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Cambridge, United Kingdom

Jackson S.E.,Lensfield Road
Topics in Current Chemistry

Hsp90 is a highly abundant and ubiquitous molecular chaperone which plays an essential role in many cellular processes including cell cycle control, cell survival, hormone and other signalling pathways. It is important for the cell's response to stress and is a key player in maintaining cellular homeostasis. In the last ten years, it has become a major therapeutic target for cancer, and there has also been increasing interest in it as a therapeutic target in neurodegenerative disorders, and in the development of anti-virals and anti-protozoan infections. The focus of this review is the structural and mechanistic studies which have been performed in order to understand how this important chaperone acts on a wide variety of different proteins (its client proteins) and cellular processes. As with many of the other classes of molecular chaperone, Hsp90 has a critical ATPase activity, and ATP binding and hydrolysis known to modulate the conformational dynamics of the protein. It also uses a host of cochaperones which not only regulate the ATPase activity and conformational dynamics but which also mediate interactions with Hsp90 client proteins. The system is also regulated by post-translational modifications including phosphorylation and acetylation. This review discusses all these aspects of Hsp90 structure and function. © Springer-Verlag Berlin Heidelberg 2011. Source

Cope S.M.,Arizona State University | Shinde S.,Arizona State University | Best R.B.,Lensfield Road | Best R.B.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | And 2 more authors.
Biophysical Journal

We report for the first time, to our knowledge, that the N-terminal loop (N-loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long and stable non-β-sheet fibers in solution under the same conditions in which human amylin (hIAPP) forms amyloid fibers. This observation applies to the cyclic, oxidized form of the N-loop but not to the linear, reduced form, which does not form fibers. Our findings indicate a potential role of direct N-loop-N-loop interactions in hIAPP aggregation, which has not been previously explored, with important implications for the mechanism of hIAPP amyloid fiber formation, the inhibitory action of IAPP variants, and the competition between ordered and disordered aggregation in peptides of the calcitonin peptide family. © 2013 The Authors. Source

Eastwood D.S.,University of Manchester | Eastwood D.S.,Research Complex at Harwell | Bayley P.M.,Lensfield Road | Chang H.J.,State University of New York at Stony Brook | And 13 more authors.
Chemical Communications

The electrodeposition of metallic lithium is a major cause of failure in lithium batteries. The 3D microstructure of electrodeposited lithium 'moss' in liquid electrolytes has been characterised at sub-micron resolution for the first time. Using synchrotron X-ray phase contrast imaging we distinguish mossy metallic lithium microstructures from high surface area lithium salt formations by their contrasting X-ray attenuation. This journal is © The Royal Society of Chemistry 20151. Source

Roberts T.J.,Lensfield Road | Roberts T.J.,TJ Roberts Research | Braban C.F.,Lensfield Road | Braban C.F.,UK Center for Ecology and Hydrology | And 10 more authors.
Chemical Geology

We report here the development and application of a compact "geochemical nose" incorporating electrochemical sensors for gas measurements in volcanic plumes. A novel element of the instrument design is the arrangement of the sensors in a parallel array that enables near-simultaneous exposure and fast response. Data analysis methods were developed that utilise the multi-sensor output currents to extract gas mixing ratio abundances and eliminate cross-sensitivities. Use of filter methods is demonstrated to remove baseline drift or instrument noise. We introduce a new approach for analysis of measurements from sensors that have a slower response time (e.g. HCl), and apply this model to estimate HCl/SO 2 ratios. We deployed the sensor system at Aso volcano, Japan, detecting emissions from its fumarole field hot crater lake, and a mixed plume. We measured SO 2, H 2S, CO and HCl, ranging in abundance from ~10 2-10 4ppbv. Neither NO 2 nor Cl 2 were detected. For the fumarolic gases, molar ratios were measured as follows: H 2S/SO 2 is ~0.15, H 2/SO 2 ~0.25, CO/SO 2 ~0.02, HCl/SO 2 ~0.1. The crater lake plume's H 2S/SO 2 is ~0.03. The compositions are discussed in terms of degassing equilibria and plume chemistry. Our instrument design represents a cost-effective, low-power and highly portable system that can be readily adapted for operational surveillance of volcanic gases. © 2012 Elsevier B.V. Source

Less R.J.,Lensfield Road | Allen L.K.,Lensfield Road | Steiner A.,University of Liverpool | Wright D.S.,Lensfield Road
Dalton Transactions

Reaction of LiAlH4 with 1,2-phenylenediamine (1H4) in THF results in formation of the metallocyclic amido-/imido complex [{Al(1H2)}2{Al(1H)2}2][Li(THF)2]4 (3), while in the presence of various Lewis base ligands 1,8-diaminonaphthalene (2H4) gives the amido-('ate') complexes [Al(2H2)2]-[Li(LL′)]+ [L = THF, L′ = PMDETA (N,N,N′,N′,N′′-pentamethyldiethylenetriamine) (4); L = L′ = TMEDA (N,N,N′,N′-tetramethylethylenediamine) (5)]. The latter complexes provide evidence of intermediates in the proposed reaction pathway for formation of the cyclic framework of the tetraanion [{Al(1H2)}2{Al(1H)2}2]4- of 3. This journal is © The Royal Society of Chemistry 2015. Source

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