bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyanionic Microbicides Modify Toll-Like Receptor-Mediated Cervicovaginal Immune Responses
Authors: Trifonova R. T. , Doncel G. F. , Fichorova R. N.
Published: January 2009

Topical microbicides are being developed as a preventative approach to reduce the sexual transmission of human immunodeficiency virus type 1 (HIV-1) and other infections. For them to be efficacious, it is believed that they should avoid inducing inflammation while allowing the vaginal epithelium to initiate protective Toll-like receptor (TLR)-mediated innate responses against pathogens. In this study, human cervical and vaginal epithelial cells were exposed to polyanionic HIV entry inhibitors and the following synthetic TLR ligands: (i) the bacterial lipoprotein Pam
3
CSK
4
, binding cell surface TLR1/TLR2; (ii) macrophage activating lipopeptide 2 (MALP-2), binding cell surface TLR2/TLR6; and (iii) the viral double-stranded RNA analog poly(I:C), recognized by intracellular TLR3. Cell activation was assessed by nuclear factor κB (NF-κB) reporter gene transactivation and cytokine production. In spite of enhancing TLR-triggered NF-κB activation, the polyanionic microbicide compounds dextran sulfate and polystyrene sulfonate significantly inhibited TLR-mediated cytokine production. They decreased cytokine mRNA and protein levels of proinflammatory (interleukin-8 [IL-8] and IL-1β) and antiviral (beta interferon) cytokines following epithelial cell stimulation with Pam
3
CSK
4
, MALP-2, or poly(I:C). These activities were associated with the sulfate/sulfonate moieties of the polyanionic compounds, since the unsulfated dextran control did not show any effects. Our data demonstrate that these microbicide compounds are capable of selectively interfering with TLR-mediated epithelial responses at different points in their signaling pathways and underscore the importance of expanding the assessment of microbicide compatibility with vaginal innate immune function. Further studies are warranted to determine the impact of this interference on HIV-1 transmission risk.
A
bla
VEB-1
Variant,
bla
VEB-6
, Associated with Repeated Elements in a Complex Genetic Structure
Authors: Zong Zhiyong , Partridge Sally R. , Iredell Jonathan R.
Published: January 2009

bla
VEB-6
was found on the
Proteus mirabilis
chromosome in a context similar to those of
bla
VEB-1a
and
bla
VEB-1b
, in a truncated gene cassette flanked by 135-bp elements and duplications of the 3′-conserved segment of class 1 integrons. A linked
aacA4-aadB-dfrA1-orfC
cassette array includes components of Tn
1331
, illustrating the complex mosaicism of multiresistance regions.
In Vitro Activity of Iclaprim against Respiratory and Bacteremic Isolates of
Streptococcus pneumoniae
Authors: Zhanel George G. , Karlowsky James A.
Published: January 2009

Iclaprim, a novel dihydrofolate reductase inhibitor, inhibited 90% of the clinical isolates (MIC
90
) of
Streptococcus pneumoniae
(
n
= 785) collected by a national surveillance program at a concentration of 1 μg/ml. The MIC
90
for iclaprim was 7 doubling dilutions lower for trimethoprim-sulfamethoxazole-susceptible isolates (
n
= 670; MIC
90
, 0.06 μg/ml) than for trimethoprim-sulfamethoxazole-resistant isolates (
n
= 115; MIC
90
, ≥8 μg/ml). The potential clinical utility of iclaprim to treat patients with pneumococcal infections may depend upon the current prevalence of resistance to trimethoprim-sulfamethoxazole in this pathogen.
Associations between Antimicrobial Resistance Phenotypes, Antimicrobial Resistance Genes, and Virulence Genes of Fecal
Escherichia coli
Isolates from Healthy Grow-Finish Pigs
Authors: Rosengren Leigh B. , Waldner Cheryl L. , Reid-Smith Richard J.
Published: January 2009

Escherichia coli
often carries linked antimicrobial resistance genes on transmissible genetic elements. Through coselection, antimicrobial use may select for unrelated but linked resistance or virulence genes. This study used unconditional statistical associations to investigate the relationships between antimicrobial resistance phenotypes and antimicrobial resistance genes in 151
E. coli
isolates from healthy pigs. Phenotypic resistance to each drug was significantly associated with phenotypic resistance to at least one other drug, and every association found that the probability of observing the outcome resistance was increased by the presence of the predictor resistance. With one exception, each statistical association that was identified between a pair of resistance genes had a corresponding significant association identified between the phenotypes mediated by those genes. This suggests that associations between resistance phenotypes might predict coselection. If this hypothesis is confirmed, evaluation of the associations between resistance phenotypes could improve our knowledge of coselection dynamics and provide a cost-effective way to evaluate existing data until large-scale genotypic data collection becomes feasible. This could enable policy makers and users of antimicrobials to consider coselection in antimicrobial use decisions. This study also considered the unconditional relationships between resistance and virulence genes in
E. coli
from healthy pigs (
aidA-1
,
eae
,
elt
,
estA
,
estB
,
fedA1
,
stx1
, and
stx2
). Positive statistical associations would suggest that antimicrobial use may select for virulence in bacteria that may contaminate food or cause diarrhea in pigs. Fortunately, the odds of detecting a virulence gene were rarely increased by the presence of an antimicrobial resistance gene. This suggests that on-farm antimicrobial use did not select for the examined virulence factors in
E. coli
carried by this population of healthy pigs.
Biogeographic Patterns in Genomic Diversity among a Large Collection ofVibrio choleraeIsolates
Authors: Keymer Daniel P. , Lam Lilian H. , Boehm Alexandria B.
Published: January 2009

Vibrio choleraestrains are capable of inhabiting multiple niches in the aquatic environment and in some cases cause disease in humans. However, the ecology and biodiversity of these bacteria in environmental settings remains poorly understood. We used the genomic fingerprinting technique enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) to profile 835 environmental isolates from waters and sediments obtained at nine sites along the central California coast. We identified 115 ERIC-PCR genotypes from 998 fingerprints, with a reproducibility of 98.5% and a discriminatory power of 0.971. When the temporal dynamics at a subset of sampling sites were explored, several genotypes provided evidence for cosmopolitan or geographically restricted distributions, and other genotypes displayed nonrandom patterns of cooccurrence. Partial Mantel tests confirmed that genotypic similarity of isolates across all sampling events was correlated with environmental similarity (0.04 ≤r≤ 0.05), temporal proximity (r= 0.09), and geographic distance (r= 0.09). A neutral community model for all sampling events explained 61% of the variation in genotype abundance. Cooccurrence indices (C-score, C-board, and Combo) were significantly different than expected by chance, suggesting that theV. choleraepopulation may have a competitive structure, especially at the regional scale. Even though stochastic processes are undoubtedly important in generating biogeographic patterns in diversity, deterministic factors appear to play a significant, albeit small, role in shaping theV. choleraepopulation structure in this system.
Sulfolobus tokodaiiST0053 Produces a Novel Thermostable, NAD-Dependent Medium-Chain Alcohol Dehydrogenase
Authors: Yanai Hisaaki , Doi Katsumi , Ohshima Toshihisa
Published: January 2009

An alcohol dehydrogenase (ADH) gene, ST0053, fromSulfolobus tokodaiiwas expressed inEscherichia coli. The purified recombinant enzyme was an NAD-dependent medium-chain ADH with high thermostability and tolerance of a wide range of pHs. This is the first step in creating an experimental functionality library of 10 genes annotated as ADHs in theS. tokodaiigenome.
Evaluation of Genotypic and Phenotypic Methods To Distinguish Clinical from Environmental
Vibrio vulnificus
Strains
Authors: Sanjuán Eva , Fouz Belén , Oliver James D. , Amaro Carmen
Published: January 2009

Vibrio vulnificus
is a heterogeneous bacterial species that comprises virulent and avirulent strains from environmental and clinical sources that have been grouped into three biotypes. To validate the typing methods proposed to distinguish clinical from environmental isolates, we performed phenotypic (API 20E, API 20NE, and BIOLOG tests) and genetic (ribotyping and DNA polymorphism at several loci) studies with a large strain collection representing different biotypes, origins, and host ranges. No phenotypic method was useful for biotyping or grouping strains with regard to the origin of an isolate, and only the BIOLOG system was reliable for identifying the strains at the species level. DNA polymorphisms divided the population into three major profiles. Profile 1 strains were
vcg
type C, 16S rRNA type B, and
vvh
type 1 and included most of the biotype 1 human septicemic isolates; profile 2 strains were
vcg
type E, 16S rRNA type A, and
vvh
type 2 and included all biotype 2 isolates together with biotype 1 isolates from fish and water and some human isolates; and profile 3 strains were
vcg
type E, 16S rRNA type AB, and
vvh
type 2 and included biotype 3 strains. Ribotyping divided the species into two groups: one group that included profile 1 biotype 1 isolates and one group that included isolates of all three biotypes with the three profiles described above. In conclusion, no genotyping system was able to distinguish either clinical strains from environmental strains or biogroups within the species
V. vulnificus
, which suggests that new typing methodologies useful for public health have to be developed for this species.
Longitudinal Study ofSalmonellaDispersion and the Role of Environmental Contamination in Commercial Swine Production Systems
Authors: Dorr Paul M. , Tadesse Daniel A. , Zewde Bayleyegn Molla , Fry Pamela , Thakur Siddhartha , Gebreyes Wondwossen A.
Published: January 2009

This study investigated the roles of various environmental sources, such as truck-washing systems, waste-processing lagoons, and other sources, as potential contributors to the exposure and dissemination ofSalmonellain commercial swine production systems. Four cohorts of nursery age swine herds which originated from distinct farm flows were selected. In addition, cross-sectional sampling of four truck wash stations selected based on the types of disinfectants and sources of water used for sanitizing trucks were tested.Salmonellaisolates were recovered from pigs (feces, cecal contents, and mesenteric lymph nodes) and environmental sources (barn floor, lagoon, barn flush, trucks, and holding pens). Antimicrobial susceptibility testing and genotyping were conducted using Kirby-Bauer disk diffusion and amplified fragment length polymorphism, respectively.Salmonellaprevalence significantly increased with age from late nursery to slaughter for all of the cohorts (P= 0.007). In two of three instances, all three pig holding pens (lairage) sampled at processing wereSalmonellapositive. The predominant antibiotypes for all sources included ACSSuT (51.8%), SSuT (16.8%), T (6%), and pansusceptible (7.4%). For the isolates obtained at the farms, the ACSSuT phenotype was 5.6 times more likely to be found in the animals than in the environment (95% confidence interval, 4.4 to 7.2 times). Serogroup B was the most common serogroup (79%), followed by serogroup E (10.4%). Despite the fact that the four production flows were independent, 1 of the 11 genotypic clusters (cluster A1) was commonly detected in any type of sample regardless of its origin. Five of the genotypic clusters (clusters A3, A4, A5, A6, and A7) contained isolates that originated from trucks and lairage swabs and also from cecal contents and/or mesenteric lymph nodes. More interestingly, genotypic clusters A3, A4, and A6 (but not clusters A5 and A7) were not detected on the farms. They originated from the trucks and lairage swabs and then were identified from the cecal contents and/or mesenteric lymph nodes. These findings underscore the significance of various environmental factors, including inadequate truck-washing systems, and emphasize the role of lairage contamination bySalmonellathat has food safety significance.
Development of a Test System To Apply Virus-Containing Particles to Filtering Facepiece Respirators for the Evaluation of Decontamination Procedures
Authors: Fisher Edward , Rengasamy Samy , Viscusi Dennis , Vo Evanly , Shaffer Ronald
Published: January 2009

A chamber to apply aerosolized virus-containing particles to air-permeable substrates (coupons) was constructed and validated as part of a method to assess the virucidal efficacy of decontamination procedures for filtering facepiece respirators. Coliphage MS2 was used as a surrogate for pathogenic viruses for confirmation of the efficacy of the bioaerosol respirator test system. The distribution of virus applied onto and within the coupons was characterized, and the repeatability of applying a targeted virus load was examined. The average viable virus loaded onto 90 coupons over the course of 5 days was found to be 5.09 ± 0.19 log
10
PFU/coupon (relative standard deviation, 4%). To determine the ability to differentiate the effectiveness of disinfecting procedures with different levels of performance, sodium hypochlorite and steam treatments were tested in experiments by varying the dose and time, respectively. The role of protective factors was assessed by aerosolizing the virus with various concentrations of the aerosol-generating medium. A sodium hypochlorite (bleach) concentration of 0.6% and steam treatments of 45 s and longer resulted in log reductions (>4 logs) which reached the detection limits for both levels of protective factors. Organic matter (ATCC medium 271) as a protective factor afforded some protection to the virus in the sodium hypochlorite experiments but was not a factor in the steam experiments. The evaluation of the bioaerosol respirator test system demonstrated a repeatable method for applying a targeted viral load onto respirator coupons and provided insight into the properties of aerosols that are of importance to the development of disinfection assays for air-permeable materials.
Transcriptional Regulation and Signal-Peptide-Dependent Secretion of Exolevanase (LsdB) in the Endophyte
Gluconacetobacter diazotrophicus
Authors: Menéndez Carmen , Banguela Alexander , Caballero-Mellado Jesús , Hernández Lázaro
Published: January 2009

Gluconacetobacter diazotrophicus
utilizes plant sucrose with a constitutively expressed levansucrase (LsdA), producing extracellular levan, which may be degraded under energetically unfavored conditions. Reverse transcriptase-PCR analysis revealed that
lsdA
and the downstream exolevanase gene (
lsdB
) form an operon.
lsdB
transcription was induced during growth with low fructose concentrations (0.44 to 33 mM) and repressed by glucose. Transport of LsdB to the periplasm involved N-terminal signal peptide cleavage. Type II secretion mutants failed to transfer LsdB across the outer membrane, impeding levan hydrolysis.
Molecular Subtyping and Distribution of the Serine Protease from Shiga Toxin-Producing
Escherichia coli
among Atypical Enteropathogenic
E. coli
Strains
Authors: Cookson Adrian L. , Bennett Jenny , Nicol Carolyn , Thomson-Carter Fiona , Attwood Graeme T.
Published: January 2009

Atypical enteropathogenic
Escherichia coli
(aEPEC) and Shiga toxin-producing
E. coli
(STEC) were examined to determine the prevalence and sequence of
espP
, which encodes a serine protease. These analyses indicated shared
espP
sequence types between the two
E. coli
pathotypes and thus provide further insights into the evolution of aEPEC and STEC.
Image Analysis Software Based on Color Segmentation for Characterization of Viability and Physiological Activity of Biofilms
Authors: Chávez de Paz Luis E.
Published: January 2009

The novel image analysis software package
bio
Image_L was tested to calculate biofilm structural parameters in oral biofilms stained with dual-channel fluorescent markers. By identifying color tonalities in situ, the software independently processed the color subpopulations and characterized the viability and metabolic activity of biofilms.
Reengineering of a
Corynebacterium glutamicum
l
-Arginine and
l
-Citrulline Producer
Authors: Ikeda Masato , Mitsuhashi Satoshi , Tanaka Kenji , Hayashi Mikiro
Published: January 2009

Toward the creation of a robust and efficient producer of
l
-arginine and
l
-citrulline (arginine/citrulline), we have performed reengineering of a
Corynebacterium glutamicum
strain by using genetic information of three classical producers. Sequence analysis of their
arg
operons identified three point mutations (
argR123, argG92
up
, and
argG45
) in one producer and one point mutation (
argB26
or
argB31
) in each of the other two producers. Reconstitution of the former three mutations or of each
argB
mutation on a wild-type genome led to no production. Combined introduction of
argB26
or
argB31
with
argR123
into a wild type gave rise to arginine/citrulline production. When
argR123
was replaced by an
argR
-deleted mutation (Δ
argR
), the production was further increased. The best mutation set, Δ
argR
and
argB26
, was used to screen for the highest productivity in the backgrounds of different wild-type strains of
C. glutamicum
. This yielded a robust producer, RB, but the production was still one-third of that of the best classical producer. Transcriptome analysis revealed that the
arg
operon of the classical producer was much more highly upregulated than that of strain RB. Introduction of
leuC456
, a mutation derived from a classical
l
-lysine producer and provoking global induction of the amino acid biosynthesis genes, including the
arg
operon, into strain RB led to increased production but incurred retarded fermentation. On the other hand, replacement of the chromosomal
argB
by heterologous
Escherichia coli argB
, natively insensitive to arginine, caused a threefold-increased production without retardation, revealing that the limitation in strain RB was the activity of the
argB
product. To overcome this, in addition to
argB26
, the
argB31
mutation was introduced into strain RB, which caused higher deregulation of the enzyme and resulted in dramatically increased production, like the strain with
E. coli argB
. This reconstructed strain displayed an enhanced performance, thus allowing significantly higher productivity of arginine/citrulline even at the suboptimal 38°C.
Roseophage RDJLΦ1, Infecting the Aerobic Anoxygenic Phototrophic BacteriumRoseobacter denitrificansOCh114
Authors: Zhang Yongyu , Jiao Nianzhi
Published: January 2009

A marine roseophage RDJLΦ1 lytically infectingRoseobacter denitrificansOCh114 was isolated and characterized. RDJLΦ1 can package several host cellular proteins into its virions, and its DNA is refractory to several commonly used restriction enzymes. This paper presents the first report of a bacteriophage isolated from the aerobic anoxygenic phototrophic bacteria.
Microbial Conversion of Glycerol to 1,3-Propanediol by an Engineered Strain of
Escherichia coli
Authors: Tang Xueming , Tan Yongsong , Zhu Hong , Zhao Kai , Shen Wei
Published: January 2009

In an effort to improve industrial production of 1,3-propanediol (1,3-PD), we engineered a novel polycistronic operon under the control of the temperature-sensitive lambda phage P
L
P
R
promoter regulated by the
c
I
ts
857 repressor and expressed it in
Escherichia coli
K-12 ER2925. The genes for the production of 1,3-PD in
Clostridium butyricum
,
dhaB1
and
dhaB2
, which encode the vitamin B
12
-independent glycerol dehydratase DhaB1 and its activating factor, DhaB2, respectively, were tandemly arrayed with the
E. coli yqhD
gene, which encodes the 1,3-propanediol oxidoreductase isoenzyme YqhD, an NADP-dependent dehydrogenase that can directly convert glycerol to 1,3-PD. The microbial conversion of 1,3-PD from glycerol by this recombinant
E. coli
strain was studied in a two-stage fermentation process. During the first stage, a novel high-cell-density fermentation step, there was significant cell growth and the majority of the metabolites produced were organic acids, mainly acetate. During the second stage, glycerol from the fresh medium was rapidly converted to 1,3-PD following a temperature shift from 30°C to 42°C. The by-products were mainly pyruvate and acetate. During this two-stage process, the overall 1,3-PD yield and productivity reached 104.4 g/liter and 2.61 g/liter/h, respectively, and the conversion rate of glycerol to 1,3-PD reached 90.2% (g/g). To our knowledge, this is the highest reported yield and productivity efficiency of 1,3-PD with glycerol as the sole source of carbon. Furthermore, the overall fermentation time was only 40 h, shorter than that of any other reports.
Host-Pathogen Interactions ofActinobacillus pleuropneumoniaewith Porcine Lung and Tracheal Epithelial Cells
Authors: Auger Eliane , Deslandes Vincent , Ramjeet Mahendrasingh , Contreras Irazù , Nash John H. E. , Harel Josée , Gottschalk Marcelo , Olivier Martin , Jacques Mario
Published: January 2009

Host-pathogen interactions are of great importance in understanding the pathogenesis of infectious microorganisms. We developed in vitro models to study the host-pathogen interactions of porcine respiratory tract pathogens using two immortalized epithelial cell lines, namely, the newborn pig trachea (NPTr) and St. Jude porcine lung (SJPL) cell lines. We first studied the interactions ofActinobacillus pleuropneumoniae, an important swine pathogen, using these models. Under conditions where cytotoxicity was absent or low, we showed thatA. pleuropneumoniaeadheres to both cell lines, stimulating the induction of NF-κB. The NPTr cells consequently secrete interleukin 8, while the SJPL cells do not, since they are deprived of the NF-κB p65 subunit. Cell death ultimately occurs by necrosis, not apoptosis. The transcriptomic profile ofA. pleuropneumoniaewas determined after contact with the porcine lung epithelial cells by using DNA microarrays. Genes such astadBandrcpA, members of a putative adhesin locus, and a gene whose product has high homology to the Hsf autotransporter adhesin ofHaemophilus influenzaewere upregulated, as were the genespgaBC, involved in biofilm biosynthesis, while capsular polysaccharide-associated genes were downregulated. The in vitro models also proved to be efficient with other swine pathogens, such asActinobacillus suis,Haemophilus parasuis, andPasteurella multocida. Our results demonstrate that interactions ofA. pleuropneumoniaewith host epithelial cells seem to involve complex cross talk which results in regulation of various bacterial genes, including some coding for putative adhesins. Furthermore, our data demonstrate the potential of these in vitro models in studying the host-pathogen interactions of other porcine respiratory tract pathogens.
Transmission ofToxoplasma gondiifrom Infected Dendritic Cells to Natural Killer Cells
Authors: Persson Catrine M. , Lambert Henrik , Vutova Polya P. , Dellacasa-Lindberg Isabel , Nederby Joanna , Yagita Hideo , Ljunggren Hans-Gustaf , Grandien Alf , Barragan Antonio , Chambers Benedict J.
Published: January 2009

The obligate intracellular parasiteToxoplasma gondiican actively infect any nucleated cell type, including cells from the immune system. In the present study, we observed that a large number of natural killer (NK) cells were infected byT. gondiiearly after intraperitoneal inoculation of parasites into C57BL/6 mice. Interestingly, one mechanism of NK cell infection involved NK cell-mediated targeting of infected dendritic cells (DC). Perforin-dependent killing of infected DC led to active egress of infectious parasites that rapidly infected adjacent effector NK cells. Infected NK cells were not efficiently targeted by other NK cells. These results suggest that rapid transfer ofT. gondiifrom infected DC to effector NK cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection.
Critical Role of NOD2 in Regulating the Immune Response to
Staphylococcus aureus
Authors: Deshmukh Hitesh S. , Hamburger James B. , Ahn Sun Hee , McCafferty Dewey G. , Yang Suxiao R. , Fowler Vance G.
Published: January 2009

NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role in the host response to
Staphylococcus aureus
infection is unknown. NOD2-deficient (
Nod2

−/−

) mice and wild-type (WT) littermate controls were injected intraperitoneally with
S. aureus
suspension (10
7
bacteria/g of body weight), and their survival was monitored. Cultured bone marrow-derived neutrophils were harvested from
Nod2

−/−

and WT mice and tested for cytokine production and phagocytosis. Compared to WT mice,
Nod2

−/−

mice were significantly more susceptible to
S. aureus
infection (median survival of 1.5 days versus >5 days;
P
= 0.003) and had a significantly higher bacterial tissue burden. Cultured bone marrow-derived neutrophils from
Nod2

−/−

and WT mice had similar levels of peritoneal neutrophil recruitment and intracellular killing, but bone marrow-derived neutrophils from
Nod2

−/−

mice had significantly reduced ability to internalize fluorescein-labeled
S. aureus. Nod2

−/−

mice had significantly higher levels of Th1-derived cytokines in serum (tumor necrosis factor alpha, gamma interferon, and interleukin-2 [IL-2]) compared to WT mice, whereas the levels of Th2-derived cytokines (IL-1β, IL-4, IL-6, and IL-10) were similar in
Nod2

−/−

and WT mice. Thus, mice deficient in NOD2 are more susceptible to
S. aureus
. Increased susceptibility is due in part to defective neutrophil phagocytosis, elevated serum levels of Th1 cytokines, and a higher bacterial tissue burden.
LiveBorrelia burgdorferiSpirochetes Elicit Inflammatory Mediators from Human Monocytes via the Toll-Like Receptor Signaling Pathway
Authors: Dennis Vida A. , Dixit Saurabh , O'Brien Shannon M. , Alvarez Xavier , Pahar Bapi , Philipp Mario T.
Published: January 2009

We investigated the mechanisms that lead to the production of proinflammatory mediators by human monocytes when these cells are exposed in vitro to liveBorrelia burgdorferispirochetes. We first focused on myeloid differentiation primary response protein 88 (MyD88), an adapter molecule that is essential in the Toll-like receptor (TLR) pathway. Real-time PCR, flow cytometry, and confocal microscopy experiments revealed that MyD88 was maximally expressed in THP-1 cells after 24-h stimulation of these cells with liveB. burgdorferi. Silencing of theMYD88gene by using small interfering RNA resulted in 24%, 35%, and 84% down-modulation of the production of tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), and IL-6, respectively, in THP-1 cells stimulated with liveB. burgdorferi. Specific silencing of theTLR1,TLR2, orTLR5gene by RNA interference further revealed that silencing of theTLR1andTLR2genes alone or combined, but not theTLR5gene, caused a downregulation of IL-6, IL-8, and TNF-α in liveB. burgdorferi-stimulated THP-1 cells. Overall, similar results were obtained for THP-1 cells stimulated with purified lipoproteins. Our results indicate that the TLR pathway mediates, at least in part, the release of inflammatory mediators in human monocytes stimulated with liveB. burgdorferispirochetes and furthermore suggest that the TLR-dependent interaction between these cells and live spirochetes is mediated by spirochetal lipoproteins but not by flagellin.
Immunoglobulin G Subclass-Specific Responses against
Plasmodium falciparum
Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness
Authors: Stanisic Danielle I. , Richards Jack S. , McCallum Fiona J. , Michon Pascal , King Christopher L. , Schoepflin Sonja , Gilson Paul R. , Murphy Vincent J. , Anders Robin F. , Mueller Ivo , Beeson James G.
Published: January 2009

Substantial evidence indicates that antibodies to
Plasmodium falciparum
merozoite antigens play a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Different malaria antigens induce distinct immunoglobulin G (IgG) subclass responses, but the importance of different responses in protective immunity from malaria is not known and the factors determining subclass responses in vivo are poorly understood. We examined IgG and IgG subclass responses to the merozoite antigens MSP1-19 (the 19-kDa C-terminal region of merozoite surface protein 1), MSP2 (merozoite surface protein 2), and AMA-1 (apical membrane antigen 1), including different polymorphic variants of these antigens, in a longitudinal cohort of children in Papua New Guinea. IgG1 and IgG3 were the predominant subclasses of antibodies to each antigen, and all antibody responses increased in association with age and exposure without evidence of increasing polarization toward one subclass. The profiles of IgG subclasses differed somewhat for different alleles of MSP2 but not for different variants of AMA-1. Individuals did not appear to have a propensity to make a specific subclass response irrespective of the antigen. Instead, data suggest that subclass responses to each antigen are generated independently among individuals and that antigen properties, rather than host factors, are the major determinants of IgG subclass responses. High levels of AMA-1-specific IgG3 and MSP1-19-specific IgG1 were strongly predictive of a reduced risk of symptomatic malaria and high-density
P. falciparum
infections. However, no antibody response was significantly associated with protection from parasitization per se. Our findings have major implications for understanding human immunity and for malaria vaccine development and evaluation.
Identification of a Pneumococcal Glycosidase That Modifies O-Linked Glycans
Authors: Marion Carolyn , Limoli Dominique H. , Bobulsky Gregory S. , Abraham Jessica L. , Burnaugh Amanda M. , King Samantha J.
Published: January 2009

Colonization of the airway byStreptococcus pneumoniaeis typically asymptomatic; however, progression of bacteria beyond the oronasopharynx can cause diseases including otitis media and pneumonia. The mechanisms by whichS. pneumoniaeestablishes and maintains colonization remain poorly understood. Both N-linked and O-linked glycans are abundant in the airway. Our previous research demonstrated thatS. pneumoniaecan sequentially deglycosylate N-linked glycans and suggested that this modification of sugar structures may aid in colonization. There is published evidence thatS. pneumoniaeexpresses a secreted O-glycosidase that cleaves galactose β1-3N-acetylgalactosamine (Galβ1-3GalNAc) from core-1 O-linked glycans; however, the biological function of this enzyme has not previously been determined. We established that the activity is not secreted but is instead surface associated in a sortase-dependent manner. Genome analysis revealed an open reading frame predicted to encode a sortase-dependent surface protein with sequence similarity to the O-glycosidase ofBifidobacterium longum. Deletion of this pneumococcal open reading frame confirmed that this gene encodes an O-glycosidase. Experiments using a model glycoconjugate demonstrated that this O-glycosidase, together with the neuraminidase NanA, is required forS. pneumoniaeto cleave sialylated core-1 O-linked glycans. The ability of the O-glycosidase mutant to cleave this glycan structure was restored by both genetic complementation and the addition of O-glycosidase. The mutant showed a reduction in adherence to human airway epithelial cells and a significantly decreased ability to colonize the upper respiratory tract, suggesting that cleavage of core-1 O-linked glycans enhances the ability ofS. pneumoniaeto colonize the human airway.
Pore-Forming Activity of Alpha-Toxin Is Essential for
Clostridium septicum
-Mediated Myonecrosis
Authors: Kennedy Catherine L. , Lyras Dena , Cordner Leanne M. , Melton-Witt Jody , Emmins John J. , Tweten Rodney K. , Rood Julian I.
Published: January 2009

Clostridium septicum
alpha-toxin is a β-barrel pore-forming cytolysin that is functionally similar to aerolysin. Residues important in receptor binding, oligomerization, and pore formation have been identified; however, little is known about the activity of the toxin in an infection, although it is essential for disease. We have now shown that deletion of a small portion of the transmembrane domain, so that the toxin is no longer able to form pores, completely abrogates its ability to contribute to disease, as does replacement of the sole cysteine residue with leucine. However, although previous biochemical and cytotoxicity assays clearly indicated that mutations in residues important in oligomerization, binding, and prepore conversion greatly reduced activity or rendered the toxin inactive, once the mutated toxins were overexpressed by the natural host in the context of an infection it was found they were able to cause disease in a mouse model of myonecrosis. These results highlight the importance of testing the activity of virulence determinants in the normal host background and in an infectious disease context and provide unequivocal evidence that it is the ability of alpha-toxin to form a pore that confers its toxicity in vivo.
Temporal sequence of greyscale ultrasound changes and their relationship with neovascularity and pain in the patellar tendon
Authors: Malliaras P , Purdam C , Maffulli N , Cook J
Published: January 2009

Objective

Ultrasound (US) imaging has revealed distinct types of greyscale abnormalities in the patellar and Achilles tendons, including diffusely thickened tendons and tendons containing a hypoechoic region. The relationship between these greyscale abnormalities and their clinical relevance is unknown. This study investigated the temporal sequence in greyscale abnormalities as well as the relationship between greyscale abnormalities, Doppler flow and pain.

Methods

Patellar tendon pain (single leg decline squat test) and ultrasound imaging (greyscale (normal, diffuse thickening, hypoechoic), presence of Doppler flow) were assessed bilaterally among 58 volleyball players at monthly intervals during a 5-month season. The probability of transition between the greyscale ultrasound groups was calculated for each month and totalled over the season (prospective) and the relationship between these groups and the presence and intensity of pain and the presence of Doppler flow were investigated (cross-sectional investigation).

Results

Tendons with normal US were more likely to transition to diffuse thickening than to a hypoechoic region. Tendons containing a hypoechoic region were more likely to transition to diffuse thickening rather than to a normal US appearance. Hypoechoic regions were more likely to be painful (59%) and contain Doppler flow (42%) than tendons with diffuse thickening (pain in 43% and Doppler flow in 6%).

Conclusions

The transitions identified between normal, diffusely thickened tendons and those containing a hypoechoic region suggests that these greyscale US changes may represent different phases of tendon pathology. Tendons containing a hypoechoic region are more likely to be painful and contain Doppler flow than diffusely thickened tendons.
Exercise during pregnancy and risk of maternal anaemia: a randomised controlled trial
Authors: Barakat R , Ruiz J R , Lucia A
Published: January 2009

The purpose of this randomised controlled trial was to examine the effect of regular exercise (three times/week) performed during the second and third trimester of pregnancy on the risk of prepartum maternal anaemia (haemoglobin <11 g/dl). 160 sedentary healthy women were randomly assigned either to a training or a control group (n  =  80 each). Haematological variables were recorded at baseline (first trimester) and the beginning of the second and third trimesters. The frequency of participants with maternal anaemia was similar in the two groups over gestation (and consistently <10%). The course of haematological adaptations was normal and similar in both groups, reflecting a steady fall in haemoglobin concentration over the second trimester due to haemodilution and a rise later in gestation due to haemoconcentration. In summary, regular exercise during the second half of pregnancy does not increase the risk of maternal anaemia nor does it alter haematological variables.
Anaplastic nephroblastomas express transketolase-like enzyme 1
Authors: Wu H-T , Allie N , Myer L , Govender D
Published: January 2009

Aim:

Transketolase-like enzyme 1 (TKTL1) is a glycolytic enzyme that has been found to be upregulated in several tumours, and it is associated with tumour progression. Nephroblastoma is the commonest paediatric renal malignancy and has a good prognosis except for those with anaplasia. To the best of the authors’ knowledge, the expression of TKTL1 in nephroblastomas has not been studied before and the aim of this study was to compare the immunoexpression of TKTL1 in anaplastic and non-anaplastic nephroblastomas.

Methods:

Twenty-eight patients who had nephrectomies for nephroblastomas were studied. Archival formalin-fixed paraffin-wax-embedded tissue sections were stained with monoclonal TKTL1 antibody.

Results:

Six of the 15 anaplastic nephroblastomas showed staining in 80–100% of the tumour (p = 0.36). None of the 13 non-anaplastic nephroblastomas showed TKTL1 staining in >80% of the tumour.

Conclusion:

TKTL1 expression is associated with the presence of anaplasia and may be a mechanism via which anaplastic tumour cells thrive under different conditions. Glycolytic inhibitors may play a role in anaplastic nephroblastomas.
Climate change and ecosystem response in the northern Columbia River basin — A paleoenvironmental perspective
Authors: Walker Ian R. , Pellatt Marlow G.
Published: January 2009

A comprehensive review of Holocene paleoenvironmental data has been prepared, providing the basis for evaluating natural variability in climate and ecosystem dynamics in the northern Columbia River basin. The paleoenvironmental record reveals four major climatic shifts and a number of less well-defined climatic changes throughout the Holocene. The major climate changes are (1) a cool or cold, late-glacial climate at the end of the last glaciation (>11 500 cal. year BP), (2) an interval of drought and maximum summer warmth during the early Holocene (ca. 10500 to 8000 cal. year BP), (3) a mid-Holocene trend towards a cooler, more moist climate (ca. 8000 to ca. 4000 cal. year BP), and (4) a relatively stable climate persisting from ca. 4000 cal. year BP until the arrival of European settlers. Air temperatures have warmed by about 1 °C over the past century. Minor climate events that are emerging as global in nature include Little Ice Age (1200–150 BP) conditions, and a late Holocene cool wet period (3500–2500 BP). These are observed in some study sites examined in this paper and may be related to large-scale cycles of 2800–2000 and 1500 years. A discussion of changing atmospheric circulation patterns, and the causes of long-term climatic change are included, together with a discussion of the implications of the paleoenvironmental record for understanding future climate, and the likely response of communities and ecosystems.
Brown Norway rats show impaired nNOS-mediated information transfer in renal autoregulationThis article is part of a Special Issue on Information Transfer in the Microcirculation.
Authors: Wang Xuemei , Cupples William A.
Published: January 2009

Nonselective inhibition of NO synthase (NOS) augments myogenic autoregulation of renal blood flow (RBF) and profoundly reduces RBF. Previously in Wistar rats, we showed that augmented autoregulation, but not vasoconstriction, is duplicated by intrarenal inhibition of neuronal NOS (nNOS), whereas intrarenal inhibition of inducible NOS (iNOS) has no effect on RBF or on RBF dynamics. Thus macula densa nNOS transfers information from tubuloglomerular feedback to the afferent arteriole. This information flow requires that macula densa nNOS can sufficiently alter ambient NO concentration, that is, that endothelial NOS (eNOS) and iNOS do not alter local NO concentration. Because the Brown Norway rat often shows exaggerated responses to NOS inhibition and has peculiarities of renal autoregulation that are related to NO, we used this strain to study systemic and renal vascular responses to NOS inhibition. The first experiment showed transient blood pressure reduction by bolus i.v. acetylcholine that was dose-dependent in both strains and substantially prolonged in Brown Norway rats. The depressor response decayed more rapidly after nonselective NOS inhibition and the difference between strains was lost, indicating a greater activity of eNOS in Brown Norway rats. In Brown Norway rats, selective inhibition of iNOS reduced RBF (–16% ± 7%) and augmented myogenic autoregulation, whereas nNOS inhibition reduced RBF (–25% ± 4%) and did not augment myogenic autoregulation. The significant responses to intrarenal iNOS inhibition, the reduced modulation of autoregulation by nNOS inhibition, and the enhanced endothelial depressor response suggest that physiological signalling by NO within the kidney is impaired in Brown Norway rats because of irrelevant or inappropriate input of NO by eNOS and iNOS.
ELIMINATION OF IR/UV VIA GRAVITY IN NONCOMMUTATIVE FIELD THEORY
Authors: KERSTING N. , YAN J.
Published: January 2009

Models of particle physics with Noncommutative Geometry (NCG) generally suffer from a manifestly non-Wilsonian coupling of infrared and ultraviolet degrees of freedom known as the "IR/UV Problem" which would tend to compromise their phenomenological relevance. In this letter we explicitly show how one may remedy this by coupling NCG to gravity. In the simplest scenario, the Lagrangian gets multiplied by a nonconstant background metric; in ϕ-4 theory the theorem that ∫ d4x ϕ⋆ϕ=∫ d4x ϕ2 is no longer true and the field propagator gets modified by a factor which depends on both NCG and the variation of the metric. A suitable limit of this factor as the propagating momentum gets asymptotically large then eradicates the IR/UV problem. With gravity and NCG coupled to each other, one might expect antisymmetric components to arise in the metric. Cosmological implications of such are subsequently discussed.
PLANCK SCALE COSMOLOGY IN RESUMMED QUANTUM GRAVITY
Authors: WARD B. F. L.
Published: January 2009

We show that, by using resummation techniques based on the extension of the methods of Yennie, Frautschi and Suura to Feynman's formulation of Einstein's theory, we get quantum field theoretic predictions for the UV fixed-point values of the dimensionless gravitational and cosmological constants. Connections to the phenomenological asymptotic safety analysis of Planck scale cosmology by Bonanno and Reuter are discussed.
NONCOMMUTATIVE CONFORMAL FIELD THEORY IN THE TWIST-DEFORMED CONTEXT
Authors: LIZZI FEDELE , VITALE PATRIZIA
Published: January 2009

We discuss conformal symmetry on the two-dimensional noncommutative plane equipped with Moyal product in the twist deformed context. We show that the consistent use of the twist procedure leads to results which are free from ambiguities. This lends support to the importance of the use of twist symmetries in noncommutative geometry.
R-PARITY VIOLATING U(1)′-EXTENDED SUPERSYMMETRIC STANDARD MODEL
Authors: LEE HYE-SUNG
Published: January 2009

Supersymmetry is one of the best motivated new physics scenarios. To build a realistic supersymmetric standard model, however, a companion symmetry is necessary to address various issues. While R-parity is a popular candidate that can address the proton and dark matter issues simultaneously, it is not the only option for such a property. We review how a TeV scale U(1)′ gauge symmetry can replace the R-parity. Discrete symmetries of the U(1)′ can make the model still viable and attractive with distinguishable phenomenology. For instance, with a residual discrete symmetry of the U(1)′, Z6 = B3 × U2, the proton can be protected by the baryon triality (B3) and a hidden sector dark matter candidate can be protected by the U-parity (U2).
SIMPLE TWO HIGGS DOUBLET MODEL
Authors: JORA RENATA , MOUSSA SHERIF , NASRI SALAH , SCHECHTER JOSEPH , SHAHID M. NAEEM
Published: January 2009

We study a simple two-Higgs doublet model which reflects, in a phenomenological way, the idea of compositeness for the Higgs sector. It is relatively predictive. In one scenario, it allows for a "hidden" usual Higgs particle in the 100 GeV region and a possible dark matter candidate.
THE PRODUCTION OF THE NEUTRAL AND CHARGED TOP PIONS ASSOCIATED WITH THE W BOSON AT THE ILC
Authors: LIU YAO-BEI , WANG SHUAI-WEI
Published: January 2009

The top pions [Formula: see text] are the typical particles predicted by the top-color-assisted technicolor (TC2) model, and the observation of these particles can be regarded as the direct evidence of the TC2 model. In this paper, we study the charged and neutral top pion production process [Formula: see text]. The results show that the production rates can reach the level of tens of fb with reasonable parameter values. So one can expect that enough signals could be produced in the International Linear Collider (ILC) experiments. Furthermore, the flavor-changing (FC) decay mode [Formula: see text] is the best channel for detecting the neutral top pion, due to the clean SM background. With a large number of events and the clean background, the neutral top pion should be observable in future ILC experiments.
SURFACES OBTAINED FROM ℂPN-1 SIGMA MODELS
Authors: GRUNDLAND A. M. , YURDUŞEN İ.
Published: January 2009

In this paper, the Weierstrass technique for harmonic maps S2 → ℂPN-1 is employed in order to obtain surfaces immersed in multidimensional Euclidean spaces. It is shown that if the ℂPN-1 model equations are defined on the sphere S2 and the associated action functional of this model is finite, then the generalized Weierstrass formula for immersion describes conformally parametrized surfaces in the su (N) algebra. In particular, for any holomorphic or antiholomorphic solution of this model the associated surface can be expressed in terms of an orthogonal projector of rank (N - 1). The implementation of this method is presented for two-dimensional conformally parametrized surfaces immersed in the su (3) algebra. The usefulness of the proposed approach is illustrated with examples, including the dilation-invariant meron-type solutions and the Veronese solutions for the ℂP2 model. Depending on the location of the critical points (zeros and poles) of the first fundamental form associated with the meron solution, it is shown that the associated surfaces are semiinfinite cylinders. It is also demonstrated that surfaces related to holomorphic and mixed Veronese solutions are immersed in ℝ8 and ℝ3, respectively.
STATE EQUATION FOR THE THREE-DIMENSIONAL SYSTEM OF "COLLAPSING" HARD SPHERES
Authors: KLEBANOV I. , GINCHITSKII N. , GRITSAY P.
Published: January 2009

By the Wertheim method, the exact solution of the Percus–Yevick integral equation for a system of particles with the "repulsive step potential" interacting ("collapsing" hard spheres) is obtained. On the basis of this solution, the state equation for the "repulsive step potential" is built and determined, that the Percus–Yevick equation does not show the Van der Waals loop for "collapsing" hard spheres.
ANALYSIS ON GLOBAL STABILITY OF STOCHASTIC NEURAL NETWORKS OF NEUTRAL TYPE
Authors: PARK JU H. , KWON O. M.
Published: January 2009

In this paper, the problem of global asymptotic stability of stochastic neural networks of neutral type is considered. Based on the Lyapunov stability theory, a new delay-dependent stability criterion for the network is derived in terms of LMI (linear matrix inequality). A numerical example is given to show the effectiveness of the proposed method.