Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats

Recent epidemiological studies suggest that high meat intake is associated with promotion of colon cancer linked to haem-iron intake. We previously reported that dietary haem, in the form of either haemoglobin or meat, promotes precancerous lesions in the colon of rats given a low-calcium diet. The mechanism of promotion by haem is not known, but is associated with increased lipid peroxidation in faecal water and strong cytotoxic activity of faecal water on a cancerous mouse colonic epithelial cell line. To better understand the involvement of faecal water components of haem-fed rats in colon cancer promotion, we explored the effect of faecal water on normal (Apc +/+) or premalignant cells (Apc Min/+). Further, we tested if this effect was correlated to lipoperoxidation and 4-hydroxynonenal (HNE). We show here for the first time that heterozygote Apc mutation represents a strong selective advantage, via resistance to apoptosis induction (caspase 3 pathway), for colonic cells exposed to a haem-iron induced lipoperoxidation. The fact that HNE treatment of the cells provoked the same effects as the faecal water of rats fed the haem-rich diet suggests that this compound triggers apoptosis in those cells. We propose that this mechanism could be involved in the promotion of colon carcinogenesis by haem in vivo

A Peroxisomal Lon Protease and Peroxisome Degradation by Autophagy Play Key Roles in Vitality of Hansenula polymorpha Cells

In eukaryote cells various mechanisms exist that are responsible for the removal of non-functional proteins. Here we show that in the yeast Hansenula polymorpha (H. polymorpha) a peroxisomal Lon protease, Pln, plays a role in degradation of unfolded and non-assembled peroxisomal matrix proteins. In addition, we demonstrate that whole peroxisomes are constitutively degraded by autophagy during normal vegetative growth of WT cells. Deletion of both H. polymorpha PLN and ATG1, required for autophagy, resulted in a significant increase in peroxisome numbers, paralleled by a decrease in cell viability relative to WT cells. Also, in these cells and in cells of PLN and ATG1 single deletion strains, the intracellular levels of reactive oxygen species had increased relative to WT controls. The enhanced generation of reactive oxygen species may be related to an uneven distribution of peroxisomal catalase activities in the mutant cells, as demonstrated by cytochemistry. We speculate that in the absence of HpPln or autophagy unfolded and non-assembled peroxisomal matrix proteins accumulate, which can form aggregates and lead to an imbalance in hydrogen peroxide production and degradation in some of the organelles.

Stable isotopes reveal dietary shifts associated with social change in Hellenistic, Roman and Late Antique Knossos

Knossos was an important city on Crete and within Mediterranean networks in terms of trade and political status, though its status differed throughout the Hellenistic, Roman and Late Antique periods. This paper uses stable carbon and nitrogen isotope analysis to consider whether people at Knossos had differential diets due to the social, political, cultural, and economic changes across this time frame, factoring in age, sex and social status. Samples of human bone were selected to represent this range of time periods and variables. In this initial study, a small but insignificant increase in δ13C values was observed between the Hellenistic and Roman periods and there was a significant increase in δ15N values for the Late Antique period. No relationship between δ13C or δ15N and age was observed and while the female and male means were similar, the females had wider ranging values. No significant differences were detected by social status as represented by tomb type but there were small sample sizes for several of the tomb types. The results indicated a C3 terrestrial diet with meat or other animal products included for most individuals. The slight increase in δ13C values in the Roman period may represent either the introduction of a small amount of C4 plant or marine food, or very low trophic level marine foods into some Roman diets. The higher δ13C and, in particular, δ15N values observed in the Late Antique samples, suggests an increased consumption of seafood, potentially linked to Christian dietary practices or advances in fishing technologies and preservation techniques. The wider spread values of females compared to males, indicating a more varied diet, could have resulted from differential participation in religious institutions connected to food or may have been caused by greater nutritional stress in females in relation to pregnancy and reproductive issues. This study does not show a pattern of higher animal protein consumption in times of economic and cultural growth and prosperity but differences were detected between the different time periods in connection with the concurrent socio-economic changes

Children's Concepts of General Divisions of Time, Historical Time, and Time and the Life Cycle

Higher Educatio

A variational approach for retrieving ice cloud properties from infrared measurements: application in the context of two IIR validation campaigns

Cirrus are cloud types that are recognized to have a strong impact on the Earth-atmosphere radiation balance. This impact is however still poorly understood, due to the difficulties in describing the large variability of their properties in global climate models. Consequently, numerous airborne and space borne missions have been dedicated to their study in the last decades. The satellite constellation A-Train has proven to be particularly helpful to study cirrus on global scale due to such instruments as the Infrared Imaging Radiometer (IIR), which shows great sensitivity to the radiative and microphysical properties of these clouds. This study presents an algorithm that uses thermal infrared measurements to retrieve the optical thickness of cirrus and the effective size of their ice crystals. This algorithm is based on an optimal estimation scheme, which possesses the advantage of attributing precise uncertainties to the retrieved parameters. Two IIR airborne validation campaigns have been chosen as case studies. It is observed that optical thicknesses could be accurately retrieved but that large uncertainties may occur on the effective diameters. Strong agreements have been found between the products of our algorithm when separately applied to the measurements of IIR and of the airborne radiometer CLIMAT-AV, which comforts the results of previous validations of IIR level-1 measurements. Comparisons with in situ observations and with operational products of IIR also show confidence in our results. However, we have found that the quality of our retrievals can be strongly impacted by uncertainties related to the choice of a pristine crystal model and by poor constraints on the properties of possible liquid cloud layers underneath cirrus. Simultaneous retrievals of liquid clouds radiative and microphysical properties or the use of different ice crystal models should therefore be considered to improve the quality of the results

Estimation de probabilités par un algorithme génétique adapté.

International audienceIn the insurance comparison domain, data constantly evolve, implying some difficulties to directly exploit them. Indeed, most of the classical learning methods require data descriptors equal to both learning and test samples. To answer business expectations, online forms where data come from are regularly modified. This constant modification of features and data descriptors makes statistical analysis more complex. A first work with statistical methods has been realized. This method relies on likelihood and models selection with the Bayesian information criterion. Unfortunately, this method is very expensive in computation time. Moreover, with this method, all models should be exhaustively compared, what is materially unattainable, so the search space is limited to a specific models family. In this work, we propose to use a genetic algorithm (GA) specifically adapted to overcome the statistical method defaults and shows its performances on real datasets provided by the company MeilleureAssur-ance.com

Estimation de probabilités par algorithme génétique

National audienc

Diagenesis in salt dome roof strata: barite - calcite assemblage in Jebel Madar, Oman

Halokinesis causes a dynamic structural evolution with the development of faults and fractures, which can act as either preferential fluid pathways or barriers. Reconstructing reactive fluid flow in salt dome settings remains a challenge. This contribution presents for the first time a spatial distribution map of diagenetic phases in a salt dome in northern Oman. Our study establishes a clear link between structural evolution and fluid flow leading to the formation of diagenetic products (barite and calcite) in the salt dome roof strata. Extensive formation of diagenetic products occurs along NNE-SSW to NE-SW faults and fractures, which initiated during the Santonian (Late Cretaceous) and were reactivated in the Miocene, but not along the E-W fault, which was generated during Early Paleocene time. We propose that the diagenetic products formed by mixing of a warm (100 °C) saline (17 wt% NaCl eq.) 87Sr enriched (87Sr/86Sr: 0.71023) fluid with colder (35 °C) meteoric fluid during Miocene to Pleistocene. The stable sulphur and strontium isotope composition and fluid inclusion data indicate that a saline fluid, with sulfate source derived from the Ara Group evaporite and Haima Supergroup layers, is the source for barite formation at about 100 °C, predominantly at fault conjunctions and minor faults away from the main graben structure in the dome. In the Miocene, the saline fluid probably ascended along a halokinesis-related fault due to fluid overpressure (due to the rising salt and impermeable layers in the overlying stratigraphic sequence), and triggered the formation of barite due mixing with barium-rich fluids, accompanied by a drop in temperature. Subsequently, evolving salt doming with associated fault activity and erosion of the Jebel allows progressively more input of colder meteoric fluids, which mix with the saline warmer fluid, as derived from stable isotope data measured in the progressively younger barite-associated calcite, fault zone calcite and macro-columnar calcite. The reconstructed mixing model indicates a 50/50 to 90/10 meteoric/saline fluid mixing ratio for the formation of fault zone calcite, and a 10 times higher concentration of carbon in the saline fluid end member compared to the meteoric fluid end member. The presented mixing model of salt-derived fluids with meteoric fluids is suggested to be a general model applicable to structural diagenetic evolution of salt domes world wide