bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilocus Sequence Typing of
Oenococcus oeni
: Detection of Two Subpopulations Shaped by Intergenic Recombination
Authors: Bilhère Eric , Lucas Patrick M. , Claisse Olivier , Lonvaud-Funel Aline 
Published: December 2008

ABSTRACT

Oenococcus oeni
is the acidophilic lactic acid bacterial species most frequently associated with malolactic fermentation of wine. Since the description of the species (formerly
Leuconostoc oenos
), characterization of indigenous strains and industrially produced cultures by diverse typing methods has led to divergent conclusions concerning the genetic diversity of strains. In the present study, a multilocus sequence typing (MLST) scheme based on the analysis of eight housekeeping genes was developed and tested on a collection of 43 strains of diverse origins. The eight targeted loci were successfully amplified and sequenced for all isolates. Only three to 11 different alleles were detected for these genes. The average nucleotide diversity also was rather limited (0.0011 to 0.0370). Despite this limited allelic diversity, the combination of alleles of each strain disclosed 34 different sequence types, which denoted a significant genotypic diversity. A phylogenetic analysis of the concatenated sequences showed that all strains form two well distinct groups of 28 and 15 strains. Interestingly, the same groups were defined by pulsed-field gel electrophoresis, although this method targets different genetic variations. A minimum spanning tree analysis disclosed very few and small clonal complexes. In agreement, statistical analyses of MLST data suggest that recombination events were important during
O. oeni
evolution and contributed to the wide dissemination of alleles among strains. Taken together, our results showed that MLST is more efficient than pulsed-field gel electrophoresis for typing
O. oeni
strains, and they provided a picture of the
O. oeni
population that explains some conflicting results previously obtained.
Phosphoethanolamine Substitution of Lipid A and Resistance ofNeisseria gonorrhoeaeto Cationic Antimicrobial Peptides and Complement-Mediated Killing by Normal Human Serum
Authors: Lewis Lisa A. , Choudhury Biswa , Balthazar Jacqueline T. , Martin Larry E. , Ram Sanjay , Rice Peter A. , Stephens David S. , Carlson Russell , Shafer William M. 
Published: December 2008

ABSTRACTThe capacity ofNeisseria gonorrhoeaeto cause disseminated gonococcal infection requires that such strains resist the bactericidal action of normal human serum. The bactericidal action of normal human serum againstN. gonorrhoeaeis mediated by the classical complement pathway through an antibody-dependent mechanism. The mechanism(s) by which certain strains of gonococci resist normal human serum is not fully understood, but alterations in lipooligosaccharide structure can affect such resistance. During an investigation of the biological significance of phosphoethanolamine extensions from lipooligosaccharide, we found that phosphoethanolamine substitutions from the heptose II group of the lipooligosaccharide β-chain did not impact levels of gonococcal (strain FA19) resistance to normal human serum or polymyxin B. However, loss of phosphoethanolamine substitution from the lipid A component of lipooligosaccharide, due to insertional inactivation oflptA, resulted in increased gonococcal susceptibility to polymyxin B, as reported previously forNeisseria meningitidis. In contrast to previous reports withN. meningitidis, loss of phosphoethanolamine attached to lipid A rendered strain FA19 susceptible to complement killing. Serum killing of thelptAmutant occurred through the classical complement pathway. Both serum and polymyxin B resistance as well as phosphoethanolamine decoration of lipid A were restored in thelptA-null mutant by complementation with wild-typelptA. Our results support a role for lipid A phosphoethanolamine substitutions in resistance of this strict human pathogen to innate host defenses.
Streptococcus agalactiae
CspA Is a Serine Protease That Inactivates Chemokines
Authors: Bryan Joshua D. , Shelver Daniel W. 
Published: December 2008

ABSTRACT

Streptococcus agalactiae
(group B
Streptococcus
[GBS]) remains a leading cause of invasive infections in neonates and has emerged as a pathogen of the immunocompromised and elderly populations. The virulence mechanisms of GBS are relatively understudied and are still poorly understood. Previous evidence indicated that the GBS
cspA
gene is necessary for full virulence and the cleavage of fibrinogen. The predicted
cspA
product displays homology to members of the extracellular cell envelope protease family. CXC chemokines, many of which can recruit neutrophils to sites of infection, are important signaling peptides of the immune system. In this study, we purified CspA and demonstrated that it readily cleaved the CXC chemokines GRO-α, GRO-β, GRO-γ, neutrophil-activating peptide 2 (NAP-2), and granulocyte chemotactic protein 2 (GCP-2) but did not cleave interleukin-8. CspA did not cleave a panel of other test substrates, suggesting that it possesses a certain degree of specificity. CXC chemokines also underwent cleavage by whole GBS cells in a
cspA
-dependent manner. CspA abolished the abilities of three representative CXC chemokines, GRO-γ, NAP-2, and GCP-2, to attract and activate neutrophils. Genetic and biochemical evidence indicated that CspA is a serine protease with S575 at its active site. D180 was also implicated as part of the signature serine protease catalytic triad, and both S575 and D180 were required for both N-terminal and C-terminal autocatalytic processing of CspA.
T-POP Array Identifies EcnR and PefI-SrgD as Novel Regulators of Flagellar Gene Expression
Authors: Wozniak Christopher E. , Lee Changhan , Hughes Kelly T. 
Published: December 2008

ABSTRACTThe T-POP transposon was employed in a general screen for tetracycline (Tet)-induced chromosomal loci that exhibited Tet-activated or Tet-repressed expression of afliC-lactranscriptional fusion. Insertions that activated flagellar transcription were located in flagellar genes. T-POP insertions that exhibited Tet-dependentfliC-lacinhibition were isolated upstream of theecnR, fimZ, pefI-srgD, rcsB, andydiVgenes and in the flagellar geneflgA, which is located upstream of the anti-σ28factor geneflgM. When expressed from the chromosomal ParaBADpromoter, EcnR, FimZ, PefI-SrgD, and RcsB inhibited the transcription of the flagellar class 1flhDCoperon. YdiV, which is weakly homologous to EAL domain proteins involved in cyclic-di-GMP regulation, appears to act at a step after class 1 transcription. By using a series of deletions of the regulatory genes to try to disrupt each pathway, these regulators were found to act largely independently of one another. These results identify EcnR and PefI-SrgD as additional components of the complex regulatory network controlling flagellar expression.
Archaeal ApbC/Nbp35 Homologs Function as Iron-Sulfur Cluster Carrier Proteins
Authors: Boyd Jeffrey M. , Drevland Randy M. , Downs Diana M. , Graham David E. 
Published: December 2008

ABSTRACT

Iron-sulfur clusters may have been the earliest catalytic cofactors on earth, and most modern organisms use them extensively. Although members of the
Archaea
produce numerous iron-sulfur proteins, the major cluster assembly proteins found in the
Bacteria
and
Eukarya
are not universally conserved in archaea. Free-living archaea do have homologs of the bacterial
apbC
and eukaryotic
NBP35
genes that encode iron-sulfur cluster carrier proteins. This study exploits the genetic system of
Salmonella enterica
to examine the in vivo functionality of
apbC
/
NBP35
homologs from three archaea:
Methanococcus maripaludis
,
Methanocaldococcus jannaschii
, and
Sulfolobus solfataricus.
All three archaeal homologs could correct the tricarballylate growth defect of an
S. enterica apbC
mutant. Additional genetic studies showed that the conserved Walker box serine and the Cys-X-X-Cys motif of the
M. maripaludis
MMP0704 protein were both required for function in vivo but that the amino-terminal ferredoxin domain was not. MMP0704 protein and an MMP0704 variant protein missing the N-terminal ferredoxin domain were purified, and the Fe-S clusters were chemically reconstituted. Both proteins bound equimolar concentrations of Fe and S and had UV-visible spectra similar to those of known [4Fe-4S] cluster-containing proteins. This family of dimeric iron-sulfur carrier proteins evolved before the archaeal and eukaryal lineages diverged, representing an ancient mode of cluster assembly.
Surface Translocation byLegionella pneumophila: a Form of Sliding Motility That Is Dependent upon Type II Protein Secretion
Authors: Stewart Catherine R. , Rossier Ombeline , Cianciotto Nicholas P. 
Published: December 2008

ABSTRACTLegionella pneumophilaexhibits surface translocation when it is grown on a buffered charcoal yeast extract (BCYE) containing 0.5 to 1.0% agar. After 7 to 22 days of incubation, spreading legionellae appear in an amorphous, lobed pattern that is most manifest at 25 to 30°C. All nineL. pneumophilastrains examined displayed the phenotype. Surface translocation was also exhibited by some, but not all, otherLegionellaspecies examined.L. pneumophilamutants that were lacking flagella and/or type IV pili behaved as the wild type did when plated on low-percentage agar, indicating that the surface translocation is not swarming or twitching motility. A translucent film was visible atop the BCYE agar, advancing ahead of the spreading legionellae. Based on its abilities to disperse water droplets and to promote the spreading of heterologous bacteria, the film appeared to manipulate surface tension and, as such, acted like a surfactant. Indeed, a sample obtained from the film rapidly dispersed when it was spotted onto a plastic surface.L. pneumophilatype II secretion (Lsp) mutants, but not their complemented derivatives, were defective for both surface translocation and film production. In contrast, mutants defective for type IV secretion exhibited normal surface translocation. Whenlspmutants were spotted onto film produced by the wild type, they were able to spread, suggesting that type II secretion promotes the elaboration of theLegionellasurfactant. Together, these data indicate thatL. pneumophilaexhibits a form of surface translocation that is most akin to “sliding motility” and uniquely dependent upon type II secretion.
Characterization of a
Coxiella burnetii ftsZ
Mutant Generated by
Himar1
Transposon Mutagenesis
Authors: Beare Paul A. , Howe Dale , Cockrell Diane C. , Omsland Anders , Hansen Bryan , Heinzen Robert A. 
Published: December 2008

ABSTRACT

Coxiella burnetii
is a gram-negative obligate intracellular bacterium and the causative agent of human Q fever. The lack of methods to genetically manipulate
C. burnetii
significantly impedes the study of this organism. We describe here the cloning and characterization of a
C. burnetii ftsZ
mutant generated by
mariner
-based
Himar1
transposon (Tn) mutagenesis.
C. burnetii
was coelectroporated with a plasmid encoding the
Himar1
C9 transposase variant and a plasmid containing a
Himar1
transposon encoding chloramphenicol acetyltransferase, mCherry fluorescent protein, and a ColE1 origin of replication. Vero cells were infected with electroporated
C. burnetii
and transformants scored as organisms replicating in the presence of chloramphenicol and expressing mCherry. Southern blot analysis revealed multiple transpositions in the
C. burnetii
genome and rescue cloning identified 30 and 5 insertions in coding and noncoding regions, respectively. Using micromanipulation, a
C. burnetii
clone was isolated containing a Tn insertion within the C terminus of the cell division gene
ftsZ
. The
ftsZ
mutant had a significantly lower growth rate than wild-type bacteria and frequently appeared as filamentous forms displaying incomplete cell division septa. The latter phenotype correlated with a deficiency in generating infectious foci on a per-genome basis compared to wild-type organisms. The mutant FtsZ protein was also unable to bind the essential cell division protein FtsA. This is the first description of
C. burnetii
harboring a defined gene mutation generated by genetic transformation.
Parmenides' Modal Fallacy
Authors: Lewis Frank 
Published: December 2008

AbstractIn his great poem, Parmenides uses an argument by elimination to select the correct "way of inquiry" from a pool of two, the ways of is and of is not, joined later by a third, "mixed" way of is and is not. Parmenides' first two ways are soon given modal upgrades – is becomes cannot not be, and is not becomes necessarily is not (B2, 3-6) – and these are no longer contradictories of one another. And is the common view right, that Parmenides rejects the "mixed" way because it is a contradiction? I argue that the modal upgrades are the product of an illicit modal shift. This same shift, built into two Exclusion Arguments, gives Parmenides a novel argument to show that the "mixed" way fails. Given the independent failure of the way of is not, Parmenides' argument by elimination is complete.
Truth as a Value in Plato's Republic
Authors: Woolf Raphael 
Published: December 2008

AbstractTo what extent is possession of truth considered a good thing in the Republic? Certain passages of the dialogue appear to regard truth as a universal good, but others are more circumspect about its value, recommending that truth be withheld on occasion and falsehood disseminated. I seek to resolve this tension by distinguishing two kinds of truths, which I label 'philosophical' and 'non-philosophical'. Philosophical truths, I argue, are considered unqualifiedly good to possess, whereas non-philosophical truths are regarded as worth possessing only to the extent that possession conduces to good behaviour in those who possess them. In the non-philosophical arena it is an open question, to be determined on a case-by-case basis, whether falsehood is more efficacious in furthering this practical aim than truth.
Textkritischer Kommentar zu ausgewählten Stellen des Lukas- und des Johannesevangeliums
Authors: Victor Ulrich 
Published: December 2008

AbstractBecause of the completely contaminated textual tradition of the NT, it is essential that the textual critic as a rule confines himself to the instruments of philology and exegesis, the so-called internal criteria. The customary evaluation of manuscripts and manuscript groups according to their assumed quality and value within the tradition or according to their geographical distribution on the one hand ignores the reality of the transmission, and is on the other hand not a rationally defensible procedure. In this contribution I will demonstrate the arbitrary nature of the customary approach, while showing at the same time the gains to be made for the text by applying internal criteria.
A Feasibility Study of Valerian Extract for Sleep Disturbance in Person With Arthritis
Authors: Taibi Diana M. , Bourguignon Cheryl , Gill Taylor Ann 
Published: December 2008

Objectives: To present a pilot study of valerian to explore issues of feasibility and efficacy in studies of sedative herbs for arthritis-related sleep disturbance. Methods: Fifteen persons with arthritis and mild sleep disturbance were randomized to receive 600 mg valerian ( Valeriana officinalis, n = 7) or placebo ( n = 8) for five nights. Results: Protocol adherence (dosing and data collection) was high. Allocation concealment was successful using a novel approach for matching the placebo on the distinctive odor of valerian. Nonsignificant differences between the groups were found on all sleep outcomes, measured by daily diaries and wrist actigraphy. Conclusion: The study methods were feasible, except for recruitment issues (addressed in the discussion), and may guide the testing of other sedative herbs for persons with arthritis. Although efficacy outcomes were inconclusive due to the small sample size of this study, recent evidence from larger trials of valerian also does not support its efficacy.
Association analyses of the interaction between the ADSS and ATMgenes with schizophrenia in a Chinese population
Authors: Zhang Fuquan , Xu Yong , Liu Pozi , Fan Hua , Huang Xuezhu , Sun Gaoxiang , Song Yuqing , Sham Pak C 
Published: December 2008

Abstract

Background
The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes.

Methods
Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform.

Results
There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10.

Conclusion
These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population.
Revised estimates of influenza-associated excess mortality, United States, 1995 through 2005
Authors: Foppa Ivo M , Hossain Md Monir 
Published: December 2008

Abstract
Background
Excess mortality due to seasonal influenza is thought to be substantial. However, influenza may often not be recognized as cause of death. Imputation methods are therefore required to assess the public health impact of influenza. The purpose of this study was to obtain estimates of monthly excess mortality due to influenza that are based on an epidemiologically meaningful model.

Methods and Results
U.S. monthly all-cause mortality, 1995 through 2005, was hierarchically modeled as Poisson variable with a mean that linearly depends both on seasonal covariates and on influenza-certified mortality. It also allowed for overdispersion to account for extra variation that is not captured by the Poisson error. The coefficient associated with influenza-certified mortality was interpreted as ratio of total influenza mortality to influenza-certified mortality. Separate models were fitted for four age categories (<18, 18–49, 50–64, 65+). Bayesian parameter estimation was performed using Markov Chain Monte Carlo methods. For the eleven year study period, a total of 260,814 (95% CI: 201,011–290,556) deaths was attributed to influenza, corresponding to an annual average of 23,710, or 0.91% of all deaths.

Conclusion
Annual estimates for influenza mortality were highly variable from year to year, but they were systematically lower than previously published estimates. The excellent fit of our model with the data suggest validity of our estimates.
Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma
Authors: Kreisl Teri N. , Kim Lyndon , Moore Kraig , Duic Paul , Royce Cheryl , Stroud Irene , Garren Nancy , Mackey Megan , Butman John A. , Camphausen Kevin , Park John , Albert Paul S. , Fine Howard A. 
Published: December 2008

Purpose To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma. Patients and Methods Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m2 or 125 mg/m2 every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks. Results Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days. Conclusion We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.
Validation of a Colorectal Cancer Risk Prediction Model Among White Patients Age 50 Years and Older
Authors: Park Yikyung , Freedman Andrew Nathan , Gail Mitchell H. , Pee David , Hollenbeck Albert , Schatzkin Arthur , Pfeiffer Ruth M. 
Published: December 2008

Purpose Validation of an absolute risk prediction model for colorectal cancer (CRC) by using a large, population-based cohort. Patients and Methods The National Institutes of Health (NIH) –American Association of Retired Persons (AARP) diet and health study, a prospective cohort study, was used to validate the model. Men and women age 50 to 71 years at baseline answered self-administered questionnaires that asked about demographic characteristics, diet, lifestyle, and medical histories. We compared expected numbers of CRC patient cases predicted by the model to the observed numbers of CRC patient cases identified in the NIH-AARP study overall and in subgroups defined by risk factor combinations. The discriminatory power was measured by the area under the receiver-operating characteristic curve (AUC). Results During an average of 6.9 years of follow-up, we identified 2,092 and 832 incident CRC patient cases in men and women, respectively. The overall expected/observed ratio was 0.99 (95% CI, 0.95 to 1.04) in men and 1.05 (95% CI, 0.98 to 1.11) in women. Agreement between the expected and the observed number of cases was good in most risk factor categories, except for in subgroups defined by CRC screening and polyp history. This discrepancy may be caused by differences in the question on screening and polyp history between two studies. The AUC was 0.61 (95% CI, 0.60 to 0.62) for men and 0.61 (95% CI, 0.59 to 0.62) for women, which was similar to other risk prediction models. Conclusion The absolute risk model for CRC was well calibrated in a large prospective cohort study. This prediction model, which estimates an individual's risk of CRC given age and risk factors, may be a useful tool for physicians, researchers, and policy makers.