Thermal Adaptation of Conformational Dynamics in Ribonuclease H

The relationship between inherent internal conformational processes and enzymatic activity or thermodynamic stability of proteins has proven difficult to characterize. The study of homologous proteins with differing thermostabilities offers an especially useful approach for understanding the functional aspects of conformational dynamics. In particular, ribonuclease HI (RNase H), an 18 kD globular protein that hydrolyzes the RNA strand of RNA:DNA hybrid substrates, has been extensively studied by NMR spectroscopy to characterize the differences in dynamics between homologs from the mesophilic organism E. coli and the thermophilic organism T. thermophilus. Herein, molecular dynamics simulations are reported for five homologous RNase H proteins of varying thermostabilities and enzymatic activities from organisms of markedly different preferred growth temperatures. For the E. coli and T. thermophilus proteins, strong agreement is obtained between simulated and experimental values for NMR order parameters and for dynamically averaged chemical shifts, suggesting that these simulations can be a productive platform for predicting the effects of individual amino acid residues on dynamic behavior. Analyses of the simulations reveal that a single residue differentiates between two different and otherwise conserved dynamic processes in a region of the protein known to form part of the substrate-binding interface. Additional key residues within these two categories are identified through the temperature-dependence of these conformational processes

Artificial economic life: a simple model of a stockmarket

We describe a model of a stockmarket in which independent adaptive agents can buy and sell stock on a central market. The overall market behavior, such as the stock price time series, is an emergent property of the agents' behavior. This approach to modelling a market is contrasted with conventional rational expectations approaches. Our model does not necessarily converge to an equilibrium, and can show bubbles, crashes, and continued high trading volume.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31402/1/0000319.pd

Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.

The Piwi-interacting RNA (piRNA) pathway safeguards genomic integrity by silencing transposable elements (transposons) in the germline. While Piwi is the central piRNA factor, others including Asterix/Gtsf1 have also been demonstrated to be critical for effective silencing. Here, using enhanced crosslinking and immunoprecipitation (eCLIP) with a custom informatic pipeline, we show that Asterix/Gtsf1 specifically binds tRNAs in cellular contexts. We determined the structure of mouse Gtsf1 by NMR spectroscopy and identified the RNA-binding interface on the protein's first zinc finger, which was corroborated by biochemical analysis as well as cryo-EM structures of Gtsf1 in complex with co-purifying tRNA. Consistent with the known dependence of long terminal repeat (LTR) retrotransposons on tRNA primers, we demonstrate that LTR retrotransposons are, in fact, preferentially de-repressed in Asterix mutants. Together, these findings link Asterix/Gtsf1, tRNAs, and LTR retrotransposon silencing and suggest that Asterix exploits tRNA dependence to identify transposon transcripts and promote piRNA silencing

Finding a moral homeground: appropriately critical religious education and transmission of spiritual values

Values-inspired issues remain an important part of the British school curriculum. Avoiding moral relativism while fostering enthusiasm for spiritual values and applying them to non-curricular learning such as school ethos or children's home lives are challenges where spiritual, moral, social and cultural (SMSC) development might benefit from leadership by critical religious education (RE). Whether the school's model of spirituality is that of an individual spiritual tradition (schools of a particular religious character) or universal pluralistic religiosity (schools of plural religious character), the pedagogy of RE thought capable of leading SMSC development would be the dialogical approach with examples of successful implementation described by Gates, Ipgrave and Skeie. Marton's phenomenography, is thought to provide a valuable framework to allow the teacher to be appropriately critical in the transmission of spiritual values in schools of a particular religious character as evidenced by Hella's work in Lutheran schools

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).