bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Expression of the Smb Bacteriocin in
Streptococcus mutans
Isolates
Authors: Yonezawa Hideo , Kuramitsu Howard K. , Nakayama Shu-ichi , Mitobe Jiro , Motegi Mizuho , Nakao Ryoma , Watanabe Haruo , Senpuku Hidenobu 
Published: May 2008

ABSTRACT

The two-component lantibiotic Smb is produced by
Streptococcus mutans
GS5. In the present study, we identified seven strains of
S. mutans
containing the
smb
gene cluster. These strains could be classified into high- and low-level Smb producers relative to the levels of Smb production by indicator strains in vitro. This classification was dependent upon the transcription levels of the structural
smbA
and
smbB
genes. Sequence analysis upstream of
smbA
in the high- and low-level Smb-producing strains revealed differences at nucleotide position −46 relative to the
smbA
start codon. Interestingly, the transcription start site was present upstream of the point mutation, indicating that both groups of strains have the same promoter constructs and that the differential expression of
smbA
and
smbB
mRNA occurred subsequent to transcription initiation. In addition,
smbA
::
lacZ
fusion expression was higher when it was regulated by the sequences of strains with high-level Smb activity than when it was regulated by the comparable region from strains with low-level Smb activity. Taken together, we conclude that high- or low-level Smb expression is dependent on the presence of a G or a T nucleotide at position −46 relative to the
smbA
translational start site in
S. mutans
Smb producers.
Postantibiotic Effects and Bactericidal Activities of Levofloxacin and Gatifloxacin at Concentrations Simulating Those of Topical Ophthalmic Administration against Fluoroquinolone-Resistant and Fluoroquinolone-Sensitive Methicillin-Resistant
Staphylococcus aureus
Strains
Authors: Hoshi Saichi , Kikuchi Ken , Sasaki Takashi , Sotozono Chie , Kinoshita Shigeru , Hiramatsu Keiichi 
Published: May 2008

ABSTRACT

The bactericidal activities and postantibiotic effects (PAEs) of levofloxacin and gatifloxacin at concentrations corresponding to those in antibiotic eye drops against methicillin-resistant
Staphylococcus aureus
strains were determined. Levofloxacin and gatifloxacin at concentrations simulating those in eye drops showed lower bactericidal activities and shorter PAEs against fluoroquinolone-resistant strains than against fluoroquinolone-sensitive strains.
Evaluation of Antibiotic Therapy for Eradication of “
Candidatus
Helicobacter heilmannii”
Authors: Matsui Hidenori , Aikawa Chihiro , Sekiya Yukie , Takahashi Shinichi , Murayama Somay Yamagata , Nakamura Masahiko 
Published: May 2008

ABSTRACT

Triple-agent therapy with lansoprazole (15 mg/kg)-clarithromycin (50 mg/kg)-amoxicillin (50 mg/kg) twice daily for 7 days fully cleared “
Candidatus
Helicobacter heilmannii” from infected mouse stomachs. Moreover, gastric mucosa-associated lymphoid tissue lymphoma-like lesions in the stomach nearly disappeared in the treated mice 4 months after the therapy.
Differential Activation of Human and Mouse Toll-Like Receptor 4 by the Adjuvant Candidate LpxL1 ofNeisseria meningitidis
Authors: Steeghs Liana , Keestra A. Marijke , van Mourik Andries , Uronen-Hansson Heli , van der Ley Peter , Callard Robin , Klein Nigel , van Putten Jos P. M. 
Published: May 2008

ABSTRACTNeisseria meningitidisLpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in futureN. meningitidisvaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties. Unexpectedly, purified LpxL1 LPS displayed minimal human DC-stimulating properties compared to wild-type LPS. Although whole bacteria induced DC maturation and activation irrespective of their type of LPS, the LpxL1 mutant failed to activate the human recombinant TLR4/MD-2 complex expressed in HeLa cells. Similarly, purified LpxL1 LPS was unable to activate human TLR4/MD-2 and it even acted as an antagonist of wild-type LPS. Both wild-type and LpxL1 LPSs activated the murine TLR4/MD-2 complex, consistent with their abilities to induce maturation and activation of murine DC. Assays with cells transfected with different combinations of human and murine TLR4 and MD-2 indicated that TLR4 was a more-major determinant of the LPS response than MD-2. The species-specific activation of the TLR4/MD-2 complex by LpxL1 LPS may have an impact on the use of LpxL1 LPS as an adjuvant and the use of murine immunization models in human meningococcal vaccine development.
Proteomic Analysis of and Immune Responses toEhrlichia chaffeensisLipoproteins
Authors: Huang Haibin , Lin Mingqun , Wang Xueqi , Kikuchi Takane , Mottaz Heather , Norbeck Angela , Rikihisa Yasuko 
Published: May 2008

ABSTRACTEhrlichia chaffeensisis an obligately intracellular gram-negative bacterium and is the etiologic agent of human monocytic ehrlichiosis (HME). AlthoughE. chaffeensisinduces the generation of several cytokines and chemokines by leukocytes,E. chaffeensislacks lipopolysaccharide and peptidoglycan. Bioinfomatic analysis of theE. chaffeensisgenome, however, predicted genes encoding 15 lipoproteins and 3 posttranslational lipoprotein-processing enzymes. The present study showed that by use of multidimensional liquid chromatography followed by tandem mass spectrometry, all predicted lipoproteins as well as lipoprotein-processing enzymes were expressed byE. chaffeensiscultured in the human promyelocytic leukemia cell line HL-60. Consistent with this observation, a signal peptidase II inhibitor, globomycin, was found to inhibitE. chaffeensisinfection and lipoprotein processing in HL-60 cell culture. To study in vivoE. chaffeensislipoprotein expression and host immune responses toE. chaffeensislipoproteins, 13E. chaffeensislipoprotein genes were cloned into a mammalian expression vector. When the DNA constructs were inoculated into naïve dogs, or when dogs were infected withE. chaffeensis, the animals developed delayed-type hypersensitivity reactions at cutaneous sites of the DNA construct deposition and serum antibodies to these lipoproteins. This is the first demonstration of lipoprotein expression and elicitation of immune responses by a member of the orderRickettsiales. Multiple lipoproteins expressed byE. chaffeensisin vitro and in vivo may play key roles in pathogenesis and immune responses in HME.
The Absence of Toll-Like Receptor 4 Signaling in C3H/HeJ Mice Predisposes Them to Overwhelming Rickettsial Infection and Decreased Protective Th1 Responses
Authors: Jordan Jeffrey M. , Woods Michael E. , Olano Juan , Walker David H. 
Published: May 2008

ABSTRACTThe importance of toll-like receptor 4 (TLR4) in immunity to rickettsiae remains elusive. To investigate the role of TLR4 in protection against rickettsioses, we utilized C3H/HeJ mice, which are naturally defective in TLR4 signaling, and compared the responses of C3H/HeN and C3H/HeJ mice following intravenous inoculation withRickettsia conorii. Mice genetically defective in TLR4 signaling developed overwhelming, fatal rickettsial infections when given an inoculum that was nonfatal for TLR4-competent mice. In addition, mice lacking the ability to signal through TLR4 had significantly greater rickettsial burdens in vivo. Moreover, we observed greater concentrations of the cytokines interleukin 6 (IL-6), tumor necrosis factor alpha, IL-12p40, IL-12p70, and IL-17 in the sera of mice with intact TLR4 function as well as significantly greater quantities of activated CD4+and CD8+T lymphocytes. Additionally, we also observed that Th17 cells were present only in TLR4-competent mice, suggesting an important role for TLR4 ligation in the activation of this subset. In agreement with these data, we also observed significantly greater percentages of immunosuppressive regulatory T cells in the spleen during infection in TLR4-defective mice. Together, these data demonstrate that, while rickettsiae do not contain endotoxic lipopolysaccharide, they nevertheless initiate TLR4-specific immune responses, and these responses are important in protection.
CcpA-Mediated Repression of Streptolysin S Expression and Virulence in the Group A Streptococcus
Authors: Kinkel Traci L. , McIver Kevin S. 
Published: May 2008

ABSTRACT

CcpA is the global mediator of carbon catabolite repression (CCR) in gram-positive bacteria, and growing evidence from several pathogens, including the group A streptococcus (GAS), suggests that CcpA plays an important role in virulence gene regulation. In this study, a deletion of
ccpA
in an invasive M1 GAS strain was used to test the contribution of CcpA to pathogenesis in mice. Surprisingly, the Δ
ccpA
mutant exhibited a dramatic “hypervirulent” phenotype compared to the parental MGAS5005 strain, reflected as increased lethality in a model of systemic infection (intraperitoneal administration) and larger lesion size in a model of skin infection (subcutaneous administration). Expression of
ccpA
in
trans
from its native promoter was able to complement both phenotypes, suggesting that CcpA acts to repress virulence in GAS. To identify the CcpA-regulated gene(s) involved, a transcriptome analysis was performed on mid-logarithmic-phase cells grown in rich medium. CcpA was found to primarily repress 6% of the GAS genome (124 genes), including genes involved in sugar metabolism, transcriptional regulation, and virulence. Notably, the entire
sag
operon necessary for streptolysin S (SLS) production was under CcpA-mediated CCR, as was SLS hemolytic activity. Purified CcpA-His bound specifically to a
cre
within
sagAp
, demonstrating direct repression of the operon. Finally, SLS activity is required for the increased virulence of a Δ
ccpA
mutant during systemic infection but did not affect virulence in a wild-type background. Thus, CcpA acts to repress SLS activity and virulence during systemic infection in mice, revealing an important link between carbon metabolism and GAS pathogenesis.
Cathelicidin LL-37 in Severe
Streptococcus pyogenes
Soft Tissue Infections in Humans
Authors: Johansson Linda , Thulin Pontus , Sendi Parham , Hertzén Erika , Linder Adam , Åkesson Per , Low Donald E. , Agerberth Birgitta , Norrby-Teglund Anna 
Published: May 2008

ABSTRACT
Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococci (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial loads in the tissue even late after the onset of infection. Antimicrobial peptides are important components of the innate host defense, and cathelicidins have been shown to protect against murine necrotic skin infections caused by GAS. However, it has been demonstrated that the streptococcal cysteine protease SpeB proteolytically inactivates the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsy specimens. The results showed large amounts of LL-37, both the proform (hCAP18) and the mature peptide, in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct colocalization between the bacteria and LL-37 could be noted, and bacterial loads showed positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with large amounts of SpeB. Confocal microscopy confirmed strong colocalization of GAS, SpeB, and LL-37 at the bacterial surface. Taken together, the findings of this study provide in vivo support of the hypothesis that SpeB-mediated inactivation of LL-37 at the streptococcal surface represents a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.
Aspergillus fumigatus
Stimulates Leukocyte Adhesion Molecules and Cytokine Production by Endothelial Cells In Vitro and during Invasive Pulmonary Disease
Authors: Chiang Lisa Y. , Sheppard Donald C. , Gravelat Fabrice N. , Patterson Thomas F. , Filler Scott G. 
Published: May 2008

ABSTRACT

Invasive aspergillosis is characterized by hyphal invasion of the blood vessels, which contributes to the pathogenesis of this disease. During this angioinvasion,
Aspergillus fumigatus
interacts with the endothelial cell lining of the blood vessels. We investigated the response of vascular endothelial cells to
A. fumigatus
infection in vitro and in mouse models of invasive pulmonary aspergillosis. Infection with hyphae, but not with conidia, stimulated endothelial cells to synthesize E-selectin, vascular cell adhesion molecule 1 (VCAM-1), interleukin 8, and tumor necrosis factor alpha (TNF-α) in vitro. Killed hyphae induced approximately 40% less stimulation than did live hyphae. Endothelial cell stimulation required contact between the hyphae and endothelial cells but not endocytosis of the organisms. Studies with Δ
gliP
and Δ
stuA
null mutants of
A. fumigatus
indicated that the extent of endothelial cell stimulation was not influenced by gliotoxin or other StuA-dependent factors synthesized by
A. fumigatus
. In neutropenic mice infected with wild-type
A. fumigatus
, increased pulmonary expression of E-selectin, cytokine-induced neutrophil chemoattractant (KC), and TNF-α occurred only when neutropenia had resolved. In nonneutropenic mice immunosuppressed with corticosteroids,
A. fumigatus
stimulated earlier pulmonary expression of E-selectin, VCAM-1, and KC, while expression of intercellular adhesion molecule 1 and TNF-α was suppressed. In both mouse models, expression of E-selectin and KC was associated with high pulmonary fungal burden, angioinvasion, and neutrophil adherence to endothelial cells. Therefore, the expression of leukocyte adhesion molecules and secretion of proinflammatory cytokines by endothelial cells in response to
A. fumigatus
could enhance the host defense against this organism by contributing to the recruitment of activated leukocytes to sites of angioinvasion.
Epidermal Growth Factor Inhibits
Campylobacter jejuni
-Induced Claudin-4 Disruption, Loss of Epithelial Barrier Function, and
Escherichia coli
Translocation
Authors: Lamb-Rosteski Jennifer M. , Kalischuk Lisa D. , Inglis G. Douglas , Buret Andre G. 
Published: May 2008

ABSTRACT

Campylobacter jejuni
is a leading cause of acute bacterial enteritis in humans. Poultry serves as a major reservoir of
C. jejuni
and is thought to act as a principal vehicle of transmission to humans. Epidermal growth factor (EGF) is a small amino acid peptide that exerts a broad range of activities on the intestinal epithelium. The aims of this study were to determine the effect of EGF on
C. jejuni
intestinal colonization in newly hatched chicks and to characterize its effects on
C. jejuni
-induced intestinal epithelial barrier disruption. White Leghorn chicks were treated with EGF daily, starting 1 day prior to
C. jejuni
infection, and were compared to control and
C. jejuni
-infected, EGF-treated chicks. Infected chicks shed
C. jejuni
in their feces throughout the study period.
C. jejuni
colonized the small intestine and cecum, disseminated to extraintestinal organs, and caused jejunal villus atrophy. EGF reduced jejunal colonization and dissemination of
C. jejuni
to the liver and spleen. In EGF-treated
C. jejuni
-infected chicks, villus height was not significantly different from that in untreated
C. jejuni
-infected chicks or controls. In vitro,
C. jejuni
attached to and invaded intestinal epithelial cells, disrupted tight junctional claudin-4, and increased transepithelial permeability.
C. jejuni
also promoted the translocation of noninvasive
Escherichia coli
C25. These
C. jejuni
-induced epithelial abnormalities were abolished by pretreatment with EGF, and the effect was dependent upon activation of the EGF receptor. These findings highlight EGF's ability to alter colonization of
C. jejuni
in the intestinal tract and to protect against pathogen-induced barrier defects.
AspectML
Authors: Dantas Daniel S. , Walker David , Washburn Geoffrey , Weirich Stephanie 
Published: May 2008

This article defines AspectML, a typed functional, aspect-oriented programming language. The main contribution of AspectML is the seamless integration of polymorphism, run-time type analysis and aspect-oriented programming language features. In particular, AspectML allows programmers to define type-safe polymorphic advice using pointcuts constructed from a collection of polymorphic join points. AspectML also comes equipped with a type inference algorithm that conservatively extends Hindley--Milner type inference. To support first-class polymorphic point-cut designators, a crucial feature for developing aspect-oriented profiling or logging libraries, the algorithm blends the conventional Hindley--Milner type inference algorithm with a simple form of local type inference.
We give our language operational meaning via a type-directed translation into an expressive type-safe intermediate language. Many complexities of the source language are eliminated in this translation, leading to a modular specification of its semantics. One of the novelties of the intermediate language is the definition of polymorphic labels for marking control-flow points. When a set of labels is assembled as a pointcut, the type of each label is an instance of the type of the pointcut.
Size-change termination with difference constraints
Authors: Ben-Amram Amir M. 
Published: May 2008

This article considers an algorithmic problem related to the termination analysis of programs. More specifically, we are given bounds on differences in sizes of data values before and after every transition in the program's control-flow graph. Our goal is to infer program termination via the following reasoning (“the size-change principle”): if in any infinite (hypothetic) execution of the program, some size must descend unboundedly, the program must always terminate, since infinite descent of a natural number is impossible.The problem of inferring termination from such abstract information is not the halting problem for programs and may well be decidable. If this is the case, the decision algorithm forms a “back end” of a termination verifier, and it is interesting to find out the computational complexity of the problem.A restriction of the problem described above, which only uses monotonicity information (but not difference bounds), is already known to be decidable. We prove that the unrestricted problem is undecidable, which gives a theoretical argument for studying restricted cases. We consider a case where the termination proof is allowed to make use of at most one bound per target variable in each transition. For this special case, which we claim is practically significant, we give (for the first time) an algorithm and show that the problem is in PSPACE, in fact that it is PSPACE-complete. The algorithm is based on combinatorial arguments and results from the theory of integer programming not previously used for similar problems.The algorithm has interesting connections to other work in termination, in particular to methods for generating linear ranking functions or invariants.
Data Quality Assessment and the Long-Term Trend of Ground Solar Radiation in China
Authors: Shi Guang-Yu , Hayasaka Tadahiro , Ohmura Atsumu , Chen Zhi-Hua , Wang Biao , Zhao Jian-Qi , Che Hui-Zheng , Xu Li 
Published: May 2008

Abstract
Solar radiation is one of the most important factors affecting climate and the environment. Routine measurements of irradiance are valuable for climate change research because of long time series and areal coverage. In this study, a set of quality assessment (QA) algorithms is used to test the quality of daily solar global, direct, and diffuse radiation measurements taken at 122 observatories in China during 1957–2000. The QA algorithms include a physical threshold test (QA1), a global radiation sunshine duration test (QA2), and a standard deviation test applied to time series of annually averaged solar global radiation (QA3). The results show that the percentages of global, direct, and diffuse solar radiation data that fail to pass QA1 are 3.07%, 0.01%, and 2.52%, respectively; the percentages of global solar radiation data that fail to pass the QA2 and QA3 are 0.77% and 0.49%, respectively. The method implemented by the Global Energy Balance Archive is also applied to check the data quality of solar radiation in China. Of the 84 stations with a time series longer that 20 yr, suspect data at 35 of the sites were found. Based on data that passed the QA tests, trends in ground solar radiation and the effect of the data quality assessment on the trends are analyzed. There is a decrease in ground solar global and direct radiation in China over the years under study. Although the quality assessment process has significant effects on the data from individual stations and/or time periods, it does not affect the long-term trends in the data.
An Urban Parameterization for a Global Climate Model. Part I: Formulation and Evaluation for Two Cities
Authors: Oleson K. W. , Bonan G. B. , Feddema J. , Vertenstein M. , Grimmond C. S. B. 
Published: May 2008

Abstract
Urbanization, the expansion of built-up areas, is an important yet less-studied aspect of land use/land cover change in climate science. To date, most global climate models used to evaluate effects of land use/land cover change on climate do not include an urban parameterization. Here, the authors describe the formulation and evaluation of a parameterization of urban areas that is incorporated into the Community Land Model, the land surface component of the Community Climate System Model. The model is designed to be simple enough to be compatible with structural and computational constraints of a land surface model coupled to a global climate model yet complex enough to explore physically based processes known to be important in determining urban climatology. The city representation is based upon the “urban canyon” concept, which consists of roofs, sunlit and shaded walls, and canyon floor. The canyon floor is divided into pervious (e.g., residential lawns, parks) and impervious (e.g., roads, parking lots, sidewalks) fractions. Trapping of longwave radiation by canyon surfaces and solar radiation absorption and reflection is determined by accounting for multiple reflections. Separate energy balances and surface temperatures are determined for each canyon facet. A one-dimensional heat conduction equation is solved numerically for a 10-layer column to determine conduction fluxes into and out of canyon surfaces. Model performance is evaluated against measured fluxes and temperatures from two urban sites. Results indicate the model does a reasonable job of simulating the energy balance of cities.
Inverse Parameter Estimation of the Turbulent Surface Layer from Single-Level Data and Surface Temperature
Authors: Martano P. 
Published: May 2008

Abstract
A simple inverse parameter estimation method is used in a practical diagnostic approach to obtain the surface roughness lengths and surface resistance parameters from a chi-square cost function containing measurements of wind speed and air surface temperature differences in the atmospheric surface layer. The estimated parameters allow the calculation of the turbulent fluxes of momentum and heat and the surface-layer profiles of wind speed temperature and humidity from single-level data of wind speed and variance, air temperature and humidity, surface temperature, and total heat flux (sum of sensible and latent fluxes, estimated as net radiation minus soil heat flux). The procedure, which is potentially applicable when fast response data are not available without the necessity of external parameters (with the exception of the displacement height), is tested over a field dataset in southern Italy.