scholarly journals A Negative Feedback Regulates The Flow Of Signal Through Akt/mTORC1/S6K1 Pathway

2017 ◽  
Author(s):  
Poulami Dutta ◽  
Vimalathithan Devaraj ◽  
Biplab Bose
Keyword(s):  
Mathematical Model ◽  
Protein Synthesis ◽  
Growth Factors ◽  
Negative Feedback ◽  
Akt Pathway ◽  
Mitogenic Effect ◽  
Fast Oscillation ◽  
Feedback Controls ◽  
Flow Through ◽  
The Difference

AbstractSeveral growth factors, cytokines, hormones activate PI3K/Akt pathway. Akt is a key node in this pathway and activates different downstream paths. One such path is Akt/mTORC1/S6K1 that controls protein synthesis, cell survival, and proliferation. Here we show that a negative feedback controls activation of S6K1 through this pathway. Due to this negative feedback, a sustained phospho-Akt signal generates a transient pulse of phospho-S6K1. We have created a mathematical model for this circuit. Analysis of this model shows that the negative feedback acts as a filter and preferentially allows a signal, with sharp and faster rise of phospho-Akt, to induce pronounced activation of S6K1. It blocks an input with a fast oscillation of phospho-Akt to flow through this path. We show that this negative feedback leads to differential activation of S6K1 by Insulin and Insulin-like Growth Factor 1. Such differential effect may explain the difference in the mitogenic effect of these two molecules.

scholarly journals On an Optimal Choice of Pre-Perforated Tipping Paper and Porous Plug Wrap Paper

2005 ◽  
Vol 21 (6) ◽  
pp. 358-367
Author(s):  
B Eitzinger
Keyword(s):  
Mathematical Model ◽  
Layered Structure ◽  
Coefficient Of Variation ◽  
Statistical Significance ◽  
Statistical Investigation ◽  
Optimal Choice ◽  
Porous Plug ◽  
Simple Estimate ◽  
Flow Through ◽  
The Difference

AbstractTo minimize the effect of permeability variations of tipping and plug wrap paper on the degree of filter ventilation and consequently on the smoke yields, a mathematical model for the flow through a layered structure of perforated tipping paper and porous plug wrap paper was derived. The output of the model was compared to experimental data and a very good agreement was found.A statistical investigation revealed that measured permeability values of tipping and plug wrap papers are normally distributed. Furthermore, it was shown that the statistical distribution of the total permeability of the layered structure cannot be distinguished from a normal distribution at reasonable levels of statistical significance.Based on these investigations and on the mathematical model, expressions for the expected value and the coefficient of variation of the total permeability were derived. It was shown that in spite of the non-linear model the difference between the exact expected total permeability and a simple estimate calculated from the expected permeabilities of tipping and plug wrap is sufficiently small, such that for all practical purposes this estimate can be used.The coefficient of variation of the total permeability was then minimized. The solution of this optimisation problem delivered practically applicable design rules for the permeabilities of tipping and plug wrap papers. It was shown that the minimal coefficient of variation of the total permeability is lower than the coefficient of variation of the permeability of tipping and plug wrap paper. Typically an optimal design can be achieved by choosing the tipping paper permeability between 10% and 50% higher than the total permeability. A simple example demonstrated the usefulness of this approach.

Study of pumping effect in flow-through electrolysers

1983 ◽  
Vol 48 (8) ◽  
pp. 2232-2248 ◽  
Author(s):  
Ivo Roušar ◽  
Michal Provazník ◽  
Pavel Stuhl
Keyword(s):  
Natural Convection ◽  
Balance Equation ◽  
Volume Fraction ◽  
Industrial Applications ◽  
Pumping Effect ◽  
Flow Through ◽  
The Mean ◽  
The Difference

In electrolysers with recirculation, where a gas is evolved, the pumping of electrolyte from a lower to a higher level can be effected by natural convection due to the difference between the densities of the inlet electrolyte and the gaseous emulsion at the outlet. An accurate balance equation for calculation of the rate of flow of the pumped liquid is derived. An equation for the calculation of the mean volume fraction of bubbles in the space between the electrodes is proposed and verified experimentally on a pilot electrolyser. Two examples of industrial applications are presented.

scholarly journals Analysis of Performance of the Wind-Driven Pulverizing Aerator Based on Average Wind Speeds in the Conditions of Góreckie Lake

Energies ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2796
Author(s):  
Andrzej Osuch ◽  
Ewa Osuch ◽  
Stanisław Podsiadłowski ◽  
Piotr Rybacki
Keyword(s):  
Mathematical Model ◽  
Wind Speed ◽  
Water Pump ◽  
Average Wind Speed ◽  
Flow Rates ◽  
Wind Speeds ◽  
Average Wind ◽  
Flow Through ◽  
Analysis Of Performance ◽  
Research Period

In the introduction to this paper, the characteristics of Góreckie lake and the construction and operation of the wind-driven pulverizing aerator are presented. The purpose of this manuscript is to determine the efficiency of the pulverizing aerator unit in the windy conditions of Góreckie Lake. The efficiency of the pulverization aerator depends on the wind conditions at the lake. It was necessary to conduct thorough research to determine the efficiency of water flow through the pulverization segment (water pump). It was necessary to determine the rotational speed of the paddle wheel, which depended on the average wind speed. Throughout the research period, measurements of hourly average wind speed were carried out. It was possible to determine the efficiency of the machine by developing a dedicated mathematical model. The latest method was used in the research, consisting of determining the theoretical volumetric flow rates of water in the pulverizing aerator unit, based on average hourly wind speeds. Pulverization efficiency under the conditions of Góreckie Lake was determined based on 6600 average wind speeds for spring, summer and autumn, 2018. Based on the model, the theoretical efficiency of the machine was calculated, which, under the conditions of Góreckie Lake, amounted to 75,000 m3 per year.

scholarly journals Antiproliferative function of glia maturation factor beta.

1990 ◽  
Vol 1 (10) ◽  
pp. 741-746 ◽  
Author(s):  
R Lim ◽  
W X Zhong ◽  
A Zaheer
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Target Cell ◽  
G1 Phase ◽  
Glia Maturation Factor ◽  
Pituitary Extract ◽  
Mitogenic Effect ◽  
Maturation Factor ◽  
Cultured Astrocytes

Recombinant human glia maturation factor beta (GMF-beta) reversibly inhibits the proliferation of neoplastic cells in culture by arresting the cells in the G0/G1 phase. This phenomenon is not target-cell specific, as neural and nonneural cells are equally inhibited. When tested simultaneously, GMF-beta suppresses the mitogenic effect of acidic fibroblasts growth factor (aFGF), but the two are synergistic in promoting the morphologic differentiation of cultured astrocytes. GMF-beta also counteracts the growth-stimulating effect of pituitary extract and cholera toxin on Schwann cells. The results underscore the regulatory role of GMF-beta and its intricate interaction with the mitogenic growth factors.

Mechanisms of renal tubular cell hypertrophy: mitogen-induced suppression of proteolysis

1997 ◽  
Vol 273 (3) ◽  
pp. C843-C851 ◽  
Author(s):  
H. A. Franch ◽  
P. V. Curtis ◽  
W. E. Mitch
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Degradation ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Renal Tubular Cell ◽  
Kidney Cells ◽  
Tgf Beta ◽  
Lysosomal Proteolysis

The combination of epidermal growth factor (EGF) plus transforming growth factor-beta 1 (TGF-beta 1) causes hypertrophy in renal epithelial cells. One mechanism contributing to hypertrophy is that EGF induces activation of the cell cycle and increases protein synthesis, whereas TGF-beta 1 prevents cell division, thereby converting hyperplasia to hypertrophy. To assess whether suppression of proteolysis is another mechanism causing hypertrophy induced by these growth factors, we measured protein degradation in primary cultures of proximal tubule cells and in cultured NRK-52E kidney cells. A concentration of 10(-8) M EGF alone or EGF plus 10(-10) M TGF-beta 1 decreased proteolysis by approximately 30%. TGF-beta 1 alone did not change protein degradation. Using inhibitors, we examined which proteolytic pathway is suppressed. Neither proteasome nor calpain inhibitors prevented the antiproteolytic response to EGF + TGF-beta 1. Inhibitors of lysosomal proteases eliminated the antiproteolytic response to EGF + TGF-beta 1, suggesting that these growth factors act to suppress lysosomal proteolysis. This antiproteolytic response was not caused by impaired EGF receptor signaling, since lysosomal inhibitors did not block EGF-induced protein synthesis. We conclude that suppression of lysosomal proteolysis contributes to growth factor-mediated hypertrophy of cultured kidney cells.

Cell-free, protein-synthesizing system of photosynthetic and heterotrophic Rhodospirillum rubrum

1976 ◽  
Vol 22 (2) ◽  
pp. 304-308
Author(s):  
C. T. Chow
Keyword(s):  
Protein Synthesis ◽  
Protease Activity ◽  
Rhodospirillum Rubrum ◽  
Chemical Compounds ◽  
Protein Synthesis Inhibitors ◽  
Free Protein ◽  
Two Systems ◽  
The Difference ◽  
Vitro Protein

An active in vitro protein-synthesizing system has been developed from Rhodospirillum rubrum grown under either photosynthetic or heterotrophic conditions. A protease activity has been found in both of these systems, and this activity can be readily inactivated by treating the cells with KCl and phenylmethyl sulfonylfluoride. The difference in protein-synthesizing activity between the photosynthetic and the heterotrophic systems has been tested in regard to the requirement of various chemicals and the response to protein synthesis inhibitors or various chemical compounds. It has been concluded that only minor differences in protein-synthesizing activity exist between these two systems.

Effect of prolonged exposition to growth factors differently on proliferation of CRC cell cultures encapsulated in alginate.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15610-e15610
Author(s):  
Svetlana Yu. Filippova ◽  
Anastasia O. Sitkovskaya ◽  
Irina V. Mezhevova ◽  
Sofia V. Timofeeva ◽  
Tatiana V. Shamova ◽  
...  
Keyword(s):  
Growth Factors ◽  
Culture Media ◽  
Alginate Beads ◽  
Encapsulated Cells ◽  
Test Systems ◽  
The Difference ◽  
High Doses ◽  
Culturing Conditions ◽  
Ht 29 ◽  
Resistant Cells

e15610 Background: Cancer stem cells (CSCs) are promising targets in modern oncology. A lot of CSCs enrichment and cultivation techniques are being currently developed. Most of the approaches deploy high doses of growth factors in culture media, - EGF and FGF2 above all, - without prior testing. Since prolonged exposition to growth factors may cause paradoxical growth inhibition it is worth developing test systems to evaluate culturing conditions before establishing the main experiment. Encapsulation in alginate may serve as a promising approach to develop such test-systems due to alginate reduced ability to adsorb proteins and maintain proper attachment to the ECM of non-stem cell even in the presence of serum. It is important to notice that serum addition may be crucial during initial stages of primary CSCs culture establishment. The aim of the study was to test EGF and FGF2 effects on anoikis resistant cells growth in permanent colorectal cancer cell lines. Methods: The cells of Caco-2, HT-29, and HCT 116 cultures were encapsulated in 1% alginate beads at a concentration of 100 000 cells/ml. Subsequently encapsulated cells were kept in 2 variants of culture media: DMEM/F12 + 10%FBS with and without addition of growth factors (EGF 20 ng/ml, FGF2 10 ng/ml). The cultivation was carried out for 10 days, after that the colonies area (A) was measured. Data are given as: Mean ± 95% confidence interval. Results: The average area of Caco-2 culture colonies increased significantly with the addition of growth factors (FBS only A = 1755.16±195.87 μm2, with additional growth factors Af = 3270.57±274.91 μm2), the difference was significant (t = 8.83, n = 300, p < 0,05). The area of HCT116 colonies after growth factors addition increased only slightly (A = 2844.89±461.57 μm2, Af = 3530.31±503.85 μm2), the difference nevertheless did not reach significant values (t = 1.94, n = 300, p > 0.05). At the same time, the area of HT-29 colonies significantly decreased in the culture medium containing additional growth factors (A = 4605.10±324.02 μm2, Af = 3167.85±249.07 μm2), the difference was significant (t = 6.92, n = 300, p < 0.05). Conclusions: Combining alginate encapsulation and colonies size measurement enabled us to evaluate culturing conditions of anoikis resistant cells in permanent CRC cultures and proved growth factors addition to be an ambiguous practice in CSCs research. This tactics can be applied in a broad spectrum of tasks concerning more effective CSCs medium formulations development.

Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction

2021 ◽  
Author(s):  
Feng Li-Li ◽  
Li Bo-Wen ◽  
Xi Yue ◽  
Tian Zhen-Jun ◽  
Cai Meng-Xin
Keyword(s):  
Myocardial Infarction ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Aerobic Exercise ◽  
Muscle Atrophy ◽  
Cell Apoptosis ◽  
Exercise Group ◽  
Skeletal Muscle Atrophy ◽  
Akt Pathway

Objectives: Myocardial infarction (MI)-induced heart failure (HF) is commonly accompanied with profound effects on skeletal muscle. With the process of MI-induced HF, perturbations in skeletal muscle contribute to muscle atrophy. Exercise is viewed as a feasible strategy to prevent muscle atrophy. The aims of this study were to investigate whether exercise could alleviate MI-induced skeletal muscle atrophy via insulin-like growth factor 1 (IGF-1) pathway in mice. Materials and Methods: Male C57/BL6 mice were used to establish the MI model and divided into three groups: sedentary MI group, MI with aerobic exercise group and MI with resistance exercise group, sham-operated group was used as control. Exercise-trained animals were subjected to four-weeks of aerobic exercise (AE) or resistance exercise (RE). Cardiac function, muscle weight, myofiber size, levels of IGF-1 signaling and proteins related to myogenesis, protein synthesis and degradation and cell apoptosis in gastrocnemius muscle were detected. And H2O2-treated C2C12 cells were intervened with recombinant human IGF-1, IGF-1R inhibitor NVP-AEW541 and PI3K inhibitor LY294002 to explore the mechanism. Results：Exercises up-regulated the IGF-1/IGF-1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling, increased the expressions of Pax7, myogenic regulatory factors (MRFs) and protein synthesis, reduced protein degradation and cell apoptosis in MI-mice. In vitro, IGF-1 up-regulated the levels of Pax7 and MRFs, mTOR and P70S6K, reduced MuRF1, MAFbx and inhibited cell apoptosis via IGF-1R-PI3K/Akt pathway. Conclusion: AE and RE, safely and effectively, alleviate skeletal muscle atrophy by regulating the levels of myogenesis, protein degradation and cells apoptosis in mice with MI via activating IGF-1/IGF-1R-PI3K/Akt pathway.

Effect of small doses of 5-hydroxytryptamine (serotonin) on pulmonary circulation in the closed-chest dog

1959 ◽  
Vol 197 (5) ◽  
pp. 963-967 ◽  
Author(s):  
John T. Shepherd ◽  
David E. Donald ◽  
Erland Linder ◽  
H. J. C. Swan
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Blood Flow ◽  
Pulmonary Veins ◽  
Pulmonary Vessels ◽  
Isolated Perfused Lung ◽  
Small Doses ◽  
Perfused Lung ◽  
Anesthetized Dogs ◽  
Flow Through ◽  
The Difference

5-Hydroxytryptamine (serotonin) was infused into anesthetized dogs at a rate of 20 µg/kg/min. In nine sets of observations on three dogs the increase in the difference of pressure between the pulmonary artery and the left atrium, which averaged 55%, consistently exceeded the increase in pulmonary blood flow, which averaged 16%. 5-HT therefore is a potent constrictor of pulmonary vessels, even in small concentrations. No changes in the pulmonary-artery wedge and pulmonary-vein pressures were detected during the infusions of 5-HT, nor was there any change in the volume of blood between the pulmonary artery and the root of the aorta. With this dose of 5-HT the principal site of the increased resistance to flow through the lungs appeared to be in the precapillary vessels. In the isolated perfused lung, moderate constriction of pulmonary veins also was produced by large doses of 5-HT.

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