bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Interactions between Coexisting Toxin-Antitoxin Systems of the
ccd
Family in
Escherichia coli
O157:H7
Authors: Wilbaux Myriam , Mine Natacha , Guérout Anne-Marie , Mazel Didier , Van Melderen Laurence
Published: January 2007

Toxin-antitoxin (TA) systems are widely represented on mobile genetic elements as well as in bacterial chromosomes. TA systems encode a toxin and an antitoxin neutralizing it. We have characterized a homolog of the
ccd
TA system of the F plasmid (
ccd
F
) located in the chromosomal backbone of the pathogenic O157:H7
Escherichia coli
strain (
ccd
O157
). The
ccd
F
and the
ccd
O157
systems coexist in O157:H7 isolates, as these pathogenic strains contain an F-related virulence plasmid carrying the
ccd
F
system. We have shown that the chromosomal
ccd
O157
system encodes functional toxin and antitoxin proteins that share properties with their plasmidic homologs: the CcdB
O157
toxin targets the DNA gyrase, and the CcdA
O157
antitoxin is degraded by the Lon protease. The
ccd
O157
chromosomal system is expressed in its natural context, although promoter activity analyses revealed that its expression is weaker than that of
ccd
F
.
ccd
O157
is unable to mediate postsegregational killing when cloned in an unstable plasmid, supporting the idea that chromosomal TA systems play a role(s) other than stabilization in bacterial physiology. Our cross-interaction experiments revealed that the chromosomal toxin is neutralized by the plasmidic antitoxin while the plasmidic toxin is not neutralized by the chromosomal antitoxin, whether expressed ectopically or from its natural context. Moreover, the
ccd
F
system is able to mediate postsegregational killing in an
E. coli
strain harboring the
ccd
O157
system in its chromosome. This shows that the plasmidic
ccd
F
system is functional in the presence of its chromosomal counterpart.
Disruption of a Sugar Transporter Gene Cluster in a Hyperthermophilic Archaeon Using a Host-Marker System Based on Antibiotic Resistance
Authors: Matsumi Rie , Manabe Kenji , Fukui Toshiaki , Atomi Haruyuki , Imanaka Tadayuki
Published: January 2007

We have developed a gene disruption system in the hyperthermophilic archaeonThermococcus kodakaraensisusing the antibiotic simvastatin and a fusion gene designed to overexpress the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene (hmgTk) with the glutamate dehydrogenase promoter. With this system, we disrupted theT. kodakaraensisamylopullulanase gene (apuTk) or a gene cluster which includesapuTkand genes encoding components of a putative sugar transporter. Disruption plasmids were introduced into wild-typeT. kodakaraensisKOD1 cells, and transformants exhibiting resistance to 4 μM simvastatin were isolated. The transformants exhibited growth in the presence of 20 μM simvastatin, and we observed a 30-fold increase in intracellular HMG-CoA reductase activity. The expected gene disruption via double-crossover recombination occurred at the target locus, but we also observed recombination events at thehmgTklocus when the endogenoushmgTkgene was used. This could be avoided by using the corresponding gene fromPyrococcus furiosus(hmgPf) or by linearizing the plasmid prior to transformation. While both gene disruption strains displayed normal growth on amino acids or pyruvate, cells without the sugar transporter genes could not grow on maltooligosaccharides or polysaccharides, indicating that the gene cluster encodes the only sugar transporter involved in the uptake of these compounds. The ΔapuTkstrain could not grow on pullulan and displayed only low levels of growth on amylose, suggesting that ApuTkis a major polysaccharide-degrading enzyme inT. kodakaraensis.
The Redox Regulator Fnr Is Required for Fermentative Growth and Enterotoxin Synthesis in
Bacillus cereus
F4430/73
Authors: Zigha Assia , Rosenfeld Eric , Schmitt Philippe , Duport Catherine
Published: January 2007

Glucose-grown cells of
Bacillus cereus
respond to anaerobiosis and low extracellular oxidoreduction potentials (ORP), notably by enhancing enterotoxin production. This response involves the ResDE two-component system. We searched the
B. cereus
genome for other redox response regulators potentially involved in this adaptive process, and we identified one gene encoding a protein predicted to have an amino acid sequence 58% identical (80% similar) to that of the
Bacillus subtilis
Fnr redox regulator. The
fnr
gene of the food-borne pathogen
B. cereus
F4430/73 has been cloned and partially characterized. We showed that
fnr
was up-regulated during anaerobic fermentation, especially when fermentation occurred at low ORP (under highly reducing conditions). The expression of
fnr
was down-regulated in the presence of O
2
and nitrate which, unlike fumarate, stimulated the respiratory pathways. The inactivation of
B. cereus fnr
abolished fermentative growth but only moderately affected aerobic and anaerobic nitrate respiratory growth. Analyses of glucose by-products and the transcription profiles of key catabolic genes confirmed the strong regulatory impact of Fnr on
B. cereus
fermentative pathways. More importantly, the
fnr
mutation strongly decreased the expression of PlcR-dependent
hbl
and
nhe
genes, leading to the absence of hemolysin BL (Hbl) and nonhemolytic enterotoxin (Nhe) secretion by the mutant. These data indicate that
fnr
is essential for both fermentation and toxinogenesis. The results also suggest that both Fnr and the ResDE two-component system belong to a redox regulatory pathway that functions at least partially independently of the pleiotropic virulence gene regulator PlcR to regulate enterotoxin gene expression.
The Quorum-Sensing Hybrid Histidine Kinase LuxN of
Vibrio harveyi
Contains a Periplasmically Located N Terminus
Authors: Jung Kirsten , Odenbach Tina , Timmen Melanie
Published: January 2007

Hydropathy profile analyses of the amino acid sequence of the quorum-sensing hybrid histidine kinase LuxN of
Vibrio harveyi
predict a periplasmic location of the N terminus. To test this, two-hybrid proteins consisting of LuxN and an N-terminally fused maltose-binding protein with or without a leader sequence were analyzed with regard to the enzymatic activities of LuxN, protease accessibility, and complementation of an
Escherichia coli malE
mutant. The results strongly support a periplasmic location of the N terminus, implying that LuxN is anchored with nine transmembrane domains in the cytoplasmic membrane.
A Novel Deaminase Involved in Chloronitrobenzene and Nitrobenzene Degradation with
Comamonas
sp. Strain CNB-1
Authors: Liu Lei , Wu Jian-Feng , Ma Ying-Fei , Wang Sheng-Yue , Zhao Guo-Ping , Liu Shuang-Jiang
Published: January 2007

Comamonas
sp. strain CNB-1 degrades nitrobenzene and chloronitrobenzene via the intermediates 2-aminomuconate and 2-amino-5-chloromuconate, respectively. Deamination of these two compounds results in the release of ammonia, which is used as a source of nitrogen for bacterial growth. In this study, a novel deaminase was purified from
Comamonas
strain CNB-1, and the gene (
cnbZ
) encoding this enzyme was cloned. The N-terminal sequence and peptide fingerprints of this deaminase were determined, and BLAST searches revealed no match with significant similarity to any functionally characterized proteins. The purified deaminase is a monomer (30 kDa), and its
V
max
values for 2-aminomuconate and 2-amino-5-chloromuconate were 147 μmol·min
−1
·mg
−1
and 196 μmol·min
−1
·mg
−1
, respectively. Its catalytic products from 2-aminomuconate and 2-amino-5-chloromuconate were 2-hydroxymuconate and 2-hydroxy-5-chloromuconate, respectively, which are different from those previously reported for the deaminases of
Pseudomonas
species. In the catalytic mechanism proposed, the α-carbon and nitrogen atoms (of both 2-aminomuconate and 2-amino-5-chloromuconate) were simultaneously attacked by a hydroxyl group and a proton, respectively. Homologs of
cnbZ
were identified in the genomes of
Bradyrhizobium japonicum
,
Rhodopseudomonas palustris
, and
Roseiflexus
sp. strain RS-1; these genes were previously annotated as encoding hypothetical proteins of unknown function. It is concluded that CnbZ represents a novel enzyme that deaminates xenobiotic compounds and/or α-amino acids.
UvrD Limits the Number and Intensities of RecA-Green Fluorescent Protein Structures in
Escherichia coli
K-12
Authors: Centore Richard C. , Sandler Steven J.
Published: January 2007

RecA is important for recombination, DNA repair, and SOS induction. In
Escherichia coli
, RecBCD, RecFOR, and RecJQ prepare DNA substrates onto which RecA binds. UvrD is a 3′-to-5′ helicase that participates in methyl-directed mismatch repair and nucleotide excision repair.
uvrD
deletion mutants are sensitive to UV irradiation, hypermutable, and hyper-rec. In vitro, UvrD can dissociate RecA from single-stranded DNA. Other experiments suggest that UvrD removes RecA from DNA where it promotes unproductive reactions. To test if UvrD limits the number and/or the size of RecA-DNA structures in vivo, an
uvrD
mutation was combined with
recA-gfp
. This
recA
allele allows the number of RecA structures and the amount of RecA at these structures to be assayed in living cells.
uvrD
mutants show a threefold increase in the number of RecA-GFP foci, and these foci are, on average, nearly twofold higher in relative intensity. The increased number of RecA-green fluorescent protein foci in the
uvrD
mutant is dependent on
recF
,
recO
,
recR
,
recJ
, and
recQ
. The increase in average relative intensity is dependent on
recO
and
recQ
. These data support an in vivo role for UvrD in removing RecA from the DNA.
Negative Regulation ofBacillus anthracisSporulation by the Spo0E Family of Phosphatases
Authors: Bongiorni Cristina , Stoessel Ricarda , Perego Marta
Published: January 2007

The initiation of sporulation inBacillusspecies is controlled by the phosphorelay signal transduction system. Multiple regulatory elements act on the phosphorelay to modulate the level of protein phosphorylation in response to cellular, environmental, and metabolic signals. InBacillus anthracisnine possible histidine sensor kinases can positively activate the system, while two response regulator aspartyl phosphate phosphatases of the Rap family negatively impact the pathway by dephosphorylating the Spo0F intermediate response regulator. In this study, we have characterized theB. anthracismembers of the Spo0E family of phosphatases that specifically dephosphorylate the Spo0A response regulator of the phosphorelay and master regulator of sporulation. The products of four genes were able to promote the dephosphorylation of Spo0A∼P in vitro. The overexpression of two of theseB. anthracisSpo0E-like proteins from a multicopy vector consistently resulted in a sporulation-deficient phenotype. A third gene was found to be not transcribed in vivo. A fourth gene encoded a prematurely truncated protein due to a base pair deletion that nevertheless was subject to translational frameshift repair in anEscherichia coliprotein expression system. A fifth Spo0E-like protein has been structurally and functionally characterized as a phosphatase of Spo0A∼P by R. N. Grenha et al. (J. Biol. Chem.281:37993-38003, 2006). We propose that these proteins may contribute to maintainB. anthracisin the transition phase of growth during an active infection and therefore contribute to the virulence of this organism.
The IclR-Type Transcriptional Repressor LtbR Regulates the Expression of Leucine and Tryptophan Biosynthesis Genes in the Amino Acid ProducerCorynebacterium glutamicum
Authors: Brune Iris , Jochmann Nina , Brinkrolf Karina , Hüser Andrea T. , Gerstmeir Robert , Eikmanns Bernhard J. , Kalinowski Jörn , Pühler Alfred , Tauch Andreas
Published: January 2007

The transcriptional regulator Cg1486 ofCorynebacterium glutamicumATCC 13032 is a member of the IclR protein family and belongs to the conserved set of regulatory proteins in corynebacteria. A defined deletion in the cg1486 gene, now designatedltbR(leucine and tryptophan biosynthesis regulator), led to the mutant strainC. glutamicumIB1486. According to whole-genome expression analysis by DNA microarray hybridizations, transcription of theleuBandleuCDgenes encoding enzymes of the leucine biosynthesis pathway was enhanced inC. glutamicumIB1486 compared with the wild-type strain. Moreover, the genes of thetrpEGDCFBAoperon involved in tryptophan biosynthesis ofC. glutamicumshowed an enhanced expression in the cg1486 mutant strain. Bioinformatics pattern searches in the upstream regions of the differentially expressed genes revealed the common 12-bp motif CA(T/C)ATAGTG(A/G)GA that is located downstream of the −10 region of the mapped promoter sequences. DNA band shift assays with a streptavidin-tagged LtbR protein demonstrated the specific binding of the purified protein to 40-mers containing the 12-bp motif localized in front ofleuB,leuC, andtrpE, thereby confirming the direct regulatory role of LtbR in the expression of the leucine and tryptophan biosynthesis pathway genes ofC. glutamicum. Genes homologous withltbRwere detected upstream of theleuCDgenes in almost all sequenced genomes of bacteria belonging to the taxonomic classActinobacteria. TheltbR-like genes ofCorynebacterium diphtheriae,Corynebacterium jeikeium,Mycobacterium bovis, andBifidobacterium longumwere cloned and shown to complement the deregulation ofleuB,leuCD, andtrpEgene expression inC. glutamicumIB1486.
Frequency of theTMPRSS2:ERGgene fusion is increased in moderate to poorly differentiated prostate cancers
Authors: Rajput Ashish B , Miller Melinda A , De Luca Alessandro , Boyd Niki , Leung Sam , Hurtado-Coll Antonio , Fazli Ladan , Jones Edward C , Palmer Jodie B , Gleave Martin E , Cox Michael E , Huntsman David G
Published: January 2007

Background:

Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes,ERGorETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5′ end of the androgen-regulated serine proteaseTMPRSS2(21q22.2) to the 3′ end of eitherERG(21q22.3) orETV1(7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes,ETV1orERG.

Aim:

To determine the frequency of rearrangements involvingTMPRSS2,ERG, orETV1genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs).

Methods:

Two independent assays, aTMPRSS2break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis.

Results:

A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements.TMPRSS2:ERGfusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017).TMPRSS2:ETV1gene fusions were not detected in any of the cases tested.TMPRSS2:ERGfusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed.

Conclusion:

This study indicates thatTMPRSS2:ERGgene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.
Gross synovial fluid analysis in the differential diagnosis of joint effusion
Authors: Abdullah S , Young-Min S A , Hudson S J , Kelly C A , Heycock C R , Hamilton J D
Published: January 2007

Aims:

To develop an objective and easy to complete standardised questionnaire for documentation of synovial fluid (SF) gross appearance and use it in the assessment of patients presenting to the rheumatology service with a joint effusion.

Methods:

A standardised questionnaire to record the gross appearance of SF was developed. Interobserver error in recorded observations and direct gross analysis of synovial fluid between four observers was calculated in a pilot study. In a prospective study over 8 months, SF gross analysis and cell count were documented in all patients presenting with a joint effusion. Fusch Rosenthal manual counting chamber was used for calculating SF cell counts.

Results:

There was good interobserver agreement on direct gross analysis and between questionnaire assessors (mean κ 0.889). 80 SF samples were collected. Gross analysis was performed in all samples and cell count in 72. Of the specimens thought to be inflammatory on gross analysis, 31% were found to be non-inflammatory based on cell count; however, 12 of these patients had an established inflammatory arthritis. Gross analysis had a sensitivity of 94% and specificity of 58% when used to determine whether SF is inflammatory or non-inflammatory. The positive and negative predictive values were 0.69 and 0.91 respectively.

Conclusions:

SF cell count did not add any information when SF gross analysis suggested a non-inflammatory process. Gross analysis was better than cell count to determine a potentially septic joint fluid. Further work needs to be done on the value of SF cell counts if gross analysis suggests the fluid to be inflammatory.
Patient self management of oral anticoagulation in routine care in the UK
Authors: McCahon D , Murray E T , Jowett S , Sandhar H S , Holder R L , Hussain S , O’Donoghue B , Fitzmaurice D A
Published: January 2007

Background:

Self management of anticoagulation: a randomised trial (SMART) was the first large scale UK trial to assess clinical and cost effectiveness of patient self management (PSM) of oral anticoagulation therapy compared to routine care. SMART showed that while PSM was as clinically effective as routine care, it was not as cost effective. SMART adds to the growing body of trial data to support PSM; however there are no data on clinical effectiveness and cost of PSM in routine care.

Aim:

To evaluate clinical effectiveness of PSM compared to routine care outside trial conditions.

Methods:

A retrospective multicentre matched control study. 63 PSM patients from primary care in the West Midlands were matched by age and international normalised ratio (INR) target with controls. INR results were collected for the period 1 July 2003–30 June 2004. The primary outcome measure was INR control.

Results:

38 PSM and 40 control patients were recruited. INR percentage time in range was 70% PSM vs 64% controls. 60% PSM were having a regular clinical review, 45% were performing an internal quality control (IQC) test and 82% were performing external quality assurance (EQA) on a regular basis.

Conclusion:

PSM outside trial conditions is as clinically effective as routine UK care.
Frequency and reliability of oestrogen receptor, progesterone receptor and HER2 in breast carcinoma determined by immunohistochemistry in Australasia: results of the RCPA Quality Assurance Program
Authors: Francis Glenn D , Dimech Margaret , Giles Leanne , Hopkins Alison
Published: January 2007

Background and Aims:

Immunohistochemistry (IHC) has replaced radioligand binding assay for the determination of oestrogen receptor (ER) status in breast carcinoma. IHC is also used for assessment of progesterone receptor (PR) and HER2. The Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) introduced a breast markers module in 2003 to evaluate the performance of laboratories with IHC for ER, PR and HER2.

Methods:

An audit of laboratories reporting breast carcinomas was performed in 2005 and 2006 to evaluate in-house results. Laboratories were asked to submit the hormone receptor and HER2 status on each invasive breast carcinoma for the previous 6 month period up to a maximum of 100 cases. The time periods were 1 July 2004 to 31 December 2004, and 1 July 2005 to 31 December 2005. A total of 55 laboratories returned information for 2004 and 67 for 2005.

Results:

Complete data on 8128 patients was returned for both surveys, 3353 cases for 2004 and 4775 for 2005. The results were similar for both surveys. Of the 8128 cases, 59.0% were ER+/PR+, 15.9% ER+/PR−, 2.4% ER−/PR+ and 22.7% ER−/PR−. HER2 data were submitted for a total of 6512 patients (excludes 52 patients with incomplete data sets); 17.1% were reported as 3+ positive on IHC, 12.5% as 2+ and 70.4% as negative.

Conclusions:

A laboratory audit was introduced into the RCPA QAP for breast markers due to concerns raised by participating laboratories about technical differences in supplied tissues for testing. This audit indicates that overall the results for ER, PR and HER2 fall inside established parameters. However, a number of individual laboratories do not meet the target values and variation in results would impact on patient treatment decisions.
Best practice in primary care pathology: review 9
Authors: Smellie W S A , Shaw N , Bowlees R , Taylor A , Howell-Jones R , McNulty C A M
Published: January 2007

This ninth best-practice review examines two series of common primary care questions in laboratory medicine: (i) potassium abnormalities and (ii) venous leg ulcer microbiology. The review is presented in question-and-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.
Health response of two communities to military antennae in Cyprus
Authors: Preece A W , Georgiou A G , Dunn E J , Farrow S C
Published: January 2007

Objectives:This study investigated concerns that have been raised about past and future health effects caused by high power transmissions of high frequency (7–30 MHz) radio waves from military antenna systems at Akrotiri, Cyprus.

Methods:A cross-sectional study of three villages (two exposed, one unexposed) collected longitudinal and short-term radiofrequency measurements. Health data were collected using questionnaires containing information on demographic factors, specific illnesses, general health (SF-36 well-being questionnaire), reproductive history, childhood illnesses, risk perception and mortality. Analysis was with SPSS v11.5 using cross tabulations of non-parametric data and tests for significance. Key health outcomes were subjected to logistic regression analysis.

Results:Field strengths within the two “exposed” villages were a maximum of 0.30 (Volts/Vm−1metre) from the 17.6 MHz military transmissions and up to 1.4 Vm−1from unspecified sources, mainly cell phone frequencies. The corresponding readings in the control village were <0.01 Vm−1. Compared with the control village there were highly significant differences in the reporting of migraine (OR 2.7, p<0.001), headache (OR 3.7, p<0.001), and dizziness (OR 2.7, p<0.001). Residents of the exposed villages showed greater negative views of their health in all eight domains of the SF-36. There were also higher levels of perceived risk, particularly to noise and electromagnetic “pollution”. All three villages reported higher values of risk perception than a UK population. There was no evidence of birth abnormalities or differences in gynaecological or obstetric history. Numbers of cancers were too small to show differences.

Conclusion:It was clear that even this close (1–3 km) to powerful transmissions, the dominant sources of radiofrequency fields were cell phone and national broadcast systems. There was no excess of cancer, birth defects or obstetric problems. There was heightened risk perception and a considerable excess of migraine, headache and dizziness, which appears to share a gradient with radiofrequency exposure. The authors report this association but suggest this is unlikely to be an effect of radiofrequency and more likely to be antenna visibility or aircraft noise.
Literature review of cancer mortality and incidence among dentists
Authors: Simning Adam , van Wijngaarden Edwin
Published: January 2007

This review assesses the epidemiological literature describing dentist mortality and cancer incidence risk. In the dental workplace a variety of hazards may have been historically present or currently exist which can impact dentists’ long-term health, including their mortality and cancer incidence. The epidemiological literature of dentistry’s health outcomes was reviewed with a focus on all cancers combined and cancers of the brain, lung, reproductive organs and skin. Relevant studies were identified using MEDLINE and NIOSHTIC through early 2006 and from references cited in the articles obtained from these databases. Dentist cancer mortality and incidence generally showed a favourable risk pattern for lung cancer and overall cancer occurrence. Nevertheless, several studies reported an increased risk for certain cancers, such as those of the skin and, to a lesser extent, the brain and female breast. These elevated risks may be related to social status or education level, or may alternatively represent the impact of hazards in the workplace. The evidence for an increased mortality or cancer incidence risk among dentists must be interpreted in light of methodological limitations of published studies. Future studies of dentists would benefit from the assessment of specific occupational exposures rather than relying on job title alone.
Mortality study update of acrylamide workers
Authors: Swaen Gerard M H , Haidar Salma , Burns Carol J , Bodner Kenneth , Parsons Tracy , Collins James J , Baase Catherine
Published: January 2007

Objective:The authors examined the long-term health effects of occupational exposure to acrylamide among production and polymerisation workers.

Methods:An earlier study of 371 acrylamide workers was expanded to include employees hired since 1979. In this updated study, 696 acrylamide workers were followed from 1955 through 2001 to ascertain vital status and cause of death. Exposure to acrylamide was retrospectively assessed based on personal samples from the 1970s onwards and area samples over the whole study period.

Results:Fewer of the acrylamide workers died (n = 141) compared to an expected number of 172.1 (SMR 81.9, 95% CI 69.0 to 96.6). No cause-specific SMR for any of the investigated types of cancer was exposure related. The authors did, however, find more pancreatic cancer deaths than expected (SMR 222.2, 95% CI 72.1 to 518.5). With respect to non-malignant disease, more diabetes deaths were observed than expected (SMR 288.7, 95% CI 138.4 to 531.0). To assess the influence of regional factors, the analysis was repeated with an internal reference population. The elevated SMR for diabetes persisted.

Conclusion:This study provides little evidence for a cancer risk from occupational exposure to acrylamide at production facilities. However, the increased rates of pancreatic cancer in this study and another larger study of acrylamide production workers indicate that caution is needed to rule out a cancer risk. The authors believe that the excess of diabetes mortality in this study is most likely not related to acrylamide exposure, because a larger study of acrylamide workers reported a deficit in this cause of death. The authors conclude that the increased SMR for diabetes mortality is probably not related to regional influences.
Effort-reward imbalance, procedural injustice and relational injustice as psychosocial predictors of health: complementary or redundant models?
Authors: Kivimäki Mika , Vahtera Jussi , Elovainio Marko , Virtanen Marianna , Siegrist Johannes
Published: January 2007

Objective:

Effort-reward imbalance at work is an established psychosocial risk factor but there are also newer conceptualisations, such as procedural injustice (decisions at work lack consistency, openness and input from all affected parties) and relational injustice (problems in considerate and fair treatment of employees by supervisors). The authors examined whether procedural injustice and relational injustice are associated with employee health in addition to, and in combination with, effort-reward imbalance.

Methods:

Prospective survey data from two cohorts related to public-sector employees: the 10-Town study (n = 18 066 (78% women, age range 19–62) and the Finnish Hospital Personnel study (n = 4833, 89% women, age range 20–60). Self-rated poor health, minor psychiatric morbidity and doctor-diagnosed depression were assessed at baseline (2000–2) and at follow-up (2004). To determine incident morbidity, baseline cases were excluded.

Results:

In multivariate models including age, sex, occupational status and all three psychosocial factors as predictors, high effort-reward imbalance and either high procedural injustice or high relational injustice were associated with increased morbidity at follow-up in both cohorts. After combining procedural and relational injustice into a single measure of organisational injustice, high effort-reward imbalance and high injustice were both independently associated with health. For all outcome measures, a combination of high effort-reward imbalance and high organisational injustice was related to a greater health risk than high effort-reward imbalance or injustice alone.

Conclusion:

Evidence from two independent occupational cohorts suggests that procedural and relational components of injustice, as a combined index, and effort-reward imbalance are complementary risk factors.
Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis
Authors: Eiselein Larissa , Wilson Dennis W. , Lamé Michael W. , Rutledge John C.
Published: January 2007

Products generated from lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TGRL) are reported to increase endothelial layer permeability. We hypothesize that these increases in permeability result from the active rearrangement and dissolution of the junctional barrier in human aortic endothelial cells, as well as induction of the apoptotic cascade. Human aortic endothelial cells were treated with TGRL lipolysis products generated from coincubation of human TGRL plus lipoprotein lipase. Measurement of transendothelial electrical resistance demonstrated a time-dependent decrease in endothelial barrier function in response to TGRL lipolysis products. Immunofluorescent localization of zonula occludens-1 (ZO-1) showed radial rearrangement along cell borders after 1.5 h of treatment with lipolysis products. A concurrent redistribution of F-actin from the cell body to the cell margins was observed via rhodamine phalloidin staining. Immunofluorescent imaging for occludin and vascular endothelial cadherin showed that these proteins relocalize as well, although these changes are less prominent than for ZO-1. Western analysis of cells exposed to lipolysis products for 3 h revealed the fragmentation of ZO-1, a reduction in occludin, and no change of vascular endothelial cadherin. Lipolysis products also increased caspase-3 activity and induced nuclear fragmentation. Treatments did not cause oncosis in cells at any point during the incubation. These results demonstrate that TGRL lipolysis products play an important role in the regulation of endothelial permeability, the organization of the actin cytoskeleton, the localization and expression of junctional proteins, especially ZO-1, and the induction of apoptosis.
Chronic nitric oxide synthase inhibition blunts endothelium-dependent function of conduit coronary arteries, not arterioles
Authors: Ingram David G. , Newcomer Sean C. , Price Elmer M. , Eklund Kevin E. , McAllister Richard M. , Laughlin M. Harold
Published: January 2007

Current literature suggests that chronic nitric oxide synthase (NOS) inhibition has differential effects on endothelium-dependent dilation (EDD) of conduit arteries vs. arterioles. Therefore, we hypothesized that chronic inhibition of NOS would impair EDD of porcine left anterior descending (LAD) coronary arteries but not coronary arterioles. Thirty-nine female Yucatan miniature swine were included in the study. Animals drank either tap water or water with NG-nitro-l-arginine methyl ester (l-NAME; 100 mg/l), resulting in control and chronic NOS inhibition (CNI) groups, respectively. Treatment was continued for 1–3 mo (8.3 ± 0.6 mg·kg−1·day−1). In vitro EDD of coronary LADs and arterioles was assessed via responses to ADP (LADs only) and bradykinin (BK), and endothelium-independent function was assessed via responses to sodium nitroprusside (SNP). Chronic NOS inhibition diminished coronary artery EDD to ADP and BK. Incubating LAD rings with l-NAME decreased relaxation responses of LADs from control pigs but not from CNI pigs such that between-group differences were abolished. Neither indomethacin (Indo) nor sulfaphenazole incubation significantly affected relaxation responses of LAD rings to ADP or BK. Coronary arteries from CNI pigs showed enhanced relaxation responses to SNP. In contrast to coronary arteries, coronary arterioles from CNI pigs demonstrated preserved EDD to BK and no increase in dilation responses to SNP. l-NAME, Indo, and l-NAME + Indo incubation did not result in significant between-group differences in arteriole dilation responses to BK. These results suggest that although chronic NOS inhibition diminishes EDD of LAD rings, most likely via a NOS-dependent mechanism, it does not affect EDD of coronary arterioles.
The elevated blood pressure of humanGRK4γA142Vtransgenic mice is not associated with increased ROS production
Authors: Wang Zheng , Armando Ines , Asico Laureano D. , Escano Crisanto , Wang Xiaoyan , Lu Quansheng , Felder Robin A. , Schnackenberg Christine G. , Sibley David R. , Eisner Gilbert M. , Jose Pedro A.
Published: January 2007

G protein-coupled receptor (GPCR) kinases (GRKs) regulate the sensitivity of GPCRs, including dopamine receptors. The GRK4 locus is linked to, and some of its polymorphisms are associated with, human essential hypertension. Transgenic mice overexpressing human (h) GRK4γ A142V on a mixed genetic background (C57BL/6J and SJL/J) have impaired renal D1-dopamine receptor (D1R) function and increased blood pressure. We now report that hGRK4γ A142V transgenic mice, in C57BL/6J background, are hypertensive and have higher blood pressures than hGRK4γ wild-type transgenic and nontransgenic mice. The hypertensive phenotype is stable because blood pressures in transgenic founders and F6 offspring are similarly increased. To determine whether the hypertension is associated with increased production of reactive oxygen species (ROS), we measured renal NADPH oxidase (Nox2 and Nox4) and heme oxygenase (HO-1 and HO-2) protein expressions and urinary excretion of 8-isoprostane and compared the effect of Tempol on blood pressure in hGRK4γ A142V transgenic mice and D5R knockout (D5−/−) mice in which hypertension is mediated by increased ROS. The expressions of Nox isoforms and HO-2 and the urinary excretion of 8-isoprostane were similar in hGRK4γ A142V transgenic mice and their controls. HO-1 expression was increased in hGRK4γ A142V relative to hGRK4γ wild-type transgenic mice. In contrast with the hypotensive effect of Tempol in D5−/−mice, it had no effect in hGRK4γ A142V transgenic mice. We conclude that the elevated blood pressure of hGRK4γ A142V transgenic mice is due mainly to the effect of hGRK4γ A142V transgene acting via D1R and increased ROS production is not a contributor.
Peroxisome proliferator-activated receptor-δ polymorphisms are associated with physical performance and plasma lipids: the HERITAGE Family Study
Authors: Hautala Arto J. , Leon Arthur S. , Skinner James S. , Rao D. C. , Bouchard Claude , Rankinen Tuomo
Published: January 2007

We tested the hypothesis that peroxisome proliferator-activated receptor-δ (PPARδ) gene polymorphisms are associated with cardiorespiratory fitness and plasma lipid responses to endurance training. Associations between the PPARδ exon 4 +15 C/T and exon 7 +65 A/G polymorphisms and maximal exercise capacity and plasma lipid responses to 20 wk of endurance training were investigated in healthy white ( n = 477) and black ( n = 264) subjects. In black subjects, the exon 4 +15 C/C homozygotes showed a smaller training-induced increase in maximal oxygen consumption ( P = 0.028) than the C/T and T/T genotypes. Similarly, a lower training response in maximal power output was observed in the exon 4 +15 C/C homozygotes ( P = 0.005) compared with the heterozygotes and the T/T homozygotes in black subjects, and a similar trend was evident in white subjects ( P = 0.087). In white subjects, baseline apolipoprotein A-1 (Apo A-1)levels were higher in the exon 4 +15 C/C ( P = 0.011) and exon 7 +65 G/G ( P = 0.05) genotypes compared with those in the other genotypes. In white subjects, exon 4 +15 C/C ( P = 0.0025) and exon 7 +65 G/G ( P = 0.011) genotypes showed significantly greater increases in plasma high-density lipoprotein-cholesterol (HDL-C) levels with endurance training than in the other genotypes, whereas in black subjects the exon 4 +15 CC homozygotes tended to increase ( P = 0.057) their Apo A-1 levels more than the T allele carriers. DNA sequence variation in the PPARδ locus is a potential modifier of changes in cardiorespiratory fitness and plasma HDL-C in healthy individuals in response to regular exercise.
Ventricular fibrillation in myopathic human hearts: mechanistic insights from in vivo global endocardial and epicardial mapping
Authors: Massé Stéphane , Downar Eugene , Chauhan Vijay , Sevaptsidis Elias , Nanthakumar Kumaraswamy
Published: January 2007

Ventricular fibrillation (VF) is an important cause of sudden cardiac death and cardiovascular mortality in patients with cardiomyopathy. Although it was generally believed that chaotic reentrant wavefronts underlie VF in humans, there is emerging evidence of spatiotemporal organization during early VF. The mechanism of this organization of electrical activity in early VF is unknown in myopathic hearts. We studied early VF in vivo, intraoperatively in five cardiomyopathic patients. Simultaneous electrograms were obtained from the epicardium and endocardium in left ventricular cardiomyopathy and from the endocardium in right ventricular myopathy. The Hilbert transform was used to derive the phase of the electrograms. Rotors were identified by isolating phase singularity points. Rotors were present in all of the myopathic hearts studied during VF and cumulatively lasted a mean of 3.2 ± 2.0 s of the 7.0 ± 4.0 s of the VF segments analyzed. For each surface mapped, 3.6 ± 2.9 rotors were identified for the duration mapped. The average number of cycles completed by these rotors was 4.9 ± 4.9. The longest rotor lasted 10.2 ± 6.2 rotations and lasted 2.0 ± 1.2 s. The rotors on the endocardium had a cycle length of 192 ± 33 ms compared with 220 ± 15 ms on the epicardium ( P = 0.08). There is centrifugal activation of electrical activity from these rotors, and they give rise to domains that activate at faster rates with evidence of conduction block at the border with slower domains. These rotors frequently localized to border regions of myocardium with bipolar electrogram amplitude of <0.5 mV. The organization of electrical activity during early VF in myopathic human hearts is characterized by wavefronts emanating from a few rotors.
Limitations to vasodilatory capacity and V̇o2 maxin trained human skeletal muscle
Authors: Barden Jeremy , Lawrenson Lesley , Poole Jennifer G. , Kim Jeannie , Wray D. Walter , Bailey Damian M. , Richardson Russell S.
Published: January 2007

To further explore the limitations to maximal O2consumption (V̇o2 max) in exercise-trained skeletal muscle, six cyclists performed graded knee-extensor exercise to maximum work rate (WRmax) in hypoxia (12% O2), hyperoxia (100% O2), and hyperoxia + femoral arterial infusion of adenosine (ADO) at 80% WRmax. Arterial and venous blood sampling and thermodilution blood flow measurements allowed the determination of muscle O2delivery and O2consumption. At WRmax, O2delivery rose progressively from hypoxia (1.0 ± 0.04 l/min) to hyperoxia (1.20 ± 0.09 l/min) and hyperoxia + ADO (1.33 ± 0.05 l/min). Leg V̇o2 maxvaried with O2availability (0.81 ± 0.05 and 0.97 ± 0.07 l/min in hypoxia and hyperoxia, respectively) but did not improve with ADO-mediated vasodilation (0.80 ± 0.09 l/min in hyperoxia + ADO). Although a vasodilatory reserve in the maximally working quadriceps muscle group may have been evidenced by increased leg vascular conductance after ADO infusion beyond that observed in hyperoxia (increased blood flow but no change in blood pressure), we recognize the possibility that the ADO infusion may have provoked vasodilation in nonexercising tissue of this limb. Together, these findings imply that maximally exercising skeletal muscle may maintain some vasodilatory capacity, but the lack of improvement in leg V̇o2 maxwith significantly increased O2delivery (hyperoxia + ADO), with a degree of uncertainty as to the site of this dilation, suggests an ADO-induced mismatch between O2consumption and blood flow in the exercising limb.
Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone
Authors: Garg Puneet , Martin Christopher F. , Elms Shawn C. , Gordon Frank J. , Wall Susan M. , Garland Christopher J. , Sutliff Roy L. , O'Neill W. Charles
Published: January 2007

Studies in rat aorta have shown that the Na-K-2Cl cotransporter NKCC1 is activated by vasoconstrictors and inhibited by nitrovasodilators, contributes to smooth muscle tone in vitro, and is upregulated in hypertension. To determine the role of NKCC1 in systemic vascular resistance and hypertension, blood pressure was measured in rats before and after inhibition of NKCC1 with bumetanide. Intravenous infusion of bumetanide sufficient to yield a free plasma concentration above the IC50for NKCC1 produced an immediate drop in blood pressure of 5.2% ( P < 0.001). The reduction was not prevented when the renal arteries were clamped, indicating that it was not due to a renal effect of bumetanide. Bumetanide did not alter blood pressure in NKCC1-null mice, demonstrating that it was acting specifically through NKCC1. In third-order mesenteric arteries, bumetanide-inhibitable efflux of86Rb was acutely stimulated 133% by phenylephrine, and bumetanide reduced the contractile response to phenylephrine, indicating that NKCC1 influences tone in resistance vessels. The hypotensive effect of bumetanide was proportionately greater in rats made hypertensive by a 7-day infusion of norepinephrine (12.7%, P < 0.001 vs. normotensive rats) but much less so when hypertension was produced by a fixed aortic coarctation (8.0%), again consistent with an effect of bumetanide on resistance vessels rather than other determinants of blood pressure. We conclude that NKCC1 influences blood pressure through effects on smooth muscle tone in resistance vessels and that this effect is augmented in hypertension.
Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung
Authors: Schindler Margrid B. , Hislop Alison A. , Haworth Sheila G.
Published: January 2007

The response of pulmonary arteries to endothelin-1 (ET-1) changes with age in normal pigs and is abnormal in pulmonary hypertension. The purpose of this study was to determine if the same is true of the pulmonary veins. We studied the wall structure and functional response to ET-1 in pulmonary veins from normal pigs from fetal life to adulthood and from pigs subjected to chronic hypobaric hypoxia either from birth for 3 days or from 3 to 6 days of age. In isolated normal veins, the contractile response decreased by 40% between late fetal life and 14 days of age with a concomitant twofold increase in endothelium-dependent relaxant response. The ETA antagonist BQ-123 reduced the contractile response significantly more in newborn than older animals, whereas the ET-B antagonist BQ-788 had no effect in fetal animals and maximally increased contraction at 14 days of age. Hypoxic exposure significantly increased pulmonary vein smooth muscle area and contractile response to ET-1. The relaxation response was impaired following hypoxic exposure from birth but not from 3 to 6 days of age. The ETA antagonist BQ-123 decreased contractile and increased dilator responses significantly more than in age-matched controls. Thus pulmonary veins show age-related changes similar to those seen in the pulmonary arteries with a decrease in ETA-mediated contractile and increase in ET-B-mediated relaxant response with age. Contractile response was also increased in hypoxia as in the arteries. This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension.
Adaptación de la escala de Orientación a la Dominancia Social al castellano: validación de la Dominancia Grupal y la Oposición a la Igualdad como factores subyacentes
Authors: Silván-Ferrero María del Prado , Bustillos Antonio
Published: January 2007

Pratto, Sidanius, Stallwarth y Malle (1994) formularon la Teoría de la Dominancia Social para expresar el deseo de los individuos por establecer y mantener la jerarquía social y la subordinación de grupos inferiores a los superiores. Para medir las diferencias individuales en este constructo elaboraron la escala de la Orientación a la Dominancia Social (SDO). Recientes investigaciones han señalado la existencia de una estructura bifactorial de la escala: Antiigualitarismo y Orientación a la Dominancia Grupal (Jost y Thompson, 2000; Sidanius y Peña, 2002), a pesar de que en la formulación original se abogaba por la presencia de un constructo unitario.

El presente estudio tiene como finalidad validar la escala de Orientación a la Dominancia Social en una muestra española, así como comprobar qué estructura factorial es más adecuada. Nuestros resultados muestran una buena fiabilidad de la adaptación y validez predictiva. Por su parte, los análisis factoriales realizados muestran un mejor apoyo para la estructura en dos factores propuesta por Jost y Thompson (2000).
Múltiples focos de identificación en las organizaciones: comparación de su poder predictivo sobre los resultados grupales, profesionales y organizacionales
Authors: Topa Gabriela , Palací Francisco
Published: January 2007

El principal objetivo de este estudio ha sido mostrar la existencia de diferentes focos de identificación en la vida de las organzaciones: grupal, personal y organizacional y sus relaciones con actitudes y conductas de los empleados. El análisis factorial confirmatorio con una muestra de empleados (N= 133) mostró la identificación grupal, profesional y organizacional como dimensiones diferentes aunque relacionadas. A través de un modelo de ecuaciones estructurales se prueba que cada foco de identificación será mejor predictor de los resultados en su mismo plano y peor predictor de los resultados en diferentes planos. Los resultados se discuten de cara a sus implicaciones teóricas y aplicadas.
El anuncio político televisivo como herramienta de comunicación electoral. Análisis de caso: los anuncios de la campaña para las elecciones legislativas de marzo de 2004 en España
Authors: García-Beaudoux Virginia , D'Adamo Orlando
Published: January 2007

En este trabajo se analizan los contenidos de la comunicación política de campaña electoral que llega a los votantes a través de una herramienta de comunicación específica: el spot político. Se examina una muestra de 28 anuncios electorales televisivos correspondientes a las elecciones legislativas que tuvieron lugar en España en marzo de 2004. No es nuestra intención explicar el modo en que los ciudadanos televidentes experimentan el visionado de los anuncios de campaña. Nuestro foco, en cambio, está puesto en los anuncios mismos porque entendemos que esas pequeñas historias políticas que se narran en los anuncios de TV ponen al descubierto las estrategias que eligen partidos y candidatos para aproximarse a los electores al suponer que serán las más eficaces a la hora de atraer su voto.