bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type IV Pili and the CcpA Protein Are Needed for Maximal Biofilm Formation by the Gram-Positive Anaerobic Pathogen
Clostridium perfringens
Authors: Varga John J. , Therit Blair , Melville Stephen B. 
Published: September 2008

ABSTRACT

The predominant organizational state of bacteria in nature is biofilms. Biofilms have been shown to increase bacterial resistance to a variety of stresses. We demonstrate for the first time that the anaerobic gram-positive pathogen
Clostridium perfringens
forms biofilms. At the same concentration of glucose in the medium, optimal biofilm formation depended on a functional CcpA protein. While the ratio of biofilm to planktonic growth was higher in the wild type than in a
ccpA
mutant strain in middle to late stages of biofilm development, the bacteria shifted from a predominantly biofilm state to planktonic growth as the concentration of glucose in the medium increased in a CcpA-independent manner. As is the case in some gram-negative bacteria, type IV pilus (TFP)-dependent gliding motility was necessary for efficient biofilm formation, as demonstrated by laser confocal and electron microscopy. However, TFP were not associated with the bacteria in the biofilm but with the extracellular matrix. Biofilms afforded
C. perfringens
protection from environmental stress, including exposure to atmospheric oxygen for 6 h and 24 h and to 10 mM H
2
O
2
for 5 min. Biofilm cells also showed 5- to 15-fold-increased survival over planktonic cells after exposure to 20 μg/ml (27 times the MIC) of penicillin G for 6 h and 24 h, respectively. These results indicate
C. perfringens
biofilms play an important role in the persistence of the bacteria in response to environmental stress and that they may be a factor in diseases, such as antibiotic-associated diarrhea and gas gangrene, that are caused by
C. perfringens
.
AsopBDeletion Mutation Enhances the Immunogenicity and Protective Efficacy of a Heterologous Antigen Delivered by Live AttenuatedSalmonella entericaVaccines
Authors: Li Yuhua , Wang Shifeng , Xin Wei , Scarpellini Giorgio , Shi Zhaoxing , Gunn Bronwyn , Roland Kenneth L. , Curtiss Roy 
Published: September 2008

ABSTRACTSopB is a virulence factor ofSalmonellaencoded by SPI-5.Salmonella sopBdeletion mutants are impaired in their ability to cause local inflammatory responses and fluid secretion into the intestinal lumen and also can enhance the immunogenicity of a vectored antigen. In this study, we evaluated the effects on immunogenicity and the efficacy of asopBdeletion mutation on twoSalmonella entericaserovar Typhimurium vaccine strains with different attenuating mutations expressing a highly antigenic α-helical region of theStreptococcus pneumoniaesurface protein PspA from an Asd+-balanced lethal plasmid. After oral administration to mice, the two pairs of strains induced high levels of serum antibodies specific for PspA as well as toSalmonellaantigens. The levels of antigen-specific serum immunoglobulin G (IgG) and mucosal IgA were higher in mice immunized withsopBmutants. Enzyme-linked immunospot assay results indicated that the spleen cells from mice immunized with asopBmutant showed higher interleukin-4 and gamma interferon secretion levels than did the mice immunized with the isogenicsopB+strain. ThesopBmutants also induced higher numbers of CD4+CD44hiCD62Lhiand CD8+CD44hiCD62Lhicentral memory T cells. Eight weeks after primary oral immunization, mice were challenged with 100 50% lethal doses of virulentS. pneumoniaeWU2. Immunization with either of thesopBmutant strains led to increased levels of protection compared to that with the isogenicsopB+parent. Together, these results demonstrate that the deletion ofsopBleads to an overall enhancement of the immunogenicity and efficacy of recombinant attenuatedSalmonellavaccine strains.
Intervacuolar Transport and Unique Topology of GRA14, a Novel Dense Granule Protein inToxoplasma gondii
Authors: Rome Michael E. , Beck Josh R. , Turetzky Jay M. , Webster Paul , Bradley Peter J. 
Published: September 2008

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite that resides in the cytoplasm of its host in a unique membrane-bound vacuole known as the parasitophorous vacuole (PV). The membrane surrounding the parasite is remodeled by the dense granules, secretory organelles that release an array of proteins into the vacuole and to the PV membrane (PVM). Only a small portion of the protein constituents of the dense granules have been identified, and little is known regarding their roles in infection or how they are trafficked within the infected host cell. In this report, we identify a novel secreted dense granule protein, GRA14, and show that it is targeted to membranous structures within the vacuole known as the intravacuolar network and to the vacuolar membrane surrounding the parasite. We disruptedGRA14and exploited the knockout strain to show that GRA14 can be transferred between vacuoles in a coinfection experiment with wild-type parasites. We also show that GRA14 has an unexpected topology in the PVM with its C terminus facing the host cytoplasm and its N terminus facing the vacuolar lumen. These findings have important implications both for the trafficking of GRA proteins to their ultimate destinations and for expectations of functional domains of GRA proteins at the host-parasite interface.
Deletion of BBA64, BBA65, and BBA66 Loci Does Not Alter the Infectivity ofBorrelia burgdorferiin the Murine Model of Lyme Disease
Authors: Maruskova Mahulena , Seshu J. 
Published: September 2008

ABSTRACTBorrelia burgdorferi, the causative agent of Lyme disease, alters its gene expression in response to highly disparate environmental signals encountered in its tick vector versus vertebrate hosts. Whole-genome transcriptional profile analysis ofB. burgdorferi, propagated in vitro under mammalian-host-specific conditions, revealed significant upregulation of several linear plasmid 54 (lp54)-encoded open reading frames (ORFs). Among these ORFs, BBA64, BBA65, and BBA66 have been shown to be upregulated in response to multiple mammalian-host-specific signals. Recently, we determined that there was no significant difference in the ability of BBA64−mutant to infect C3H/HeN mice compared to its isogenic control strains, suggesting thatB. burgdorferimight utilize multiple, functionally related determinants to establish infection. We further generated BBA65−and BBA66−single mutants in a noninfectious, lp25−clonal isolate ofB. burgdorferistrain B31 (ML23) and complemented them with the minimal region of lp25 (BBE22) required for restoring the infectivity. In addition, we generated a BBA64−BBA65−BBA66−triple mutant using an infectious, clonal isolate ofB. burgdorferistrain B31 (5A11) that has all of the infection-associated plasmids. There were no significant differences in the ability to isolate viable spirochetes from different tissues of C3H/HeN mice infected via intradermal needle inoculation with either the individual single mutants or the triple mutant compared to their respective isogenic parental strains at days 21 and 62 postinfection. These observations suggest thatB. burgdorferican establish infection in the absence of expression of BBA64, BBA65, and BBA66 in the murine model of Lyme disease.
Anaplasma phagocytophilumIncreases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function
Authors: Thomas Venetta , Samanta Swapna , Fikrig Erol 
Published: September 2008

ABSTRACTAnaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, is an unusual obligate intracellular pathogen that persists in neutrophils.A. phagocytophilumincreases the binding of a repressor, CCAAT displacement protein (CDP), to the gp91phoxpromoter, thereby diminishing the host oxidative burst. We now show thatA. phagocytophiluminfection also enhances the binding of CDP to the promoters of human neutrophil peptide 1 and C/EBPε—molecules important for neutrophil defense and maturation—suggesting that this is a general strategy used by this pathogen to alter polymorphonuclear leukocyte function. To explore the mechanism by whichA. phagocytophilumincreases CDP activity, we assessed the effects of this microbe on cathepsin L, a protease that cleaves CDP into a form with increased DNA binding ability.A. phagocytophiluminfection resulted in elevated cathepsin L activity and the proteolysis of CDP. Blocking the action of cathepsin L with a chemical inhibitor or small interfering RNA targeting of this molecule caused a marked reduction in the degree ofA. phagocytophiluminfection. These data demonstrate that increasing cathepsin L activity is a strategy used byA. phagocytophilumto alter CDP activity and thereby globally influence neutrophil function. As therapeutic options forA. phagocytophilumand related organisms are limited, these results also identify a cellular pathway that may be targeted for the treatment ofA. phagocytophiluminfection.
Bacillus anthracis
Edema Toxin Activates Nuclear Glycogen Synthase Kinase 3β
Authors: Larabee Jason L. , DeGiusti Kevin , Regens James L. , Ballard Jimmy D. 
Published: September 2008

ABSTRACT

Bacillus anthracis
edema toxin (ET) generates high levels of cyclic AMP and impacts a complex network of signaling pathways in targeted cells. In the current study, we sought to identify kinase signaling pathways modulated by ET to better understand how this toxin alters cell physiology. Using a panel of small-molecule inhibitors of mammalian kinases, we found that inhibitors of glycogen synthase kinase 3 beta (GSK-3β) protected cells from ET-induced changes in the cell cycle. GSK-3β inhibitors prevented declines in cellular levels of cyclin D1 and c-Jun following treatment of macrophages with ET. Strikingly, cell fractionation experiments and confocal immunofluorescence microscopy revealed that ET activates a compartmentalized pool of GSK-3β residing in the nuclei, but not in the cytoplasm, of macrophages. To investigate the outcome of this event, we examined the cellular location and activation state of β-catenin, a critical substrate of GSK-3β, and found that the protein was inactivated within the nucleus following intoxication with ET. To determine if ET could overcome the effects of stimuli that inactivate GSK-3β, we examined the impact of the toxin on the Wnt signaling pathway. The results of these experiments revealed that by targeting GSK-3β residing in the nucleus, ET circumvents the upstream cytoplasmic inactivation of GSK-3β, which occurs following exposure to Wnt-3A. These findings suggest ET arrests the cell cycle by a mechanism involving activation of GSK-3β residing in the nucleus, and by using this novel mechanism of intoxication, ET avoids cellular systems that would otherwise reverse the effects of the toxin.
Pertussis Toxin Inhibits Early Chemokine Production To Delay Neutrophil Recruitment in Response toBordetella pertussisRespiratory Tract Infection in Mice
Authors: Andreasen Charlotte , Carbonetti Nicholas H. 
Published: September 2008

ABSTRACTPertussis is an acute respiratory disease of humans caused by the bacteriumBordetella pertussis. Pertussis toxin (PT) plays a major role in the virulence of this pathogen, including important effects that it has soon after inoculation. Studies in our laboratory and other laboratories have indicated that PT inhibits early neutrophil influx to the lungs and airways in response toB. pertussisrespiratory tract infection in mice. Previous in vitro and in vivo studies have shown that PT can affect neutrophils directly by ADP ribosylating Giproteins associated with surface chemokine receptors, thereby inhibiting neutrophil migration in response to chemokines. However, in this study, by comparing responses to wild-type (WT) and PT-deficient strains, we found that PT has an indirect inhibitory effect on neutrophil recruitment to the airways in response to infection. Analysis of lung chemokine expression indicated that PT suppresses early neutrophil recruitment by inhibiting chemokine upregulation in alveolar macrophages and other lung cells in response toB. pertussisinfection. Enhancement of early neutrophil recruitment to the airways in response to WT infection by addition of exogenous keratinocyte-derived chemokine, one of the dominant neutrophil-attracting chemokines in mice, further revealed an indirect effect of PT on neutrophil chemotaxis. Additionally, we showed that intranasal administration of PT inhibits lipopolysaccharide-induced chemokine gene expression and neutrophil recruitment to the airways, presumably by modulation of signaling through Toll-like receptor 4. Collectively, these results demonstrate how PT inhibits early inflammatory responses in the respiratory tract, which reduces neutrophil influx in response toB. pertussisinfection, potentially providing an advantage to the pathogen in this interaction.
The Gamma Interferon (IFN-γ)-Inducible GTP-Binding Protein IGTP Is Necessary forToxoplasmaVacuolar Disruption and Induces Parasite Egression in IFN-γ-Stimulated Astrocytes
Authors: Melzer T. , Duffy A. , Weiss L. M. , Halonen S. K. 
Published: September 2008

ABSTRACTToxoplasma gondiiis a common central nervous system infection in individuals with immunocompromised immune systems, such as AIDS patients. Gamma interferon (IFN-γ) is the main cytokine mediating protection againstT. gondii. Our previous studies found that IFN-γ significantly inhibitsT. gondiiin astrocytes via an IFN-γ-inducible GTP-binding protein (IGTP)-dependent mechanism. The IGTP-dependent-, IFN-γ-stimulated inhibition is not understood, but recent studies found that IGTP induces disruption of the parasitophorous vacuole (PV) in macrophages. In the current study, we have further investigated the mechanism of IFN-γ inhibition and the role of IGTP in the vacuolar disruption in murine astrocytes. Vacuolar disruption was found to be dependent upon IGTP, as PV disruption was not observed in IGTP-deficient (IGTP−/−) astrocytes and PV disruption could be induced in IGTP−/−astrocytes transfected with IGTP. Live-cell imaging studies using green fluorescent protein-IGTP found that IGTP is delivered to the PV via the host cell endoplasmic reticulum (ER) early after invasion and that IGTP condenses into vesicle-like structures on the vacuole just prior to PV disruption, suggesting that IGTP is involved in PV disruption. Intravacuolar movement of the parasite occurred just prior to PV disruption. In some instances, IFN-γ induced parasite egression. Electron microscopy and immunofluorescence studies indicate that the host cell ER fuses with the PV prior to vacuolar disruption. On the basis of these results, we postulate a mechanism by which ER/PV fusion is a crucial event in PV disruption. Fusion of the ER with the PV, releasing calcium into the vacuole, may also be the mechanism by which intravacuolar parasite movement and IFN-γ-induced parasite egression occur.
How do different cigarette design features influence the standard tar yields of popular cigarette brands sold in different countries?
Authors: O’Connor R J , Hammond D , McNeill A , King B , Kozlowski L T , Giovino G A , Cummings K M 
Published: September 2008

Objectives:To examine the associations among cigarette design features and tar yields of leading cigarette brands sold in the United States, Canada, Australia and the United Kingdom.Methods:Government reports and numbers listed on packs were used to obtain data on International Organization for Standardization (ISO)/Federal Trade Commission (FTC) yields for the tar of 172 cigarette varieties sold in the United States, Canada, Australia and the United Kingdom. We used standardised methods to measure the following 11 cigarette design parameters: filter ventilation, cigarette pressure drop, filter pressure drop, tobacco rod length, filter length, cigarette diameter, tipping paper length, tobacco weight, filter weight, rod density and filter density.Results:Filter ventilation was found to be the predominant design feature accounting for the variations between brands in ISO/FTC tar yields in each of the four countries. After accounting for filter ventilation, design parameters such as overwrap length, tobacco weight and rod density played comparatively minor roles in determining tar yields.Conclusions:Variation in ISO/FTC tar yields are predicted by a limited set of cigarette design features, especially filter ventilation, suggesting that governments should consider mandatory disclosure of cigarette design parameters as part of comprehensive tobacco product regulations.
Constituents in tobacco and smoke emissions from Canadian cigarettes
Authors: Hammond D , O’Connor R J 
Published: September 2008

Background:There is relatively little information available about the chemical constituents of tobacco and individual toxic emissions from cigarettes and other tobacco products.Objective:To characterise 21 constituents in whole tobacco and 41 constituents in the smoke emissions of Canadian cigarettes, as well as to compare differences between domestic and imported brands.Methods:All data were released as part of Canada’s Tobacco Reporting Regulations. Data are reported for 247 brands tested in 2004.Results:The results indicate significant differences in the constituent levels of domestic and imported cigarette tobacco. Levels of ammonia compounds were significantly higher in imported “US blended” tobacco compared to domestically manufactured brands. Toxic emissions for tobacco-specific nitrosamines were significantly higher for imported cigarettes under both the ISO and Canadian Intense testing methods; however domestic cigarettes had higher levels of other toxic constituents, including benzo[a]pyrene. The findings also highlight the extent to which nicotine, heavy metals and tobacco-specific nitrosamines are “transferred” from the whole tobacco to the smoke.Conclusions:The findings illustrate important differences between domestically manufactured Virginia flue-cured cigarettes and imported US blended cigarettes. Although the findings suggest that domestic cigarettes had lower levels of constituents such as ammonia, which are associated with increased “additives”, Canadian cigarettes were by no means “additive-free.” Overall, these findings provide important benchmarks for making historical and international comparisons across brands on key constituents.
Long-term effects of nestling condition on blood parasite resistance in blue tits (Cyanistes caeruleus)
Authors: Stjernman M. , Råberg L. , Nilsson J.-Å. 
Published: September 2008

Little is know about whether the conditions experienced during ontogeny affect resistance to parasites later in life in wild animals. Here, we used a population of blue tits ( Cyanistes caeruleus (L., 1758)) to investigate to what extent conditions experienced during the nestling stage could explain the ability to control blood parasite ( Haemoproteus majoris (Laveran, 1902)) infections 1 year later. Although short-term effects may be expected based on the well-known sensitivity of the immune system to current conditions, it is less known whether this translates into a permanent alteration of parasite resistance. By relating nestling condition (measured as body mass or size-corrected body mass) at the beginning and end of the nestling stage to parasite intensity of individual recruiting birds 1 year later, we indeed found significant positive effects of both early and late nestling condition on the long-term ability to control parasites. These results indicate that parasites may be important as a mechanistic explanation for the trade-off between number and quality of offspring. It further points to the potential relevance for maternal effects in host–parasite interactions.
Effects of high food-demand fish removal in groups of juvenile sea bass (Dicentrarchus labrax)
Authors: Di-Poi Carole , Beauchaud Marilyn , Bouchut Colette , Dutto Gilbert , Covès Denis , Attia Joël 
Published: September 2008

In self-feeding conditions, a few individual sea bass ( Dicentrarchus labrax (L., 1758)) display strong activity in striking the food dispenser, whereas the remaining individuals of the group actuate the feeder weakly or never. Here, we investigated the effects of removal of the individuals showing dominant activity on the social and feeding behaviours in groups of juvenile sea bass. Following removal, new fish showing a dominant self-feeding activity quickly appear. They always come from the group of fish that have a low number of triggering actuations. This observation shows that it takes less time, about 5 days after the removal of dominant triggerers vs. 14 days at the beginning, for the re-establishment of the behavioural structure, suggesting the possibility of social transmission between individuals. The fish that show weak triggering activity seem to reach the high-food triggering level without obvious signs of competition. This experiment reveals the importance of the food-demand behavioural structure: the fish displaying the highest activity lead to a general food distribution and play a dominant role in feeding the entire group. Functional plasticity in this role within individuals is also demonstrated, indicating that the high-triggering function is essential for the group and not for the individual themselves.
WHAT TYPE OF DYNAMICS ARISE IN E0-DILATIONS OF COMMUTING QUANTUM MARKOV SEMIGROUPS?
Authors: SHALIT ORR MOSHE 
Published: September 2008

Let H be a separable Hilbert space, and let ϕ and θ be two strongly commuting CP0-semigroups on B(H). In a previous paper we constructed a Hilbert space K ⊇ H and two (strongly) commuting E0-semigroups α and β such that [Formula: see text] for all s, t ≥ 0 and all A ∈ B(K). In this note we prove that if ϕ is not an automorphism semigroup, then the semigroup α (given by the above mentioned construction) is cocycle conjugate to the minimal *-endomorphic dilation of ϕ, and that if ϕ is an automorphism semigroup, then α is also an automorphism semigroup. In particular, we conclude that if ϕ is not an automorphism semigroup and has a bounded generator (in particular, if H is finite dimensional), then α is a type I E0-semigroup.
MTHFR Genotype and Colorectal Adenoma Recurrence: Data from a Double-blind Placebo-controlled Clinical Trial
Authors: Levine A. Joan , Wallace Kristin , Tsang Shirley , Haile Robert W. , Saibil Fred , Ahnen Dennis , Cole Bernard F. , Barry Elizabeth L. , Munroe David J. , Ali Iqbal U. , Ueland Per , Baron John A. 
Published: September 2008

Abstract
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. We assessed the association between two common MTHFR variants, 677C&gt;T and 1298A&gt;C, and adenoma recurrence in the context of a randomized double- blind clinical trial of aspirin use and folate supplementation. We used generalized linear regression to estimate risk ratios and 95% confidence intervals (95% CI) for recurrence, adjusting for age, sex, clinical center, follow-up time, and treatment status. Neither MTHFR polymorphism was associated with overall or advanced adenoma recurrence. Compared with those with two wild-type alleles, the relative risk for advanced adenoma was 0.75 (95% CI, 0.36-1.55) for the MTHFR 677 TT genotype and 1.16 (95% CI, 0.58-2.33) for the MTHFR 1298 CC genotype. The effect of folate supplementation on recurrence risk did not differ by genotype. Our findings indicate that the MTHFR genotype does not change adenoma risk in a manner similar to its effect on colorectal cancer, and does not modify the effect of folate supplementation on metachronous adenoma risk. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2409–15)