bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Adenylate Cyclase-Controlled Signaling Network Regulates
Pseudomonas aeruginosa
Virulence in a Mouse Model of Acute Pneumonia
Authors: Smith Roger S. , Wolfgang Matthew C. , Lory Stephen 
Published: February 2004

ABSTRACT

Infections caused by the opportunistic pathogen
Pseudomonas aeruginosa
involve the interplay of several bacterial virulence factors. It has recently been established that the delivery of toxic effector proteins by the type III secretion system is an important virulence mechanism in several animal models. Furthermore, the expression of the type III secretion system and its effectors has been correlated with a poor clinical outcome during human infections. A novel cyclic AMP (cAMP) regulatory network that controls the expression of virulence factors, including the type III secretion system, was examined to determine its contribution to
P. aeruginosa
colonization and dissemination in a mouse pneumonia model. Mutants lacking the two genome-encoded adenylate cyclases, CyaA and CyaB, and the cAMP-dependent regulator Vfr were examined. Based on the enumeration of bacteria in lungs, livers, and spleens, as well as the assessment of mouse lung pathology, mutations in the
cyaB
and
vfr
genes resulted in a more significantly attenuated phenotype than mutations in
cyaA
. Moreover, in this model, expression of the type III secretion system was essential for lung colonization and pathology. Strains with mutations in the
exsA
gene, which encodes a type III regulatory protein, or
pscC
, which encodes an essential component of the secretion apparatus, were also significantly attenuated. Finally, we demonstrate that virulence can be restored in an adenylate cyclase mutant by the overexpression of
exsA
, which specifically restores expression of the type III secretion system in the absence of a functional cAMP-dependent regulatory network.
CNLAC1Is Required for Extrapulmonary Dissemination ofCryptococcus neoformansbut Not Pulmonary Persistence
Authors: Noverr Mairi C. , Williamson Peter R. , Fajardo Ryan S. , Huffnagle Gary B. 
Published: February 2004

ABSTRACTThe pathogenic yeastCryptococcus neoformansproduces a laccase enzyme (CNLAC1), which catalyzes the synthesis of melanin in the presence of phenolic compounds. A number of genes have been implicated in the regulation of laccase and melanization, includingIPC1,GPA1,MET3, andSTE12. Albino mutants derived from random mutagenesis techniques may contain mutations in genes that regulate multiple virulence factors, includingCNLAC1. The goal of our study is to investigate the role ofCNLAC1in virulence and evasion of pulmonary host defenses after infection via the respiratory tract. Using a set of congenic laccase-positive (2E-TUC-4) and laccase-deficient (2E-TU-4) strains, we found that both strains are avirulent at a lower dose (104CFU/mouse) in mice. After the infectious dose was increased to 106CFU/mouse, 70% mortality was observed in mice infected with 2E-TUC-4 compared to no mortality in mice infected with 2E-TU-4 at day 30 postinfection. This observation confirms the requirement forCNLAC1in virulence. Interestingly, we observed no differences between the two strains in pulmonary growth or in elicitation of cellular immune responses in the lung. The only measurable defect of 2E-TU-4 was in dissemination to extrapulmonary sites. To examine the role ofCNLAC1in dissemination, mice were infected intravenously. By week 3 postinfection, equal numbers of strains 2E-TUC-4 and 2E-TU-4 were recovered from the brain and spleen. This observation indicates thatCNLAC1facilitates escape from the lung, but not growth in the lungs or brain, and suggests a novel role forCNLAC1in virulence during an infection aquired via the respiratory tract.
Conservation and Diversity of
sap
Homologues and Their Organization among
Campylobacter fetus
Isolates
Authors: Tu Zheng-Chao , Hui John , Blaser Martin J. 
Published: February 2004

ABSTRACT

Campylobacter fetus
surface layer proteins (SLPs), encoded by
sapA
homologues, are important in virulence. In wild-type
C. fetus
strain 23D, all eight
sapA
homologues are located in the 54-kb
sap
island, and SLP expression reflects the position of a unique
sapA
promoter in relation to the
sapA
homologues. The extensive homologies in the
sap
island include both direct and inverted repeats, which allow DNA rearrangements, deletion, or duplication; these elements confer substantial potential for genomic plasticity. To better understand
C. fetus sap
island diversity and variation mechanisms, we investigated the organization and distribution of
sapA
homologues among 18
C. fetus
strains of different subspecies, serotypes, and origins. For all type A strains, the boundaries of the
sap
island were relatively consistent. A 187-bp noncoding DNA insertion near the upstream boundary of the
sap
island was found in two of three reptile strains studied. The
sapA
homologue profiles were strain specific, and six new
sapA
homologues were recognized. Several homologues from reptile strains are remarkably conserved in relation to their corresponding mammalian homologues. In total, the observed differences suggest that the
sap
island has evolved differing genotypes that are plastic, perhaps enabling colonization of varied niches, in addition to antigenic variation.
Attenuation of Late-Stage Disease in Mice Infected bythe
Mycobacterium tuberculosis
Mutant Lacking theSigF Alternate Sigma Factor and Identification ofSigF-Dependent Genes by MicroarrayAnalysis
Authors: Geiman Deborah E. , Kaushal Deepak , Ko Chiew , Tyagi Sandeep , Manabe Yukari C. , Schroeder Benjamin G. , Fleischmann Robert D. , Morrison Norman E. , Converse Paul J. , Chen Ping , Bishai William R. 
Published: February 2004

ABSTRACT

The
Mycobacterium tuberculosis
alternate sigma factor, SigF, is
expressed during stationary growth phase and under stress conditions in
vitro. To better understand the function of SigF we studied the
phenotype of the
M. tuberculosis
Δ
sigF
mutant
in vivo during mouse infection, tested the mutant as a vaccine in
rabbits, and evaluated the mutant's microarray expression profile
in comparison with the wild type. In mice the growth rates of theΔ
sigF
mutant and wild-type strains were nearly
identical during the first 8 weeks after infection. At 8 weeks, theΔ
sigF
mutant persisted in the lung, while the wild
type continued growing through 20 weeks. Histopathological analysis
showed that both wild-type and mutant strains had similar degrees of
interstitial and granulomatous inflammation during the first 12 weeks
of infection. However, from 12 to 20 weeks the mutant strain showed
smaller and fewer lesions and less inflammation in the lungs and
spleen. Intradermal vaccination of rabbits with the
M.
tuberculosis
Δ
sigF
strain, followed by aerosol
challenge, resulted in fewer tubercles than did intradermal
M.
bovis
BCG vaccination. Complete genomic microarray analysis
revealed that 187 genes were relatively underexpressed in the absence
of SigF in early stationary phase, 277 in late stationary phase, and
only 38 genes in exponential growth phase. Numerous regulatory genes
and those involved in cell envelope synthesis were down-regulated in
the absence of SigF; moreover, the Δ
sigF
mutant strain
lacked neutral red staining, suggesting a reduction in the expression
of envelope-associated sulfolipids. Examination of
5′-untranslated sequences among the downregulated genes
revealed multiple instances of a putative SigF consensus recognition
sequence: GGTTTCX
18
GGGTAT.
These results indicate that in the mouse the
M.
tuberculosis
Δ
sigF
mutant strain persists in the
lung but at lower bacterial burdens than wild type and is attenuated by
histopathologic assessment. Microarray analysis has identified
SigF-dependent genes and a putative SigF consensus recognition
site.
Protective Efficacy of Antigenic Fractions in Mouse Models of Cryptococcosis
Authors: Mansour Michael K. , Yauch Lauren E. , Rottman James B. , Levitz Stuart M. 
Published: February 2004

ABSTRACTInfections due to the encapsulated fungusCryptococcus neoformansare a significant cause of morbidity and mortality in patients with impaired T-cell function, particularly those with AIDS. Presumably then, T-cell responses to cryptococcal antigens are critical for protection against this ubiquitous fungus. To test the protective efficacy of these antigens as vaccine candidates, secreted cryptococcal antigens were separated by concanavalin A affinity chromatography into adherent (mannoprotein [MP]) and nonadherent (flowthrough [FT]) fractions, and the fractions were tested in murine models of disseminated cryptococcosis. Compared with adjuvant alone, C57BL/6 mice that received two inoculations of MP and FT exhibited prolonged survival and reduced brain and kidney fungal loads following intravenous challenge withC. neoformansstrain B3501. MP-immunized animals had increased brain levels of tumor necrosis factor alpha, gamma interferon, and interleukin-2. Histopathologic examination revealed that compared with organs from mice that received only adjuvant, MP-immunized mice were able to recruit a stronger cellular infiltrate in brain, kidney, and liver in response to cryptococcal infection. Conjugated O-linked glycans were necessary for optimal MP-mediated protection, because chemical O deglycosylation reduced the protective efficacy of MP immunization. FT and MP immunization protected B-cell-deficient, but not T-cell-deficient mice, suggesting that protection was T-cell mediated. CBA/J mice also benefited from immunization with FT and MP, although the benefits were more modest than those seen with C57BL/6 mice. Thus, both MP and FT fractions ofC. neoformanscontain components that protect mice from disseminated cryptococcosis, and this protection appears to be T-cell mediated.
OspB Antibody Prevents
Borrelia burgdorferi
Colonization of
Ixodes scapularis
Authors: Fikrig Erol , Pal Utpal , Chen Manchuan , Anderson John F. , Flavell Richard A. 
Published: February 2004

ABSTRACT

Borrelia burgdorferi
outer surface protein OspB is expressed by spirochetes in the
Ixodes scapularis
gut.
ospB
is transcribed from a bicistronic operon with
ospA
, a known spirochete adhesion gene in the tick gut. Here we examine whether OspB also has a specific function in ticks. OspB specifically binds to a protein or protein complex within the tick gut. We also assessed whether selected nonborreliacidal OspB antibodies or F(ab)
2
fragments interfere with
B. burgdorferi
-tick attachment in vivo. We examined engorged ticks that fed on
B. burgdorferi
N40-infected
scid
mice that had been treated with OspB F(ab)
2
fragments. Control F(ab)
2
fragments did not interfere with
B. burgdorferi
colonization of the tick gut, whereas OspB F(ab)
2
fragments significantly inhibited the attachment of spirochetes to the tick gut. These studies show that nonbactericidal OspB antibodies interfere with
B. burgdorferi
colonization of
I. scapularis
, highlighting a specific role for OspB in spirochete- arthropod interactions and suggesting new antibody-mediated strategies for interfering with
B. burgdorferi
transmission.
Determination of Surface-Exposed, Functional Domains of Gonococcal Transferrin-Binding Protein A
Authors: Yost-Daljev Mary Kate , Cornelissen Cynthia Nau 
Published: February 2004

ABSTRACTThe gonococcal transferrin receptor is composed of two distinct proteins, TbpA and TbpB. TbpA is a member of the TonB-dependent family of integral outer membrane transporters, while TbpB is lipid modified and thought to be peripherally surface exposed. We previously proposed a hypothetical topology model for gonococcal TbpA that was based upon computer predictions and similarity with other TonB-dependent transporters for which crystal structures have been determined. In the present study, the hemagglutinin epitope was inserted into TbpA to probe the surface topology of this protein and secondarily to test the functional impacts of site-specific mutagenesis. Twelve epitope insertion mutants were constructed, five of which allowed us to confirm the surface exposure of loops 2, 3, 5, 7, and 10. In contrast to the predictions set forth by the hypothetical model, insertion into the plug region resulted in an epitope that was surface accessible, while epitope insertions into two putative loops (9 and 11) were not surface accessible. Insertions into putative loop 3 and β strand 9 abolished transferrin binding and utilization, and the plug insertion mutant exhibited decreased transferrin-binding affinity concomitant with an inability to utilize it. Insertion into putative β strand 16 generated a mutant that was able to bind transferrin normally but that was unable to mediate utilization. Mutants with insertions into putative loops 2, 9, and 11 maintained wild-type binding affinity but could utilize only transferrin in the presence of TbpB. This is the first demonstration of the ability of TbpB to compensate for a mutation in TbpA.
Rat Neutrophils Prevent the Development of Tuberculosis
Authors: Sugawara Isamu , Udagawa Tadashi , Yamada Hiroyuki 
Published: February 2004

ABSTRACT

To understand the role of neutrophils in the development of rat tuberculosis in vivo, we utilized lipopolysaccharide (LPS)-induced neutrophilia in the lungs. LPS (50 μg/ml) was administered intratracheally to male Fischer rats. Rats were then infected with
Mycobacterium tuberculosis
by an airborne route. Intratracheal injection of LPS significantly blocked the development of pulmonary granulomas and significantly reduced pulmonary CFU (
P
< 0.01). LPS treatment with amphotericin B (an LPS inhibitor) or neutralizing anti-rat neutrophil antibody reversed the development of pulmonary lesions. LPS-induced transient neutrophilia prevented early mycobacterial infection. The timing of LPS administration was important. When given intratracheally at least 10 days after aerial infection, LPS did not prevent development of tuberculosis. Neutrophils obtained by bronchoalveolar lavage killed
M. tuberculosis
cells. These results indicate clearly that neutrophils participate actively in defense against early-phase tuberculosis.
Mycobacterial Purified Protein Derivatives Stimulate Innate Immunity: Malawians Show Enhanced Tumor Necrosis Factor Alpha, Interleukin-1β (IL-1β), and IL-10 Responses Compared to Those of Adolescents in the United Kingdom
Authors: Weir Rosemary E. , Black Gillian F. , Dockrell Hazel M. , Floyd Sian , Fine Paul E. M. , Chaguluka Steven D. , Stenson Sally , King Elizabeth , Nazareth Bernadette , Warndorff David K. , Ngwira Bagrey , Crampin Amelia C. , Mwaungulu Lorren , Sichali Lifted , Jarman Elizabeth , Donovan Linda , Blackwell Jenefer M. 
Published: February 2004

ABSTRACTTo investigate the role of innate immunity in variable efficacy ofMycobacterium bovisBCG vaccination in Malawi and the United Kingdom, we examined 24-h tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-10 responses to mycobacterial purified protein derivatives (PPDs). The rank order in stimulatory potency for different PPDs was the same for all three cytokines. Before vaccination Malawians made higher pro- and anti-inflammatory responses than did United Kingdom subjects. Fewer than 5% of United Kingdom subjects made IL-10 in response to any PPD, compared to 19 to 57% responders among Malawians. Priming for regulatory IL-10 may contribute to the smaller increase in gamma interferon responses in Malawians compared to United Kingdom subjects following BCG vaccination.
Detection of Antibodies to Toxin-Coregulated Pili in Sera from Cholera Patients
Authors: Attridge Stephen R. , Wallerström Gun , Qadri Firdausi , Svennerholm Ann-Mari 
Published: February 2004

ABSTRACT

Monoclonal antibodies (MAbs) were prepared against toxin-coregulated pili (TCP) isolated from
Vibrio cholerae
O1 El Tor. Despite their limited bactericidal potential, two MAbs were able to mediate biotype-specific protection against experimental cholera in infant mice. These MAbs were used in immunoblotting studies to assess seroconversion to El Tor TCP following cholera. Clear anti-pilus responses were observed in five of nine patients.
Impacts of
sarA
and
agr
in
Staphylococcus aureus
Strain Newman on Fibronectin-Binding Protein A Gene Expression and Fibronectin Adherence Capacity In Vitro and in Experimental Infective Endocarditis
Authors: Xiong Yan-Qiong , Bayer Arnold S. , Yeaman Michael R. , van Wamel Willem , Manna Adhar C. , Cheung Ambrose L. 
Published: February 2004

ABSTRACT

We investigated the impacts of
sarA
and
agr
on
fnbA
expression and fibronectin-binding capacity in
Staphylococcus aureus
in vitro and in experimental endocarditis. Although
sarA
up-regulated and
agr
down-regulated both
fnbA
expression and fibronectin binding in vitro and in vivo,
fnbA
expression was positively regulated in the absence of both global regulators. Thus, additional regulatory loci contribute to
fnbA
regulation and fibronectin-binding capacities in
S. aureus
.
The effects of occupational exposure to chlorpyrifos on the peripheral nervous system: a prospective cohort study
Authors: Albers J W , Garabrant D H , Schweitzer S J , Garrison R P , Richardson R J , Berent S 
Published: February 2004

Aims:To determine whether chronic occupational exposure to chlorpyrifos at levels associated with various aspects of manufacturing produced a clinically evident or subclinical peripheral neuropathy.Methods:Clinical and quantitative nerve conduction study (NCS) examinations were performed on two occasions on chlorpyrifos manufacturing workers who had measurable chlorpyrifos exposure and a referent group. Baseline evaluations were performed on 53 of 66 eligible chlorpyrifos subjects and on 60 of 74 eligible referent subjects; one-year evaluations were completed on 111 of the 113 subjects evaluated at baseline.Results:Chlorpyrifos and referent groups differed significantly in measures of 3,5,6 trichloro-2-pyridinol excretion and plasma butyrylcholinesterase (BuChE) activity, indicating substantially higher exposures among chlorpyrifos subjects. Few subjects had clinically important neurological symptoms or signs. NCS results were comparable to control values, and there were no significant group differences in NCS results at baseline, one year, or change over one year. No chlorpyrifos subject fulfilled conventional criteria for confirmed peripheral neuropathy at baseline or one-year examinations. The odds ratios for developing any diagnosable level of peripheral neuropathy among the chlorpyrifos subjects was not increased at baseline or at one year compared to referents at baseline. Mixed regression models used to evaluate subclinical group-by-time interactions showed numerous significant NCS differences attributable to near-nerve temperature differences among all subjects between the baseline and one-year examinations, but only a few disparate effects related to group.Conclusions:Chronic chlorpyrifos exposure during the manufacturing process sufficient to produce biological effects on BuChE activity was not associated with clinically evident or subclinical peripheral neuropathy at baseline or with measurable deterioration among chlorpyrifos subjects compared to referents after one year of additional exposure.
DEVELOPMENT OF A UNIFIED TENSOR CALCULUS FOR THE EXCEPTIONAL LIE ALGEBRAS
Authors: MACFARLANE A. J. , PFEIFFER HENDRYK 
Published: February 2004

The uniformity of the decomposition law, for a family ℱ of Lie algebras which includes the exceptional Lie algebras, of the tensor powers ad ⊗n of their adjoint representations ad is now well known. This paper uses it to embark on the development of a unified tensor calculus for the exceptional Lie algebras. It deals explicitly with all the tensors that arise at the n=2 stage, obtaining a large body of systematic information about their properties and identities satisfied by them. Some results at the n=3 level are obtained, including a simple derivation of the dimension and Casimir eigenvalue data for all the constituents of ad ⊗3. This is vital input data for treating the set of all tensors that enter the picture at the n=3 level, following a path already known to be viable for [Formula: see text]. The special way in which the Lie algebra [Formula: see text] conforms to its place in the family ℱ alongside the exceptional Lie algebras is described.
Archaeology and the History of Early Islam: The First Seventy Years
Authors: Johns Jeremy 
Published: February 2004

AbstractThe rarity of material evidence for the religion of Islam during the first seventy years of the hijra (622-92 CE) has been used to attack the traditional positivist account of the rise of Islam. However, the earliest declarations of Islam are to be found on media produced by the early Islamic state. It is therefore mistake to read too much significance into the absence of such declarations prior to the formation of that state by Abd al-Malik (685-705 CE). There is little prospect that archaeology will uncover new evidence of Islam from the first seventy years. Le manque de données matérielles sur la religion de l'Islam pendant les sept premières décennies de l'hégire (622-92) a été utilisé pour réfuter la théorie positiviste traditionelle de l'essor de l'Islam. Cependant, les premières déclarations de l'Islam sont à trouver dans des oeuvres produites par l'Etat islamique à ses débuts. Il est donc erroné d'attribuer trop de sens à l'absence de telles déclarations avant la formation de cet Etat par Abd al-Malik (685-705). Il y a peu de perspectives de nouvelles découvertes archéologiques sur l'Islam des sept premières décennies.
ΛΟΓΟΣ UND ΜΥΘΟΣ IN PLATONISCHEN JENSEITSVORSTELLUNGEN
Authors: Kuch Heinrich 
Published: February 2004

AbstractThis contribution considers the evidence of λογος and μυος in Plato's metaphysical exposés Grg. 523a1-527e7, Phd. 107c1-115a7, R. 614a5-621d3 and Phdr. 246a3-257b6. The two terms differ widely. λογος proves to be the central idea of Platonic philosophy, meaning in particular philosophical arguing, investigation, debate, concept. Understood as a discourse on mythical level μυος is without doubt a remarkable phenomenon in Plato's dialogues, especially when it exhibits divinatory dimensions. But it can be a simple story-telling, too. Abandoning the reality μυος fails to come up to the whole truth. It goes without saying that both λογος and μυος have further significant semantic facets. Although they seem sometimes to approach each other, λογος and μυος are basically different, as the texts display in detail.
ORAL AND WRITTEN SOURCES IN ATHENIAN FORENSIC RHETORIC
Authors: Rydberg-Cox Jeffrey 
Published: February 2004

AbstractAthens in the fifth and fourth centuries witnessed an increase in the use of written materials such as evidence in the law courts, the revision and writing down of laws, the establishment of state archives, and the emergence of books. While many authors praised writing for its positive impact, other writers viewed it as an object of concern. In this paper, I explore the contexts in which Athenian orators used this ambivalence about writing in support of their cases. I demonstrate that the sorts of writing that are praised or attacked in Athenian forensic orations fall into three broad categories, written laws, written contracts, and written evidence. In most cases, the discussion does not revolve around writing in general, but rather focuses on promoting or discrediting an individual piece of writing to suit the needs of the case.