Air pollution and allergic airway diseases

In the last decades, many studies have shown an increase in the prevalence of allergic rhinitis and asthma mainly in urban communities, especially in industrialized countries. Airborne pollutants such as diesel exhaust particles, ozone, nitrogen dioxide and sulphur dioxide have been implicated in the initiation and exacerbation of allergic airway diseases. Epidemiologic studies have shown clear associations between air pollution and allergic diseases, in vivo and in vitro studies have provided biologic link and potential molecular mechanisms. Particulate and gaseous pollutants can act both on the upper and lower airways to initiate and exacerbate cellular inflammation through interaction with the innate immune system. As a consequence, increased non-specific airway hyper-responsiveness and airway resistance have been observed in man. Diesel exhaust particles can both induce and exacerbate in vivo allergic responses. They can also modify the immune system's handling of the allergen. The effects of gaseous pollutants on immune responses to allergens are not fully understood. We review the different mechanisms involved in the enhancement of allergic inflammation by urban air pollutants, including effects on cytokine and chemokine production, as well as activation of different immune cells. We discuss the hypothesis that pollutants' effects on the immune system involve hierarchical oxidative stress. Susceptibility genes to air pollution inducing allergic diseases are also discussed.     

Ionizing radiation induces a Yap1-dependent peroxide stress response in yeast

Repair of DNA damage is fundamental for cellular tolerance to ionizing radiation (IR) and many IR-induced DNA lesions are thought to occur as a result of oxidative stress. We investigated the physiological effects of IR in Saccharomyces cerevisiae by performing protein expression profiles in cells exposed to electron pulse irradiation. Transient induction of several antioxidant enzymes in wild-type cells, but not in cells lacking the oxidative stress regulator Yap1, indicated that IR exposure causes cellular oxidative stress. Yap1 activation involved oxidation to the intramolecular disulfide bond, a signature of activation by peroxide, and was dependent on the Yap1 peroxide sensor Orp1/Gpx3. H(2)O(2) was produced in the culture medium of irradiated cells and was both necessary and sufficient for IR-induced Yap1 activation. When IR was performed in the presence of N(2)O, obviating H(2)O(2) production and increasing hydroxyl radical ((*)OH) production, the Yap1 response was lost, indicating that Yap1 was unable to respond to (*)OH or (*)OH-induced damage. However, the Yap1 response to IR did not seem to be a primary determinant of cellular IR tolerance. Altogether, these data provide a molecular demonstration that cells experience in vivo peroxide stress during IR and indicate that the H(2)O(2) produced cannot account for IR toxicity.     

Visualization of ribonucleotide reductase catalytic oxidation establishes thioredoxins as its major reductants in yeast

Thioredoxins and/or glutaredoxins assist ribonucleotide reductase, and other such enzymes that require disulfide bond reduction during their catalytic cycle. In Saccharomyces cerevisiae, the presence of either pathway is essential but which of these pathways operates in ribonucleotide reductase reduction and how this function contributes to the pathways' essential nature have not been definitively established. We have identified two in vivo redox forms of the S. cerevisiae ribonucleotide reductase R1 subunit, which correspond to catalytically reduced or oxidized enzymes. Cells lacking thioredoxins, which exhibit an elongated S phase, accumulate R1 in its oxidized form and also contain significantly decreased deoxyribonucleotide levels during the S phase. Overexpressing R1 in these cells increases both the amount of the R1 reduced form and the concentrations of deoxyribonucleotides and accelerates DNA replication. These results establish thioredoxins as the major RNR reducing system in yeast and indicate that impaired RNR reduction accounts for the S phase defects of thioredoxin-deficient cells.     

Expanding neuronal layers by the local division of committed precursors

A general strategy in vertebrate neural development is for neuronal precursors to stop dividing, to begin to differentiate, and then to migrate to their final destination. In this issue of Neuron, however, Godhino et al. provide evidence that some neuronal precursors undergo a terminal symmetric cell division at their final destination to form an entire neuronal layer.     

The genome of <Emphasis Type="Italic">Apis mellifera</Emphasis>: dialog between linkage mapping and sequence assembly

Two independent genome projects for the honey bee, a microsatellite linkage map and a genome sequence assembly, interactively produced an almost complete organization of the euchromatic genome. Assembly 4.0 now includes 626 scaffolds that were ordered and oriented into chromosomes according to the framework provided by the third-generation linkage map (AmelMap3). Each construct was used to control the quality of the other. The co-linearity of markers in the sequence and the map is almost perfect and argues in favor of the high quality of both.     

Conceptual bases for quantifying the role of the environment on gene evolution: the participation of positive selection and neutral evolution

To demonstrate that a given change in the environment has contributed to the emergence of a given genotypic and phenotypic shift during the course of evolution, one should ask to what extent such shifts would have occurred without environmental change. Of course, such tests are rarely practical but phenotypic novelties can still be correlated to genomic shifts in response to environmental changes if enough information is available. We surveyed and re-evaluated the published data in order to estimate the role of environmental changes on the course of species and genomic evolution. Only a few published examples clearly demonstrate a causal link between a given environmental change and the fixation of a genomic variant resulting in functional modification (gain, loss or alteration of function). Many others suggested a link between a given phenotypic shift and a given environmental change but failed to identify the underlying genomic determinant(s) and/or the associated functional consequence(s). The proportion of genotypic and phenotypic variation that is fixed concomitantly with environmental changes is often considered adaptive and hence, the result of positive selection, even though alternative causes, such as genetic drift, are rarely investigated. Therefore, the second aim herein is to review evidence for the mechanisms leading to fixation.     

The differential expression of ribosomal 18S RNA paralog genes from the chaetognath <Emphasis Type="Italic">Spadella cephaloptera</Emphasis>

Chaetognaths constitute a small marine phylum of approximately 120 species. Two classes of both 18S and 28S rRNA gene sequences have been evidenced in this phylum, even though significant intraindividual variation in the sequences of rRNA genes is unusual in animal genomes. These observations led to the hypothesis that this unusual genetic characteristic could play one or more physiological role(s). Using in situ hybridization on the frontal sections of the chaetognath Spadella cephaloptera, we found that the 18S Class I genes are expressed in the whole body, with a strong expression throughout the gut epithelium, whereas the expression of the 18S Class II genes is restricted to the oocytes. Our results could suggest that the paralog products of the 18S Class I genes are probably the "housekeeping" 18S rRNAs, whereas those of class II would only be essential in specific tissues. These results provide support for the idea that each type of 18S paralog is important for specific cellular functions and is under the control of selective factors.     

French tradition and the rise of Evo-devo

The limited value most French biologists attributed to Darwinism and Mendelism in the first half of the twentieth century, and their conviction that these theories were at best insufficient to explain evolution and development, probably created conditions propitious to the development of Evo-devo at the end of the century. The separation between embryology and evolution did not exist in French biology as it did in American genetics: explanations for these two phenomena were sought equally in the “organization” of the egg. The major contribution of French biologists to Evo-devo was clearly the invention of the notion of the regulatory gene by Jacob and Monod; not the operon model per se, but the introduction of a hierarchy between two different kinds of genes. The consequence, the rise of the developmental gene concept, was not immediate, and required the active role of other biologists such as Antonio Garcia-Bellido, Allan Wilson and Stephen Jay Gould. Various obstacles had to be overcome for this concept of developmental gene to be fully accepted.     

Production of <Emphasis Type="Italic">in vitro</Emphasis> amplified DNA pseudolibraries and high-throughput cDNA target amplification

Background  

Many structural biology- and high-throughput laboratories experience the acquisition of multiple cDNAs from different sources as a rather time- and resource-consuming procedure. The techniques presented here solve these problems.