Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes

Background  

With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements.     

Description de Falklandia gen.n. de I'Ocean Austral et définition des Lysianassoidea uristidiens (Crustacea, Amphipoda)

The revision of the antarctic–subantarctic species Orchomenopsis reducta Schellenberg, 1931, has led to its attribution to a new, highly apomorphic genus: Falklandia gen.n. A new definition of the uristid group is given and Falklandia with 36 other lysianassoid genera are attributed to this supposedly monophyletic group.     

Use of ATP bioluminescence measurements for the estimation of biomass during biological humification

Summary The development of the microflora during the humification of grape pulp has been investigated by the determination of ATP using the bioluminescence technique. Several extraction methods were tested including the use of dimethylsulphoxide, trichloroacetic acid, grinding and ultrasonification. Dimethylsulphoxide and ultrasonification for 15 sec appeared to be the most effective. The ATP extract was stabilized when it was mixed with 0.75 mM glycine, 4.4 mM Mg-EDTA, pH 7.5 and frozen. The relative error of the ATP assay by bioluminescence did not exceed 6.5%. This method allowed us to show that at least five distinct reproducible microbial phases exist during grape pulp humification. These results show that the microbial biomass changes noticeably and at distinct times during composting.     

Cyanide-Resistant Root Respiration and Tap Root Formation in Two Subspecies of Hypochaeris radicata

Root respiration of the tap root forming species Hypochaeris radicata L. was measured during tap root formation. A comparison was made of two subspecies: H. radicata L. ssp. radicata L., a subspecies from relatively rich soils, and H. radicata L. ssp. ericetorum Van Soest, a subspecies from poor acidic soils. Root respiration was high and to a large extent inhibited by hydroxamic acid (SHAM) before the start of the tap root formation, indicating a high activity of an alternative non-phosphorylative electron transport chain. The rate of root respiration was much lower and less sensitive to SHAM when a considerable tap root was present. However, root respiration was also cyanide-resistant when a tap root was present, indicating that the alternative pathway was still present. A decreased rate of root respiration coincided with an increase of the content of storage carbohydrates, mainly in the tap root. The level of reducing sugars was constant throughout the experimental period, and it was concluded that the activity of the alternative oxidative pathway was significant in oxidation of sugars that could not be utilized for purposes like energy production, the formation of intermediates for growth or for storage. Root respiration decreased after the formation of a tap root. This decrease could neither be attributed to a gradual disappearance of the alternative chain, nor to a decreased level of reducing sugars. No differences in respiratory metabolism between the two subspecies have been observed, suggesting that a high activity of the alternative oxidative pathway is not significant in adaptation of the present two subspecies to relatively nutrient-rich or poor soils.     

Comparison of basic peptides- and lipid-based strategies for the delivery of splice correcting oligonucleotides

Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of numerous diseases. The use of antisense oligonucleotides (ON) to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. Oligonucleotides can be designed to repair genetic mutations, to modify genomic sequences in order to compensate for gene deletions, or to modify RNA processing in order to improve the effects of the underlying gene mutation. Steric block ON approach have proven to be effective in experimental model for various diseases. Here, we describe our experience in investigating two strategies for ON delivery: ON conjugation with basic peptides and lipid-based particulate system (lipoplex). Basic peptides or Cell Penetrating Peptides (CPP) such as the TAT-derived peptide appear to circumvent many problems associated with ON and drug delivery. This strategy may represent the next paradigm in our ability to modulate cell function and offers a unique avenue for the treatment of disease. Lipoplexes result from the intimate interaction of ON with cationic lipids leading to ON carrying particles able to be taken up by cells and to release ON in the cytoplasm. We have used as an experimental model the correction of a splicing alteration of the mutated β-globin intron causing thalassemia. Data on cell penetration and efficacy of correction of specific steric block ON delivered either by basic peptides or lipoplex are described. A comparison of the properties of both delivery systems is made respective to the use of this new class of therapeutic molecules.