bluuebunny/crossref_metadata_2025_split huggingface dataset:
EspA, an Orphan Hybrid Histidine Protein Kinase, Regulates the Timing of Expression of Key Developmental Proteins of
Myxococcus xanthus
Authors: Higgs Penelope I. , Jagadeesan Sakthimala , Mann Petra , Zusman David R. 
Published: April 2008

ABSTRACT

Myxococcus xanthus
undergoes a complex starvation-induced developmental program that results in cells forming multicellular fruiting bodies by aggregating into mounds and then differentiating into spores. This developmental program requires at least 72 h and is mediated by a temporal cascade of gene regulators in response to intra- and extracellular signals.
espA
mutants, encoding an orphan hybrid histidine kinase, alter the timing of this developmental program, greatly accelerating developmental progression. Here, we characterized EspA and demonstrated that it autophosphorylates in vitro on the conserved histidine residue and then transfers the phosphoryl group to the conserved aspartate residue in the associated receiver domain. The conserved histidine and aspartate residues were both required for EspA function in vivo. Analysis of developmental gene expression and protein accumulation in
espA
mutants indicated that the expression of the A-signal-dependent
spi
gene was not affected but that the MrpC transcriptional regulator accumulated earlier, resulting in earlier expression of its target, the FruA transcriptional regulator. Early expression of FruA correlated with acceleration of both the aggregation and sporulation branches of the developmental program, as monitored by early methylation of the FrzCD chemosensory receptor and early expression of the sporulation-specific
dev
and Mxan_3227 (Ω7536) genes. These results show that EspA plays a key role in the timing of expression of genes necessary for progression of cells through the developmental program.
Mutations in
ampG
or
ampD
Affect Peptidoglycan Fragment Release from
Neisseria gonorrhoeae
Authors: Garcia Daniel L. , Dillard Joseph P. 
Published: April 2008

ABSTRACT

Neisseria gonorrhoeae
releases peptidoglycan fragments during growth. The majority of the fragments released are peptidoglycan monomers, molecules known to increase pathogenesis through the induction of proinflammatory cytokines and responsible for the killing of ciliated epithelial cells. In other gram-negative bacteria such as
Escherichia coli
, these peptidoglycan fragments are efficiently degraded and recycled. Peptidoglycan fragments enter the cytoplasm from the periplasm via the AmpG permease. The amidase AmpD degrades peptidoglycan monomers by removing the disaccharide from the peptide. The disaccharide and the peptide are further degraded and are then used for new peptidoglycan synthesis or general metabolism. We examined the possibility that peptidoglycan fragment release by
N. gonorrhoeae
results from defects in peptidoglycan recycling. The deletion of
ampG
caused a large increase in peptidoglycan monomer release. Analysis of cytoplasmic material showed peptidoglycan fragments as recycling intermediates in the wild-type strain but absent from the
ampG
mutant. An
ampD
deletion reduced the release of all peptidoglycan fragments and nearly eliminated the release of free disaccharide. The
ampD
mutant also showed a large buildup of peptidoglycan monomers in the cytoplasm. The introduction of an
ampG
mutation in the
ampD
background restored peptidoglycan fragment release, indicating that events in the cytoplasm (metabolic or transcriptional regulation) affect peptidoglycan fragment release. The
ampD
mutant showed increased metabolism of exogenously added free disaccharide derived from peptidoglycan. These results demonstrate that
N. gonorrhoeae
has an active peptidoglycan recycling pathway and can regulate peptidoglycan fragment metabolism, dependent on the intracellular concentration of peptidoglycan fragments.
Glycine Betaine Uptake by the ProXVWZ ABC Transporter Contributes to the Ability ofMycobacterium tuberculosisTo Initiate Growth in Human Macrophages
Authors: Price Christopher T. D. , Bukka Archana , Cynamon Michael , Graham James E. 
Published: April 2008

ABSTRACTMycobacterium tuberculosismaintains a large genetic capacity necessary for growth in different environments during infection and survival upon aerosol transmission to new hosts. Screening for bacterial RNAs produced in response to host interactions produced candidate lists where we notedproXVWZ, annotated as encoding a putative glycine betaine or proline transporter. As high surface-to-volume ratios make bacterial cells particularly vulnerable to changes in water availability, we investigated the contributions of this transporter to the ability ofM. tuberculosisto colonize macrophages. An H37RvproXVWZmutant was impaired for initial survival and intracellular growth and exhibited reduced growth at elevated medium osmolarity. This defect could be complemented by restoringproXVWZand was attributable to a failure to accumulate the compatible solute glycine betaine. We then demonstrated that ProXVWZ allowsM. tuberculosisto obtain betaine from host macrophages and thereby contributes to early steps in colonizing this niche.
Functional and Phylogenetic Characterization of Vaginolysin, the Human-Specific Cytolysin fromGardnerella vaginalis
Authors: Gelber Shari E. , Aguilar Jorge L. , Lewis Kanako L. T. , Ratner Adam J. 
Published: April 2008

ABSTRACTPore-forming toxins are essential to the virulence of a wide variety of pathogenic bacteria.Gardnerella vaginalisis a bacterial species associated with bacterial vaginosis (BV) and its significant adverse sequelae, including preterm birth and acquisition of human immunodeficiency virus.G. vaginalismakes a protein toxin that generates host immune responses and has been hypothesized to be involved in the pathogenesis of BV. We demonstrate thatG. vaginalisproduces a toxin (vaginolysin [VLY]) that is a member of the cholesterol-dependent cytolysin (CDC) family, most closely related to intermedilysin fromStreptococcus intermedius. Consistent with this predicted relationship, VLY lyses target cells in a species-specific manner, dependent upon the complement regulatory molecule CD59. In addition to causing erythrocyte lysis, VLY activates the conserved epithelial p38 mitogen-activated protein kinase pathway and induces interleukin-8 production by human epithelial cells. Transfection of human CD59 into nonsusceptible cells renders them sensitive to VLY-mediated lysis. In addition, a single amino acid substitution in the VLY undecapeptide [VLY(P480W)] generates a toxoid that does not form pores, and introduction of the analogous proline residue into another CDC, pneumolysin, significantly decreases its cytolytic activity. Further investigation of the mechanism of action of VLY may improve understanding of the functions of the CDC family as well as diagnosis and therapy for BV.
Identification ofEscherichia coliYgaF as anl-2-Hydroxyglutarate Oxidase
Authors: Kalliri Efthalia , Mulrooney Scott B. , Hausinger Robert P. 
Published: April 2008

ABSTRACTYgaF, a protein of previously unknown function inEscherichia coli, was shown to possess noncovalently bound flavin adenine dinucleotide and to exhibitl-2-hydroxyglutarate oxidase activity. The inability of anaerobic, reduced enzyme to reverse the reaction by reducing the product α-ketoglutaric acid is explained by the very high reduction potential (+19 mV) of the bound cofactor. The likely role of this enzyme in the cell is to recover α-ketoglutarate mistakenly reduced by other enzymes or formed during growth on propionate. On the basis of the identified function, we propose that this gene be renamedlhgO.
Opr86 Is Essential for Viability and Is a Potential Candidate for a Protective Antigen against Biofilm Formation byPseudomonas aeruginosa
Authors: Tashiro Yosuke , Nomura Nobuhiko , Nakao Ryoma , Senpuku Hidenobu , Kariyama Reiko , Kumon Hiromi , Kosono Saori , Watanabe Haruo , Nakajima Toshiaki , Uchiyama Hiroo 
Published: April 2008

ABSTRACTPseudomonas aeruginosais an opportunistic bacterial pathogen that is one of the most refractory to therapy when it forms biofilms in the airways of cystic fibrosis patients. To date, studies regarding the production of an immunogenic and protective antigen to inhibit biofilm formation byP. aeruginosahave been superficial. The previously uncharacterized outer membrane protein (OMP) Opr86 (PA3648) ofP. aeruginosais a member of the Omp85 family, of which homologs have been found in all gram-negative bacteria. Here we verify the availability of Opr86 as a protective antigen to inhibit biofilm formation byP. aeruginosaPAO1 and several other isolates. A mutant was constructed in which Opr86 expression could be switched on or off through atacpromoter-controlledopr86gene. The result, consistent with previous Omp85 studies, showed that Opr86 is essential for viability and plays a role in OMP assembly. Depletion of Opr86 resulted in streptococci-like morphological changes and liberation of excess membrane vesicles. A polyclonal antibody against Opr86 which showed reactivity to PAO1 cells was obtained. The antibody inhibited biofilm formation by PAO1 and the other clinical strains tested. Closer examination of early attachment revealed that cells treated with the antibody were unable to attach to the surface. Our data suggest that Opr86 is a critical OMP and a potential candidate as a protective antigen against biofilm formation byP. aeruginosa.
The risk for a cruciate ligament injury of the knee in adolescents and young adults: a population-based cohort study of 46 500 people with a 9 year follow-up
Authors: Parkkari J , Pasanen K , Mattila V M , Kannus P , Rimpelä A 
Published: April 2008

Objectives:The knee joint is the most common site for injury among younger people, the injury often resulting in expensive (surgical) treatment, long-term rehabilitation and permanent functional impairment and disability.Methods:We investigated the incidence and risk factors for a major knee-ligament injury in an adolescent Finnish population. A population-based cohort of 46 472 adolescents was followed for an average of 9 years. All patients hospitalised with the diagnosis of anterior or posterior cruciate ligament injury (ACL or PCL injury) were included in the analysis.Results:265 (0.6%) people (194 male and 71 female subjects) from the total cohort of 46 472 were treated for a cruciate ligament injury of the knee during the follow-up period, giving an injury incidence of 60.9 (95% CI 53.6 to 68.2) per 100 000 person-years. When the socioeconomic, health and lifestyle background variables were taken into account, the adjusted hazard ratio for a cruciate ligament injury of the knee was 8.5 (95% CI 4.3 to 16.4) for female and 4.0 (95% CI 2.7 to 6.1) for male subjects who participated in organised sports ⩾4 times/week.Conclusions:The general risk for a cruciate ligament injury of the knee is relatively low among adolescents and young adults, but participation in organised sports increases the risk significantly. The risk is especially high in active young women. Preventive measures should be adopted to decrease the short-term and long-term burden of these severe injuries.
Peer Review/Fair Review. How did A.V. Hill understand the VO2max and the "plateau phenomenon"? Still no clarity?
Authors: Noakes Timothy David 
Published: April 2008

Introduction/Purpose:A recent editorial in Medicine and Science in Sports and Exercise concludes that the study of Hawkins and colleagues confirms “beyond any doubt the proposition of Hill and Lupton”. It is not clear which of Hill and Lupton’s propositions have been proved “beyond any doubt”.Methods:A review of all the relevant publications of A.V. Hill and his colleagues.Results:Hill and Lupton believed (i) that myocardial ischemia limits maximal exercise performance by inducing circulatory failure; ((ii) that a “governor” protects the ischemic heart by causing a “slowing of the circulation” during maximal exercise; ((iii) that the oxygen cost of running increases exponentially at speeds above 16km per hour; and ((iv) that humans reach their highest measurable oxygen consumption of about 4 litres per minute at that running speed. Hill and Lupton neither invented the concept of the “plateau phenomenon” not did they utilized this concept to establish that a “true” maximum oxygen consumption (VO2max) had been achieved. Nor did they measure cardiac output during exercise.Conclusion:Accepting uncritically this modern interpretation of Hill and Luptons’ theory that the cardiac output limits maximal exercise performance whether or not the plateau phenomenon is present fails to answer the question first posed more than 20 years ago: What causes the termination of exercise when the “true” VO2max is achieved without the “plateau phenomenon”? According to the Hill and Lupton model, this cannot be because a limiting cardiac output has been reached. Since a majority of maximal exercise tests terminate in the absence of the “plateau phenomenon”, this is a seemingly an important question.
Comparison of aspects of smoking among the four histological types of lung cancer
Authors: Kenfield S A , Wei E K , Stampfer M J , Rosner B A , Colditz G A 
Published: April 2008

Background:The magnitude of the link between cigarette smoking and lung cancer may vary by histological type.Methods:We used polytomous logistic regression to evaluate whether aspects of smoking have different effects across four histological types in the Nurses’ Health Study.Results:From 1976 to 2002, we identified 1062 cases of lung cancer: squamous cell (n  201), small cell (n  236), adenocarcinoma (n  543) and large cell carcinoma (n  82), among 65 560 current or former smokers. Risk reduction after quitting ranged from an 8 reduction (relative risk (RR): 0.92, 95 CI 0.91 to 0.94) to a 17 reduction (RR: 0.83, 95 CI 0.80 to 0.86) per year for adenocarcinoma and small cell carcinoma, respectively, with a 9 reduction observed for large cell carcinoma and an 11 reduction observed for squamous cell carcinoma. The association of age at smoking initiation and former cigarette smoking was similar across types, while the association of smoking duration differed. The risk of adenocarcinoma increased by 6 per year of smoking, compared to 7 for large cell, 10 for squamous cell and 12 for small cell. The 6 difference between adenocarcinoma and small cell carcinoma is equivalent to a 3.2 to 9.7-fold increase in risk for 20 years of smoking.Conclusions:The effects of the number of cigarettes smoked per day and years since quitting smoking are different across the major types of lung cancer, which are fully appreciated at long durations of smoking and smoking cessation. Smoking prevention and cessation should continue to be the focus of public health efforts to reduce lung cancer incidence and mortality.
A logic of nonmonotone inductive definitions
Authors: Denecker Marc , Ternovska Eugenia 
Published: April 2008

Well-known principles of induction include monotone induction and different sorts of nonmonotone induction such as inflationary induction, induction over well-founded sets and iterated induction. In this work, we define a logic formalizing induction over well-founded sets and monotone and iterated induction. Just as the principle of positive induction has been formalized in FO(LFP), and the principle of inflationary induction has been formalized in FO(IFP), this article formalizes the principle of iterated induction in a new logic for Nonmonotone Inductive Definitions (ID-logic). The semantics of the logic is strongly influenced by the well-founded semantics of logic programming.
This article discusses the formalisation of different forms of (non-)monotone induction by the well-founded semantics and illustrates the use of the logic for formalizing mathematical and common-sense knowledge. To model different types of induction found in mathematics, we define several subclasses of definitions, and show that they are correctly formalized by the well-founded semantics. We also present translations into classical first or second order logic. We develop modularity and totality results and demonstrate their use to analyze and simplify complex definitions. We illustrate the use of the logic for temporal reasoning. The logic formally extends Logic Programming, Abductive Logic Programming and Datalog, and thus formalizes the view on these formalisms as logics of (generalized) inductive definitions.
Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status
Authors: Bågeman Erika , Ingvar Christian , Rose Carsten , Jernström Helena 
Published: April 2008

Abstract
CYP1A2 plays a key role in the metabolism of both estrogen and coffee. Women with higher coffee intake and the CYP1A2*1F A/A genotype have a ratio of high 2-hydroxyestrone (2-OHE1) to 16α-OHE1. 2-OHE1 is a weak estrogen and may even block the estrogen receptor (ER), whereas 16α-OHE1 is procarcinogenic. We hypothesized that moderate to high coffee consumption (≥2 cups per day) combined with the CYP1A2*1F A/A genotype would be associated with a later age at diagnosis and a greater proportion of ER-negative (ER−) tumors among patients with breast cancer. We genotyped 458 patients with breast cancer (age, 25-99 years) in Lund, Sweden, for CYP1A2*1F. Information on lifestyle factors and tumor characteristics were obtained from preoperative questionnaires and pathology reports. Among patients with CYP1A2*1F A/A (51.3%), moderate to high consumption was associated with a later age at diagnosis compared with low coffee consumption (59.8 versus 52.6 years, P = 0.0004). These patients were also more likely to have ER− tumors than patients with low consumption (14.7% versus 0%, P = 0.018). Coffee was not associated with ER status or age at diagnosis in patients with at least one C allele. Age at diagnosis was not associated with ER status in patients with CYP1A2*1F A/A, but younger patients (&lt;50 years) with at least one C allele were more likely to have ER− tumors compared with older patients (odds ratio, 4.2; 95% confidence interval, 1.9-9.3; P = 0.0002). These findings raise the hypothesis that coffee slows the growth of ER-positive tumors in patients with CYP1A2*1F A/A and may have implications for breast cancer if confirmed. (Cancer Epidemiol Biomarkers Prev 2008;17(4):895–901)
Prediagnostic Use of Hormone Therapy and Mortality After Breast Cancer
Authors: Newcomb Polly A. , Egan Kathleen M. , Trentham-Dietz Amy , Titus-Ernstoff Linda , Baron John A. , Hampton John M. , Stampfer Meir J. , Willett Walter C. 
Published: April 2008

Abstract
Background: A few studies have observed reduced breast cancer mortality in women who used hormone therapy before diagnosis. Due to the high prevalence of past and current hormone use, it is important to investigate whether these preparations are related to breast cancer mortality.
Methods: To evaluate the influence of prediagnostic use of hormone therapy on breast cancer mortality, a prospective cohort of 12,269 women ages 50 years or more diagnosed with incident invasive breast cancer and residents of Wisconsin, Massachusetts, or New Hampshire were enrolled in three phases beginning in 1988. They were followed for death until December 31, 2005, using the National Death Index. Cumulative mortality and multivariable adjusted hazard rate ratios for breast cancer and other mortality causes were calculated for women according to any hormone therapy use, and for exclusive use of estrogen or estrogen-progestin (EP).
Results: During an average 10.3 years of follow-up, 1,690 deaths from breast cancer were documented. Cumulative mortality from breast cancer was lower among hormone therapy users, specifically current users at the time of diagnosis, and EP users, compared with nonusers. Adjusted survival varied by type and duration of hormone therapy before diagnosis. A reduced risk of death from breast cancer was associated with EP preparations (hazard rate ratio, 0.73; 0.59-0.91) and with ≥5 years of EP use (0.60; 0.43-0.84). No association was observed for women who were former or current users of E-alone preparations.
Conclusions: Although use of combined EP preparations increases breast cancer risk, in this study, use of these hormones before diagnosis was associated with reduced risk of death after a breast cancer diagnosis. The better survival among users, particularly of EP, persisted after adjustment of screening, stage, and measured confounders. (Cancer Epidemiol Biomarkers Prev 2008;17(4):864–71)
Association between Genetic Polymorphisms of Macrophage Scavenger Receptor 1 Gene and Risk of Prostate Cancer in the Health Professionals Follow-up Study
Authors: Chen Yen-Ching , Giovannucci Edward , Kraft Peter , Hunter David J. 
Published: April 2008

Abstract
Background: Macrophage scavenger receptor 1 (MSR1) is involved in chronic inflammation, which is a risk factor for prostate cancer. Association studies assessing the relationship between sequence variants of MSR1 and prostate cancer are inconsistent. We hypothesized that sequence variants of MSR1 were associated with prostate cancer risk.
Methods: In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped three common (&gt;5%) single nucleotide polymorphisms (SNP) that have been reported previously to be associated with risk of prostate cancer.
Results: None of these MSR1 SNPs nor estimated haplotypes were associated with prostate cancer risk (P for the global test for haplotypes = 0.89). These MSR1 SNPs also did not appear to be associated with higher-grade or advanced-stage prostate cancer.
Conclusion: The association between these sequence variants of MSR1 and the risk of prostate cancer was null. Further study of aggressive prostate cancer may be warranted, as we had limited power to assess these. (Cancer Epidemiol Biomarkers Prev 2008;17(4):1001–3)
Genetic Polymorphisms Involved in Insulin-like Growth Factor (IGF) Pathway in Relation to Mammographic Breast Density and IGF Levels
Authors: Diorio Caroline , Brisson Jacques , Bérubé Sylvie , Pollak Michael 
Published: April 2008

AbstractThe insulin-like growth factor (IGF) pathway is believed to play a role in carcinogenesis of the mammary gland. Single nucleotide polymorphisms (SNPs) of IGF-I, IGF-binding protein-3 (IGFBP-3), IGF receptor 1, insulin receptor substrate 1, and phosphoinositide-3-kinase, catalytic, β polypeptide genes, which are members of the IGF pathway, have been associated with risk of common cancers, breast density, and/or IGF levels but results remain inconclusive. Thus, we evaluated the association of 11 targeted IGF pathway SNPs with circulating IGF levels and mammographic breast density. Among 741 white premenopausal women, blood samples were collected at time of screening mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate linear models were used to examine the associations. Women carrying increasing number of copies of the rare allele of IGF-I rs1520220 and rs6220 SNPs had increased percent breast density (Ptrend = 0.04 and 0.06, respectively). Carriers of increasing number of copies of the rare allele of phosphoinositide-3-kinase, catalytic, β polypeptide rs361072 SNP had decreased percent (Ptrend = 0.04) and absolute (Ptrend = 0.02) breast density. An association of insulin receptor substrate 1 rs1801278 SNP with absolute density (Ptrend = 0.03) was also observed. All four IGFBP-3 SNPs (including rs2854744) were associated with IGF-I and IGFBP-3 levels. This study shows that several components of the IGF pathway are associated with breast density or IGF levels. Our findings provide additional support for the idea that several components of the IGF pathway may affect breast cancer risk and that this effect on breast cancer development may be mediated, at least in part, through its influence on the morphogenesis of breast tissue. (Cancer Epidemiol Biomarkers Prev 2008;17(4):880–8)