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311.
Stephen J. P. Blake Alan L. H. Ching Tony J. Kenna Ryan Galea Justin Large Hideo Yagita Raymond J. Steptoe 《PloS one》2015,10(3)
Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells. 相似文献
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313.
Andrew J. Kroll Tiffany S. Garcia Jay E. Jones Katie Dugger Blake Murden Josh Johnson Summer Peerman Ben Brintz Michael Rochelle 《PloS one》2015,10(11)
Plethodontid salamanders are diverse and widely distributed taxa and play critical roles in ecosystem processes. Due to salamander use of structurally complex habitats, and because only a portion of a population is available for sampling, evaluation of sampling designs and estimators is critical to provide strong inference about Plethodontid ecology and responses to conservation and management activities. We conducted a simulation study to evaluate the effectiveness of multi-scale and hierarchical single-scale occupancy models in the context of a Before-After Control-Impact (BACI) experimental design with multiple levels of sampling. Also, we fit the hierarchical single-scale model to empirical data collected for Oregon slender and Ensatina salamanders across two years on 66 forest stands in the Cascade Range, Oregon, USA. All models were fit within a Bayesian framework. Estimator precision in both models improved with increasing numbers of primary and secondary sampling units, underscoring the potential gains accrued when adding secondary sampling units. Both models showed evidence of estimator bias at low detection probabilities and low sample sizes; this problem was particularly acute for the multi-scale model. Our results suggested that sufficient sample sizes at both the primary and secondary sampling levels could ameliorate this issue. Empirical data indicated Oregon slender salamander occupancy was associated strongly with the amount of coarse woody debris (posterior mean = 0.74; SD = 0.24); Ensatina occupancy was not associated with amount of coarse woody debris (posterior mean = -0.01; SD = 0.29). Our simulation results indicate that either model is suitable for use in an experimental study of Plethodontid salamanders provided that sample sizes are sufficiently large. However, hierarchical single-scale and multi-scale models describe different processes and estimate different parameters. As a result, we recommend careful consideration of study questions and objectives prior to sampling data and fitting models. 相似文献
314.
Excess body mass index‐ and waist circumference‐years and incident cardiovascular disease: The CARDIA study 下载免费PDF全文
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316.
Richard T. Addo Kenneth Davis Ruhi Ubale Joel S. Owen E. Blake Watkins 《AAPS PharmSciTech》2015,16(1):30-34
Proton pump inhibitors (PPIs) are used extensively for the relief of gastroesophageal reflux, peptic ulcers, and other hypersecretory conditions. Some of the commonly used PPIs—omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole—were used in this study with the aim of developing a rapid ultra performance liquid chromatography (UPLC) method for detecting each and allowing separation and quantification of a mixture of PPIs. An analysis of samples was performed on a UPLC system equipped with a quaternary solvent delivery system, a refrigerated sample manager, a column heater, a photo diode array detector scanning from 210 to 400 nm, and a C18 analytical column (50 mm × 3.0 mm, 1.7-μm particle size). The chromatographic analysis of the PPI samples and standards was performed using gradient elution with acetonitrile and water. The calibration curve range varied for each of the PPIs ranging from a lower limit of 0.75–1.78 μg/mL to a maximum concentration of 200 μg/mL with a regression coefficient (r2) of ≥0.98. The accuracy and precision were calculated, and the %RSD was determined to be ≤0.21% (intraday) and ≤5% (interday). The LOD was 0.23–0.59 μg/mL and the LOQ was 0.71–1.78 μg/mL for each of the drugs analyzed. The method was capable of detecting and quantifying each drug in a mixture with good resolution and a total run time of less than 5 min. Herein, we report an efficient and rapid analytical method for the simultaneous detection of multiple PPIs in a mixture.KEY WORDS: HPLC, method development, proton pump inhibitors, simultaneous analysis, UPLC 相似文献
317.
Comparison of a Modified Mid‐Coronal Sectioning Technique and Wilson's Technique when Conducting Eye and Brain Examinations in Rabbit Teratology Studies 下载免费PDF全文
318.
Guangxi Wu He Zhao Chenhao Li Menaka Priyadarsani Rajapakse Wing Cheong Wong Jun Xu Charles W. Saunders Nancy L. Reeder Raymond A. Reilman Annika Scheynius Sheng Sun Blake Robert Billmyre Wenjun Li Anna Floyd Averette Piotr Mieczkowski Joseph Heitman Bart Theelen Markus S. Schr?der Paola Florez De Sessions Geraldine Butler Sebastian Maurer-Stroh Teun Boekhout Niranjan Nagarajan Thomas L. Dawson Jr. 《PLoS genetics》2015,11(11)
Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are associated with common skin disorders. To characterize the genetic basis of the unique phenotypes of Malassezia spp., we sequenced the genomes of all 14 accepted species and used comparative genomics against a broad panel of fungal genomes to comprehensively identify distinct features that define the Malassezia gene repertoire: gene gain and loss; selection signatures; and lineage-specific gene family expansions. Our analysis revealed key gene gain events (64) with a single gene conserved across all Malassezia but absent in all other sequenced Basidiomycota. These likely horizontally transferred genes provide intriguing gain-of-function events and prime candidates to explain the emergence of Malassezia. A larger set of genes (741) were lost, with enrichment for glycosyl hydrolases and carbohydrate metabolism, concordant with adaptation to skin’s carbohydrate-deficient environment. Gene family analysis revealed extensive turnover and underlined the importance of secretory lipases, phospholipases, aspartyl proteases, and other peptidases. Combining genomic analysis with a re-evaluation of culture characteristics, we establish the likely lipid-dependence of all Malassezia. Our phylogenetic analysis sheds new light on the relationship between Malassezia and other members of Ustilaginomycotina, as well as phylogenetic lineages within the genus. Overall, our study provides a unique genomic resource for understanding Malassezia niche-specificity and potential virulence, as well as their abundance and distribution in the environment and on human skin. 相似文献
319.
Giok S. Liem Frankie K. F. Mo Elizabeth Pang Joyce J. S. Suen Nelson L. S. Tang Kun M. Lee Claudia H. W. Yip Wing H. Tam Rita Ng Jane Koh Christopher C. H. Yip Grace W. S. Kong Winnie Yeo 《PloS one》2015,10(10)