Telomeres and Genomic Instability from Precancerous Lesions to Advanced Cancer – Understanding Through Ovarian Cancer

Genetic instability plays an important role in ovarian carcinogenesis. Genetic instability is one of the characteristics shared by most human cancers and seems to exist (at various levels) at all stages of the disease, from precancerous lesions to advanced cancer. It is possible that this instability is one of the first trigger events, which would facilitate the subsequent establishment of all the other cancer hallmarks. Telomere shortening appears to take place in most human preinvasive epithelial lesions: short telomeres are found in up to 88% of early precancerous conditions of the bladder, cervix, colon, esophagus, or prostate. However, little is known about ovarian carcinogenesis and telomere shortening. Recent evidence has shown that the fallopian tube may be the origin of ovarian cancer. A new tubal carcinogenic sequence has been described with precancerous lesions that could metastasize to the ovary and result in invasive ovarian cancer. In this review, we will describe the degree of telomere shortening and genomic instability (estimated by the expression of DNA damage response proteins, such as H2AX, Chk2, ATM, 53BP1, p53, and TRF2, and by array comparative genomic hybridization) in early preinvasive stages of ovarian cancer (serous tubal intraepithelial carcinoma (STIC)), ovarian high-grade serous carcinoma, and benign controls. Given that STICs have the shortest telomeres, they could be in a telomere crisis phase preceding genomic stabilization due to telomerase activation (see appended diagram). Concordant results were obtained in immunohistochemical and molecular studies. The expression of all DNA damage proteins increased from benign fallopian tubes to STICs suggesting an early activation of the DNA damage response (DDR) pathways in STICs and indicating that genomic instability may occur early in the precancerous lesions of high-grade serous ovarian cancer (HGSC). In this chapter, we propose to review current knowledge about the function of human telomeres and telomerase and their relevance in genomic instability in cancer and to focus on specific results for ovarian cancer

Simulation of consumer exposure to deoxynivalenol according to wheat crop management and grain segregation: Case studies and methodological considerations

International audienceWe combined agronomic data and a model simulating exposure based on consumption data to assess the impact of crop management and grain segregation procedures on consumer exposure to deoxynivalenol. We used three scenarios of soil tillage at a regional scale and three scenarios of grain segregation for a supply area. The soil tillage scenarios were applied to a range of mean crop contamination levels, with various coefficients representing the degree of tillage. The grain segregation scenarios were applied to two real datasets of DON content distributions. We found that the increase in consumer exposure in response to increases in "risky" crop management practices such as direct-drilling depends largely on mean contamination and on the value of the tillage coefficient. The results for grain segregation procedures showed that exposure was most strongly affected by contamination distributions as the segregation procedure minimising risk differed for the two datasets

Development and physiology of the brown alga Ectocarpus siliculosus: two centuries of research

International audienceBrown algae share several important features with land plants, such as their photoautotrophic nature and their cellulose‐containing wall, but the two groups are distantly related from an evolutionary point of view. The heterokont phylum, to which the brown algae belong, is a eukaryotic crown group that is phylogenetically distinct not only from the green lineage, but also from the red algae and the opisthokont phylum (fungi and animals). As a result of this independent evolutionary history, the brown algae exhibit many novel features and, moreover, have evolved complex multicellular development independently of the other major groups already mentioned. In 2004, a consortium of laboratories, including the Station Biologique in Roscoff and Genoscope, initiated a project to sequence the genome of Ectocarpus siliculosus, a small filamentous brown alga that is found in temperate, coastal environments throughout the globe. The E. siliculosus genome, which is currently being annotated, is expected to be the first completely characterized genome of a multicellular alga. In this review we look back over two centuries of work on this brown alga and highlight the advances that have led to the choice of E. siliculosus as a genomic and genetic model organism for the brown algae

Arthropod distribution in a tropical rainforest: tackling a four dimensional puzzle

Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date moststudies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/ litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods

Arthropod distribution in a tropical rainforest: tackling a four dimensional puzzle

Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods1012CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSolVin-Solvay SA; Smithsonian Institution; Smithsonian Tropical Research Institute; United Nations Environment Programme; Smithsonian Institution; Smithsonian National Museum of Natural History; European Science Foundation (ESF); Global Canopy Programme; Czech Science foundation GACR grant; European Social Fund (ESF); Ministry of Education, Youth & Sports - Czech Republic; French National Research Agency (ANR); Research Council of Norway; Grant Agency of the Czech Republi