bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and Mechanisms of Broad-Spectrum β-Lactam Resistance inEnterobacteriaceae: a Children's Hospital Experience
Authors: Qin Xuan , Zerr Danielle M. , Weissman Scott J. , Englund Janet A. , Denno Donna M. , Klein Eileen J. , Tarr Phillip I. , Kwong Justin , Stapp Jennifer R. , Tulloch Luis G. , Galanakis Emmanouil
Published: September 2008

The objective of this study was to investigate the trends and patterns of resistance in β-lactamase-producing members of the familyEnterobacteriaceaein a children's hospital over a 9-year period (1999 to 2007). Clinically significant isolates of theEnterobacteriaceaewere screened for patterns of broad-spectrum resistance to β-lactams. The strains likely to be resistant were subsequently confirmed by an inhibitor-based disc test. The plasmid-mediated resistance determinants in these isolates were identified by PCR and by in vitro transformation, which successfully reproduced the AmpC phenotype unrestricted by the species of the host organisms. Among 8,048Enterobacteriaceaeisolates belonging to the four chromosomalampC-negative or -nonfunctional genera, 86 (1.07%) isolates (56Escherichia coliisolates, 22Klebsiellaspecies isolates, 1Proteus mirabilisisolate, and 7Salmonellaspecies isolates) exhibited broad-spectrum β-lactam resistance patterns. These organisms collectively produced three classes of β-lactamases, including class A extended-spectrum β-lactamases (n= 47), class C or AmpC β-lactamases (n= 36, including 4 isolates that produced both class A and class C enzymes), and class A or B carbapenem-hydrolyzing β-lactamases (n= 3). The proportion increased from 0.46% during the first 3 years to 1.84% during the last 3 years (relative risk [RR], 4.04; 95% confidence interval [CI], 2.28 to 7.42;P< 0.001). The increase was mainly due to the emergence of a plasmid-mediatedblaCMY-2β-lactamase, the incidence of which increased from 0.11% during the first 3 years to 0.96% during the last 3 years (RR, 9.11; 95% CI, 2.76 to 30.1;P= 0.001). Class A-type resistance increased slightly during the study period, from 0.35% during the first 3 years to 0.85% during the last 3 years (RR, 2.42; 95% CI, 1.15 to 5.07;P= 0.02). AProteus mirabilisstrain was documented to possess a novelblaDHAdeterminant. Of special concern, three carbapenemase-producing isolates were identified between 2003 and 2006. The infections caused by resistant isolates of theEnterobacteriaceaemainly affected hospitalized patients with underlying conditions; however, 19 (22%) episodes were of community onset in otherwise well children. The rate of resistance to broad-spectrum β-lactams among isolates of theEnterobacteriaceaeis increasing in children in both hospital- and community-acquired settings, and the resistance is driven largely by plasmid-mediated AmpC β-lactamases. These data have important implications for empirical antimicrobial strategies targeting serious pediatric infections. Further study of this problem is warranted.
Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E2in Infected Murine Osteoblasts
Authors: Somayaji Shankari N. , Ritchie Samantha , Sahraei Mahnaz , Marriott Ian , Hudson Michael C.
Published: September 2008

Osteomyelitis is an inflammatory disease of the bone that is characterized by the presence of necrotic bone tissue and increased osteoclast activity.Staphylococcus aureusis responsible for approximately 80% of all cases of human osteomyelitis. While the disease is especially difficult to treat, the pathogenesis ofS. aureus-induced osteomyelitis is poorly understood. Elucidating the molecular mechanisms by whichS. aureusinduces osteomyelitis could lead to a better understanding of the disease and its progression and development of new treatments. Osteoblasts can produce several soluble factors that serve to modulate the activity or formation of osteoclasts. Receptor activator of NF-κB ligand (RANK-L) and prostaglandin E2(PGE2) are two such molecules which can promote osteoclastogenesis and stimulate bone resorption. In addition, previous studies in our laboratory have shown that osteoblasts produce inflammatory cytokines, such as interleukin 6, following infection withS. aureus, which could induce COX-2 and in turn PGE2, further modulating osteoclast recruitment and differentiation. Therefore, we hypothesized that following infection withS. aureus, osteoblasts will express increased levels of RANK-L and PGE2. The results presented in this study provide evidence for the first time that RANK-L mRNA and protein and PGE2expression are upregulated inS. aureus-infected primary osteoblasts. In addition, through the use of the specific COX-2 inhibitor NS 398, we show that when PGE2production is inhibited, RANK-L production is decreased. These data suggest a mechanism whereby osteoblasts regulate the production of RANK-L during infection.
Detrimental Role of CC Chemokine Receptor 4 in Murine Polymicrobial Sepsis
Authors: Traeger Tobias , Kessler Wolfram , Assfalg Volker , Cziupka Katharina , Koerner Pia , Dassow Constanze , Breitbach Katrin , Mikulcak Marlene , Steinmetz Ivo , Pfeffer Klaus , Heidecke Claus-Dieter , Maier Stefan
Published: September 2008

CC chemokine receptor 4 (CCR4) and its two ligands, CCL17 and CCL22, are critically involved in different immune processes. In models of lipopolysaccharide-induced shock, CCR4-deficient (CCR4−/−) mice showed improved survival rates associated with attenuated proinflammatory cytokine release. Using CCR4−/−mice with a C57BL/6 background, this study describes for the first time the role of CCR4 in a murine model of polymicrobial abdominal sepsis, the colon ascendens stent peritonitis (CASP). CASP-induced sepsis led to a massive downregulation of CCR4 in lymphoid and nonlymphoid tissues, whereas the expression of CCL17 and CCL22 was independent of the presence of CCR4. After CASP, CCR4−/−animals showed a strongly enhanced bacterial clearance in several organs but not in the peritoneal lavage fluid and the blood. In addition, significantly reduced levels of proinflammatory cytokines/chemokines were measured in organ supernatants as well as in the sera of CCR4−/−mice. CCR4 deficiency consequently resulted in an attenuated severity of systemic sepsis and a strongly improved survival rate after CASP or CASP with intervention. Thus, our data provide clear evidence that CCR4 plays a strictly detrimental role in the course of polymicrobial sepsis.
RipA, a Cytoplasmic Membrane Protein Conserved amongFrancisellaSpecies, Is Required for Intracellular Survival
Authors: Fuller James R. , Craven Robin R. , Hall Joshua D. , Kijek Todd M. , Taft-Benz Sharon , Kawula Thomas H.
Published: September 2008

Francisella tularensisis a highly virulent bacterial pathogen that invades and replicates within numerous host cell types, including macrophages and epithelial cells. In an effort to better understand this process, we screened a transposon insertion library of theF. tularensislive vaccine strain (LVS) for mutant strains that invaded but failed to replicate within alveolar epithelial cell lines. One such strain isolated from this screen contained an insertion in the gene FTL_1914, which is conserved among all sequencedFrancisellaspecies yet lacks significant homology to any gene with known function. A deletion strain lacking FTL_1914 was constructed. This strain did not replicate in either epithelial or macrophage-like cells, and intracellular replication was restored by the wild-type allele intrans. Based on the deletion mutant phenotype, FTL_1914 was termedripA(required forintracellularproliferation, factorA). Following uptake by J774.A1 cells,F. tularensisLVSΔripAcolocalized with LAMP-1 then escaped the phagosome at the same rate and frequency as wild-type LVS-infected cells. Electron micrographs of theF. tularensisLVS ΔripAmutant demonstrated the reentry of the mutant bacteria into double membrane vacuoles characteristic of autophagosomes in a process that was not dependent on replication. TheF. tularensisLVSΔripAmutant was significantly impaired in its ability to persist in the lung and in its capacity to disseminate and colonize the liver and spleen in a mouse model of pulmonary tularemia. The RipA protein was expressed during growth in laboratory media and localized to the cytoplasmic membrane. Thus, RipA is a cytoplasmic membrane protein conserved amongFrancisellaspecies that is required for intracellular replication within the host cell cytoplasm as well as disease progression, dissemination, and virulence.
Proteomic Analysis of
Leptospira interrogans
Shed in Urine of Chronically Infected Hosts
Authors: Monahan Avril M. , Callanan John J. , Nally Jarlath E.
Published: September 2008

Leptospirosis is a global zoonotic disease. The causative agent, pathogenic
Leptospira
species, survives in the renal tubules of chronically infected hosts, from where leptospires are shed via urine into the environment. Infection of new hosts can present as an array of acute and chronic disease processes reflecting variations in host-pathogen interactions. The present study was designed to reproduce the carrier phase of infection in
Rattus norvegicus
, thus facilitating shedding of leptospires in urine. Leptospires shed in urine were collected for proteomic analysis because these organisms reflect a naturally virulent form of
Leptospira
associated with infection of new hosts. Experimentally infected rats remained clinically asymptomatic but shed leptospires in urine for several months at concentrations of up to 10
7
leptospires/ml of urine. Proteomic analysis of rat urine-isolated leptospires compared to in vitro-cultivated leptospires confirmed differential protein and antigen expression, as demonstrated by two-dimensional gel electrophoresis and immunoblotting. Furthermore, while serum from chronically infected rats reacted with many antigens of in vitro-cultivated
Leptospira
, few antigens of rat urine-isolated
Leptospira
were reactive. Results confirm that differential protein expression by
Leptospira
during chronic infection facilitates its persistence in the presence of a specific host antibody response.
Functional Analysis of the
Salmonella
Pathogenicity Island 2-Mediated Inhibition of Antigen Presentation in Dendritic Cells
Authors: Halici Serkan , Zenk Sebastian F. , Jantsch Jonathan , Hensel Michael
Published: September 2008

Salmonella enterica
is a facultative intracellular pathogen that is able to modify host cell functions by means of effector proteins translocated by the type III secretion system (T3SS) encoded by
Salmonella
Pathogenicity Island 2 (SPI2). The SPI2-T3SS is also active in
Salmonella
after uptake by murine bone marrow-derived dendritic cells (BM-DC). We have previously shown that intracellular
Salmonella
interfere with the ability of BM-DC to stimulate antigen-dependent T-cell proliferation in an SPI2-T3SS-dependent manner. We observed that
Salmonella
-mediated inhibition of antigen presentation could be restored by external addition of peptides on major histocompatibility complex class II (MHC-II). The processing of antigens in
Salmonella
-infected cells was not altered; however, the intracellular loading of peptides on MHC-II was reduced as a function of the SPI2-T3SS. We set out to identify the effector proteins of the SPI2-T3SS involved in inhibition of antigen presentation and demonstrated that effector proteins SifA, SspH2, SlrP, PipB2, and SopD2 were equally important for the interference with antigen presentation, whereas SseF and SseG contributed to a lesser extent to this phenotype. These observations indicate the presence of a host cell-specific virulence function of a novel subset of SPI2-effector proteins.
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

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

SopB 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

Toxoplasma 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

Borrelia 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

Anaplasma 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

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

Pertussis 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

Toxoplasma 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.
Structural reanalysis for a modified structure
Authors: Lee Eun-Taik , Eun Hee-Chang
Published: September 2008

Structural reanalysis aims to determine the variations in the displacement of a structure due to the addition or deletion of elements without solving the full degrees of freedom. The iterations change the design parameters at each step and utilize the factorization of the stiffness matrix of the initial design. This study develops a new reanalysis method to determine the additional forces that act on the initial structure and the displacements of the modified structure. It utilizes the compatibility conditions at the interfaces between the initial structure and the added or deleted members as static constraints, and applies the generalized inverse method to describe the static behavior of the constrained structure. The structural elements that are added may be statically stable substructures or floating members that possess rigid-body freedom. Examples are included to show the effectiveness of the proposed method.
Hydraulic performance of damaged-end corrugated steel pipe culverts
Authors: Kells J. A.
Published: September 2008

Culverts are a common and physically simple type of hydraulic structure, which are often fabricated as circular, corrugated steel pipe (CSP) sections. Because of the relatively thin wall of CSP, the ends of such pipe are frequently in a damaged condition. It is hypothesized that the hydraulic impact of the damage is often quite significant, resulting in reduced discharge capacity and (or) increased headwater ponding. The study reported in this paper was focused on an evaluation of the hydraulic impact of various levels of damage to the end sections of a culvert operating under either inlet or outlet control. In general, it was found that, for end damage deformations up to 1/4 of the pipe diameter, the discharge coefficient is reduced by approximately 10%, while the loss coefficients are increased by about 48% and 35% for inlet and outlet control modes of operation, respectively. For greater degrees of damage, the hydraulic performance is considerably worse.
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.
SELF-DUAL VORTICES IN THE ABELIAN CHERN–SIMONS MODEL WITH TWO COMPLEX SCALAR FIELDS
Authors: DUAN YI-SHI , ZHANG LI-DA , LIU YU-XIAO
Published: September 2008

Making use of ϕ-mapping topological current method, we discuss the self-dual vortices in the Abelian Chern–Simons model with two complex scalar fields. For each scalar field, an exact nontrivial equation with a topological term which is missing in many references is derived analytically. The general angular momentum is obtained. The magnetic flux which relates the two scalar fields is calculated. Furthermore, we investigate the vortex evolution processes, and find that because of the presence of the vortex molecule, these evolution processes are more complicated than the vortex evolution processes in the corresponding single scalar field model.
DIRAC SPINORS IN SOLENOIDAL FIELD AND SELF-ADJOINT EXTENSIONS OF ITS HAMILTONIAN
Authors: GIRI PULAK RANJAN
Published: September 2008

We discuss Dirac equation and its solution in the presence of solenoid (infinitely long) field in (3+1) dimensions. Starting with a very restricted domain for the Hamiltonian, we show that a one-parameter family of self-adjoint extensions are necessary to make sure the correct evolution of the Dirac spinors. Within the extended domain bound state (BS) and scattering state (SS) solutions are obtained. We argue that the existence of bound state in such system is basically due to the breaking of classical scaling symmetry by the quantization procedure. A remarkable effect of the scaling anomaly is that it puts an open bound on both sides of the spectrum, i.e. E ∈ (-M, M) for ν2[0, 1)! We also study the issue of relationship between scattering state and bound state in the region ν2 ∈ [0, 1) and recovered the BS solution and eigenvalue from the SS solution.
ALGEBRAIC CONDITIONS FOR CONVERGENCE OF A QUANTUM MARKOV SEMIGROUP TO A STEADY STATE
Authors: FAGNOLA FRANCO , REBOLLEDO ROLANDO
Published: September 2008

Let [Formula: see text] be a uniformly continuous quantum Markov semigroup on [Formula: see text] with generator represented in a standard GKSL form [Formula: see text] and a faithful normal invariant state ρ. In this note we give new algebraic conditions for proving that [Formula: see text] converges towards a steady state, possibly different from ρ. Indeed, we show that this happens whenever the commutator of [Formula: see text] (i.e. its fixed point algebra) coincides with the commutator of [Formula: see text] (where δH(X) = [H, X]) for some n ≥ 1. As an application we discuss the convergence to the unique invariant state of a spin chain model.
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.
A CHARACTERIZATION OF PROBABILITY MEASURES IN TERMS OF WICK PRODUCT INEQUALITIES
Authors: STAN AUREL I.
Published: September 2008

It is known that if X is a normally distributed random variable, and ♢ and E denote the Wick product and expectation, respectively, then for any non-negative integers m and n, and any polynomial functions f and g of degrees at most m and n, respectively, the following inequality holds: [Formula: see text] We show that this result can be extended to a random variable X, not necessary Gaussian, having an infinite support and finite moments of all orders, if and only if its Szegö–Jacobi sequence {ωk}k ≥ 1 is super-additive.
ANALYSIS OF THE STOCHASTIC FITZHUGH–NAGUMO SYSTEM
Authors: BONACCORSI STEFANO , MASTROGIACOMO ELISA
Published: September 2008

In this paper we study a system of stochastic differential equations with dissipative nonlinearity which arise in certain neurobiology models. Besides proving existence, uniqueness and continuous dependence on the initial datum, we shall mainly be concerned with the asymptotic behaviour of the solution. We prove the existence of an invariant ergodic measure ν associated with the transition semigroup Pt; further, we identify its infinitesimal generator in the space L2 (H; ν).
SEMIDIRECT PRODUCTS IN ALGEBRAIC LOGIC AND SOLUTIONS OF THE QUANTUM YANG–BAXTER EQUATION
Authors: RUMP WOLFGANG
Published: September 2008

A semidirect product is introduced for cycloids, i.e. sets with a binary operation satisfying (x · y) · (x · z) = (y · x) · (y · z). Special classes of cycloids arise in the combinatorial theory of the quantum Yang–Baxter equation, and in algebraic logic. In the first instance, semidirect products can be used to construct new solutions of the quantum Yang–Baxter equation, while in algebraic logic, they lead to a characterization of L-algebras satisfying a general Glivenko type theorem.
SOME PROPERTIES ON ISOCLINISM OF LIE ALGEBRAS AND COVERS
Authors: SALEMKAR ALI REZA , BIGDELY HADI , ALAMIAN VAHID
Published: September 2008

In this paper, we give some equivalent conditions for Lie algebras to be isoclinic. In particular, it is shown that if two Lie algebras L and K are isoclinic then L can be constructed from K and vice versa using the operations of forming direct sums, taking subalgebras, and factoring Lie algebras. We also study connection between isoclinic and the Schur multiplier of Lie algebras. In addition, we deal with some properties of covers of Lie algebras whose Schur multipliers are finite dimensional and prove that all covers of any abelian Lie algebra have Hopfian property. Finally, we indicate that if a Lie algebra L belongs to some certain classes of Lie algebras then so does its cover.
Cohesin and Human Disease
Authors: Liu Jinglan , Krantz Ian D.
Published: September 2008

Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases.
The role of GM-CSF in adipose tissue inflammation
Authors: Kim Dong-Hoon , Sandoval Darleen , Reed Jacquelyn A. , Matter Emily K. , Tolod Emeline G. , Woods Stephen C. , Seeley Randy J.
Published: September 2008

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine that has a central action to reduce food intake and body weight. Consistent with this, GM-CSF knockout mice are more obese and hyperphagic than wild-type mice. However, in lung, GM-CSF is an important determinant of macrophage infiltration. Consequently, we sought to determine if GM-CSF might contribute to adipose tissue macrophage accumulation, insulin resistance, and low-grade inflammation that occurs when animals gain weight on a high-fat diet (HFD). We therefore determined how targeted genetic disruption of GM-CSF can affect adipose tissue macrophage and cytokine gene expression as well as glucose homeostasis by performing hyperinsulinemic-euglycemic clamps. The number of macrophages and CCR2 gene expression in adipose tissue of GM-CSF knockout mice was decreased relative to those in wild-type mice, and the adipocyte size of mesenteric fat was increased in GM-CSF knockout mice on a HFD compared with wild-type mice. The level of mRNA of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and macrophage inflammatory protein-1α was significantly lower in mesenteric fat of GM-CSF knockout mice on the HFD than in wild-type mice. Using the hyperinsulinemic-euglycemic clamp technique, GM-CSF knockout mice had greater overall insulin sensitivity. This increase was due to enhanced peripheral uptake and utilization of glucose rather than to increased hepatic insulin sensitivity. Collectively, the data suggest that the GM-CSF knockout mutation ameliorates peripheral insulin resistance in spite of increased adiposity by reducing inflammation in adipose tissue in response to a HFD.
Amino acid regulation of TOR complex 1
Authors: Avruch Joseph , Long Xiaomeng , Ortiz-Vega Sara , Rapley Joseph , Papageorgiou Angela , Dai Ning
Published: September 2008

TOR complex 1 (TORC1), an oligomer of the mTOR (mammalian target of rapamycin) protein kinase, its substrate binding subunit raptor, and the polypeptide Lst8/GβL, controls cell growth in all eukaryotes in response to nutrient availability and in metazoans to insulin and growth factors, energy status, and stress conditions. This review focuses on the biochemical mechanisms that regulate mTORC1 kinase activity, with special emphasis on mTORC1 regulation by amino acids. The dominant positive regulator of mTORC1 is the GTP-charged form of the ras-like GTPase Rheb. Insulin, growth factors, and a variety of cellular stressors regulate mTORC1 by controlling Rheb GTP charging through modulating the activity of the tuberous sclerosis complex, the Rheb GTPase activating protein. In contrast, amino acids, especially leucine, regulate mTORC1 by controlling the ability of Rheb-GTP to activate mTORC1. Rheb binds directly to mTOR, an interaction that appears to be essential for mTORC1 activation. In addition, Rheb-GTP stimulates phospholipase D1 to generate phosphatidic acid, a positive effector of mTORC1 activation, and binds to the mTOR inhibitor FKBP38, to displace it from mTOR. The contribution of Rheb's regulation of PL-D1 and FKBP38 to mTORC1 activation, relative to Rheb's direct binding to mTOR, remains to be fully defined. The rag GTPases, functioning as obligatory heterodimers, are also required for amino acid regulation of mTORC1. As with amino acid deficiency, however, the inhibitory effect of rag depletion on mTORC1 can be overcome by Rheb overexpression, whereas Rheb depletion obviates rag's ability to activate mTORC1. The rag heterodimer interacts directly with mTORC1 and may direct mTORC1 to the Rheb-containing vesicular compartment in response to amino acid sufficiency, enabling Rheb-GTP activation of mTORC1. The type III phosphatidylinositol kinase also participates in amino acid-dependent mTORC1 activation, although the site of action of its product, 3′OH-phosphatidylinositol, in this process is unclear.
β-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes
Authors: Sinha Jyoti , Chen Frank , Miloh Tamir , Burns Robert C. , Yu Zhisheng , Shneider Benjamin L.
Published: September 2008

β-Klotho, a newly described membrane protein, regulates bile acid synthesis. Fibroblast growth factor-15 (FGF-15) and FGF receptor-4 (FGFR4) knockout mice share a similar phenotype with β-Klotho-deficient mice. FGF-15 secretion by the intestine regulates hepatic bile acid biosynthesis. The effects of β-Klotho and FGF-15 on the ileal apical sodium bile transporter (ASBT) are unknown. β-Klotho siRNA treatment of the mouse colon cancer cell line, CT-26, and the human intrahepatic biliary epithelial cells (HIBEC) resulted in upregulation of endogenous ASBT expression that was associated with reduced expression of the farnesoid X receptor (FXR) and the short heterodimer partner (SHP). Silencing β-Klotho activated the ASBT promoter in CT-26, Mz-ChA-1 (human cholangiocarcinoma), and HIBEC cells. Site-directed mutagenesis of liver receptor homolog-1 (mouse) or retinoic acid receptor/retinoid X receptor (RAR/RXR) (human) cis-elements attenuated the basal activity of the ASBT promoter and abrogated its response to β-Klotho silencing. siSHP, siFXR, or dominant-negative FXR treatment also eliminated the β-Klotho response. FGF-15 secretion into cell culture media by CT-26 cells was diminished after siFGF-15 or siβ-Klotho treatment and enhanced by chenodeoxycholic acid. Exogenous FGF-19 repressed ASBT protein expression in mouse ileum, gallbladder, and in HIBEC and repressed ASBT promoter activity in Caco-2, HIBEC, and Mz-ChA-1 cells. Promoter repression was dependent on the expression of FGFR4. These results indicate that both β-Klotho and FGF-15/19 repress ASBT in enterocytes and cholangiocytes. These novel signaling pathways need to be considered in analyzing bile acid homeostasis.