Journal de la Societe de biologie最新文献

Animal models allowing more sensitive and early detection of tumorigenesis and metastasis are instrumental in the fight for developing effective therapies against aggressive forms of cancer. In the present chapter, the advantages and limitations of the bioluminescent imaging (BLI) approach are discussed. Although BLI provides rapid, highly sensitive, noninvasive and quantitative detection of small tumors and micrometastases, several issues like the low anatomic resolution or the attenuation of the luminescent signal with tissue depth must be considered when using this technology.

Agars and carrageenans are sulphated galactans which assemble in the red algal cell wall as a dense network of semi-crystalline fibers. These polysaccharides are degraded in heterogeneous phase by bacterial enzymes, namely agarases and carageenases. Crystallographic as well as enzymologic investigations of the sulphated galactans/galactanases systems highlight that the properties of these catalysts are well adapted to the degradation of solid polyanionic substrates. Indeed, as for cellulases or amylases, they are able to depolymerize their respective substrates according to a processive mode of action. However, at the molecular level, they are distinguished by the ionic nature of the interactions involved which do not allow the direct transposition of the processivity models developed for the degradation of neutral polysaccharides.

Diabetes mellitus is a chronic disease whose prevalence is increasing worldwide. It remains associated with a high risk of severe complications, essentially micro- and macro-vascular complications. Type 1 diabetes is an auto-immune disease that leads to the destruction of insulin-secreting B cells and therefore requires an intensive optimised exogenous insulin therapy. Type 2 diabetes is a polygenic disease whose expression is favoured by inadequate lifestyle, leading to obesity. It combines a relative insulin secretory defect and insulin resistance, the latter being associated with various other cardiovascular risk factors. Treatment consists of lifestyle modifications first, then the prescription of various glucose-lowering oral drugs and finally, when requested, insulin therapy. A multi-risk intervention is mandatory to improve the cardiovascular prognosis. The prevention of diabetes and its complications is a major public health objective.

In this review, we shall first present a short summary of Maillard's carrier, his pioneering work for the introduction of chemistry in medicine and a short description of the reaction he described in 1912 between reducing sugars and amino groups on proteins, part of his PhD thesis. This reaction was rediscovered several decades later by biochemists. Nowadays an increasing number of teams specialise in the study of the Maillard reaction, because of its importance in aging and age-related pathologies. After a short description of this reaction, we report the importance of receptors recognising a variety of AGE-s and mediating their effect on cells and tissues. The importance of glycoxidation is mentioned, mediating the release of free radicals (ROS-s) directly involved in a number of noxious effects of AGE-s, such as crosslinking and even mutagenesis. All these - in his time - unforeseen consequences of this reaction have made Maillard the best known French scientist in international scientific circles.

What does mRNA become at the issue of translation in eukaryotic cells? It can be directly degraded or stored for further use. In some cases, the underlying molecular mechanisms have been studied in detail by biochemical approaches, as examplified by the most recently discovered regulation pathway, RNA interference. However, the cellular context of these regulations has often been ignored, as if these reactions took place diffusely throughout the cytoplasm. Two new structures involved therein have now been described: GW bodies (or P-bodies) and stress granules. The first studies suggested that they were specifically devoted to mRNA degradation and mRNA storage, respectively. This framework is changing rapidly with obvious functional overlapping between both structures.

By contrast with a wide definition of the 'epigenetic variation', including all changes in gene expression that do not result from alteration of the gene structure, a more restricted class had been defined, initially in plants, under the name 'paramutation'. It corresponds to epigenetic modifications distinct from the regulatory interactions of the cell differentiation pathways, mitotically stable and sexually transmitted with non-Mendelian patterns. This class of epigenetic changes appeared for some time restricted to the plant world, but examples progressively accumulated of epigenetic inheritance in organisms ranging from mice to humans. Occurrence of paramutation in the mouse and possible mechanisms were then established in the paradigmatic case of a mutant phenotype maintained and hereditarily transmitted by wild type homozygotes. Together with recent findings in plants indicative of a necessary step of RNA amplification in the reference maize paramutation, the mouse studies point to a new role of RNA, as an inducer and hereditary determinant of epigenetic variation. Given the known presence of a wide range of RNAs in human spermatozoa, as well as a number of unexplained cases of familial disease predisposition and transgenerational maintenance, speculations can be extended to possible roles of RNA-mediated inheritance in human biology and pathology.

Bone is a common metastatic site for many cancers. Tumor cells located in the bone marrow cavity disturb the natural balance (bone remodelling) established between new bone formation performed by osteoblasts and bone resorption carried out by osteoclasts. Tumor cells produce many factors including growth factors and cytokines (PTHrP, ET-1, BMPs, others...) that stimulate either ostoclast activity leading to osteolytic lesions or osteoblast activity generating osteosclerotic bone metastases. Growth factors released from resorbed bone matrix or throughout osteoblastic bone formation sustain tumor growth. Therefore, bone metastases are the site of vicious cycles wherein tumor growth and bone metabolism sustain each other.

Various aspects of the social life of bacteria are exposed here, in the light of recently published discoveries on the adaptive mechanisms of bacterial adhesion and biofilm formation, and on their importance at all ecological levels. There is now a need for studying models such as macrophytic algae and their associated microbial flora in order to integrate observations on simple laboratory models into the spatio-temporal perspective afforded by evolutionarily stable biocenoses.

Gene expression regulation is crucial for organism survival. Each step has to be regulated, from the gene to the protein. mRNA can be stored in the cell without any direct translation. This process is used by the cell to control protein synthesis rapidly at the right place, at the right time. Protein synthesis costs a lot of energy for the cell, so that a precise control of this process is required. Translation initiation represents an important step to regulate gene expression. Many factors that can bind mRNA and recruit different partners are involved in the inhibition or stimulation of protein synthesis. Oceans contain an important diversity of organisms that are used as important models to analyse gene expression at the translational level. These are useful to study translational control in different physiological processes for instance cell cycle (meiosis during meiotic maturation of starfish oocytes, mitosis following fertilization of sea urchin eggs) or to understand nervous system mechanisms (aplysia). All these studies will help finding novel actors involved in translational control and will thus be useful to discover new targets for therapeutic treatments against human diseases.

mRNA translation is now recognized as a important regulatory step for gene expression in different physiological and pathophysiological processes including cell proliferation and apoptosis. B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of resting lymphocytes and defective apoptosis. The mRNA cap-binding protein eIF4E (eukaryotic Initiation Factor 4E) and its repressor 4E-BP (eIF4E Binding protein) are crucial translational regulators that have been involved in survival and apoptosis processes of cells. We have shown that the release of eIF4E from its translational repressor 4E-BP is an important event for the first mitotic division triggered by fertilization and that the degradation of 4E-BP is a new means to regulate 4E-BP function that has to be analyzed in other physiological and physiopathological processes. In this chapter, we describe recent advances illustrating the importance of eIF4E and 4E-BP in cancer processes, suggesting that these actors can be targeted for potential therapy against cancer in general and LLC in particular.