MODELLING HEAT GENERATION DURING FRICTION AND VISCOPLASTIC DEFORMATION BASED ON THE EXAMPLE OF THE YENISEI SHEAR ZONE (EASTERN SIBERIA)

Deviations of the РТ parameters from the background values, corresponding to the lithostatic pressure and the standard geotherm characteristic of the neighboring crustal blocks of the Yenisei Ridge, were recorded by geothermobarometry in the zones of dislocation metamorphism of the Yenisei regional shear zone (Eastern Siberia). To explain the reason for large deviations from metamorphic conditions for shear and collision, we worked out 3D and 2D thermomechanical numerical models. The paper presents two- and three-dimensional models of dissipative heating during friction and visco-plastic deformations. The modelling results are compared with geological observations on the metamorphic grade and the scale of deformations of the Yenisei regional shear zone. A detailed consideration is being given to the ratio of heat released during friction at the contact of shear fault blocks, or during viscous deformations of the rheologically layered zone of tectonic flow and blastomylonitization. Estimates of the magnitude of dissipative heating are obtained for typical parameters of shear zones. The model of viscous deformation of a shear zone of finite width, taking into account the rheological layering of the crust, predicts dissipative heating by 200–310 °C at strain rates of 2–4 cm/year. The model of obduction of the tectonic plate with a thrusting velocity of 5 cm/year yields estimates of frictional heating of rocks at the contact of blocks no higher than 130–190 °C. The characteristic time period of the stationary dissipative regime formation is 6–8 million years. Dissipative heating could be a heat source for the metamorphic complexes of the Yenisei regional shear zone, though melting conditions of metapelite were not attained

МОДЕЛИРОВАНИЕ ТЕПЛОГЕНЕРАЦИИ ПРИ ТРЕНИИ И ВЯЗКОПЛАСТИЧЕСКОЙ ДЕФОРМАЦИИ НА ПРИМЕРЕ ПРИЕНИСЕЙСКОЙ СДВИГОВОЙ ЗОНЫ (ВОСТОЧНАЯ СИБИРЬ)

Deviations of the РТ parameters from the background values, corresponding to the lithostatic pressure and the standard geotherm characteristic of the neighboring crustal blocks of the Yenisei Ridge, were recorded by geothermobarometry in the zones of dislocation metamorphism of the Yenisei regional shear zone (Eastern Siberia). To explain the reason for large deviations from metamorphic conditions for shear and collision, we worked out 3D and 2D thermomechanical numerical models. The paper presents two- and three-dimensional models of dissipative heating during friction and visco-plastic deformations. The modelling results are compared with geological observations on the metamorphic grade and the scale of deformations of the Yenisei regional shear zone. A detailed consideration is being given to the ratio of heat released during friction at the contact of shear fault blocks, or during viscous deformations of the rheologically layered zone of tectonic flow and blastomylonitization. Estimates of the magnitude of dissipative heating are obtained for typical parameters of shear zones. The model of viscous deformation of a shear zone of finite width, taking into account the rheological layering of the crust, predicts dissipative heating by 200–310 °C at strain rates of 2–4 cm/year. The model of obduction of the tectonic plate with a thrusting velocity of 5 cm/year yields estimates of frictional heating of rocks at the contact of blocks no higher than 130–190 °C. The characteristic time period of the stationary dissipative regime formation is 6–8 million years. Dissipative heating could be a heat source for the metamorphic complexes of the Yenisei regional shear zone, though melting conditions of metapelite were not attained.В зонах дислокационного неопротерозойского метаморфизма Приенисейской региональной сдвиговой зоны (ПРСЗ) (Восточная Сибирь) геотермобарометрическими методами зафиксированы отклонения РТ-параметров от фоновых значений, соответствующих литостатическому давлению и стандартной палеогеотерме, характерной для соседних блоков коры Енисейского кряжа. Для объяснения причин значительных отклонений условий метаморфизма при сдвиге и коллизии нами разработаны 3D и 2D термомеханические численные модели. В работе представлены результаты двух- и трехмерного моделирования диссипативного нагрева при трении и вязкопластических деформациях. Результаты моделирования сравниваются с геологическими данными о степени метаморфизма и масштабе деформаций ПРСЗ. Детально рассматривается вопрос о соотношении величины тепловыделения при трении на контакте блоков сдвиговых разломов либо при вязких деформациях в реологически расслоенной зоне тектонического течения и бластомилонитизации. Получены оценки величины диссипативного нагрева при типичных параметрах сдвиговых зон, а также с учетом наличия расплава. Модель вязкого деформирования сдвиговой зоны конечной ширины в неоднородной по реологии и составу коре предсказывает диссипативный нагрев на 200–310 °С при скорости деформации 2–4 см/год. Модель обдукции тектонической пластины со скоростью надвигания 5 см/год дает оценки нагрева пород при трении на контакте блоков не более 130–190 °С. Характерное время установления стационарного режима диссипативного нагрева в режиме сдвига составляет 6–8 млн лет. Для метаморфических комплексов ПРСЗ диссипативный нагрев мог являться тепловым источником метаморфизма и мигматизации, однако условия формирования крупных гранитных интрузий не достигались

Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery

Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53. A lead peptide was identified that activated intracellular p53 with negligible nonspecific cytotoxicity, however it still bound serum avidly and only showed a marginal improvement in cellular potency. These hurdles were overcome by successfully identifying a pyridinium-based cationic lipid formulation, which significantly improved the activity of the stapled peptide in a p53 reporter cell line, principally through increased vesicular escape. These studies under score that stapled peptides, which are cell permeable and target specific, can be identified with rigorous experimental design and that these properties can be improved through use with lipid based formulations. This work should facilitate the clinical translation of stapled peptides

DIAPH1-MFN2 Interaction Regulates Mitochondria-SR/ER Contact and Modulates Ischemic/Hypoxic Stress

Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages. Solution structure studies affirm the interaction between the Diaphanous Inhibitory Domain and the cytosolic GTPase domain of MFN2. In male rodent and human cardiomyocytes, DIAPH1-MFN2 interaction regulates mitochondrial turnover, mitophagy, and oxidative stress. Introduction of synthetic linker construct, which shorten the mitochondria-SR/ER distance, mitigated the molecular and functional benefits of DIAPH1 silencing in ischemia. This work establishes fundamental roles for DIAPH1-MFN2 interaction in the regulation of mitochondria-SR/ER contact networks. We propose that targeting pathways that regulate DIAPH1-MFN2 interactions may facilitate recovery from tissue ischemia

The complete sequence of the Acacia ligulata chloroplast genome reveals a highly divergent clpP1 gene

Legumes are a highly diverse angiosperm family that include many agriculturally important species. To date, 21 complete chloroplast genomes have been sequenced from legume crops confined to the Papilionoideae subfamily. Here we report the first chloroplast genome from the Mimosoideae, Acacia ligulata, and compare it to the previously sequenced legume genomes. The A. ligulata chloroplast genome is 158,724 bp in size, comprising inverted repeats of 25,925 bp and single-copy regions of 88,576 bp and 18,298 bp. Acacia ligulata lacks the inversion present in many of the Papilionoideae, but is not otherwise significantly different in terms of gene and repeat content. The key feature is its highly divergent clpP1 gene, normally considered essential in chloroplast genomes. In A. ligulata, although transcribed and spliced, it probably encodes a catalytically inactive protein. This study provides a significant resource for further genetic research into Acacia and the Mimosoideae. The divergent clpP1 gene suggests that Acacia will provide an interesting source of information on the evolution and functional diversity of the chloroplast Clp protease comple