bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust Stimulation of Humoral and Cellular Immune Responses following Vaccination with Antigen-Loaded β-Glucan Particles
Authors: Huang Haibin , Ostroff Gary R. , Lee Chrono K. , Specht Charles A. , Levitz Stuart M. 
Published: July 2010

ABSTRACTβ-Glucan particles (GPs) are purifiedSaccharomyces cerevisiaecell walls treated so that they are primarily β1,3-d-glucans and free of mannans and proteins. GPs are phagocytosed by dendritic cells (DCs) via the Dectin-1 receptor, and this interaction stimulates proinflammatory cytokine secretion by DCs. As the hollow, porous GP structure allows for high antigen loading, we hypothesized that antigen-loaded GPs could be exploited as a receptor-targeted vaccine delivery system. Ovalbumin (OVA) was electrostatically complexed inside the hollow GP shells (GP-OVA). Incubation of C57BL/6J mouse bone marrow-derived DCs with GP-OVA resulted in phagocytosis, upregulation of maturation markers, and rapid proteolysis of OVA. Compared with free OVA, GP-OVA was >100-fold more potent at stimulating the proliferation of OVA-reactive transgenic CD8+OT-I and CD4+OT-II T cells, as measured byin vitro[3H]thymidine incorporation using DCs as antigen-presenting cells. Next, immune responses in C57BL/6J mice following subcutaneous immunizations with GP-OVA were compared with those in C57BL/6J mice following subcutaneous immunizations with OVA absorbed onto the adjuvant alum (Alum/OVA). Vaccination with GP-OVA stimulated substantially higher antigen-specific CD4+T-cell lymphoproliferative and enzyme-linked immunospot (ELISPOT) responses than that with Alum/OVA. Moreover, the T-cell responses induced by GP-OVA were Th1 biased (determined by gamma interferon [IFN-γ] ELISPOT assay) and Th17 biased (determined by interleukin-17a [IL-17a] ELISPOT assay). Finally, both the GP-OVA and Alum/OVA formulations induced strong secretions of IgG1 subclass anti-OVA antibodies, although only GP-OVA induced secretion of Th1-associated IgG2c antibodies. Thus, the GP-based vaccine platform combines adjuvanticity and antigen delivery to induce strong humoral and Th1- and Th17-biased CD4+T-cell responses.IMPORTANCEMost licensed vaccines work by promoting protective antibody responses. However, for many infectious diseases, antibody-mediated protection appears to play a relatively minor role, and vaccination has met with limited success. While live-attenuated organisms generally elicit T-cell responses, their use in vaccines is limited by the potential for causing disease. Thus, there is an urgent need for new vaccine platforms that deliver antigens in such a manner as to promote strong T-cell-mediated responses. Here we designed a novel vaccine platform consisting of yeast-derived β-glucan particles (GPs) that combines antigen delivery and adjuvant activity. GPs loaded with the model antigen ovalbumin (OVA) stimulated robust humoral and T-cell responses in mice. In addition, the cellular response was Th1 and Th17 biased. This work has implications for the design of vaccines that stimulate biased T-cell responses as well as for understanding how immunity to fungal pathogens develops.
The immediate effects of foot orthoses on functional performance in individuals with patellofemoral pain syndrome
Authors: Barton C J , Menz H B , Crossley K M 
Published: July 2010

ObjectivePatellofemoral pain syndrome (PFPS) often results in reduced functional performance. There is growing evidence for the use of foot orthoses to treat this multifactorial condition. In this study, the immediate effects of foot orthoses on functional performance and the association of foot posture and footwear with improvements in function were evaluated.MethodsFifty-two individuals with PFPS (18–35 years) were prescribed prefabricated foot orthoses (Vasyli Pro; Vasyli International, Labrador, Australia). Functional outcome measures evaluated included the change in (1) pain and (2) ease of a single-leg squat on a five-point Likert scale, and change in the number of (3) pain-free step downs and (4) single-leg rises from sitting. The association of foot posture using the Foot Posture Index, navicular drop and calcaneal angle relative to subtalar joint neutral; and the footwear motion control properties scale score with improved function were evaluated using Spearman's ρ statistics.ResultsPrefabricated foot orthoses produced significant improvements (p<0.05) for all functional outcome measures. A more pronated foot type and poorer footwear motion control properties were found to be associated with reduced pain during the single-leg squat and improvements in the number of pain-free single-leg rises from sitting when wearing foot orthoses. In addition, a more pronated foot type was also found to be associated with improved ease of completing a single-leg squat when wearing foot orthoses.ConclusionPrefabricated foot orthoses provide immediate improvements in functional performance, and these improvements are associated with a more pronated foot type and poorer footwear motion control properties.Keywordsfoot orthoses; patellofemoral pain syndrome; functional performance; knee pain; insoles.
Performance and response to defoliation of Sanguisorba officinalis (Rosaceae) seedlings from mown and successional habitats
Authors: Musche Martin , Settele Josef , Durka Walter 
Published: July 2010

In agricultural habitats, selection may favour plants that show a pronounced ability to tolerate stress induced by specific management methods. However, genetic erosion associated with habitat fragmentation may diminish this ability. To assess the role of mowing as a selection pressure and the impact of fragmentation processes on the ability to tolerate foliage loss, we grew 215 plants of the perennial herb Sanguisorba officinalis L. originating from 16 differently sized populations, located in mown meadows and successional fallows, in a common environment, and measured their performance and response to defoliation. Plants from meadows and fallows neither differed in performance characters nor in their ability to compensate for foliage loss. However, independently from the habitat of origin, populations slightly differed in performance. This variation was not due to differences in population size, plant density, or level of genetic variation, indicating its independence from genetic erosion, which may go along with habitat fragmentation. Rather, these differences between populations appear to be the outcome of unknown selection pressures or random genetic drift. Plants from successional fallows retain their potential to cope with mowing, presumably due to the low generation turnover of the perennial species. Selection by mowing may act over time scales larger than those reflected by the developmental stage of the current habitats.
Characterization of the ATP-translocating properties of the predictedArabidopsis thalianamitochondrial adenine nucleotide translocator 2
Authors: Kharenko Olesya A. , Loewen Michele C. 
Published: July 2010

In this study we demonstrate that the predicted Arabidopsis thaliana (L.) Heynh. mitochondrial adenine nucleotide translocator 2 (ANT2) mediates ATP translocation. The demonstration that recombinantly produced ANT2 mediates ATP uptake into proteoliposomes, confirms previous sequence-based identification of the protein as a member of the adenine nucleotide translocator family. Expressed in Saccharomyces cerevisiae with a C-terminal His6 tag, localization was confirmed in yeast membrane extracts. The recombinant protein was solubilized with Triton X-100, enriched by immobilized metal affinity chromatography, and reconstituted into liposomes. Functionality of the reconstituted protein was confirmed by demonstration of pyridoxal 5′-phosphate-sensitive [3H]ATP uptake. Transport assays showed first order kinetic uptake of ATP with an approximate Kmvalue of 15 µmol·L–1. Competition assays indicated that the reconstituted protein had highest specificity for ATP. Overall, these results indicate that Arabidopsis ANT2 is an adenine nucleotide translocator.
Comparison of gene order ofGIGANTEAloci in yellow-poplar, monocots, and eudicots
Authors: Liang Haiying , Barakat Abdelali , Schlarbaum Scott E. , Mandoli Dina F. , Carlson John E. 
Published: July 2010

GIGANTEA plays an important role in the control of circadian rhythms and photoperiodic flowering. The GIGANTEA gene has been studied in various species, but not in basal angiosperms. Moreover, to the best of our knowledge, no study of the genome organization of a basal angiosperm has yet been published. In this study, we sequenced a bacterial artificial chromosome (BAC) harboring GIGANTEA from yellow-poplar ( Liriodendron tulipifera L.) and compared the genomic organization of this gene in yellow-poplar with that in other species from various angiosperm clades. This is the first report on the gene structure and organization of a large contig in any basal angiosperm species. The BAC clone, covering a region of approximately 122 kb from the yellow-poplar genome, was sequenced and assembled by coupling the 454 pyrosequencing technology with ABI capillary sequencing. In addition to GIGANTEA, the gene RPS18.A (encoding ribosomal protein S18.A) was found in this segment of the genome. We found that gene content and order in this region of the yellow-poplar genome were similar to those in the corresponding region in eudicots but not in Oryza sativa and Sorghum bicolor , implying that clustering of the GIGANTEA and RPS18.A genes is ancestral and separation of the genes occurred after the phylogenetic split of monocots from dicots. Phylogenetic analysis of GIGANTEA amino acid sequences placed yellow-poplar closer to eudicots than to monocots. In addition, evidence for transposition and large insertions and duplications was found, suggesting multiple and complex mechanisms of basal angiosperm genome evolution.
Regional-scale landslide susceptibility mapping using the weights of evidence method: an example applied to linear infrastructure
Authors: Quinn P. E. , Hutchinson D. J. , Diederichs M. S. , Rowe R. K. 
Published: July 2010

Large landslides are common in the gently sloping clay plains of the Saint Lawrence Lowlands of eastern Canada. These tend to occur along rivers carved into the marine soils deposited in the former Champlain Sea, which occupied the area roughly 10 000 years ago. This paper presents a landslide susceptibility model, developed at the regional scale using a bivariate statistical method: the weights of evidence method. The analysis considers the association of existing large landslides in a portion of the study area with key terrain features, such as ground elevation, flow accumulation in adjacent streams, soil type, soil thickness, and land use. The resulting model identifies three different levels of susceptibility: low, low to moderate, and moderate to high. These descriptors are related statistically to the probability of encountering existing large landslides within 500 m, 1 or 2 km, respectively. The model is tested along primary railway corridors and isolates 8% of the total length for further consideration of landslide hazard. Reconnaissance level air photo survey results further reduce the length of corridor with elevated susceptibility to 2% of the total length, thus focusing the application of additional resources to a very small proportion of the total inventory.
Large-deformation finite element analysis of pipe penetration and large-amplitude lateral displacement
Authors: Wang Dong , White David J. , Randolph Mark F. 
Published: July 2010

Seabed pipelines must be designed to accommodate thermal expansion — which is commonly achieved through controlled lateral buckling — and to resist damage from submarine slides. In both cases, the pipe moves laterally by a significant distance and the overall pipeline response is strongly influenced by the lateral pipe–soil resistance. Here, the process of pipe penetration and lateral displacement is investigated using a large-deformation finite element method, with a softening rate–dependent soil model being incorporated. The calculated soil flow mechanisms, pipe resistances, and trajectories agree well with plasticity solutions and centrifuge test data. It was found that the lateral resistance is strongly influenced by soil heave during penetration and the berm formed ahead of the pipe during lateral displacement. For “light” pipes, the pipe rises to the soil surface and the soil failure mechanism involves sliding at the base of the berm. In contrast, “heavy” pipes dive downwards and a deep shearing zone is mobilized, expanding with continuing lateral movement. The different responses are reconciled by defining an “effective embedment” that includes the effect of the soil berm or wall ahead of the pipe. The relationship between normalized lateral resistance and effective embedment is well fitted using a power law.
A novel approach for the improvement of ethanol fermentation by Saccharomyces cerevisiae
Authors: Hou Lihua , Cao Xiaohong , Wang Chunling 
Published: July 2010

Fermentation properties under the control of multiple genes are difficult to alter with traditional methods in Saccharomyces cerevisiae . Here, a novel genome engineering approach is developed to improve ethanol production in very high gravity fermentation with 300 g/L glucose as the carbon source. This strategy involved constructing aneuploid strains on the base of tetraploid cells. The tetraploid strain was constructed by using the plasmid YCplac33-GHK, which harbored the HO gene encoding the site-specific Ho endonucleases. The aneuploid strain, WT4-M, was selected and screened after the tetraploid cells were treated with methyl benzimidazole-2-yl-carbamate to induce loss of mitotic chromosomes. It was found that aneuploid strain WT4-M not only exhibited an increase in ethanol production and osmotic and thermal tolerance, but also an improvement in the sugar–ethanol conversion rate. Notably, WT4-M provided up to 9.8% improvement in ethanol production compared with the control strain. The results demonstrated that the strategy of aneuploidy was valuable for creating yeast strains with better fermentation characteristics.
Comparison of integron-linked antibiotic resistance genes in strains ofSalmonellaspp. isolated from swine in Chile in 2005 and 2008
Authors: Lapierre Lisette , San Martín Betty , Araya-Jordán Carolina , Borie Consuelo 
Published: July 2010

Salmonella spp. isolates obtained from healthy swine in 2008 were analyzed for antibiotic resistance phenotypes and genotypes. The resistance profiles of the 2008 isolates were compared with those of a Salmonella collection isolated from the same geographical area in 2005. The 2008 isolates consisted of strains that were 97% oxytetracycline resistant, 33.3% amoxicillin resistant, 31.8% amoxicillin- plus clavulanic acid resistant, 27.5% trimethoprim–sulfamethoxazole resistant, 17.3% streptomycin resistant, and 7.2% enrofloxacin–ciprofloxacin resistant. The presence of integrons and resistance genes and their topological association in resistant strains was assessed by PCR. The prevalence of class 1 integrons was the highest, at 46.2%, while class 2 integrons were present in 17.9% of the isolates. In strains that harboured class 1 integrons, we identified 3 different gene cassette arrangements; a single class 2 integron arrangement of dfrA1–sat1–aadA1 was found. Comparison of these results with data obtained from the 2005 isolates showed that Salmonella strains resistant to amoxicillin and amoxicillin plus clavulanic acid had clearly emerged over the span of 3 years, along with an increase in the prevalence of class 1 integrons and the acquisition of new gene cassette arrangements. These findings highlight the need for continual monitoring of regional isolates to establish more efficient vigilance programs that can address variations in resistance over short periods of time within the same geographical area.
Acute effects of endothelin receptor antagonists on hepatic hemodynamics of cirrhotic and noncirrhotic ratsThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Cavasin Maria A. , Semus Hillary , Pitts Kelly , Peng Yanyu , Sandoval Jennifer , Chapo Joseph , Plato Craig F. 
Published: July 2010

Hepatic and circulating endothelin-1 (ET-1) are increased in patients with cirrhosis and in cirrhotic animals. However, the distinct roles of ET receptor subtypes ETAand ETBin cirrhosis and portal hypertension (PHT) have not been clearly elucidated. Thus, we studied the effects of selective ET-1 antagonists (ETA-ant or ETB-ant) and nonselective ET-1 antagonist (ETA/B-ant) on hepatic hemodynamics in cirrhotic rats. Liver fibrosis and PHT were induced by complete bile duct ligation (BDL) in rats. Two weeks after BDL or sham surgery, hemodynamic responses were measured during intraportal infusion of incremental doses of the following ET-ants: (i) BQ-123, (ii) BQ-788, and (iii) bosentan. After equilibration with vehicle, doses of ET-ants were infused for 30 min periods, and steady-state systemic and hepatic hemodynamics, portal venous pressure (PVP), and hepatic blood flow (HBF) were measured. BDL induced significant PHT and elevated concentrations of plasma ET-1 compared with sham. ETA-ant decreased PVP of cirrhotic rats but had no effect on sham, whereas ETB-ant increased PVP in sham but had no effect in BDL. Nonselective ETA/B-ant decreased PVP of BDL similarly to ETA-ant. Both ETA-ant and ETB-ant decreased local HBF, whereas a nonselective antagonist did not change HBF in sham; however no significant changes were observed in HBF of BDL rats with any of the antagonists. These findings suggest ETAactivation contributes to PHT in cirrhotic rats, whereas ETB-mediated portal depressor effects are attenuated in cirrhotic rats compared with noncirrhotic rats.
Combination therapy of zibotentan with cisplatinum and paclitaxel is an effective regimen for epithelial ovarian cancerThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Rosanò Laura , Cianfrocca Roberta , Spinella Francesca , Di Castro Valeriana , Natali Pier Giorgio , Bagnato Anna 
Published: July 2010

In human ovarian carcinoma, the endothelin-1 (ET-1) / endothelin A receptor (ETAR) axis is overexpressed, correlating with tumor grade. Moreover, ETAR activation by ET-1 affects cell proliferation, survival, angiogenesis, and invasion. ETAR blockade with zibotentan (ZD4054), a specific ETAR antagonist, significantly inhibits ovarian cancer growth in vitro and in vivo, underscoring the relevance of this pathway as a target for cancer therapy. Since clinical trial results have defined the combination of platinum and taxane as the standard of care in the management of ovarian cancer, here we explored the therapeutic efficacy of the integration of zibotentan with cytotoxic drugs having different modes of action. We found that the combination of zibotentan with cisplatinum as well as zibotentan with paclitaxel was more effective at inhibiting ovarian cancer HEY cell proliferation induced by endogenous ET-1 than were the single agents alone. However, a significantly enhanced efficacy was observed when we combined zibotentan, cisplatinum, and paclitaxel. Accordingly, in HEY xenografts the coadministration of zibotentan with cisplatinum enhanced the efficacy of the cytotoxic drug alone in controlling tumor growth, associated with reduction in proliferation index and microvessel density. Remarkably, the combination of zibotentan with both cisplatinum and paclitaxel was very effective in inhibiting tumor growth, neovascularization, and cell proliferation, representing a preclinical endpoint to guide combination therapy in clinical trials.
Mitochondrial Chaperone Trap1 and the Calcium Binding Protein Sorcin Interact and Protect Cells against Apoptosis Induced by Antiblastic Agents
Authors: Landriscina Matteo , Laudiero Gabriella , Maddalena Francesca , Amoroso Maria Rosaria , Piscazzi Annamaria , Cozzolino Flora , Monti Maria , Garbi Corrado , Fersini Alberto , Pucci Piero , Esposito Franca 
Published: July 2010

Abstract
TRAP1, a mitochondrial chaperone (Hsp75) with antioxidant and antiapoptotic functions, is involved in multidrug resistance in human colorectal carcinoma cells. Through a proteomic analysis of TRAP1 coimmunoprecipitation complexes, the Ca2+-binding protein Sorcin was identified as a new TRAP1 interactor. This result prompted us to investigate the presence and role of Sorcin in mitochondria from human colon carcinoma cells. Using fluorescence microscopy and Western blot analysis of purified mitochondria and submitochondrial fractions, we showed the mitochondrial localization of an isoform of Sorcin with an electrophoretic motility lower than 20 kDa that specifically interacts with TRAP1. Furthermore, the effects of overexpressing or downregulating Sorcin and/or TRAP1 allowed us to demonstrate a reciprocal regulation between these two proteins and to show that their interaction is required for Sorcin mitochondrial localization and TRAP1 stability. Indeed, the depletion of TRAP1 by short hairpin RNA in colorectal carcinoma cells lowered Sorcin levels in mitochondria, whereas the depletion of Sorcin by small interfering RNA increased TRAP1 degradation. We also report several lines of evidence suggesting that intramitochondrial Sorcin plays a role in TRAP1 cytoprotection. Finally, preliminary evidence that TRAP1 and Sorcin are both implicated in multidrug resistance and are coupregulated in human colorectal carcinomas is provided. These novel findings highlight a new role for Sorcin, suggesting that some of its previously reported cytoprotective functions may be explained by involvement in mitochondrial metabolism through the TRAP1 pathway. Cancer Res; 70(16); 6577–86. ©2010 AACR.
Low-Field Magnetic Resonance Imaging to Visualize Chronic and Cycling Hypoxia in Tumor-Bearing Mice
Authors: Yasui Hironobu , Matsumoto Shingo , Devasahayam Nallathamby , Munasinghe Jeeva P. , Choudhuri Rajani , Saito Keita , Subramanian Sankaran , Mitchell James B. , Krishna Murali C. 
Published: July 2010

Abstract
Tumors exhibit fluctuations in blood flow that influence oxygen concentrations and therapeutic resistance. To assist therapeutic planning and improve prognosis, noninvasive dynamic imaging of spatial and temporal variations in oxygen partial pressure (pO2) would be useful. Here, we illustrate the use of pulsed electron paramagnetic resonance imaging (EPRI) as a novel imaging method to directly monitor fluctuations in oxygen concentrations in mouse models. A common resonator platform for both EPRI and magnetic resonance imaging (MRI) provided pO2 maps with anatomic guidance and microvessel density. Oxygen images acquired every 3 minutes for a total of 30 minutes in two different tumor types revealed that fluctuation patterns in pO2 are dependent on tumor size and tumor type. The magnitude of fluctuations in pO2 in SCCVII tumors ranged between 2- to 18-fold, whereas the fluctuations in HT29 xenografts were of lower magnitude. Alternating breathing cycles with air or carbogen (95% O2 plus 5% CO2) distinguished higher and lower sensitivity regions, which responded to carbogen, corresponding to cycling hypoxia and chronic hypoxia, respectively. Immunohistochemical analysis suggests that the fluctuation in pO2 correlated with pericyte density rather than vascular density in the tumor. This EPRI technique, combined with MRI, may offer a powerful clinical tool to noninvasively detect variable oxygenation in tumors. Cancer Res; 70(16); 6427–36. ©2010 AACR.