22 research outputs found

    The Rodin-Ohno hypothesis that two enzyme superfamilies descended from one ancestral gene: an unlikely scenario for the origins of translation that will not be dismissed

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    Background Because amino acid activation is rate-limiting for uncatalyzed protein synthesis, it is a key puzzle in understanding the origin of the genetic code. Two unrelated classes (I and II) of contemporary aminoacyl-tRNA synthetases (aaRS) now translate the code. Observing that codons for the most highly conserved, Class I catalytic peptides, when read in the reverse direction, are very nearly anticodons for Class II defining catalytic peptides, Rodin and Ohno proposed that the two superfamilies descended from opposite strands of the same ancestral gene. This unusual hypothesis languished for a decade, perhaps because it appeared to be unfalsifiable. Results The proposed sense/antisense alignment makes important predictions. Fragments that align in antiparallel orientations, and contain the respective active sites, should catalyze the same two reactions catalyzed by contemporary synthetases. Recent experiments confirmed that prediction. Invariant cores from both classes, called Urzymes after Ur = primitive, authentic, plus enzyme and representing ~20% of the contemporary structures, can be expressed and exhibit high, proportionate rate accelerations for both amino-acid activation and tRNA acylation. A major fraction (60%) of the catalytic rate acceleration by contemporary synthetases resides in segments that align sense/antisense. Bioinformatic evidence for sense/antisense ancestry extends to codons specifying the invariant secondary and tertiary structures outside the active sites of the two synthetase classes. Peptides from a designed, 46-residue gene constrained by Rosetta to encode Class I and II ATP binding sites with fully complementary sequences both accelerate amino acid activation by ATP ~400 fold. Conclusions Biochemical and bioinformatic results substantially enhance the posterior probability that ancestors of the two synthetase classes arose from opposite strands of the same ancestral gene. The remarkable acceleration by short peptides of the rate-limiting step in uncatalyzed protein synthesis, together with the synergy of synthetase Urzymes and their cognate tRNAs, introduce a new paradigm for the origin of protein catalysts, emphasize the potential relevance of an operational RNA code embedded in the tRNA acceptor stems, and challenge the RNA-World hypothesis. Reviewers This article was reviewed by Dr. Paul Schimmel (nominated by Laura Landweber), Dr. Eugene Koonin and Professor David Ardell

    Man to man violence: how masculinity may work as a dynamic risk factor

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    This article presents masculinity as a dynamic risk factor in offences of violence between men. It argues that existing interventions into such violence, in prison, hospital and community settings may be enhanced by incorporating masculinity as a dynamic risk factor alongside other dynamic risk factors such as difficulties in anger management, social skills deficits or problems in moral reasoning. Masculinity is defined as a common denominator of men, as men, across social divisions, as opposed to existing approaches to men's identity, as men, which employ the concept of different 'masculinities' being produced by men in different social positions. The latter approach, while useful in terms of discovering men's personal identity, may be less useful in terms of explaining commonality between men, across other axes of social identity, and consequent broad patterns of violence between men. The development of masculinity as a dynamic risk factor depends on isolating masculinity from other axes of men's identity. It is argued that the individual man may demonstrate his masculinity by two categories of violence to other men: violence which includes victims in the category 'man' as worthy rivals and violence which excludes victims from the category 'man' as unworthy of being there. Masculinity as a dynamic risk factor in man to man violence is developed with particular reference to racism and homophobia

    Employee Participation in Cause-Related Marketing Strategies: A Study of Management Perceptions from British Consumer Service Industries

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    cause-related marketing, human resource management, corporate social responsibility, organisa- tional legitimacy, social alliance, stakeholder engagement, employee participation,
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