Antileukemic activity of aminoparthenolide analogs

A series of aminoparthenolide analogs have been synthesized through a diastereoselective conjugate addition of several primary and secondary amines to the α-methylene-γ-butyrolactone function of the very lipophilic sesquiterpene lactone, parthenolide. Seventeen of the above amines derivatives were evaluated in a full panel of 60 cancer cell lines for anticancer activity. Compound 12, derived from tyramine, was found to be cytostatic as well as cytotoxic toward acute lymphoblastic leukemia cells (ALL, CCRF-CEM) at nanomolar concentrations, while the (R)-(1,2,3,4-tetrahydro-1-naphthyl)amino derivative 9 was found to be cytostatic toward human anaplastic large T-cell lymphoma (SR) cells at concentrations below 10 nM.     

Fecundity and Longevity of Green Vegetable Bug,Nezara viridula, Following Parasitism byTrichopoda giacomellii

The effects of parasitism by the ArgentinianTrichopoda giacomellii(Blanchard) on reproduction and longevity of its host,Nezara viridula(L.) are reported. Parasitoid larvae suppress egg maturation, reducing by 70% the fecundity of mature female hosts during the period of larval development. Egg viability was not affected, but mating frequency was reduced by approximately 50%. When parasitized as newly eclosed adults, 84% of females fail to reproduce. In male hosts, fertility and mating frequency were not affected during the period of larval parasitoid development. In male and reproductively immature female hosts, death was coincident with, or occurred shortly after parasitoid emergence (2–4 days); in mature females, death occurred on average 2 weeks after larval parasitoid emergence. Host mortality occurred as a consequence of tissue damage incurred as the parasitoid larvae emerged from the host. Some individuals survived parasitism though no further reproductive activity (mating or oviposition) occurred. The effectiveness ofT. giacomelliias a biological control agent is discussed in relation to its impact on reproduction and survival of its host and contrasted with the action of otherTrichopodaspecies.     

External thoracic scent efferent system of Scutelleridae (Hemiptera: Heteroptera)

The metathoracic scent glands in the Heteroptera produce defence secretions which are spread outside the body through and by using the thoracic external scent efferent system. That complex system was studied in 18 species from 11 genera of four subfamilies, Elvisurinae, Eurygastrinae, Hoteinae and Scutellerinae of the family Scutelleridae (Pentatomoidea). The results have been compared with published data. The pattern of that system is more consistent at the level of genus, mostly very similar in the congeneric species, but mostly variable within higher taxonomic levels, tribes and subfamilies. Five types of the external scent efferent system are recognized within the family Scutelleridae, basic two of them in studied species: (i) peritreme well developed, covering large part of metapleuron, evaporatorium small, developed only on metapleuron, (ii) evaporatorium large, more conspicuous than moderate-sized to small peritreme, extending to mesopleuron as large structure. The results do not support a hypothesis that the system of structures associated externally with metathoracic scent glands is in correlation with type of a habitat. However, these structures are well usable as diagnostic characters for scutellerid genera (e.g. Cantao, Hyperonchus, Scutellera and Solenosthedium).     

Methods and approaches for the comprehensive characterization and quantification of cellular proteomes using mass spectrometry.

Proteomics has been proposed as one of the key technologies in the postgenomic era. So far, however, the comprehensive analysis of cellular proteomes has been a challenge because of the dynamic nature and complexity of the multitude of proteins in cells and tissues. Various approaches have been established for the analyses of proteins in a cell at a given state, and mass spectrometry (MS) has proven to be an efficient and versatile tool. MS-based proteomics approaches have significantly improved beyond the initial identification of proteins to comprehensive characterization and quantification of proteomes and their posttranslational modifications (PTMs). Despite these advances, there is still ongoing development of new technologies to profile and analyze cellular proteomes more completely and efficiently. In this review, we focus on MS-based techniques, describe basic approaches for MS-based profiling of cellular proteomes and analysis methods to identify proteins in complex mixtures, and discuss the different approaches for quantitative proteome analysis. Finally, we briefly discuss novel developments for the analysis of PTMs. Altered levels of PTM, sometimes in the absence of protein expression changes, are often linked to cellular responses and disease states, and the comprehensive analysis of cellular proteome would not be complete without the identification and quantification of the extent of PTMs of proteins.     

Nonlinear effects of temperature on body form and developmental canalization in the threespine stickleback

Theoretical models predict that nonlinear environmental effects on the phenotype also affect developmental canalization, which in turn can influence the tempo and course of organismal evolution. Here, we used an oceanic population of threespine stickleback (Gasterosteus aculeatus) to investigate temperature‐induced phenotypic plasticity of body size and shape using a paternal half‐sibling, split‐clutch experimental design and rearing offspring under three different temperature regimes (13, 17 and 21 °C). Body size and shape of 466 stickleback individuals were assessed by a set of 53 landmarks and analysed using geometric morphometric methods. At approximately 100 days, individuals differed significantly in both size and shape across the temperature groups. However, the temperature‐induced differences between 13 and 17 °C (mainly comprising relative head and eye size) deviated considerably from those between 17 and 21 °C (involving the relative size of the ectocoracoid, the operculum and the ventral process of the pelvic girdle). Body size was largest at 17 °C. For both size and shape, phenotypic variance was significantly smaller at 17 °C than at 13 and 21 °C, indicating that development is most stable at the intermediate temperature matching the conditions encountered in the wild. Higher additive genetic variance at 13 and 21 °C indicates that the plastic response to temperature had a heritable basis. Understanding nonlinear effects of temperature on development and the underlying genetics are important for modelling evolution and for predicting outcomes of global warming, which can lead not only to shifts in average morphology but also to destabilization of development.     

Lung epithelial cells release ATP during ozone exposure: signaling for cell survival

The common air pollutant ozone causes acute toxicity to human airways. In primary and transformed epithelial cells from all levels of human or rat airways, ozone levels relevant to air pollution (50-200 ppb) increased extracellular [ATP] within 7-30 min. A human bronchial epithelial cell line (16HBE14o(-)) that forms electrically resistant polarized monolayers had up to 10-fold greater apical than basolateral surface extracellular [ATP] within 7 min of ozone exposure. Increased extracellular [ATP] appeared due to ATP secretion or release because (1) inhibition of ectonucleotidase (cell surface enzyme(s) which degrade ATP) by ozone did not occur until >120 min of ozone exposure and (2) brefeldin A, a secretory inhibitor, eliminated elevation of extracellular [ATP] without affecting intracellular ATP. Extracellular ATP protected against ozone toxicity in a P2Y receptor-dependent manner as (1) removal of ATP and adenosine by apyrase and adenosine deaminase, respectively, potentiated ozone toxicity, (2) extracellular supplementation with ATP, a poorly hydrolyzable ATP analog ATPgammaS, or UTP inhibited apoptotic and necrotic ozone-mediated cell death, and (3) ATP-mediated protection was eliminated by P2 and P2Y receptor inhibitors suramin and Cibacron blue (reactive blue 2), respectively. The decline in glucose uptake caused by prolonged ozone exposure was prevented by supplemental extracellular ATP, an effect blocked by suramin. Further, Akt and ERK phosphorylation resulted from exposure to supplemental extracellular ATP. Thus, extracellularly released ATP signals to prevent ozone-induced death and supplementation with ATP or its analogs can augment protection, at least in part via Akt and /or ERK signaling pathways and their metabolic effects.     

Genetic Diversity of Brazilian Aedes aegypti: Patterns following an Eradication Program

Background

Aedes aegypti is the most important vector of dengue fever in Brazil, where severe epidemics have recently taken place. Ae. aegypti in Brazil was the subject of an intense eradication program in the 1940s and 50s to control yellow fever. Brazil was the largest country declared free of this mosquito by the Pan-American Health Organization in 1958. Soon after relaxation of this program, Ae. aegypti reappeared in this country, and by the early 1980s dengue fever had been reported. The aim of this study is to analyze the present-day genetic patterns of Ae. aegypti populations in Brazil.

Methodology/Principal Findings

We studied the genetic variation in samples of 11 widely spread populations of Ae. aegypti in Brazil based on 12 well-established microsatellite loci. Our principal finding is that present-day Brazilian Ae. aegypti populations form two distinct groups, one in the northwest and one in the southeast of the country. These two groups have genetic affinities to northern South American countries and the Caribbean, respectively. This is consistent with what has been reported for other genetic markers such as mitochondrial DNA and allele frequencies at the insecticide resistance gene, kdr.

Conclusions/Significance

We conclude that the genetic patterns in present day populations of Ae. aegypti in Brazil are more consistent with a complete eradication of the species in the recent past followed by re-colonization, rather than the alternative possibility of expansion from residual pockets of refugia. At least two colonizations are likely to have taken place, one from northern South American countries (e.g., Venezuela) that founded the northwestern group, and one from the Caribbean that founded the southeastern group. The proposed source areas were never declared free of Ae. aegypti.     

Clustered miRNAs and their role in biological functions and diseases

MicroRNAs (miRNAs) are endogenous, small non‐coding RNAs known to regulate expression of protein‐coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein‐coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self‐renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.