bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Characterization of Peptide-Mediated Inhibition of
Porphyromonas gingivalis
Biofilm Formation
Authors: Daep Carlo Amorin , James DeAnna M. , Lamont Richard J. , Demuth Donald R. 
Published: September 2006

ABSTRACT

Porphyromonas gingivalis
is a periodontal pathogen whose primary niche is the anaerobic environment of subgingival dental plaque, but initial colonization of the oral cavity is likely to occur on supragingival surfaces that already support robust biofilm communities. Our studies have shown that
P. gingivalis
adheres to
Streptococcus gordonii
through interaction of the minor fimbrial antigen Mfa1 with a specific region of the streptococcal SspB polypeptide (residues 1167 to 1193) designated BAR. We show that a synthetic peptide comprising the BAR sequence potently inhibits
P. gingivalis
adherence to
S. gordonii
(50% inhibitory concentration = 1.3 μM) and prevents the development of
P. gingivalis
biofilms. However, a retroinverso peptide that possessed the same side chain topology as that of BAR was inactive, suggesting that interactions of Mfa1 with the peptide backbone of BAR are important for binding. A conformationally constrained analog of BAR inhibited
P. gingivalis
adherence and biofilm formation but at a lower specific activity than that of BAR. Therefore, to further define the structural features of the Mfa1-BAR interaction, we functionally screened combinatorial libraries of BAR in which active site residues (Asn
1182
, Thr
1184
, and Val
1185
) were replaced with each of the 19 common amino acids. Peptides containing positively charged amino acids at position 1182 or hydrophobic residues at position 1185 bound
P. gingivalis
more efficiently than did control peptides containing Asn and Val at these positions, suggesting that electrostatic and hydrophobic interactions may contribute to Mfa1-SspB binding. In contrast, replacement of Pro or Gly at these positions was detrimental to adherence, suggesting that perturbation of the BAR secondary structure influences activity. The net effect of substitutions for Thr
1184
was less pronounced either positively or negatively than that at the other sites. These results define physicochemical characteristics of the interacting interface of Mfa1 and SspB and suggest that peptides or peptidomimetics with greater specific inhibitory activity than that of BAR can be developed. These compounds may represent potential therapeutics that target some of the first molecular interactions that allow
P. gingivalis
to colonize the oral cavity.
Expression of the Lipopolysaccharide-Modifying Enzymes PagP and PagL Modulates the Endotoxic Activity ofBordetella pertussis
Authors: Geurtsen Jeroen , Steeghs Liana , Hamstra Hendrik-Jan , ten Hove Jan , de Haan Alex , Kuipers Betsy , Tommassen Jan , van der Ley Peter 
Published: September 2006

ABSTRACTLipopolysaccharide (LPS) is one of the major constituents of the gram-negative bacterial cell envelope. Its endotoxic activity causes the relatively high reactogenicity of whole-cell vaccines. Several bacteria harbor LPS-modifying enzymes that modulate the endotoxic activity of the LPS. Here we evaluated whether two such enzymes, i.e., PagP and PagL, could be useful tools for the development of an improved and less reactogenic whole-cell pertussis vaccine. We showed that expression of PagP and PagL inBordetella pertussisleads to increased and decreased endotoxic activity of the LPS, respectively. As expected, PagP activity also resulted in increased endotoxic activity of whole bacterial cells. However, more unexpectedly, this was also the case for PagL. This paradoxical result may be explained, in part, by an increased release of LPS, which we observed in the PagL-expressing cells.
Multivalent Recombinant Protein Vaccine against Coccidioidomycosis
Authors: Tarcha Eric J. , Basrur Venkatesha , Hung Chiung-Yu , Gardner Malcolm J. , Cole Garry T. 
Published: September 2006

ABSTRACTCoccidioidomycosis is a human respiratory disease that is endemic to the southwestern United States and is caused by inhalation of the spores of a desert soilborne fungus. Efforts to develop a vaccine against this disease have focused on identification of T-cell-reactive antigens derived from the parasitic cell wall which can stimulate protective immunity againstCoccidioides posadasiiinfection in mice. We previously described a productive immunoproteomic/bioinformatic approach to the discovery of vaccine candidates which makes use of the translated genome ofC. posadasiiand a computer-based method of scanning deduced sequences of seroreactive proteins for epitopes that are predicted to bind to human major histocompatibility (MHC) class II-restricted molecules. In this study we identified a set of putative cell wall proteins predicted to contain multiple, promiscuous MHC II binding epitopes. Three of these were expressed byEscherichia coli, combined in a vaccine, and tested for protective efficacy in C57BL/6 mice. Approximately 90% of the mice survived beyond 90 days after intranasal challenge, and the majority cleared the pathogen. We suggest that the multicomponent vaccine stimulates a broader range of T-cell clones than the single recombinant protein vaccines and thereby may be capable of inducing protection in an immunologically heterogeneous human population.
Mutations within the Catalytic Motif of DNA Adenine Methyltransferase (Dam) of
Aeromonas hydrophila
Cause the Virulence of the Dam-Overproducing Strain To Revert to That of the Wild-Type Phenotype
Authors: Erova Tatiana E. , Fadl Amin A. , Sha Jian , Khajanchi Bijay K. , Pillai Lakshmi L. , Kozlova Elena V. , Chopra Ashok K. 
Published: September 2006

ABSTRACT

In this study, we demonstrated that the methyltransferase activity associated with Dam was essential for attenuation of
Aeromonas hydrophila
virulence. We mutated aspartic acid and tyrosine residues to alanine within the conserved DPPY catalytic motif of Dam and transformed the pBAD/
dam
D/A
, pBAD/
dam
Y/A
, and pBAD/
dam
AhSSU
(with the native
dam
gene) recombinant plasmids into the
Escherichia coli
GM33 (
dam
-deficient) strain. Genomic DNA (gDNA) isolated from either of the
E. coli
GM33 strains harboring the pBAD vector with the mutated
dam
gene was resistant to DpnI digestion and sensitive to DpnII restriction endonuclease cutting. These findings were contrary to those with the gDNA of
E. coli
GM33 strain containing the pBAD/
dam
AhSSU
plasmid, indicating nonmethylation of
E. coli
gDNA with mutated Dam. Overproduction of mutated Dam in
A. hydrophila
resulted in bacterial motility, hemolytic and cytotoxic activities associated with the cytotoxic enterotoxin (Act), and protease activity similar to that of the wild-type (WT) bacterium, which harbored the pBAD vector and served as a control strain. On the contrary, overproduction of native Dam resulted in decreased bacterial motility, increased Act-associated biological effects, and increased protease activity. Lactone production, an indicator of quorum sensing, was increased when the native
dam
gene was overexpressed, with its levels returning to that of the control strain when the
dam
gene was mutated. These effects of Dam appeared to be mediated through a regulatory glucose-inhibited division A protein. Infection of mice with the mutated Dam-overproducing strains resulted in mortality rates similar to those for the control strain, with 100% of the animals dying within 2 to 3 days with two 50% lethal doses (LD
50
s) of the WT bacterium. Importantly, immunization of mice with a native-Dam-overproducing strain at the same LD
50
did not result in any lethality and provided protection to animals after subsequent challenge with a lethal dose of the control strain.
Gingipains from
Porphyromonas gingivalis
W83 Synergistically Disrupt Endothelial Cell Adhesion and Can Induce Caspase-Independent Apoptosis
Authors: Sheets Shaun M. , Potempa Jan , Travis James , Fletcher Hansel M. , Casiano Carlos A. 
Published: September 2006

ABSTRACT

We have shown previously that gingipains from
Porphyromonas gingivalis
W83 can induce cell detachment, cell adhesion molecule (CAM) cleavage, and apoptosis in endothelial cells; however, the specific roles of the individual gingipains are unclear. Using purified gingipains, we determined that each of the gingipains can cleave CAMs to varying degrees with differing kinetics. Kgp and HRgpA work together to quickly detach endothelial cells. Interestingly, in the absence of active caspases, both gingipain-active W83 extracts and purified HRgpA and RgpB induce apoptotic morphology, suggesting that the gingipains can induce both caspase-dependent and caspase-independent apoptosis. Using z-VAD-FMK to inhibit Kgp activity and leupeptin to inhibit Rgp activity in gingipain-active W83 extracts, we investigated the relative significance of the synergistic role of the gingipains. z-VAD-FMK or leupeptin delayed, but did not inhibit, cell detachment induced by gingipain-active W83 extracts or purified gingipains. There was partial cleavage of N-cadherin and cleavage of VE-cadherin was not inhibited. Degradation of integrin β1 was inhibited only in the presence of z-VAD-FMK. These results further clarify the role
P. gingivalis
plays in tissue destruction occurring in the periodontal pocket.
Mapping of the
Plasmodium chabaudi
Resistance Locus
char2
Authors: Lin Enmoore , Pappenfuss Tony , Tan Rachel B. , Senyschyn Danielle , Bahlo Melanie , Speed Terence P. , Foote Simon J. 
Published: September 2006

ABSTRACT

Animals congenic for the
char2
host response locus to the murine malarial parasite
Plasmodium chabaudi
have been bred, and they demonstrated a phenotypic difference from the parental lines. These congenic lines have been crossed back to the parental line to generate recombinants across the congenic intervals. The recombinants were inbred, and the subcongenic intervals were fixed. These lines were then challenged with parasites and assessed as being either resistant or susceptible. From the analysis of many subcongenic lines, it has become obvious that there are at least two loci underlying the
char2
locus and that both of these mediate resistance when the haplotype derives from the resistant C57BL/6 strain.
Induction of Neutrophil Chemotaxis by the Quorum-Sensing Molecule
N
-(3-Oxododecanoyl)-
l
-Homoserine Lactone
Authors: Zimmermann Sabine , Wagner Christof , Müller Wencke , Brenner-Weiss Gerald , Hug Friederike , Prior Birgit , Obst Ursula , Hänsch Gertrud Maria 
Published: September 2006

ABSTRACT

Acyl homoserine lactones are synthesized by
Pseudomonas aeruginosa
as signaling molecules which control production of virulence factors and biofilm formation in a paracrine manner. We found that
N
-(3-oxododecanoyl)-
l
-homoserine lactone (3OC12-HSL), but not its 3-deoxo isomer or acyl-homoserine lactones with shorter fatty acids, induced the directed migration (chemotaxis) of human polymorphonuclear neutrophils (PMN) in vitro. By use of selective inhibitors a signaling pathway, comprising phosphotyrosine kinases, phospholipase C, protein kinase C, and mitogen-activated protein kinase C, could be delineated. In contrast to the well-studied chemokines complement C5a and interleukin 8, the chemotaxis did not depend on pertussis toxin-sensitive G proteins, indicating that 3OC12-HSL uses another signaling pathway. Strong evidence for the presence of a receptor for 3OC12-HSL on PMN was derived from uptake studies; by use of radiolabeled 3OC12-HSL, specific and saturable binding to PMN was seen. Taken together, our data provide evidence that PMN recognize and migrate toward a source of 3OC12-HSL (that is, to the site of a developing biofilm). We propose that this early attraction of PMN could contribute to prevention of biofilm formation.
Sixty years on: the price of assembling military gas masks in 1940
Authors: McDonald J C , Harris J M , Berry G 
Published: September 2006

Background:Between 1940 and 1944 military gas masks with filter pads containing 20% crocidolite were assembled in a Nottingham factory.Methods:Records supplied by the late Professor Stephen Jones were of 1154 persons, mainly women, who had worked in the factory during this period; they included many deaths from mesothelioma. A systematic effort was therefore made to establish causes of death for the whole cohort.Results:Of 640 employees with full name and sex recorded, 567 (89%) were traced. Of these, 491 had died, including 65 from mesothelioma, though only 54 were certified as such. After exclusion of these 54, standardised mortality ratios were significantly raised for respiratory cancer (SMR 2.5) and carcinomatosis (SMR 3.2). The pattern of mortality in the remaining 514 employees without full identification was similar, but a low tracing rate (40%) did not justify their further analysis. The first death from mesothelioma was in 1963 (22 years after first exposure) and the last in 1994, whereas a further 5.0 cases would have been expected between 1996 and 2003 (p = 0.0065).Conclusion:These findings in a cohort followed over 60 years after brief exposure to crocidolite confirm a high and specific risk of mesothelioma (28% peritoneal) and perhaps of lung cancer some 20–50 years later. The statistically significant absence of further mesothelioma cases during the past eight years suggests that crocidolite, though durable, is slowly removed.
DESCRIPTION OF SEISMIC EVENTS USING WAVELET TRANSFORM
Authors: ČASTOVÁ NINA , HORÁK DAVID , KALÁB ZDENĚK 
Published: September 2006

This paper deals with engineering application of wavelet transform for processing of real seismological signals. Methodology for processing of these slight signals using wavelet transform is presented in this paper. Briefly, three basic aims are connected with this procedure:. 1. Selection of optimal wavelet and optimal wavelet basis B opt for selected data set based on minimal entropy: B opt = arg min B E(X,B). The best results were reached by symmetric complex wavelets with scaling coefficients SCD-6. 2. Wavelet packet decomposition and filtration of data using universal criterion of thresholding of the form [Formula: see text], where σ is minimal variance of the sum of packet decomposition of chosen level. 3. Cluster analysis of decomposed data. All programs were elaborated using program MATLAB 5.
Factors associated with women's antenatal plans to use a baby walker: A cross sectional study
Authors: Illingworth Rachel , Kendrick Denise , Collier Jacqueline , Woods Amanda , Wattse Kim , Dewey Michael , Chen Chih-Mei 
Published: September 2006

Objective The objective of these analyses was to explore maternal antnatal decisions about baby walker use, factors associated with these decisions and the relationship between antenatal plans to use a walker and postnatal walker use. Design Cross sectional study. Setting Mothers-to-be (n = 1174) participating in a cluster randomised controlled trial of an educational package to reduce walker use in 64 general practices in the East Midlands of the United Kingdom. Method Data on plans to use a walker, socio-demographic and ecnomic characteristics, partner's views on walker use, knowledge of walker-related injury and attitudes towards walkers were collected at entry to the trial by means of a self-completion questionnaire. Data on post-natal walker use was collected by postal questionnaire nine months after delivery. Results The majority of mothers-to-be (74 per cent) had already decided whether or not to use a walker prior to the birth of their baby and onthird were planning to do so. Several factors were identified which may be useful for identifying mothers-to-be who are undecided about walker use antenatally; these include partner's views on walkers, parity, houing tenure and attitudes towards walkers. Antenatal plans about walker use had high positive and negative predictive values for predicting posnatal walker use. Conclusion Education regarding walker use will be an important method for reducing walker use until walkers are no longer available to purchase first or second hand. The results of this study will assist health professionals in identifying which mothers-to-be are likely to be undcided about walker use and this group may be more receptive to health education than those who have already made a decision.
Men's health-is there a ‘popular press’ potential?
Authors: Clements Angela , Parry-Langdon Nina , Roberts Chris 
Published: September 2006

Objective To examine the types of health messages delivered to males and females through the'popular' media of magazines that have a health content, and to consider the potential for'popular' magazines to play a role in communicating health promotion messages to men. Design A qualitative approach that subscribes to content analysis of a sample of 'popular' women's and men's magazines over a six month period. Method Analysis of 23 women's weekly and monthly magazines and six men's monthly magazines that had a health content took place over a period of six months. Content analysis identified an analytical frame-work of four themes general health and healthy lifestyle issues, medical issues, letters to a doctor/other health‘expert’ and letters to an ‘agony aunt’ through which health promotion messages in the magazines were examined. Descriptive codes were developed from repeated reviews of the messages. Codes were then indexed and grouped into themes. Based on these themes, a set of typologies was developed. Results The initial examination of health promotion messages identified three typologies for communication. A set of seven categories emerged that highlight different styles and formats adopted by magazines for delivering and communicating health messages. Conclusion The opportunity for the delivery of timely health promotion messages directly to men is potentially high. In particular, the typology outlined in these results highlights the use of different communication styles and formats to appeal to different target groups in the delivery of health information. There are also opportunities to work in partnership with magazines aimed at both men and women to ensure that male health is placed more firmly on their health agenda.
The Post man’s still delivering
Authors: Hagerty Bill 
Published: September 2006

BJR editor Hagerty interviews Leonard Downie Jr, the Washington Post's executive editor for the past 15 years. He is the longest serving editor of any major newspaper in the United States, yet remains largely anonymous outside the industry. Downie's views on the British media include: "...there is a general tendency in the British media [for writers] to be essayists rather than reporters. There's a lot of detail that doesn't appear in most British reporting - it's more impressionistic, more analytical, and it's less deep and less facts-seeking. I particularly admire the proper analysis and the level of intellectual engagement, which is very high... But one thing that... disturbs me is the whole lobby system - the conspiring with officialdom to produce stories that are almost impossible to trace the origins of and to be misleading to the public as a result. It makes government more opaque rather than more transparent..." And he also observes: "The depths of investigative reporting and accountability reporting here, and the premium on accuracy, is paramount. In Britain, the Daily and Sunday Telegraph, for example, are both very aggressive newspapers right now, but every time they report something that interests us, the first thing we have to do is check it out. Just because they've reported it doesn't mean it's true. I would hate for people to see The Washington Post that way."
Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function
Authors: Del Prete Annalisa , Shao Wen-Hai , Mitola Stefania , Santoro Giuseppe , Sozzani Silvano , Haribabu Bodduluri 
Published: September 2006

AbstractTrafficking of dendritic cells (DCs) to peripheral tissues and to secondary lymphoid organs depends on chemokines and lipid mediators. Here, we show that bone marrow–derived DCs (BM-DCs) express functional leukotriene B4 (LTB4) receptors as observed in dose-dependent chemotaxis and calcium mobilization responses. LTB4, at low concentrations, promoted the migration of immature and mature DCs to CCL19 and CCL21, which was associated with a rapid (30-minute) increase of CCR7 expression at the membrane level. At longer incubation times (6 hours), gene array analysis revealed a promoting role of LTB4, showing a significant increase of CCR7 and CCL19 mRNA levels. BM-DCs cultured from BLT1−/− or BLT1/2−/− mice showed a normal phenotype, but in vivo BLT1/2−/−DCs showed dramatic decrease in migration to the draining lymph nodes relative to wild-type (WT) DCs. Consistent with these observations, BLT1/2−/− mice showed a reduced response in a model of 2,4-dinitro-fluorobenzene (DNFB)–induced contact hypersensitivity. Adoptive transfer of 2,4-dinitrobenzene sulfonic acid (DNBS)–pulsed DCs directly implicated the defect in DC migration to lymph node with the defect in contact hypersensitivity. These results provide strong evidence for a role of LTB4 in regulating DC migration and the induction of adaptive immune responses.
Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations
Authors: Stamatopoulos Kostas , Belessi Chrysoula , Moreno Carol , Boudjograh Myriam , Guida Giuseppe , Smilevska Tatjana , Belhoul Lynda , Stella Stefania , Stavroyianni Niki , Crespo Marta , Hadzidimitriou Anastasia , Sutton Laurent , Bosch Francesc , Laoutaris Nikolaos , Anagnostopoulos Achilles , Montserrat Emili , Fassas Athanasios , Dighiero Guillaume , Caligaris-Cappio Federico , Merle-Béral Hélène , Ghia Paolo , Davi Frédéric 
Published: September 2006

AbstractThe chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous (“stereotyped”) complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered “confirmed.” The remaining subsets comprised pairs of sequences and were considered “potential”; public database CLL sequences were found to be members of 9 of 22 “potential” subsets, thereby allowing us to consider them also “confirmed.” The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is “CLL-related.” CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients.