Structure of the Mammalian Ribosome-Sec61 Complex to 3.4 Å Resolution

Cotranslational protein translocation is a universally conserved process for secretory and membrane protein biosynthesis. Nascent polypeptides emerging from a translating ribosome are either transported across or inserted into the membrane via the ribosome-bound Sec61 channel. Here, we report structures of a mammalian ribosome-Sec61 complex in both idle and translating states, determined to 3.4 and 3.9 Å resolution. The data sets permit building of a near-complete atomic model of the mammalian ribosome, visualization of A/P and P/E hybrid-state tRNAs, and analysis of a nascent polypeptide in the exit tunnel. Unprecedented chemical detail is observed for both the ribosome-Sec61 interaction and the conformational state of Sec61 upon ribosome binding. Comparison of the maps from idle and translating complexes suggests how conformational changes to the Sec61 channel could facilitate translocation of a secreted polypeptide. The high-resolution structure of the mammalian ribosome-Sec61 complex provides a valuable reference for future functional and structural studies

Shining Light on Modifications of Gravity

Many modifications of gravity introduce new scalar degrees of freedom, and in such theories matter fields typically couple to an effective metric that depends on both the true metric of spacetime and on the scalar field and its derivatives. Scalar field contributions to the effective metric can be classified as conformal and disformal. Disformal terms introduce gradient couplings between scalar fields and the energy momentum tensor of other matter fields, and cannot be constrained by fifth force experiments because the effects of these terms are trivial around static non-relativistic sources. The use of high-precision, low-energy photon experiments to search for conformally coupled scalar fields, called axion-like particles, is well known. In this article we show that these experiments are also constraining for disformal scalar field theories, and are particularly important because of the difficulty of constraining these couplings with other laboratory experiments.Comment: 20 pages, 10 figures. v2: Matches version accepted by JCAP; additional discussion of the strong coupling scale. Conclusions unchange

Review article – The effects of clinical support surfaces on pressure as a risk factor in the development of pressure ulcers, from a radiographical perspective: a narrative literature review

Purpose: Pressure ulcers are a high cost, high volume issue for health and medical care providers, having a detrimental effect on patients and relatives. Pressure ulcer prevention is widely covered in the literature, but little has been published regarding the risk to patients in the radiographical setting. This review of the current literature is to identify findings relevant to radiographical context. Methods: Literature searching was performed using Science Direct and Medline databases. The search was limited to articles published in the last ten years to remain current and excluded studies containing participants less than 17 years of age. In total 14 studies were acquired; three were excluded as they were not relevant. The remaining 11 studies were compared and reviewed. Discussion: Eight of the studies used ‘healthy’ participants and three used symptomatic participants. Nine studies explored interface pressure with a range of pressure mat technologies, two studies measured shear (MRI finite element modelling, and a non-invasive instrument), and one looked at blood flow and haemoglobin oxygenation. A range of surfaces were considered from trauma, nursing and surgical backgrounds for their ability to reduce pressure including standard mattresses, high specification mattresses, rigid and soft layer spine boards, various overlays (gel, air filled, foam). Conclusion: The current literature is not appropriate for the radiographic patient and cannot be extrapolated to a radiologic context. Sufficient evidence is presented in this review to support the need for further work specific to radiography in order to minimise the development of PU in at risk patients

Optimization problems in electron microscopy of single particles

The final publication is available at Springer via http://dx.doi.org/10.1007/s10479-006-0078-8Electron Microscopy is a valuable tool for the elucidation of the three-dimensional structure of macromolecular complexes. Knowledge about the macromolecular structure provides important information about its function and how it is carried out. This work addresses the issue of three-dimensional reconstruction of biological macromolecules from electron microscopy images. In particular, it focuses on a methodology known as “single-particles” and makes a thorough review of all those steps that can be expressed as an optimization problem. In spite of important advances in recent years, there are still unresolved challenges in the field that offer an excellent testbed for new and more powerful optimization techniques.We acknowledge partial support from the “Comunidad Autónoma de Madrid” through grants CAM-07B-0032-2002, GR/SAL/0653/2004 and GR/SAL/0342/2004, the “Comisión Interministerial de Ciencia yTecnologia” of Spain through grants BIO2001-1237, BIO2001-4253-E, BIO2001-4339-E, BIO2002- 10855-E, BFU2004-00217/BMC, the Spanish FIS grant (G03/185), the European Union through grants QLK2- 2000-00634, QLRI-2000-31237, QLRT-2000-0136, QLRI-2001-00015, FP6-502828 and the NIH through grant HL70472. Alberto Pascual and Roberto Marabini acknowledge support by the Spanish Ramon y Cajal Program

Spherically symmetric analysis on open FLRW solution in non-linear massive gravity

We study non-linear massive gravity in the spherically symmetric context. Our main motivation is to investigate the effect of helicity-0 mode which remains elusive after analysis of cosmological perturbation around an open Friedmann-Lemaitre-Robertson-Walker (FLRW) universe. The non-linear form of the effective energy-momentum tensor stemming from the mass term is derived for the spherically symmetric case. Only in the special case where the area of the two sphere is not deviated away from the FLRW universe, the effective energy momentum tensor becomes completely the same as that of cosmological constant. This opens a window for discriminating the non-linear massive gravity from general relativity (GR). Indeed, by further solving these spherically symmetric gravitational equations of motion in vacuum to the linear order, we obtain a solution which has an arbitrary time-dependent parameter. In GR, this parameter is a constant and corresponds to the mass of a star. Our result means that Birkhoff's theorem no longer holds in the non-linear massive gravity and suggests that energy can probably be emitted superluminously (with infinite speed) on the self-accelerating background by the helicity-0 mode, which could be a potential plague of this theory.Comment: 16 pages, references added; minor modification to match version published in JCA

Massive Gravity on de Sitter and Unique Candidate for Partially Massless Gravity

We derive the decoupling limit of Massive Gravity on de Sitter in an arbitrary number of space-time dimensions d. By embedding d-dimensional de Sitter into d+1-dimensional Minkowski, we extract the physical helicity-1 and helicity-0 polarizations of the graviton. The resulting decoupling theory is similar to that obtained around Minkowski. We take great care at exploring the partially massless limit and define the unique fully non-linear candidate theory that is free of the helicity-0 mode in the decoupling limit, and which therefore propagates only four degrees of freedom in four dimensions. In the latter situation, we show that a new Vainshtein mechanism is at work in the limit m^2\to 2 H^2 which decouples the helicity-0 mode when the parameters are different from that of partially massless gravity. As a result, there is no discontinuity between massive gravity and its partially massless limit, just in the same way as there is no discontinuity in the massless limit of massive gravity. The usual bounds on the graviton mass could therefore equivalently well be interpreted as bounds on m^2-2H^2. When dealing with the exact partially massless parameters, on the other hand, the symmetry at m^2=2H^2 imposes a specific constraint on matter. As a result the helicity-0 mode decouples without even the need of any Vainshtein mechanism.Comment: 30 pages. Some clarifications and references added. New subsection 'Symmetry and Counting in the Full Theory' added. New appendix 'St\"uckelberg fields in the Na\"ive approach' added. Matches version published in JCA

Structure and uncoating of immature adenovirus

Maturation via proteolytical processing is a common trait in the viral world, and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins, but ends with proteolytically processed versions in the mature virion; and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytical processing are not infectious. We present the 3D structure of immature adenovirus particles, as represented by the thermosensitive mutant Ad2 ts1 grown under nonpermissive conditions, and compare it with the mature capsid. Our 3DEM maps at subnanometer resolution indicate that adenovirus maturation does not involve large scale conformational changes in the capsid. Difference maps reveal the location of unprocessed peptides pIIIa and pVI and help to define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.This work was supported by grants from the Ministerio de Ciencia e Innovación of Spain (BFU2007-60228 to C.S.M. and BIO2007-67150-C03-03 to R.M.), the Comunidad Autónoma de Madrid and Consejo Superior de Investigaciones Científicas (CCG08-CSIC/SAL-3442 to C.S.M.) and the National Institutes of Health (5R01CA111569 to D.T.C., R0141599 to W.F.M. and GM037705 to S.J.F.). R.M.-C. is a recipient of a PFIS fellowship from the Instituto de Salud Carlos III of Spain. A.J.P.-B. holds a CSIC JAE-Doc postdoctoral position, partially funded by the European Social FundPeer reviewe