bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensing DNA methylation in the protozoan parasite Entamoeba histolytica
Authors: Lavi Tal , Isakov Elada , Harony Hala , Fisher Ohad , Siman‐Tov Rama , Ankri Serge
Published: October 2006

In the protozoan parasite Entamoeba histolytica, 5‐methylcytosine (m5C) was found predominantly in repetitive elements. Its formation is catalysed by Ehmeth, a DNA methyltransferase that belongs to the Dnmt2 subfamily. Here we describe a 32 kDa nuclear protein that binds in vitro with higher affinity to the methylated form of a DNA encoding a reverse transcriptase of an autonomous non‐long‐terminal repeat retrotransposon (RT LINE) compared with the non‐methylated RT LINE. This protein, named E. histolytica‐methylated LINE binding protein (EhMLBP), was purified from E. histolytica nuclear lysate, identified by mass spectrometry, and its corresponding gene was cloned. EhMLBP corresponds to a gene of unknown function that shares strong homology with putative proteins present in Entamoeba dispar and Entamoeba invadens. In contrast, the homology dropped dramatically when non‐Entamoebidae sequences were considered and only a weak sequence identity was found with Trypanosoma and several prokaryotic histone H1. Recombinant EhMLBP showed the same binding preference for methylated RT LINE as the endogenous EhMLBP. Deletion mapping analysis localized the DNA binding region at the C‐terminal part of the protein. This region is sufficient to assure the binding to methylated RT LINE with high affinity. Western blot and immunofluorescence microscopy, using an antibody raised against EhMLBP, showed that it has a nuclear localization. Chromatin immunoprecipitation (ChIP) confirmed that EhMLBP interacts with RT LINE in vivo. Finally, we showed that EhMLBP can also bind rDNA episome, a DNA that is methylated in the parasite. This suggests that EhMLBP may serve as a sensor of methylated repetitive DNA. This is the first report of a DNA‐methylated binding activity in protozoa.
Certain clinically‐utilized antibiotics enhance the behavioural effects of cocaine
Authors: Overton Paul G. , Marrow Lynne P. , Brain Paul F. , Clark David
Published: October 2006

Cytochrome P‐450s (CYPs) belonging to subfamilies 2B and 3A are the major CYPs involved in the N ‐demethylation of cocaine in the rat. However, the effects of inhibitors of these enzymes on the behavioural actions of cocaine are unknown. Hence, the effects of the CYP 3A inhibitors troleandomycin and erythromycin, and the CYP 2B (and 3A) inhibitor chloramphenicol, were examined on the locomotor activating effects of cocaine (20 mg/kg i.p.). Troleandomycin, chloramphenicol and erythromycin all potentiated the locomotor activating effects of cocaine, although the effect was only statistically significant for the first two drugs. Since variation exists in the human population with respect to the catalytic activity of CYP 3A isozymes, which are the principal cocaine N ‐demethylators in humans, inhibition of CYP 3A by troleandomycin in the rat may be useful as a model of the human cocaine “poor metabolizer” phenotype.
Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase: clinical features of alcoholics with ALDH2*2
Authors: Nakamura Kazuhiko , Iwahashi Kazuhiko , Itoh Masahiro , Ameno Kiyoshi , Yoshihara Eiji , Fukunishi Isao , Suwaki Hiroshi
Published: October 2006

In a person with inactive ALDH2 (ALDH2*2) the blood aldehyde concentration tends to rise faster and higher and there are flushing responses which are considered to be a restraint against excessive alcohol drinking. The subjects in this study comprised 71 Japanese alcoholics. Psychiatrists interviewed the patients concerning the clinical features. Alcoholics homozygous (n = 59) for ALDH2*1/ALDH2*1 (Group I) and those heterozygous (n = 12) for ALDH2*1/ALDH2*2 (Group II) were compared. Group II alcoholics included significantly more cases of guilt or personality disorder. These findings indicate that alcoholics with the ALDH2*2 genotype showed generally typical clinical features.
Prior exposure to a behaviorally sensitizing regimen of d‐methamphetamine does not alter the striatal dopaminergic damage induced by a neurotoxic regimen
Authors: Miller Diane B. , O'Callaghan James P. , Johnson E. Anne
Published: October 2006

Repeated exposure to psychostimulant drugs such as d‐methamphetamine (d‐METH) and cocaine can be associated with extremely long‐lived changes in dopamine systems at the behavioral, cellular and molecular level. Sensitization or an enhanced response to drug exposure is one such change. Investigations of these phenomena at the cellular and molecular levels are being conducted in the hope that this will aid in understanding how such adaptations might contribute to drug addition. Repeated exposure to certain amphetamines can also result in damage to dopaminergic pathways. Although some of the same molecular adaptations and mechanisms are suspected to occur or play a role in the neurotoxic sequelae associated with psychostimulant exposure, there has been little attempt to examine the relationship among these phenomena. Here we utilized C57BL/6J female mice to examine whether exposure to a sensitizing regimen of d‐METH would impact the degree of neural injury induced by a subsequent exposure to a neurotoxic regimen of the same psychostimulant. Every other day exposure to d‐METH (1.0 or 2.0 mg/kg) for 11 days produced a behavioral sensitization, as evidenced by a significant increase in the degree of locomotor activity induced by each subsequent exposure to d‐METH. Following a 5‐day period of no drug exposure sensitized mice were given a neurotoxic regiment of d‐METH (a total of four injections of 10.0 mg/kg, one every 2 hours) and striatal tissue examined 72 hours later. All groups, whether drug‐naive or sensitized previously to d‐METH, showed exactly the same degree of dopaminergic striatal damage induced by a neurotoxic regimen. This was evidenced by equivalent reductions in dopamine and elevations in GFAP protein, a marker of astrocytic response to injury, GFAP. The inability of a sensitizing regimen to either exacerbate or lessen the neurotoxic actions of the same compound suggests that the molecular and cellular control of these two aspects of psychostimulant exposure may differ.
The effects of acute cocaine administration in paradoxical sleep‐deprived rats
Authors: Andersen Monica L. , Palma Beatriz D. , Rueda Adriana D. , Tufik Sergio
Published: October 2006

Recent studies demonstrate the action of cocaine on reward pathways, which are activated by pleasant stimuli. Cocaine's mechanism of action involves the blockade of dopamine and norepinephrine reuptake by the presynaptic terminal. Paradoxical sleep (PS) deprivation is known to induce several behavioural alterations most of which suggest the occurrence of supersensitivity of D 2 and a subsensitivity of b 1 and b 2 receptors.The present study sought to examine the effects of PS deprivation on the actions of cocaine on the erection and ejaculation behaviours in rats. Four different doses of cocaine (3.5, 7.0, 15.0 and 30.0 mg/kg) were acutely administered to Wistar male rats, at the end of a 4‐day period of PS deprivation or at the equivalent time‐point to control animals. Moreover, 15 mg/kg of cocaine were administered in animals submitted to immobilization, footshock and forced swimming. The data were analysed by the Chi‐square test, and revealed that only PS‐deprived animals exhibited penile erections and ejaculation behaviours, which were absent in control animals. PS deprivation increases the sexual behaviour of male rats, probably due to its action on dopaminergic systems. However, further studies need to be carried out in order to clarify the mechanisms involved between PS deprivation and cocaine.
Dopamine D4 receptor gene and severity of dependence
Authors: Lusher Joanne , Ebersole Lorna , Ball David
Published: October 2006

Family, twin and adoption studies demonstrate that substance dependence is determined partially by genes. Recent studies in opiate‐dependent subjects have found a significant excess of the long‐long (LL) allele of the 48bp repeat in the coding sequence of the DRD4 gene. This study examined this association further in a sample of 60 opiate dependent, 51 alcohol‐dependent and 64 normal, healthy control subjects. No significant association between the polymorphism at DRD4 and opiate or alcohol abuse was found. However, results yielded a significant main effect on severity of dependence, demonstrating that individuals with the LL allele rated their severity of dependence significantly higher than those who had the short‐short (SS) allele :[F(2, 101) = 5.0, p < 0.01]. This study suggests that the DRD4 gene does not directly influence vulnerability to substance dependence, but that possession of the LL genotype significantly increases severity of dependence.
PRECLINICAL STUDY: Schedule‐induced alcohol drinking: non‐selective effects of acamprosate and naltrexone
Authors: Escher Tobie , Mittleman Guy
Published: October 2006

Acamprosate and naltrexone are therapeutically effective drugs that promote abstinence and prevent drinking relapse among alcohol‐dependent patients, and dose‐dependently decrease alcohol self‐administration in animals. The purpose of this experiment was to investigate the behavioral specificity of acamprosate and naltrexone treatment in mice on alcohol drinking elicited in a schedule‐induced polydipsia (SIP) task. Food‐deprived male C57BL/6J (B6) mice were divided into three groups assigned to a 5% alcohol SIP, water SIP, or a 1‐hour limited access regulatory water drinking task. Injections (intraperitoneal) of acute (0, 50, 100, 200, 400 mg/kg) and chronic (2 × 100 mg/kg, 10 days) acamprosate, or naltrexone (0, 1.0, 2.5, 5.0 mg/kg) were administered. Behavioral drug specificity was determined by comparing alterations in alcohol or water consumption in SIP with alterations in limited access drinking. Additionally, drug effects on drinking‐specific measures (g/kg consumption and lick efficiency) were compared with those of non‐drinking measures (head entries for food and locomotor activity) during SIP. In comparison with saline injections, acute acamprosate (400 mg/kg) reduced both alcohol and water drinking in both SIP and the regulatory drinking conditions, but had no significant effects on non‐drinking measures. Chronic administration of acamprosate reduced both alcohol and water drinking during SIP, but did not significantly affect regulatory drinking or non‐drinking measures. Naltrexone (1.0, 2.5, 5.0 mg/kg) reduced alcohol and water drinking in both paradigms, and at the highest dose, significantly reduced head entries for food. These results indicate that acamprosate (acute and chronic) and naltrexone are relatively non‐selective in their effects on alcohol self‐administration in this task.
PRECLINICAL STUDY: Effects of venlafaxine and desipramine on heroin‐induced conditioned place preference in the rat
Authors: Tzschentke Thomas M. , Magalas Zofia , De Vry Jean
Published: October 2006

Venlafaxine, an antidepressant with serotonin and noradrenaline reuptake inhibiting properties, has been reported to reduce acquisition (but not maintenance) of heroin intravenous self‐administration (IVSA) in rats. The present study investigated whether this phase‐dependent effect is due to an antidepressant‐induced attenuation of the rewarding effect of heroin, as assessed in the conditioned place preference (CPP) paradigm. In order to study the effects of venlafaxine and the tricyclic antidepressant desipramine on acquisition and expression of heroin CPP, both compounds were administered prior to the conditioning sessions (together with heroin), or prior to the expression test after conditioning, respectively. As clinical evidence indicates that antidepressants require repeated administration for full efficacy, additional experiments were performed in which both antidepressants were administered for 2 weeks prior to conditioning, or for 1 week prior to the expression test, respectively. When tested alone, heroin [0.05–3.16 mg/kg intraperitoneally (i.p.)] produced a dose‐dependent CPP, whereas the antidepressants (1–21.5 mg/kg i.p.) produced neither a CPP nor a conditioned place aversion (CPA). For both antidepressants (10 mg/kg i.p.), neither acute nor repeated pretreatment affected acquisition or expression of heroin (0.5 mg/kg) CPP. Thus, the present study does not support the hypothesis that the previously observed attenuation of acquisition of heroin IVSA by venlafaxine is due to an antidepressant‐induced attenuation of the rewarding effect of heroin. It is conceivable, however, that the rewarding effect of the 0.5 mg/kg dose of heroin was too pronounced to be susceptible to modulation by antidepressants. Alternatively, the modulation of acquisition of heroin IVSA in the previous study may be related to mechanisms that cannot be modelled with the CPP paradigm.
REVIEW: Targeting treatments for alcohol dependence: the pharmacogenetics of naltrexone
Authors: Oslin David W. , Berrettini Wade H. , O’Brien Charles P.
Published: October 2006

Alcohol dependence is one of the leading causes of morbidity worldwide, yet only a minority of those afflicted engages in treatment. While increasing access to treatment is an important public health approach, increasing the success of treatment is also likely to lead to greater engagement. However, alcohol dependence is a complex disorder likely to consist of several biological subtypes. Recent evidence from a number of different studies has suggested that genetic variation in the mu‐opioid receptor has a significant influence on clinical presentation of alcohol problems and response to treatment with an opioid antagonist. Most notably, the A118G polymorphism of the mu‐receptor gene has been demonstrated to predict clinical response to naltrexone in alcohol‐dependent individuals. This article reviews the biological correlates and outlines a scientific agenda for better understanding the role of opioid neurotransmission in the etiology, maintenance and treatment of alcohol dependence.
Increased mutations of CD72 transcript in B‐lymphocytes from adolescent patients with systemic lupus erythematosus
Authors: Kaneko Utako , Toyabe Shin‐ichi , Hara Masanori , Uchiyama Makoto
Published: October 2006

Recent studies have shown that B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE). Abnormal expression of molecules engaging in B‐cell receptor (BCR) signaling and resultant hyperactivity of B cells has been reported in both mouse models of lupus and patients with SLE. CD72 on B cells is unique in that it regulates BCR signaling both positively and negatively. We analyzed the expression of CD72 protein and mRNA in peripheral blood B cells from adolescent patients with SLE. The expression level of CD72 on B cells of the patients was decreased compared with that on B cells of controls. Sequence analysis of CD72 mRNA showed significantly increased nucleotide mutations, including both nucleotide substitutions and deletions. Almost all (95.6%) of the CD72 transcripts from the patients had different nucleotide sequences from those of the wild type. About half (41.3%) of the mutations were point mutations located close to the sequence of the immunoreceptor tyrosine‐based inhibitory motif (ITIM), which negatively regulates BCR signaling. These results indicate that increased nucleotide mutation of CD72 mRNA accounts for the decreased expression level of CD72 in B cells, and it might be related to hyperactivity of B cells in patients with SLE.
Mechanism of prolonged gene expression by Epstein–Barr virus‐based plasmid in porcine cells
Authors: Son Jung Kyu , Oh Sang Taek , Cho Sung Kyu , Yoon Kun Ho , Lee Suk Kyeong
Published: October 2006

Abstract:  Background:  We previously showed that an Epstein‐Barr virus (EBV)‐based plasmid, pEBVGFP, exerts prolonged gene expression in porcine neonatal pancreatic cell clusters (NPCCs). In this study, the mechanism underlying this was investigated.

Methods:  GFP expression was analyzed in porcine cells transfected with pEBVGFP by FACS analysis and confocal microscopy. The possible integration of pEBVGFP into the chromosomal DNA was analyzed by Southern blot. Self‐replication of the EBV‐based plasmid in porcine cells was investigated by PCR. The NPCCs were immunostained to characterize cells transfected with pEBVGFP.

Results:  The EBV based plasmid provided prolonged GFP expression in porcine cells and duct cells were the main cells transfected among NPCCs. Southern blot showed that the transfected pEBVGFP stayed for a long time as an episome rather than integrating into the chromosomal DNA. pEBVGFP isolated from the transfected porcine cells had methylated CpG suggesting that they self‐replicated in those cells.

Conclusions:  The EBV‐based plasmid may be useful for genetically manipulating porcine cells to enhance their value as xenotransplantation sources.
Prenatal diagnosis of haemophilia A by chorionic villus sampling and cordocentesis: All India Institute of Medical Science experience
Authors: Ranjan R. , Biswas A. , Kannan M. , Meena A. , Deka D. , Saxena R.
Published: October 2006

Background and Objective  We looked at the two most commonly used methods for prenatal diagnosis, cordocentesis and chorionic villus sampling for prenatal diagnosis of haemophilia A in an Indian setting.

Material and Methods  The study sample included 16 families which reported to us for prenatal diagnosis of haemophilia A at All India Institute of Medical Science, New Delhi, India. Prenatal tests were done on chorionic villus samples or on cord blood (cordocentesis). Molecular work‐up included the use of indirect mutation analysis in the form of linkage markers like CA‐13, CA‐22, Xba1 and Bcl1 as well as direct mutation analysis in the form of inversion 1 and 22 detection. Non‐molecular work‐up included primarily factor VIII assays.

Result  Chorionic villus sampling was performed in eight mothers. Of the other eight mothers, six underwent cord blood factor VIII assays because these had absence of family history and were negative for linkage and inversion 1 and 22. One patient had a female child and another had a fetus that showed congenital abnormalities.

Conclusion  We found that the choice of either technique, chorionic villus or cordocentesis, is not really an alternative, but rather dependent on the gestational age of presentation.
International Dissemination of a High Virulence Rabbit Staphylococcus aureus Clone
Authors: Vancraeynest D. , Haesebrouck F. , Deplano A. , Denis O. , Godard C. , Wildemauwe C. , Hermans K.
Published: October 2006

High virulence rabbit Staphylococcus aureus strains cause chronic and spreading problems of mastitis, pododermatitis and subcutaneous abscesses on rabbit flock level, whereas infections with low virulence strains are limited to individual rabbits. In the present report, 13 high virulence rabbit S. aureus strains, selected out of a large collection of strains isolated in five European countries between 1983 and 2004, were genotyped using pulsed‐field gel electrophoresis, spa typing, multilocus sequence typing (MLST) and accessory gene regulator (agr) group typing. Two low virulence rabbit S. aureus strains were also included in the study. The results indicate the clonal origin of high virulence rabbit S. aureus strains present in Europe. Furthermore, the results of MLST and spa typing form a basis for international epidemiology of rabbit S. aureus strains, as these DNA sequence‐based typing techniques can easily be used for intercentre comparisons.
Molecular Typing of Staphylococcus aureus Isolated from Cows, Goats and Sheep with Intramammary Infections on the Basis of Gene Polymorphisms and Toxins Genes
Authors: Vimercati C. , Cremonesi P. , Castiglioni B. , Pisoni G. , Boettcher P. J. , Stella A. , Vicenzoni G. , Moroni P.
Published: October 2006

We investigated 116 Staphylococcus aureus isolates from cows, goats and sheep with intramammary infections (IMI) in Italy to provide information about the spread of enterotoxigenic strains and to compare strains isolated from different ruminant species. The isolates were typed by restriction fragment length polymorphism (RFLP) analysis of the coagulase (coa) gene, by analysis of polymorphisms of the X region of protein A (spa) gene and by detection of genes encoding enterotoxins (sea, seb, sec, sed, see, seg, seh, sei, sej and sel). Seven different coa types and 12 different spa types were distinguished. On the basis of polymerase chain reaction‐RFLP, 29 different coa subtypes were identified. Two different coa subtypes accounted for 49% and 67% of bovine and ovine isolates respectively. Only seven coa subtypes were observed in isolates from more than one host species and no coa subtype was present in isolates from all three ruminant species. Furthermore, 85 of the isolates (73%) harboured at least one enterotoxin gene (se) with a predominance of sea, sed and sej among isolates from bovine IMI, and sec and sel among isolates from caprine and ovine IMI. Comparing the S. aureus isolates on the basis of gene polymorphisms and presence of se genes, significant differences were found in distributions of genotypes among isolates from cows, goats and sheep.
Phylogenetic Analysis of Anaplasma marginale Strains from Paraná State, Brazil, Using the msp1α and msp4 genes
Authors: Vidotto M. C. , Kano S. F. , Gregori F. , Headley S. A. , Vidotto O.
Published: October 2006

Anaplasma marginale is an obligate intraerythrocytic rickettsial pathogen (order, Rickettsiales: family, Anaplasmataceae) that causes bovine anaplasmosis. This disease is widely distributed in tropical and sub‐tropical regions of the world and causes important economic losses to cattle production. Major surface protein (MSP)1a (msp1α gene) is one of the six MSPs identified on A. marginale from cattle, whose sequence and size vary according to the number of tandem 28‐ to 29‐amino acid repeats. This study characterized the msp1α and msp4 genes obtained from three distinct Brazilian herds from the State of Paraná. Three strains of the msp1α and one strain of the msp4 gene were sequenced. The strains evaluated revealed PCR products of different size, representing three, five and six internal repeats. Sequence analyses confirmed the number of tandem sequence copies and revealed a high degree of sequence identity with strains from other Brazilian States, as well as strains from the USA, Europe and Israel. The msp1α DNA and amino acid sequences from A. marginale and DNA sequences of msp4 strains did not reveal distinct phylogeographical segregation. However, the amino acid sequences of msp4 demonstrated definite phylogeographical relationship. These results suggest that the amino acid sequences of msp4 should be used for phylogenetic identification of A. marginale strains and may be an important tool for the epidemiology and control of anaplasmosis. Additionally, the close similarity of the Paraná strains of A. marginale with strains from USA, Europe and Asia may reflect the introduction of these genes during the development of the Brazilian bovine herd.
Molecular Typing and Anti‐microbial Susceptibility of Clinical Isolates of Streptococcus equi ssp. zooepidemicus from Equine Bacterial Endometritis
Authors: Luque I. , Fernández‐Garayzábal J. F. , Blume V. , Maldonado A. , Astorga R. , Tarradas C.
Published: October 2006

The anti‐microbial susceptibility and genetic diversity of 65 strains of Streptococcus equi ssp. zooepidemicus (Sez) isolated from mares presenting clinical signs of endometritis was determined by disk agar diffusion and pulsed field gel electrophoresis (PFGE) methods, respectively. Overall, Sez isolates were susceptible to β‐lactams, enrofloxacin, trimethoprim‐sulfamethoxazole and gentamicin. These anti‐microbials could be recommended as empiric anti‐microbial therapy in cases of endometritis caused by Sez. Pulsed field gel electrophoresis typing revealed a great genetic diversity (56 different PFGE macrorestriction profiles) and a low level of genetic relatedness amongst the isolates.
Correlation between the soil seed bank and weed populations in maize fields
Authors: RAHMAN ANIS , JAMES TREVOR K. , GRBAVAC NIK
Published: October 2006

Annual weed populations establish every year from persistent seed banks in the soil. This 3 year study investigated the relationship between the number of weed seeds in the soil seed bank and the resultant populations of major broadleaf and grass weeds in 30 maize fields. After planting the crop, 1 m2 areas were protected from the pre‐emergence herbicide application. Soil samples were collected soon after spraying to a depth of 100 mm and the weed seeds therein were enumerated. The emerged weed seedlings in the field sampling areas were counted over the following 8 weeks. Up to 67 broadleaf species and five grass weeds were identified, although not all were found at every site and some were specific to a region or soil type. For the most abundant weeds in the field plots, on average 2.1–8.2% of the seeds of the broadleaf species and 6.2–11.9% of the seeds of the grass weeds in the soil seed bank emerged in any one year, depending on the species. Overall, the results showed a strong linear relationship between the seed numbers in the soil and the seedling numbers in the field for all the grasses and for most broadleaf weeds. For some species, like Trifolium repens, only a weak relationship was observed. In the case of Chenopodium album, which had the largest seed bank, there was evidence of asymptotic behavior, with seedling emergence leveling off at high seed numbers. An estimate of the soil seed bank combined with knowledge of the germination and behavior of specific weed species would thus have good potential for predicting future weed infestations in maize fields.
Localized lesions of arcopallium intermedium of the lateral forebrain caused a handling‐cost aversion in the domestic chick performing a binary choice task
Authors: Aoki Naoya , Csillag Andras , Matsushima Toshiya
Published: October 2006

Behavioral effects of handling cost (time and/or energetic cost for food consumption) on choice were examined using domestic chicks trained in operant task reinforced by delayed food rewards. When scattered sesame was delivered in more demanding conditions, a colored cue bead associated with six grains (‘large’ and ‘costly’ reward) was chosen progressively less frequently against another bead associated with one grain (‘small’ and ‘not costly’ reward). The choice thus proved to be highly sensitive to the anticipated handling cost. Excitotoxic lesion of the bilateral arcopallium intermedium also selectively reduced the choice of the six grains, while leaving actual cost investment (number of pecks and handling time) unaltered. No significant changes occurred in choices between one grain of sesame (‘small’ and ‘not costly’ reward) and one grain of barley (or a ball composed of six sesame grains glued by starch; ‘large’ and ‘not costly’ reward), indicating that choice based on anticipated food amount was not impaired. On the other hand, lesion of the ventral striatum did not change the choice ratio in any trial types. Operant peck latencies somewhat depended on food rewards, but were not affected by lesions of the arcopallium or the ventral striatum. The arcopallium could contribute to foraging behaviors by enabling chicks to overcome the handling cost, thus gaining more beneficial food. Furthermore, the present results indicate doubly dissociated functional roles of the ventral striatum and the arcopallium, the former in the cost of traveling for food and the latter in the cost of handling food, respectively.
Altered subcellular location of phosphorylated Smads in Alzheimer's disease
Authors: Ueberham Uwe , Ueberham Elke , Gruschka Hildegard , Arendt Thomas
Published: October 2006

A number of growth factors and cytokines, such as transforming growth factor beta 1 (TGF‐β1), is elevated in Alzheimer's disease (AD), giving rise to activated intracellular mitogenic signaling cascades. Activated mitogenic signaling involving the mitogen‐activated protein kinases (MAPKs) and other protein kinases might alter the phosphorylation states of structural proteins such as tau, resulting in hyperphosphorylated deposits. Many intracellular signaling proteins are potential targets of misregulated phosphorylation and dephosphorylation. Recently, a crosstalk between MAPKs and Smad proteins, both involved in mediating TGF‐β1 signaling, has been reported. Although TGF‐β1 has previously been shown to be involved in the pathogenesis of AD, the role of Smad proteins has not been investigated. In this study we thus analysed the subcellular distribution of phosphorylated Smad2 and Smad3 in the hippocampus of both normal and AD brains. Here we report on strong nuclear detection of phosphorylated Smad2 and Smad3 in neurons of control brains. In AD brains these phosphorylated proteins were additionally found in cytoplasmic granules in hippocampal neurons, within amyloid plaques and attached to neurofibrillary tangles. Our data suggest a critical role of Smad proteins in the pathogenesis of AD.
Implementing plant hydraulic architecture within the LPJ Dynamic Global Vegetation Model
Authors: Hickler Thomas , Prentice I. Colin , Smith Benjamin , Sykes Martin T. , Zaehle Sönke
Published: October 2006

Aim  To implement plant hydraulic architecture within the Lund–Potsdam–Jena Dynamic Global Vegetation Model (LPJ–DGVM), and to test the model against a set of observational data. If the model can reproduce major patterns in vegetation and ecosystem processes, we consider this to be an important linkage between plant physiology and larger‐scale ecosystem dynamics.

Location  The location is global, geographically distributed.

Methods  A literature review was carried out to derive model formulations and parameter values for representing the hydraulic characteristics of major global plant functional types (PFTs) in a DGVM. After implementing the corresponding formulations within the LPJ–DGVM, present‐day model output was compared to observational data.

Results  The model reproduced observed broad‐scale patterns in potential natural vegetation, but it failed to distinguish accurately between different types of grassland and savanna vegetation, possibly related to inadequate model representations of water fluxes in the soil and wildfire effects. Compared to a version of the model using an empirical formulation for calculating plant water supply without considering plant hydraulic architecture, the new formulation improved simulated patterns of vegetation in particular for dry shrublands. Global‐scale simulation results for runoff and actual evapotranspiration (AET) corresponded well to available data. The model also successfully reproduced the magnitude and seasonal cycle of AET for most EUROFLUX forests, while modelled variation in NPP across a large number of sites spanning several biomes showed a strong correlation with estimates from field measurements.

Main conclusions  The model was generally confirmed by comparison to observational data. The novel model representation of water flow within plants makes it possible to resolve mechanistically the effects of hydraulic differences between plant functional groups on vegetation structure, water cycling, and competition. This may be an advantage when predicting ecosystem responses to nonextant climates, in particular in areas dominated by dry shrubland vegetation.
Is there a connection between weather at departure sites, onset of migration and timing of soaring‐bird autumn migration in Israel?
Authors: Shamoun‐Baranes Judy , Van Loon Emiel , Alon Dan , Alpert Pinhas , Yom‐Tov Yoram , Leshem Yossi
Published: October 2006

Aims Different aspects of soaring‐bird migration are influenced by weather. However, the relationship between weather and the onset of soaring‐bird migration, particularly in autumn, is not clear. Although long‐term migration counts are often unavailable near the breeding areas of many soaring birds in the western Palaearctic, soaring‐bird migration has been systematically monitored in Israel, a region where populations from large geographical areas converge. This study tests several fundamental hypotheses regarding the onset of migration and explores the connection between weather, migration onset and arrival at a distant site.

Location Globally gridded meteorological data from the breeding areas in north‐eastern Europe were used as predictive variables in relation to the arrival of soaring migrants in Israel.

Methods Inverse modelling was used to study the temporal and spatial influence of weather on initiation of migration based on autumn soaring‐bird migration counts in Israel. Numerous combinations of migration duration and temporal influence of meteorological variables (temperature, sea‐level pressure and precipitable water) were tested with different models for meteorological sensitivity.

Results The day of arrival in Israel of white storks, honey buzzards, Levant sparrowhawks and lesser spotted eagles was significantly and strongly related to meteorological conditions in the breeding area days or even weeks before arrival in Israel. The cumulative number of days or cumulative value above or below a meteorological threshold performed significantly better than other models tested. Models provided reliable estimates of migration duration for each species.

Main conclusions The meteorological triggers of migration at the breeding grounds differed between species and were related to deteriorating living conditions and deteriorating migratory flight conditions. Soaring birds are sensitive to meteorological triggers at the same period every year and their temporal response to weather appears to be constrained by their annual routine.
This Year’s Model: influences on board and director evaluation*
Authors: Long Tracy
Published: October 2006

Over the last few years corporate governance codes and shareholder expectations have increased the need for boards of directors to demonstrate effective leadership, quality decision‐making processes and the ability to exercise corporate controls. Shareholders and stakeholders continue to focus on indicators such board structure, composition and non‐executive independence as proxies for effectiveness, often without an increased under‐standing of the environment in which boards of directors make decisions, or the behaviour and dynamics of individuals. In order specifically to address this issue the Combined Code, published in 2003, stated that a board should undertake annually “a formal and rigorous evaluation of its own performance, that of the committees and individual directors” (Financial Reporting Council, 2003, p. 10. TheCombined Code on Corporate Governance. London: Financial Reporting Council), although it omitted to give formal guidance on evaluation methods, or the disclosure of outcomes to shareholders.

This paper draws on earlier research (Long, 2004) in order to contribute to an improved understanding of the role and effectiveness of board evaluation, and to add to the policy debate by identifying board dynamics which influence the environment in which boards operate. It suggests that the evaluation process should interpret specific influences on the environment in which boards make their decisions – company lifecycle, corporate structure, board culture and embedded process – highlighting distinct board roles and responsibilities, and diverse levels of individual approach, expectation and contribution. The author draws on her work through Boardroom Review to explore ways in which board evaluation can achieve a range of corporate objectives which extend beyond compliance, and encourages boards and their chairmen to adopt a thoughtful and thorough approach to this year’s evaluation model.
The Eviction of Critical Perspectives from Gentrification Research
Authors: SLATER TOM
Published: October 2006

Recent years have seen an extraordinary resurgence of interest in the process of gentrification, accompanied by a surge of articles published on the topic. This article looks at some recent literature — both scholarly and popular — and considers the reasons why the often highly critical perspectives on gentrification that we saw in earlier decades have dwindled. Whilst a number of reasons could be put forward, three in particular are discussed. First, the resilience of theoretical and ideological squabbles over the causes of gentrification, at the expense of examining its effects; second, the demise of displacement as a defining feature of the process and as a research question; and third, the pervasive influence of neoliberal urban policies of ‘social mix’ in central city neighbourhoods. It is argued that the ‘eviction’ of critical perspectives from a field in which they were once plentiful has serious implications for those at risk from gentrification, and that reclaiming the term from those who have sugarcoated what was not so long ago a ‘dirty word’ (Smith, 1996) is essential if political challenges to the process can be effective.
‘Hair Wash’ or ‘Head Bath’ Triggering Migraine - Observations in 94 Indian Patients
Authors: Ravishankar K
Published: October 2006

Identification of trigger factors is helpful in the diagnosis and management of migraine. Common triggers of migraine are well established but ‘hair wash or head bath’ as a trigger for migraine has so far not been reported. This prospective study analysed this unusual trigger link in 94 out of 1500 Indian patients who fulfilled the International Headache Society criteria for migraine. In 11 patients, hair wash was the only trigger; in 45 patients hair wash was one of the triggers and in 38 patients hair wash was a trigger concurrently and in combination with another common trigger. The effect of episodic and long-term prophylaxis in preventing this trigger-like headache has been analysed. The underlying pathophysiological basis is not established but it is important for this unusual regional trigger to be identified and incorporated in the management strategy.
Genetics of psoriasis
Authors: Jullien D , Barker JN
Published: October 2006

Psoriasis is a chronic inflammatory disease of unknown cause with variable clinical expression. In the absence of clearly identified psoriasis autoantigen, there is debate as to whether it can be considered an autoimmune disease. However, considerable evidence obtained from twin studies, demographic studies, and genome‐wide scans performed in several extended patient cohorts and carefully selected psoriasis pedigrees, clearly established that genetics is a key component in the development of psoriasis. The common thought is that psoriasis has a multifactorial mode of inheritance, and that in order for an individual to develop clinical lesions, several psoriasis‐susceptibility genes have to interact together and with various environmental factors. This article reviews some past and current findings on the genetics of psoriasis.
Autism spectrum disorder in the second year: stability and change in syndrome expression
Authors: Chawarska Katarzyna , Klin Ami , Paul Rhea , Volkmar Fred
Published: October 2006

Objectives:  Increasing numbers of young children referred for a differential diagnosis of autism spectrum disorders (ASD) necessitates better understanding of the early syndrome expression and the utility of the existing state‐of‐the art diagnostic methods in this population.

Method:  Out of 31 infants under the age of 2 years referred for a differential diagnosis, 19 were diagnosed with autism, and 9 with pervasive developmental disorder – not otherwise specified (PDD‐NOS) when reassessed at 3 years. We examined 1) the symptoms of ASD in the second year and changes in the syndrome expression by the age of three; 2) relationship between expert‐assigned clinical diagnosis and diagnostic classification based on Autism Diagnostic Observation Schedule‐Generic (ADOS‐G) and Autism Diagnostic Interview‐Revised (ADI‐R) in the second year; 3) the relationship between direct observation and parental report of ASD symptoms.

Results:  Symptoms of autism and PDD‐NOS in the second year were pronounced and stability of the clinical diagnosis was high. The agreement between clinician‐assigned autism but not PDD‐NOS diagnosis and the ADOS‐G was high. However, sensitivity of the ADI‐R diagnostic classification of autism was poor. Comparison of concurrent parental report and direct observation revealed discrepancies in severity ratings of key dyadic social behaviors. Changes in communication reflected acquisition of language accompanied by the emergence of unusual language characteristics. Symptoms of social dysfunction were relatively stable over time, and so was the severity of stereotyped behaviors.

Conclusions:  The study provides support for stability of clinical diagnosis and syndrome expression in the second year and highlights advantages and limitations of the ADI‐R and ADOS‐G for diagnosing and documenting symptoms of ASD in infants.
The cannabinoid system and its pharmacological manipulation – a review, with emphasis upon the uptake and hydrolysis of anandamide
Authors: Fowler Christopher J.
Published: October 2006

Although cannabis has been used both recreationally and for medicinal purposes since ancient times, it was not until the 1990s that the receptors responsible for many of the actions of Δ9‐tetrahydrocannabinol, the main psychoactive ingredient of cannabis, were cloned. Since then, our knowledge of the endogenous cannabinoid system, its physiology, pharmacology and therapeutic potential have expanded enormously. In the present review, the cannabinoid system is described, with particular emphasis on the mechanisms of removal and metabolism of the endocannabinoid signalling molecule anandamide. The current literature shows that cells can accumulate anandamide, and that this process can be disrupted pharmacologically, but that the nature of the mechanism(s) involved remains a matter of some debate. The main enzyme for the hydrolysis of anandamide, fatty acid amide hydrolase, is well characterized, and molecules selectively inhibiting this enzyme have potential therapeutic utility in a number of areas, in particular for the treatment of pain conditions.
Auditors' Response to Political Connections and Cronyism in Malaysia
Authors: GUL FERDINAND A.
Published: October 2006

This paper extends the literature on the role of political economy in financial reporting and auditing by testing two hypotheses. The first hypothesis predicts that there will be a greater increase in audit effort and audit fees for Malaysian firms with political connections, as a result of the Asian financial crisis, than for non‐politically connected firms because these firms have a higher risk of financial misstatements. The second hypothesis predicts that the audit fees of politically connected firms will decline when capital controls are introduced by the government as a ploy to financially assist politically connected firms to rebound from the crisis, and thus reduces the risk of financial misstatements. The results show that there is a greater increase in audit fees for firms with political connections than for non‐politically connected firms as a result of the Asian financial crisis. However, there is a decline in audit fees for politically connected firms after the capital controls are implemented.
Synthesis and Electrical Characterization of the Polymorphic Indium Tin Oxide Nanocrystalline Powders
Authors: Seo Kyung‐Han , Lee Joon‐Hyung , Kim Jeong‐Joo , Bertoni M. I. , Ingram B. J. , Mason T. O.
Published: October 2006

Nanocrystalline powders of two indium tin oxide (ITO) polymorphs—rhombohedral and cubic—were prepared by a co‐precipitation process. The temperature and aging time of precipitates after co‐precipitation were controlled to obtain selectively the two different crystal structures. X‐ray diffraction and transmission electron microscopy were used to characterize the powders. The electrical conductivity of the two ITO powders was determined by the powder solution composite method. The conductivities obtained were 0.26±0.04 and 0.65±0.17 S/cm for the rhombohedral and cubic ITO samples, respectively, the first such report for the rhombohedral phase.
Domain Switching Under Cyclic Mechanical Loading in Lead Zirconate Titanate
Authors: Pojprapai (Imlao) Soodkhet , Jones Jacob L. , Hoffman Mark , Vogel Sven C.
Published: October 2006

The domain‐switching behavior of lead zirconate titanate (PZT) during mechanical cyclic loading between 10 and 150 MPa was investigated by in situ time‐of‐flight neutron diffraction. The domain‐switching behavior was represented by a change of the pole density distribution during cycling. With increasing number of cycles, domain switching becomes saturated, correlating with a decrease in the rate of remnant strain accumulation in the stress–strain curve. Moreover, a relationship was demonstrated between the macroscopic strain and that developed from ferroelastic domain switching. The contribution of ferroelastic strain to the macroscopic strain was calculated from an orientation average of the domain switching distributions and the c/a ratio. The results show that nearly 80% of macroscopic strain arises from ferroelastic domain switching during mechanical cyclic loading.
Effect of Polystyrene Addition on Freeze Casting of Ceramic/Camphene Slurry for Ultra‐High Porosity Ceramics with Aligned Pore Channels
Authors: Koh Young‐Hag , Lee Eun‐Jung , Yoon Byung‐Ho , Song Ju‐Ha , Kim Hyoun‐Ee , Kim Hae‐Won
Published: October 2006

We investigated the effect of polystyrene (PS) addition on the freezing behavior of a very dilute alumina/camphene slurry with an initial solid loading of 5 vol% for the fabrication of ultra‐high porosity ceramics with aligned pore channels. To accomplish this, slurries with various PS contents (10, 20, and 30 vol% in relation to the alumina powders) were prepared by ball milling at 60°C and then cast into molds at a constant temperature of 20°C. After removing the frozen camphene, the samples were heat treated to burn out the organic phases and sinter the alumina walls. The addition of the PS binder remarkably enhanced the green strength of the sample, making it possible to handle it without difficulty. All of the sintered samples showed ultra‐high porosities of >88% without the collapse of the porous structure, wherein the pore channels were completely interconnected. Three distinctive zones having different pore structures were observed, viz. the outer shell with elongated pores, the inner zone with long aligned pore channels, and the center with equiaxed pores. The content of the PS polymer significantly affected the pore morphologies in the three distinctive zones. In addition, it was found that the addition of the PS polymer was highly beneficial to the alignment of the pore channels.
Microscale Inhomogeneities in Aluminum Solution‐Doping of Silica‐Based Optical Fibers
Authors: Tang Feng Z. , McNamara Pamela , Barton Geoffrey W. , Ringer Simon P.
Published: October 2006

The microstructure of aluminum (Al) solution‐doped soot layers in modified chemical vapor deposition fabrication of silica‐based optical fibers has been studied. It is shown that such Al doping is predominantly determined by deposition temperature. Radial and longitudinal Al doping distributions have been investigated in soot layers, in fully sintered glass layers, and in collapsed preforms. Formation mechanisms are discussed.