bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Haptic Macrophages in Regulation of Idiosyncratic Drug Reactions
Authors: Ju Cynthia
Published: January 2009

Idiosyncratic drug reactions (IDR) account for approximately 6%-10% of all adverse drug reactions. The unpredictable and serious nature of these reactions makes them a significant economic burden and safety concern to the health care community and the pharmaceutical industry. Clinical and laboratory evidence suggests that adverse immune responses against drug—protein adducts play a role in the pathogenesis of IDR. However, it remains unclear why only a small percentage of patients are susceptible to developing these reactions. We hypothesized that most patients develop immunological tolerance against drug—protein adducts as a default mechanism, and that IDRs can only occur when this tolerance is deficient or abrogated in susceptible individuals. Using a murine model of 2,4-dinitrochlorobenzene (DNCB)—induced delayed type hypersensitivity (DTH) reaction, our previously published data demonstrated that intravenous pretreatment of mice with dinitrophenyl-bovine serum albumin (DNP-BSA) induced immunological tolerance to subsequent DNCB sensitization, and that hepatic macrophages (Kupffer cells, KC) played an important role in mediating such tolerance. Further mechanistic investigation revealed that KC, acting as incompetent antigen-presenting cells, cannot elicit strong T cell reactions, and that they actively suppress T cell activation through production of prostaglandins. These findings suggest that KCs may play a critical role in regulating immune reactions within the liver and contributing to liver-mediated systemic immune tolerance.
Understanding Identity Theft
Authors: Copes Heith , Vieraitis Lynne M.
Published: January 2009

Researchers typically label acts as “white-collar” based on the respectable status of the offender (populist perspective) or on the characteristics of the offense (patrician perspective). However, some crimes, such as identity theft are not easily classified into either of these categories. The current study is designed to contextualize previous research and to situate the crime of identity theft within these two broad perspectives of white-collar crime. To do this, 59 identity thieves incarcerated in federal prisons were interviewed to offer the offenders’ perspectives on existing research describing characteristics of thieves and the techniques they employ to complete their crimes. Results show that identity thieves are a diverse group in terms of demographic characteristics (age, race, gender, and social class), employment, and criminal histories. They employed a variety of methods to both acquire information and convert it to cash. The most common methods of acquiring information were to buy it from others or to steal it from mailboxes or trashcans. They also used numerous methods to convert these identities into valuable goods, which included accessing existing accounts, applying for new credit, and obtaining loans. Thus, the findings show that identity theft is difficult to classify as white-collar crime.
Assessing Citizenship Behavior in Educational Contexts
Authors: Chen Sylvia Xiaohua , Carey Timothy Patrick
Published: January 2009

The present study developed a measure to assess citizenship behavior in educational settings and examined its antecedents and consequences in the cultural context. The results of this study provided discriminant validity for the newly extracted two-factor structure, that is, self-regulation and other-orientation. The authors identified both factors' motivation and personality correlates and added self-construals to predict citizenship behavior. Self-regulated citizenship behavior was positively related to intrinsic motivation and conscientiousness but negatively related to amotivation, whereas other-oriented citizenship behavior was significantly related to interdependent self-construal. Their differential effects on predicting life satisfaction showed that citizenship behavior has its own specific characteristics in educational contexts compared with industrial and organizational settings. Our findings also demonstrated the importance of cultural self-views in understanding communal behavior.
An Exploratory Study of Local Homeland Security Preparedness
Authors: Pelfrey William V.
Published: January 2009

As an artifact of the war on terror, local law enforcement agencies have been asked to serve as the “eyes and ears” of federal intelligence agencies. The federal Office of Domestic Preparedness (ODP) has assembled a set of guidelines to assist agencies in terrorism prevention and weapons of mass destruction identification. However, there is a dearth of metrics and measurement tools available to assess preparedness. Based on ODP guidelines, a methodology to tap preparedness levels is defined. Additionally, preliminary findings from an assessment of a large law enforcement agency are presented. Application of this methodology will enhance the preparedness of local agencies by identifying areas of strength and those areas which require attention. Once these deficit areas are defined, policy makers can define appropriate training and programmatic changes.
Assessing the Effect of Publicly Assisted Brownfield Redevelopment on Surrounding Property Values
Authors: De Sousa Christopher A. , Wu Changshan , Westphal Lynne M.
Published: January 2009

This study measures and compares the impact of publicly assisted brownfield redevelopment on nearby residential property values in Milwaukee and Minneapolis. It also examines the influence of land use, neighborhood characteristics, and other redevelopment factors on this impact. The research approach incorporates a hedonic method to quantify nearby property value effects at more than 100 brownfield projects, and stakeholder interviews are used to assess perceived impacts to real estate conditions. The results reveal that the spillover effect in terms of raising surrounding property values is significant in both quantity and geographic scope, as redevelopment led to a net increase of 11.4% in nearby housing prices in Milwaukee and 2.7% in Minneapolis. It also reveals that project size, value, and the amount of public funding have minor impacts on this effect; factors such as proximity to major roads, distance from rail, and higher incomes have greater positive impacts.
Demonstrating the Interplay of Leaders and Followers
Authors: Sronce Robin , Arendt Lucy A.
Published: January 2009

Classroom discussions of leadership often neglect the essential role of followers. These discussions do little to address the reality of our students’ predominant roles as followers within organizations. We describe the Origami Frog exercise, an experiential exercise that enables students to discover how follower behaviors impact group process and outcomes. Students are asked to play either leader or follower roles, and followers are asked to exhibit either Effective or Passive follower behaviors. Predictably, different follower roles interact with leader behaviors to yield different consequences. The Origami Frog exercise is complex enough that followers can significantly influence results and yet simple enough that the exercise and its relevant pre- and postdiscussion can be accomplished in a 50-min class.
The Effectiveness of a Career Decision-Making Course
Authors: Fouad Nadya , Cotter Elizabeth W. , Kantamneni Neeta
Published: January 2009

This study examined the effectiveness of a college career course designed to increase career decision-making confidence and facilitate career exploration. Participants were 73 students from a large Midwestern university (65.6% women, 34.4% men, mean age 18.56). Students were given questionnaires assessing career decision-making difficulties, career decision-making self-efficacy, and perception of career and educational barriers during the first and fifteenth weeks of the course. Repeated measures analyses were conducted to examine possible differences in students' responses before and after the course. Results indicated that on completion of the course students' career decision-making difficulties decreased, career self-efficacy increased, and perceptions of barriers did not change.
Nail Toxicity Induced by Cancer Chemotherapy
Authors: Gilbar Peter , Hain Alice , Peereboom Veta-Marie
Published: January 2009

Purpose. To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management.

Data sources. A search of MEDLINE and EMBASE (1966—2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references.

Data extraction. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity.

Data synthesis. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.

Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs. J Oncol Pharm Practice (2009) 15: 143—155.
Antineoplastic agent workplace contamination study: the Alberta Cancer Board Pharmacy perspective Phase III
Authors: Bigelow Susan , Schulz Heidi , Dobish Roxanne , Chambers Carole R
Published: January 2009

Objective. To continue with workplace contamination monitoring in the Alberta Cancer Board (ACB) pharmacy practice environment.

Setting. The ACB in the Canadian province of Alberta which includes two public tertiary centers and 19 associated community satellite sites based around the province in existing hospitals.

Methods. After the completion of a Phase 1 and Phase 11 study,1 which investigated the feasibility of routine monitoring of antineoplastic agent contamination in the pharmacy practice environment, it was decided to launch a Phase III study. The Phase III study would be done at the Cross Cancer Institute in the main pharmacy department as well as at a brand new satellite pharmacy within the CCI hospital. Samples would be taken in these areas as well as on the outer exterior of latex gloves worn to prepare cyclophosphamide and other antineoplastics.

Results. The result determined that the area in front of the biological safety cabinet in the main CCI pharmacy department as well as the exterior of the latex gloves showed evidence of cyclophosphamide contamination. The results from the sample taken in the new satellite pharmacy showed no evidence of cyclophosphamide contamination.

Conclusion. Results from this study prompted a decision to launch a Phase IV study to determine the feasibility within our network, for routine monitoring as well as sampling throughout the clean room beyond the BSC.
Sleep Enhances Off-line Spatial and Temporal Motor Learning After Stroke
Authors: Siengsukon Catherine , Boyd Lara A.
Published: January 2009

Background. Individuals with chronic stroke demonstrate sleep-dependent off-line motor learning of a continuous tracking task. However, it remains unclear which aspects of learned movements are preferentially enhanced by sleep (ie, spatial accuracy and/or the time lag of tracking). Objective. The purpose of this study was to investigate whether spatial tracking accuracy, temporal tracking accuracy, or both are enhanced by sleep during off-line motor learning after stroke. Methods. Individuals with chronic stroke and control participants either practiced a continuous tracking task in the evening and underwent retention testing the following morning (sleep groups) or practiced the task in the morning and underwent retention testing in the evening (no-sleep groups). Results. Individuals with stroke who slept between practice and retention testing demonstrated off-line improvements in both spatial and temporal elements of tracking at retention. Participants with a stroke who stayed awake between practice and retention testing did not demonstrate off-line improvements in either spatial tracking accuracy or the time lag of tracking. Control participants did not demonstrate sleep- or time-dependent enhancement of either component of the movement task. Time of day of testing was not a factor in practice related changes in motor performance. Conclusion. This study provides the first evidence that sleep enhances motor learning through both improved spatial tracking accuracy and anticipation of upcoming movements, as demonstrated by a reduction in the time lag of tracking in individuals following stroke. We propose that the cerebellum and hippocampus are likely important neural correlates associated with sleep-dependent off-line motor skill learning.
Training With Virtual Visual Feedback to Alleviate Phantom Limb Pain
Authors: Mercier Catherine , Sirigu Angela
Published: January 2009

Background. Performing phantom movements with visual virtual feedback, or mirror therapy, is a promising treatment avenue to alleviate phantom limb pain. However the effectiveness of this approach appears to vary from one patient to another. Objective. To assess the individual response to training with visual virtual feedback and to explore factors influencing the response to that approach. Methods. Eight male participants with phantom limb pain (PLP) resulting from either a traumatic upper limb amputation or a brachial plexus avulsion participated in this single case multiple baseline study. Training was performed 2 times per week for 8 weeks where a virtual image of a missing limb performing different movements was presented and the participant was asked to follow the movements with his phantom limb. Results. Patients reported an average 38% decrease in background pain on a visual analog scale (VAS), with 5 patients out of 8 reporting a reduction greater than 30%. This decrease in pain was maintained at 4 weeks postintervention in 4 of the 5 participants. No significant relationship was found between the long-term pain relief and the duration of the deafferentation or with the immediate pain relief during exposure to the feedback. Conclusions. These results support the use of training with virtual feedback to alleviate phantom limb pain. Our observations suggest that between-participant differences in the effectiveness of the treatment might be related more to a difference in the susceptibility to the virtual visual feedback, than to factors related to the lesion, such as the duration of the deafferentation.
Minorities and Disease Prevention in Pharmacy Practice
Authors: Lenz Thomas L.
Published: January 2009

Minority populations tend to have a disproportionately higher incidence of several chronic diseases such as hypertension, obesity, and diabetes mellitus. Knowing disease prevalence information about certain minority populations can help pharmacists and other health care professionals focus disease prevention strategies. In addition, knowing which factors influence participation and adherence to lifestyle intervention strategies can aid health care professionals when designing programs that can effectively work to prevent and control chronic diseases. Given the current timing and discussion on health care reform, pharmacists should take this opportunity to design inter-professional programs aimed at reducing the burdens of chronic disease with the use of lifestyle intervention strategies. This article presents these issues in greater detail.
Hyperaldosteronism in pregnancy
Authors: Escher Geneviève
Published: January 2009

Aldosterone is a key regulator of electrolyte and water homeostasis and plays a central role in blood pressure regulation. Hormonal changes during pregnancy, among them increased progesterone and aldosterone production, lead to the required plasma volume expansion of the maternal body as an accommodation mechanism for fetus growth. This review discusses the regulation of aldosterone production by aldosterone synthase (CYP11B2); the impact on aldosterone secretion due to the presence of a chimeric gene originating from a crossover between CYP11B1 and CYP11B2 in glucocorticoid remediable aldosteronism (GRA) — the inherited form of hypertension; enhanced aldosterone production in aldosterone-producing adenoma (APA); and idiopathic hyperaldosteronism (IHA). Features of hyperaldosteronism are also found in patients with apparent mineralocorticoid excess (AME), in which glucocorticoids exacerbate activation of the mineralocorticoid receptor (MR) because of a defect in the 11β-hydroxysteroid dehydrogenase type 2 enzyme. Regulation of aldosterone production and tissue-specific activation of the mineralocorticoid receptor are prerequisites for optimal control of body fluids and blood pressure during pregnancy and contribute largely to the wellbeing of the mother-to-be.
C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function
Authors: Bossi Fleur , Rizzi Lucia , Bulla Roberta , Debeus Alessandra , Tripodo Claudio , Picotti Paola , Betto Elena , Macor Paolo , Pucillo Carlo , Würzner Reinhard , Tedesco Francesco
Published: January 2009

We describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane-associated C7 (mC7) was indistinguishable from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinflammatory effect of SC5b-9. Our data disclose the possibility of a novel role of mC7 that acts as a trap for the late complement components to control excessive inflammation induced by SC5b-9.
IL-17–producing human peripheral regulatory T cells retain suppressive function
Authors: Beriou Gaëlle , Costantino Cristina M. , Ashley Charles W. , Yang Li , Kuchroo Vijay K. , Baecher-Allan Clare , Hafler David A.
Published: January 2009

Although implicated in antagonistic functions, both regulatory T cells (Tregs) and Th17 effector cells play an important role in controlling autoimmune pathogenesis. Paradoxically, recent studies indicate that Tregs have the capacity to produce interleukin-17 (IL-17), although the ability of these cells to retain their suppressive function remains unknown. Here we report that human Tregs within the CD4+CD45RA−CD25highCCR6+HLA-DR−FoxP3+ population produce IL-17 when activated in the presence of the proinflammatory cytokines IL-1β and IL-6, whereas IL-17 secretion was inhibited by TGFβ. To assess the ability of a single Treg to secrete IL-17 and to suppress in vitro immune function, we isolated clones from this population. We found that IL-17+/FoxP3+ Treg clones retain suppressive function and exhibit the plasticity to secrete IL-17 or suppress depending on the nature of the stimulus provided. IL-17 production by these Treg clones was accompanied by sustained FoxP3 expression and concomitant, but reversible, loss of suppressive activity. Our data demonstrate that at the single cell level a subset of in vitro suppressive FoxP3+ cells can be driven to secrete IL-17 under inflammatory conditions. These findings suggest a new mechanism by which inflammation can drive Tregs to secrete IL-17, thereby dampening suppression and promoting an inflammatory milieu.
Principal component tests: applied to temporal gene expression data
Authors: Zhang Wensheng , Fang Hong-Bin , Song Jiuzhou
Published: January 2009

Background

Clustering analysis is a common statistical tool for knowledge discovery. It is mainly conducted when a project still is in the exploratory phase without any priori hypotheses. However, the statistical significance testing between the clusters can be meaningful in helping the researchers to assess if the classification results from implementing a clustering algorithm need to be improved, even after the cluster number has been determined by a well-established criterion. This is important when we want to identify highly-specific patterns through classification.

Results

We proposed to use a principal component (PC) test, which is an implementation of an exact F statistic for the measures at multiple endpoints based on elliptical distribution theory, to assess the statistical significance between clusters. A challenge in the implementation is the choice of the number (q) of principal components to be considered, which can severely influence the statistical power of the method. We optimized the determination via validation according to a permutation test based on the clustering to be evaluated. The method was applied to a public dataset in classifying genes according to their temporal gene expression profiles.

Conclusion

The results demonstrated that the PC testing were useful for determining the optimal number of clusters.
Studying the unfolding process of protein G and protein L under physical property space
Authors: Zhao Liling , Wang Jihua , Dou Xianghua , Cao Zanxia
Published: January 2009

Background

The studies on protein folding/unfolding indicate that the native state topology is an important determinant of protein folding mechanism. The folding/unfolding behaviors of proteins which have similar topologies have been studied under Cartesian space and the results indicate that some proteins share the similar folding/unfolding characters.

Results

We construct physical property space with twelve different physical properties. By studying the unfolding process of the protein G and protein L under the property space, we find that the two proteins have the similar unfolding pathways that can be divided into three types and the one which with the umbrella-shape represents the preferred pathway. Moreover, the unfolding simulation time of the two proteins is different and protein L unfolding faster than protein G. Additionally, the distributing area of unfolded state ensemble of protein L is larger than that of protein G.

Conclusion

Under the physical property space, the protein G and protein L have the similar folding/unfolding behaviors, which agree with the previous results obtained from the studies under Cartesian coordinate space. At the same time, some different unfolding properties can be detected easily, which can not be analyzed under Cartesian coordinate space.
Analysis on relationship between extreme pathways and correlated reaction sets
Authors: Xi Yanping , Chen Yi-Ping Phoebe , Cao Ming , Wang Weirong , Wang Fei
Published: January 2009

Background

Constraint-based modeling of reconstructed genome-scale metabolic networks has been successfully applied on several microorganisms. In constraint-based modeling, in order to characterize all allowable phenotypes, network-based pathways, such as extreme pathways and elementary flux modes, are defined. However, as the scale of metabolic network rises, the number of extreme pathways and elementary flux modes increases exponentially. Uniform random sampling solves this problem to some extent to study the contents of the available phenotypes. After uniform random sampling, correlated reaction sets can be identified by the dependencies between reactions derived from sample phenotypes. In this paper, we study the relationship between extreme pathways and correlated reaction sets.

Results

Correlated reaction sets are identified for E. coli core, red blood cell and Saccharomyces cerevisiae metabolic networks respectively. All extreme pathways are enumerated for the former two metabolic networks. As for Saccharomyces cerevisiae metabolic network, because of the large scale, we get a set of extreme pathways by sampling the whole extreme pathway space. In most cases, an extreme pathway covers a correlated reaction set in an 'all or none' manner, which means either all reactions in a correlated reaction set or none is used by some extreme pathway. In rare cases, besides the 'all or none' manner, a correlated reaction set may be fully covered by combination of a few extreme pathways with related function, which may bring redundancy and flexibility to improve the survivability of a cell. In a word, extreme pathways show strong complementary relationship on usage of reactions in the same correlated reaction set.

Conclusion

Both extreme pathways and correlated reaction sets are derived from the topology information of metabolic networks. The strong relationship between correlated reaction sets and extreme pathways suggests a possible mechanism: as a controllable unit, an extreme pathway is regulated by its corresponding correlated reaction sets, and a correlated reaction set is further regulated by the organism's regulatory network.
Generation of a predicted protein database from EST data and application to iTRAQ analyses in grape (Vitis vinifera cv. Cabernet Sauvignon) berries at ripening initiation
Authors: Lücker Joost , Laszczak Mario , Smith Derek , Lund Steven T
Published: January 2009

Background

iTRAQ is a proteomics technique that uses isobaric tags for relative and absolute quantitation of tryptic peptides. In proteomics experiments, the detection and high confidence annotation of proteins and the significance of corresponding expression differences can depend on the quality and the species specificity of the tryptic peptide map database used for analysis of the data. For species for which finished genome sequence data are not available, identification of proteins relies on similarity to proteins from other species using comprehensive peptide map databases such as the MSDB.

Results

We were interested in characterizing ripening initiation ('veraison') in grape berries at the protein level in order to better define the molecular control of this important process for grape growers and wine makers. We developed a bioinformatic pipeline for processing EST data in order to produce a predicted tryptic peptide database specifically targeted to the wine grape cultivar, Vitis vinifera cv. Cabernet Sauvignon, and lacking truncated N- and C-terminal fragments. By searching iTRAQ MS/MS data generated from berry exocarp and mesocarp samples at ripening initiation, we determined that implementation of the custom database afforded a large improvement in high confidence peptide annotation in comparison to the MSDB. We used iTRAQ MS/MS in conjunction with custom peptide db searches to quantitatively characterize several important pathway components for berry ripening previously described at the transcriptional level and confirmed expression patterns for these at the protein level.

Conclusion

We determined that a predicted peptide database for MS/MS applications can be derived from EST data using advanced clustering and trimming approaches and successfully implemented for quantitative proteome profiling. Quantitative shotgun proteome profiling holds great promise for characterizing biological processes such as fruit ripening initiation and may be further improved by employing preparative techniques and/or analytical equipment that increase peptide detection sensitivity via a shotgun approach.
A gene catalogue for post-diapause development of an anhydrobiotic arthropod Artemia franciscana
Authors: Chen Wie-Hua , Ge Xiaomeng , Wang Weiwei , Yu Jun , Hu Songnian
Published: January 2009

Background

Diapause is a reversible state of developmental suspension and found among diverse taxa, from plants to animals, including marsupials and some other mammals. Although previous work has accumulated ample data, the molecular mechanism underlying diapause and reactivation from it remain elusive.

Results

Using Artemia franciscana, a model organism to study the development of post-diapause embryos in Arthropod, we sequenced random clones up to a total of 28,039 ESTs from four cDNA libraries made from dehydrated cysts and three time points after rehydration/reactivation, which were assembled into 8,018 unigene clusters. We identified 324 differentially-expressed genes (DEGs, P < 0.05) based on pairwise comparisons of the four cDNA libraries. We identified a group of genes that are involved in an anti-water-deficit system, including proteases, protease inhibitors, heat shock proteins, and several novel members of the late embryogenesis abundant (LEA) protein family. In addition, we classified most of the up-regulated genes after cyst reactivation into metabolism, biosynthesis, transcription, and translation, and this result is consistent with the rapid development of the embryo. Some of the specific expressions of DEGs were confirmed experimentally based on quantitative real-time PCR.

Conclusion

We found that the first 5-hour period after rehydration is most important for embryonic reactivation of Artemia. As the total number of expressed genes increases significantly, the majority of DEGs were also identified in this period, including a group of water-deficient-induced genes. A group of genes with similar functions have been described in plant seeds; for instance, one of the novel LEA members shares ~70% amino-acid identity with an Arabidopsis EM (embryonic abundant) protein, the closest animal relative to plant LEA families identified thus far. Our findings also suggested that not only nutrition, but also mRNAs are produced and stored during cyst formation to support rapid development after reactivation.
OxyGene: an innovative platform for investigating oxidative-response genes in whole prokaryotic genomes
Authors: Thybert David , Avner Stéphane , Lucchetti-Miganeh Céline , Chéron Angélique , Barloy-Hubler Frédérique
Published: January 2009

Background

Oxidative stress is a common stress encountered by living organisms and is due to an imbalance between intracellular reactive oxygen and nitrogen species (ROS, RNS) and cellular antioxidant defence. To defend themselves against ROS/RNS, bacteria possess a subsystem of detoxification enzymes, which are classified with regard to their substrates. To identify such enzymes in prokaryotic genomes, different approaches based on similarity, enzyme profiles or patterns exist. Unfortunately, several problems persist in the annotation, classification and naming of these enzymes due mainly to some erroneous entries in databases, mistake propagation, absence of updating and disparity in function description.

Description

In order to improve the current annotation of oxidative stress subsystems, an innovative platform named OxyGene has been developed. It integrates an original database called OxyDB, holding thoroughly tested anchor-based signatures associated to subfamilies of oxidative stress enzymes, and a new anchor-driven annotator, forab initiodetection of ROS/RNS response genes. All complete Bacterial and Archaeal genomes have been re-annotated, and the results stored in the OxyGene repository can be interrogated via a Graphical User Interface.

Conclusion

OxyGene enables the exploration and comparative analysis of enzymes belonging to 37 detoxification subclasses in 664 microbial genomes. It proposes a new classification that improves both the ontology and the annotation of the detoxification subsystems in prokaryotic whole genomes, while discovering new ORFs and attributing precise function to hypothetical annotated proteins. OxyGene is freely available at:http://www.umr6026.univ-rennes1.fr/english/home/research/basic/software
Insulin-like growth factor I promotes cord blood T cell maturation through monocytes and inhibits their apoptosis in part through interleukin-6
Authors: Law Helen KW , Tu Wenwei , Liu Enmei , Lau Yu Lung
Published: January 2009

Background

The functional immaturity of T cells contributes to the susceptibility of neonates to infections and the less severe graft-versus-host disease associated with cord blood (CB) transplantation. We have previously reported that insulin-like growth factor – I (IGF-I) promotes the phytohaemagglutinin (PHA)-induced CB T cell maturation and inhibits their apoptosis in mononuclear cell (MC) culture. We hypothesized that the effects of IGF-I may be mediated by accessory cells and soluble factors.

Results

This study showed that the kinetics of PHA-induced maturation in purified CD3+ T cell was delayed compared to that in CBMC. The addition of autologous CD14+ monocytes increased T cell maturation and potentiated the effect of IGF-I. The addition of IL-6 had no effect on CB T cell maturation but it reduced PHA-induced apoptosis significantly. We further demonstrated that the neutralisation of IL-6 in CBMC culture partially abrogated the anti-apoptotic effect of IGF-1 on T cells. The anti-apoptotic effect of IL-6 was not mediated via the reduction of Fas expression in T cell subsets.

Conclusion

Our results suggested that the maturation effect of IGF-1 is partially mediated by monocytes and the anti-apoptotic effect in part via IL-6. Further investigation is needed to explore the therapeutic use of IGF-I in enhancing neonatal immunity.
A novel DNA-binding protein modulating methicillin resistance in Staphylococcus aureus
Authors: Ender Miriam , Berger-Bächi Brigitte , McCallum Nadine
Published: January 2009

Background

Methicillin resistance in Staphylococcus aureus is conferred by the mecA-encoded penicillin-binding protein PBP2a. Additional genomic factors are also known to influence resistance levels in strain specific ways, although little is known about their contribution to resistance phenotypes in clinical isolates. Here we searched for novel proteins binding to the mec operator, in an attempt to identify new factor(s) controlling methicillin resistance phenotypes.

Results

Analysis of proteins binding to a DNA fragment containing the mec operator region identified a novel, putative helix-turn-helix DNA-binding protein, SA1665. Nonpolar deletion of SA1665, in heterogeneously methicillin resistant S. aureus (MRSA) of different genetic backgrounds, increased methicillin resistance levels in a strain dependent manner. This phenotype could be fully complemented by reintroducing SA1665 in trans. Northern and Western blot analyses, however, revealed that SA1665 had no visible influence on mecA transcription or amounts of PBP2a produced.

Conclusion

SA1665 is a new chromosomal factor which influences methicillin resistance in MRSA. Although SA1665 bound to the mecA promoter region, it had no apparent influence on mecA transcription or translation, suggesting that this predicted DNA-binding protein modulates resistance indirectly, most likely through the control of other genomic factors which contribute to resistance.
The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis
Authors: Chen Suet Nee , Ballantyne Christie M , Gotto Antonio M , Marian Ali J
Published: January 2009

Background

Case-control Genome-Wide Association Studies (GWAS) have identified single nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). The locus does not contain a clear candidate gene. Hence, the results of GWAS have raised an intense interest in delineating the basis for the observed association. We analyzed association of 4 SNPs at the 9p21 locus with the severity and progression of coronary atherosclerosis, as determined by serial quantitative coronary angiograms (QCA) in the well-characterized Lipoprotein Coronary Atherosclerosis Study (LCAS) population. The LCAS is a randomized placebo-control longitudinal follow-up study in patients with CAD conducted to test the effects of fluvastatin on progression or regression of coronary atherosclerosis.

Methods

Extensive plasma lipid levels were measured at the baseline and 2 1/2 years after randomization. Likewise serial QCA was performed at the baseline and upon completion of the study. We genotyped the population for 4 SNPs, previously identified as the susceptibility SNPs for CAD in GWAS, using fluorogenic 5' nuclease assays. We reconstructed the haplotypes using Phase 2, analyzed SNP and haplotype effects using the Thesias software as well as by the conventional statistical methods.

Results

Only Caucasians were included since they comprised 90% of the study population (332/371 with available DNA sample). The 4 SNPs at the 9p21 locus were in tight linkage disequilibrium, leading to 3 common haplotypes in the LCAS population. We found no significant association between quantitative indices of severity of coronary atherosclerosis, such as minimal lumen diameter and number of coronary lesions or occlusions and the 9p21 SNPs and haplotypes. Likewise, there was no association between quantitative indices of progression of coronary atherosclerosis and the SNPs or haplotypes. Similarly, we found no significant SNP or haplotype effect on severity and progression of coronary atherosclerosis.

Conclusion

We conclude the 4 SNPs at the 9p21 locus analyzed in this study do not impart major effects on the severity or progression of coronary atherosclerosis. The effect size may be very modest or the observed association of the CAD with SNPs at the 9p21 locus in the case-control GWAS reflect involvement of vascular mechanisms not directly related to the severity or progression of coronary atherosclerosis.
Outcome and patients' satisfaction after functional treatment of acute lateral ankle injuries at emergency departments versus family doctor offices
Authors: Schwab Patrik R , Benneker Lorin M , Eggli Stefan , Zimmermann Heinz , Exadaktylos Aristomenis K
Published: January 2009

Background

In some Western countries, more and more patients seek initial treatment even for minor injuries at emergency units of hospitals. The initial evaluation and treatment as well as aftercare of these patients require large amounts of personnel and logistical resources, which are limited and costly, especially if compared to treatment by a general practitioner. In this study, we investigated whether outsourcing from our level 1 trauma center to a general practitioner has an influence on patient satisfaction and compliance.

Methods

This prospective, randomized study, included n = 100 patients who suffered from a lateral ankle ligament injury grade I-II (16, 17). After radiological exclusion of osseous lesions, the patients received early functional treatment and were shown physical therapy exercises to be done at home, without immobilization or the use of stabilizing ortheses. The patients were randomly assigned into two groups of 50 patients each: Group A (ER): Follow-up and final examination in the hospital's emergency unit. Group B (GP): Follow-up by general practitioner, final examination at hospital's emergency unit. The patients were surveyed regarding their satisfaction with the treatment and outcome of the treatment.

Results

Female and male patients were equally represented in both groups. The age of the patients ranged from 16 – 64 years, with a mean age of 34 years (ER) and 35 years (GP). 98% (n = 98) of all patients were satisfied with their treatment, and 93% (n = 93) were satisfied with the outcome. For these parameters no significant difference between the two groups could be noted (p = 0.7406 and 0.7631 respectively). 39% of all patients acquired stabilizing ortheses like ankle braces (Aircast, Malleoloc etc.) on their own initiative. There was a not significant tendency for more self-acquired ortheses in the group treated by general practicioners (p = 0,2669).

Conclusion

Patients who first present at the ER with a lateral ankle ligament injury grade I-II can be referred to a general practitioner for follow-up treatment without affecting patient satisfaction regarding treatment and treatment outcome.
A resampling-based meta-analysis for detection of differential gene expression in breast cancer
Authors: Gur-Dedeoglu Bala , Konu Ozlen , Kir Serkan , Ozturk Ahmet Rasit , Bozkurt Betul , Ergul Gulusan , Yulug Isik G
Published: January 2009

Background

Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures.

Methods

A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis.

Results

The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results.

Conclusion

The proposed meta-analysis approach has the ability to detect a set of differentially expressed genes with the least amount of within-group variability, thus providing highly stable gene lists for class prediction. Increased statistical power and stringent filtering criteria used in the present study also make identification of novel candidate genes possible and may provide further insight to improve our understanding of breast cancer development.
Autocrine regulation of cell proliferation by estrogen receptor-alpha in estrogen receptor-alpha-positive breast cancer cell lines
Authors: Tan Huining , Zhong Yili , Pan Zhongzong
Published: January 2009

Background

Estrogen receptor-α (ERα) is essential for mammary gland development and is a major oncogene in breast cancer. Since ERα is not colocalized with the cell proliferation marker Ki-67 in the normal mammary glands and the majority of primary breast tumors, it is generally believed that paracrine regulation is involved in ERα mediated cell proliferation. In the paracrine model, ERα-positive cells don't proliferate but will release some paracrine growth factors to stimulate the neighboring cells to proliferate. In a subpopulation of cancer cells in some primary breast tumors, however, ERα does colocalize with the cell proliferation marker Ki-67, suggesting an autocrine regulation by ERα in some primary breast tumors.

Methods

Colocalization of ERα with Ki-67 in ERα-positive breast cancer cell lines (MCF-7, T47D, and ZR75-1) was evaluated by immunofluorescent staining. Cell cycle phase dependent expression of ERα was determined by co-immunofluorescent staining of ERα and the major cyclins (D, E, A, B), and by flow cytometry analysis of ERαhighcells. To further confirm the autocrine action of ERα, MCF-7 cells were growth arrested by ICI182780 treatment, followed by treatment with EGFR inhibitor, before estrogen stimulation and analyses for colocalization of Ki-67 and ERα and cell cycle progression.

Results

Colocalization of ERα with Ki-67 was present in all three ERα-positive breast cancer cell lines. Unlike that in the normal mammary glands and the majority of primary breast tumors, ERα is highly expressed throughout the cell cycle in MCF-7 cells. Without E2 stimulation, MCF-7 cells released from ICI182780 treatment remain at G1 phase. E2 stimulation of ICI182780 treated cells, however, promotes the expression and colocalization of ERα and Ki-67 as well as the cell cycle progressing through the S and G2/M phases. Inhibition of EGFR signaling does not inhibit the autocrine action of ERα.

Conclusion

Our data indicate that ERα can mediate estrogen-induced cell proliferation in an autocrine mode in ERα-positive breast cancer cell lines. All of the three ERα-positive cell lines used in our study showed colocalization of ERα and Ki-67, indicating that these cell lines might be originated from primary tumor cells with autocrine regulation.
Depression and anxiety as major determinants of neck pain: a cross-sectional study in general practice
Authors: Blozik Eva , Laptinskaya Daria , Herrmann-Lingen Christoph , Schaefer Helene , Kochen Michael M , Himmel Wolfgang , Scherer Martin
Published: January 2009

Background

Although psychosocial factors are known to be highly linked with neck pain, current therapies focus on somatically based interventions such as medicinal or manipulatory therapies. This study examines how socio-demographic, psychosocial and medical history and health-promoting lifestyle factors interact with neck pain in general practice patients.

Methods

This is a cross-sectional survey including 448 patients from a general practice setting in Germany. Participants completed a comprehensive questionnaire including the Neck Pain and Disability Scale German version (NPAD-d) and the Hospital Anxiety and Depression Scale. Crude and adjusted regression analyses were done to assess the relationship between neck pain and socio-demographic, psychosocial and medical history and health-promoting lifestyle factors.

Results

Both in crude and adjusted regression analyses, depression and anxiety were highly significantly linked with increasing levels of neck pain. Educational level, deficits in social support and physical exercise were associated with neck pain in bivariate analyses, but these associations did not persist with adjustment for depression and anxiety. When investigating levels of depression and anxiety by NPAD-d quartile subgroups, those who were identified to have depressive mood or to be anxious were very likely to be in the group with the highest levels of neck pain.

Conclusion

The higher the neck pain level, the more attention should be paid to psychosocial distress as a related burden. Further research is needed to elucidate the causality and the direction of the association between psychosocial distress and neck pain and to determine the benefit of psychosocial interventions.