bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reductions in Skin and Systemic Parasite Burdens as a Combined Effect of Topical Paromomycin and Oral Miltefosine Treatment of Mice Experimentally Infected with
Leishmania
(
Leishmania
)
amazonensis
Authors: Aguiar Marta Gontijo , Pereira Aline Márcia Machado , Fernandes Ana Paula , Ferreira Lucas Antonio Miranda 
Published: August 2010

ABSTRACT

This study aimed to investigate the activity of a combination of topical paromomycin gel and oral miltefosine for the treatment of experimental cutaneous leishmaniasis caused by
Leishmania
(
Leishmania
)
amazonensis
. The efficacy of the combination, evaluated by measuring lesion size and parasite burden in the skin and spleen, was assessed in BALB/c mice infected by
L
. (
L.
)
amazonensis
. The miltefosine was administered orally at 10 mg/kg of body weight/day for 10 days, while 10% paromomycin gel was applied topically twice a day for 20 days. Treatment of the experimentally infected animals with a topical paromomycin-oral miltefosine combination induced a statistically significant reduction in lesion size and parasite burden in the skin and spleen, with complete healing of ulcers, compared with those treated with a placebo group. A combination of topical paromomycin gel and oral miltefosine provided enhanced efficacy in the treatment of
L.
(
L.
)
amazonensis
-infected mice, showing activity higher than that observed for the monotherapeutic regimens.
Bactericidal Potencies of New Regimens Are Not Predictive of Their Sterilizing Potencies in a Murine Model of Tuberculosis
Authors: Andries Koen , Gevers Tom , Lounis Nacer 
Published: August 2010

ABSTRACT

TMC207, rifapentine, and moxifloxacin are in clinical testing for the treatment of tuberculosis. Five experimental regimens with various combinations of TMC207, rifapentine, moxifloxacin, and pyrazinamide were tested for their bactericidal and sterilizing potencies in Swiss mice intravenously inoculated with
Mycobacterium tuberculosis
bacilli. TMC207 had the strongest bactericidal efficacy, while rifapentine was the strongest contributor to sterilizing efficacy. The rank order of sterilizing potencies was different from the rank order of bactericidal potencies, underlining the importance of prioritizing new regimens designed to shorten the treatment duration by their sterilizing potencies rather than by their bactericidal potencies. Both 3 months of treatment with a regimen combining TMC207, pyrazinamide, and rifapentine and 5 months of treatment with a regimen combining TMC207, pyrazinamide, and moxifloxacin resulted in relapse rates similar to the rate obtained by 6 months of treatment with rifampin-isoniazid-pyrazinamide.
New Candidate Vaccines against Blood-StagePlasmodium falciparumMalaria: Prime-Boost Immunization Regimens Incorporating Human and Simian Adenoviral Vectors and Poxviral Vectors Expressing an Optimized Antigen Based on Merozoite Surface Protein 1
Authors: Goodman Anna L. , Epp C. , Moss D. , Holder A. A. , Wilson J. M. , Gao G. P. , Long C. A. , Remarque E. J. , Thomas A. W. , Ammendola V. , Colloca S. , Dicks M. D. J. , Biswas S. , Seibel D. , van Duivenvoorde L. M. , Gilbert S. C. , Hill A. V. S. , Draper S. J. 
Published: August 2010

ABSTRACTAlthough merozoite surface protein 1 (MSP-1) is a leading candidate vaccine antigen for blood-stage malaria, its efficacy in clinical trials has been limited in part by antigenic polymorphism and potentially by the inability of protein-in-adjuvant vaccines to induce strong cellular immunity. Here we report the design of novel vectoredPlasmodium falciparumvaccines capable of overcoming such limitations. We optimized an antigenic insert comprising the four conserved blocks of MSP-1 fused to tandemly arranged sequences that represent both allelic forms of the dimorphic 42-kDa C-terminal region. Inserts were expressed by adenoviral and poxviral vectors and employed in heterologous prime-boost regimens. Simian adenoviral vectors were used in an effort to circumvent preexisting immunity to human adenoviruses. In preclinical studies these vaccines induced potent cellular immune responses and high-titer antibodies directed against MSP-1. The antibodies induced were found to have growth-inhibitory activity against dimorphic allelic families ofP. falciparum. These vectored vaccines should allow assessment in humans of the safety and efficacy of inducing strong cellular as well as cross-strain humoral immunity toP. falciparumMSP-1.
CD4+CD25+Foxp3+Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?
Authors: Gonçalves Raquel M. , Salmazi Karina C. , Santos Bianca A. N. , Bastos Melissa S. , Rocha Sandra C. , Boscardin Sílvia B. , Silber Ariel M. , Kallás Esper G. , Ferreira Marcelo U. , Scopel Kézia K. G. 
Published: August 2010

ABSTRACTClearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections withPlasmodium falciparumandP. vivaxin the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+CD25+Foxp3+Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third ofP. vivax-infected patients, but noP. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.
Invasion of Bovine Peripheral Blood Mononuclear Cells and Erythrocytes byMycoplasma bovis
Authors: van der Merwe Jacques , Prysliak Tracy , Perez-Casal Jose 
Published: August 2010

ABSTRACTMycoplasma bovisis a small, cell wall-less bacterium that contributes to a number of chronic inflammatory diseases in both dairy and feedlot cattle, including mastitis and bronchopneumonia. Numerous reports have implicatedM. bovisin the activation of the immune system, while at the same time inhibiting immune cell proliferation. However, it is unknown whether the specific immune-cell populationM. bovisis capable of attaching to and potentially invading. Here, we demonstrate that incubation ofM. bovisMb1 with bovine peripheral blood mononuclear cells (PBMC) resulted in a significant reduction in their proliferative responses while still remaining viable and capable of gamma interferon secretion. Furthermore, we show thatM. bovisMb1 can be found intracellularly (suggesting a role for either phagocytosis or attachment/invasion) in a number of select bovine PBMC populations (T cells, B cells, monocytes, γδ T cells, dendritic cells, NK cells, cytotoxic T cells, and T-helper cells), as well as red blood cells, albeit it at a significantly lower proportion.M. bovisMb1 appeared to display three main patterns of intracellular staining: diffuse staining, an association with the intracellular side of the cell membrane, and punctate/vacuole-like staining. The invasion of circulating immune cells and erythrocytes could play an important role in disease pathogenesis by aiding the transport ofM. bovisfrom the lungs to other sites.
LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an
Escherichia coli
Strain Obtained from a Nonmammalian Host
Authors: Nawar Hesham F. , King-Lyons Natalie D. , Hu John C. , Pasek Raymond C. , Connell Terry D. 
Published: August 2010

ABSTRACT

Two families of bacterial heat-labile enterotoxins (HLTs) have been described: the type I HLTs are comprised of cholera toxin (CT) of
Vibrio cholerae
, LT-I of
Escherichia coli
, and several related HLTs; the type II HLTs are comprised of LT-IIa and LT-IIb. Herein, we report LT-IIc, a new type II HLT encoded from an enterotoxigenic
E. coli
(ETEC) strain isolated from an avian host. Using a mouse Y1 adrenal cell bioassay, LT-IIc was shown to be less cytotoxic than CT, LT-IIa, or LT-IIb. Cytotoxicity of LT-IIc was partially neutralized by antisera recognizing LT-IIa or LT-IIb but not by anti-CT antiserum. Genes encoding putative A polypeptide and B polypeptides of LT-IIc were arranged in an operon which was flanked by potential prophage sequences. Analysis of the nucleotide and predicted amino acid sequences demonstrated that the A polypeptide of LT-IIc has moderate homology to the A polypeptides of CT and LT-I and high homology to the A polypeptides of LT-IIa and LT-IIb. The B polypeptide of LT-IIc exhibited no significant homology to the B polypeptides of CT and LT-I and only moderate homology to the B polypeptides of LT-IIa and LT-IIb. The binding pattern of LT-IIc for gangliosides was distinctive from that of either LT-IIa or LT-IIb. The data suggest that other types of the type II HLT subfamily are circulating in the environment and that host specificity of type II HLT is likely governed by changes in the B polypeptide which mediate binding to receptors.
The Inflammatory Response Induced by Aspartic Proteases of
Candida albicans
Is Independent of Proteolytic Activity
Authors: Pietrella Donatella , Rachini Anna , Pandey Neelam , Schild Lydia , Netea Mihai , Bistoni Francesco , Hube Bernhard , Vecchiarelli Anna 
Published: August 2010

ABSTRACT

The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast
Candida albicans
. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca
2+
influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of
C. albicans
with the host.
Gelatinase Contributes to the Pathogenesis of Endocarditis Caused byEnterococcus faecalis
Authors: Thurlow Lance R. , Thomas Vinai Chittezham , Narayanan Sanjeev , Olson Sally , Fleming Sherry D. , Hancock Lynn E. 
Published: August 2010

ABSTRACTThe Gram-positive pathogenEnterococcus faecalisis a leading agent of nosocomial infections, including urinary tract infections, surgical site infections, and bacteremia. Among the infections caused byE. faecalis, endocarditis remains a serious clinical manifestation and unique in that it is commonly acquired in a community setting. Infective endocarditis is a complex disease, with many host and microbial components contributing to the formation of bacterial biofilm-like vegetations on the aortic valve and adjacent areas within the heart. In the current study, we compared the pathogenic potential of the vancomycin-resistantE. faecalisV583 and three isogenic protease mutants (ΔgelE, ΔsprE, and ΔgelEΔsprEmutants) in a rabbit model of enterococcal endocarditis. The bacterial burdens displayed by GelE−mutants (ΔgelEand ΔgelEΔsprEmutants) in the heart were significantly lower than those of V583 or the SprE−mutant. Vegetations on the aortic valve infected with GelE−mutants (ΔgelEand ΔgelEΔsprEmutants) also showed a significant increase in deposition of fibrinous matrix layer and increased chemotaxis of inflammatory cells. In support of a role for proteolytic modulation of the immune response toE. faecalis, we also demonstrate that GelE can cleave the anaphylatoxin complement C5a and that this proteolysis leads to decreased neutrophil migrationin vitro.In vivo, a decreased heterophil (neutrophil-like cell) migration was observed at tissue sites infected with GelE-producing strains but not at those infected with SprE-producing strains. Taken together, these observations suggest that of the two enterococcal proteases, gelatinase is the principal mediator of pathogenesis in endocarditis.
Impacts of salinity and simulated herbivory on survival and reproduction of the threatened Gulf of St. Lawrence Aster,Symphyotrichum laurentianum
Authors: Ancheta Justin , Heard Stephen B. , Lyons Jeremy W. 
Published: August 2010

Halophytic plants may experience joint, and potentially interacting, effects of salinity and herbivory on their survival and reproduction. We investigated the impacts of salinity and (simulated) herbivory on fitness in the Gulf of St. Lawrence Aster ( Symphyotrichum laurentianum (Fernald) Nesom; Asteraceae). In natural populations, this species experiences varying soil salinity and spill-over herbivory from insects associated with neighbouring seaside goldenrod ( Solidago sempervirens L.). We subjected S. laurentianum individuals to three levels of simulated herbivory (0%, 20%, and 40% leaf-area removal) and three levels of salinity (0, 10, and 20 g·L–1) in three runs of a growth-chamber experiment. The effects of salinity and herbivory were always additive. Salinity consistently and strongly reduced survivorship, by as much as 80% at 20 g·L–1salt, but significantly affected the seed set of survivors in only one run. Herbivory reduced survival significantly in one run (by 42% at 40% leaf-area removal) and reduced seed set of survivors (by 36% at 40% leaf-area removal) in another. While both stresses can have important effects on S. laurentianum fitness, the effects of salinity were more consistently strong than were the effects of herbivory, for both survival and seed set.
Mapping genetic variation and seed zones forBromus carinatusin the Blue Mountains of eastern Oregon, USAIn this article, mention of companies or trade names does not constitute an endorsement of any product or procedure.
Authors: Johnson R. C. , Erickson Vicky J. , Mandel Nancy L. , St Clair J. Bradley , Vance-Borland Kenneth W. 
Published: August 2010

Seed transfer zones ensure that germplasm selected for restoration is suitable and sustainable in diverse environments. In this study, seed zones were developed for mountain brome ( Bromus carinatus Hook. & Arn.) in the Blue Mountains of northeastern Oregon and adjoining Washington. Plants from 148 Blue Mountain seed source locations were evaluated in common-garden studies at two contrasting test sites. Data on phenology, morphology, and production were collected over two growing seasons. Plant traits varied significantly and were frequently correlated with annual precipitation and annual maximum temperature at seed source locations (P < 0.05). Plants from warmer locations generally had higher dry matter production, longer leaves, wider crowns, denser foliage, and greater plant height than those from cooler locations. Regression models of environmental variables with the first two principal components (PC 1 and PC 2) explained 46% and 40% of the total variation, respectively. Maps of PC 1 and PC 2 generally corresponded to elevation, temperature, and precipitation gradients. The regression models developed from PC 1 and PC 2 and environmental variables were used to map seed transfer zones. These maps will be useful in selecting mountain brome seed sources for habitat restoration in the Blue Mountains.
Phosphorus and land-use changes are significant drivers of cladoceran community composition and diversity: an analysis over spatial and temporal scales
Authors: Richard Albert Marc , Chen Guangjie , MacDonald Graham K. , Vermaire Jesse C. , Bennett Elena M. , Gregory-Eaves Irene 
Published: August 2010

We conducted paleolimnological studies over spatial and temporal gradients to define the responses of subfossil cladoceran community composition and diversity to changes in land use and phosphorus concentrations in shallow lakes. We predicted that watershed disturbance by humans, through its impact on water quality, would explain significant variation in cladoceran diversity and composition. Across lakes, water-column total phosphorus concentration was a significant (p < 0.05) predictor of the subfossil cladoceran community composition. Chydorid diversity was also found to be related significantly to phosphorus concentration (r = –0.55, p < 0.05) and the proportion of disturbed land in the watershed (r = –0.47, p < 0.05). However, net load of phosphorus to the watershed rather than proportion of watershed disturbance was a significant predictor of chydorid diversity (r = –0.86, p < 0.001) in our temporal analysis of an eutrophying lake. Given that phosphorus loading to surface waters is often related to phosphorus concentrations in soils, we suggest that the net phosphorus load to the watershed is a more sensitive metric of land-use change and necessary for detecting ecological responses in time series data.
Are seasonal lakes as productive as permanent lakes? A case study from Ireland
Authors: Cunha Pereira Helder , Allott Norman , Coxon Catherine 
Published: August 2010

This paper compares, for the first time, nutrient levels and chlorophyll a measured in a set of seasonal lakes with those reported for permanent lakes in the literature. Twenty-two turloughs (karstic seasonal lakes) in western Ireland were sampled monthly from the onset of flooding (October) until they dried out (6 to 9 months). The turloughs showed similar levels of nutrients and chlorophyll a to those reported for Irish and international lakes. Chlorophyll a peaked between November and February in the majority of turloughs, sometimes with values higher than those measured in mesotrophic lakes in summer. A significant log-linear regression was found between total phosphorus and chlorophyll a, which suggests P limitation of algal biomass in the majority of the turloughs. The regression characteristics were not significantly different than those described in similar studies of permanent lakes. Patterns in seasonal variation of nutrients are also presented, their underlying causes being discussed in relation to their transport within catchments. Our results show that despite being predominantly winter phenomena, turloughs can be as productive as permanent lakes.
Elastic properties of zinc-phosphate glasses doped with erbium trioxide
Authors: Eraiah B. , Ramakrishnaiah  , Anavekar R. V. 
Published: August 2010

New glasses of the system xEr2O3-(60-x)ZnO-40P2O5 (where x = 0.1 to 0.5 mol%) have been prepared by using a conventional meltquenching method. We have measured the densities of these glasses by using a displacement method, and corresponding molar volumes have also been calculated. We have measured both longitudinal and transverse ultrasonic sound velocities of these glasses using a pulse-echo superposition method. These ultrasonic velocities have been used to calculate the elastic moduli, Poisson ratio, and Debye temperatures. The variations of density, molar volume, ultrasonic sound velocities, elastic moduli, Poisson ratio, and Debye temperature have been discussed with respect to Er2O3 concentration.
Quantitative spectroscopy of the aurora. VI. The auroral spectrum from 275 to 815 nm observed by the OSIRIS spectrograph on board the Odin spacecraft
Authors: Gattinger R. L. , Vallance Jones A. , Degenstein D. A. , Llewellyn E. J. 
Published: August 2010

Terrestrial auroral spectra over the 275 to 815 nm wavelength range have been recorded by the OSIRIS imaging spectrograph on board the Odin spacecraft. The spectra are from the dark polar region and are averaged over limb tangent altitudes from 100 to 105 km. All wavelengths are exposed simultaneously, thus avoiding the effect of temporal intensity variations inherently present in spectrally scanning systems. Particular care has been taken to quantify the relative spectral sensitivity over the entire wavelength range, and there is an estimated 5% precision in the measurements. To maintain accurate on-orbit spectral calibrations, an atmospheric radiation model with multiple Rayleigh scatter is employed to regularly update the OSIRIS spectral response throughout the mission. A calibrated auroral spectrum is presented, together with matching synthetic spectra for many of the observed features, for potential use as a reference spectrum in general atmospheric research. The relative intensities of the brighter auroral band systems and atomic lines are reviewed. Finally, the observed spectrum is made freely available in digital format in long term archives.
The first-order structural phase transition of YSb
Authors: Fu Hongzhi , Liu WenFang , Gao Tao 
Published: August 2010

The high-pressure induced phase transition of YSb has been studied using the density functional theory method within the generalized gradient approximation. It was found that the first-order structural phase transition began to occur at 30.8 GPa, agreeing well with available experiments and theoretical calculations. In this phase transition, we do not find changes in the heat capacity and thermal expansion coefficients at lower and higher temperature, but the transition pressures decrease with temperature. The bulk modulus and Debye temperature decrease with increasing temperature, while they increase with increasing pressure. Also, the density of states and band structure of these two compounds with B1 and B2 structures have been presented and analyzed.