The major impediments to axonal regeneration in the central nervous system are growth‐inhibitory proteins present in the myelin sheath, and Nogo‐A is one of the most potent inhibitors synthesized by oligodendrocytes. However, neuronal expression of Nogo‐A during development suggests that it may have an additional role. The spatio‐temporal regulation of both Nogo‐A mRNA and protein expression was examined by in situ hybridization and immunohistochemistry in the developing rat olfactory system. During embryonic and postnatal development (from E13 to P6), Nogo‐A mRNA and protein were strongly expressed by differentiating neurons in the olfactory epithelium and in the olfactory bulb. From the second postnatal week, a progressive down‐regulation of both Nogo‐A mRNA and protein occurred, such that only a weak expression persisted in the adult olfactory system. Using double‐immunostainings in the adult olfactory epithelium, we determined that Nogo‐A was preferentially expressed by immature olfactory receptor neurons extending axonal processes toward the olfactory bulb. At all developmental stages, Nogo‐A protein was preferentially targeted in olfactory axons emerging from the olfactory epithelium. Using an in vitro model of olfactory axon growth, we demonstrated that, in addition to its presence along the entire axon length, Nogo‐A accumulated in axonal growth cone and at axonal branching points, with a distribution similar to that of microtubule‐associated proteins. Moreover, Nogo‐A was transiently expressed in dendritic processes in the postnatal olfactory bulb. Together, our data suggest that, in non‐pathological conditions, Nogo‐A may be involved in the processes of axonal growth and dendritic modeling through the regulation of microtubule dynamics.
Clinical application of neurotrophic factors: the potential for primary auditory neuron protection
Authors: Gillespie Lisa N. , Shepherd Robert K.
Published: November 2005

Sensorineural hearing loss, as a result of damage to or destruction of the sensory epithelia within the cochlea, is a common cause of deafness. The subsequent degeneration of the neural elements within the inner ear may impinge upon the efficacy of the cochlear implant. Experimental studies have demonstrated that neurotrophic factors can prevent this degeneration in animal models of deafness, and can even provide functional benefits. Neurotrophic factor therapy may therefore provide similar protective effects in humans, resulting in improved speech perception outcomes among cochlear implant patients. There are, however, numerous issues pertaining to delivery techniques and treatment regimes that need to be addressed prior to any clinical application. This review considers these issues in view of the potential therapeutic application of neurotrophic factors within the auditory system.
Rapid modulatory effect of estradiol on acetylcholine‐induced Ca2+signal is mediated through cyclic‐GMP cascade in LHRH‐releasing GT1‐7 cells
Authors: Morales Araceli , Díaz Mario , Guelmes Pedro , Marín Raquel , Alonso Rafael
Published: November 2005

Hypothalamic luteinizing hormone‐releasing hormone neurons (LHRH) form the final pathway for the central control of reproduction through the release of LHRH into the pituitary‐hypothalamic system. We previously found that LHRH‐producing GT1‐7 cells respond to acetylcholine (ACh) with an increase in intracellular calcium ([Ca2+]i) through activation of muscarinic receptors. This effect is acutely modulated by 17β‐estradiol in a manner compatible with specific membrane binding sites. Because increasing evidence suggests that second messengers are involved in the rapid action of estradiol, the aim of the present study was to identify the pathway underlying estrogen actions on ACh‐induced Ca2+signals. 8‐Bromoguanosine 3′,5′‐cyclic monophosphate (10 µm) and C‐type natriuretic peptide (10 µm) mimicked the effect of estradiol. On the contrary, neither dibutyryl cAMP (100 µm), forskolin (100 nmor 10 µm), or sodium nitroprusside (10 µm) induced any modification of [Ca2+]iin response to ACh. The effect of estradiol on calcium transients was totally blocked by two different cGMP‐dependent protein kinase (PKG) inhibitors. In addition, phosphorylation of inositol 1,4,5‐triphosphate (IP3) receptor was rapidly induced by estradiol but totally blocked when the cells were pretreated with a PKG inhibitor. We conclude that physiological concentrations of estradiol reduce ACh‐induced Ca2+transients via a mechanism involving a membrane‐associated guanylate cyclase, which finally induces a PKG‐dependent IP3receptor phosphorylation that modifies calcium release from the endoplasmic reticulum.
Socioeconomic Status Modifies the Sex Difference in Spatial Skill
Authors: Levine Susan C. , Vasilyeva Marina , Lourenco Stella F. , Newcombe Nora S. , Huttenlocher Janellen
Published: November 2005

We examined whether the male spatial advantage varies across children from different socioeconomic (SES) groups. In a longitudinal study, children were administered two spatial tasks requiring mental transformations and a syntax comprehension task in the fall and spring of second and third grades. Boys from middle-and high-SES backgrounds outperformed their female counterparts on both spatial tasks, whereas boys and girls from a low-SES group did not differ in their performance level on these tasks. As expected, no sex differences were found on the verbal comprehension task. Prior studies have generally been based on the assumption that the male spatial advantage reflects ability differences in the population as a whole. Our finding that the advantage is sensitive to variations in SES provides a challenge to this assumption, and has implications for a successful explanation of the sex-related difference in spatial skill.
“We All Look the Same to Me”
Authors: Johnson Kareem J. , Fredrickson Barbara L.
Published: November 2005

Extrapolating from the broaden-and-build theory, we hypothesized that positive emotion may reduce the own-race bias in facial recognition. In Experiments 1 and 2, Caucasian participants (N = 89) viewed Black and White faces for a recognition task. They viewed videos eliciting joy, fear, or neutrality before the learning (Experiment 1) or testing (Experiment 2) stages of the task. Results reliably supported the hypothesis. Relative to fear or a neutral state, joy experienced before either stage improved recognition of Black faces and significantly reduced the own-race bias. Discussion centers on possible mechanisms for this reduction of the own-race bias, including improvements in holistic processing and promotion of a common in-group identity due to positive emotions.
Perceiving Sex Directly and Indirectly
Authors: Johnson Kerri L. , Tassinary Louis G.
Published: November 2005

We employed a novel technique to explore how the body's motion and morphology affect judgments of sex and gender. Stimuli depicted animated human walkers that varied in motion (gait patterns varying shoulder swagger and hip sway) and in morphology (waist-to-hip ratio). The potency of morphology in categorical sex judgments was confirmed. Visual scanning of the walkers was concentrated in the waist and hip region of the body (Study 1a). This targeted scanning was attenuated, however, when the sex of the target had been prespecified (Study 1b). Body motion permitted categorical judgments of sex, but these judgments were mediated by perceived gender (Study 2). These studies provide converging evidence for the primacy of the body's shape in categorical judgments of sex.
A cross‐national survey of cultural expectations and sex‐role standards in reading
Authors: Downing John , Dwyer Carol A. , Feitelson Dina , Jansen Mogens , Kemppainen Ritva , Matihaldi Hilkka‐Liisa , Reggi David R. , Sakamoto Takahiko , Taylor Hugh , Thackray Derek V. , Thomson Douglas
Published: November 2005

Cultural expectations and sex‐role standards about reading in Canada, Denmark, England, Finland, Israel, Japan, and U.S.A. were investigated. A picture test showing various activities and objects including reading and books was administered in each country to six sub‐samples that approximated to the levels: students in grades I, IV, VIII, and XII, college students, and adults. Subjects had to ascribe the activity or object as being appropriate for either a boy or a girl. The results were consistent with the hypothesis that cultural expectations and sex‐role standards about reading are congruent within one country but that they differ between countries. In particular, boys in Canada and the U.S.A. rapidly learn to perceive reading as a feminine activity, whereas Danish and Japanese males at all ages consistently view reading as acceptable masculine behaviour.
Learning to read: a psycholinguistic analysis of transitional processing
Authors: Donald David R.
Published: November 2005

In the last decade a shift in view of the reading process, from basically an‘analytic’to a‘constructivist‐psycholinguistic’view, has become apparent. The basis of this shift is analysed. The question of whether the process of learning‐to‐read, i.e. the transition from initial reading to fluent reading, can be understood in the same light is raised. It is argued that although the process of learning‐to‐read can be viewed essentially as a constructive process, developmental constraints require a modified view of the róle of constituent processing strategies. Implications of this modified view are suggested for the evaluation and teaching of reading.
Reading retardation or linguistic deficit? I: interpreting reading test performances of hearing‐impaired adolescents
Authors: Webster A. , Wood D.J. , Griffiths A.J.
Published: November 2005

The performances of 120 children – 60 hearing and 60 hearing‐impaired – on the Brimer Wide‐span Reading Test were compared. These children fell into three groups of 40 (20 hearing‐impaired, 20 hearing) and were matched for reading ages at 7:0‐7:10, 8:0‐8:10 and 9:0‐9:10 years respectively. Their reading test performances were analysed in detail to reveal marked differences both in frequency of errors and error types between the deaf and hearing children at all reading ages. The hearing‐impaired children attempted significantly more test items than the hearing children of matched reading age. They made more errors and significantly more of their errors were classified as‘non‐linguistic’in nature. The implications of these results both for the nature of reading processes in the hearing‐impaired and the value of tests in measuring their reading abilities are discussed.
Context Cues in Early Reading
Authors: Beardsley Gillian
Published: November 2005

An investigation was carried out to examine any significant differences in the use of four types of context cues by good and poor readers in the early stages of their reading development. Sentences incorporating proactive and retroactive syntactic, and proactive and retroactive semantic cues were presented in the form of deletions at three levels of difficulty. Sixty‐four subjects, 32 of each sex, were drawn equally from the six to seven and seven to eight year age levels and subdivided into groups of good and poor readers. Results indicated that all groups other than the youngest poor readers found the proactive semantic cues the most useful and made miscues displaying semantic associations across cue types. Implications for an understanding of strategies employed in early reading and approaches for instruction are discussed.
Orthographic structures: grapheme patterns in child and adult texts
Authors: Brian Thompson G.
Published: November 2005

Descriptive statistics of grapheme patterns to which child readers are initially exposed were determined, with the purpose of providing a data source for research on children's knowledge and use of orthographic structures in reading and spelling English. The frequency of occurrence of grapheme patterns in the texts of two series of children's initial reading books were analysed by a classification of bigram components relevant to commonly postulated orthographic structures such as ‘letter cluster’, ‘blend’ and ‘digraph’. Frequencies among both word tokens and word types were tabulated for consonant‐value and vowel‐value bigrams for different spatial positions within words. Initial graphemes of words were also analysed by membership of such bigrams. Comparisons were made with similar tabulations derived from the Solso and Juel (1980) tables for adult texts. Although there was appreciable agreement, there were some notable instances of grapheme patterns which occurred with relatively high frequency in children's initial reading, but relatively low frequency in adult texts.
Factors influencing anaphoric processing in ESL reading comprehension
Authors: Parish Charles , Perkins Kyle
Published: November 2005

The purpose of this study was to investigate the effects of some factors that influence English as Second Language (ESL) readers’ ability to resolve anaphoric expressions. Fifty full‐time ESL students randomly drawn from three different proficiency levels served as unpaid volunteers for the project. Data were elicited by means of multiple‐choice and cloze tests. The experimental design contains one between‐subjects factor (proficiency level) and three within‐subjects factors, all orthogonally manipulated (number of antecedents, case of pronominal anaphor, and propositional distance from antecedent). A four‐way mixed ANOVA for the multiple‐choice tests indicated significant effects for proficiency level, case of anaphor, and the interaction of case and number of antecedents. A similar four‐way ANOVA for the cloze tests indicated significant effects for proficiency level, number of antecedents, case of anaphor, distance from antecedent, and for the interactions of case and antecedents, antecedents and distance, and case and distance. Similarities in the findings from this study and other first and second language studies are noted. Latent trait measurement procedures were employed to produce a rank order of difficulty for the different item types examined in this study.
Ocular dominance, reading and spelling: a reassessment of a measure associated with specific reading difficulties
Authors: Newman S. P. , Karle H. , Wadsworth J. F. , Archer R. , Hockly R. , Rogers P.
Published: November 2005

The association of reading disability with perceptuomotor problems has had a chequered history. This study examines the relationship between a new test of ocular dominance and reading and spelling ability in a group of 323 schoolchildren. Similar rates for unfixed ocular dominance were found for poor readers as in comparable studies. The rates of unstable ocular dominance did not differ between those with reading and spelling difficulties and controls. These findings in a ‘blind’ study question the role of this test of eye dominance as a diagnosis of ‘dyslexia’.
Dark‐interval‐threshold, illumination level and children's reading performance
Authors: Riding R. J. , Pugh J. C.
Published: November 2005

Nine‐year‐old children were given a test of dark‐interval threshold (DIT), and two parallel forms of the Neale Analysis of Reading Ability, one at low and the other at high illumination. DIT was measured by determining the shortest interval which caused a white disc viewed in a tachistoscope to disappear when the experimenter switched briefly to a second (black) field for an interval which ranged from 20 ms to 300 ms. A reasonable range of individual differences in DIT was found. There was a significant interaction (p<0.05) between DIT and illumination level in their effect on reading accuracy. Children who had a short DIT read more accurately in high than in low illumination, and the performance was reversed for long DIT subjects.
The nature of reader ability differences in lexical access
Authors: Briggs Pamela , Underwood Geoffrey
Published: November 2005

Can good and poor readers be differentiated by their use of word‐naming and lexical access codes? Poor readers experience extreme difficulty in decoding nonsense words, indicating that they cannot use the spelling to sound rules which underlie the indirect phonological route to word pronunciation. However, recent evidence suggests that poor readers do use a phonological route for lexical access in word and picture naming tasks which rely upon the production of a phonological code. Is this also true of other tasks, which are not dependent upon phonological representation? Two such tasks are described in the present study: one involving picture‐word interference, and the other involving a lexical decision paradigm. Results showed that poor readers do use a phonological route to lexical access independent of task demand. A review of findings in this area to date shows several inconsistencies, and an attempt is made to resolve these by drawing on Stanovich's (1980) interactive‐compensatory model of reading.
The comprehension of first and second‐language prose
Authors: Lasisi M. J. , Falodun Sola , Onyehalu A. S.
Published: November 2005

How does national culture interact with second‐language reading comprehension? This study investigated the effect of cultural medium of presentation, language, and sequence of cultural/foreign and first‐language/second‐language presentation on the literal and interpretative comprehension of Form I (seventh grade) bilingual Nigerian students. Data were analysed using ANOVA. Previous studies concerning schema theories were upheld in that the present results for Experiment 1 revealed significantly superior scores for culturally related English language text when compared with scores for foreign‐based passages written in English. The data from Experiment 2 also revealed similar results when the subjects were presented with the same Experiment 1 foreign‐based passages written in English and with translations of these English passages to the mother tongue. In spite of sequencing, scores were higher for the first‐language passages. For both experiments, scores were higher at the literal level and sequencing was found to have little effect in enhancing comprehension of culturally unfamiliar material.
Reading strategies of good and poor readers in word and phrase presentation
Authors: Beveridge Michael , Edmundson Susan
Published: November 2005

This paper reports two experiments which use a micro‐computer driven self‐paced reading task to examine the reading strategies of good and poor readers. Unlike previous work using this technique the children were able to regress to earlier parts of the texts by pressing the appropriate computer key. The main focus of the experiments is on the relationship between reading strategies, reading ability and the length of the textual units which are presented to the children. Reading ability is found to influence reading strategies differently according to whether text is presented in single words or in phrases. A similar result is found for the time taken to read the texts. The results are discussed in the light of current theories of text processing. However the main point of the paper is to illustrate the use of a potentially powerful diagnostic tool which will operate on computers currently available in schools.
Are numbers logographs?
Authors: Green David , Meara Paul , Court Stephen
Published: November 2005

Researchers generally assume that logographs such as numerals form a homogeneous set. This paper presents a study whose results challenge that assumption. Using a visual search task, it is shown that native Chinese speakers, who can read and speak English, process strings of Chinese numerals differently from the way they process strings of Western numerals. The different pattern of results found with these two sets of numerals also contrasts with the pattern typically found when native English speakers process Western numerals. An explanation of this result is proposed based on the notion that visual search functions can be the outcome of the combined effect of different basic search procedures.