Accumulation of Polychlorinated Biphenyls in Adipocytes: Selective Targeting to Lipid Droplets and Role of Caveolin-1

Background : Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that preferentially accumulate in lipid-rich tissues of contaminated organisms. Although the adipose tissue constitutes a major intern reservoir of PCBs and recent epidemiological studies associate PCBs to the development of obesity and its related disorders, little is known about the mechanisms involved in their uptake by the adipose tissue and their intracellular localization in fat cells

Повышение эффективности разработки объекта М на примере месторождения "Х" (Томская область)

В данной работе помимо характеристики геологического строения нефтяного объекта М1 и текущего состояния его разработки рассмотрены проводимые геолого-технические мероприятия, принцип их действия и проведена оценка их технологической эффективности, рекомендуется оптимизация разработки объекта М1 путем бурения зарезок боковых стволов с аварийных скважин в зоны локализации остаточных запасов. Результаты работы могут быть использованы при проектировании разработки месторождений-аналогов с запасами палеозойских углеводородов.As part of this work, in addition to the characteristics of the geological structure and the development of the project, geological and technical measures are being carried out, the principle of their operation and their technological efficiency are assessed, optimization of the development of the drilling facility due to sidetracks with emergency wells in the areas of residual reserves localization is recommended. be used in the design of field development - analogues with reserves of the Paleozoic hydrocarbons

Development of the Commercial Manufacturing Process for Ipatasertib

Ipatasertib is a potent small molecule Akt kinase inhibitor currently tested in Phase III clinical trials for the treatment of metastatic castration-resistant prostate cancer and triple negative metastatic breast cancer. In this paper an overview of the development achievements towards the commercial manufacturing process is given. The convergent synthesis consists of ten steps with eight isolated intermediates and utilizes a wide range of chemical techniques and technologies to build-up this complex drug. All three stereocenters are introduced using enzyme or metal catalysis

Ionization-induced thermally activated defect-annealing process in SiC

International audienceIonizing events can lead to panoply of irradiation effects, and in silicon carbide (SiC), they drastically modify the defect production rate or the initial density. To better understand this phenomenon, 6H-SiC single crystals were first predamaged using low-velocity 100-keV Fe+ ions at three fluences in the range of 1014cm−2 to induce three different initial disorder levels peaking at values between ∼0.8 and 1 (1 corresponding to full amorphization). Crystals were then submitted to swift heavy ion irradiation in the 1013cm−2 fluence range at both low (∼100 K) and high (∼770 K) temperature. Rutherford backscattering spectrometry in channeling conditions revealed that swift ions allow annealing part of the initial damage, the recovery efficiency increasing with the irradiation temperature and reaching 75% in initially severely disordered crystals. This temperature effect has been qualitatively predicted by molecular dynamics simulations. Transmission electron microscopy allowed imaging both the recovery and the difference in the microstructure of the layers irradiated at low or high temperature. Recovery cross sections are found to lie in the range of a few square nanometers, consistent with previously reported values. A scenario for a general, two-step annealing mechanism referred to as an ionization-activated, thermally assisted defect-annealing (IATADA) process is proposed. This mechanism rationalizes the diverse descriptions reported so far in the literature

Structural changes induced by heavy ion irradiation in titanium silicon carbide

International audienceCarbide-type ceramics, which have remarkable thermomechanical properties, are sensed to manufacture the fuel cladding of Generation IV reactors that should work at high temperature. The MAX phases, and more particularly titanium silicon carbide, are distinguished from other materials by their ability to have some plasticity, even at room temperature. For this study, polycrystalline Ti3SiC2 was irradiated with ions of different energies, which allow to discriminate the effect of both electronic and nuclear interactions. After characterization by low-incidence X-ray diffraction and cross-sectional transmission electron microscopy, it appears that Ti3SiC2 is not sensitive to electronic excitations while nuclear shocks damage its structure. The results show the creation of many defects and disorder in the structure, an expansion of the hexagonal close-packed lattice along the c axis, and an increase in the microstrain yield

Efficient in vitro adipocyte model of long-term lipolysis: A tool to study the behavior of lipophilic compounds.

The triglycerides (TGs) stored in the white adipose tissue are mobilized during periods of negative energy balance. To date, there is no in vitro model of adipocytes imitating a long period of negative energy balance in which triglycerides are highly mobilized. Such model would allow studying the mobilization of TGs and lipophilic compounds trapped within the adipose tissue (e.g., pollutants and vitamins). The present study aims at developing a performing long-term in vitro lipolysis in adipocytes, resulting in a significant decrease of TG stores. Lipolysis was induced on differentiated rat adipocytes by a lipolytic medium with or without isoproterenol for 12 h. The condition with isoproterenol was duplicated, once with medium renewal every 3 h and once without medium renewal. Adding isoproterenol efficiently triggered lipolysis in a short time (3 h). However, a single stimulation by isoproterenol, without medium renewal, was not sufficient to reduce the TG content during a longer term (12 h). A reesterification of fatty acids occurred after a few hours of lipolysis, resulting in a novel increase of cellular lipids. Regular medium renewal combined with repeated isoproterenol stimulations led to almost emptied cells after 12 h. However, medium renewal without isoproterenol stimulation for 12 h was as efficient in terms of lipid mobilization. Our study demonstrates that, over a short-term period, isoproterenol is required to exert a significant lipolytic effect on adipocytes. During a long-term period, the presence of isoproterenol is no longer essential. Instead, medium renewal becomes the main factor involved in cell emptying. The efficiency of this protocol was demonstrated by visual tracking of the cells and by monitoring the dynamics of release of a lipophilic compound, PCB-153, from adipocytes during lipolysis