ON THE RELEVANCE OF THE CORE HELIX ALPHA 6 TO KINESIN ACTIVITY GENERATION

2009 ◽  
Vol 04 (01n02) ◽  
pp. 63-75 ◽  
Author(s):  
NIKOLINA KALCHISHKOVA ◽  
KONRAD J. BÖHM
Keyword(s):  
Structural Organization ◽  
Atp Hydrolysis ◽  
Catalytic Core ◽  
Microtubule Binding ◽  
The Core ◽  
Activity Generation ◽  
Core Elements ◽  
High Level ◽  
Β Sheet

KIF5A and Eg5 are plus-end directed motor proteins with conserved motor domains. The catalytic cores of both motors comprise a central β-sheet consisting of eight β-strands surrounded by six α-helices. Notwithstanding the high level of similarity in their structural organization, Eg5 moves significantly slower than KIF5A. Recently, we reported that neck linker and neck elements of KIF5A and Eg5 contribute to velocity regulation. As the neck linker of both motors is known to be connected to the catalytic core via helix α6, the question arises if also helix α6 and strand β8 as the last core elements might be involved in velocity regulation. To elucidate the role these structures in kinesin activity generation we constructed KIF5A- and Eg5-based chimeras in which the β8 strand, helix α6, the neck linker, and the neck were interchanged. Additionally, we studied the role of α6 and β8 in ATP hydrolysis and microtubule binding by expression of truncated KIF5A and Eg5 constructs lacking both strand β8 and helix α6, or α6 only. The results obtained suggest that strand β8 and helix α6 are not involved in microtubule-binding, but α6 is an obligate and kinesin type-specific structure required to generate ATPase activity.

Reply to Comments

2019 ◽  
Vol 41 (2) ◽  
pp. 287-300
Author(s):  
Allen Buchanan ◽  
Russell Powell
Keyword(s):  
Social Sciences ◽  
Moral Psychology ◽  
Moral Theory ◽  
Moral Progress ◽  
Evolutionary Explanation ◽  
The Core ◽  
Use Of Data ◽  
The Social ◽  
Core Elements

Abstract Commentators on The Evolution of Moral Progress: A Biocultural Theory raise a number of metaethical and moral concerns with our analysis, as well as some complaints regarding how we have interpreted and made use of the contemporary evolutionary and social sciences of morality. Some commentators assert that one must already presuppose a moral theory before one can even begin to theorize moral progress; others query whether the shift toward greater inclusion is really a case of moral progress, or whether our theory can be properly characterized as ‘naturalistic’. Other commentators worry that we have uncritically accepted the prevailing evolutionary explanation of morality, even though it gives short shrift to the role of women or presupposes an oversimplified view of the environment in which the core elements of human moral psychology are thought to have congealed. Another commentator laments that we did not make more extensive use of data from the social sciences. In this reply, we engage with all of these constructive criticisms and show that although some of them are well taken, none undermine the core thesis of our book.

scholarly journals Hypersensitive Site 2 Specifies a Unique Function within the Human β-Globin Locus Control Region To Stimulate Globin Gene Transcription

1999 ◽  
Vol 19 (4) ◽  
pp. 3062-3072 ◽  
Author(s):  
Jörg Bungert ◽  
Keiji Tanimoto ◽  
Sunil Patel ◽  
Qinghui Liu ◽  
Mark Fear ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Gene Transcription ◽  
Control Region ◽  
Globin Gene ◽  
Dnase I ◽  
The Core ◽  
Core Elements ◽  
Transgenic Lines ◽  
High Level ◽  
Chromatin Opening

ABSTRACT The human β-globin locus control region (LCR) harbors both strong chromatin opening and enhancer activity when assayed in transgenic mice. To understand the contribution of individual DNase I hypersensitive sites (HS) to the function of the human β-globin LCR, we have mutated the core elements within the context of a yeast artificial chromosome (YAC) carrying the entire locus and then analyzed the effect of these mutations on the formation of LCR HS elements and expression of the genes in transgenic mice. In the present study, we examined the consequences of two different HS2 mutations. We first generated seven YAC transgenic lines bearing a deletion of the 375-bp core enhancer of HS2. Single-copy HS2 deletion mutants exhibited severely depressed HS site formation and expression of all of the human β-globin genes at every developmental stage, confirming that HS2 is a vital, integral component of the LCR. We also analyzed four transgenic lines in which the core element of HS2 was replaced by that of HS3 and found that while HS3 is able to restore the chromatin-opening activity of the LCR, it is not able to functionally replace HS2 in mediating high-level globin gene transcription. These results continue to support the hypothesis that HS2, HS3, and HS4 act as a single, integral unit to regulate human globin gene transcription as a holocomplex, but they can also be interpreted to say that formation of a DNase I hypersensitive holocomplex alone is not sufficient for mediating high-level globin gene transcription. We therefore propose that the core elements must productively interact with one another to generate a unique subdomain within the nucleoprotein holocomplex that interacts in a stage-specific manner with individual globin gene promoters.

C1-Inactivator as a Determining Factor in Contact Activation of Fibrinolysis

1975 ◽  
Author(s):  
C. Kluft
Keyword(s):  
Fibrinolytic Activity ◽  
Slow Rate ◽  
Contact Activation ◽  
Activation Rate ◽  
Activity Generation ◽  
High Level ◽  
Fletcher Factor ◽  
Determining Factor

The rate of contact activation of fibrinolysis is considered to reflect the activation rate of proactivator and Hageman factor. This study was undertaken to determine the role of Cl-inactivator in this process.Contact activation of fibrinolysis was performed according to Ogston et al. (1969), J. Clin. Invest. 48, 1786-1801. The rate of activity generation was measured in plasma with various levels of Cl-inactivator and appeared to be dependent on that level; i.e., a high level of Cl-inactivator corresponds with a slow rate of activity generation.It has recently been demonstrated that the fibrinolytic activity of euglobulin fractions is strongly inhibited by Cl-inactivator also present in this fraction. The activity generation of contact activation is found to be accompanied by a gradual decrease in functional Cl-inactivator in the euglobulin fraction. The fibrinolytic activity is set free by this disappearance of inhibition.It is concluded that the rate of contact activation of fibrinolysis must be interpreted in terms of the inactivation of Cl-inactivator rather than of the activation of proenzymes. All enzymes capable of inactivating Cl-inactivator can contribute to the process of contact activation of fibrinolysis. This mechanism might account for the observed defects in fibrinolysis in vitro in Fletcher Factor deficient patients.

scholarly journals Modeling the role of voyaging in the coastal spread of the Early Neolithic in the West Mediterranean

2017 ◽  
Vol 114 (5) ◽  
pp. 897-902 ◽  
Author(s):  
Neus Isern ◽  
João Zilhão ◽  
Joaquim Fort ◽  
Albert J. Ammerman
Keyword(s):  
Long Range ◽  
Simulation Study ◽  
Cultural Interaction ◽  
Early Neolithic ◽  
The West ◽  
The Core ◽  
Core Elements

The earliest dates for the West Mediterranean Neolithic indicate that it expanded across 2,500 km in about 300 y. Such a fast spread is held to be mainly due to a demic process driven by dispersal along coastal routes. Here, we model the Neolithic spread in the region by focusing on the role of voyaging to understand better the core elements that produced the observed pattern of dates. We also explore the effect of cultural interaction with Mesolithic populations living along the coast. The simulation study shows that (i) sea travel is required to obtain reasonable predictions, with a minimum sea-travel range of 300 km per generation; (ii) leapfrog coastal dispersals yield the best results (quantitatively and qualitatively); and (iii) interaction with Mesolithic people can assist the spread, but long-range voyaging is still needed to explain the archaeological pattern.

Enunciation

2021 ◽  
Author(s):  
Russell Smith
Keyword(s):  
Literary Theory ◽  
Language Use ◽  
Jacques Lacan ◽  
Julia Kristeva ◽  
Human Sciences ◽  
The Core ◽  
Core Elements ◽  
General Linguistics ◽  
The Individual

Enunciation refers to the act of making a spoken or written statement, as opposed to the content of the statement. It is associated with the work of French linguist Émile Benveniste, whose Problems in General Linguistics (1966) argued that formalist and structuralist accounts of language fail to pay sufficient attention to the fact that many of the core elements of any language, such as the pronouns “I” and “you,” are entirely dependent for their function on the unique circumstances in which they are enunciated. Enunciation thus describes the process by which a speaker or writer takes up the position of a linguistic subject. Benveniste further argued that all acts of language use are fundamentally dialogical in nature, although the individual acts of speaking and listening, writing and reading may be widely separated in place and time. These questions played a pivotal role in the shift, both in literary theory and in the human sciences more broadly, from structuralism to poststructuralism through the course of the late 1960s and early 1970s. This involved a shift from the study of language as a signifying system, to the study of discourse as the range of different processes by which individual acts of speaking and writing, listening and reading, are framed in advance by formal and informal rules and conventions. Every actual instance of language use is inseparable from its enunciative situation, and this entails attention to the questions of who is speaking, to whom, and why? As developed in different ways by theorists such as Julia Kristeva and Jacques Lacan, Roland Barthes and Michel Foucault, the linguistics of enunciation would raise profound questions about the role of language in the formation of subjectivity and in the discursive operation of power.

Financialization, securitization and the decline of pubs in Britain

2020 ◽  
Vol 20 (6) ◽  
pp. 1293-1311
Author(s):  
Liam Keenan
Keyword(s):  
Political Economy ◽  
Shareholder Value ◽  
Rapid Rate ◽  
Short Term ◽  
Firm Level ◽  
Unit Of Analysis ◽  
The Core ◽  
Core Elements ◽  
Political Economy Approach

Abstract Pubs in Britain are closing at a rapid rate. While changing regulatory, demographic and consumer trends have weakened the viability of pubs businesses in recent years, less is known about the role of Pub Companies, or ‘pubcos’, in contributing to the decline of the sector. Reflecting the core elements of financialization, pubcos acquire assets through securitization, prioritize shareholder value and operate under short-term financial targets and metrics. Adopting an institutionally sensitive geographical political economy approach, this article analyzes the ways in which pubcos, through financialization and securitization, have transformed the ownership and geographies of pubs in Britain. Foregrounding the firm as the unit of analysis, it emphasizes the importance of firm agency in creating more granular understandings of the geographical causes and implications of securitization. Analyzing the interrelationships between actors involved in the securitization process, particularly tensions between shareholders and bondholders, this article makes a novel contribution around the variegated, contradictory and conflicted nature of firm-level financialization.

Environments for Entrepreneurship Development: Key Dimensions and Research Implications

1994 ◽  
Vol 18 (4) ◽  
pp. 43-62 ◽  
Author(s):  
Devi R. Gnyawali ◽  
Daniel S. Fogel
Keyword(s):  
Environmental Conditions ◽  
New Venture ◽  
New Venture Creation ◽  
Venture Creation ◽  
Five Dimensions ◽  
Creation Process ◽  
The Core ◽  
Core Elements ◽  
Key Dimensions

An integrated framework is not available for studying the environmental conditions conducive for entrepreneurship despite their importance for the emergence and growth of enterprises in a country. This paper develops such a framework consisting of five dimensions of entrepreneurial environments and links these dimensions to the core elements of the new venture creation process. Specific emphasis is given to the role of environmental conditions in developing opportunities and in enhancing entrepreneurs’ propensity and ability to enterprise. The paper outlines some propositions and research implications of the integrated model and offers initial guidelines for formulating public policies to develop entrepreneurial environments.

scholarly journals Exploring the Possible Applicability of Yagya in Present Time: A Review

2020 ◽  
Author(s):  
Vandana Shrivastava ◽  
Saurabh Mishra ◽  
Alka Mishra
Keyword(s):  
Mode Of Action ◽  
Review Article ◽  
Present Review ◽  
Integrative Approach ◽  
Management Approach ◽  
Therapeutic Procedure ◽  
Indian Culture ◽  
The Core ◽  
Core Elements

Yagya has been one of the core elements of the ancient Indian Culture ever since the Vedic era, and is also an effective therapeutic procedure. The present review article explores the applicability of Yagya during the present time, wherein the principles, procedure and the possible mode of action of Yagya have been described; the efficacy of Ayurvedic medicines and medicinal herbs in the management of various diseases caused by viruses, as well as the diseases that have symptoms similar to those prevalent during present time, have been discussed; the ethnobotanical use of herbal fumigation in the management of various diseases, has been presented; as well as, the efficacy of Yagya Therapy / Integrative approach (including Yagya Therapy) in the management of symptoms of various disease conditions has been illustrated. The review also briefly illustrates the ancient Ayurvedic perspective about epidemics and the possible role of Yagya as a management approach for the same. Based on the information presented herein, the applicability of Yagya in the present time seems to be a promising possibility, that is worth exploring further through proper experimentation and analysis.

Oxford Handbook of Surgical Nursing

2016 ◽  
Keyword(s):  
Multidisciplinary Team ◽  
Surgical Care ◽  
Surgical Patients ◽  
Care Needs ◽  
The Core ◽  
Before And After ◽  
Core Elements ◽  
Clinical Advances

The Oxford Handbook of Surgical Nursing is aimed at nurses who care for patients before and after surgery on the main ward areas of a surgical facility. The care needs of surgical patients are core to the role of the nurse and have undergone significant specialization, with the increasing technological and clinical advances in surgery. In addition, the role of the nurse in these areas has changed markedly, undertaking more procedures as well as aspects of assessment, investigation, and treatment as part of the multidisciplinary team. The Oxford Handbook of Surgical Nursing provides a guide relating to all the core elements of surgical care.

scholarly journals Voa1p Functions in V-ATPase Assembly in the Yeast Endoplasmic Reticulum

2008 ◽  
Vol 19 (12) ◽  
pp. 5131-5142 ◽  
Author(s):  
Margret Ryan ◽  
Laurie A. Graham ◽  
Tom H. Stevens
Keyword(s):  
Endoplasmic Reticulum ◽  
Atp Hydrolysis ◽  
Yeast Cells ◽  
Yeast Saccharomyces Cerevisiae ◽  
Growth Defects ◽  
The Core ◽  
Golgi Compartment ◽  
Assembly Factor ◽  
Two Sectors

The yeast Saccharomyces cerevisiae vacuolar ATPase (V-ATPase) is a multisubunit complex divided into two sectors: the V1 sector catalyzes ATP hydrolysis and the V0 sector translocates protons, resulting in acidification of its resident organelle. Four protein factors participate in V0 assembly. We have discovered a fifth V0 assembly factor, Voa1p (YGR106C); an endoplasmic reticulum (ER)-localized integral membrane glycoprotein. The role of Voa1p in V0 assembly was revealed in cells expressing an ER retrieval-deficient form of the V-ATPase assembly factor Vma21p (Vma21pQQ). Loss of Voa1p in vma21QQ yeast cells resulted in loss of V-ATPase function; cells were unable to acidify their vacuoles and exhibited growth defects typical of cells lacking V-ATPase. V0 assembly was severely compromised in voa1 vma21QQ double mutants. Isolation of V0–Vma21p complexes indicated that Voa1p associates most strongly with Vma21p and the core proteolipid ring of V0 subunits c, c′, and c″. On assembly of the remaining three V0 subunits (a, d, and e) into the V0 complex, Voa1p dissociates from the now fully assembled V0–Vma21p complex. Our results suggest Voa1p functions with Vma21p early in V0 assembly in the ER, but then it dissociates before exit of the V0–Vma21p complex from the ER for transport to the Golgi compartment.

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