bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cluster of Four Surface Antigen Genes Specifically Expressed in Bradyzoites,SAG2CDXY, Plays an Important Role inToxoplasma gondiiPersistence
Authors: Saeij Jeroen P. J. , Arrizabalaga Gustavo , Boothroyd John C. 
Published: March 2008

ABSTRACTToxoplasma gondiiis one of the most successful protozoan parasites of warm-blooded animals. Stage-specific expression of its surface molecules is thought to be key to its ability to establish chronic infection in immunocompetent animals. The rapidly dividing tachyzoite stage displays a different subset of family of surface antigen 1 (SAG1)-related sequences (SRSs) from that displayed by the encysted bradyzoite stage. It is possible that this switch is necessary to protect the bradyzoites against an immune response raised against the tachyzoite stage. Alternatively, it might be that bradyzoite SRSs evolved to facilitate invasion of different cell types, such as those found in the brain, where cysts develop, or the small intestine, where bradyzoites must enter after oral infection. Here we studied the function of a cluster of four tandem genes, encoding bradyzoite SRSs called SAG2C, -D, -X, and -Y. Using bioluminescence imaging of mice infected with parasites expressing firefly luciferase (FLUC) driven by theSAG2Dpromoter, we show stage conversion for the first time in living animals. A truncated version of theSAG2Dpromoter (SAG2Dmin) gave efficient expression of FLUC in both tachyzoites and bradyzoites, indicating that the bradyzoite specificity of the completeSAG2Dpromoter is likely due to an element(s) that normally suppresses expression in tachyzoites. Comparing mice infected with the wild type or a mutant where theSAG2CDXYcluster of genes has been deleted (ΔSAG2CDXY), we demonstrate that whereas ΔSAG2CDXYparasites are less capable of maintaining a chronic infection in the brain, they do not show a defect in oral infectivity.
Heterogeneity in the Polarity of Nra Regulatory Effects on Streptococcal Pilus Gene Transcription and Virulence
Authors: Luo Feng , Lizano Sergio , Bessen Debra E. 
Published: March 2008

ABSTRACT

Transcription of several key virulence factors of
Streptococcus pyogenes
is under the control of Mga and Nra/RofA. In an M serotype 49 (M49) strain, Nra is a negative regulator of pilus gene transcription; also, Nra represses
mga
expression, leading to downregulation of the M protein surface fibril and secreted cysteine protease SpeB. In this report, the role of Nra in the virulence of an M53 classical skin strain was investigated. In contrast to the case for the M49 strain, Nra functions as a positive regulator of pilus gene transcription in the M53 strain, and inactivation of
nra
leads to loss of virulence in a humanized mouse model of superficial skin infection. Furthermore, Nra has no measurable effect on
mga
transcription in the M53 strain; this finding is further supported by a lack of detectable Nra effects on M protein- and SpeB-dependent phenotypes. Whereas MsmR is reported to activate
nra
and pilus gene transcription in the M49 strain, in the M53 strain it acts as a repressor of these genes. In both strains, MsmR and Nra form a feed-forward loop network motif for pilus gene transcription, but their effects have opposite signs. The findings demonstrate key strain-specific differences in the transcriptional circuitry governing virulence gene expression in
S. pyogenes
and its impact on pathogenesis.
Vibrio parahaemolyticusInhibition of Rho Family GTPase Activation Requires a Functional Chromosome I Type III Secretion System
Authors: Casselli Timothy , Lynch Tarah , Southward Carolyn M. , Jones Bryan W. , DeVinney Rebekah 
Published: March 2008

ABSTRACTVibrio parahaemolyticusis a leading cause of seafood-borne gastroenteritis; however, its virulence mechanisms are not well understood. The identification of type III secreted proteins has provided candidate virulence factors whose functions are still being elucidated. Genotypic strain variability contributes a level of complexity to understanding the role of different virulence factors. The ability ofV. parahaemolyticusto inhibit Rho family GTPases and cause cytoskeletal disruption was examined with HeLa cells. After HeLa cells were infected, intracellular Rho activation was inhibited in response to external stimuli. In vitro activation of Rho, Rac, and Cdc42 isolated from infected HeLa cell lysates was also inhibited, indicating that the bacteria were specifically targeting GTPase activation. The inhibition of Rho family GTPase activation was retained for clinical and environmental isolates ofV. parahaemolyticusand was dependent on a functional chromosome I type III secretion system (CI-T3SS). GTPase inhibition was independent of hemolytic toxin genotype and the chromasome II (CII)-T3SS. Rho inhibition was accompanied by a shift in the total actin pool to its monomeric form. These phenotypes were abrogated in a mutant strain lacking the CI-T3S effector Vp1686, suggesting that the inhibiting actin polymerization may be a downstream effect of Vp1686-dependent GTPase inhibition. Although Vp1686 has been previously characterized as a potential virulence factor in macrophages, our findings reveal an effect on cultured HeLa cells. The ability to inhibit Rho family GTPases independently of the CII-T3SS and the hemolytic toxins may provide insight into the mechanisms of virulence used by strains lacking these virulence factors.
Both CD4
+
and CD8
+
T Cells Respond to Antigens Fused to Anthrax Lethal Toxin
Authors: Shaw Christine A. , Starnbach Michael N. 
Published: March 2008

ABSTRACT

The lethal toxin produced by
Bacillus anthracis
is a bipartite toxin in which the first protein, protective antigen (PA), transports the second protein, lethal factor, across the host cell membrane. We have previously shown that CD8
+
T-cell epitopes fused to a nontoxic derivative of lethal factor (LFn) are delivered into the host cell cytosol in a PA-dependent manner. Delivery of these antigens targets them to the intracellular major histocompatibility complex (MHC) class I processing and presentation pathway and leads to the stimulation of antigen-specific CD8
+
T cells in vivo. In this report, we describe the generation and characterization of LFn fusion proteins that include not only a CD8
+
T-cell epitope but also a CD4
+
T-cell epitope. We first show that these fusion proteins induce antigen-specific CD4
+
T-cell responses following incubation with dendritic cells in vitro or injection into mice. Stimulation of CD4
+
T cells by LFn fusion proteins does not require PA but is enhanced by PA in vitro. We also show that a single LFn fusion protein and PA can deliver antigen to both the MHC class II and the MHC class I pathways, resulting in the simultaneous induction of antigen-specific CD4
+
T cells and antigen-specific CD8
+
T cells in the same mouse. These results suggest that this toxin delivery system is capable of stimulating protective immune responses where effective immunization requires stimulation of both classes of T cells.
L’activité physique chez les Autochtones au CanadaCet article est tiré d’un supplément intituléAdvancing physical activity measurement and guidelines in Canada: a scientific review and evidence-based foundation for the future of Canadian physical activity guidelines(Favoriser les lignes directrices et la mesure de l’activité physique au Canada: examen scientifique et justification selon les données probantes pour l’avenir des lignes directrices de l’activité physique canadienne) publié parPhysiologie appliquée, nutrition et métabolismeet laRevue canadienne de santé publique. On peut aussi mentionner Appl. Physiol. Nutr. Metab. 32 (Suppl. 2F) ou Can. J. Public Health 98 (Suppl. 2).
Authors: Young T. Kue , Katzmarzyk Peter T. 
Published: March 2008

Cet article présente un bilan des pratiques de l’activité physique, des facteurs et des conséquences de même que des effets de plusieurs interventions menées pour accroître la pratique de l’activité physique chez les Aborigènes du Canada et des États-Unis. Peu d’études nationales ont été menées à propos de la pratique de l’activité physique chez les peuples aborigènes. Les données les plus récentes proviennent de l’Enquête régionale longitudinale sur la santé des Premières Nations (2002–2003) : 21 % des adultes (hommes, 27 %, femmes, 15 %) font en une journée au moins 30 min d’activité physique d’intensité modérée à vigoureuse, et ce, 4 jours ou plus par semaine. Cet article indique les défis particuliers auxquels les Aborigènes sont confrontés et souligne le besoin pour cette population de s’approprier le savoir collectif à propos de la quantité d’activité physique à pratiquer et des modalités à suivre pour la promotion et le maintien de la santé. En ce moment, des individus travaillent à adapter le guide d’activité physique aux Premières Nations, aux Inuits et aux Métis. Les prochaines études devraient porter sur les niveaux, minimal et optimal, de pratique de l’activité physique chez ces populations afin qu’elles en retirent les bienfaits au plan de la santé.
Prostate-Specific Membrane Antigen Expression Is a Potential Prognostic Marker in Endometrial Adenocarcinoma
Authors: Mhawech-Fauceglia Paulette , Smiraglia Dominic J. , Bshara Wiam , Andrews Christopher , Schwaller Juerg , South Stacey , Higgs Donald , Lele Shashikant , Herrmann Francois , Odunsi Kunle 
Published: March 2008

Abstract
The aim of this study was to determine the role of prostate-specific membrane antigen (PSMA) as a prognostic marker in endometrial adenocarcinoma (EAC) and to explore whether its down-regulation could be due to epigenetic mechanism. First, we examined the expression and the prognostic value of PSMA by semiquantitative reverse transcription-PCR and immunohistochemistry in EAC tissue samples. Second, to explore the role of CpG methylation in down-regulation PSMA in EAC, we evaluated PSMA CpG island methylation using methylation-specific PCR in cells lines and in a subset of patients' samples. Furthermore, association of the status of tumor methylation to the clinical and histologic variables was also evaluated. Higher PSMA mRNA levels were associated with stage I (P = 0.046) and PSMA protein intensity by immunohistochemistry (P = 0.032). In multivariate analysis, loss of PSMA expression was associated with a worse disease-free survival (P = 0.02). PSMA was methylated in prostate cell lines (DU145 and PC3) and endometrial cell lines. In addition, PSMA was methylated in 5 of 18 samples (all 5 had low PSMA mRNA value). There was a significant association between PSMA methylation and loss of protein expression by immunohistochemistry and PSMA-RNA level with P value of 0.036 and 0.011, respectively. In addition, there was an association between PSMA methylation and tumor size (P = 0.025). In summary, (a) PSMA is underexpressed in advanced stage EAC, (b) loss of PSMA expression can be considered as a prognostic marker in patients with EAC, and (c) loss of PSMA expression in a subset of EAC cases could be due to epigenetic silencing. (Cancer Epidemiol Biomarkers Prev 2008;17(3):571–7)
Progestin Treatment Induces Apoptosis and Modulates Transforming Growth Factor-β in the Uterine Endometrium
Authors: Rodriguez Gustavo C. , Rimel B.J. , Watkin William , Turbov Jane M. , Barry Cathy , Du Hongyan , Maxwell George L. , Cline J.M. 
Published: March 2008

AbstractBackground: Epidemiologic, animal, and human data suggest that progestins are potent endometrial cancer preventive agents. In the ovarian surface epithelium, progestins have been hypothesized to confer a cancer preventive effect via apoptosis and modulation of transforming growth factor-β (TGF-β). Given that the ovarian epithelium and endometrium share a common embryologic origin and similar reproductive and hormonal risk factors for malignancy, we tested the hypothesis that progestins confer biological effects in the endometrium similar to those in the ovary.Methods: Postmenopausal female macaques (n = 78) were randomized into four groups to receive a diet for 36 months containing no hormone versus conjugated equine estrogen (CEE), medroxyprogesterone acetate (MPA), or CEE + MPA. The endometrium was then examined immunohistochemically for treatment-specific changes using antibodies to activated caspase-3 (for apoptosis), Ki-67 (proliferation), and the TGF-β1, TGF-β2, and TGF-β3 isoforms.Results: Percentages of caspase-positive endometrial glandular cells were 3- to 5-fold higher in CEE + MPA–treated animals compared with all others (P &lt; 0.05). Caspase-expressing cells were six times more numerous in the endometrial stroma of animals treated with MPA alone relative to other groups (P &lt; 0.0001). Induction of endometrial glandular cell apoptosis in the CEE + MPA–treated group was associated with a dramatic increase in expression of TGF-β2 and TGF-β3 in the stromal compartment of the endometrium (P &lt; 0.0001).Conclusion: Progestin treatment activates chemopreventive biological effects in the endometrium that are similar to those in the ovarian surface epithelium. These data may facilitate identification of a chemopreventive approach that dramatically lessens the risk of both uterine and ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):578–84)
DNA Repair Gene XPD Polymorphisms and Cancer Risk: A Meta-analysis Based on 56 Case-Control Studies
Authors: Wang Fan , Chang Dong , Hu Fu-lan , Sui Hong , Han Bing , li Dan-dan , Zhao Ya-shuang 
Published: March 2008

AbstractGenetic variations in the XPD gene may increase cancer susceptibility by affecting the capacity for DNA repair. Several studies have investigated this possibility; however, the conclusions remain controversial. Therefore, we did a systematic review and executed a meta-analysis to explore the association. From 56 studies, a total of 61 comparisons included 25,932 cases and 27,733 controls concerning the Lys751Gln polymorphism; 35 comparisons included 16,781 cases and 18,879 controls in the case of Asp312Asn were reviewed. In this analysis, small associations of the XPD Lys751Gln polymorphism with cancer risk for esophageal cancer [for Lys/Gln versus Lys/Lys: odds ratio (OR), 1.34; 95% confidence interval (95% CI), 1.10-1.64; for Gln/Gln versus Lys/Lys: OR, 1.61; 95% CI, 1.16-2.25] and acute lymphoblastic leukemia (for Gln/Gln versus Lys/Lys: OR, 1.83; 95% CI, 1.21-2.75) are revealed. Overall, individuals with the Gln/Gln genotype have a small cancer risk compared with Lys/Lys genotype for the reviewed cancer in total (OR, 1.10; 95% CI, 1.03-1.16). Subtle but significant cancer risk was observed for the XPD Asp312Asn polymorphism in bladder cancer (for Asp/Asn versus Asp/Asp: OR, 1.24; 95% CI, 1.06-1.46). No significant associations were found for other cancers separately and all the reviewed cancer in total assessed for the Asp312Asn polymorphism. Our study suggests that XPD is a candidate gene for cancer susceptibility regardless of environmental factors. (Cancer Epidemiol Biomarkers Prev 2008;17(3):507–17)
Does Breast Size Modify the Association between Mammographic Density and Breast Cancer Risk?
Authors: Stuedal Anne , Ma Huiyan , Bernstein Leslie , Pike Malcolm C. , Ursin Giske 
Published: March 2008

Abstract
Background: Both the absolute and the percent of mammographic density are strong and independent risk factors for breast cancer. Previously, we showed that the association between mammographic density and breast cancer risk tended to be weaker in African American than in White U.S. women. Because African American women have a larger breast size, we assessed whether the association between mammographic density and breast cancer was less apparent in large than in small breasts.
Methods: We assessed mammographic density on mammograms from 348 African American and 507 White women, 479 breast cancer patients and 376 control subjects, from a case-control study conducted in Los Angeles County. We estimated odds ratios (OR) for breast cancer with increasing mammographic density, and the analyses were stratified by mammographic breast area.
Results: Median breast size was 168.4 cm2 in African American women and 121.7 cm2 in White women (P for difference &lt;0.001). For absolute density, adjusted ORs (95% confidence intervals) per increase of 10 cm2 were 1.32 (1.13-1.54), 1.14 (1.03-1.26), and 1.02 (0.98-1.07) in the first, second, and third tertiles of breast area, respectively (P for effect modification by breast area = 0.005). The results for percent density were similar although weaker; adjusted ORs per 10% increase (absolute value) in percent density were 1.22 (1.05-1.40), 1.22 (1.06-1.41), and 1.03 (0.90-1.18 P for effect modification by breast area = 0.34).
Conclusion: Our results indicate that the association between mammographic density and breast cancer may be weaker in women with larger breasts. (Cancer Epidemiol Biomarkers Prev 2008;17(3):621–7)
Multiple Diagnostic X-rays for Spine Deformities and Risk of Breast Cancer
Authors: Ronckers Cécile M. , Doody Michele M. , Lonstein John E. , Stovall Marilyn , Land Charles E. 
Published: March 2008

Abstract
Background: Ionizing radiation is a well-established human mammary carcinogen. Women historically monitored by radiography at young ages for abnormal spinal curvature are an exposed population suitable for investigating radiation-related risk and its variation by modifying factors. In this historic cohort, 95% of daily dose increments (when exposure to the breast occurred) were under 2.4 cGy, with mean 1.1 cGy.
Methods: A retrospective cohort of 3,010 women, diagnosed with spinal curvature between 1912 and 1965 in 14 U.S. pediatric orthopedic centers and who completed a questionnaire by telephone interview or mail survey in 1992, were studied for risk of breast cancer by radiation dose to the breast (mean, 12 cGy) after adjustment for established breast cancer risk factors.
Results: A borderline-significant radiation dose response (excess relative risk/Gy = 2.86; P = 0.058; one-tailed P = 0.029) was observed during 118,905 woman-years of follow-up (median, 35.5 years) based on 78 cases of invasive breast cancer. The dose response was significantly greater (P = 0.03) for women who reported a family history of breast cancer in first- or second-degree relatives (excess relative risk/Gy = 8.37; 95% confidence interval, 1.50-28.16). Radiation-related risk did not vary significantly by stage of reproductive development at exposure.
Conclusions: Assuming that repair of radiation-related DNA damage requires at most a few hours, our data argue against existence of a low-dose threshold on the order of 1 to 3 cGy for radiation exposure contributing to breast carcinogenesis. The possibility that a family history of breast cancer may have enhanced a carcinogenic radiation effect requires confirmation in other studies. (Cancer Epidemiol Biomarkers Prev 2008;17(3):605–13)
Postmenopausal Hormone Therapy and Lung Cancer Risk in the Cancer Prevention Study II Nutrition Cohort
Authors: Rodriguez Carmen , Spencer Feigelson Heather , Deka Anusila , Patel Alpa V. , Jacobs Eric J. , Thun Michael J. , Calle Eugenia E. 
Published: March 2008

Abstract
Background: Studies of postmenopausal hormone therapy and lung cancer incidence have reported positive, negative, and null associations. Most of these studies, however, have had limited ability to control rigorously for cigarette smoking or to examine risk separately by smoking status.
Methods: We examined the association between postmenopausal hormone therapy and lung cancer incidence by smoking status among 72,772 women in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate rate ratios (RR).
Results: During follow-up from 1992 to 2003, we identified 659 cases of incident lung cancer. Current use of any postmenopausal hormone therapy was significantly associated with decreased risk of incident lung cancer [multivariate RR, 0.76; 95% confidence interval (95% CI), 0.62-0.92]. Similar risk estimates were observed for unopposed estrogen use (RR, 0.76; 95% CI, 0.60-0.94) and for estrogen plus progestin (RR, 0.76; 95% CI, 0.57-1.01). Risk associated with current use of postmenopausal hormone therapy was decreased among never smokers (RR, 0.56; 95% CI, 0.33-0.95) as well as current smokers (RR, 0.76; 95% CI, 0.55-1.05) and former smokers (RR, 0.76; 95% CI, 0.58-0.99). Former hormone use was not associated with lung cancer. No trend with duration of hormone use was detected.
Conclusion: These results support the hypothesis that postmenopausal hormone therapy is associated with reduced risk of lung cancer, although the absence of a dose-response relationship weakens the evidence for causality. (Cancer Epidemiol Biomarkers Prev 2008;17(3):655–60)
Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China
Authors: Andreotti Gabriella , Chen Jinbo , Gao Yu-Tang , Rashid Asif , Chen Bingshu E. , Rosenberg Philip , Sakoda Lori C. , Deng Jie , Shen Ming-Chang , Wang Bing-Sheng , Han Tian-Quan , Zhang Bai-He , Yeager Meredith , Welch Robert , Chanock Stephen , Fraumeni Joseph F. , Hsing Ann W. 
Published: March 2008

Abstract
Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C&gt;T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C&gt;T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C&gt;T, EX4+56C&gt;T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C&gt;T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct. (Cancer Epidemiol Biomarkers Prev 2008;17(3):525–34)
Genetic Polymorphisms and Head and Neck Cancer Outcomes: A Review
Authors: Hopkins Jessica , Cescon David W. , Tse Darren , Bradbury Penelope , Xu Wei , Ma Clement , Wheatley-Price Paul , Waldron John , Goldstein David , Meyer Francois , Bairati Isabelle , Liu Geoffrey 
Published: March 2008

AbstractHead and neck cancer (HNC) patients have variable prognoses even within the same clinical stage and while receiving similar treatments. The number of studies of genetic polymorphisms as prognostic factors of HNC outcomes is growing. Candidate polymorphisms have been evaluated in DNA repair, cell cycle, xenobiotic metabolism, and growth factor pathways. Polymorphisms of XRCC1, FGFR, and CCND1 have been consistently associated with HNC survival in at least two studies, whereas most of the other polymorphisms have either conflicting data or were from single studies. Heterogeneity and lack of description of patient populations and lack of accounting for multiple comparisons were common problems in a significant proportion of studies. Despite a large number of exploratory studies, large replication studies in well-characterized HNC populations are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(3):490–9)