bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coxsackievirus B3 Proteins Directionally Complement Each Other To Downregulate Surface Major Histocompatibility Complex Class I
Authors: Cornell Christopher T. , Kiosses William B. , Harkins Stephanie , Whitton J. Lindsay 
Published: April 2007

ABSTRACT

Picornaviruses carry a small number of proteins with diverse functions that subvert and exploit the host cell. We have previously shown that three coxsackievirus B3 (CVB3) proteins (2B, 2BC, and 3A) target the Golgi complex and inhibit protein transit. Here we investigate these effects in more detail and evaluate the distribution of major histocompatibility complex (MHC) class I molecules, which are critical mediators of the CD8
+
T-cell response. We report that concomitant with viral protein synthesis, MHC class I surface expression is rapidly downregulated during infection. However, this phenomenon may not result solely from inhibition of anterograde trafficking; we propose a new mechanism whereby the CVB3 2B and 2BC proteins upregulate the internalization of MHC class I (and possibly other surface proteins), perhaps by focusing of endocytic vesicles at the Golgi complex. Thus, our findings indicate that CVB3 carries at least three nonstructural proteins that directionally complement one another; 3A disrupts the Golgi complex to inhibit anterograde transport, while 2B and/or 2BC upregulates endocytosis, rapidly removing proteins from the cell surface. Taken together, these effects may render CVB3-infected cells invisible to CD8
+
T cells and untouchable by many antiviral effector molecules. This has important implications for immune evasion by CVB3.
Effects of Viral Strain, Transgene Position, and Target Cell Type on Replication Kinetics, Genomic Stability, and Transgene Expression of Replication-Competent Murine Leukemia Virus-Based Vectors
Authors: Paar Matthias , Schwab Sonja , Rosenfellner Doris , Salmons Brian , Günzburg Walter H. , Renner Matthias , Portsmouth Daniel 
Published: April 2007

ABSTRACT
The limited efficiency of in vivo gene transfer by replication-deficient retroviral vectors remains an obstacle to achieving effective gene therapy for solid tumors. One approach to circumvent this problem is the use of replication-competent retroviral vectors. However, the application of such vectors is at a comparatively early stage and the effects which virus strain, transgene cassette position, and target cell can exert on vector spread kinetics, genomic stability, and transgene expression levels remain to be fully elucidated. Thus, in this study a panel of vectors allowing the investigation of different design features on an otherwise genetically identical background were analyzed with respect to these readout parameters in cultures of both murine and human cells and in preformed tumors in nude mice. The obtained data revealed that (i) Moloney murine leukemia virus (Mo-MLV)-based vectors spread with faster kinetics, drive higher levels of transgene expression, and are more stable than equivalent Akv-MLV-based vectors; (ii) vectors containing the transgene cassette directly downstream of the envelope gene are genomically more stable than those containing it within the 3′-long terminal repeat U3 region; and (iii) the genomic stability of both strains seems to be cell line dependent.
Activated CD34-Derived Langerhans Cells Mediate Transinfection with Human Immunodeficiency Virus
Authors: Fahrbach Kelly M. , Barry Sheila M. , Ayehunie Seyoum , Lamore Sarah , Klausner Mitchell , Hope Thomas J. 
Published: April 2007

ABSTRACT

Langerhans cells (LCs) are a subset of dendritic cells (DCs) that reside within epidermal and mucosal tissue. Because of their location, LCs are potentially the first cells to encounter human immunodeficiency virus (HIV) during sexual transmission. We report that LCs purified from CD34
+
-derived DCs can facilitate the transinfection of target cells but only after activation. Virions were observed in an intracellular compartment that contains several tetraspanins, in addition to the unique LC markers langerin and CD1a. This reveals that the trafficking of HIV within LCs is reminiscent of that which occurs in mature monocyte-derived DCs and that it varies with the activation state of the cell. The observation that activated LCs can mediate transinfection suggests a potential role for these cells in the known increase in HIV transmission associated with sexually transmitted infections that would cause inflammation of the genital lining.
Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein
Authors: Kochs Georg , García-Sastre Adolfo , Martínez-Sobrido Luis 
Published: April 2007

ABSTRACTThe replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-α/β) system. This virus-host interplay is dependent on the production of IFN-α/β and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-β promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.
Prion Protein Alleles Showing a Protective Effect on the Susceptibility of Sheep to Scrapie and Bovine Spongiform Encephalopathy
Authors: Vaccari Gabriele , D'Agostino Claudia , Nonno Romolo , Rosone Francesca , Conte Michela , Di Bari Michele Angelo , Chiappini Barbara , Esposito Elena , De Grossi Luigi , Giordani Francesco , Marcon Stefano , Morelli Luisella , Borroni Renata , Agrimi Umberto 
Published: April 2007

ABSTRACT
The susceptibility of sheep to classical scrapie and bovine spongiform encephalopathy (BSE) is mainly influenced by prion protein (PrP) polymorphisms A136V, R154H, and Q171R, with the ARR allele associated with significantly decreased susceptibility. Here we report the protective effect of the amino acid substitution M137T, I142K, or N176K on the ARQ allele in sheep experimentally challenged with either scrapie or BSE. Such observations suggest the existence of additional PrP alleles that significantly decrease the susceptibility of sheep to transmissible spongiform encephalopathies, which may have important implications for disease eradication strategies.
How exposure information can enhance our understanding of child traffic “death leagues”
Authors: Christie Nicola , Cairns Sally , Towner Elizabeth , Ward Heather 
Published: April 2007

Objectives:To explore whether population-based fatality rates and measures of traffic exposure can be combined to provide a more comprehensive measure of safety. To illustrate how this could be achieved using surveys from a range of Organisation for Economic Cooperation and Development (OECD) countries. To discuss why exposure is important.Design and setting:Fatality data were obtained from the International Road Traffic and Accident Database and travel data from surveys among government transport administrations in each country.Methods:Comparable exposure data were obtained for children aged 10–14 years from the UK, the USA, Germany, The Netherlands, Norway, Sweden, Switzerland and New Zealand. Fatality rates for children travelling as pedestrians, cyclists and car occupants were calculated based on (1) per head of population and (2) a combination of rate per head population and per kilometre travelled.Results:In this study, exposure-based fatality rates suggest a more polarized distribution rather than a graduated league. The USA and the UK were at the lower end of the table for child pedestrian safety; Germany for car-occupant safety, Sweden and New Zealand performed less well. For cycling, the inclusion of exposure data considerably changes positions within the table. Countries with higher cycling levels like The Netherlands perform better than those with low levels like the UK and New Zealand.Conclusions:Exposure-based fatality rates can help us to understand whether policies reduce exposure or whether they increase safety, given a similar level of exposure. Data need to be harmonized across OECD countries for a better understanding of the risks and links between health and sustainable travel.
Pediatricians’ involvement in gun injury prevention
Authors: Olson L M , Christoffel K K , O’Connor K G 
Published: April 2007

Background:Injuries from small arms are of concern internationally. The health perspective is an emerging aspect of international work to reduce these injuries. This aspect has been evident in US firearm injury prevention work for over a decade, exhibited by strong statements from the American Academy of Pediatrics (AAP) to remove firearms from children’s environments.Objectives:To assess trends among US pediatricians related to firearm injury prevention counseling practices and attitudes toward gun legislation.Design:National random sample, mailed surveys of AAP members: (1) 1994 (response rate  = 68.9%, n = 982); (2) 2000 (response rate  = 62.4%, n = 922). χ2Tests were used to assess bivariate relationships and logistic regression to assess multivariate relationships regarding counseling practices.Results:Respondents in both years believed that violence prevention should be a priority for pediatricians (91.4% and 92.0%) and reported always or sometimes recommending handgun removal from the home (46.2% and 55.9%, respectively). In 2000, 74% of the respondents were comfortable discussing firearm safety; fewer thought they had sufficient training (32.7%) or time (27.5%) to discuss firearms. In 1994 and 2000, the likelihood of counseling on handgun removal was positively related to recent experience treating a gun injury, female sex and not owning a gun. In both years, >80% of pediatricians thought that gun control legislation or regulations would reduce injury and death.Conclusions:US pediatricians continue to adopt policies promoting gun injury prevention. The practices and attitudes of pediatricians may be important for public education strategies regarding firearm injury prevention in the US and internationally.
A risky treat: exploring parental perceptions of the barriers to seating their children in the rear seats of passenger vehicles
Authors: Lennon Alexia 
Published: April 2007

Background:Sitting in the rear seat of a vehicle rather than in the front seat reduces children’s risk of injury or death by ⩾35% in the event of a crash. As road trauma is a leading cause of child morbidity and mortality in highly motorised nations, even in countries where restraint use is high, encouraging parents to place children in the rear seats of vehicles offers a low-cost avenue to improving children’s overall health. However, little is known about the factors that affect parents’ decisions about seating positions.Objective:To explore parental perceptions of barriers to placing their children in the rear seat of passenger vehicles whenever possible.Design and subjects:Focus group discussions were held with urban parent-drivers to elicit their concerns about children’s car safety and barriers to rear-seat use.Results:Most parents had a rule that children should sit in the rear seat. Parents said that they relaxed these rules for a variety of reasons including social pressure, perceptions of the trip as short and because children regard sitting in the front seat as a treat. Parenting style, child cooperativeness, social pressure and inability to justify the risk of injury were identified as barriers to rear-seat travel.Conclusions:Effective interventions to increase the proportion of children travelling in the rear seat should address parents’ experiences of pressure to relax seating rules and risk perception, as well as provide strategies that support sound parental safety decisions.
“Risk Watch”: Cluster randomised controlled trial evaluating an injury prevention program
Authors: Kendrick Denise , Groom Lindsay , Stewart Jane , Watson Michael , Mulvaney Caroline , Casterton Rebecca 
Published: April 2007

Objective:to evaluate the effectiveness of a school-based injury prevention program.Design:Cluster randomised controlled trial.Setting:20 primary schools in Nottingham, UK.Participants:459 children aged 7 to 10 years.Intervention:The “Risk Watch” program delivered by teachers, aimed at improving bike and pedestrian, falls, poisoning and fire and burns safety.Main outcome measures:Safety knowledge, observed safety skills and self-reported safety behaviour.Results:At follow-up, intervention group children correctly answered more fire and burn prevention knowledge questions than control group children (difference between means 7.0% (95% CI 1.5% to12.6%)). Children in intervention group schools were more likely to know the correct actions to take if clothes catch fire and the correct way to wear a cycle helmet (difference between school means 35.3% (95% CI 22.7% to 47.9%) and 6.3% (95% CI 1.4% to 11.1%) respectively). They were also more likely to know the correct actions to take in a house fire and on finding tablets (OR 2.80 (95% CI 1.08 to 7.22) and OR 3.50 (95% CI 1.18 to 10.38) respectively) and correctly demonstrated more safety skills than control group children (difference between means 11.9% (95% CI 1.4% to 22.5%)). There was little evidence to suggest the first year of the program impacted on self-reported safety behaviours.Conclusions:The Risk Watch program delivered by teachers in primary schools increased some aspects of children’s safety knowledge and skills and primary schools should consider delivering this program. Longer term, larger scale evaluations are required to examine retention of knowledge and skills and impact on safety behaviours and child injury rates.
Le cycle de Gédéon ou la condamnation du refus de la royauté
Authors: de Castelbajac Isabelle 
Published: April 2007

AbstractFar from exemplifying the anti-monarchist position of the Deuteronomistic author, Gideon's cycle underlines his impiety, which, unlike in the case of Abimelek, shows itself not through his thirst for leadership, but through his refusal to carry out the functions assigned by Yahweh. The portrait of a Gideon, as a Canaanite leader, contrasts with the proto-royal portrait of the Israelite Gideon, who is both a war leader and champions Yahweh's cult. The Canaanite figure not only rejects the signs of his divine appointment, whether they show themselves in the divine call or through military victories, but also is responsible for the institution of an idolatrous cult. The Deuteronomistic author thus resets distinct bodies of old traditions, establishing a close link between Gideon-Yerubaal and Abimelek. But the writing of Abimelek's cycle seems to be older than Gideon's one.
Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune diseases
Authors: Zöller Margot , Gupta Pooja , Marhaba Rachid , Vitacolonna Mario , Freyschmidt-Paul Pia 
Published: April 2007

AbstractCD44 plays an important role in leukocyte extravasation, which is fortified in autoimmune diseases and delayed-type hypersensitivity (DTH) reactions. There is additional evidence that distinct CD44 isoforms interfere with the extravasation of selective leukocyte subsets. We wanted to explore this question in alopecia areata (AA), a hair-follicle centric autoimmune disease, and in a chronic eczema. The question became of interest because AA is treated efficiently by topical application of a contact sensitizer, such that a mild DTH reaction is maintained persistently. Aiming to support the therapeutic efficacy of a chronic eczema in AA by anti-CD44 treatment, it became essential to control whether a blockade of migration, preferentially of AA effector cells, could be achieved by CD44 isoform-specific antibodies. Anti-panCD44 and anti-CD44 variant 10 isoform (CD44v10) inhibited in vitro migration of leukocytes from untreated and allergen-treated, control and AA mice. In vivo, both antibodies interfered with T cell and monocyte extravasation into the skin; only anti-panCD44 prevented T cell homing into lymph nodes. Contributing factors are disease-dependent alterations in chemokine/chemokine receptor expression and a blockade of CD44 on endothelial cells and leukocytes. It is important that CD44 can associate with several integrins and ICAM-1. Associations depend on CD44 activation and vary with CD44 isoforms and leukocyte subpopulations. CD44 standard isoform preferentially associates with CD49d in T cells and CD44v10 with CD11b in monocytes. Accordingly, anti-panCD44 and anti-CD49d inhibit T cell, anti-CD11b, and anti-CD44v10 macrophage migration most efficiently. Thus, allergen treatment of AA likely can be supported by targeting AA T cells selectively via a panCD44-CD49d-bispecific antibody.
Caspase-1 inflammasomes in infection and inflammation
Authors: Lamkanfi Mohamed , Kanneganti Thirumala-Devi , Franchi Luigi , Núñez Gabriel 
Published: April 2007

AbstractNucleotide-binding and oligomerization domain-like receptors (NLRs) constitute a family of germline-encoded pattern-recognition receptors, which allow the host to respond rapidly to a wide variety of pathogenic microorganisms. Here, we discuss recent advances in the study of a subset of NLRs, which control the activation of caspase-1 through the assembly of large protein complexes, inflammasomes. The NALP1b inflammasome recognizes anthrax lethal toxin, and flagellin from Salmonella and Legionella induces assembly of the Ipaf inflammasome. Cryopyrin/NALP3 mediates caspase-1 activation in response to a wide variety of bacterial ligands, imidazoquinolines, dsRNA, and the endogenous danger signal uric acid. The importance of these cytosolic receptors in immune regulation is underscored by the identification of mutations in cryopyrin/NALP3, which are genetically linked to human autoinflammatory disorders.
General practitioner (GP) cardiac troponin test requesting: findings from a clinical laboratory audit
Authors: Sodi Ravinder , Hine Trevor , Shenkin Alan 
Published: April 2007

Background: There is limited data and literature on the issue of cardiac troponin test requesting by general practitioners (GPs). It was therefore our aim to audit the cardiac troponin test requests made by GPs in our community with a view to develop an informed strategy for assay provision and reporting of results. Methods: A retrospective audit was undertaken of data in our laboratory database for all cardiac troponin T (cTnT) tests requested by GPs between January and June 2005. A prospective audit was then carried out between July and December 2005 using the telephone interview method. The number and distribution of tests, the reasons for the request and the intended action by the GPs were quantified. Results: Forty-five of 46 of the results of both the retrospective and prospective audits were negative based on the 99th percentile level with less than 10% imprecision (cTnT <0.03 μg/L). During the one-year study period, we had requests from 24 general practices with a mean and mode of two and one requests per general practice respectively. The most common reason for the request was found to be chest pain that had occurred more than 24 h ago. Conclusion: Bearing in mind the limitations of an audit study, our findings obviate the use of cTnT in general practice. We suggest that the laboratory should liase with the GP and advise referral for specialist care if clinical suspicion of acute coronary syndrome is high.
EDTA analysis on the Roche MODULAR® analyser
Authors: Davidson D F 
Published: April 2007

Background: Patient specimens can be subject to subtle interference from cross contamination by liquid-based, potassium-containing EDTA anticoagulant, leading to misinterpretation of results. A rapid method for EDTA analysis to detect such contamination is described. Method: An in-house EDTA assay on the Roche MODULAR® analyser was assessed for accuracy and precision by comparison with an adjusted calcium difference measurement (atomic absorption and o-cresolphthalein complexone colorimetry). Results: EDTA method versus adjusted calcium difference showed: slope = 1.038 (95% confidence interval [CI] 0.949-1.131); intercept = 0.073 (95% CI 0.018-0.132) mmol/L; r = 0.914; n = 94. However, inter-assay precision of the calcium difference method was estimated to be poorer (coefficient of variation 24.8% versus 3.4% for the automated colorimetric method at an EDTA concentration of 0.25 mmol/L). Unequivocal contamination was observed at an EDTA concentration of -0.2 mmol/L. The automated method showed positive interference from haemolysis and negative interference from oxalate. The method was unaffected by lipaemia (triglycerides <20 mmol/L), icterus (bilirubin <500 μmol/L), glucose (<100 mmol/L), iron (<100 μmol/L), and citrate, phosphate or fluoride (all <2.5 mmol/L). Conclusion: The automated colorimetric assay described is an accurate, precise and rapid (3 min) means of detecting EDTA contamination of unhaemolysed biochemistry specimens.
Showing smokers with vascular disease images of their arteries to motivate cessation: A pilot study
Authors: Shahab Lion , Hall Sue , Marteau Theresa 
Published: April 2007

Objectives. To examine the potential impact of visual personalized biomarker feedback on intention to stop smoking and to evaluate possible underlying causal pathways.Design. This study is a pilot for a randomized controlled trial. Outcome measures were assessed immediately after the intervention and at 4 weeks follow‐up.Method. Twenty‐three smokers attending a cardiovascular outpatient clinic in London were randomly allocated to one of two groups: to either receive a print‐out of an ultrasound image of their carotid artery showing atherosclerotic plaque alongside an image of a disease‐free artery, or to receive routine verbal feedback.Results. The intervention significantly increased perceptions of susceptibility to smoking‐related diseases (Cohen's h = 0.99) and led to increases both in engagement in smoking cessation behaviours (Cohen's h = 0.79) and intentions to stop smoking (Cohn's d = 0.44). The latter was moderated by self‐efficacy: the intervention increased intention to stop smoking only in people with higher levels of self‐efficacy with regard to stopping smoking.Conclusion. This study provides preliminary support for the potential effectiveness of personalized biomarker feedback to increase intentions to stop smoking. It also highlights the need to target and increase self‐efficacy in smoking cessation interventions.