bluuebunny/crossref_metadata_2025 huggingface dataset:
Microevolution and Patterns of Dissemination of the JP2 Clone of
Aggregatibacter
(
Actinobacillus
)
actinomycetemcomitans
Authors: Haubek Dorte , Poulsen Knud , Kilian Mogens
Published: March 2007

The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of
Aggregatibacter
(
Actinobacillus
)
actinomycetemcomitans
were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82
A. actinomycetemcomitans
strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes
hbpA
and
tbpA
. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.
Wild-Type and Interleukin-10-Deficient Regulatory T Cells Reduce Effector T-Cell-Mediated Gastroduodenitis in Rag2−/−Mice, but Only Wild-Type Regulatory T Cells SuppressHelicobacter pyloriGastritis
Authors: Lee Chung-Wei , Rao Varada P. , Rogers Arlin B. , Ge Zhongming , Erdman Susan E. , Whary Mark T. , Fox James G.
Published: March 2007

CD4+CD45RBhiCD25−effector T cells (TE) promoteHelicobacter pylorigastritis in mice, and CD4+CD45RBloCD25+regulatory T cells (TR) are anti-inflammatory. Using adoptive transfer intoH. pylori-infected Rag2−/−mice, we evaluated effects of wild-type (wt) C57BL/6 or congenic interleukin-10-deficient (IL-10−/−) TRcells on gastritis, gastric cytokines, andH. pyloricolonization. Infected Rag2−/−mice colonized in the corpus and antrum with 105to 106H. pyloriCFU/gram without associated gastritis. TEcell transfer caused morbidity and anH. pylori-independent pangastritis and duodenitis (gastroduodenitis) associated with increased expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha. TEcell transfer toH. pylori-infected mice led to additive corpus gastritis associated with inflammatory cytokine expression and reduced colonization. wt TRcells reduced morbidity,H. pyloricorpus gastritis, gastroduodenitis, and inflammatory cytokine expression and reversed the decline inH. pyloricolonization attributable to TEcells. Although less effective than wt TRcells, IL-10−/−TRcells also reduced morbidity and gastroduodenitis but did not reduceH. pyloricorpus gastritis or impact TEcell inhibition of colonization. Gastric tissues from mice receiving wt TRcells expressed higher levels of Foxp3 compared to recipients of IL-10−/−TRcells, consistent with lower regulatory activity of IL-10−/−TRcells. These results demonstrate that wt TRcells suppressed TE-cell-mediatedH. pylori-independent gastroduodenitis andH. pylori-dependent corpus gastritis more effectively than IL-10−/−TRcells. Compartmental differences in TE-cell- andH. pylori-mediated inflammation and in regulatory effects between wt TRand IL-10−/−TRcells suggest that IL-10 expression by wt TRcells is important to regulatory suppression of gastric inflammation.
Deficiencies of Myeloid Differentiation Factor 88, Toll-Like Receptor 2 (TLR2), or TLR4 Produce Specific Defects in Macrophage Cytokine Secretion Induced byHelicobacter pylori
Authors: Obonyo Marygorret , Sabet Mojgan , Cole Sheri P. , Ebmeyer Joerg , Uematsu Satoshi , Akira Shizuo , Guiney Donald G.
Published: March 2007

Helicobacter pyloriis a gram-negative microaerophilic bacterium that colonizes the gastric mucosa, leading to disease conditions ranging from gastritis to cancer. Toll-like receptors (TLRs) play a central role in innate immunity by their recognition of conserved molecular patterns on bacteria, fungi, and viruses. Upon recognition of microbial components, these TLRs associate with several adaptor molecules, including myeloid differentiation factor 88 (MyD88). To investigate the contribution of the innate immune system toH. pyloriinfection, bone marrow-derived macrophages from mice deficient in TLR2, TLR4, TLR9, and MyD88 were infected withH. pyloriSS1 and SD4 for 24 or 48 h. We demonstrate that MyD88 was essential forH. pyloriinduction of all cytokines investigated except alpha interferon (IFN-α). The secretion of IFN-α was substantially increased from cells deficient in MyD88.H. pyloriinduced interleukin-12 (IL-12) and IL-10 through TLR4/MyD88 signaling. In addition,H. pyloriinduced less IL-6 and IL-1β in TLR2-deleted macrophages, suggesting that the MyD88 pathway activated by TLR2 stimulation is responsible forH. pyloriinduction of the host proinflammatory response (IL-6 and IL-1β). These observations are important in light of a recent report on IL-6 and IL-1β playing a role in the development ofH. pylori-related gastric cancer. In conclusion, our study demonstrates thatH. pyloriactivates TLR2 and TLR4, leading to the secretion of distinct cytokines by macrophages.
The ChrA-ChrS and HrrA-HrrS Signal Transduction Systems Are Required for Activation of the
hmuO
Promoter and Repression of the
hemA
Promoter in
Corynebacterium diphtheriae
Authors: Bibb Lori A. , Kunkle Carey A. , Schmitt Michael P.
Published: March 2007

Transcription of the
Corynebacterium diphtheriae hmuO
gene, which encodes a heme oxygenase involved in heme iron utilization, is activated in a heme- or hemoglobin-dependent manner in part by the two-component system ChrA-ChrS. Mutation of either the
chrA
or the
chrS
gene resulted in a marked reduction of hemoglobin-dependent activation at the
hmuO
promoter in
C. diphtheriae
; however, it was observed that significant levels of hemoglobin-dependent expression were maintained in the mutants, suggesting that an additional activator is involved in regulation. A BLAST search of the
C. diphtheriae
genome sequence revealed a second two-component system, encoded by DIP2268 and DIP2267, that shares similarity with ChrS and ChrA, respectively; we have designated these genes
hrrS
(DIP2268) and
hrrA
(DIP2267). Analysis of
hmuO
promoter expression demonstrated that hemoglobin-dependent activity was fully abolished in strains from which both the
chrA
-
chrS
and the
hrrA
-
hrrS
two-component systems were deleted. Similarly, deletion of the sensor kinase genes
chrS
and
hrrS
or the genes encoding both of the response regulators
chrA
and
hrrA
also eliminated hemoglobin-dependent activation at the
hmuO
promoter. We also show that the regulators ChrA-ChrS and HrrA-HrrS are involved in the hemoglobin-dependent repression of the promoter upstream of
hemA
, which encodes a heme biosynthesis enzyme. Evidence for cross talk between the ChrA-ChrS and HrrA-HrrS systems is presented. In conclusion, these findings demonstrate that the ChrA-ChrS and HrrA-HrrS regulatory systems are critical for full hemoglobin-dependent activation at the
hmuO
promoter and also suggest that these two-component systems are involved in the complex mechanism of the regulation of heme homeostasis in
C. diphtheriae
.
A Genetic Screen forMycobacterium tuberculosisMutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System
Authors: MacGurn Jason A. , Cox Jeffery S.
Published: March 2007

After phagocytosis, the intracellular pathogenMycobacterium tuberculosisarrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set ofM. tuberculosismutants specifically attenuated for growth in mice to identify strains that failed to arrest phagosome maturation and trafficked to late phagosomal compartments. We identified 10 such mutants that could be partitioned into two classes based on the kinetics of trafficking. Importantly, four of these mutants harbor mutations in genes that encode components of the ESX-1 secretion system, a pathway critical forM. tuberculosisvirulence. Although ESX-1 is required, the known ESX-1 secreted proteins are dispensable for phagosome maturation arrest, suggesting that a novel effector required for phagosome maturation arrest is secreted by ESX-1. Other mutants identified in this screen had mutations in genes involved in lipid synthesis and secretion and in molybdopterin biosynthesis, as well as in genes with unknown functions. Most of these trafficking mutants exhibited a corresponding growth defect during macrophage infection, but two mutants grew like wild-typeM. tuberculosisduring macrophage infection. Our results support the emerging consensus that multiple factors fromM. tuberculosis, including the ESX-1 secretion system, are involved in modulating trafficking within the host.
GLOBAL GAUGE FIXING FOR CONNECTIONS WITH SMALL CURVATURE ON T2
Authors: NISHINOU TAKEO
Published: March 2007

In this paper, we will construct a global gauge for connections with small curvature on the trivial complex rank 2 bundle on T2. In this gauge the connection matrix A satisfies [Formula: see text].
Endogenous urokinase lacks antifibrotic activity during progressive renal injury
Authors: Yamaguchi Ikuyo , Lopez-Guisa Jesus M. , Cai Xiaohe , Collins Sarah J. , Okamura Daryl M. , Eddy Allison A.
Published: March 2007

Interstitial fibrosis is a universal feature of progressive kidney disease. Urokinase-type plasminogen activator (uPA) is thought to participate for several reasons: 1) uPA is produced predominantly in kidney, 2) its inhibitor plasminogen activator inhibitor-1 (PAI-1) is a strong promoter of interstitial fibrosis, whereas its receptor (uPAR) attenuates renal fibrosis, 3) uPA reduces fibrosis in liver and lung, and 4) uPA can activate hepatocyte growth factor (HGF), a potent antifibrotic growth factor. The present study tested the hypothesis that endogenous uPA reduces fibrosis severity by investigating the unilateral ureteral obstruction (UUO) model in wild-type (WT) and uPA−/− mice. Several outcomes were measured: renal collagen 3–21 days after UUO, macrophage accumulation (F4/80 Western blotting), interstitial myofibroblast density (α-smooth muscle actin immunostaining), and tubular injury (E-cadherin and Ksp-cadherin Western blotting). None of these measures differed significantly between WT and uPA−/− mice. uPA genetic deficiency was not associated with compensatory changes in renal uPAR mRNA levels, PAI-1 protein levels, or tissue plasminogen activator activity levels after UUO. Despite the known ability of uPA to activate latent HGF, immunoblotting failed to detect significant differences in levels of the active HGF α-chain and phosphorylated cMET (the activated HGF receptor) between the WT and uPA−/− groups. These findings suggest that the profibrotic actions of PAI-1 are uPA independent and that an alternative pathway must activate HGF in kidney. Finally, these results highlight a significant organ-specific difference in basic fibrogenic pathways, as enhanced uPA activity has been reported to attenuate pulmonary and hepatic fibrosis.
Activity-Dependent Initiation of a Prolonged Depolarization inAplysiaBag Cell Neurons: Role for a Cation Channel
Authors: Hung Anne Y. , Magoski Neil S.
Published: March 2007

The translation of prior activity into changes in excitability is essential for memory and the initiation of behavior. After brief synaptic input, the bag cell neurons of Aplysia californica undergo a nearly 30-min afterdischarge to release egg-laying hormone. The present study examines a prolonged depolarization in cultured bag cell neurons. A 5-Hz, 10-s action potential train elicited a depolarization of about 10 mV, which lasted ≤30 min and was reduced by calmodulin kinase inhibition. Very broad action potentials (resulting from TEA application) decreased prolonged depolarization amplitude, indicating that strong Ca2+influx did not necessarily promote the response. The prolonged depolarization current ( IPD) was recorded after 5-Hz, 10-s trains of square voltage pulses of varying duration (10–150 ms). Despite Ca2+influx increasing steadily with pulse duration, IPDwas most reliably initiated at 100 ms, suggesting a Ca2+window or limit exists for triggering IPD. Consistent with this, modestly broader action potentials, evoked by lengthening the train current-pulse duration, resulted in smaller prolonged depolarizations. With respect to the properties of IPD, it displayed a linear current–voltage relationship with a reversal potential of about −45 mV that was shifted to approximately −25 mV by lowering internal K+or about −56 mV by lowering external Na+and Ca2+. IPDwas blocked by Gd3+, but was not antagonized by MDL-123302A, SKF-96365, 2-APB, tetrodotoxin, or flufenamic acid. Optimal Ca2+influx may activate calmodulin kinase and a voltage-independent, nonselective cation channel to initiate the prolonged depolarization, thereby contributing to the afterdischarge and reproduction.
Comparison of Clinical and Administrative Data Sources for Hospital Coronary Artery Bypass Graft Surgery Report Cards
Authors: Shahian David M. , Silverstein Treacy , Lovett Ann F. , Wolf Robert E. , Normand Sharon-Lise T.
Published: March 2007

Background—

Regardless of statistical methodology, public performance report cards must use the highest-quality validated data, preferably from a prospectively maintained clinical database. Using logistic regression and hierarchical models, we compared hospital cardiac surgery profiling results based on clinical data with those derived from contemporaneous administrative data.

Methods and Results—

Fiscal year 2003 isolated coronary artery bypass grafting surgery results based on an audited and validated Massachusetts clinical registry were compared with those derived from a contemporaneous state administrative database, the latter using the inclusion/exclusion criteria and risk model of the Agency for Healthcare Research and Quality. There was a 27.4% disparity in isolated coronary artery bypass grafting surgery volume (4440 clinical, 5657 administrative), a 0.83% difference in observed in-hospital mortality (2.05% versus 2.88%), corresponding differences in risk-adjusted mortality calculated by various statistical methodologies, and 1 hospital classified as an outlier only with the administrative data–based approach. The discrepancies in volumes and risk-adjusted mortality were most notable for higher-volume programs that presumably perform a higher proportion of combined procedures that were misclassified as isolated coronary artery bypass grafting surgery in the administrative cohort. Subsequent analyses of a patient cohort common to both databases revealed the smoothing effect of hierarchical models, a 9% relative difference in mortality (2.21% versus 2.03%) resulting from nonstandardized mortality end points, and 1 hospital classified as an outlier using logistic regression but not using hierarchical regression.

Conclusions—

Cardiac surgery report cards using administrative data are problematic compared with those derived from audited and validated clinical data, primarily because of case misclassification and nonstandardized end points.
Factors Associated With Mortality and Reoperation in 377 Children With Total Anomalous Pulmonary Venous Connection
Authors: Karamlou Tara , Gurofsky Rebecca , Al Sukhni Eisar , Coles John G. , Williams William G. , Caldarone Christopher A. , Van Arsdell Glen S. , McCrindle Brian W.
Published: March 2007

Background—

We sought to determine era-specific changes in the incidence of mortality and reoperation in children with total anomalous pulmonary venous connection.

Methods and Results—

We reviewed the records of 377 children presenting from 1946 to 2005 with total anomalous pulmonary venous connection. Multivariable parametric regression models determined the incidence and risk factors for death and reoperation after repair. Pulmonary venous connection was supracardiac in 44%, infracardiac in 26%, cardiac in 21%, and mixed in 9%. Pulmonary venous obstruction was present in 48% at presentation, most frequently with infracardiac connection type (
P
<0.001). In total, 327 patients were repaired (median age, 1.7 months). Overall survival from repair was 65±6% at 14 years, with a current survival of 97%. Significant (
P
<0.01) incremental risk factors for postrepair death were cardiac connection type, earlier operation year, younger age at repair, use of epinephrine postoperatively, and postoperative pulmonary venous obstruction. More recent operation year was associated with younger age at repair (
P
<0.001), decreased use of deep hypothermic circulatory arrest (
P
<0.001), and use of specific drugs postoperatively (
P
<0.001). Risk-adjusted estimated 1-year survival for a patient repaired at birth with unfavorable morphology in 2005 is 37% (95% CI, 8 to 80) compared with 96% (95% CI, 91 to 99) for a patient with favorable morphology repaired at 1 year of age. Freedom from reoperation was 82±6% at 11 years after repair, with increased risk associated with mixed connection type (
P
=0.04) and postoperative pulmonary venous obstruction (
P
<0.001).

Conclusions—

Mortality after total anomalous pulmonary venous connection repair has decreased but remains highest in young patients and in those with cardiac connection type or pulmonary venous obstruction. Unfavorable anatomic characteristics remain important determinants of postrepair survival despite improved perioperative care.
Tumor Necrosis Factor-α Mediates Cardiac Remodeling and Ventricular Dysfunction After Pressure Overload State
Authors: Sun Mei , Chen Manyin , Dawood Fayez , Zurawska Urszula , Li Jeff Y. , Parker Thomas , Kassiri Zamaneh , Kirshenbaum Lorrie A. , Arnold Malcolm , Khokha Rama , Liu Peter P.
Published: March 2007

Background—

Pressure overload is accompanied by cardiac myocyte apoptosis, hypertrophy, and inflammatory/fibrogenic responses that lead to ventricular remodeling and heart failure. Despite incomplete understanding of how this process is regulated, the upregulation of tumor necrosis factor (TNF)-α after aortic banding in the myocardium is known. In the present study, we tested our hypothesis that TNF-α regulates the cardiac inflammatory response, extracellular matrix homeostasis, and ventricular hypertrophy in response to mechanical overload and contributes to ventricular dysfunction.

Methods and Results—

C57/BL wild-type mice and TNF-knockout (TNF
−/−
) mice underwent descending aortic banding or sham operation. Compared with sham-operated mice, wild-type mice with aortic banding showed a significant increase in cardiac TNF-α levels, which coincided with myocyte apoptosis, inflammatory response, and cardiac hypertrophy in week 2 and a significant elevation in matrix metalloproteinase-9 activity and impaired cardiac function in weeks 2 and 6. Compared with wild-type mice with aortic banding, TNF
−/−
mice with aortic banding showed attenuated cardiac apoptosis, hypertrophy, inflammatory response, and reparative fibrosis. These mice also showed reduced cardiac matrix metalloproteinase-9 activity and improved cardiac function.

Conclusions—

Findings from the present study have suggested that TNF-α contributes to adverse left ventricular remodeling during pressure overload through regulation of cardiac repair and remodeling, leading to ventricular dysfunction.
Oxygen Activates the Rho/Rho-Kinase Pathway and Induces RhoB and ROCK-1 Expression in Human and Rabbit Ductus Arteriosus by Increasing Mitochondria-Derived Reactive Oxygen Species
Authors: Kajimoto Hidemi , Hashimoto Kyoko , Bonnet Sandra N. , Haromy Alois , Harry Gwyneth , Moudgil Rohit , Nakanishi Toshio , Rebeyka Ivan , Thébaud Bernard , Michelakis Evangelos D. , Archer Stephen L.
Published: March 2007

Background—

Constriction of the ductus arteriosus (DA) is initiated at birth by inhibition of O
2
-sensitive K
+
channels in DA smooth muscle cells. Subsequent membrane depolarization and calcium influx through L-type calcium channels initiates functional closure. We hypothesize that Rho-kinase activation is an additional mechanism that sustains DA constriction.

Methods and Results—

The effect of increased P
o
2
on the activity and expression of Rho-kinase was assessed in DAs from neonates with hypoplastic left-heart syndrome (n=15) and rabbits (339 term and 99 preterm rabbits). Rho-kinase inhibitors (Y-27632 and fasudil) prevent and reverse O
2
constriction. Heterogeneity exists in the sensitivity of constrictors (P
o
2
=endothelin=phenylephrine>KCl) and of fetal vessels (DA=pulmonary artery>aorta) to Rho-kinase inhibition. Inhibition of L-type calcium channels (nifedipine) or removal of extracellular calcium inhibits approximately two thirds of O
2
constriction. Residual DA constriction reflects calcium sensitization, which persists after removal of extracellular calcium and blocking of sarcoplasmic reticulum Ca
2+
-ATPase. In term DA, an increase in P
o
2
activates Rho-kinase and thereby increases RhoB and ROCK-1 expression. Activation of Rho-kinase in DA smooth muscle cells is initiated by a P
o
2
-dependent, rotenone-sensitive increase in mitochondrion-derived reactive O
2
species. O
2
effects on Rho-kinase are mimicked by exogenous H
2
O
2
. In preterm DAs, immaturity of mitochondrial reactive oxygen species generation is associated with reduced and delayed O
2
constriction and lack of P
o
2
-dependent upregulation of Rho-kinase expression.

Conclusions—

O
2
activates Rho-kinase and increases Rho-kinase expression in term DA smooth muscle cells by a redox-regulated, positive-feedback mechanism that promotes sustained vasoconstriction. Conversely, Rho-kinase inhibitors may be useful in maintaining DA patency, as a bridge to congenital heart surgery.
Six-Month Outcome of Emergency Percutaneous Coronary Intervention in Resuscitated Patients After Cardiac Arrest Complicating ST-Elevation Myocardial Infarction
Authors: Garot Philippe , Lefevre Thierry , Eltchaninoff Hélène , Morice Marie-Claude , Tamion Fabienne , Abry Bernard , Lesault Pierre-François , Le Tarnec Jean-Yves , Pouges Claude , Margenet Alain , Monchi Mehran , Laurent Ivan , Dumas Pierre , Garot Jérôme , Louvard Yves
Published: March 2007

Background—

The outcome of resuscitated patients after cardiac arrest complicating acute myocardial infarction remains poor, primarily because of the relatively low success rates of cardiopulmonary resuscitation management. Existing data suggest potential beneficial effects of early myocardial reperfusion, but the predictors of survival in these patients remain unknown.

Methods and Results—

From 1995 to 2005, 186 patients (78% men; mean age, 60.4±13.8 years) underwent immediate percutaneous coronary intervention after successful resuscitation for cardiac arrest complicating acute myocardial infarction. Prompt prehospital management was performed by mobile medical care units in 154 of 186 patients, whereas 32 had in-hospital cardiac arrest. Infarct location was anterior in 105 patients (56%), and shock was present on admission in 96 (52%). Percutaneous coronary intervention (stenting rate 90%) was successful in 161 of 186 patients (87%). Six-month survival rate was 100 of 186 (54%), and 6-month survival free of neurological sequelae was 46%. By multivariate analysis, predictors of 6-month survival were a shorter interval between the onset of cardiac arrest and arrival of a first responder (odds ratio, 0.67; 95% CI, 0.54 to 0.84), a shorter interval between the onset of cardiac arrest and return of spontaneous circulation (odds ratio, 0.91; 95% CI, 0.87 to 0.96), and absence of diabetes (odds ratio, 7.30; 95% CI, 1.80 to 29.41).

Conclusions—

In patients with resuscitated cardiac arrest complicating acute myocardial infarction, prompt prehospital management and early revascularization were associated with a 54% survival rate at 6 months. A strategy including adequate prehospital management, early revascularization, and specific care in dedicated intensive care units should be strongly considered in resuscitated patients after cardiac arrest complicating acute myocardial infarction.
Amplified Expression Profiling of Platelet Transcriptome Reveals Changes in Arginine Metabolic Pathways in Patients With Sickle Cell Disease
Authors: Raghavachari Nalini , Xu Xiuli , Harris Amy , Villagra Jose , Logun Carolea , Barb Jennifer , Solomon Michael A. , Suffredini Anthony F. , Danner Robert L. , Kato Gregory , Munson Peter J. , Morris Sidney M. , Gladwin Mark T.
Published: March 2007

Background—

In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, which suggests that pathological platelet activation may contribute to sickle cell disease vasculopathy.

Methods and Results—

Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate in the present study the feasibility of comparative platelet transcriptome studies on clinical samples from single donors by the application of RNA amplification followed by microarray-based analysis of 54 000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by >10-fold increased expression compared with the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the present study included 82% or 70% of platelet-abundant genes identified in 2 previous gene expression studies on nonamplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to those of 12 black control subjects, at a 3-fold cutoff and 5% false-discovery rate, we identified ≈100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways with real-time polymerase chain reaction and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels.

Conclusions—

The present studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology.
Increasing Cardiovascular Disease Burden Due to Diabetes Mellitus
Authors: Fox Caroline S. , Coady Sean , Sorlie Paul D. , D’Agostino Ralph B. , Pencina Michael J. , Vasan Ramachandran S. , Meigs James B. , Levy Daniel , Savage Peter J.
Published: March 2007

Background—

Marked reductions in cardiovascular disease (CVD) morbidity and mortality have occurred in the United States over the last 50 years. We tested the hypothesis that the relative burden of CVD attributable to diabetes mellitus (DM) has increased over the past 5 decades.

Methods and Results—

Participants aged 45 to 64 years from the Framingham Heart Study, who attended examinations in an “early” time period (1952 to 1974), were compared with those who attended examinations in a later time period (1975 to 1998). The risk of CVD events (n=133 among those with and 1093 among those without DM) attributable to DM in the 2 time periods was assessed with Cox proportional hazards models; population attributable risk of DM as a CVD risk factor was calculated for each time period. The age- and sex-adjusted hazard ratio for DM as a CVD risk factor was 3.0 (95% CI, 2.3 to 3.9) in the earlier time period and 2.5 (95% CI, 1.9 to 3.2) in the later time period. The population attributable risk for DM as a CVD risk factor increased from 5.4% (95% CI, 3.8% to 6.9%) in the earlier time period to 8.7% (95% CI, 5.9% to 11.4%) in the later time period (
P
for attributable risk ratio=0.04), although multivariable adjustment resulted in attenuation of these findings (
P
=0.12); most of these observations were found among men.

Conclusions—

The proportion of CVD attributable to DM has increased over the past 50 years in Framingham. These findings emphasize the need for increased efforts to prevent DM and to aggressively treat and control CVD risk factors among those with DM.
High Prevalence of Sleep Apnea Syndrome in Patients With Long-Term Pacing
Authors: Garrigue Stéphane , Pépin Jean-Louis , Defaye Pascal , Murgatroyd Francis , Poezevara Yann , Clémenty Jacques , Lévy Patrick
Published: March 2007

Background—

Cardiovascular diseases leading to pacemaker implantations are suspected of being associated with a high rate of undiagnosed sleep apnea syndrome (SAS). We sought to determine the prevalence and consequences of SAS in pacemaker patients according to pacing indications: heart failure, symptomatic diurnal bradycardia, and atrioventricular block.

Methods and Results—

Ninety-eight consecutive patients (mean age, 64±8 years) not known to have sleep apnea were included; 29 patients were paced for dilated cardiomyopathy (29%), 33 for high-degree atrioventricular block (34%), and 36 for sinus node disease (37%). All underwent Epworth Sleepiness Scale assessment and polysomnography with the pacemaker programmed to right ventricular DDI pacing mode (lower pacing rate, 50 pulses per minute). SAS was defined as an apnea-hypopnea index ≥10/h. Mean Epworth Sleepiness Scale was in the normal range (7±4), although 13 patients (25%) had an abnormal score >11/h. Fifty-seven patients (59%) had SAS; of these, 21 (21.4%) had a severe SAS (apnea-hypopnea index >30/h). In patients with heart failure, 50% presented with SAS (mean apnea-hypopnea index, 11±7) compared with 68% of patients with atrioventricular block (mean apnea-hypopnea index, 24±29) and 58% with sinus node disease (mean apnea-hypopnea index, 19±23).

Conclusions—

In paced patients, there is an excessively high prevalence of undiagnosed SAS (59%). Whether treating SAS would have changed the need for pacing is unknown. Treatment effects should be further evaluated particularly because these patients are less symptomatic than typical SAS patients. In any case, SAS should be systematically searched for in paced patients owing to potential detrimental effects on their cardiovascular evolution.
A Synthetic Vision System Using Directionally Selective Motion Detectors to Recognize Collision
Authors: Yue Shigang , Rind F. Claire
Published: March 2007

Reliably recognizing objects approaching on a collision course is extremely important. A synthetic vision system is proposed to tackle the problem of collision recognition in dynamic environments. The system combines the outputs of four whole-field motion-detecting neurons, each receiving inputs from a network of neurons employing asymmetric lateral inhibition to suppress their responses to one direction of motion. An evolutionary algorithm is then used to adjust the weights between the four motion-detecting neurons to tune the system to detect collisions in two test environments. To do this, a population of agents, each representing a proposed synthetic visual system, either were shown images generated by a mobile Khepera robot navigating in a simplified laboratory environment or were shown images videoed outdoors from a moving vehicle. The agents had to cope with the local environment correctly in order to survive. After 400 generations, the best agent recognized imminent collisions reliably in the familiar environment where it had evolved. However, when the environment was swapped, only the agent evolved to cope in the robotic environment still signaled collision reliably. This study suggests that whole-field direction-selective neurons, with selectivity based on asymmetric lateral inhibition, can be organized into a synthetic vision system, which can then be adapted to play an important role in collision detection in complex dynamic scenes.
English as a Global Language
Authors: Foley Joseph A.
Published: March 2007

The argument put forward here is that we are witnessing the emergence of a concept of English as a lingua franca, which creates a set of attitudes about correctness and in particular ‘grammatical correctness’. The traditional ‘nativespeaker’ as final arbiter can only apply to English as a national language. It is the non-native speaker who is becoming the model for English as a global language.
Assessing University Students
Authors: Qian David D.
Published: March 2007

In order to motivate university students to improve their English profi-ciency, the Hong Kong government decided to adopt a common exit English language test for all graduating students. In the process of selecting a suitable measure for this purpose, an empirical study with a sample of over 240 students was conducted to compare two English proficiency tests, the English Test of the Graduating Students' Language Proficiency Assessment (GSLPA) and the Academic Version of the International English Language Testing System (IELTS). The comparisons covered both speaking and writing components of the two tests, based on information provided by the two tests as well as performances of the participating candidates on the components under study. Results indicate: (1) that GSLPA writing and speaking scores distinguish candidates' abilities more clearly than the corresponding scores on the IELTS but IELTS overall scores, generated from writing, speaking, reading and listening sub-scores, have a discriminating power similar to that of GSLPA; (2) that the GSLPA and IELTS writing subtests basically measure different skills; and (3) that the constructs of the GSLPA and IELTS speaking subtests, while having their own distinctive features, overlap by about 48%. This paper recommends options for improving the current assessment framework for graduating university students and discusses the possible impact of such a test on English language teaching and learning.
Meanings of Sisterhood and Developmental Disability
Authors: McGraw Lori A. , Walker Alexis J.
Published: March 2007

Integrating thought from critical feminist and disability theorists via a strategic social constructionist perspective, the authors analyzed 10 in-depth qualitative interviews to begin to understand the dialogue between (a) how nondisabled sisters understand themselves and their siblings with developmental disabilities and (b) wider systems of power or discourse. The women in this exploratory study described themselves as good sisters by portraying their siblings with disabilities as normal, emphasizing opportunities for moral enhancement, minimizing personal sacrifices, and accepting the gendered nature of family care. This study suggests that nondisabled sisters co-opt ideology that holds women accountable for moral conduct in families to oppose discourse that devalues people with disabilities. This ideology does not, however, help them transcend a gender system that requires mothers and sisters but not fathers and brothers to engage in family care.
Integrating Black Consciousness and Critical Race Feminism Into Family Studies Research
Authors: Few April L.
Published: March 2007

The author examines the advantages and challenges of using Black feminist theory and critical race feminist theory to study the lives of Black women and families in family studies. The author addresses the ways in which these per spectives, both of which are intentional in their analyses of intersectionality and the politics of location, are also distinct. She provides empirical examples from how family researchers have used Black feminist theory or a critical race fem inist lens to examine the lives of Black women and families, and suggests ways for colleagues to embrace an explicit integration of Black consciousness and critical race feminist perspectives in family studies.
Feminist-Informed Critical Multiculturalism
Authors: McDowell Teresa , Fang Shi-Ruei Sherry
Published: March 2007

In this article, the authors draw from feminist, critical, and multicultural research traditions to identify fundamental assumptions for researching from a feminist-informed, critical, multicultural stance. Core considerations include amplifying marginalized voices, interrogating the politics of knowledge production, ensuring research benefits to those at the center of analysis, attending to culture and context, holding ourselves accountable as researchers for our own multicultural competence, and using diverse methodologies to support social equity. They offer examples of critical multicultural research and argue for the potential of this approach to contribute to a corrective research agenda in the field of family studies.
Women's Rights and Wedding Bells
Authors: Adams Michele
Published: March 2007

Researchers suggest that backlashes to feminism may appear in the form of pro-family campaigns. Social scientists have observed themes in the current pro-marriage movement to support this claim; others note historical cycles of pro-family backlash to feminism. This article is a sociohistorical analysis of texts from a leading organized advocate of 19th-century pro-family reform that examines emergent rhetorical themes illustrative of a backlash to women's rights. I draw on critical feminist theory to suggest that these strategic rhetorical themes were used to stimulate 19th-century women's ambivalence about family and independence. I also briefly engage gender social movement's literature and research on current pro-family campaigns to point out similarities between the backlash rhetorical strategies of the historical and current movements. In accord with previous feminist scholarship, this study is important in “making visible” the often hidden antifeminist bias in pro-family rhetoric.
Reflections From the Trenches
Authors: Sharp Elizabeth A. , Bermudez J. Maria , Watson Wendy , Fitzpatrick Jacki
Published: March 2007

In this article, we share our challenges and positive experiences of using feminist pedagogy to teach an undergraduate course on gender development. We use a developmental contextual, feminist perspective to address issues related to (a) internalized sexism, (b) contrasts in student's religious beliefs and sexism, (c) students' developmental level, and (d) teaching intersectionality. In response to the challenges, we offer practical applications of integrating feminist pedagogy in the classroom. Finally, we delineate the ways in which our application of feminist pedagogy has benefited us in our growth and offer suggestions for future research.
Gender, Genocide, and Ethnicity
Authors: Manoogian Margaret M. , Walker Alexis J. , Richards Leslie N.
Published: March 2007

Women use legacies to help family members articulate family identity, learn family history, and provide succeeding generations with information about family culture. Using feminist standpoint theory and the life-course perspective, this qualitative study examined the intergenerational transmissions that 30 older Armenian American mothers received and transmitted to succeeding generations within the sociohistorical experience of genocide. Mothers passed on legacies that included family stories, rituals/activities, and possessions. Because of multiple losses during the Armenian Genocide, they emphasized legacies that symbolized connection to family, underscored family cohesion, and accentuated ethnic identity. Tensions were evident as well because women's sense of responsibility for legacies clashed with their limited cultural knowledge, few inherited possessions, and the inevitable assimilation of their children and grandchildren into the dominant U.S. culture.
Using Propensity Scoring to Estimate Program-Related Subgroup Impacts in Experimental Program Evaluations
Authors: Schochet Peter Z. , Burghardt John
Published: March 2007

This article discusses the use of propensity scoring in experimental program evaluations to estimate impacts for subgroups defined by program features and participants' program experiences. The authors discuss estimation issues and provide specification tests. They also discuss the use of an overlooked data collection design—obtaining predictions that program intake staff make about applicants' likely program assignments and experiences—that could improve the quality of matched comparison samples. They demonstrate the effectiveness of this approach in producing credible subgroup findings using data from a large-scale experimental evaluation of Job Corps, the nation's largest federal education and training program for disadvantaged youths.
Issues, Challenges, and Solutions in Translating Study Instruments
Authors: Weeks Amanda , Swerissen Hal , Belfrage John
Published: March 2007

Cross-cultural adaptation of study instruments is a difficult, time-consuming, but arguably cost-effective process. If conducted properly, it has the advantage that the translated study instruments are accurate, easy to understand, accessible, and culturally appropriate to the target audience and produce reliable and valid data. This article explores issues, challenges, and solutions for translating a set of research instruments used in a randomized, controlled trial for four separate community languages (Chinese, Vietnamese, Greek, Italian).
A Repeated Observation Approach for Estimating the Street Homeless Population
Authors: Berry Brent
Published: March 2007

Risks of life on the street caused by inclement weather, harassment, and assault threaten the unsheltered homeless population. We address some challenges of enumerating the street homeless population by testing a novel capture-recapture (CR) estimation approach that models individuals' intermittent daytime visibility. We tested walking and vehicle-based variants of CR in downtown Toronto in March. Estimates that assume individual variability of sighting probabilities are most consistent with our knowledge of the homeless and achieve the most favorable confidence intervals, estimated detection probabilities, and coefficient of variation. Estimation bias from interobserver discrepancies, duplicate counting, and violation of the closed population assumption were minimized with uniform identification criteria, training, and sampling design. Bias caused by the social grouping of the homeless was small. Despite the limitations of visual identification, CR approaches as part of a multiple-method program can aid community responses to immediate needs on the street, especially during the harsh winter months.
Introduction
Authors: Volpi Frédéric , Turner Bryan S.
Published: March 2007

A global transformation of modes of religious authority has been taking place at an increasing pace in recent years. The social and political implications of the growing dominance of neo-scripturalist discourses on Islam have been particularly noticeable after 11 September 2001. This evolution of religiosity, which is mediated by mass media and new media technology, creates the conditions of existence of a post-Weberian and post-Durkheimian order. In this new social context, legitimacy (and legitimate violence) can be more easily disconnected from the institutionalized framework of religious and political authority. Both in Muslim countries and in Western democracies, the attempt by Islamic activists to make the Shari’a relevant in contemporary settings creates new opportunities and challenges for legal pluralism. At the same time, the multiplication of Muslim voices claiming to be able to interpret the sacred texts, particularly in virtual communities, creates an increasingly inchoate ‘noise’ about Islamic orthodoxy. In the context of an exponential increase in the global possibilities for religious identification and expression, the growth of neo-scripturalist interpretations of Islam reflects a quest for parsimony and stability.
Conceptions of Authority in Iraqi Shi’ism
Authors: Gleave Robert
Published: March 2007

One of the most obvious differences between recent Shi’ite and Sunni political activism is the dominance of clerical leadership in the former and lay leadership in the latter. This article examines the reasons for this difference, analysing the authority theories of three contemporary Iraqi Shi’ite clerics. Ayatallah Baqir al-Hakim, until his death in 2003, was the ideologue of the Supreme Council for Islamic Revolution in Iraq, the military wing of which is the Badr Corps. Ayatallah Kazim al-Ha’iri is considered the successor of the late Ayatallah Sadiq al-Sadr; the latter was the ideological inspiration for the Mehdi Army led by Sadiq al-Sadr’s son Muqtada al-Sadr. The relationship between Ha’iri and Muqtada has been tested in the recent past, and the two have distanced themselves from each other. In 2004, Ha’iri officially announced that Muqtada is not his representative in Iraq. Hence the analysis in this article represents the tradition of Shi’i thought from which Muqtada has emerged, rather than the specific doctrine to which he subscribes. Muqtada’s legal doctrine is difficult to ascertain given that he has not yet written a comprehensive work of jurisprudence. Grand Ayatallah Ali Sistani is certainly the most internationally respected of the three scholars. Considered the leading Ayatallah in Iraq (and perhaps the Shi’ite world in general), Sistani successfully negotiated the end to the occupation of Najaf by the Mehdi Army and is credited with masterminding the success of the United Iraqi Alliance in the Iraqi elections of January 2005. This article compares and contrasts the three thinkers’ theories of religious and political authority, including their differing conceptions of the ulama (scholarly elite) and their power within the community. This leads on to a brief consideration of the political theories of Baqir al-Hakim and Ha’iri.