Dynamics of auger working body of a multifunctional conveyor

A mathematical model of bending oscillations of a multifunctional conveyor working body with consideration of the angular velocity of its rotation and the motion along its outdoor medium is developed. Based on this model, the analytical relations were defined that describe the laws of changing the defining parameters of the working body oscillations for both non - resonant and resonant cases. The amplitude of the transition through the resonance is found to depend greatly on the relative quantity of medium motion and the rate of transition through the resonance

Chlorine-binding structures: role and organization in different proteins

The review focuses on chloride-binding structures in the proteins of bacteria, plants, viruses and animals. The structure and amino acid composition of the chloride-binding site and its role in the functioning of structural, regulatory, transport, receptor, channel proteins, transcription factors and enzymes are considered. Data on the important role of chloride-binding structures and chloride anions in the polymerization of fibrin are presented

Aggregation of platelets, proliferation of endothelial cells and motility of cancer cells are mediated by the Bβ1(15)-42 residue of fibrin(ogen)

The fibrinogen molecule contains multiple binding motifs for different types of cellular receptors, acting as a molecular link between coagulation and cell adhesion. In this study we generated a truncated form of the fibrinogen molecule lacking the Bβ1-42 sequence by site-specific proteolysis and evaluated the role of the fragment in adhesive capabilities of platelets, endothelial and cancer cells. Fibrinogen with the removed Bβ1-42 sequence and fibrin without the Bβ15-42 fragment (desβ1-42 fibrinogen and desABβ15-42 fibrin) were obtained by proteolysis using the specific protease from the venom of Echis multisquamatis. The cleaved fragment was purified by HPLC and was identified using MALDI-TOF. ADP- and collagen-induced aggregation of washed platelets in the presence of fibrinogen desBβ1-42 was studied using an aggregometer. Proliferation of mice aortic endothelial cells (MAEC) and human umbilical vein endothelial cells (HUVEC) was studied using the fibrin desABβ15-42 as the scaffold. Cell viability was quantified by the MTT test (MAEC). Generation time was calculated for the estimation of proliferative activity of HUVEC. Lung cancer cell line Н1299 was used to evaluate cancer cell motility in vitro using the scratch assay. Direct comparison of cellular behavior in the presence of truncated vs native forms demonstrated attenuated cell adhesion in the presence of fibrinogen desBβ1-42 and fibrin desBβ15-42. The platelet aggregation rate was only slightly decreased in the presence of fibrinogen desBβ1-42 but resulted in 15-20% disaggregation of adhered platelets. We also observed the substantial decrease of generation time of HUVEC and inhibition of viability of MAEC cells grown on scaffolds of a desABβ15-42 matrix. Finally, desBβ1-42 modulated the motility of H1299 cells in vitro and suppressed the wound healing by 20% compared to the full-length fibrinogen. We postulate that fragment 1-42 of the BβN-domain of fibrinogen is not sufficient for platelet aggregation, however it may contribute to platelet clot formation in later stages. At the same time, this fragment may be important for establishing proper cell-to-cell contacts and cell viability of endothelial cells. Also, 1-42 amino acid fragment of the BβN-domain supported the migration of cancer cells suggesting that interactions of fibrinogen with cancer cells could be a target for anticancer therapy. The Bβ1-42 fragment of fibrinogen contributes to efficient intracellular interactions of different types of cells, including platelets, endothelial cells and cancer cells

Expression of hexokinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase genes in ERN1 knockdown glioma U87 cells: effect of hypoxia and glutamine or glucose deprivation

Endoplasmic reticulum stress, as well as hypoxia and ischemia, are important factors for tumor neovascularization and growth. Cancer cells preferentially utilize glycolysis in order to satisfy their increased energetic and biosynthetic requirements. High glucose metabolism of cancer cells is caused by a combination of hypoxia-responsive transcription factors, activation of oncogenic proteins and the loss of tumor suppressor function and is realized in part by activating a family of regulatory bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB) and hexokinase 2. We have studied the effect of hypoxia and ischemia on the expression of PFKFB and hexokinase genes in glioma cell line U87 under knockdown of endoplasmic reticulum–nuclei-1 (ERN1) sensing and signaling enzyme. It was shown that loss of the signaling enzyme ERN1 function leads to an increase in the expression levels of HK1, HK2, PFKFB3 and PFKFB4 mRNA. Moreover, the expression levels of all studied genes increase under hypoxia in control and ERN1-deficient glioma cells; however knockdown of ERN1 suppresses the effect of hypoxia. Besides, HK2 and PFKFB4 are more sensitive to hypoxia than HK1 and PFKFB3. Glucose or glutamine deprivation conditions have different effects on the expression levels of these genes and its effect depends mainly on ERN1 function. Expression levels of alternative splice variants of PFKFB3 and PFKFB4 mRNA change at used experimental conditions in a fashion similar to the basic PFKFB variants. Thus, the expression of hexokinase and PFKFB genes is mainly dependent on ERN1 signaling enzyme function in normal, hypoxic and ischemic conditions

Molecular mechanisms of regulation of gene expression at hypoxia

Hypoxia is one of powerful inducers of expression of a large group of genes, including genes which control glycolysis, angiogenesis and proliferation supportingcell surviving at low oxygen condition. However, in tumor cells hypoxia was observed at normal oxygen tension condition as a result of its decreased utilization. Moreover, hypoxia is an obligate component of malignant tumor growth and substantially controls glycolysis, angiogenesis and proliferation processes. Data concerning molecular mechanisms of activation of hypoxia inducible transcription factor HIF in cells at hypoxia and in malignant tumors, as well as its role of in the regulation of gene expressions have been analyzed. The mechanisms of interaction of the transcription factor HIF with specific hypoxic regulatory elements in the promoter region of genes activated by hypoxia were examined