bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of the glycine reuptake inhibitor R213129 on the central nervous system and on scopolamine-induced impairments in psychomotor and cognitive function in healthy subjects
Authors: Liem-Moolenaar M , Zoethout RWM , de Boer P , Schmidt M , de Kam ML , Cohen AF , Franson KL , van Gerven JMA
Published: February 2010

In this study the effects of R213129, a selective glycine transporter 1 inhibitor, on central nervous system function were investigated in healthy males in the absence and presence of scopolamine. This was a double-blind, placebo-controlled, 4-period crossover ascending dose study evaluating the following endpoints: body sway, saccadic and smooth pursuit eye movements, pupillometry, electroencephalography, visual analogue scales for alertness, mood, calmness and psychedelic effects, adaptive tracking, finger tapping, Visual and Verbal Learning Task, Stroop test, hormone levels and pharmacokinetics. R213129 dose levels were selected based on exposure levels that blocked the GlyT1 sites >50% in preclinical experiments. Forty-three of the 45 included subjects completed the study. Scopolamine significantly affected almost every central nervous system parameter measured in this study. R213129 alone compared with placebo did not elicit pharmacodynamic changes. R213129 had some small effects on scopolamine-induced central nervous system impairments. Scopolamine-induced finger tapping impairment was further enhanced by 3 mg R213129 with 2.0 taps/10 seconds (95% CI -4.0, -0.1), electroencephalography alpha power was increased by 10 mg R213129 with respectively 12.9% (0.7, 26.6%), scopolamine-induced impairment of the Stroop test was partly reversed by 10 mg R213129 with 59 milliseconds (-110, -7). Scopolamine produced robust and consistent effects in psychomotor and cognitive function in healthy volunteers. The most logical reason for the lack of R213129 effects seems to be that the central nervous system concentrations were too low. The effects of higher doses in healthy volunteers and the clinical efficacy in patients remain to be established.
Antagonist—agonist combinations as therapies for heroin addiction: back to the future?
Authors: Nutt David J
Published: February 2010

Psychopharmacology is a powerful approach to the treatment of many psychiatric disorders. In this article I discuss the conceptual and practical issues in relation to the use of mu opioid receptor agonist, antagonist and partial agonist drugs in the treatment of opioid addiction, as this is one therapeutic area where all three types of agents are currently available. The choice of pharmacological agent is largely determined by patient profile, existence of ongoing drug misuse, and the kinetics of the drugs available. These principles, however, can be applied to other disorders as and when other pharmacological approaches become refined in these areas.
Central nervous system effects of haloperidol on THC in healthy male volunteers
Authors: Liem-Moolenaar M , te Beek E T , de Kam M L , Franson K L , Kahn R S , Hijman R , Touw D , van Gerven J MA
Published: February 2010

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced ‘psychotomimetic’ effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced ‘high’ feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in ‘feeling high’. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers.
PG01037, a novel dopamine D3receptor antagonist, inhibits the effects of methamphetamine in rats
Authors: Higley Amanda E , Spiller Krista , Grundt Peter , Newman Amy Hauck , Kiefer Stephen W , Xi Zheng-Xiong , Gardner Eliot L
Published: February 2010

Our previous studies have shown that the selective dopamine D3receptor antagonists SB-277011A or NGB 2904 significantly attenuate cocaine self-administration under a progressive-ratio reinforcement schedule and cocaine-, methamphetamine- or nicotine-enhanced brain stimulation reward. However, the poor bioavailability of SB-277011A has limited its potential use in humans. In the present study, we investigated the effects of the novel D3receptor antagonist PG01037 on methamphetamine self-administration, methamphetamine-associated cue-induced reinstatement of drug seeking and methamphetamine-enhanced brain stimulation reward. Rats were allowed to intravenously self-administer methamphetamine under fixed-ratio 2 and progressive-ratio reinforcement conditions, and then the effects of PG01037 on methamphetamine self-administration and cue-induced reinstatement were assessed. Additional groups of rats were trained for intracranial electrical brain stimulation reward and the effects of PG01037 and methamphetamine on brain stimulation reward were assessed. Acute intraperitoneal administration of PG01037 (3, 10, 30 mg/kg) failed to alter methamphetamine or sucrose self-administration under fixed-ratio 2 reinforcement, but significantly lowered the break-point levels for methamphetamine or sucrose self-administration under progressive-ratio reinforcement. In addition, PG01037 significantly inhibited methamphetamine-associated cue-triggered reinstatement of drug-seeking behavior and methamphetamine-enhanced brain stimulation reward. These data suggest that the novel D3antagonist PG01037 significantly attenuates the rewarding effects as assessed by progressive-ratio self-administration and brain stimulation reward, and inhibits methamphetamine-associated cue-induced reinstatement of drug-seeking behavior These findings support the potential use of PG01037 or other selective D3antagonists in the treatment of methamphetamine addiction.
Decreased GABAAand GABABreceptor functional activity in cannabinoid CB1receptor knockout mice
Authors: Urigüen Leyre , García-Gutiérrez María S , Manzanares Jorge
Published: February 2010

The interaction between brain GABAergic and endocannabinoid systems was evaluated by examining the quantitative and functional status of GABAergic receptors in cannabinoid CB1receptor knockout (CB1-/-) mice. To this aim, GABAA([3H]-Muscimol binding assay), GABAB(baclofen-stimulated [35S]-GTPγS binding assay), GABAAα1, GABAAα2and GABAAγ2receptors gene expression (real-time reverse transcriptase polymerase chain reaction [PCR]) were carried out in CB1-/-and wild-type mice (CB1+/+). [3H]-Muscimol binding assays revealed significant reduction in the density of GABAAreceptors in CA2 (30%) and DG (28%) of the hippocampus, thalamus (40%), cingulate (28%) and motor cortex (35%) of CB1-/-mice. Functional activity of metabotropic GABABreceptors was measured by evaluating the ability of GABABagonist baclofen to stimulate [35S]-GTPγS binding. The results showed significant reduced [35S]-GTPγS binding in CA1 (61%), CA3 (51%) and DG (60%) of CB1-/-mice compared with CB1+/+mice. Real-time reverse transcriptase PCR was carried out for evaluating gene expression of α1, α2and γ2subunits of GABAAreceptor in the amygdala. The results showed significant reduced GABAAα1(50%) and GABAAα2(40%) receptor subunits gene expression in the amygdala of CB1-/-mice. No difference was observed in GABAAγ2receptor subunit gene expression. This study provides strong evidence of the involvement of CB1receptors in the control of GABAergic responses mediated by GABAAand GABABreceptors, and suggests a possible role of the endocannabinoid system in the regulation of anxiety-related disorders.
CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity
Authors: Gillman P Ken
Published: February 2010

Methylene blue has only recently been noted to cause severe central nervous system toxicity. Methylene blue is used for various conditions, including, intravenously, in methemoglobinemia, vasoplegia and as an aid to parathyroidectomy (at doses of 1–7.5 mg kg−1). This review of the current evidence concludes that 13 of 14 of the reported cases of CNS toxicity were serotonin toxicity that met the Hunter Serotonin Toxicity Criteria. That has important preventative and treatment implications. Serotonin toxicity is precipitated by the monoamine oxidase inhibitor (MAOI) property of methylene blue interacting with serotonin reuptake inhibitors. Serotonin toxicity is reviewed, using the lessons inherent in the methylene blue story and experience, to illustrate how the mechanisms and potency of serotonergic drugs interact to determine severity. Recent human data showed that an intravenous dose of only 0.75 mg kg−1of methylene blue produced a peak plasma concentration of 500 ng ml−1(1.6 µM), indicating that the concentration in the central nervous system reaches a level that inhibits monoamine oxidase A. That is consonant with the actual occurrence of severe serotonin toxicity in humans at the dose of only 1 mg kg−1. It seems that all proposed uses of methylene blue entail levels that block monoamine oxidase, so cessation of serotonin reuptake inhibitors should be very carefully considered before using methylene blue.
Exploring Sex Disparity in Sentencing Outcomes: A Focus on Narcotics Offenders in South Korea
Authors: Hartley Richard D. , Kwak Dae-Hoon , Park MiRang , Lee Min-Sik
Published: February 2010

Most research on sentencing outcomes reveals that legally relevant factors such as the seriousness of the offense and prior criminal record are primary determinants. There is, however, a substantial body of research that finds that extralegal factors such as a defendant’s sex also influence these outcomes. Most of these latter studies conclude that female defendants receive less severe outcomes compared to their male counterparts. Most of this research, however, is limited to Western societies. To extend this body of research, the current study examines sex differences in sentencing practices for a sample of narcotics offenders in South Korea. Results support previous research; female drug offenders in South Korea are generally treated more leniently than their male counterparts. Tests for interaction effects reveal that the defendant’s sex also interacts with other constellations of factors to produce lenient treatment for certain female defendants. These tests, however, also reveal that lenient sentence outcomes are not extended to all female defendants; those with prior drug convictions do not fare better than their male counterparts at the incarceration decision.
Acquired Microcephaly, Regression of Milestones, Mitochondrial Dysfunction, and Episodic Rigidity in a 46,XY Male With a De Novo MECP2 Gene Mutation
Authors: Condie John , Goldstein Joshua , Wainwright Mark S.
Published: February 2010

We report a case of acquired microcephaly in a male infant. Testing for mutations in the MECP2 gene identified a de novo hemizygous c.378-3C>G mutation at a highly conserved 3′ splice site, consistent with Rett syndrome. Other distinctive features included periodic hypertonicity, decreased mitochondrial complex III activity, and abnormal magnetic resonance imaging (MRI) T2 signal in the pons. Rett syndrome was originally described in females with a clinical phenotype of deceleration of head growth, abnormal hand movements, and developmental regression. The clinical diagnosis can now be supported by genetic testing for MECP2 mutations, and the phenotype of disorder has expanded. Cases of Rett syndrome in males are rare and a total of 17 such cases have been reported. This case extends the clinical phenotype of Rett syndrome in males and associates this mutation with mitochondrial dysfunction.
Prediction of Progressive Damage State at the Hot Spots using Statistical Estimation
Authors: Banerjee Sourav , Qing Xinlin P. , Beard Shawn , Chang Fu-Kuo
Published: February 2010

The conventional prediction of fatigue crack growth relies on a priori data set and hence, a calibration procedure is required. However, the occurrence of damage and the prediction of damage growth in real time are very unpredictable. Several factors inherently influence the wave signal and make it difficult for the user to interpret the data through direct comparison. To minimize this error in damage estimation, a statistical approach would be the best available solution. A model which can explicitly represent the a priori data set and can also estimate the output parameter (such as damage quantity) from the current data set is extremely important. Simultaneously, there should be a minimum power consumption for the proposed algorithm. Hence, in this effort a two-step analysis is adopted. First, the signal features are extracted using newly proposed discrete time energy model and then Gaussian mixture model (GMM) is used as a classification modeling technique to estimate and quantify the progressive damage. In this article, the effort is not limited to estimating the damage growth but extended to generate an ‘early alarm system’. The early alarm system is achieved by the damage occurrence identification and damage extent which can be calculated using the Mahalanobis distance. GMM is frequently used in the field of computer science for pattern recognition and classification. This would be the first attempt towards implementing such models for hot spot monitoring problems.
Adaptive Control to Mitigate Damage Impact on Structural Response
Authors: Bitaraf Maryam , Barroso Luciana R. , Hurlebaus Stefan
Published: February 2010

The use of semi-active devices for natural hazard mitigation is particularly attractive as they do not destabilize the structure and have the ability of adapting to varying usage patterns and loading conditions. However, even in the presence of supplemental control devices, extreme earthquake, wind loads, and deterioration caused by corrosion or fatigue may result in structural damage. Adaptive control approaches are attractive methods to control the structural performance of the structure as it can deal with these changes. In this study, first, the behavior of a 3-story building is controlled by a direct adaptive control approach using active devices, and then, magnetorheological (MR) dampers are controlled by the direct adaptive method. This control approach is used to reduce the impact of damage in the 3-story building. In the analysis of the structure, some stiffness reduction is assumed as a result of potential damage in different stories of the building. The controlled damaged structure responses under different ground motions are presented and compared with the uncontrolled damaged structure behavior. The goal of the adaptive control method in this research is to force the damaged structure to behave like an undamaged structure which performs acceptably. The effectiveness of this method in controlling the MR dampers is then verified.
Impact Damage of 3D Cellular Woven Composite from Unit-cell Level Analysis
Authors: Yuyuan Tang  , Baozhong Sun  , Bohong Gu
Published: February 2010

The high ratio of strength/area density of 3D cellular woven composite (3DCWC) leads the widely potential application of the composite in aircraft, vehicle, and sports facilities. The objectives of this investigation are to characterize the microstructures, impact responses, and failure modes of the 3DCWC under transverse impact. The 3D woven fabrics and composites were manufactured based on 3D angle-interlock woven fabric with cellular structures. The impact responses and energy absorption of the 3DCWC were tested with a modified split Hopkinson bar apparatus. A unit-cell model of the composite was established from the microstructure features, i.e., same fiber volume fraction and mechanical behaviors. A user subroutine VUMAT (FORTRAN Vectorized User-Material) was developed and connected with a commercial available finite element method (FEM) software package Abaqus/Explicit for calculating the impact responses of the composite. This subroutine describes the elasto-plastic constitutive equations of the unit-cell, maximum stress failure criteria, and critical damage area failure criteria. It was found that there is a good agreement of the impact load-displacement, failure modes between FEM calculation and experimental. This proves the validity of the unit-cell model, failure criteria and user-defined subroutine VUMAT. The user-defined subroutine VUMAT can also be extended to characterize the impact responses of the 3DCWC engineering structures.
Damage Micromechanics for Constitutive Relations and Failure of Microcracked Quasi-Brittle Materials
Authors: Feng Xi-Qiao , Yu Shou-Wen
Published: February 2010

This article addresses several issues in damage micromechanics for microcracked brittle or quasi-brittle solids, with major attention paid on summarizing some recent works of the present authors. First, we discuss the methods for characterizing evolutionary damage of microcracks and introduce the concept of orientation domain of microcrack growth. Second, we describe how to calculate the macroscopically effective constitutive relation of microcracking solids under complex loading. Third, the effective medium or effective field methods for estimating the effective elastic moduli of microcracked solids are formulated into a universal framework. Fourth, a subregion method is suggested to calculate the effective elastic moduli, fracture strength, and failure process of solids containing a large number and/or a high density of microcracks. Additionally, this method is combined with the finite element method to simulate the damage evolution and failure process of engineering structures.
On ‘possibility’
Authors: Guyer Jane I.
Published: February 2010

The article originates in a response to discuss ‘How Is Anthropology Going?’. Perceiving a new pattern in the almost 90 years looking backward and forward from my own undergraduate training, I concentrate on the recurrent concept of human ‘possibility’. Its changing referents are traced over four 20-year cycles, starting with Malinowski and Benedict (1920s and 1930s), moving to Gellner’s Thought and Change (1965), Marcus and Fischer’s Anthropology as Cultural Critique (1986), Graeber’s Possibilities (2008) and Rabinow’s Marking Time (2008). Particular attention is paid to the temporal horizons implied in the term and the forms of ethical, political and aesthetic agency one can infer from the orientations, tensions and attractions that horizons of possibility have inspired.
White Backlash, ‘Unfairness’ and Justifications of British National Party (BNP) Support
Authors: Rhodes James
Published: February 2010

In 2005, Roger Hewitt published White Backlash and the Politics of Multiculturalism . Using qualitative research conducted in Greenwich, London and via an engagement with political and media discourses, he traced the emergence of a new theme within white racism. This article will outline the origins and development of ‘white backlash’, from Conservative MP Enoch Powell’s infamous ‘Rivers of Blood’ speech in 1968 through Thatcherism, and examine the re-emergence of notions of ‘unfairness’ to whites as a result of the actions of both New Labour and the British National Party (BNP). Using qualitative interviews with BNP voters in Burnley, Lancashire, England, the way in which individuals sought to ‘justify’ their actions with recourse to notions of ‘unfairness’ and ‘equality’ will be examined. It will be suggested that BNP supporters viewed multiculturalism and its perceived allies, positive discrimination and political correctness, to be the harbingers of a policy that institutionalized the exclusion of white residents.
A random effect multiplicative heteroscedastic model for bacterial growth
Authors: Cao Ricardo , Francisco-Fernández Mario , Quinto Emiliano J
Published: February 2010

Background

Predictive microbiology develops mathematical models that can predict the growth rate of a microorganism population under a set of environmental conditions. Many primary growth models have been proposed. However, when primary models are applied to bacterial growth curves, the biological variability is reduced to a single curve defined by some kinetic parameters (lag time and growth rate), and sometimes the models give poor fits in some regions of the curve. The development of a prediction band (from a set of bacterial growth curves) using non-parametric and bootstrap methods permits to overcome that problem and include the biological variability of the microorganism into the modelling process.

Results

Absorbance data fromListeria monocytogenescultured at 22, 26, 38, and 42°C were selected under different environmental conditions of pH (4.5, 5.5, 6.5, and 7.4) and percentage of NaCl (2.5, 3.5, 4.5, and 5.5). Transformation of absorbance data to viable count data was carried out. A random effect multiplicative heteroscedastic model was considered to explain the dynamics of bacterial growth. The concept of a prediction band for microbial growth is proposed. The bootstrap method was used to obtain resamples from this model. An iterative procedure is proposed to overcome the computer intensive task of calculating simultaneous prediction intervals, along time, for bacterial growth. The bands were narrower below the inflection point (0-8 h at 22°C, and 0-5.5 h at 42°C), and wider to the right of it (from 9 h onwards at 22°C, and from 7 h onwards at 42°C). A wider band was observed at 42°C than at 22°C when the curves reach their upper asymptote. Similar bands have been obtained for 26 and 38°C.

Conclusions

The combination of nonparametric models and bootstrap techniques results in a good procedure to obtain reliable prediction bands in this context. Moreover, the new iterative algorithm proposed in this paper allows one to achieve exactly the prefixed coverage probability for the prediction band. The microbial growth bands reflect the influence of the different environmental conditions on the microorganism behaviour, helping in the interpretation of the biological meaning of the growth curves obtained experimentally.
An effective approach for identification of in vivo protein-DNA binding sites from paired-end ChIP-Seq data
Authors: Wang Congmao , Xu Jie , Zhang Dasheng , Wilson Zoe A , Zhang Dabing
Published: February 2010

Background

ChIP-Seq, which combines chromatin immunoprecipitation (ChIP) with high-throughput massively parallel sequencing, is increasingly being used for identification of protein-DNA interactions in vivo in the genome. However, to maximize the effectiveness of data analysis of such sequences requires the development of new algorithms that are able to accurately predict DNA-protein binding sites.

Results

Here, we present SIPeS (S ite I dentification from P aired-e nd S equencing), a novel algorithm for precise identification of binding sites from short reads generated by paired-end solexa ChIP-Seq technology. In this paper we used ChIP-Seq data from the Arabidopsis basic helix-loop-helix transcription factor ABORTED MICROSPORES (AMS), which is expressed within the anther during pollen development, the results show that SIPeS has better resolution for binding site identification compared to two existing ChIP-Seq peak detection algorithms, Cisgenome and MACS.

Conclusions

When compared to Cisgenome and MACS, SIPeS shows better resolution for binding site discovery. Moreover, SIPeS is designed to calculate the mappable genome length accurately with the fragment length based on the paired-end reads. Dynamic baselines are also employed to effectively discriminate closely adjacent binding sites, for effective binding sites discovery, which is of particular value when working with high-density genomes.
Sp1 and KLF15 regulate basal transcription of the human LRP5 gene
Authors: Li Jiangxia , Yang Yang , Jiang Baichun , Zhang Xiyu , Zou Yongxin , Gong Yaoqin
Published: February 2010

Background

LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear.

Results

In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs.

Conclusions

Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.
Transcriptional profiling of Actinobacillus pleuropneumoniae during the acute phase of a natural infection in pigs
Authors: Deslandes Vincent , Denicourt Martine , Girard Christiane , Harel Josée , Nash John HE , Jacques Mario
Published: February 2010

Background

Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, a respiratory disease which causes great economic losses worldwide. Many virulence factors are involved in the pathogenesis, namely capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In order to identify genes that are expressed in vivo during a natural infection, we undertook transcript profiling experiments with an A. pleuropneumoniae DNA microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of App serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in length.

Results

Transcriptional profiling of A. pleuropneumoniae recovered from the lung of a pig suffering from a natural infection or following growth of the bacterial isolate in BHI medium was performed. An RNA extraction protocol combining beadbeating and hot-acid-phenol was developed in order to maximize bacterial mRNA yields and quality following total RNA extraction from lung lesions. Nearly all A. pleuropneumoniae transcripts could be detected on our microarrays, and 150 genes were deemed differentially expressed in vivo during the acute phase of the infection. Our results indicate that, for example, gene apxIVA from an operon coding for RTX toxin ApxIV is highly up-regulated in vivo, and that two genes from the operon coding for type IV fimbriae (APL_0878 and APL_0879) were also up-regulated. These transcriptional profiling data, combined with previous comparative genomic hybridizations performed by our group, revealed that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and that 3 of them code for products that are predicted outer membrane proteins (genes irp and APL_0959, predicted to code for a TonB-dependent receptor and a filamentous hemagglutinin/adhesin respectively) or lipoproteins (gene APL_0920). Only 4 of 72 up-regulated genes had previously been identified in controled experimental infections.

Conclusions

These genes that we have identified as up-regulated in vivo, conserved across serotypes and coding for potential outer membrane proteins represent potential candidates for the development of a cross-protective vaccine against porcine pleuropneumonia.
Genome-wide investigation and functional characterization of the β-ketoadipate pathway in the nitrogen-fixing and root-associated bacterium Pseudomonas stutzeriA1501
Authors: Li Danhua , Yan Yongliang , Ping Shuzhen , Chen Ming , Zhang Wei , Li Liang , Lin Wenna , Geng Lizhao , Liu Wei , Lu Wei , Lin Min
Published: February 2010

Background

Soil microorganisms are mainly responsible for the complete mineralization of aromatic compounds that usually originate from plant products or environmental pollutants. In many cases, structurally diverse aromatic compounds can be converted to a small number of structurally simpler intermediates, which are metabolized to tricarboxylic acid intermediates via the β-ketoadipate pathway. This strategy provides great metabolic flexibility and contributes to increased adaptation of bacteria to their environment. However, little is known about the evolution and regulation of the β-ketoadipate pathway in root-associated diazotrophs.

Results

In this report, we performed a genome-wide analysis of the benzoate and 4-hydroxybenzoate catabolic pathways ofPseudomonas stutzeriA1501, with a focus on the functional characterization of the β-ketoadipate pathway. TheP. stutzeriA1501 genome contains sets of catabolic genes involved in the peripheral pathways for catabolism of benzoate (ben) and 4-hydroxybenzoate (pob), and in the catechol (cat) and protocatechuate (pca) branches of the β-ketoadipate pathway. A particular feature of the catabolic gene organization in A1501 is the absence of thecatRandpcaKgenes encoding a LysR family regulator and 4-hydroxybenzoate permease, respectively. Furthermore, the BenR protein functions as a transcriptional activator of thebenoperon, while transcription from thecatBCpromoter can be activated in response to benzoate. Benzoate degradation is subject to carbon catabolite repression induced by glucose and acetate in A1501. The HPLC analysis of intracellular metabolites indicated that low concentrations of 4-hydroxybenzoate significantly enhance the ability of A1501 to degrade benzoate.

Conclusions

The expression of genes encoding proteins involved in the β-ketoadipate pathway is tightly modulated by both pathway-specific and catabolite repression controls in A1501. This strain provides an ideal model system for further study of the evolution and regulation of aromatic catabolic pathways.
Genomic and evolutionary comparisons of diazotrophic and pathogenic bacteria of the order Rhizobiales
Authors: Carvalho Fabíola M , Souza Rangel C , Barcellos Fernando G , Hungria Mariangela , Vasconcelos Ana Tereza R
Published: February 2010

Background

Species belonging to the Rhizobiales are intriguing and extensively researched for including both bacteria with the ability to fix nitrogen when in symbiosis with leguminous plants and pathogenic bacteria to animals and plants. Similarities between the strategies adopted by pathogenic and symbiotic Rhizobiales have been described, as well as high variability related to events of horizontal gene transfer. Although it is well known that chromosomal rearrangements, mutations and horizontal gene transfer influence the dynamics of bacterial genomes, in Rhizobiales, the scenario that determine pathogenic or symbiotic lifestyle are not clear and there are very few studies of comparative genomic between these classes of prokaryotic microorganisms trying to delineate the evolutionary characterization of symbiosis and pathogenesis.

Results

Non-symbiotic nitrogen-fixing bacteria and bacteria involved in bioremediation closer to symbionts and pathogens in study may assist in the origin and ancestry genes and the gene flow occurring in Rhizobiales. The genomic comparisons of 19 species of Rhizobiales, including nitrogen-fixing, bioremediators and pathogens resulted in 33 common clusters to biological nitrogen fixation and pathogenesis, 15 clusters exclusive to all nitrogen-fixing bacteria and bacteria involved in bioremediation, 13 clusters found in only some nitrogen-fixing and bioremediation bacteria, 01 cluster exclusive to some symbionts, and 01 cluster found only in some pathogens analyzed. In BBH performed to all strains studied, 77 common genes were obtained, 17 of which were related to biological nitrogen fixation and pathogenesis. Phylogenetic reconstructions for Fix, Nif, Nod, Vir, and Trb showed possible horizontal gene transfer events, grouping species of different phenotypes.

Conclusions

The presence of symbiotic and virulence genes in both pathogens and symbionts does not seem to be the only determinant factor for lifestyle evolution in these microorganisms, although they may act in common stages of host infection. The phylogenetic analysis for many distinct operons involved in these processes emphasizes the relevance of horizontal gene transfer events in the symbiotic and pathogenic similarity.
Identification of genes associated with growth cessation and bud dormancy entrance using a dormancy-incapable tree mutant
Authors: Jiménez Sergio , Li Zhigang , Reighard Gregory L , Bielenberg Douglas G
Published: February 2010

Background

In many tree species the perception of short days (SD) can trigger growth cessation, dormancy entrance, and the establishment of a chilling requirement for bud break. The molecular mechanisms connecting photoperiod perception, growth cessation and dormancy entrance in perennials are not clearly understood. The peach [Prunus persica (L.) Batsch] evergrowing (evg) mutant fails to cease growth and therefore cannot enter dormancy under SD. We used the evg mutant to filter gene expression associated with growth cessation after exposure to SD. Wild-type and evg plants were grown under controlled conditions of long days (16 h/8 h) followed by transfer to SD (8 h/16 h) for eight weeks. Apical tissues were sampled at zero, one, two, four, and eight weeks of SD and suppression subtractive hybridization was performed between genotypes at the same time points.

Results

We identified 23 up-regulated genes in the wild-type with respect to the mutant during SD exposure. We used quantitative real-time PCR to verify the expression of the differentially expressed genes in wild-type tissues following the transition to SD treatment. Three general expression patterns were evident: one group of genes decreased at the time of growth cessation (after 2 weeks in SD), another that increased immediately after the SD exposure and then remained steady, and another that increased throughout SD exposure.

Conclusions

The use of the dormancy-incapable mutant evg has allowed us to reduce the number of genes typically detected by differential display techniques for SD experiments. These genes are candidates for involvement in the signalling pathway leading from photoperiod perception to growth cessation and dormancy entrance and will be the target of future investigations.
Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia
Authors: Grissa Oussama , Yessoufou Akadiri , Mrisak Inès , Hichami Aziz , Amoussou-Guenou Daniel , Grissa Abir , Djrolo François , Moutairou Kabir , Miled Abdelhedi , Khairi Hédi , Zaouali Monia , Bougmiza Iheb , Zbidi Aabdelkarim , Tabka Zouheir , Khan Naim A
Published: February 2010

Background

Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth.

Methods

30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR.

Results

The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women.

Conclusions

Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.
Comparative transfection of DNA into primary and transformed mammalian cells from different lineages
Authors: Maurisse Rosalie , De Semir David , Emamekhoo Hamid , Bedayat Babak , Abdolmohammadi Alireza , Parsi Hooman , Gruenert Dieter C
Published: February 2010

Background

The delivery of DNA into human cells has been the basis of advances in the understanding of gene function and the development of genetic therapies. Numerous chemical and physical approaches have been used to deliver the DNA, but their efficacy has been variable and is highly dependent on the cell type to be transfected.

Results

Studies were undertaken to evaluate and compare the transfection efficacy of several chemical reagents to that of the electroporation/nucleofection system using both adherent cells (primary and transformed airway epithelial cells and primary fibroblasts as well as embryonic stem cells) and cells in suspension (primary hematopoietic stem/progenitor cells and lymphoblasts). With the exception of HEK 293 cell transfection, nucleofection proved to be less toxic and more efficient at effectively delivering DNA into the cells as determined by cell proliferation and GFP expression, respectively. Lipofectamine and nucleofection of HEK 293 were essentially equivalent in terms of toxicity and efficiency. Transient transfection efficiency in all the cell systems ranged from 40%-90%, with minimal toxicity and no apparent species specificity. Differences in efficiency and toxicity were cell type/system specific.

Conclusions

In general, the Amaxa electroporation/nucleofection system appears superior to other chemical systems. However, there are cell-type and species specific differences that need to be evaluated empirically to optimize the conditions for transfection efficiency and cell survival.
General practitioners' opinions on how to improve treatment of mental disorders in primary health care. Interviews with one hundred Norwegian general practitioners
Authors: Mykletun Arnstein , Knudsen Ann Kristin , Tangen Tone , Øverland Simon
Published: February 2010

Background

Improvements in treatment of mental disorders are repeatedly called for. General practitioners (GPs) are responsible for the majority of treatment of mental disorders. Consequently, we interviewed GPs about their opinions on how treatment of mental disorders in primary health care contexts could be improved.

Methods

Among GPs affiliated within the Norwegian reimbursement system, we approached 353, and made contact with 246 GP's. One-hundred of these agreed to participate in our study, and 95 of them expressed opinions on how to improve treatment of mental disorders. The telephone interviews were based on open-ended questions, responses were transcribed continuously, and content analysis was applied. Results are presented both as frequency tables of common responses, and as qualitative descriptions and quotations of opinions.

Results

Nearly all (95%) of the GPs had suggestions on how to improve treatment of mental disorders in primary health care. Increased capacity in secondary health care was suggested by 59% of GPs. Suggestions of improved collaboration with secondary health care were also common (57%), as were improvements of GPs' skills and knowledge relevant for diagnosing and treating mental disorders (40%) and more time for patients with mental disorders in GP contexts (40%).

Conclusions

The GPs' suggestions are in line with international research and debate. It is thought-provoking that the majority of GPs call for increased capacity in secondary care, and also better collaboration with secondary care. Some GPs made comparisons to the health care system for physical disorders, which is described as better-functioning. Our study identified no simple short-term cost-effective interventions likely to improve treatment for mental disorders within primary health care. Under-treatment of mental disorders is, however, also associated with significant financial burdens.
A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior
Authors: Zhang Chuanfu , Xu Yuanyong , Jia Leili , Yang Yutao , Wang Yong , Sun Yansong , Huang Liuyu , Qiao Fei , Tomlinson Stephen , Liu Xuelin , Zhou Yusen , Song Hongbin
Published: February 2010

Background

Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.

Presentation of the hypothesis

Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.

Testing the hypothesis

CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via invivoand in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.

Implications of the hypothesis

CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.
Facilitation of Synaptic Transmission and Pain Responses by CGRP in the Amygdala of Normal Rats
Authors: Han Jeong S , Adwanikar Hita , Li Zhen , Ji Guangchen , Neugebauer Volker
Published: February 2010

Calcitonin gene-related peptide (CGRP) plays an important role in peripheral and central sensitization. CGRP also is a key molecule in the spino-parabrachial-amygdaloid pain pathway. Blockade of CGRP1 receptors in the spinal cord or in the amygdala has antinociceptive effects in different pain models. Here we studied the electrophysiological mechanisms of behavioral effects of CGRP in the amygdala in normal animals without tissue injury. Whole-cell patch-clamp recordings of neurons in the latero-capsular division of the central nucleus of the amygdala (CeLC) in rat brain slices showed that CGRP (100 nM) increased excitatory postsynaptic currents (EPSCs) at the parabrachio-amygdaloid (PB-CeLC) synapse, the exclusive source of CGRP in the amygdala. Consistent with a post-synaptic mechanism of action, CGRP increased amplitude, but not frequency, of miniature EPSCs and did not affect paired-pulse facilitation. CGRP also increased neuronal excitability. CGRP-induced synaptic facilitation was reversed by an NMDA receptor antagonist (AP5, 50 μM) or a PKA inhibitor (KT5720, 1 μM), but not by a PKC inhibitor (GF109203X, 1 μM). Stereotaxic administration of CGRP (10 μM, concentration in microdialysis probe) into the CeLC by microdialysis in awake rats increased audible and ultrasonic vocalizations and decreased hindlimb withdrawal thresholds. Behavioral effects of CGRP were largely blocked by KT5720 (100 μM) but not by GF109203X (100 μM). The results show that CGRP in the amygdala exacerbates nocifensive and affective behavioral responses in normal animals through PKA- and NMDA receptor-dependent postsynaptic facilitation. Thus, increased CGRP levels in the amygdala might trigger pain in the absence of tissue injury.
Isolated hepatic actinomycosis: a case report
Authors: Lall Thomas , Shehab Thomas M , Valenstein Paul
Published: February 2010

Introduction

Actinomyces are slow growing, non-spore forming, gram-positive, branching bacilli that thrive in anaerobic and microareophilic conditions. Actinomyces are more commonly associated with oral and cervicofacial infections. Hepatic involvement in infections of the abdomen (known as isolated hepatic actinomycosis) is rare, accounting for only 5% of all cases of actinomycosis.

Case presentation

We present the case of a 75-year-old Caucasian woman with a 3-month history of night sweats, fever, chills, abdominal bloating, anorexia, weight-loss, and early satiety. The patient was found to have isolated hepatic actinomycosis infection after undergoing a laparotomy with a biopsy of the liver. The patient has now recovered.

Conclusion

Isolated hepatic actinomycosis is a rare and often overlooked etiology for a liver mass. Given its subacute presentation and nondescript symptomatology, physicians should be aware of this differential and the potential pitfalls in diagnosis and management.