bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Characterization of the SloR Metalloregulome in
Streptococcus mutans
Authors: O'Rourke Kevin P. , Shaw Jeremy D. , Pesesky Mitchell W. , Cook Brian T. , Roberts Susanne M. , Bond Jeffrey P. , Spatafora Grace A. 
Published: November 2009

ABSTRACT

Streptococcus mutans
is the primary causative agent of human dental caries, a ubiquitous infectious disease for which effective treatment strategies remain elusive. We investigated a 25-kDa SloR metalloregulatory protein in this oral pathogen, along with its target genes that contribute to cariogenesis. Previous studies have demonstrated manganese- and SloR-dependent repression of the
sloABCR
metal ion transport operon in
S. mutans
. In the present study, we demonstrate that
S. mutans
coordinates this repression with that of certain virulence attributes. Specifically, we noted virulence gene repression in a manganese-containing medium when SloR binds to promoter-proximal sequence palindromes on the
S. mutans
chromosome. We applied a genome-wide approach to elucidate the sequences to which SloR binds and to reveal additional “class I” genes that are subject to SloR- and manganese-dependent repression. These analyses identified 204
S. mutans
genes that are preceded by one or more conserved palindromic SloR recognition elements (SREs). We cross-referenced these genes with those that we had identified previously as SloR and/or manganese modulated in microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) experiments. From this analysis, we identified a number of
S. mutans
virulence genes that are subject to transcriptional upregulation by SloR and noted that such “class II”-type regulation is dependent on direct SloR binding to promoter-distal SREs. These observations are consistent with a bifunctional role for the SloR metalloregulator and implicate it as a target for the development of therapies aimed at alleviating
S. mutans
-induced caries formation.
Regulatory Interactions of a Virulence-Associated Serine/Threonine Phosphatase-Kinase Pair in
Bacillus anthracis
Authors: Shakir Salika M. , Bryant Katie M. , Larabee Jason L. , Hamm Elaine E. , Lovchik Julie , Lyons C. Rick , Ballard Jimmy D. 
Published: November 2009

ABSTRACT

In the current study, we examined the regulatory interactions of a serine/threonine phosphatase (BA-Stp1), serine/threonine kinase (BA-Stk1) pair in
Bacillus anthracis
.
B. anthracis
STPK101, a null mutant lacking BA-Stp1 and BA-Stk1, was impaired in its ability to survive within macrophages, and this correlated with an observed reduction in virulence in a mouse model of pulmonary anthrax. Biochemical analyses confirmed that BA-Stp1 is a PP2C phosphatase and dephosphorylates phosphoserine and phosphothreonine residues. Treatment of BA-Stk1 with BA-Stp1 altered BA-Stk1 kinase activity, indicating that the enzymatic function of BA-Stk1 can be influenced by BA-Stp1 dephosphorylation. Using a combination of mass spectrometry and mutagenesis approaches, three phosphorylated residues, T165, S173, and S214, in BA-Stk1 were identified as putative regulatory targets of BA-Stp1. Further analysis found that T165 and S173 were necessary for optimal substrate phosphorylation, while S214 was necessary for complete ATP hydrolysis, autophosphorylation, and substrate phosphorylation. These findings provide insight into a previously undescribed Stp/Stk pair in
B. anthracis
.
Requirements for Germination ofClostridium sordelliiSporesIn Vitro
Authors: Ramirez Norma , Abel-Santos Ernesto 
Published: November 2009

ABSTRACTClostridium sordelliiis a spore-forming, obligately anaerobic, Gram-positive bacterium that can cause toxic shock syndrome after gynecological procedures. Although the incidence ofC. sordelliiinfection is low, it is fatal in most cases. Since spore germination is believed to be the first step in the establishment ofBacilliandClostridiainfections, we analyzed the requirements forC. sordelliispore germinationin vitro. Our data showed thatC. sordelliispores require three structurally different amino acids and bicarbonate for maximum germination. Unlike the case forBacillispecies,d-alanine had no effect onC. sordelliispore germination.C. sordelliispores germinated only in a narrow pH range between 5.7 and 6.5. In contrast,C. sordelliispore germination was significantly less sensitive to temperature changes than that of theBacilli. The analysis of the kinetics ofC. sordelliispore germination showed strong allosteric behavior in the binding ofl-phenylalanine andl-alanine but not in that of bicarbonate orl-arginine. By comparing germinant apparent binding affinities to their knownin vivoconcentrations, we postulated a mechanism for differentialC. sordelliispore activation in the female reproductive tract.
Gene Cluster Involved in the Biosynthesis of Griseobactin, a Catechol-Peptide Siderophore of
Streptomyces
sp. ATCC 700974
Authors: Patzer Silke I. , Braun Volkmar 
Published: November 2009

ABSTRACT

The main siderophores produced by streptomycetes are desferrioxamines. Here we show that
Streptomyces
sp. ATCC 700974 and several
Streptomyces griseus
strains, in addition, synthesize a hitherto unknown siderophore with a catechol-peptide structure, named griseobactin. The production is repressed by iron. We sequenced a 26-kb DNA region comprising a siderophore biosynthetic gene cluster encoding proteins similar to DhbABCEFG, which are involved in the biosynthesis of 2,3-dihydroxybenzoate (DHBA) and in the incorporation of DHBA into siderophores via a nonribosomal peptide synthetase. Adjacent to the biosynthesis genes are genes that encode proteins for the secretion, uptake, and degradation of siderophores. To correlate the gene cluster with griseobactin synthesis, the
dhb
genes in ATCC 700974 were disrupted. The resulting mutants no longer synthesized DHBA and griseobactin; production of both was restored by complementation with the
dhb
genes. Heterologous expression of the
dhb
genes or of the entire griseobactin biosynthesis gene cluster in the catechol-negative strain
Streptomyces lividans
TK23 resulted in the synthesis and secretion of DHBA or griseobactin, respectively, suggesting that these genes are sufficient for DHBA and griseobactin biosynthesis. Griseobactin was purified and characterized; its structure is consistent with a cyclic and, to a lesser extent, linear form of the trimeric ester of 2,3-dihydroxybenzoyl-arginyl-threonine complexed with aluminum under iron-limiting conditions. This is the first report identifying the gene cluster for the biosynthesis of DHBA and a catechol siderophore in
Streptomyces
.
Agreement in diagnosing occupational asthma by occupational and respiratory physicians who report to surveillance schemes for work-related ill-health
Authors: Turner Susan , McNamee Roseanne , Roberts Catherine , Bradshaw Lisa , Curran Andrew , Francis Mandy , Fishwick David , Agius Raymond 
Published: November 2009

ObjectivesTo assess diagnostic agreement for occupational asthma, and to identify case and rater characteristics associated with this diagnosis.MethodsSummaries of possible occupational asthma cases were sent to 104 occupational and respiratory physicians. Raters assigned likelihood scores (0–100%) of occupational asthma based on case histories (phase 1), and on histories plus investigative procedures (phase 2). Interclass correlation coefficients were calculated as statistical measures of reliability for occupational asthma scores. Comparisons between mean scores were assessed for statistical significance using tests based on multilevel models. RRs were calculated to summarise effects of raters' demographics, and of supplying investigative procedures information.ResultsOccupational asthma scores showed limited agreement within each group of (occupational or respiratory) physicians, but scores were not systematically different. The difference between mean overall scores was 2.1% (52.1% occupational physicians; 50.0% respiratory physicians) in phase 1 (95% CI −2.6 to 6.8, p=0.37). In phase 2, mean overall scores were 46.1% (occupational physicians) and 41.5% (respiratory physicians); the difference in mean overall scores was 4.6% (95% CI −3.5 to 12.5, p=0.27). Raters with General Medical Council registration ≥1986 were more likely to give a positive occupational asthma diagnosis. In phase 2, male raters were more likely to label cases as occupational asthma than female raters (RR 4.5, 95% CI 3.3 to 6.0).ConclusionsThe RR of a positive occupational asthma diagnosis was unaffected by clinical speciality. Further work on why physicians consider cases to be occupational asthma will assist better diagnosis and prevention of this disease.
Employee control over working times and risk of cause-specific disability pension: the Finnish Public Sector Study
Authors: Vahtera Jussi , Laine Sari , Virtanen Marianna , Oksanen Tuula , Koskinen Aki , Pentti Jaana , Kivimaki Mika 
Published: November 2009

ObjectiveTo examine the association between worktime control and subsequent disability pension among employees.MethodsTwo scores of worktime control (self-assessed and co-worker assessed) were obtained from a survey in 2000–2001 (score range 1–5) among 30 700 public sector employees (78% women) aged 18–64 years. Information on cause-specific disability pension during follow-up was collected from national registers.ResultsDuring a mean follow-up of 4.4 years, 1178 employees were granted disability pensions (incidence per 1000 person-years: 9.2 in women and 8.7 in men). The most common causes of a disability pension were musculoskeletal disorders (43% of all pensions), mental disorders (25%), tumours (8%) and diseases of the circulatory system (6%) and nervous system (6%). A one unit increase in self-assessed and co-worker assessed worktime control score was associated with a 41–48% decrease in risk of disabling musculoskeletal disorders in men and a 33–35% decrease in women. This association was robust to adjustment for 17 baseline covariates (in men and women combined, adjusted HR 0.76, 95% CI 0.67 to 0.87 and 0.64, 95% CI 0.51 to 0.79 per one unit increase in self-assessed and co-worker assessed worktime control, respectively). Self-assessed, but not co-worker assessed, worktime control was also associated with risk of disability retirement due to mental disorders in women. Disability pensions from other disease categories were not related to worktime control.ConclusionsIn these public sector employees, high worktime control was associated with reduced risk of early retirement caused by musculoskeletal disorders independent of baseline characteristics.
An approach for estimating the health effects of changes over time in air pollution: an illustration using cardio-respiratory hospital admissions in London
Authors: Tonne Cathryn , Beevers Sean , Kelly Frank J , Jarup Lars , Wilkinson Paul , Armstrong Ben 
Published: November 2009

ObjectivesFirst, we present a general analytical approach to estimating the association between medium-term changes in air pollution and health across small areas. As a specific illustration, we then applied the approach to data on London residents from a 4-year period to test whether reductions in traffic-related air pollution were associated with reductions in cardio-respiratory hospital admissions.MethodsA binomial distribution was used to model change in admissions over time in each small area, which was measured as the proportion of admissions in 2003–2004 out of admissions over all study years (2001–2004). Annual average concentrations of nitrogen oxides (NOx) were modelled using an emissions-dispersion model. The association between change in NOxand change in hospital admissions was estimated using logistic regression and an instrumental variable approach.ResultsFor some diagnostic groups, suggestive associations between reductions in NOxand reductions in admissions were observed, for example, OR=0.97 (95% CI 0.96 to 0.99) for an IQR decrease in NOx(3 μg/m3) and all respiratory admissions. Accounting for spatial dependence attenuated several of the associations; for respiratory admissions, the OR was 1.00 (95% CI 0.98 to 1.02), leaving only that for bronchiolitis significant (OR=0.91; 95% CI 0.84 to 0.99). In this particular illustration, the instrumental variable approach did not appear to add information.ConclusionsIn this illustration, there was relatively limited power to detect an association between changes in air pollution and hospital admissions over time. However, the analytical approach could deliver more robust estimates of the health effects of changes in air pollution in settings with greater spatial contrast in changes in air pollution over time.
Dermal exposure to polycyclic aromatic hydrocarbons in asphalt workers
Authors: Fustinoni Silvia , Campo Laura , Cirla Piero E , Martinotti Irene , Buratti Marina , Longhi Omar , Foà Vito , Bertazzi PierAlberto 
Published: November 2009

ObjectivesTo assess dermal exposure to 16 polycyclic aromatic hydrocarbons (PAHs) in asphalt workers by applying polypropylene pads to six body sites (neck, shoulder, upper arm, wrist, groin, ankle), to identify the compounds and exposure sites most representative, and to integrate dermal exposure results with environmental and biological data.MethodsTwenty-four asphalt workers were recruited. Dermal exposure was assessed during a single work shift. Sixteen PAHs (from naphthalene to indeno[1,2,3-cd]pyrene) were quantified via gas chromatography-mass spectrometry. Airborne exposure, urinary PAHs and monohydroxy metabolites were also investigated.ResultsPhenanthrene (PHE), present in all samples, was the most abundant compound (median 0.805–1.825 ng/cm2). Benzo[a]pyrene (BaP) was present in 75% of the samples (0.046–0.101 ng/cm2). Wrist had the highest contamination, with median PHE, pyrene (PYR), and BaP concentrations of 1.825, 0.527, and 0.063 ng/cm2. PHE and PYR on wrist correlated with almost all 3- to 4-ring PAHs (0.405≤r≤0.856), but not with BaP; BaP correlated with almost all 4- to 6- ring PAHs (0.584≤r≤0.633). Significant correlations were observed between PHE level, airborne exposure, and the corresponding urinary PHE and monohydroxy metabolites. For PYR, significant correlations existed only between urinary PYR and monohydroxy metabolites. Multiple linear regression analysis revealed that 42% of the end-of-shift monohydroxy metabolites were the result of airborne exposure, dermal exposure, and baseline levels of biomarkers.ConclusionsDermal exposure to PAHs was in the low ng/cm2range. PHE or PYR and BaP were the most representative compounds and the wrist was the best location to perform dermal exposure assessments. Both dermal and airborne exposure contributed to the total body burden of PAHs, though the relative contribution was analyte-dependent.
Selecting an appropriate biomonitoring strategy to evaluate dermal exposure to opioid narcotic analgesics in pharmaceutical production workers
Authors: Van Nimmen N F J , Poels K L C , Severi M J , Godderis L , Veulemans H A F 
Published: November 2009

ObjectivesIn a follow-up study of previous research, in which exposure pathways for opioid narcotic analgesics were identified in pharmaceutical workers involved in drug synthesis, the current research focused on the selection of an appropriate biomonitoring strategy.MethodsSix opioid narcotic production workers were intensively monitored during a (1 week) fentanyl production campaign. A systematic sampling scheme was followed that provided information about hand contamination and biomarker levels at multiple time points.ResultsLinear mixed-effects models, incorporating half-shift and end-of-shift hand contamination levels, showed a positive and significant correlation with fentanyl urinary excretion occurring at many of the 4 h time lags investigated (4–28 h). Optimum model characteristics, including both minimal between- and within-worker variability, were obtained at lag times of 24 h and 20 h, respectively, advocating a pre-shift urine sampling strategy on the following day. In addition, for these lag times the portion of the variability explained by the model was maximal. Furthermore, using a distributed lag model, it was demonstrated that urinary fentanyl levels were positively correlated with hand contamination levels measured at the preceding four 8 h time lags (8–32 h), although statistical significance was only shown for a lag time of 24 h.ConclusionFentanyl levels in pre-shift urine samples reflect dermal exposure to the compound during the previous day. Thus, in the specific working environment investigated, a biological monitoring protocol evaluating pre-shift urinary fentanyl levels could provide an adequate risk estimate in individual workers.
Excessive Glenohumeral Horizontal Abduction as Occurs during the Late Cocking Phase of the Throwing Motion can be Critical for Internal Impingement
Authors: Mihata Teruhisa , McGarry Michelle H. , Kinoshita Mitsuo , Lee Thay Q. 
Published: November 2009

Background The objective of this study was to determine the effects of increased horizontal abduction with maximum external rotation, as occurs during the late cocking phase of throwing motion, on shoulder internal impingement. Hypothesis An increase in glenohumeral horizontal abduction will cause overlap of the rotator cuff insertion with respect to the glenoid and increase pressure between the supraspinatus and infraspinatus tendon insertions on the greater tuberosity and the glenoid. Study Design Controlled laboratory study. Methods Eight cadaveric shoulders were tested with a custom shoulder testing system with the specimens in 60° of glenohumeral abduction and maximum external rotation. The amount of internal impingement was evaluated by assessing the location of the supraspinatus and infraspinatus articular insertions on the greater tuberosity relative to the glenoid using a MicroScribe 3DLX. Pressure in the posterior-superior quadrant of the glenoid was measured using Fuji prescale film. Data were obtained with the humerus in the scapular plane and 15°, 30°, and 45° of horizontal abduction from the scapular plane. Results At 30° and 45° of horizontal abduction, the articular margin of the supraspinatus and infraspinatus tendons was anterior to the posterior edge of the glenoid and less than 2 mm from the glenoid rim in the lateral direction; the contact pressure was also greater than that found in the scapular plane and 15° of horizontal abduction. Conclusion Horizontal abduction beyond the coronal plane increased the amount of overlap and contact pressure between the supraspinatus and infraspinatus tendons and glenoid. Clinical Relevance Excessive glenohumeral horizontal abduction beyond the coronal plane may cause internal impingement, which may lead to rotator cuff tears and superior labral anterior to posterior (SLAP) lesions.
Effect of Graft Selection on the Incidence of Postoperative Infection in Anterior Cruciate Ligament Reconstruction
Authors: Barker Joseph U. , Drakos Mark C. , Maak Travis G. , Warren Russell F. , Williams Riley J. , Allen Answorth A. 
Published: November 2009

Background Knee joint infection is a potentially devastating complication of anterior cruciate ligament (ACL) reconstruction. There is a theoretical increased risk of infection with the use of allograft material. Hypothesis An allograft ACL reconstruction predisposes patients to a higher risk of bacterial infection. Study Design Cohort Study; Level of evidence, 3. Methods All primary ACL reconstructions performed at our institution between January 2002 and December 2006 were reviewed; 3126 total procedures were identified. A retrospective medical record review was performed to determine the incidence of infection, offending organism, time after surgery until presentation, infection treatment, and graft salvage as an outcome of graft choice. Results Of the 3126 ACL reconstructions, 1777 autografts and 1349 allografts were performed. Eighteen infections were identified (0.58%). Infections occurred in 6 of the 1349 allografts (0.44%), 7 of the 1430 bone-patellar tendon-bone (BPTB) autografts (0.49%), and 5 of the 347 hamstring autografts (1.44%). Five grafts were removed because of graft incompetence or loosening: 3 hamstring tendon, 1 BPTB, and 1 allograft. The most common organism isolated was Staphylococcus aureus. Hamstring tendon autograft had an increased incidence of infection compared with both BPTB autograft and allograft (P < .05), with a trend toward a more common need for graft removal (P = .09). Allograft reconstructions were equally likely to have graft salvage as autograft reconstructions. Conclusion Hamstring tendon autografts have a higher incidence of infection than BPTB autografts or allografts. The use of allograft material in ACL reconstructions does not increase the risk of infection or the need for graft removal with infection.
Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma
Authors: Chauhan Dharminder , Singh Ajita V. , Ciccarelli Bryan , Richardson Paul G. , Palladino Michael A. , Anderson Kenneth C. 
Published: November 2009

Abstract
Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib (Velcade) and, importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib. Here we demonstrate that combining NPI-0052 and lenalidomide (Revlimid) induces synergistic anti-MM activity in vitro using MM-cell lines or patient MM cells. NPI-0052 plus lenalidomide-induced apoptosis is associated with (1) activation of caspase-8, caspase-9, caspase-12, caspase-3, and poly(ADP) ribose polymerase; (2) activation of BH-3 protein BIM; (3) translocation of BIM to endoplasmic reticulum; (4) inhibition of migration of MM cells and angiogenesis; and (5) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. Importantly, blockade of BIM using siRNA significantly abrogates NPI-0052 plus lenalidomide-induced apoptosis. Furthermore, studies using biochemical inhibitors of caspase-8 versus caspase-9 demonstrate that NPI-0052 plus lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling. In animal tumor model studies, low-dose combination of NPI-0052 and lenalidomide is well tolerated, significantly inhibits tumor growth, and prolongs survival. Taken together, our study provides the preclinical rationale for clinical protocols evaluating lenalidomide together with NPI-0052 to improve patient outcome in MM.
Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation
Authors: Aubin Éric , Lemieux Réal , Bazin Renée 
Published: November 2009

AbstractSeveral clinical studies done with intravenous immunoglobulin (IVIg)–treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcγRIIb-independent, suggesting that IVIg must interfere with activating FcγRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.