Displacement of plasma protein and conduction velocity in rats under action of acceleration forces and hypokinesia

The permeability of capillary vessels was investigated in order to determine if acceleration alone or following prolonged hypokinesia would induce changes in the vascular wall leading to the penetration by l-albumins and/or proteins with larger molecules. In rats undergoing action of +5 Gz accelerations, no increase in vascular permeability, as tested with the use of (Cr-5k)-globulin, was demostrated. In rats immobilized for 4 weeks before centrifugation, rather weak migration of (Cr-51)-globulin from the vessels was observed. Immobilization resulted also in lowering of conduction velocity in the sciatic nerve

Determination of oxygen tension in the subcutaneous tissue of cosmonauts during the Salyut-6 mission

A polarographic technique was used to measure the oxygen tension in subcutaneous tissue of the forearm of a cosmonaut prior to, after, and on the fourth day of a space mission performed by Salut-6. A drop in the oxygen exchange rate in the peripheral tissues during weightlessness was observed. The mechanisms of this change are studied, taking into consideration the blood distribution in the organism and microcirculation disorders reflected by a decreased blood flow rate in arterial-venous junctions

Investigation of cooling properties of the gaseous medium of a space station

An investigation of cooling properties of the gaseous medium was performed in the biosatellite Kosmos-936 as well as in the orbital complexes Soyuz-28/Salyut-6 and Soyuz-30/Salyut-6 with the aid of an especially constructed electric dynamic catathermometer. In this instrument current was measured which was necessary to keep a steady settled temperature of the sensing device. The investigation was performed because of the disturbed heat exhange of the human body caused by lack of natural convection in weightlessness. The instrument also enabled objective estimation of the temperature of the cosmonaut's ody in six optionally selected regions. The results obtained by means of the catathermometer will also enable defining the appropriate hygienic conditions of the gaseous medium of space stations

Osteosarcoma : searching for new treatment options

Osteosarcoma is the most frequent malignant bone tumor affecting mainly adolescents and people older than 50years old. Current treatment involves chemotherapy and surgical removal. Despite efforts to find a cure, there is 70% 5year survival rate. For patients that present  metastasis at the moment of diagnosis, the prognosis is worse. Additionally, many do not respond well to chemotherapy. The aim of this research was to find new treatment options for patients with osteosarcoma. I searched for inhibitors that could sensitize osteosarcoma cells to chemotherapy. In this thesis, it is shown that targeting cell cycle regulators, proteins involved in apoptosis inhibition, and cellular pathways involved in survival, proliferation and migration are  promising candidates for further research.Toxicolog

Studying the Use of Earth in Early Architecture of Southwest and Central Asia

Using case studies from Aşıklı Höyük, Çatalhöyük, Boncuklu Tarla, Göbekli Tepe (all Turkey), and Monjukli Depe (southern Turkmenistan), this study presents a framework for in-depth research on prehistoric earthen architecture in southwestern and central Asia. It demonstrates the challenges and potential for innovative and comparative studies based on interdisciplinary approaches and the use of architectural, microstratigraphic, and microarchaeological analyses. Furthermore, it sheds new light on issues related to various aspects of building continuity which is commonly recognised as a very important phenomenon in the Neolithic but could have different facets. The study attempts to discuss the reasons behind the local decisions to use and recycle specified building materials. In addition, it evaluates – in relation to particular sites – the usefulness of specific analyses for reconstruction of daily, seasonal, or annual practices. Advanced analyses of floors and fire installations, for instance, can contribute not only to the identification of indoor and outdoor surfaces but also to a better understanding of activity areas and the intensity of use within particular spaces. Variations and different combinations of mudbrick, mortar, and plaster recipes allow for insights into how earth and sediment material were used to mark collective and individual identity through the performance of a building. Recognising reused materials and features allows us to trace further the nature of prehistoric societies and local architectural dialects

FAST-NMR - Functional Annotation Screening Technology Using NMR Spectroscopy

An abundance of protein structures emerging from structural genomics and the Protein Structure Initiative (PSI) are not amenable to ready functional assignment because of a lack of sequence and structural homology to proteins of known function. We describe a high-throughput NMR methodology (FAST-NMR) to annotate the biological function of novel proteins through the structural and sequence analysis of protein-ligand interactions. This is based on basic tenets of biochemistry where proteins with similar functions will have similar active sites and exhibit similar ligand binding interactions, despite global differences in sequence and structure. Protein-ligand interactions are determined through a tiered NMR screen using a library composed of compounds with known biological activity. A rapid co-structure is determined by combining the experimental identification of the ligand-binding site from NMR chemical shift perturbations with the proteinligand docking program AutoDock. Our CPASS (Comparison of Protein Active Site Structures) software and database is then used to compare this active site with proteins of known function. The methodology is demonstrated using unannotated protein SAV1430 from Staphylococcus aureus

FAST-NMR - Functional Annotation Screening Technology Using NMR Spectroscopy

An abundance of protein structures emerging from structural genomics and the Protein Structure Initiative (PSI) are not amenable to ready functional assignment because of a lack of sequence and structural homology to proteins of known function. We describe a high-throughput NMR methodology (FAST-NMR) to annotate the biological function of novel proteins through the structural and sequence analysis of protein-ligand interactions. This is based on basic tenets of biochemistry where proteins with similar functions will have similar active sites and exhibit similar ligand binding interactions, despite global differences in sequence and structure. Protein-ligand interactions are determined through a tiered NMR screen using a library composed of compounds with known biological activity. A rapid co-structure is determined by combining the experimental identification of the ligand-binding site from NMR chemical shift perturbations with the proteinligand docking program AutoDock. Our CPASS (Comparison of Protein Active Site Structures) software and database is then used to compare this active site with proteins of known function. The methodology is demonstrated using unannotated protein SAV1430 from Staphylococcus aureus

Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin

High-grade conventional osteosarcoma is the most common primary bone tumor. Prognosis for osteosarcoma patients is poor and resistance to chemotherapy is common. We performed an siRNA screen targeting members of the Bcl-2 family in human osteosarcoma cell lines to identify critical regulators of osteosarcoma cell survival. Silencing the anti-apoptotic family member Bcl-xL but also the pro-apoptotic member Bak using a SMARTpool of siRNAs as well as 4/4 individual siRNAs caused loss of viability. Loss of Bak impaired cell cycle progression and triggered autophagy. Instead, silencing Bcl-xL induced apoptotic cell death. Bcl-xL was expressed in clinical osteosarcoma samples but mRNA or protein levels did not significantly correlate with therapy response or survival. Nevertheless, pharmacological inhibition of a range of Bcl-2 family members showed that inhibitors targeting Bcl-xL synergistically enhanced the response to the chemotherapeutic agent, doxorubicin. Indeed, in osteosarcoma cells strongly expressing Bcl-xL, the Bcl-xL-selective BH3 mimetic, WEHI-539 potently enhanced apoptosis in the presence of low doses of doxorubicin. Our results identify Bcl-xL as a candidate drug target for sensitization to chemotherapy in patients with osteosarcoma

Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin

High-grade conventional osteosarcoma is the most common primary bone tumor. Prognosis for osteosarcoma patients is poor and resistance to chemotherapy is common. We performed an siRNA screen targeting members of the Bcl-2 family in human osteosarcoma cell lines to identify critical regulators of osteosarcoma cell survival. Silencing the anti-apoptotic family member Bcl-xL but also the pro-apoptotic member Bak using a SMARTpool of siRNAs as well as 4/4 individual siRNAs caused loss of viability. Loss of Bak impaired cell cycle progression and triggered autophagy. Instead, silencing Bcl-xL induced apoptotic cell death. Bcl-xL was expressed in clinical osteosarcoma samples but mRNA or protein levels did not significantly correlate with therapy response or survival. Nevertheless, pharmacological inhibition of a range of Bcl-2 family members showed that inhibitors targeting Bcl-xL synergistically enhanced the response to the chemotherapeutic agent, doxorubicin. Indeed, in osteosarcoma cells strongly expressing Bcl-xL, the Bcl-xL-selective BH3 mimetic, WEHI-539 potently enhanced apoptosis in the presence of low doses of doxorubicin. Our results identify Bcl-xL as a candidate drug target for sensitization to chemotherapy in patients with osteosarcoma.Toxicolog