Epithelium Expressing the E7 Oncoprotein of HPV16 Attracts Immune-Modulatory Dendritic Cells to the Skin and Suppresses Their Antigen-Processing Capacity

Antigen presenting cells (APCs) in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV) infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.     

Temporal Variation in Seed Predation by Insects in a Population of Syagrus romanzoffiana (Arecaceae) in Santa Catarina Island, SC, Brazil

Insect seed predation may vary depending on seed production. The present study considers the hypothesis that the rates of seed predation tend to be smaller in years of higher fruit production. Thus, we monitored the production of fruits and predation of seeds of the palm Syagrus romanzoffiana over 2?years in the Atlantic Forest (Parque Municipal da Lagoa do Peri, Florianópolis, SC, Brazil), between July 2006 and June 2008. Plots of 0.25?m² were fitted under 20 mother plants and fruits were monthly collected for assessment of abundance and seed predation. There was variation in fruit production between the 2?years and among reproductive plants. Predation rates were high and occurred in the predispersal phase by the Curculionidae Revena rubiginosa Boheman, Anchylorhynchus aegrotus Fahraeus, and Anchylorhynchus variabilis Gyllenhal. Seed predation by these species of Anchylorhynchus is first registered in the present study. In average, about 60% of the seeds monthly produced in the population tend to escape insect predation in year of high or low production, becoming available for recruitment. The predation rate was not related to the amount of fruits produced per reproductive plant. Also, different than expected, there was a positive relation between the rates of seed predation and the total of fruits produced monthly on the plots. Thus, no evidence for the satiation of insect seed predators was found in this study with S. romanzoffiana.     

Studies on PVP hydrogel-supported luminol chemiluminescence: 2. Luminometer calibration and potential analytical applications.

The use of poly(N-vinyl-2-pyrrolidone) (PVP) hydrogel-supported luminol chemiluminescence (CL) for the automatic determination of hydrogen peroxide and the quantification of the antiradical capacity of Trolox is described. The hydrogel containing luminol and hemin is prepared directly on a 96-well microplate and can be stored for up to 3 months without significant decrease in CL quantum yields. Furthermore, this system can also be used as a secondary light standard for the calibration of microplate luminometers.     

Is Bagging Effective in the Classification of Small-Sample Genomic and Proteomic Data?

There has been considerable interest recently in the application of bagging in the classification of both gene-expression data and protein-abundance mass spectrometry data. The approach is often justified by the improvement it produces on the performance of unstable, overfitting classification rules under small-sample situations. However, the question of real practical interest is whether the ensemble scheme will improve performance of those classifiers sufficiently to beat the performance of single stable, nonoverfitting classifiers, in the case of small-sample genomic and proteomic data sets. To investigate that question, we conducted a detailed empirical study, using publicly-available data sets from published genomic and proteomic studies. We observed that, under t-test and RELIEF filter-based feature selection, bagging generally does a good job of improving the performance of unstable, overfitting classifiers, such as CART decision trees and neural networks, but that improvement was not sufficient to beat the performance of single stable, nonoverfitting classifiers, such as diagonal and plain linear discriminant analysis, or 3-nearest neighbors. Furthermore, as expected, the ensemble method did not improve the performance of these classifiers significantly. Representative experimental results are presented and discussed in this work.     

Interior decoration: Tropomyosin in actin dynamics and cell migration

Cell migration and invasion requires the precise temporal and spatial orchestration of a variety of biological processes. Filaments of polymerized actin are critical players in these diverse processes, including the regulation of cell anchorage points (both cell-cell and cell-extracellular matrix), the uptake and delivery of molecules via endocytic pathways and the generation of force for both membrane protrusion and retraction. How the actin filaments are specialized for each of these discrete functions is yet to be comprehensively elucidated. The cytoskeletal tropomyosins are a family of actin associating proteins that form head-to-tail polymers which lay in the major groove of polymerized actin filaments. In the present review we summarize the emerging isoform-specific functions of tropomyosins in cell migration and invasion and discuss their potential roles in the specialization of actin filaments for the diverse cellular processes that together regulate cell migration and invasion.Key words: tropomyosin, actin, migration, invasion, cytoskeleton, actin dynamics, adhesionActin is the most abundant protein in eukaryotic cells and is critical for maintaining structural integrity. The polymerization of globular (G)-actin monomers forms actin filaments (F-actin),¹ which play a role in diverse and complex cellular functions including intercellular transport of organelles and vesicles,^2,3 cytokinesis,⁴ apoptosis⁵ and cell motility.⁶ Intricate details describing the molecular scale interactions between regulatory proteins and actin have been extensively investigated but the mechanistic control of diverse actin filament functions remain largely unclear. Recent improvements in analysis techniques⁷ and the use of physiologically relevant models of 3D cell culturing⁸ have now begun to reveal mechanisms of actin cytoskeleton regulation. Accruing evidence suggests that the actin decorating protein tropomyosin is a key regulator of actin filament specialization. Of particular interest is the impact that tropomyosin regulation has on actin filament activity during cell migration and invasion that underpins immunological cell homing, development, wound healing and metastasis.     

Prodrug thiamine analogs as inhibitors of the enzyme transketolase

Transketolase, a key enzyme in the pentose phosphate pathway, has been suggested as a target for inhibition in the treatment of cancer. Compound 5a ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of the transketolase cofactor thiamine, is a potent transketolase inhibitor but suffers from poor pharmacokinetics due to high clearance and C(max) linked toxicity. An efficient way of improving the pharmacokinetic profile of 5a is to prepare oxidized prodrugs which are slowly reduced in vivo yielding longer, sustained blood levels of the drug. The synthesis of such prodrugs and their evaluation in rodent models is reported.     

Studies on the mitogenic effect of transferrin by membrane signal transduction

One of the earliest events leading to cell activation and growth is the hydrolysis of inositol phospholipids producing various membrane signals induced by an interaction between growth factors or hormones with their respective receptors on the cell membrane [1].To demonstrate the mitogenic action of transferrin,our results show that an addition of transferrin to “serum-deprived” rat hepatoma cells produced a rapid but transient rise in inositol 1,4,5-trisphosphate(IP3) level,and at the same time,an increased intracellular Ca^2 activity and a cytoplasmic alkalinization were observed.These signal transductions further lend support to the mitogenic nature of transferrin.In addition,a possible link between the receptor-mediated endocytosis of transferrin with the generation of intracellular signals is discussed herewith.     

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1

Background  

Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear.     

Chemical composition, seasonal variation, and biosynthetic considerations of essential oils from Baccharis microdonta and B. elaeagnoides (Asteraceae)

The chemical composition and seasonal variation throughout one year of the essential oils from leaves of Baccharis microdonta and B. elaeagnoides, collected in Campos do Jordão, SP, were investigated. The composition of the latter species has been described for the first time. By GC (RI) and GC/MS analysis, 43 compounds were identified, and a predominance of oxygenated sesquiterpene derivatives was found in both species. The main components of the B. microdonta oils were elemol ( 31 ; 11.7–30.6%), spathulenol ( 34 ; 4.7–9.1%), β‐caryophyllene ( 19 ; 3.7–6.2%), and germacrene D ( 24 ; 2.9–12.2%), and those of the B. elaeagnoides oils were 34 (10.1–21.5%), viridiflorol ( 35 ; 3.6–18.4%), 24 (0.9–13.8%), and 19 (3.5–9.4%). The identified compounds were grouped according to their respective C‐skeletons, and the percentages of occurrence of the C‐skeletons in the essential oils of leaves collected in the four seasons allowed identifying the preferential accumulation of different types of C‐skeletons as well as the seasonal variation of the biosynthetic routes over the studied period.     

Evolutionary dynamics of mating system shifts in Arabidopsis lyrata

Outcrossing is the prevalent mode of reproduction in plants and animals despite its substantial costs, while selfing and mixed mating occur at much lower frequency. Comparative research on plants has demonstrated the lability of self‐incompatibility, but there is little information about the transition on a within‐species level from self‐incompatibility to predominant selfing. We studied variation in mating system among 18 populations of Arabidopsis lyrata within a phylogenetic context to shed light on the evolution of selfing. Realized and potential mating systems were assessed by genetic analysis with microsatellite markers and hand‐self‐pollinations on 30 plants from each population. The fraction of self‐incompatible plants in a population was highly correlated with the outcrossing rate, showing that the spread of self‐compatibility is accompanied by or soon followed by an increase in the rate of selfing. The four predominantly selfing populations (outcrossing rates < 0.25) fell into more than one phylogenetic cluster, suggesting that the transition to selfing occurred more than once independently. Hence, A. lyrata offers an opportunity for the comparative analysis of outcrossing as a predominant mode of reproduction in plants and of the causes of the shift to selfing.