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Bywater R.P.,Magdalen College
Naturwissenschaften | Year: 2012

The notion that RNA must have had a unique and decisive role in the development of life needs hardly be questioned. However, the chemical complexity and other properties of RNA, such as high solubility in water and vulnerability to degradation, make it improbable that RNA could have had an early presence in the development of life on Earth or on any comparable telluric planet. Rather, the task of origin of life research must surely be to identify those chemical processes which could have taken place on Earth that could accumulate the complexity and rich molecular information content needed to sustain primitive life, and ultimately give rise to RNA. A collection of likely chemical precursors to modern biomolecules is listed here together with calculations of their molecular complexity. These complexity scores are then used to propose an ordering, on a timescale, of when they might have appeared on Earth. These pre-RNA living systems would have flourished during the first ~0.3 Gyrs after the start of the Archaean era (~4.2 Gyr ago). If there ever was an "RNA-world" it could have started after that initial period (~3.9 Gyrs ago), later to be complemented with the appearance of duplex DNA at about ~3.6 Gyrs ago, some time before the earliest known stromatolites (~3.4 Gyr). © Springer-Verlag 2012.

Jacobs B.M.,Magdalen College
Schizophrenia Research | Year: 2015

Schizophrenia is a devastating and prevalent psychiatric illness. Progress in understanding the basic pathophysiological processes underlying this disorder has been hindered by the lack of appropriate models. With the advent of induced pluripotent stem cell (iPSC) technology, it is now possible to generate live neurons in vitro from somatic tissue of schizophrenia patients. Despite its several limitations, this revolutionary technology has already helped to advance our understanding of schizophrenia. The phenotypic insights garnered with iPSC models of schizophrenia include transcriptional dysregulation, oxidative stress synaptic dysregulation, and neurodevelopmental abnormalities. Potential pitfalls of this work include the possibility of introducing random genetic mutations during the reprogramming process, the inadequacy of using neurons from other patients as controls, the inability to capture the complex environmental contribution to schizophrenia pathogenesis, the difficulty in modelling neurodevelopment, and the difficulty in modelling the interaction of multiple neuronal and non-neuronal cell types. However, with the increasing sophistication of available reprogramming techniques, co-culture technology, and gene correction strategies, iPSC-derived neurons will continue to elucidate how neuronal function is disrupted in schizophrenia. © 2015 Elsevier B.V.

While the genome for a given organism stores the information necessary for the organism to function and flourish it is the proteins that are encoded by the genome that perhaps more than anything else characterize the phenotype for that organism. It is therefore not surprising that one of the many approaches to understanding and predicting protein folding and properties has come from genomics and more specifically from multiple sequence alignments. In this work I explore ways in which data derived from sequence alignment data can be used to investigate in a predictive way three different aspects of protein structure: Secondary structures, inter-residue contacts and the dynamics of switching between different states of the protein. In particular the use of Kolmogorov complexity has identified a novel pathway towards achieving these goals. © 2015 Robert Paul Bywater.

Highcock E.G.,Magdalen College | Highcock E.G.,University of Oxford | Highcock E.G.,EURATOM | Schekochihin A.A.,University of Oxford | And 6 more authors.
Physical Review Letters | Year: 2012

Sheared toroidal flows can cause bifurcations to zero-turbulent-transport states in tokamak plasmas. The maximum temperature gradients that can be reached are limited by subcritical turbulence driven by the parallel velocity gradient. Here it is shown that q/Ïμ (magnetic field pitch/inverse aspect ratio) is a critical control parameter for sheared tokamak turbulence. By reducing q/Ïμ, far higher temperature gradients can be achieved without triggering turbulence, in some instances comparable to those found experimentally in transport barriers. The zero-turbulence manifold is mapped out, in the zero-magnetic-shear limit, over the parameter space (γE, q/Ïμ, R/LT), where γE is the perpendicular flow shear and R/LT is the normalized inverse temperature gradient scale. The extent to which it can be constructed from linear theory is discussed. © 2012 American Physical Society.

Seddon G.M.,Adelard Institute | Bywater R.P.,Adelard Institute | Bywater R.P.,Magdalen College
Open Biology | Year: 2012

We have developed novel strategies for contracting simulation times in protein dynamics that enable us to study a complex protein with molecular weight in excess of 34 kDa. Starting from a crystal structure, we produce unfolded and then refolded states for the protein. We then compare these quantitatively using both established and new metrics for protein structure and quality checking. These include use of the programs CONCOORD and DARVOLS. Simulation of protein-folded structure well beyond the molten globule state and then recovery back to the folded state is itself new, and our results throw new light on the protein-folding process. We accomplish this using a novel cooling protocol developed for this work. © 2012 The Authors.

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