bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Pathogenesis Assay Using
Saccharomyces
cerevisiae
and
C
aenorhabditis
elegans
Reveals Novel Roles for Yeast AP-1, Yap1, and Host Dual Oxidase BLI-3 in Fungal Pathogenesis
Authors: Jain Charu , Yun Meijiang , Politz Samuel M. , Rao Reeta Prusty 
Published: June 2009

ABSTRACT

Treatment of systemic fungal infections is difficult because of the limited number of antimycotic drugs available. Thus, there is an immediate need for simple and innovative systems to assay the contribution of individual genes to fungal pathogenesis. We have developed a pathogenesis assay using
Caenorhabditis elegans
, an established model host, with
Saccharomyces cerevisiae
as the invading fungus. We have found that yeast infects nematodes, causing disease and death. Our data indicate that the host produces reactive oxygen species (ROS) in response to fungal infection. Yeast mutants
sod1
Δ and
yap1
Δ, which cannot withstand ROS, fail to cause disease, except in
bli-3
worms, which carry a mutation in a dual oxidase gene. Chemical inhibition of the NADPH oxidase activity abolishes ROS production in worms exposed to yeast. This pathogenesis assay is useful for conducting systematic, whole-genome screens to identify fungal virulence factors as alternative targets for drug development and exploration of host responses to fungal infections.
MotX and MotY Are Required for Flagellar Rotation inShewanella oneidensisMR-1
Authors: Koerdt Andrea , Paulick Anja , Mock Marlen , Jost Kathinka , Thormann Kai M. 
Published: June 2009

ABSTRACTThe single polar flagellum ofShewanella oneidensisMR-1 is powered by two different stator complexes, the sodium-dependent PomAB and the proton-driven MotAB. In addition,Shewanellaharbors two genes with homology tomotXandmotYofVibriospecies. InVibrio, the products of these genes are crucial for sodium-dependent flagellar rotation. Resequencing ofS. oneidensisMR-1motYrevealed that the gene does not harbor an authentic frameshift as was originally reported. Mutational analysis demonstrated that both MotX and MotY are critical for flagellar rotation ofS. oneidensisMR-1 for both sodium- and proton-dependent stator systems but do not affect assembly of the flagellar filament. Fluorescence tagging of MotX and MotY to mCherry revealed that both proteins localize to the flagellated cell pole depending on the presence of the basal flagellar structure. Functional localization of MotX requires MotY, whereas MotY localizes independently of MotX. In contrast to the case inVibrio, neither protein is crucial for the recruitment of the PomAB or MotAB stator complexes to the flagellated cell pole, nor do they play a major role in the stator selection process. Thus, MotX and MotY are not exclusive features of sodium-dependent flagellar systems. Furthermore, MotX and MotY inShewanella, and possibly also in other genera, must have functions beyond the recruitment of the stator complexes.
Contribution of Citrulline Ureidase toFrancisella tularensisStrain Schu S4 Pathogenesis
Authors: Mahawar Manish , Kirimanjeswara Girish S. , Metzger Dennis W. , Bakshi Chandra Shekhar 
Published: June 2009

ABSTRACTThe citrulline ureidase (CTU) activity has been shown to be associated with highly virulentFrancisella tularensisstrains, including Schu S4, while it is absent in avirulent or less virulent strains. A definitive role of thectugene in virulence and pathogenesis ofF. tularensisSchu S4 has not been assessed; thus, an understanding of the significance of this phenotype is long overdue. CTU is a carbon-nitrogen hydrolase encoded by the citrulline ureidase (ctu) gene (FTT0435) on theF. tularensisSchu S4 genome. In the present study, we evaluated the contribution of thectugene in the virulence of category A agentF. tularensisSchu S4 by generating a nonpolar deletion mutant, the Δctumutant. The deletion of thectugene resulted in loss of CTU activity, which was restored by transcomplementing thectugene. The Δctumutant did not exhibit any growth defect under acellular growth conditions; however, it was impaired for intramacrophage growth in resting as well as gamma interferon-stimulated macrophages. The Δctumutant was further tested for its virulence attributes in a mouse model of respiratory tularemia. Mice infected intranasally with the Δctumutant showed significantly reduced bacterial burden in the lungs, liver, and spleen compared to wild-type (WT) Schu S4-infected mice. The reduced bacterial burden in mice infected with the Δctumutant was also associated with significantly lower histopathological scores in the lungs. Mice infected with the Δctumutant succumbed to infection, but they survived longer and showed significantly extended median time to death compared to that shown by WT Schu S4-infected mice. To conclude, this study demonstrates thatctucontributes to intracellular survival, in vivo growth, and pathogenesis. However,ctuis not an absolute requirement for the virulence ofF. tularensisSchu S4 in mice.
Hopanoids Are Not Essential for Growth of
Streptomyces scabies
87-22
Authors: Seipke Ryan F. , Loria Rosemary 
Published: June 2009

ABSTRACT

Hopanoids are triterpenoic, pentacyclic compounds that are structurally similar to sterols, which are required for normal cell function in eukaryotes. Hopanoids are thought to be an important component of bacterial cell membranes because they control membrane fluidity and diminish passive diffusion of ions, and a few taxons modulate their hopanoid content in response to environmental stimuli. However, to our knowledge, mutational studies to assess the importance of hopanoids in bacterial physiology have never been performed. Genome sequencing of the potato scab pathogen,
Streptomyces scabies
87-22, revealed a hopanoid biosynthetic gene cluster (HBGC) that is predicted to synthesize hopene and aminotrihydroxybacteriohopane products. Hopene was produced by fully sporulated cultures of
S. scabies
on solid ISP4 (International
Streptomyces
Project 4) medium as well as by submerged mycelia grown in liquid minimal medium. The elongated hopanoid aminotrihydroxybacteriohopane was not detected under either growth condition. Transcription of the
S. scabies
HBGC was upregulated during aerial growth, which suggests a link between hopanoid production and morphological development. Functional analysis of the
S. scabies
Δ
hop615
-
1
and Δ
hop615
-
7
mutant strains, the first hopanoid mutants created in any bacterial taxon, revealed that hopanoids are not required for normal growth or for tolerance of ethanol, osmotic and oxidative stress, high temperature, or low pH. This suggests that hopanoids are not essential for normal streptomycete physiology.
Biochemical Evidence for a Timing Mechanism in
Prochlorococcus
Authors: Axmann Ilka M. , Dühring Ulf , Seeliger Luiza , Arnold Anne , Vanselow Jens T. , Kramer Achim , Wilde Annegret 
Published: June 2009

ABSTRACT

Organisms coordinate biological activities into daily cycles using an internal circadian clock. The circadian oscillator proteins KaiA, KaiB, and KaiC are widely believed to underlie 24-h oscillations of gene expression in cyanobacteria. However, a group of very abundant cyanobacteria, namely, marine
Prochlorococcus
species, lost the third oscillator component, KaiA, during evolution. We demonstrate here that the remaining Kai proteins fulfill their known biochemical functions, although KaiC is hyperphosphorylated by default in this system. These data provide biochemical support for the observed evolutionary reduction of the clock locus in
Prochlorococcus
and are consistent with a model in which a mechanism that is less robust than the well-characterized KaiABC protein clock of
Synechococcus
is sufficient for biological timing in the very stable environment that
Prochlorococcus
inhabits.
A New Minimal Replicon ofBacillus anthracisPlasmid pXO1
Authors: Pomerantsev Andrei P. , Camp Andrew , Leppla Stephen H. 
Published: June 2009

ABSTRACTAn 8,883-bp mini-pXO1 plasmid containing a replicon fromBacillus anthracispXO1 (181.6 kb) was identified by making large deletions in the original plasmid using a newly developed Cre-loxPsystem. Portions of the truncated mini-pXO1 were cloned into anEscherichia colivector unable to replicate inB. anthracis. A 5.95-kb region encompassing three putative genes was identified as the minimal pXO1 fragment required for replication of the resulting recombinant shuttle plasmid (named pMR) inB. anthracis. Deletion analysis showed that the only genes essential for replication were the pXO1-14 and pXO1-16 genes, which are transcribed in opposite directions and encode predicted proteins of 66.5 and 67.1 kDa, respectively. The ORF14 protein contains a helix-turn-helix motif, while the ORF16 upstream region contains attributes of a theta-replicating plasmid origin of replication (Ori), namely, an exclusively A+T-containing segment, five 9-bp direct repeats, an inverted repeat, and a σA-dependent promoter for the putative replication initiator Rep protein (ORF16). Spontaneous mutations generated in the ORF14, ORF16, and Ori regions of pMR during PCR amplification produced a temperature-sensitive plasmid that is unable to replicate inB. anthracisat 37°C. The efficacy of transformation of plasmid-freeB. anthracisAmes and Sterne strains by the original pMR was ∼103CFU/μg, whileBacillus cereusstrains 569 and ATCC 10987 were transformed with efficiencies of 104and 102CFU/μg, respectively. Around 95% ofB. anthraciscells retained pMR after one round of sporulation and germination.
Genetic Variation in the Chromosome 17q23 Amplicon and Breast Cancer Risk
Authors: Kelemen Linda E. , Wang Xianshu , Fredericksen Zachary S. , Pankratz V. Shane , Pharoah Paul D.P. , Ahmed Shahana , Dunning Alison M. , Easton Douglas F. , Vierkant Robert A. , Cerhan James R. , Goode Ellen L. , Olson Janet E. , Couch Fergus J. 
Published: June 2009

Abstract
Background: Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in &gt;40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer.
Methods: We investigated 60 polymorphisms in the TUBD1, SEPT4, PRKCA, TBX2, TBX4, TEX14, TLK2, YPEL2, and PPM1E genes from this amplicon for association with breast cancer risk among 798 Caucasian breast cancer cases and 843 unaffected Caucasian controls from the Mayo Clinic.
Results: Eight polymorphisms in PRKCA, TBX4, TLK2, and YPEL2 displayed significant dose-response associations with breast cancer risk (Ptrend &lt; 0.05). Of these, PRKCA rs7342847 and TLK2 rs2245092 and rs733025 were also associated with hormone receptor–positive breast cancer: PRKCA rs7342847 (odds ratio, 0.7; 95% confidence interval, 0.6-0.9; Ptrend = 0.002) and TLK2 rs733025 and rs2245092 (both: odds ratio, 0.8; 95% confidence interval, 0.7-1.0; Ptrend = 0.03). Interactions between SEPT4 rs758377 and TEX14 rs302864 (Pinteraction = 0.0003) and between TLK2 rs733025 and YPEL2 rs16943468 (Pinteraction = 0.05) for risk of breast cancer were also observed.
Conclusion: These findings suggest that single polymorphisms and combinations of polymorphisms within candidate oncogenes from the 17q23 amplicon may influence risk of breast cancer overall and possibly specific molecular subtypes of breast tumors. The findings are discussed within the context of the results from two independent data sets. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1864–8)
Cancer Risk in Long-term Users of Valproate: A Population-Based Case-Control Study
Authors: Hallas Jesper , Friis Søren , Bjerrum Lars , Støvring Henrik , Narverud Sverre Flatabø , Heyerdahl Thomas , Grønbæk Kirsten , Andersen Morten 
Published: June 2009

Abstract
Background: Inhibitors of histone deacetylases (HDAC) have shown promise as targeted cancer therapy. Valproate, an older anticonvulsant, has been shown to possess HDAC inhibitory activity. We undertook this case-control study to clarify whether long-term users of valproate had a reduced cancer incidence. If so, it would support HDAC inhibition as a pharmacologic principle in chemoprevention.
Methods: We identified 149,417 incident cancer cases in Denmark during the study period 2000 through 2005, and 597,668 age- and gender-matched controls. Data on history of cancer, past hospital admission diagnoses, and prescription history were obtained from the Danish Cancer Registry, the Danish National Patient Registry, and the Danish Prescription Registry. Primary exposure to valproate was defined as a cumulative dose of minimum 1,500 g within the past 5 years. Confounders were controlled by conditional logistic regression.
Results: Among the cases and controls, 81 (0.05%) and 260 (0.04%), respectively, were long-term users of valproate. For cancer overall, the crude and adjusted odds ratios were 1.25 [95% confidence interval (95% CI), 0.97-1.60] and 1.21 (95% CI, 0.95-1.56), respectively. Subgroup analyses revealed no dose or duration effect for overall cancer incidence, and no specific cancer site was found to be inversely associated with long-term use of valproate. For lung cancer, we found a positive but imprecise association (adjusted odds ratio, 2.32; 95% CI, 1.12-4.79).
Conclusion: Long-term valproate use is not associated with a reduced cancer risk. Our study does not support HDAC inhibition as a pharmacologic principle for general chemoprevention. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1714–9)
Melanoma in Maori, Asian, and Pacific Peoples in New Zealand
Authors: Sneyd Mary Jane , Cox Brian 
Published: June 2009

Abstract
New Zealand Maori, Pacific, and Asian people develop melanoma less frequently than New Zealand Europeans, but little is known about melanomas that develop in these people. We examined the characteristics of melanoma in these minority ethnic groups in New Zealand. In 2007, all first primary melanomas diagnosed from January 1996 to December 2006 were extracted from the New Zealand Cancer Registry database. Melanoma was more commonly diagnosed in Maori than Asian or Pacific peoples. Age-adjusted incidence rates increased annually from 1996 to 2006 by 0.37 per 100,000 in the total population and 0.20 per 100,000 in Maori, a 12% (from 30.9 to 34.6) and 90% (from 2.3 to 4.3) increase, respectively, over the 11 years. Nodular melanoma occurred more often in Maori (15.9%) and Pacific peoples (17.1%) compared with Asians (8.7%) and New Zealand Europeans (10.5%). In Pacific peoples, acral lentiginous melanoma (22.9%) was the most common subtype. The median thickness of melanoma was 0.78 mm in New Zealand Europeans, 1.2 mm in Maori, 2.5 mm in Pacific peoples, and 0.73 mm in Asians (P &lt; 0.001, difference in medians). Thirty-seven percent of melanomas in Pacific peoples were &gt;4 mm thick compared with 7.9% in New Zealand Europeans. About 13% of Asians and 11% of Pacific peoples, compared with 4% of New Zealand Europeans with melanoma, were diagnosed by histology of metastases rather than the primary lesion. Minority ethnicities in New Zealand have a higher than expected risk of thick and more advanced melanoma, with poorer prognosis. Melanoma campaigns should include messages that incorporate the unique features of melanoma in minorities. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1706–13)
Toll-like Receptor Signaling Pathway Variants and Prostate Cancer Mortality
Authors: Stark Jennifer R. , Wiklund Fredrik , Grönberg Henrik , Schumacher Fredrick , Sinnott Jennifer A. , Stampfer Meir J. , Mucci Lorelei A. , Kraft Peter 
Published: June 2009

Abstract
An understanding of factors associated with prostate cancer (PCa) mortality is increasingly important given the biological heterogeneity of disease. Previous studies have shown that genetic variation in the Toll-like receptor (TLR) signaling pathway is associated with PCa incidence, but any role in progression and mortality is unclear. Among 1,252 PCa cases from the Cancer Prostate in Sweden study, we conducted time-to-event analyses of PCa mortality for 99 individual tagging SNPs and haploytpes from 20 genes in the TLR pathway. Cox proportional hazards models were used to estimate hazard ratios (HR) and 99% confidence intervals (99% CI). Global P values were estimated from a likelihood ratio test. During a median follow-up of 5.1 years, 191 PCa deaths occurred. Controlling for age and geographic location, two polymorphisms were statistically significantly associated with PCa mortality (P &lt; 0.01). Compared with homozygous wild-type carriers of the TLR-9 polymorphism (rs187084), the HR (99% CI) was 1.57 (1.02, 2.41) for heterozygotes and 1.02 (0.57, 1.84) for rare homozygotes (P = 0.009). For a MIC-1 SNP (rs1227732), the HR comparing carriers of at least one copy of the minor allele to wild-type homozygotes was 0.54 (99% CI: 0.34, 0.87). Only the MIC-1 SNP remained significant after additional adjustment for treatment. No significant associations were observed for common haplotypes and PCa mortality. This study highlights the importance of studies of PCa mortality because risk factors for incidence and mortality may differ. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1859–63)
Dietary Folate and Folate Vitamers and the Risk of Pancreatic Cancer in the Netherlands Cohort Study
Authors: Keszei András P. , Verhage Bas A.J. , Heinen Mirjam M. , Goldbohm Royle A. , van den Brandt Piet A. 
Published: June 2009

Abstract
An association between high intake of folate and reduced risk of cancer has been suggested by previous research. However, epidemiologic data from cohort studies regarding the relationship between dietary folate and pancreatic cancer are sparse and inconsistent. We examined the association between dietary folate intake and risk of pancreatic cancer within the Netherlands Cohort Study on diet and cancer. Men and women (120,852), ages 55 to 69 years, were recruited. Information on diet was collected at baseline by means of food frequency questionnaires, and the cohort was followed for 13.3 years. Total folate and vitamer intake were calculated using folate contents of food items derived from a validated liquid chromatography trienzyme method. Cases (n = 363) were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. A case-cohort approach was used using the follow-up data of a random subcohort (n = 5,000) identified at the onset of the cohort. Multivariable hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards model. After adjusting for age, gender, smoking status, number of years smoked, number of cigarettes smoked per day, and intake of added sugar multivariate hazard ratio comparing the highest and lowest quintiles of folate intake for pancreatic cancer risk was 1.37 (confidence interval, 0.97-1.94; Ptrend = 0.07). When folate vitamers were analyzed separately, results did not show a difference in association. Our results do not support a protective association of total dietary folate or individual folate vitamers on the risk of pancreatic cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(6):1785–91)
International Trends in Colorectal Cancer Incidence Rates
Authors: Center Melissa M. , Jemal Ahmedin , Ward Elizabeth 
Published: June 2009

AbstractBackground: Previous studies have documented significant variations in colorectal cancer incidence rates and trends regionally and across countries. However, no study has examined the worldwide pattern using the most recently updated incidence data from the IARC.Methods: We obtained sex-specific colorectal cancer incidence for 1953-57 through 1998-2002 by cancer registry from Cancer Incidence in Five Continents (CI5) databases. For 51 cancer registries with long-term incidence data, we assessed the change in the incidence rates over the past 20 years by calculating the ratio of the incidence rates in 1998-2002 to that in 1983-87.Results: Colorectal cancer incidence rates for both males and females statistically significantly increased from 1983-87 to 1998-2002 for 27 of 51 cancer registries considered in the analysis, largely confined to economically transitioning countries including Eastern European countries, most parts of Asia, and select countries of South America. These increases were more prominent for men than for women. We also observed substantial variations in colorectal cancer incidence trends within countries such as Japan. Similarly, trends in Israel and Singapore varied significantly according to ethnicity. The United States is the only country where colorectal cancer incidence rates declined in both males and females.Conclusions: Colorectal cancer incidence rates continue to increase in economically transitioning countries, with incidence rates among men in the Czech Republic and Slovakia exceeding the peak incidence observed in the United States and other long-standing developed nations. Targeted prevention and early detection programs could help reverse the trend in these countries. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1688–94)
Vitamin D Pathway Gene Variants and Prostate Cancer Risk
Authors: Holt Sarah K. , Kwon Erika M. , Peters Ulrike , Ostrander Elaine A. , Stanford Janet L. 
Published: June 2009

Abstract
Vitamin D has antiproliferative, antiangiogenic, and apoptotic properties. There is some evidence supporting an association between vitamin D–related gene variants and prostate cancer risk. We report results from this population-based case-control study of genes encoding for the vitamin D receptor (VDR), the vitamin D activating enzyme 1-α-hydroxylase (CYP27B1), and deactivating enzyme 24-hydroxylase (CYP24A1). Forty-eight tagging single nucleotide polymorphisms (tagSNP) were analyzed in 827 incident prostate cancer cases diagnosed from 2002 to 2005, and in 787 age-matched controls. Contrary to some earlier studies, we found no strong evidence of altered risk of developing prostate cancer overall or within clinical measures of tumor aggressiveness for any of the tagSNPs when they were assessed individually or in haplotypes. (Cancer Epidemiol NBiomarkers Prev 2009;18(6):1929–33)
Association of Genetic Polymorphisms, mRNA Expression ofp53andp21with Chronic Benzene Poisoning in a Chinese Occupational Population
Authors: Sun Pin , Qiu Yulan , Zhang Zhongbin , Wan Junxiang , Wang Tong , Jin Xipeng , Lan Qing , Rothman Nathaniel , Xia Zhao-lin 
Published: June 2009

AbstractDNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.32-0.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 CC/AT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1821–8)