scholarly journals ENZYME EVOLUTION: I. THE IMPORTANCE OF UNTRANSLATABLE INTERMEDIATES

Genetics ◽  
1972 ◽  
Vol 72 (2) ◽  
pp. 297-316
Author(s):  
Arthur L Koch

ABSTRACT The proportion of two allelic mutant forms of a haploid species can be calculated from six quantities, the original proportion, the two effective growth rate constants, the two mutation rate constants for the transition from one to the other, and the elapsed time. With a program for carrying out this calculation in a mini-computer, we set about investigating the rates of exploration of multiple intragene changes in populations of enormous numbers over a large number of cell generations. It seemed evident from the outset that unless in the past very different proportions of the different types of mutational changes occurred, then neither the numbers nor the times could have been of sufficient magnitude to account for enzyme evolution by multiple simultaneous changes within a gene to yield a superior protein. Rather, we propose that the more rapid path of enzyme evolution consisted of the sequence: 1) gene duplication, 2) inactivation of a gene copy by a chain-terminating mutation or other mutational change which suppresses transcription and/or translation, 3) multiple base-pair changes and/or small deletions and additions within the non-functioning gene, and finally, 4) reversion of the mutation which was suppressing translation. It is shown that this path will lead to faster advance, if the selective advantages of different forms are dependent on the function of the gene products at certain times in history, while at other times, although this function may be necessary, it is not limiting for growth.

Energies ◽  
2018 ◽  
Vol 11 (11) ◽  
pp. 3079 ◽  
Author(s):  
Leopoldo Angrisani ◽  
Francesco Bonavolontà ◽  
Annalisa Liccardo ◽  
Rosario Schiano Lo Moriello

In this paper, a logic selectivity system based on Long Range (LoRa) technology for the protection of medium-voltage (MV) networks is proposed. The development of relays that communicate with each other using LoRa allows for the combination of the cost-effectiveness and ease of installation of wireless networks with long-range coverage and reliability. The realized demonstrator to assess the proposed system is also presented in the paper; based on different types of faults and different locations, the times needed for clearing a fault and restoring the network were estimated from repeated experiments. The obtained results confirm that, with an optimized design of transmitted packets and of protocol characteristics, LoRa communication grants fault management that meets the criteria of logic selectivity, with fault isolation occurring within the maximum allowed time.


2020 ◽  
Vol 31 (4) ◽  
pp. 865-883
Author(s):  
Caroline Sundgren

PurposeNew actors have emerged in the food supply chain in response to the increased awareness of food waste and the need to distribute surplus food. The purpose of this study is to analyse the different supply chain structures that have emerged to make surplus food available to consumers.Design/methodology/approachThis study adopts a qualitative multiple-case study of three new surplus food actors: a surplus food platform, an online retailer and a surplus food terminal. Data sources included interviews, documentary evidence and participatory observations.FindingsThree different types of actor constellations in surplus food distribution have been identified: a triad, a tetrad and a chain. Both centralised (for ambient products) and decentralised supply chain structures (for chilled products) have emerged. The analysis identified weak links amongst new actors and surplus food suppliers. The new actors have adopted the roles of connector, service provider and logistics service provider and the sub-roles of mediator, auditor and consultant.Originality/valueThis paper contributes to research on closed-loop or circular supply chains for the reuse of products in the context of surplus food distribution.


1987 ◽  
Author(s):  
L Piérard ◽  
P Jacobs ◽  
D Gheysen ◽  
M Hoylaerts ◽  
A Cravador ◽  
...  

In order to produce plasminogen activators (PA) more specific and more active than their natural counterparts, we designed recombinant genes encoding mutant forms of urokinase (u-PA) and chimaeric molecules combining fragments of tissue type plasminogen activator (t-PA) and of u-PA. The following constructs have been realized : 1°) u-PA where amino acids Arg156 and Lys158 have been replaced by Thr. The purpose of this approach was to obtain a prourokinase molecule displaying similar properties as the natural single chain urokinase (scu-PA) but resistant to the cleavage by plasmin ; 2°) u-PA where the second cleavage site, Lys135-Lys136, was also eliminated either by replacing amino acid 132 to amino acid 147 by a shorter link (Ser-Thr) as found in t-PA, or by replacing the two lysines by glutamine residues. The resulting molecules correspond thus to completely uncleavable scu-PA forms ; 3°) an hybrid composed of the finger domain of t-PA and of the B-chain of u-PA ; 4°) an hybrid made of the A-chain of t-PA and of the B-chain of u-PA ; 5°) an hybrid where the kringle 2 of t-PA has been inserted between the kringle domain and the B-chain of u-PA. The last three constructs have been made to confer the fibrin binding specificity of t-PA to the B-chain of u-PA.All recombinant DNAs were introduced, via an expression vector, into R1610 and CosI cells. Secretion of the recombinant products was monitored by ELISA and activities were assayed in an immobilized system involving a monoclonal antibody (AAU2) raised against 33K u-PA, plasminogen and the specific chromogenic substrate S2251. In this assay, all recombinant products, except the plasmin resistant (156-158) scu-PA, showed apparent specific activities comparable to the activity of natural two-chain u-PA. Potential interest of these new plasminogen activators in therapy will be discussed and further characterization of the new molecules will-be presented.


1983 ◽  
Vol 61 (12) ◽  
pp. 2716-2720 ◽  
Author(s):  
John M. Roscoe

The reactions of O(3P) with the butanols were studied kinetically as a function of temperature and substrate concentration. The absolute rate constants for the gas phase reactions, in the units M−1 s−1, obey the following relations.[Formula: see text]The results suggest that although the α-CH bond in these alcohols is the most reactive one, reaction of O(3P) with other CH bonds in the alcohols is also appreciable. The kinetic data for these and other alcohols are separated into contributions from the different types of CH bonds and the results are discussed in terms of linear free energy relations.


1989 ◽  
Vol 257 (1) ◽  
pp. 191-196 ◽  
Author(s):  
A Wallace ◽  
G Rovelli ◽  
J Hofsteenge ◽  
S R Stone

In order to determine the specificity of the interaction between thrombin and glia-derived nexin (GdN), the inactivation of proteolytically modified human thrombin species by GdN has been studied. The second-order rate constants for the inactivation of alpha-, beta T-, gamma T- and epsilon-thrombin by GdN were 1.41, 0.63, 0.33 and 1.91 microM-1.s-1 respectively. The kinetic properties of gdN were also investigated in the presence of different types of heparin, fractionated according to antithrombin III-binding affinity. Association rate constants of both gdN and antithrombin III with alpha-thrombin were obtained using unfractionated, low- and high-affinity heparin types. The different heparin types gave optimal rates of inhibition at similar heparin concentrations for both inhibitors. At optimal heparin concentrations, the rate of inactivation of alpha-thrombin by GdN was 0.5-1.2 nM-1.s-1, which suggests that, under these conditions, the interaction is diffusion-controlled.


1983 ◽  
Vol 61 (9) ◽  
pp. 2037-2043 ◽  
Author(s):  
A. Baignée ◽  
J. H. B. Chenier ◽  
J. A. Howard

The major initial products of the self-reaction of α-tetralylperoxyls (C10H11O2•) in chlorobenzene at 303–353 K are equal concentrations of α-tetralol and α-tetralone in ~90% yield based on the number of initiating radicals. These yields are consistent with the non-radical (Russell) mechanism for self-reaction. Low concentrations of bis(α-tetralyl) peroxide are produced, indicating that there is a small but detectable free-radical contribution towards termination. C10H11O2• undergoes β-scission in this temperature range but steady-state concentrations of C10H11• are too low to influence the termination rate constant 2kt, or react with C10H11O2• to give (C10H11O2. α-Tetralol to α-tetralone ratios and total yields of these products are significantly less than 1 and 100%, respectively, in methanol and acetonitrile. Formaldehyde is produced in methanol indicating the involvement of α-hydroxymethylperoxyls, derived from the solvent, in termination. There is no evidence for a chain reaction or a zwitterion intermediate for self-reaction of C10H11O2• in solution.


2005 ◽  
Vol 19 (3) ◽  
pp. 565-581 ◽  
Author(s):  
Patricia Lewis

Based on an interview study of neonatal nurses, this article sets out to explore the management of emotions within a work context where their suppression is a professional requirement. Drawing on Bolton’s (2000a, 2000b) identification of different types of organizational emotionality, in particular prescriptive and philanthropic emotion management, the article seeks to demonstrate the complexities involved in the performance of emotional labour. It does this by first exploring the times when a nurse chooses to perform one form of emotion management over another (e.g. prescriptive over philanthropic). Second, the article examines the relationship between these two forms of emotion management, taking into account their gendered nature and highlighting the existence of any tensions between them. Lastly, it considers how nurses create informal communities of coping (Korczynski, 2003) as a means of dealing with the consequences of having to move between these two different forms of emotion management.


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