bluuebunny/crossref_metadata_2025 huggingface dataset:
Right‐Wing Authoritarianism, Attitude Salience, and Beliefs about Matters of Fact
Authors: Mirels Herbert L. , Dean Janet B.
Published: November 2006

Previous investigations have demonstrated a relationship between endorsement of right‐wing authoritarian (RWA) ideology and attitudes toward social and societal issues (e.g., abortion, drug use, affirmative action, and homosexuality). By contrast, the present studies examined the relationship between RWA and beliefs about matters of fact bearing on such issues (e.g., estimates of the prevalence of third trimester abortions, AIDS, concealed weapons). Studies 1 and 2 supported the propositions that high‐RWA and low‐RWA participants would show differences in their informational beliefs about sociopolitical matters consistent with differences in their respective ideologies and consistent with their putative differential cynicism about human nature. Study 3 demonstrated that the relationship between RWA and informational beliefs is amplified by the heightened salience of attitudes toward the targets of those beliefs.
Reconciliation after Genocide, Mass Killing, or Intractable Conflict: Understanding the Roots of Violence, Psychological Recovery, and Steps toward a General Theory
Authors: Staub Ervin
Published: November 2006

This article explores psychological avenues to reconciliation between groups. It describes the psychological changes in survivors, perpetrators, and passive bystanders in the course of the evolution of increasing violence and points to healing from the psychological wounds created as an essential component of reconciliation. It also explores the role of understanding the roots of genocide, and of violence between groups in general, in contributing to healing, to the creation of a shared history in place of the usually contradictory histories held by groups that have been in violent conflict, and to reconciliation in general. The role of processes that have been emphasized in the literature on reconciliation, such as truth, justice, and contact between groups are discussed. Bottom up approaches focusing on the population and top down approaches involving leaders and the media, and the importance of changes in institutions and structures are discussed. The article exemplifies many of the issues and processes by a discussion of the genocide in Rwanda, and by the description of interventions, ranging from work with small groups, including leaders and the media, to radio programs that aimed to further reconciliation, as well as research evaluating an intervention.
The Role of Popular Music in the Construction of Alternative Spiritual Identities and Ideologies
Authors: LYNCH GORDON
Published: November 2006

Setting its discussion in the wider context of the decline of institutional religion among young adults, the rise of alternative spiritualities, and the mediatization of religion, the article explores the significance of popular music in the development of alternative spiritual identities and ideologies. A summary is given of leading research conducted in this field by Christopher Partridge and Graham St. John. It is argued that they demonstrate the encoding of alternative spiritual symbols and ideologies into certain forms of popular music, they fail to give an adequate account of how audiences actively make use of this music to construct alternative spiritual identities or frameworks of meaning. The article concludes that researchers in the field of religion and popular music need to draw more on theories and methods developed in ethno‐musicology and the sociology of music, and suggests that the work of Tia De Nora on music in everyday life raises important questions about the qualities and context of the act of listening to music that could generate more nuanced accounts of how popular music shapes alternative spiritual identities and ideologies.
Does Religion Buffer the Effects of Discrimination on Mental Health? Differing Effects by Race
Authors: BIERMAN ALEX
Published: November 2006

Much research has shown that experiences of discrimination are negatively related to mental health. In this study, a national probability survey of whites and African Americans at midlife is used to examine whether attendance at religious services and religious comfort seeking protect people from the effects of discrimination on mental health, and if the protective power of religion varies by race. Results show that reports of discrimination are related to greater negative affect and less positive affect, but only attendance at religious services moderates this relationship, and then only for African Americans' negative affect. The historical involvement of African‐American religious bodies in combating discrimination may help to explain the specificity of these moderating effects.
Generations of Decline: Religious Change in 20th‐Century Britain
Authors: CROCKETT ALASDAIR , VOAS DAVID
Published: November 2006

This article analyzes the best available evidence from the major British social surveys to describe and explain the continuous decline of religion throughout the 20th century. This decline is overwhelmingly generational in nature rather than a product of particular periods such as World War II or the 1960s. Measures of religious affiliation, regular attendance at worship, and religious belief show nearly identical rates of intergenerational decline. Decline has not been offset by any positive age effects in an aging society: Britons do not get more religious as they get older. The intergenerational decline follows clear patterns of transmission of parental religious characteristics to children. Two potential modulators of decline are identified and investigated: immigration of people who are more religious than the existing population and higher fertility rates among the religiously active population. Of these only the former appears of importance. The nonwhite ethnic minority immigrant population is far more religious than the white population; however, the rates of intergenerational decline (between immigrant parents and native‐born children) are almost as high as for the white population, leading to an intergenerational convergence of levels of religiosity. Although ethnic minority populations tend to be more religious and have higher fertility rates, there is no differential fertility by religiosity among the population as a whole.
Religious Involvement, Conventional Christian, and Unconventional Nonmaterialist Beliefs
Authors: GLENDINNING TONY
Published: November 2006

This article uses a Scottish national sample to examine the relationship between church involvement, religious socialization among nonattenders, orthodox Christian beliefs, and a variety of unconventional nonmaterialist beliefs. Greater conventional religious belief is strongly associated with supposed alternatives but nonetheless, nonattenders are more likely to believe in the unconventional over and above any enduring sympathy they may hold for Christian doctrine. One group in particular stands out: belief remains high among nonattenders who once went to services regularly and seriously contemplate reengaging with organized religion. The article discusses the importance of these findings for “believing but not belonging.”
The impact of soil conservation and output diversification on farm income in Central American hillside farming
Authors: Bravo‐Ureta Boris E. , Solís Daniel , Cocchi Horacio , Quiroga Ricardo E.
Published: November 2006

This article analyzes the determinants of farm income among hillside farmers participating in natural resource management projects in El Salvador and Honduras. The farm income function was evaluated using a system of equations in which income is determined simultaneously by the farmer's decision to adopt soil conservation technologies and by the level of diversification (number of agricultural activities) on the farm. The database used comes from surveys administered to 678 beneficiaries of these projects during 2002. The econometric results suggest that all the variables related directly to land use (i.e., output diversification, soil conservation practices and structures, and the adoption of forestry systems) have a positive and statistically significant association with farm income. Also, farmers who own land enjoy higher farm incomes than those who do not. The results indicate that when investing in natural resource management projects, governments and multilateral development agencies should pay close attention to output diversification, land tenure, and human capital formation as effective instruments in increasing farm income.
Incidence and clinical characteristics of symptomatic choroidal metastasis from breast cancer
Authors: Kreusel Klaus‐Martin , Bechrakis Nikolaos E. , Krause Lothar , Wiegel Thomas , Foerster Michael H.
Published: November 2006

Purpose:  To determine the clinical incidence and characteristics of symptomatic choroidal metastasis (CM) in breast cancer.

Methods:  Forty‐six consecutive patients with CM from breast cancer were retrospectively reviewed in respect of ocular findings, medical history and systemic disease. Clinical incidence of CM was determined and compared with the incidence predicted from prevalence data obtained in ocular screening studies.

Results:  Choroidal metastasis occurred with a median interval of 42.4 months after diagnosis of breast cancer and was predominantly unilateral (63% patients) and solitary (57% affected eyes). A total of 32% of patients had no history of metastatic tumour disease, but systemic screening with CT and scintigraphy revealed metastatic disease in 100% of patients. A median number of three other organs were affected by metastasis. Median survival from diagnosis of CM was 13.1 months. The mean number of local patients diagnosed with CM was 2.9 per year, which was one order of magnitude less than predicted from clinical screening studies.

Conclusions:  Choroidal metastasis occurs in advanced metastatic breast cancer, indicating a grave vital prognosis. In a minority of patients (32%) it is the first sign of metastatic disease. The clinical incidence of CM is far smaller than predicted from prevalence data obtained from ocular screening studies.
Dynamics of water at membrane surfaces: Effect of headgroup structure
Authors: Murzyn Krzysztof , Zhao Wei , Karttunen Mikko , Kurdziel Marcin , Róg Tomasz
Published: November 2006

Atomistic molecular dynamics simulations of fully hydrated 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) bilayers in the liquid-crystalline state were carried out to investigate the effect of different lipid headgroups on the dynamics of water at the bilayer surface in short 80 ps time scales. Results obtained in these studies show that the hydrogen bonding amine group of POPE and the glycerol group of POPG slow water motion more than the equivalent choline group of POPC. Therefore, it is surprising that the effect of a POPC bilayer surface on water dynamics is similar to that of POPE and POPG bilayers. That result is due to a much higher number of water molecules interacting with the choline group of POPC than hydrogen-bonded molecules interacting with amine or glycerol groups of POPE and POPG.
Interferometric measurement of the resonant absorption and refractive index in rubidium gas
Authors: Libbrecht K. G. , Libbrecht M. W.
Published: November 2006

We present a laboratory demonstration of the Kramers-Kronig relation between the resonant absorption and refractive index in rubidium gas. Our experiment uses a rubidium vapor cell in one arm of a simple Mach-Zehnder interferometer. As the laser frequency is scanned over an atomic resonance, the interferometer output is affected by variations of both the absorption and refractive index of the gas with frequency, all of which can be calculated in a straightforward manner. Changing the vapor density and interferometer phase produces a family of different output signals. The experiment was performed using a commercially available tunable diode laser system that was designed specifically for the undergraduate physics laboratory. As a teaching tool this experiment is reliable, fun, and instructive, while it also introduces the student to some sophisticated and fundamental physical concepts.
The entropy of mixing and assimilation: An information-theoretical perspective
Authors: Ben-Naim Arieh
Published: November 2006

It is claimed that the quantity −k∑xilnxi, the so-called “entropy of mixing,” has nothing to do with the mixing process, and that, contrary to the accepted view, mixing is not an irreversible process. Instead, the process of deassimilation is introduced, and it is shown that it is an inherently irreversible process. The information-theoretical perspective of these statements is discussed for classical and quantum-mechanical systems of noninteracting particles.
Correction for the radii of curvature for electron beam trajectories in CENCO’s e/m apparatus
Authors: Howell John
Published: November 2006

An analysis of the motion of electrons in the Cenco e/m apparatus produces results that differ from those in Cenco’s operating instructions. As an electron’s speed increases in the apparatus, it is subjected to a uniform magnetic field B as well as a uniform electric field E. The B field affects the position as well as the angle at which the electron enters the E-free region. The net effect of the B field corresponds to a correction to the radius in the electron’s orbit that is approximately one-third the correction given by Cenco.
The Rayleigh-Taylor instability
Authors: Piriz A. R. , Cortázar O. D. , López Cela J. J. , Tahir N. A.
Published: November 2006

A new approach to the Rayleigh-Taylor instability is presented that yields exact solutions for the simplest cases and provides approximate but still very accurate analytical expressions for important and more complex cases involving nonideal fluids. The approach is based on Newton’s second law and allows for an intuitive and physically appealing explanation of the mechanisms underlying the instability.
The New Studio format for instruction of introductory physics
Authors: Sorensen C. M. , Churukian A. D. , Maleki S. , Zollman D. A.
Published: November 2006

We have developed the New Studio format of instruction for improved conceptual learning while retaining problem-solving skill development in large, first-year physics courses. This format retains the large lecture, but combines traditional recitation and laboratory instruction. The New Studio format integrates simplified laboratories with assigned homework problems to integrate conceptual and problem-solving skills. The studio format combines 2hours of lecture with 4hours of studio each week. The studio is taught for 2hours twice per week, and consists of up to 40 students working in groups of four at tables equipped with modern instructional technology and apparatus. The group setting allows for peer instruction and development of group skills. The combination of traditional lecture with the studio format enables a research-oriented physics department with a large service teaching load to implement research-based pedagogy. Student gains on the Force Concept Inventory were similar to other courses taught by interactive engagement methods.
Antifungal Effects on Metabolite Profiles of Medically Important Yeast Species Measured by Nuclear Magnetic Resonance Spectroscopy
Authors: Coen Muireann , Bodkin Jennifer , Power Damla , Bubb William A. , Himmelreich Uwe , Kuchel Philip W. , Sorrell Tania C.
Published: November 2006

Drug-induced inhibition of fungal growth is used in the diagnostic laboratory to predict therapeutic efficacy but is relatively slow, and determination of endpoints can be problematic. Nuclear magnetic resonance (NMR) spectroscopy identifies the metabolic complement of microorganisms while monitoring utilization of constituents of the incubation medium. This technique may provide a rapid and objective indicator of antifungal effects. We evaluated the effects of caspofungin, amphotericin B (AMB), and voriconazole on metabolic profiles of yeast species cultured in RPMI-2% glucose-morpholinepropanesulfonic acid buffer in microtiter plates in a proof-of-principle study.
1
H NMR spectra were obtained using Bruker NMR spectrometers at
1
H frequencies of 600 and 360 MHz. Metabolites were identified by two-dimensional correlation NMR spectra, and relative peak integrals were calculated from one-dimensional
1
H NMR spectra. MICs were determined by a modification of the Clinical and Laboratory Standards Institute broth microdilution method M27-A. Utilization of glucose and branched-chain and aromatic amino acid substrates was accompanied by fungal production of acetate, acetaldehyde, ethanol, formate, fumarate, glycerol, lactate, pyruvate, and succinate. Clear-cut metabolic endpoints indicating a greater than 50% reduction in substrate utilization and fungal metabolite production which correlated with MICs were noted at 16 and 24 h for all three drugs. At 8 h, reductions of greater than 50% for selected metabolites were noted for caspofungin and AMB. Direct NMR-based observation of metabolic alterations in yeast cultures reveals changes in key metabolic pathways and should be evaluated formally as a rapid technique for determining susceptibility to antifungal drugs.
Glibenclamide, a Blocker of K
+
ATP
Channels, Shows Antileishmanial Activity in Experimental Murine Cutaneous Leishmaniasis
Authors: Serrano-Martín Xenón , Payares Gilberto , Mendoza-León Alexis
Published: November 2006

Glibenclamide reduced the rate of lesion growth in BALB/c mice infected with
Leishmania
(
Leishmania
)
mexicana
, the effect was dose dependent, and the highest dose proved more effective than glucantime. Cross-resistance to glucantime was found in animals infected with a glibenclamide-resistant line, but combined therapy reduced lesion progression even in the glibenclamide-resistant strain.
Genetic Environment of Acquired
bla
ACC-1
β-Lactamase Gene in
Enterobacteriaceae
Isolates
Authors: Doloy A. , Verdet C. , Gautier V. , Decré D. , Ronco E. , Hammami A. , Philippon A. , Arlet G.
Published: November 2006

We studied the genetic organization of
bla
ACC-1
in 14 isolates of
Enterobacteriaceae
from France, Tunisia, and Germany. In a common ancestor, IS
Ecp1
was likely involved in the mobilization of this gene from the
Hafnia alvei
chromosome to a plasmid. Other genetic events involving insertion sequences (particularly IS
26
), transposons (particularly Tn
1696
), or
sulI
-type integrons have occurred, leading to complex genetic environments.
Long-Term Treatment with Lopinavir-Ritonavir Induces a Reduction in Peripheral Adipose Depots in Mice
Authors: Prot Matthieu , Heripret Laurence , Cardot-Leccia Nathalie , Perrin Christophe , Aouadi Myriam , Lavrut Thibaud , Garraffo Rodolphe , Dellamonica Pierre , Durant Jacques , Le Marchand-Brustel Yannick , Binétruy Bernard
Published: November 2006

Highly active antiretroviral therapy (HAART) of human immunodeficiency virus-infected patients is associated with adverse effects, such as lipodystrophy and hyperlipidemia. The lipodystrophic syndrome is characterized by a peripheral lipoatrophy and/or fat accumulation in the abdomen and neck. In order to get insights into the physiopathological mechanisms underlying this syndrome, we treated mice with protease inhibitors (PIs) over a long period of time. Although atazanavir-treated mice presented the same circulating triglyceride concentration as control mice, lopinavir-ritonavir-treated mice rapidly became hypertriglyceridemic, with triglyceride levels of 200 mg/dl, whereas control and atazanavir-treated animals had triglyceride levels of 80 mg/dl. These results obtained with mice reproduce the metabolic disorder observed in humans. White adipose tissue (WAT) was analyzed after 8 weeks of treatment. Compared to the control or atazanavir treatment, lopinavir-ritonavir treatment induced a significant 25% weight reduction in the peripheral inguinal WAT depot. By contrast, the profound epididymal WAT depot was not affected. This effect was associated with a 5.5-fold increase in
SREBP-1c
gene expression only in the inguinal depot. Our results demonstrate that the long-term treatment of mice with PIs constitutes an interesting experimental model with which some aspects of the lipoatrophy induced by HAART in humans may be studied.
Mutational Analysis of Class A and Class B Penicillin-Binding Proteins in
Streptococcus gordonii
Authors: Haenni Marisa , Majcherczyk Paul A. , Barblan Jean-Luc , Moreillon Philippe
Published: November 2006

High-molecular-weight (HMW) penicillin-binding proteins (PBPs) are divided into class A and class B PBPs, which are bifunctional transpeptidases/transglycosylases and monofunctional transpeptidases, respectively. We determined the sequences for the HMW PBP genes of
Streptococcus gordonii
, a gingivo-dental commensal related to
Streptococcus pneumoniae
. Five HMW PBPs were identified, including three class A (PBPs 1A, 1B, and 2A) and two class B (PBPs 2B and 2X) PBPs, by homology with those of
S. pneumoniae
and by radiolabeling with [
3
H]penicillin. Single and double deletions of each of them were achieved by allelic replacement. All could be deleted, except for PBP 2X, which was essential. Morphological alterations occurred after deletion of PBP 1A (lozenge shape), PBP 2A (separation defect and chaining), and PBP 2B (aberrant septation and premature lysis) but not PBP 1B. The muropeptide cross-link patterns remained similar in all strains, indicating that cross-linkage for one missing PBP could be replaced by others. However, PBP 1A mutants presented shorter glycan chains (by 30%) and a relative decrease (25%) in one monomer stem peptide. Growth rate and viability under aeration, hyperosmolarity, and penicillin exposure were affected primarily in PBP 2B-deleted mutants. In contrast, chain-forming PBP 2A-deleted mutants withstood better aeration, probably because they formed clusters that impaired oxygen diffusion. Double deletion could be generated with any PBP combination and resulted in more-altered mutants. Thus, single deletion of four of the five HMW genes had a detectable effect on the bacterial morphology and/or physiology, and only PBP 1B seemed redundant a priori.
High Prevalence of the K65R Mutation in Human Immunodeficiency Virus Type 1 Subtype C Isolates from Infected Patients in Botswana Treated with Didanosine-Based Regimens
Authors: Doualla-Bell Florence , Avalos Ava , Brenner Bluma , Gaolathe Tendani , Mine Madisa , Gaseitsiwe Simani , Oliveira Maureen , Moisi Daniella , Ndwapi Ndwapi , Moffat Howard , Essex Max , Wainberg Mark A.
Published: November 2006

We analyzed the reverse transcriptase genotypes of human immunodeficiency virus type 1 subtype C viruses isolated from 23 patients in Botswana treated with didanosine-based regimens. The K65R mutation was selected either alone or together with the Q151M, S68G, or F116Y substitution in viruses from seven such individuals. The results of in vitro passage experiments were consistent with an apparent increased propensity of subtype C viruses to develop the K65R substitution.
In Vitro Activities of the Novel Oxazolidinones DA-7867 and DA-7157 against Rapidly and Slowly Growing Mycobacteria
Authors: Vera-Cabrera Lucio , Brown-Elliott Barbara A. , Wallace Richard J. , Ocampo-Candiani Jorge , Welsh Oliverio , Choi Sung Hak , Molina-Torres Carmen A.
Published: November 2006

DA-7867 and DA-7157 are oxazolidinones active against pathogenic aerobic actinomycetes including
Nocardia
spp. and
Mycobacterium tuberculosis
. However, the activity of these drugs against nontuberculous mycobacterium (NTM) species is not known. In this work, we compared the susceptibilities of 122 clinical isolates and 29 reference species of both rapidly growing and slowly growing mycobacteria to linezolid, DA-7867, and DA-7157 by the broth microdilution method. The MICs for 50 and 90% of the strains tested (MIC
50
s and MIC
90
s, respectively) of DA-7867 and DA-7157 were lower than those of linezolid. In all of the cases, a MIC
90
of <8 μg/ml was observed for all of the species tested in both groups of NTM. For
M. kansasii
and
M. marinum
isolates, the MIC
90
s of both DA-7867 and DA-7157 were less than 0.5 μg/ml. These results demonstrate the potential of these compounds to treat NTM infections.
In Vitro Inhibition of
Toxoplasma gondii
by Four New Derivatives of Artemisinin
Authors: Jones-Brando Lorraine , D'Angelo John , Posner Gary H. , Yolken Robert
Published: November 2006

Toxoplasmosis, caused by the protozoan
Toxoplasma gondii
, is medically important and distributed worldwide. Currently available medications are limited in terms of efficacy and side effects. We synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of
Toxoplasma gondii
in cell culture.
Molecular Characteristics and In Vitro Susceptibility to Antimicrobial Agents, Including the Des-Fluoro(6) Quinolone DX-619, of Panton-Valentine Leucocidin-Positive Methicillin-Resistant
Staphylococcus aureus
Isolates from the Community and Hospitals
Authors: Yamamoto Tatsuo , Dohmae Soshi , Saito Kohei , Otsuka Taketo , Takano Tomomi , Chiba Megumi , Fujikawa Katsuko , Tanaka Mayumi
Published: November 2006

Highly virulent, community-acquired methicillin-resistant
Staphylococcus aureus
(MRSA) strains with Panton-Valentine leucocidin (PVL) genes have been found increasingly worldwide. Among a total of 2,101 MRSA strains isolated from patients in hospitals in Japan, two were positive for PVL genes. One strain was identified as a community-acquired MRSA strain with genotype sequence type 30 (ST30) and
spa
(staphylococcal protein A gene) type 19 from Japan and was resistant only to β-lactam antimicrobial agents. The other strain was closely related to PVL
+
multidrug-resistant, hospital-acquired MRSA strains (ST30,
spa
type 43) derived from nosocomial outbreaks in the 1980s to 1990s in Japan but with a divergent sequence type, ST765 (a single-locus variant of ST30). Twenty-two PVL
+
MRSA strains, including those from Japan and those from other countries with various sequence types (ST1, ST8, ST30, ST59, and ST80) and genotypes, were examined for susceptibility to 31 antimicrobial agents. Among the agents, DX-619, a des-fluoro(6) quinolone, showed the greatest activity, followed by rifampin and sitafloxacin, a fluoroquinolone. The data suggest that DX-619 exhibits a superior activity against PVL
+
MRSA strains with various virulence genetic traits from the community as well as from hospitals.
TherapeuticChlamydophila abortusandC. pecorumVaccination Transiently Reduces Bovine Mastitis Associated withChlamydophilaInfection
Authors: Biesenkamp-Uhe Carolin , Li Yihang , Hehnen Hans-Robert , Sachse Konrad , Kaltenboeck Bernhard
Published: November 2006

Infections withChlamydophila abortusandC. pecorumare highly prevalent in cattle and have been associated with bovine mastitis. A prospective cohort study was conducted with a herd of 140 Holstein dairy cows to investigate the influence ofChlamydophilainfection on subclinical inflammation of the bovine mammary gland as characterized by somatic cell numbers in milk. PCR detection ofC. abortusand low serum antibody levels againstChlamydophilaspp. were significantly associated with subclinical mastitis. To examine the effect of the infection by response modification, immune perturbation was done by two subcutaneous administrations of an experimental vaccine preparation of inactivatedC. abortusandC. pecorumelementary bodies. Vaccination againstChlamydophilahighly significantly decreased milk somatic cell numbers, thus reducing bovine mastitis, and increased antibody levels againstChlamydophilabut did not eliminate shedding ofC. abortusin milk as detected by PCR. The protective effect peaked at 11 weeks after vaccination and lasted for a total of 14 weeks. Vaccination with theChlamydophilavaccine, a mock vaccine, or a combination vaccine against bovine viral diseases highly significantly increasedC. abortusshedding in milk for 1 week, presumably mediated by the vaccine adjuvant. In summary, this study shows an etiological involvement of the widespreadChlamydophilainfections in bovine mastitis, a herd disease of critical importance for the dairy industry. Furthermore, this investigation shows the potential for temporary improvement of chlamydial disease by therapeutic vaccination.Chlamydophilavaccination of cattle might serve as a testing ground for vaccines against human chlamydial infections.
Growth Condition-Dependent Esp Expression by
Enterococcus faecium
Affects Initial Adherence and Biofilm Formation
Authors: Van Wamel Willem J. B. , Hendrickx Antoni P. A. , Bonten Marc J. M. , Top Janetta , Posthuma George , Willems Rob J. L.
Published: November 2006

A genetic subpopulation of
Enterococcus faecium
, called clonal complex 17 (CC-17), is strongly associated with hospital outbreaks and invasive infections. Most CC-17 strains contain a putative pathogenicity island encoding the
E. faecium
variant of enterococcal surface protein (Esp). Western blotting, flow cytometric analyses, and electron microscopy showed that Esp is expressed and exposed on the surface of
E. faecium
, though Esp expression and surface exposure are highly varied among different strains. Furthermore, Esp expression depends on growth conditions like temperature and anaerobioses. When grown at 37°C, five of six
esp
-positive
E. faecium
strains showed significantly increased levels of surface-exposed Esp compared to bacteria grown at 21°C, which was confirmed at the transcriptional level by real-time PCR. In addition, a significant increase in surface-exposed Esp was found in half of these strains when grown at 37°C under anaerobic conditions compared to the level in bacteria grown under aerobic conditions. Finally, amounts of surface-exposed Esp correlated with initial adherence to polystyrene (
R
2
= 0.7146) and biofilm formation (
R
2
= 0.7535). Polystyrene adherence was competitively inhibited by soluble recombinant N-terminal Esp. This study demonstrates that Esp expression on the surface of
E. faecium
(i) varies consistently between strains, (ii) is growth condition dependent, and (iii) is quantitatively correlated with initial adherence and biofilm formation. These data indicate that
E. faecium
senses and responds to changing environmental conditions, which might play a role in the early stages of infection when bacteria transit from oxygen-rich conditions at room temperature to anaerobic conditions at body temperature. In addition, variation of surface exposure may explain the contrasting findings reported on the role of Esp in biofilm formation.
ActA Is Required for Crossing of the Fetoplacental Barrier by
Listeria monocytogenes
Authors: Le Monnier Alban , Autret Nicolas , Join-Lambert Olivier F. , Jaubert Francis , Charbit Alain , Berche Patrick , Kayal Samer
Published: November 2006

The facultative intracellular bacterial pathogen
Listeria monocytogenes
induces severe fetal infection during pregnancy. Little is known about the molecular mechanisms allowing the maternofetal transmission of bacteria. In this work, we studied fetoplacental invasion by infecting mice with various mutants lacking virulence factors involved in the intracellular life cycle of
L. monocytogenes
. We found that the placenta was highly susceptible to bacteria, including avirulent bacteria, such as an
L. monocytogenes
mutant with an
hly
deletion (ΔLLO) and a nonpathogenic species,
Listeria innocua
, suggesting that permissive trophoblastic cells, trapping bacteria, provide a protective niche for bacterial survival. The ΔLLO mutant, which is unable to escape the phagosomal compartment of infected cells, failed to grow in the trophoblast tissue and to invade the fetus. Mutant bacteria with
inlA
and
inlB
deletion (ΔInlAB) grew in the placenta and fetus as well as did the wild-type virulent stain (EGDwt), indicating that in the murine model, internalins A and B are not involved in fetoplacental invasion by
L. monocytogenes
. Pregnant mice were then infected with an
actA
deletion (ΔActA) strain, a virulence-attenuated mutant that is unable to polymerize actin and to spread from cell to cell. With the ΔActA mutant, fetal infection occurs, but with a significant delay and restriction, and it requires a placental bacterial load 2 log units higher than that for the wild-type virulent strain. Definitive evidence for the role of ActA was provided by showing that a
actA
-complemented ΔActA mutant was restored in its capacity to invade fetuses. ActA-mediated cell-to-cell spreading plays a major role in the vertical transmission of
L. monocytogenes
to the fetus in the murine model.
Taste Receptors in the Gastrointestinal Tract. V. Acid sensing in the gastrointestinal tract
Authors: Holzer Peter
Published: November 2006

Luminal acidity is a physiological challenge in the foregut, and acidosis can occur throughout the gastrointestinal tract as a result of inflammation or ischemia. These conditions are surveyed by an elaborate network of acid-governed mechanisms to maintain homeostasis. Deviations from physiological values of extracellular pH are monitored by multiple acid sensors expressed by epithelial cells and sensory neurons. Acid-sensing ion channels are activated by moderate acidification, whereas transient receptor potential ion channels of the vanilloid subtype are gated by severe acidosis. Some ionotropic purinoceptor ion channels and two-pore domain background K+ channels are also sensitive to alterations of extracellular pH.
Spatial heterogeneity of the restitution portrait in rabbit epicardium
Authors: Pitruzzello Ann M. , Krassowska Wanda , Idriss Salim F.
Published: November 2006

Spatial heterogeneity of repolarization can provide a substrate for reentry to occur in myocardium. This heterogeneity may result from spatial differences in action potential duration (APD) restitution. The restitution portrait (RP) measures many aspects of rate-dependent restitution: the dynamic restitution curve (RC), S1-S2 RC, and short-term memory response. We used the RP to characterize epicardial patterns of spatial heterogeneity of restitution that were repeatable across animals. New Zealand White rabbit ventricles were paced from the epicardial apex, midventricle, or base, and optical action potentials were recorded from the same three regions. A perturbed downsweep pacing protocol was applied that measured the RP over a range of cycle lengths from 1,000 to 140 ms. The time constant of short-term memory measured close to the stimulus was dependent on location. In the midventricle the mean time constant was 19.1 ± 1.1 s, but it was 39% longer at the apex ( P < 0.01) and 23% longer at the base ( P = 0.03). The S1-S2 RC slope was dependent on pacing site ( P = 0.015), with steeper slope when pacing from the apex than from the base. There were no significant repeatable spatial patterns in steady-state APD at all cycle lengths or in dynamic RC slope. These results indicate that transient patterns of epicardial heterogeneity of APD may occur after a change in pacing rate. Thus it may affect cardiac electrical stability at the onset of a tachycardia or during a series of ectopic beats. Differences in restitution with respect to pacing site suggest that vulnerability may be affected by the location of reentry or ectopic foci.
Effects of cholecystokinin-8s in the nucleus tractus solitarius of vagally deafferented rats
Authors: Baptista V. , Browning K. N. , Travagli R. A.
Published: November 2006

We have shown recently that cholecystokinin octapeptide (CCK-8s) increases glutamate release from nerve terminals onto neurons of the nucleus tractus solitarius pars centralis (cNTS). The effects of CCK on gastrointestinal-related functions have, however, been attributed almost exclusively to its paracrine action on vagal afferent fibers. Because it has been reported that systemic or perivagal capsaicin pretreatment abolishes the effects of CCK, the aim of the present work was to investigate the response of cNTS neurons to CCK-8s in vagally deafferented rats. In surgically deafferented rats, intraperitoneal administration of 1 or 3 μg/kg CCK-8s increased c-Fos expression in cNTS neurons (139 and 251% of control, respectively), suggesting that CCK-8s' effects are partially independent of vagal afferent fibers. Using whole cell patch-clamp techniques in thin brain stem slices, we observed that CCK-8s increased the frequency of spontaneous and miniature excitatory postsynaptic currents in 43% of the cNTS neurons via a presynaptic mechanism. In slices from deafferented rats, the percentage of cNTS neurons receiving glutamatergic inputs responding to CCK-8s decreased by ∼50%, further suggesting that central terminals of vagal afferent fibers are not the sole site for the action of CCK-8s in the brain stem. Taken together, our data suggest that the sites of action of CCK-8s include the brain stem, and in cNTS, the actions of CCK-8s are not restricted to vagal central terminals but that nonvagal synapses are also involved.
Galectin-3 Expression Is Associated with Tumor Progression and Pattern of Sun Exposure in Melanoma
Authors: Prieto Victor G. , Mourad-Zeidan Alexandra A. , Melnikova Vladislava , Johnson Marcella M. , Lopez Adriana , Diwan A. Hafeez , Lazar Alexander J.F. , Shen Steven S. , Zhang Peter S. , Reed Jon A. , Gershenwald Jeffrey E. , Raz Avraham , Bar-Eli Menashe
Published: November 2006

Purpose: Most studies accept a multistep pathogenic process in melanoma that may include the phases of benign nevi and dysplastic nevi, melanoma, and metastatic melanoma. Dysregulation of cellular proliferation and apoptosis is probably involved in melanoma progression and response to therapy. We have studied the expression of galectin-3, a β-galactoside-binding protein involved in apoptosis, angiogenesis, and cell proliferation, in a large series of melanocytic lesions, and correlated the expression with clinical and histologic features.

Experimental Design: Tissue microarray blocks of 94 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic or nuclear expression of galectin-3.

Results: Primary and metastatic melanomas expressed galectin-3 at a significantly higher level than nevi in both cytoplasm and nuclei (P < 0.0073). There was a significant association between anatomic source (as indirect indication of level of sun-exposure) and cytoplasmic and nuclear expression. Lymph node and visceral metastases had a higher level of expression than s.c. lesions (P < 0.004). Interestingly, there was an almost significant finding of worse survival in those patients with lesions showing higher levels of cytoplasmic than nuclear galectin-3 expression (log-rank test, P = 0.06).

Conclusions: Melanocytes accumulate galectin-3 with tumor progression, particularly in the nucleus. The strong association of cytoplasmic and nuclear expression in lesions of sun-exposed areas suggests an involvement of UV light in activation of galectin-3.
A Phase I Study of OncoVEXGM-CSF, a Second-Generation Oncolytic Herpes Simplex Virus Expressing Granulocyte Macrophage Colony-Stimulating Factor
Authors: Hu Jennifer C.C. , Coffin Robert S. , Davis Ceri J. , Graham Nicola J. , Groves Natasha , Guest Peter J. , Harrington Kevin J. , James Nicholas D. , Love Colin A. , McNeish Iain , Medley Louise C. , Michael Agnieszka , Nutting Christopher M. , Pandha Hardev S. , Shorrock Claire A. , Simpson Julie , Steiner Jan , Steven Neil M. , Wright Dennis , Coombes R. Charles
Published: November 2006

Purpose: To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of the virus, look for evidence of biological activity, and identify a dosing schedule for later studies.

Experimental Design: The virus was administered by intratumoral injection in patients with cutaneous or s.c. deposits of breast, head and neck and gastrointestinal cancers, and malignant melanoma who had failed prior therapy. Thirteen patients were in a single-dose group, where doses of 106, 107, and 108 plaque-forming units (pfu)/mL were tested, and 17 patients were in a multidose group testing a number of dose regimens.

Results: The virus was generally well tolerated with local inflammation, erythema, and febrile responses being the main side effects. The local reaction to injection was dose limiting in HSV-seronegative patients at 107 pfu/mL. The multidosing phase thus tested seroconverting HSV-seronegative patients with 106 pfu/mL followed by multiple higher doses (up to 108 pfu/mL), which was well tolerated by all patients. Biological activity (virus replication, local reactions, granulocyte macrophage colony-stimulating factor expression, and HSV antigen-associated tumor necrosis), was observed. The duration of local reactions and virus replication suggested that dosing every 2 to 3 weeks was appropriate. Nineteen of 26 patient posttreatment biopsies contained residual tumor of which 14 showed tumor necrosis, which in some cases was extensive, or apoptosis. In all cases, areas of necrosis also strongly stained for HSV. The overall responses to treatment were that three patients had stable disease, six patients had tumors flattened (injected and/or uninjected lesions), and four patients showed inflammation of uninjected as well as the injected tumor, which, in nearly all cases, became inflamed.

Conclusions: Onco VEXGM-CSF is well tolerated and can be safely administered using the multidosing protocol described. Evidence of an antitumor effect was seen.
Enhanced RASGEF1A Expression Is Involved in the Growth and Migration of Intrahepatic Cholangiocarcinoma
Authors: Ura Katsuaki , Obama Kazutaka , Satoh Seiji , Sakai Yoshiharu , Nakamura Yusuke , Furukawa Yoichi
Published: November 2006

Purpose and Experimental Design: To identify novel molecular targets for the treatment of intrahepatic cholangiocarcinoma (ICC), the second most common type of primary hepatobiliary cancer, we earlier analyzed genome-wide expression profiles of genes in 25 ICCs. Among the genes whose expression levels were commonly elevated in the tumors, we identified a novel gene termed RASGEF1A that encodes a putative Ras guanine nucleotide exchange factor domain-containing protein.

Results: We showed in this article that RASGEF1A protein has a guanine nucleotide exchange activity to K-RAS, H-RAS, and N-RAS proteins in vitro. Consistently, exogenous RASGEF1A expression increased the activity of Ras. In addition, suppression of RASGEF1A by small interfering RNA retarded the growth of cholangiocarcinoma cells. Interestingly, COS7 cells expressing exogenous RASGEF1A showed enhanced cellular motility in Transwell and wound-healing assays.

Conclusions: These data suggest that elevated expression of RASGEF1A may play an essential role for proliferation and progression of ICC. Our data indicate that RASGEF1A may be a promising therapeutic target for the majority of ICCs.
Frequent Epigenetic Inactivation of Spleen Tyrosine Kinase Gene in Human Hepatocellular Carcinoma
Authors: Yuan Yunfei , Wang Jianping , Li Jinqing , Wang Li , Li Meixiang , Yang Zuli , Zhang Changqing , Dai Jia Le
Published: November 2006

Purpose: The aim of present study was to investigate the methylation and expression status of spleen tyrosine kinase (SYK) in human hepatocellular carcinoma (HCC) and to evaluate this information for its ability to predict disease prognosis. E-cadherin and TIMP-3 methylation was also analyzed here as control because both were associated with poor prognosis in some types of tumors.

Experimental Design: We analyzed the methylation status of SYK, E-cadherin, and TIMP-3 in 124 cases of HCC and assessed the correlation of such methylations with clinicopathologic variables and prognosis after tumor resection.

Results: We found that SYK, E-cadherin, and TIMP-3 genes were methylated in 27%, 27%, and 42% of HCC neoplastic tissues, respectively. The loss of SYK mRNA or Syk protein expression was highly correlated with SYK gene methylation. The patients with methylated SYK in neoplastic tissues had a significantly lower overall survival rate after hepatectomy than those with unmethylated SYK. No significant difference in overall survival rates, however, was found between groups of patients with methylated and unmethylated E-cadherin or TIMP-3. Patients with negative Syk protein expression had a significantly lower overall survival rate than those with positive Syk protein expression. Multivariate analyses indicated that factors affecting overall survival were tumor-node-metastasis stage, Child-Pugh classification, SYK methylation, or Syk protein status.

Conclusions: Our results indicate that SYK methylation and loss of Syk expression in HCC neoplastic tissues are independent biomarkers of poor patient outcome and that determination of SYK methylation or Syk expression status may offer guidance for selecting appropriate treatments.
Vascular Endothelial Growth Factor Blockade Reduces Intratumoral Regulatory T Cells and Enhances the Efficacy of a GM-CSF–Secreting Cancer Immunotherapy
Authors: Li Betty , Lalani Alshad S. , Harding Thomas C. , Luan Bo , Koprivnikar Kathryn , Huan Tu Guang , Prell Rodney , VanRoey Melinda J. , Simmons Andrew D. , Jooss Karin
Published: November 2006

Purpose: The purpose of the present study was to evaluate granulocyte macrophage colony-stimulating factor (GM-CSF)–secreting tumor cell immunotherapy in combination with vascular endothelial growth factor (VEGF) blockage in preclinical models.

Experimental Design: Survival and immune response were monitored in the B16 melanoma and the CT26 colon carcinoma models. VEGF blockade was achieved by using a recombinant adeno-associated virus vector expressing a soluble VEGF receptor consisting of selected domains of the VEGF receptors 1 and 2 (termed sVEGFR1/R2). Dendritic cell and tumor infiltrating lymphocyte activation status and numbers were evaluated by fluorescence-activated cell sorting analysis. Regulatory T cells were quantified by their CD4+CD25hi and CD4+FoxP3+ phenotype.

Results: The present study established that GM-CSF–secreting tumor cell immunotherapy with VEGF blockade significantly prolonged the survival of tumor-bearing mice. Enhanced anti-tumor protection correlated with an increased number of activated CD4+ and CD8+ tumor-infiltrating T cells and a pronounced decrease in the number of suppressive regulatory T cells residing in the tumor. Conversely, overexpression of VEGF from tumors resulted in elevated numbers of regulatory T cells in the tumor, suggesting a novel mechanism of VEGF-mediated immune suppression at the tumor site.

Conclusion: GM-CSF–secreting cancer immunotherapy and VEGF blockade increases the i.t. ratio of effector to regulatory T cells to provide enhanced antitumor responses. This therapeutic combination may prove to be an effective strategy for the treatment of patients with cancer.