scholarly journals Structure analysis of purified histone H5 and of H5 in nuclei by limited proteolysis

1992 ◽  
Vol 282 (2) ◽  
pp. 435-441
Author(s):  
M Hallupp ◽  
F Buck ◽  
W H Strätling
Keyword(s):  
Central Region ◽  
Limited Proteolysis ◽  
Structural Features ◽  
Compact Structure ◽  
Core Domain ◽  
Histone H5 ◽  
Unstructured Protein ◽  
Exposed Location

The structure of purified histone H5 in 1 M-NaClO4 and of H5 in nuclei was analysed by digestion with either one of three endoproteinases, papain, subtilisin or elastase, which preferentially cleave unstructured protein regions (and additionally with trypsin). Digestion with papain and subtilisin produced ‘limiting’ resistant peptides (p1 and s1) that contain the central region between residues 18-20 and residue 114. Digestion of purified H5 with elastase generated resistant peptides e1 and e2, and that of H5 in nuclei, peptide e2. Peptides e1 and e2 contain the region from residues 22 to 114 and 109 respectively. These results show that a central region of H5 encompassing the sequence between residues 18-22 and residue 114 is folded into a compact structure. A central structured ‘core’ domain ranging from residues 22 to 100 is defined by the limit trypsin peptide t3, which is identical to the previously described fragment GH5 [Aviles et al. (1978) Eur. J. Biochem. 88, 363-371]. Generation of peptides e2 and t3, as well as of resistant peptides of lower abundance, shows that the sites near Lys-100 and Lys-109 exhibit some proteolytic sensitivity, which may result either from an exposed location or from a locally less compact conformation. Significantly, all these structural features of H5 are manifested in the purified form as well as in nuclei. A role of the structured region from residues 101 to 114 for the interaction with linker DNA and the determination of its path is discussed.

scholarly journals Role of thiols in degradation of proteins by cathepsins

1982 ◽  
Vol 204 (2) ◽  
pp. 471-477 ◽  
Author(s):  
T Kooistra ◽  
P C Millard ◽  
J B Lloyd
Keyword(s):  
Cathepsin D ◽  
Limited Proteolysis ◽  
Lysosomal Storage ◽  
Protein Substrates ◽  
Disulphide Bonds ◽  
Protection Method ◽  
Opening Up ◽  
Lysosome Membrane

The effects of thiols on the breakdown of 125I-labelled insulin, albumin and formaldehyde-treated albumin by highly purified rat liver cathepsins B, D, H and L at pH 4.0 and 5.5 were studied. At both pH values degradation was strongly activated by the thiols cysteamine, cysteine, dithiothreitol, glutathione and 2-mercaptoethanol, and its rate increased with increasing thiol concentration. Preincubation of the protein substrates with 5 mM-glutathione did not affect concentration. Preincubation of the protein substrates with 5 mM-glutathione did not affect the rate of degradation by cathepsin D or L, and determination of free thiol groups after incubation of the proteins in the presence of glutathione but without cathepsin showed that their disulphide bonds were stable under the incubation conditions. Sephadex G-75 chromatography of the acid-soluble products of insulin digestion by cathepsin D or L suggested that thiols can reduce disulphide bonds in proteins after limited proteolysis. The resultant opening-up of the protein structure would lead to further proteolysis, so that the two processes (proteolysis and reduction) may act synergistically. By using the osmotic protection method it was shown that, at a physiological pH, cysteamine, and its oxidized form cystamine, can cross the lysosome membrane and thus may well be the physiological hydrogen donor for the reduction of disulphides in lysosomes. The results are discussed in relation to the lysosomal storage disease cystinosis.

scholarly journals The role of conformational entropy in the determination of structural-kinetic relationships for helix-coil transitions

2017 ◽  
Author(s):  
Joseph F. Rudzinski ◽  
Tristan Bereau
Keyword(s):  
Simulation Models ◽  
Structural Features ◽  
Coarse Grained ◽  
Kinetic Properties ◽  
Conformational Entropy ◽  
Peptide Backbone ◽  
The Relationship ◽  
Insight Into

Coarse-grained molecular simulation models can provide significant insight into the complex behavior of protein systems, but suffer from an inherently distorted description of dynamical properties. We recently demonstrated that, for a heptapeptide of alanine residues, the structural and kinetic properties of a simulation model are linked in a rather simple way, given a certain level of physics present in the model. In this work, we extend these findings to a longer peptide, for which the representation of configuration space in terms of a full enumeration of sequences of helical/coil states along the peptide backbone is impractical. We verify the structural-kinetic relationships by scanning the parameter space of a simple native-biased model and then employ a distinct transferable model to validate and generalize the conclusions. Our results further demonstrate the validity of the previous findings, while clarifying the role of conformational entropy in the determination of the structural-kinetic relationships. More specifically, while the global, long timescale kinetic properties of a particular class of models with varying energetic parameters but approximately fixed conformational entropy are determined by the overarching structural features of the ensemble, a shift in these kinetic observables occurs for models with a distinct representation of steric interactions. At the same time, the relationship between structure and more local, faster kinetic properties is not affected by varying the conformational entropy of the model.

scholarly journals Predicting Individual Pain Thresholds From Morphological Connectivity Using Structural MRI: A Multivariate Analysis Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Rushi Zou ◽  
Linling Li ◽  
Li Zhang ◽  
Gan Huang ◽  
Zhen Liang ◽  
...  
Keyword(s):  
Pain Sensitivity ◽  
Brain Connectivity ◽  
Structural Mri ◽  
Structural Features ◽  
Clinical Settings ◽  
Pain Thresholds ◽  
The Relationship ◽  
The Brain

Pain sensitivity is highly variable among individuals, and it is clinically important to predict an individual’s pain sensitivity for individualized diagnosis and management of pain. Literature has shown that pain sensitivity is associated with regional structural features of the brain, but it remains unclear whether pain sensitivity is also related to structural brain connectivity. In the present study, we investigated the relationship between pain thresholds and morphological connectivity (MC) inferred from structural MRI based on data of 221 healthy participants. We found that MC was highly predictive of an individual’s pain thresholds and, importantly, it had a better prediction performance than regional structural features. We also identified a number of most predictive MC features and confirmed the crucial role of the prefrontal cortex in the determination of pain sensitivity. These results suggest the potential of using structural MRI-based MC to predict an individual’s pain sensitivity in clinical settings, and hence this study has important implications for diagnosis and treatment of pain.

AT III BINDING SITE OF HEPARIN. DETERMINATION OF THE ROLE OF SULFATE GROUPS AT THE REDUCING-END DISACCHARIDE THROUGH NEW SYNTHETIC PENTASACCHARIDES

1987 ◽  
Author(s):  
M Petitou ◽  
J C Lormeau ◽  
J Choay
Keyword(s):  
Antithrombin Iii ◽  
Factor Xa ◽  
Structural Features ◽  
Sulfate Group ◽  
Naturally Occurring ◽  
At Iii ◽  
Antifactor Xa ◽  
Similar Decrease

A unique sequence is required in heparin for binding to antithrombin III (AT III) and eliciting anti-factor Xa activity. We have previously synthesized a pentasaccharide containing all the structural features of this sequence. It binds to AT III with the same affinity as high affinity heparin. The complex thus formed has a high anti-factor Xa activity. We have now synthesized a new series of α-methylated pentasaccharides which better mimic the naturally occurring configuration at C1 of the reducing-end glucosamine unit. The synthesis of the inactive pentasaccharide II allowed us to confirm in this series the essential role of the 3-sulfate group borne by glucosamine unit F. Wehave also particularly addressed the still unanswered question regarding the role of the 2-sulfate group borne by iduronic acid G and of the 6-sulfate group borne by glucosamine unit H. Pentasaccharides III and IV elicit the same anti-factor Xa activity which is substantially decreased as compared to I. A similar decrease has been recently reported for pentasaccharide V (T. Beetz & C.A.A. van Boeckel, Tetrahedron Lett., 1986, 27, 5889). We therefore conclude that the presence of both these sin fate groups is required for full expression of the antifactor Xa activity.

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.

DETERMINATION OF THE TYPE OF A SINGLE-USE GRENADE LAUNCHER BASED ON ITS COMPOSITE PARTS AND FRAGMENTS OF REACTIVE GRENADE FOUND AT THE PLACE OF ACCIDENT

2017 ◽  
Vol 17 ◽  
pp. 245-252
Author(s):  
V. V. Somov
Keyword(s):  
Combustion Chamber ◽  
Structural Features ◽  
Outlet Section ◽  
Technical Expertise ◽  
Jet Engine ◽  
Size Ofthe ◽  
Single Use ◽  
Nozzle Block ◽  
Considerable Damage

In carrying out an investigation into the explosion, among others, the investigative version of the use of a single-use reactive grenade launcher is being considered. The most common for criminal explosions are applied grenade launchers RPG-18, RPG-22, RPG-26. Their use is due to a number of such properties as small size and weight, which makes it possible to transfer them covertly, the range of the shot significantly exceeding the range of the hand grenade throw, the high detonating effect of the rocket grenade explosion. The single-use rocket launchers are generally of the same design. Their differences are in the features of the components construction and dimensional characteristics, which are given in the article. On the basis of expert practice, details ofgrenade launchers that remain at the site of the explosion and have the least damage are determined. These details are the objects of investigation of the explosion technical expertise. These objects include launchers of grenade launchers and rocket parts ofjet grenades. The design features of the launchers, their dimensional characteristics and marking symbols make it possible to determine their belonging to a specific type of jet grenade launchers. Missile parts of jet grenades differ in the form of the combustion chamber of the jet engine, nozzle, in the size ofthe outlet section of the nozzle, in the form and size of the stabilizerfeathers. To determine the belonging of the rocket part of the grenade to a specific type ofjet grenade launcher, it’s necessary to establish a set of structural features and dimensional characteristics. At considerable damage of the combustion chamber of the jet engine, as a rule, the nozzle block remains intact that allows to define diameter of critical section of a nozzle, and on it to establish type of the used single-use grenade launcher.

ІНТЕРПРЕТАЦІЯ КАТЕГОРІЇ РОЗВИТКУ В СУЧАСНІЙ ПСИХОЛОГІЇ

1970 ◽  
Vol 8 (1) ◽  
pp. 22-30
Author(s):  
Анжеліка Шамне
Keyword(s):  
Cultural Context ◽  
Developmental Psychology ◽  
Structure And Dynamics ◽  
Modern Psychology ◽  
Development Site ◽  
Approaches To Study ◽  
Methodological Approaches ◽  
Self Motion

У статті розглянуто сучасні підходи до інтерпретації категорії розвитку, розкрито теоретичні  та методологічні підходи до вивчення категорії розвитку у сучасній психології, визначено її психологічний  зміст,   моделі,   структуру   та   динаміку.   Категорія   розвитку   розглядається   як   епіцентр   наукової  проблематики у психології та як поняття інтегративного типу. Розвиток проаналізовано як категорію,  явище і проблему психології розвитку в різних аспектах аналізу. Розглянуто місце розвитку в системі  споріднених психологічних понять. У статті також аналізуються психологічні аспекти теоретичних та  методологічних  постнекласичних  тенденцій  вивчення  природи,  характеру  та  визначення  психічного  розвитку. Постнекласична парадигма та плюралістична методологія пізнання визначають розмитість  дисциплінарної мови  та  врахування  ролі  соціокультурного  контексту  при  вивченні  психологічних явищ.  Важливими тенденціями сучасного теоретико-методологічного стану психологічних досліджень розвитку  також є визнання неефективності моністичного підходу до його вивчення, взаємозв'язок теоретичних ідей  та   спроби   створення   метатеоретичних   схем,   постнекласичне   розуміння   розвитку   як   принципово  незавершеного   процесу   саморуху,   актуалізація   антропологічного   діапазону   проблем   та   посилення  спрямованості на роль культурного контексту в дослідженні розвитку людини.  The article deals with the modern approaches to the interpretation of the category of development, reveals  the theoretical and methodological approaches to study of development in modern psychology, its psychological  content, patterns, structure and dynamics. Category of development is viewed as an epicenter of scientific issues in  modern  psychology  and  the  concept  of  the  integrative  type.  Category  of  development  is  considered  as  the  phenomenon  and  the  problem  of  developmental  psychology  in  various  aspects  of  the  analysis.  Analyzed  the  development site in the related psychological concepts. The article analyzes the psychological aspects of theoretical  and methodological postnonclassical contemporary trends in the study of nature, character, and determination of  mental  development.  Postnonclassical  paradigm  and  pluralistic  methodology  of  knowledge  determine  the  disciplinary blurring and increase of the role of the analysis of socio-cultural context in the study of psychological  phenomenon. The important tendencies of modern theoretical and methodological state of psychological researches  of development are facts of inefficiency of the monistic approach to its study, interconnection of theoretical ideas  and   attempts   of  creating   metatheoretical   schemes,   postnonclassical   understanding   of   development   as   a  fundamentally  uncompleted  process  of  self-motion,  actualization  of  anthropological  range  of  problems  and  strengthening of focus on the role of cultural context in research of human development.   

Role of the family focused technologies in the clinical course of pregnancy at women of high obstetric risk

2016 ◽  
pp. 64-66
Author(s):  
S.Yu. Vdovichenko ◽  
Keyword(s):  
Comparison Group ◽  
Traditional Approach ◽  
Married Couple ◽  
Premature Births ◽  
Individual Support ◽  
The Family ◽  
Risk Patients ◽  
Individual Preparation

The objective: to show a role of the family focused technologies in depression of frequency of pathology of pregnancy at women of high obstetric risk. Patients and methods. For determination of efficiency of prophylaxis of pathology of pregnancy on the basis of use of the family focused technologies complex clinical-psychological and laboratory and tool examination of 300 women with factors of obstetric risk which were divided into two groups was conducted. In the main group – 182 women with motivation on partner labors to which provided training on system of individual preparation of married couple to labors. The comparison group consisted of 118 women who were not in prenatal training and had individual support in childbirth, with the traditional approach to pain management. Results. Use of the family focused technologies during pregnancy allows to reduce significantly the frequency of the main complications of pregnancy, especially not incubation and premature births. Conclusion. In our opinion, the technique is simple, available and can widely be used in practical health care at women with high obstetric risk. Key words: obstetric risk, the family focused technologies, prophylaxis.

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