bluuebunny/crossref_metadata_2025_split huggingface dataset:
PhiC31 integrase mediates integration in cultured synovial cells and enhances gene expression in rabbit joints
Authors: Keravala Annahita , Portlock Joylette L. , Nash Joan A. , Vitrant David G. , Robbins Paul D. , Calos Michele P. 
Published: June 2006

AbstractBackgroundGene transfer to synovium in joints has been shown to be an effective approach for treating pathologies associated with rheumatoid arthritis (RA) and related joint disorders. However, the efficiency and duration of gene delivery has been limiting for successful gene therapy for arthritis. The transient gene expression that often accompanies non‐viral gene delivery can be prolonged by integration of vector DNA into the host genome. We report a novel approach for non‐viral gene therapy to joints that utilizes phage ϕC31 integrase to bring about unidirectional genomic integration.MethodsRabbit and human synovial cells were co‐transfected with a plasmid expressing ϕC31 integrase and a plasmid containing the transgene and an attB site. Cells were cultured with or without G418 selection and the number of neo‐resistant colonies or eGFP cells determined, respectively. Plasmid rescue, PCR query, and DNA sequence analysis were performed to reveal integration sites in the rabbit and human genomes. For in vivo studies, attB‐reporter gene plasmids and a plasmid expressing ϕC31 integrase were intra‐articularly injected into rabbit knees. Joint sections were used for histological analysis of β‐gal expression, and synovial cells were isolated to measure luciferase expression.ResultsWe demonstrated that co‐transfection of a plasmid expressing ϕC31 integrase with a plasmid containing the transgene and attB increased the frequency of transgene expression in rabbit synovial fibroblasts and primary human RA synoviocytes. Plasmid rescue and DNA sequence analysis of plasmid‐chromosome junctions revealed integration at endogenous pseudo attP sequences in the rabbit genome, and PCR query detected integration at previously characterized integration sites in the human genome. Significantly higher levels of transgene expression were detected in vivo in rabbit knees after intra‐articular injection of attB‐reporter gene plasmids and a plasmid expressing ϕC31 integrase.ConclusionThe ability of ϕC31 integrase to facilitate genomic integration in synovial cells and increase transgene expression in the rabbit synovium suggests that, in combination with more efficient DNA delivery methods, this integrase system could be beneficial for treatment of rheumatoid arthritis and other joint disorders. Copyright © 2006 John Wiley & Sons, Ltd.
Activation‐induced cytidine deaminase (AID) is expressed in normal spermatogenesis but only infrequently in testicular germ cell tumours
Authors: Schreck S , Buettner M , Kremmer E , Bogdan M , Herbst H , Niedobitek G 
Published: June 2006

AbstractActivation‐induced cytidine deaminase (AID) is essential for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes in antigen‐dependent B‐cell maturation. SHM is not restricted to immunoglobulin gene loci, raising the possibility of a function for AID in other cell types. In this study, it is shown that AID is expressed in spermatocytes in the human testis. AID was mostly cytoplasmic but nuclear AID was also observed in a proportion of cells, in keeping with the DNA deamination model of AID function. Intratubular germ cell neoplasia unclassified (IGCNU), the precursor lesion of testicular cancers, was AID‐negative. Seminomas also lacked AID expression. Nuclear and cytoplasmic AID expression was observed in three of 32 mixed non‐seminomatous germ cell tumours. The results provide evidence for a physiological role for AID outside the immune system. AID expression in spermatocytes points to a role in meiosis. It remains uncertain whether AID may also contribute to the genetic aberrations characteristically found in testicular germ cell tumours. The consistent absence of detectable AID expression in atypical spermatogonia of IGCNU and its rare expression in germ cell tumours suggest that continued expression of AID is not involved in the pathogenesis of germ cell tumours. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Molecular dynamics study of conformational changes in human serum albumin by binding of fatty acids
Authors: Fujiwara Shin‐ichi , Amisaki Takashi 
Published: June 2006

AbstractHuman serum albumin (HSA) binds with fatty acids under normal physiologic conditions. To date, there is little published information on the tertiary structure of HSA–fatty acid complex in aqueous solution. In the present study, we used molecular dynamics (MD) simulations to elucidate possible structural changes of HSA brought about by the binding of fatty acids. Both unliganded HSA and HSA–fatty acid complex models for MD calculations were constructed based on the X‐ray crystal structures. Five myristates (MYRs) were bound in the HSA–fatty acid complex model. In the present MD study, the motion of domains I and III caused by the binding of MYR molecules increased the radius of gyration of HSA. Root‐mean‐square fluctuations from the MD simulations revealed that the atomic fluctuations of the specific amino acids at drug‐binding site I that can regulate the drug‐binding affinity were increased by the binding of MYR molecules. Primary internal motions, characterized by the first three principal components, were observed mainly at domains I and III in the principal component analysis for trajectory data. The directional motion projected on the first principal component of unliganded HSA was conserved in HSA–MYR complex as the third principal directional motion with higher frequency. However, the third principal directional motion in unliganded HSA turned into the first principal directional motion with lower frequency in the HSA–MYR complex. Thus, the present MD study provides insights into the possible conformational changes of HSA caused by the binding of fatty acids. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Assessing the combined effect of asbestos exposure and smoking on lung cancer: a Bayesian approach
Authors: Wraith D. , Mengersen K. 
Published: June 2006

AbstractWe review the literature on the combined association between lung cancer and two environmental exposures, asbestos exposure and smoking, and explore a Bayesian approach to assess evidence of interaction between the exposures. The meta‐analysis combines separate indices of additive and multiplicative relationships and multivariate relative risk estimates. By making inferences on posterior probabilities we can explore both the form and strength of interaction. This analysis may be more informative than providing evidence to support one relation over another on the basis of statistical significance. Overall, we find evidence for a more than additive and less than multiplicative relation. Copyright © 2006 John Wiley & Sons, Ltd.
NABP1, a novel RORγ-regulated gene encoding a single-stranded nucleic-acid-binding protein
Authors: Kang Hong Soon , Beak Ju Youn , Kim Yong-Sik , Petrovich Robert M. , Collins Jennifer B. , Grissom Sherry F. , Jetten Anton M. 
Published: June 2006

RORγ2 (retinoid-related orphan receptor γ2) plays a critical role in the regulation of thymopoiesis. Microarray analysis was performed in order to uncover differences in gene expression between thymocytes of wild-type and RORγ−/− mice. This analysis identified a novel gene encoding a 22 kDa protein, referred to as NABP1 (nucleic-acid-binding protein 1). This subsequently led to the identification of an additional protein, closely related to NABP1, designated NABP2. Both proteins contain an OB (oligonucleotide/oligosaccharide binding) motif at their N-terminus. This motif is highly conserved between the two proteins. NABP1 is highly expressed in the thymus of wild-type mice and is greatly suppressed in RORγ−/− mice. During thymopoiesis, NABP1 mRNA expression is restricted to CD4+CD8+ thymocytes, an expression pattern similar to that observed for RORγ2. These observations appear to suggest that NABP1 expression is regulated either directly or indirectly by RORγ2. Confocal microscopic analysis showed that the NABP1 protein localizes to the nucleus. Analysis of nuclear proteins by size-exclusion chromatography indicated that NABP1 is part of a high molecular-mass protein complex. Since the OB-fold is frequently involved in the recognition of nucleic acids, the interaction of NABP1 with various nucleic acids was examined. Our results demonstrate that NABP1 binds single-stranded nucleic acids, but not double-stranded DNA, suggesting that it functions as a single-stranded nucleic acid binding protein.
Gastrointestinal hormones regulating appetite
Authors: Chaudhri Owais , Small Caroline , Bloom Steve 
Published: June 2006

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance.Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation.Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood–brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain–gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance.The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain–gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.
Molecular Changes Occurring during Acquisition of Abscission Competence following Auxin Depletion in Mirabilis jalapa
Authors: Meir Shimon , Hunter Donald A. , Chen Jen-Chih , Halaly Vita , Reid Michael S. 
Published: June 2006

Abstract
To understand how auxin regulates sensitivity of abscission zone (AZ) tissues to ethylene, we used a polymerase chain reaction-based subtractive approach to identify gene transcripts in Mirabilis jalapa AZs that changed in abundance during the time the zones became competent to abscise in response to exogenous ethylene. Transcript expression was then examined in leaf and stem AZs over the period they became ethylene competent following indole-3-acetic acid (IAA) depletion either by leaf deblading, treatment with the IAA transport inhibitor naphthylphthalamic acid, or cutting the stem above a node (decapitation). Transcripts down-regulated by deblading/decapitation included Mj-Aux/IAA1 and Mj-Aux/IAA2, encoding Aux/IAA proteins, and three other transcripts showing highest identity to a polygalacturonase inhibitor protein, a β-expansin, and a β-tubulin. Application of IAA to the cut end of petioles or stumps inhibited abscission, and prevented the decline in the levels of transcripts in both AZs. Transcripts up-regulated in the AZ following deblading/decapitation or treatment with naphthylphthalamic acid were isolated from plants pretreated with 1-methylcyclopropene before deblading to help select against ethylene-induced genes. Some of the up-regulated transcripts showed identity to proteins associated with ethylene or stress responses, while others did not show homology to known sequences. Sucrose infiltration of stem stumps enhanced abscission following ethylene treatment and also enhanced the induction of some of the up-regulated genes. Our results demonstrate a correlation between acquisition of competence to respond to ethylene in both leaf and stem AZs, and decline in abundance of auxin regulatory gene transcripts.
Plastid Movement Impaired 2, a New Gene Involved in Normal Blue-Light-Induced Chloroplast Movements in Arabidopsis
Authors: Luesse Darron R. , DeBlasio Stacy L. , Hangarter Roger P. 
Published: June 2006

Abstract
Chloroplasts move in a light-dependent manner that can modulate the photosynthetic potential of plant cells. Identification of genes required for light-induced chloroplast movement is beginning to define the molecular machinery that controls these movements. In this work, we describe plastid movement impaired 2 (pmi2), a mutant in Arabidopsis (Arabidopsis thaliana) that displays attenuated chloroplast movements under intermediate and high light intensities while maintaining a normal movement response under low light intensities. In wild-type plants, fluence rates below 20 μmol m−2 s−1 of blue light lead to chloroplast accumulation on the periclinal cell walls, whereas light intensities over 20 μmol m−2 s−1 caused chloroplasts to move toward the anticlinal cell walls (avoidance response). However, at light intensities below 75 μmol m−2 s−1, chloroplasts in pmi2 leaves move to the periclinal walls; 100 μmol m−2 s−1 of blue light is required for chloroplasts in pmi2 to move to the anticlinal cell walls, indicating a shift in the light threshold for the avoidance response in the mutant. The pmi2 mutation has been mapped to a gene that encodes a protein of unknown function with a large coiled-coil domain in the N terminus and a putative P loop. PMI2 shares sequence and structural similarity with PMI15, another unknown protein in Arabidopsis that, when mutated, causes a defect in chloroplast avoidance under high-light intensities.
The Arabidopsis Flavin-Dependent Monooxygenase FMO1 Is an Essential Component of Biologically Induced Systemic Acquired Resistance
Authors: Mishina Tatiana E. , Zeier Jürgen 
Published: June 2006

Abstract
Upon localized attack by necrotizing pathogens, plants gradually develop increased resistance against subsequent infections at the whole-plant level, a phenomenon known as systemic acquired resistance (SAR). To identify genes involved in the establishment of SAR, we pursued a strategy that combined gene expression information from microarray data with pathological characterization of selected Arabidopsis (Arabidopsis thaliana) T-DNA insertion lines. A gene that is up-regulated in Arabidopsis leaves inoculated with avirulent or virulent strains of the bacterial pathogen Pseudomonas syringae pv maculicola (Psm) showed homology to flavin-dependent monooxygenases (FMO) and was designated as FMO1. An Arabidopsis knockout line of FMO1 proved to be fully impaired in the establishment of SAR triggered by avirulent (Psm avrRpm1) or virulent (Psm) bacteria. Loss of SAR in the fmo1 mutants was accompanied by the inability to initiate systemic accumulation of salicylic acid (SA) and systemic expression of diverse defense-related genes. In contrast, responses at the site of pathogen attack, including increases in the levels of the defense signals SA and jasmonic acid, camalexin accumulation, and expression of various defense genes, were induced in a similar manner in both fmo1 mutant and wild-type plants. Consistently, the fmo1 mutation did not significantly affect local disease resistance toward virulent or avirulent bacteria in naive plants. Induction of FMO1 expression at the site of pathogen inoculation is independent of SA signaling, but attenuated in the Arabidopsis eds1 and pad4 defense mutants. Importantly, FMO1 expression is also systemically induced upon localized P. syringae infection. This systemic up-regulation is missing in the SAR-defective SA pathway mutants sid2 and npr1, as well as in the defense mutant ndr1, indicating a close correlation between systemic FMO1 expression and SAR establishment. Our findings suggest that the presence of the FMO1 gene product in systemic tissue is critical for the development of SAR, possibly by synthesis of a metabolite required for the transduction or amplification of a signal during the early phases of SAR establishment in systemic leaves.
Beyond the Technocrat? The Professional Expert in Development Practice
Authors: Wilson Gordon 
Published: June 2006

AbstractThis article traces the use of the term ‘technocratic’ to describe development practice, and the concomitant use of ‘technocrat’ to describe professional experts who engage in development work. It locates the use of these terms as pejorative labels within understandings of professional experts as part of an apparatus of governmentality that depoliticizes development intervention. It argues, however, that such understandings miss the crucial point of engagement in development practice between these agents and other actors which opens ‘learning spaces’ that have the potential for a range of outcomes.
Contingency knowledge is necessary for learned motivated behaviour in humans: relevance for addictive behaviour
Authors: Hogarth Lee , Dickinson Anthony , Hutton Sam B. , Bamborough Helen , Duka Theodora 
Published: June 2006

ABSTRACTAims  Many forms of human conditioned behaviour depend upon explicit knowledge of the predictive contingency between stimuli, responses and the reinforcer. However, it remains uncertain whether the conditioning of three key behaviours in drug addiction—selective attention, instrumental drug‐seeking behaviour and emotional state—are dependent upon contingency knowledge. To test this possibility, we employed an avoidance procedure to generate rapidly these three forms of conditioned behaviour without incurring the methodological problems of drug conditioning.Design  In two experiments, participants (16 students) were trained on a schedule in which one stimulus (S +) predicted the occurrence of a startling noise, which could be cancelled by performing an instrumental avoidance response.Measurements  The allocation of attention to the S + and the rate and probability of the avoidance response in the presence of S + were measured. Following training, participants were tested for their knowledge of the stimulus–noise contingencies arranged in the study and rated the emotional qualities of the stimuli. Findings  Both experiments showed that S + gained control of selective attention, instrumental avoidance behaviour and subjective anxiety, but only in participants who reported explicit knowledge of the Pavlovian contingency between the S + and the startling noise.Conclusions  The implication of the present findings is that the control of selective attention, instrumental drug‐seeking behaviour and emotional state by drug‐paired stimuli is mediated by cognitive knowledge of the predictive contingency between the stimulus and the drug.
Effect of oral clarithromycin on gall‐bladder motility in normal subjects and those with gall‐stones
Authors: SENGUPTA S. , MODAK P. , McCAULEY N. , O'DONNELL L. J. D. 
Published: June 2006

SummaryBackgroundMotilin receptor stimulation with erythromycin has been shown to have a prokinetic effect on gall‐bladder motility in human beings.AimTo find out whether oral clarithromycin has similar prokinetic activity to erythromycin on fasting and postprandial gall‐bladder emptying in normal humans and those with gall‐stone disease.MethodsIn a blinded two‐way crossover study clarithromycin 500 mg and a placebo were administered to 10 normal subjects and 10 subjects with gall‐stone disease. Gall‐bladder volumes were assessed in the fasting and postprandial state.ResultsFasting volumes were significantly less following clarithromycin administration in both normal subjects and subjects with gall‐stones compared with placebo (12.1 ± 1.8 mL vs. 17.8 ± 2.0 mL, P < 0.05 and 16.7 ± 2 mL vs. 26.8 ± 7.2 mL, P < 0.02, mean ± S.E.M). Postprandial volumes were also significantly less following clarithromycin administration. Ejection fraction significantly increased following clarithromycin in both normal subjects (66 ± 5.8% vs. 37 ± 5.9%, P = 0.02) and subjects with gall‐stones (45 ± 3.2 vs. 20 ± 1.6%, P < 0.02).ConclusionClarithromycin enhances both fasting and postprandial gall‐bladder contraction in normal humans and also in those with gall‐stone disease.
Systematic review: does gastro‐oesophageal reflux disease progress?
Authors: FULLARD M. , KANG J. Y. , NEILD P. , POULLIS A. , MAXWELL J. D. 
Published: June 2006

SummaryBackgroundGastro‐oesophageal reflux disease affects approximately 20% of western populations. Barrett's oesophagus, associated with severe gastro‐oesophageal reflux disease, is premalignant and regular endoscopic surveillance is generally performed. In contrast, mild gastro‐oesophageal reflux disease is thought not to progress and is not generally subjected to endoscopic follow‐up.AimTo investigate whether gastro‐oesophageal reflux disease progresses endoscopically.MethodsSystematic review of the literature.ResultsWell‐designed prospective studies are few, diagnostic criteria were not always standardized, management strategies varied and various sources of bias could not be excluded. Whilst most patients do not progress to more severe forms of gastro‐oesophageal reflux disease, and some cases actually regress, progression is seen in a small proportion of patients. Annual progression rates for non‐erosive gastro‐oesophageal reflux disease developing erosive oesophagitis ranged from 0% to 30%. About 1–22% of patients with mild erosive oesophagitis developed more severe inflammation annually, while 1–13% of patients with erosive oesophagitis developed Barrett's oesophagus each year.ConclusionAlthough most patients with gastro‐oesophageal reflux disease do not progress, and some actually regress, progression does occur in a minority. Better data are required to determine whether patients with mild gastro‐oesophageal reflux disease would benefit from increased surveillance with the aim of detecting more advanced disease.