scholarly journals On the Dependence of Prion and Amyloid Structure on the Folding Environment

2021 ◽  
Vol 22 (24) ◽  
pp. 13494
Author(s):  
Irena Roterman ◽  
Katarzyna Stapor ◽  
Krzysztof Gądek ◽  
Tomasz Gubała ◽  
Piotr Nowakowski ◽  
...  
Keyword(s):  
Force Field ◽  
Structural Changes ◽  
Water Environment ◽  
Hydrophobic Core ◽  
External Force Field ◽  
Protein Status ◽  
Starting Point ◽  
Transformation Processes

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.

scholarly journals Model of Environmental Membrane Field for Transmembrane Proteins

2021 ◽  
Vol 22 (7) ◽  
pp. 3619
Author(s):  
Irena Roterman ◽  
Katarzyna Stapor ◽  
Piotr Fabian ◽  
Leszek Konieczny ◽  
Mateusz Banach
Keyword(s):  
Membrane Proteins ◽  
Protein Modification ◽  
Water Environment ◽  
Water Soluble ◽  
Hydrophobic Core ◽  
Hydrophobic Membrane ◽  
Simultaneous Exposure ◽  
Significant Group ◽  
Highly Hydrophobic

The water environment determines the activity of biological processes. The role of such an environment interpreted in the form of an external field expressed by the 3D Gaussian distribution in the fuzzy oil drop model directs the folding process towards the generation of a centrally located hydrophobic core with the simultaneous exposure of polar residues on the surface. In addition to proteins soluble in the water environment, there is a significant group of membrane proteins that act as receptors or channels, including ion channels in particular. The change of the polar (water) environment into a highly hydrophobic (membrane) environment is quite radical, resulting in a different hydrophobicity distribution within the membrane protein. Modification of the notation of the force field expressing the presence of the hydrophobic environment has been proposed in this work. A modified fuzzy oil drop model with its adaptation to membrane proteins was used to interpret the structure of membrane proteins–mechanosensitive channel. The modified model was also used to describe the so-called negative cases—i.e., for water-soluble proteins with a clear distribution consistent with the fuzzy oil drop model.

scholarly journals A importância do relacionamento bancário no financiamento das PME: estudo numa agência bancária portuguesa

2014 ◽  
Vol 12 (3) ◽  
pp. 291
Author(s):  
Armando Mendes Jorge Nogueira da Silva ◽  
Silvia Maria Graça Braga
Keyword(s):  
Regression Analysis ◽  
Risk Premium ◽  
Explanatory Model ◽  
Firm Reputation ◽  
Financial Situation ◽  
Starting Point ◽  
Variable Duration ◽  
Banking Relationships

Taking, as starting point, a sample of small and medium-sized (SME) Portuguese companies customers of credit of a given bank branch, we examine empirically the role of both banking relationships and the economic and financial situation of the firms in the determination of the funding conditions obtained. Based on multiple regression analysis, it was found that, for the explanatory model of the level of the risk premium, the variables that showed significance for such explanation were the firm reputation, the amount of credit granted and also the overall liquidity of the customer. Regarding the explanatory model of the amount of credit granted, the variable duration has a significant impact, indicating that relationships are valuable in such issue. In both models, the variables that have shown to have a greater impact on the amount and price of the granted credit available were variables related to the economic and financial performance of the firms

Mass Media

2019 ◽  
pp. 558-563
Author(s):  
Barbara Thomaß
Keyword(s):  
Mass Media ◽  
Arab World ◽  
The Political ◽  
Cultural Dimension ◽  
Media System ◽  
Pluralistic Societies ◽  
Starting Point ◽  
The Media ◽  
Transformation Processes

A normative or a functionalist perspective on the role of mass media in pluralistic societies is the starting point for analysis of the role of the media in changing societal systems. The correlation between media shifts and societal shifts is striking in transformation processes. Communication scholars have studied this correlation in respect of the transformation in Eastern Europe, the upheavals in the Arab world, but less in the various waves of transformation and case groups. The uncoupling of the media system from the political system, which is typical for the shift from a totalitarian or authoritarian society to a pluralist one, is restructuring processes with an organizational, an economic, and a cultural dimension. It has been modelled in several phases although the actual developments show how these phases can overlap, sustain setbacks, or occur rapidly. Recent research concentrates on these new patterns of transitions and the inherent conflicts.

scholarly journals Structure of the Hydrophobic Core Determines the 3D Protein Structure—Verification by Single Mutation Proteins

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 767 ◽  
Author(s):  
Mateusz Banach ◽  
Piotr Fabian ◽  
Katarzyna Stapor ◽  
Leszek Konieczny ◽  
and Irena Roterman
Keyword(s):  
Tertiary Structure ◽  
Polypeptide Chain ◽  
De Novo ◽  
Water Environment ◽  
Single Mutation ◽  
Hydrophobic Core ◽  
3D Protein Structure ◽  
Folding Process ◽  
External Force Field ◽  
A Chain

Four de novo proteins differing in single mutation positions, with a chain length of 56 amino acids, represent diverse 3D structures: monomeric 3α and 4β + α folds. The reason for this diversity is seen in the different structure of the hydrophobic core as a result of synergy leading to the generation of a system in which the polypeptide chain as a whole participates. On the basis of the fuzzy oil drop model, where the structure of the hydrophobic core is expressed by means of the hydrophobic distribution function in the form of a 3D Gaussian distribution, it has been shown that the composition of the hydrophobic core in these two structural forms is different. In addition, the use of a model to determine the structure of the early intermediate in the folding process allows to indicate differences in the polypeptide chain geometry, which, combined with the construction of a common hydrophobic nucleus as an effect of specific synergy, may indicate the reason for the diversity of the folding process of the polypeptide chain. The results indicate the need to take into account the presence of an external force field originating from the water environment and that its active impact on the formation of a hydrophobic core whose participation in the stabilization of the tertiary structure is fundamental.

scholarly journals Effect of ligands on HP-induced unfolding and oligomerization of β-lactoglobulin

2020 ◽  
Author(s):  
S. Minić ◽  
B. Annighöfer ◽  
A. Hélary ◽  
D. Hamdane ◽  
G. Hui Bon Hoa ◽  
...  
Keyword(s):  
Absorption Spectroscopy ◽  
Protein Unfolding ◽  
Structural Changes ◽  
Bioactive Molecules ◽  
Visible Absorption ◽  
Hydrophobic Cavity ◽  
Β Lactoglobulin

ABSTRACTTo probe intermediate states during unfolding and oligomerization of proteins remains a major challenge. High pressure (HP) is a powerful tool for studying these problems, revealing subtle structural changes in proteins not accessible by other means of denaturation. Bovine β-lactoglobulin (BLG), the main whey protein, has a strong propensity to bind various bioactive molecules, such as retinol and resveratrol, two ligands with different affinity and binding sites. By combining in situ HP-small-angle neutron scattering (SANS) and HP-UV/visible absorption spectroscopy, we report the specific effects of these ligands on 3D conformational and local changes in BLG induced by HP. Depending on BLG concentration, two different unfolding mechanisms are observed in situ under pressures up to ~300 MPa, mediated by the formation of disulfide bonds: either a complete protein unfolding, from native dimers to Gaussian chains, or a partial unfolding with oligomerization in tetramers. Retinol, which has a high affinity for BLG hydrophobic cavity, significantly stabilizes BLG both in 3D and local environments, by shifting the onset of protein unfolding by ~100 MPa. Increasing temperature from 30 to 37°C enhances the hydrophobic stabilization effects of retinol. In contrast, resveratrol, which has a low binding affinity for site(s) on the surface of the BLG, does not induce any significant effect on the structural changes of BLG due to pressure. HP treatment back and forth up to ~300 MPa causes irreversible covalent oligomerization of BLG. Ab initio modeling of SANS shows that the oligomers formed from BLG/retinol complex are smaller and more elongated compared to BLG without ligand or in the presence of resveratrol. By combining HP-SANS and HP-UV/vis absorption spectroscopy, our strategy highlights the crucial role of BLG hydrophobic cavity and opens up new possibilities for the structural determination of HP-induced protein folding intermediates and irreversible oligomerization.STATEMENT OF SIGNIFICANCEHigh pressure (HP) is a powerful probe to access the intermediate states of proteins through subtle structural changes not accessible by other means of denaturation. Bovine β-lactoglobulin (BLG), the main whey protein, is able to bind various bioactive molecules, such as retinol and resveratrol, exhibiting different affinity and binding sites. By combining HP-small-angle neutron scattering and HP-UV/visible absorption spectroscopy, we highlight two different mechanisms during the unfolding and oligomerization of BLG depending on protein concentration. Above all, we show that retinol significantly prevents the unfolding and oligomerization of BLG, unlike resveratrol, emphasizing the crucial role of the hydrophobic cavity in BLG stabilization. Our strategy opens up new possibilities for the structural determination of protein intermediates and oligomers using HP.

scholarly journals The Role of Albumin in Human Toxicology of Cobalt: Contribution from a Clinical Case

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Simona Catalani ◽  
Roberto Leone ◽  
Maria Cristina Rizzetti ◽  
Alessandro Padovani ◽  
Pietro Apostoli
Keyword(s):  
Whole Blood ◽  
Inductively Coupled Plasma ◽  
Colorimetric Assay ◽  
Free Fraction ◽  
Inductively Coupled ◽  
Icp Ms ◽  
Starting Point ◽  
Plasma Mass Spectrometry

The distribution and adverse effects, especially to optic and acoustic nerves, of cobalt released from a hip arthroplasty and its association with albumin were studied. The analysis of cobalt was performed in plasma, whole blood, urine, and cerebrospinal fluid by inductively coupled plasma mass spectrometry (ICP-MS). The fraction of albumin binding the metal was determined by colorimetric assay using dithiothreitol (DTT). In all the biological matrices very high levels of cobalt were measured, but contrary to expected, a higher concentration in whole blood than in plasma was observed. The determination of altered albumin confirmed this hypothesis. This evidence might indicate an alteration in the binding of cobalt to albumin and a consequent increase in the concentration of the diffusible (free) fraction of the metal. This appears an interesting starting point for further investigations for identifying and better understanding cobalt neurotoxicity, apparently not so frequent in occupational medicine and clinical practice.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

Economic Growth: New Problems and New Risks

2006 ◽  
pp. 20-37 ◽  
Author(s):  
M. Ershov
Keyword(s):  
Economic Growth ◽  
Foreign Exchange ◽  
Driving Force ◽  
Structural Changes ◽  
Rate Of Growth

The economic growth, which is underway in Russia, raises new questions to be addressed. How to improve the quality of growth, increasing the role of new competitive sectors and transforming them into the driving force of growth? How can progressive structural changes be implemented without hampering the rate of growth in general? What are the main external and internal risks, which may undermine positive trends of development? The author looks upon financial, monetary and foreign exchange aspects of the problem and comes up with some suggestions on how to make growth more competitive and sustainable.

INTERPRETATION OF SINO-RUSSIAN CULTURE AND HUMANITIES COOPERATION IN THE NEW ERA

2020 ◽  
Vol 10 (3) ◽  
pp. 186-193
Author(s):  
REN YANYAN ◽  
Keyword(s):  
Current Status ◽  
Human Relations ◽  
New Era ◽  
Russian Culture ◽  
The People ◽  
Starting Point ◽  
Cooperative Partnership ◽  
Belt And Road ◽  
The Belt And Road

The friendship between nations lies in the mutual affinity of the people, and the people’s affinity lies in the communion of hearts. The cultural and humanities cooperation between China and Russia has a long history. In recent years, under the role of the“Belt and Road” initiative, the SCO, and the Sino-Russian Humanities Cooperation Committee, Sino-Russian culture and humanities cooperation has continued to deepen. Entering a new era, taking the opportunity to promote Sino-Russian relations into a “new era China-Russia comprehensive strategic cooperative partnership”, the development of human relations between the two countries has entered a new historical starting point, while also facing a series of problems and challenges. This article is based on the current status of Sino-Russian human relations in the new era, interprets the characteristics of Sino-Russian human relations in the new era, analyzes the problems and challenges of Sino-Russian human relations in the new era, and tries to propose solutions and solutions with a view to further developing Sino-Russian cultural and humanities relations in the new era. It is a useful reference, and provides a reference for future related research, and ultimately helps the Sino-Russian cultural and humanities relations in the new era to be stable and far-reaching.

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