Studies on the Mechanism of Action of Azinomycin B:  Definition of Regioselectivity and Sequence Selectivity of DNA Cross-Link Formation and Clarification of the Role of the Naphthoate

2002 ◽  
Vol 124 (44) ◽  
pp. 13008-13017 ◽  
Author(s):  
Robert S. Coleman ◽  
Ronelito J. Perez ◽  
Christopher H. Burk ◽  
Antonio Navarro
Keyword(s):  
Mechanism Of Action ◽  
Cross Link ◽  
Sequence Selectivity ◽  
Definition Of ◽  
Azinomycin B ◽  
Link Formation

scholarly journals The inhibition of lysyl oxidase in vivo by isoniazid and its reversal by pyridoxal. Effect on collagen cross-linking in the chick embryo

1984 ◽  
Vol 221 (3) ◽  
pp. 837-843 ◽  
Author(s):  
M J Carrington ◽  
T A Bird ◽  
C I Levene
Keyword(s):  
Pyridoxal Phosphate ◽  
Isonicotinic Acid ◽  
Lysyl Oxidase ◽  
Acid Hydrazide ◽  
Chick Embryos ◽  
Cross Link ◽  
Irreversible Inhibitor ◽  
Link Formation

Isonicotinic acid hydrazide (isoniazid) causes a large increase in the salt-solubility of collagen when injected into chick embryos; this change is accompanied by the inactivation of lysyl oxidase (EC 1.4.3.13), the enzyme responsible for initiating cross-link formation in collagen and elastin. In addition, isoniazid markedly decreases the liver content of pyridoxal phosphate. The depletion of pyridoxal phosphate takes approx. 6 h, whereas the inhibition of lysyl oxidase and the increase in collagen solubility occur more slowly. A reversal of these effects of isoniazid can be produced by the subsequent injection of a stoichiometric amount of pyridoxal, supporting the role of pyridoxal as a cofactor for lysyl oxidase. Treatment of chick embryos with beta-aminopropionitrile, an irreversible inhibitor of lysyl oxidase, causes an inhibition of the enzyme, which begins to recover within 24 h but which is not affected by the administration of pyridoxal; with isoniazid inhibition, however, lysyl oxidase activity does not show any sign of recovery by 48 h. It is proposed that isoniazid may cause the inhibition of lysyl oxidase by competing for its obligatory cofactor, pyridoxal phosphate. The potential clinical implications in the therapeutic control of fibrosis are briefly discussed.

Homogeneous Zinc(II) Catalysis in Accelerated Vulcanization I. Reaction-Stage Modeling and Cross-Link Formation

1998 ◽  
Vol 71 (4) ◽  
pp. 750-765 ◽  
Author(s):  
Peter J. Nieuwenhuizen ◽  
Sandjai Timal ◽  
Jeroen M. van Veen ◽  
Jaap G. Haasnoot ◽  
Jan Reedijk
Keyword(s):  
Detailed Knowledge ◽  
Cross Link ◽  
Model Compounds ◽  
Zinc Compounds ◽  
Reaction Stage ◽  
Novel Approach ◽  
Cross Links ◽  
Link Formation ◽  
Stage Modeling

Abstract This paper reports a novel approach for the study of the mechanism of accelerated vulcanization, namely, Reaction-Stage Modeling (RSM). By carefully studying the reactivity of relevant model compounds under selected conditions, detailed knowledge about a particular reaction stage of vulcanization can be obtained. Background, experimental details and synthesis of model compounds are described. An RSM study after cross-link formation in the thiuram- and dithiocarbamate type vulcanization has been performed, and the role of zinc compounds herein was investigated. In contrast to earlier studies, it has appeared that at 140 °C, cross-links form from cross-link precursors solely via disproportionation. Allylic substitution was not observed. Zinc compounds act as catalysts for disproportionation, but especially ZDMC can be regarded as an efficient, soluble molecular turntable for sulfur atoms.

scholarly journals Third row transition metals for the treatment of cancer

2015 ◽  
Vol 373 (2037) ◽  
pp. 20140185 ◽  
Author(s):  
Timothy C. Johnstone ◽  
Kogularamanan Suntharalingam ◽  
Stephen J. Lippard
Keyword(s):  
Mechanism Of Action ◽  
Nuclear Dna ◽  
Large Family ◽  
Cell Entry ◽  
Major Groove ◽  
Cross Link ◽  
Drug Candidates ◽  
Cross Links ◽  
Dna Nucleobases ◽  
Link Formation

Platinum compounds are a mainstay of cancer chemotherapy, with over 50% of patients receiving platinum. But there is a great need for improvement. Major features of the cisplatin mechanism of action involve cancer cell entry, formation mainly of intrastrand cross-links that bend and unwind nuclear DNA, transcription inhibition and induction of cell-death programmes while evading repair. Recently, we discovered that platinum cross-link formation is not essential for activity. Monofunctional Pt compounds such as phenanthriplatin, which make only a single bond to DNA nucleobases, can be far more active and effective against a range of tumour types. Without a cross-link-induced bend, monofunctional complexes can be accommodated in the major groove of DNA. Their biological mechanism of action is similar to that of cisplatin. These discoveries opened the door to a large family of heavy metal-based drug candidates, including those of Os and Re, as will be described.

Challenges of Fear Conditioning Research in the Age of RDoC

2017 ◽  
Vol 225 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Tina B. Lonsdorf ◽  
Jan Richter
Keyword(s):  
Fear Conditioning ◽  
Clinical Diagnosis ◽  
Research Domain Criteria ◽  
Major Focus ◽  
The Future ◽  
Definition Of ◽  
Methodological Considerations ◽  
Research Domain

Abstract. As the criticism of the definition of the phenotype (i.e., clinical diagnosis) represents the major focus of the Research Domain Criteria (RDoC) initiative, it is somewhat surprising that discussions have not yet focused more on specific conceptual and procedural considerations of the suggested RDoC constructs, sub-constructs, and associated paradigms. We argue that we need more precise thinking as well as a conceptual and methodological discussion of RDoC domains and constructs, their interrelationships as well as their experimental operationalization and nomenclature. The present work is intended to start such a debate using fear conditioning as an example. Thereby, we aim to provide thought-provoking impulses on the role of fear conditioning in the age of RDoC as well as conceptual and methodological considerations and suggestions to guide RDoC-based fear conditioning research in the future.

THEORETICAL DEFINITION OF THE PLACE AND ROLE OF ANTHROPOCENTRISM IN MODERN CONSTITUTIONALISM OF STATE POWER

2019 ◽  
Vol 4 ◽  
pp. 82-88
Author(s):  
Ya.V. Yakymovych ◽  
Keyword(s):  
State Power ◽  
Definition Of

Business Model Literature Overview

2014 ◽  
pp. 79-130 ◽  
Author(s):  
Ales Novak
Keyword(s):  
Business Model ◽  
Financial Reporting ◽  
Business Models ◽  
Potential Role ◽  
Financial Instruments ◽  
Business Logic ◽  
Literature Overview ◽  
Ifrs 9 ◽  
Definition Of

The term ?business model' has recently attracted increased attention in the context of financial reporting and was formally introduced into the IFRS literature when IFRS 9 Financial Instruments was published in November 2009. However, IFRS 9 did not fully define the term ‘business model'. Furthermore, the literature on business models is quite diverse. It has been conducted in largely isolated fashion; therefore, no generally accepted definition of ?business model' has emerged. Therefore, a better understanding of the notion itself should be developed before further investigating its potential role within financial reporting. The aim of this paper is to highlight some of the perceived key themes and to identify other bases for grouping/organizing the literature based on business models. The contributions this paper makes to the literature are twofold: first, it complements previous review papers on business models; second, it contains a clear position on the distinction between the notions of the business model and strategy, which many authors identify as a key element in better explaining and communicating the notion of the business model. In this author's opinion, the term ‘strategy' is a dynamic and forward-looking notion, a sort of directional roadmap for future courses of action, whereas, ‘business model' is a more static notion, reflecting the conceptualisation of the company's underlying core business logic. The conclusion contains the author's thoughts on the role of the business model in financial reporting.

The Role of Moral Education on the Dress Code in the Higher Learning Institution

Sains Insani ◽  
2016 ◽  
Vol 1 (1) ◽  
pp. 10-14
Author(s):  
Ira Meilita Ibrahim ◽  
Taufik A. Latif ◽  
Afi Roshezry Abu Bakar ◽  
Muthualagan Thangavelu
Keyword(s):  
Moral Education ◽  
Private University ◽  
Public University ◽  
Higher Learning ◽  
Private Institutions ◽  
Dress Code ◽  
Institutions Of Higher Learning ◽  
The World ◽  
Definition Of

The advancement of European dress to the rest of the world was linked to the definition of civilization as “a stage of social development considered to be more advanced” and “polite and good-mannered”. The widespread of their fashion style in the 19th and 20th centuries influenced the way the rest of the world attire. The fashion trend and dressing style thus change the purpose of dressing through time. The dressing style in campuses especially in private institutions of higher learning is under particular scrutiny, as it is often said to be inappropriate for a learning environment. This study looked at the importance of moral education, and its role in implementing the dress code for students among university students especially between two types of university i.e. public university and private university. It looked on the dressing style of students, both male and female, and the factors that lead to their dressing pattern which is common among students. This study also advocated the students’ understanding of the content of dress codes in their learning institution and the role played by moral education in regard to dress code. The overall study highlighted students’ perception towards the implementation of the dress code and punishment in their learning institution. The methodologies used to carry out this study are questionnaires and interviews. This study will therefore ascertain the important of dress code among students at higher learning institution and the role of moral education in cultivating values in order to dress properly or decently. Key Words: moral education, dress code, higher learning institution, civilization.

SOME ASPECTS OF THE FUNCTION OF FSH- AND LH-LIKE HORMONES IN NORMAL AND HYPOPHYSECTOMIZED FEMALE RATS, IN CONNECTION WITH RESERPINE ADMINISTRATION

1965 ◽  
Vol 49 (1) ◽  
pp. 28-38
Author(s):  
M. Grönroos ◽  
E. Mäkinen ◽  
K. Lahtinen ◽  
R. Tirri
Keyword(s):  
Mechanism Of Action ◽  
Biological Effect ◽  
Female Rats ◽  
Histological Picture ◽  
Peripheral Effect ◽  
Pituitary Secretion

ABSTRACT The effect of reserpine on the secretion of FSH and LH was studied as well as the role of the peripheral effect of reserpine after hypophysectomy. The results in the unoperated animals suggest that reserpine inhibits the pituitary secretion of both FSH and LH. Both these hormones combined with reserpine had a very different biological effect than was seen without reserpine. HCG (LH-like) and particularly PMS (FSH-like) hormones combined with reserpine caused definite enlargement of the ovaries. In the hypophysectomized groups, the effect of the PMS and HCG hormones administered together with reserpine or without it was the same with regard to the weight of the ovaries, but not with regard to their histological picture. On the basis of these results, reserpine may be said to have a peripheral effect although the nature of its mechanism of action is difficult to state. Reserpine probably affects the ovaries by inhibiting the follicular cycle and, consequently, the formation of new and more mature follicles.

Two Representations of the Moscow Art Theater Audience

2020 ◽  
Vol 17 (5) ◽  
pp. 462-476
Author(s):  
Alexander A. Ushkarev ◽  
Galina G. Gedovius ◽  
Tatyana V. Petrushina
Keyword(s):  
Online Community ◽  
Modern Art ◽  
Virtual Space ◽  
Demographic Parameters ◽  
Cultural Consumption ◽  
Cultural Activity ◽  
Behavioral Differences ◽  
Technological Revolution ◽  
Definition Of

The technological revolution of recent decades has already brought art to the broadest masses, and the unexpected intervention of the pandemic has significantly accelerated the process of migration of theatrical art to the virtual space, causing the corresponding dynamics of the audience. What is the theater audience in the era of digitalization and the spread of alternative forms of cultural consumption? How does the theater build its relationship with the audience today? In search of answers, we conducted a series of sociological surveys of the Chekhov Moscow Art Theater’s audience — both at the theater’s performances and in the online community of its fans. The purpose of this phase of the study was to answer the fundamental questions: do spectators surveyed in the theater and those surveyed online represent the same audience; what are their main differences; and what are the drivers of their spectator behavior? The article presents the main results of a comparative analysis of two images of the Moscow Art Theatre’s audience based on a number of content parameters by two types of surveys, as well as the results of a regression analysis of the theater attendance. The study resulted in definition of the qualitative and behavioral differences between the theater visitors and the viewers surveyed online, and identification of the factors of theater attendance for both of the represented audience groups. The study made it possible to clarify the role of age and other socio-demographic parameters in cultural activity, as well as the influence of preferred forms of cultural consumption (live contacts or online views) on one’s attitude to art, motivation and spectator behavior. The conclusions of the study, despite the uniqueness of the object, reflect the general patterns of the modern art audience’s dynamics.

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