Prion protein-specific antibodies that detect multiple TSE agents with high sensitivity

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays

Search for quark compositeness in dijet angular distributions from pp collisions at √s̅ = 7 TeV

Peer reviewe

Search for supersymmetry in pp collisions at 7 TeV in events with jets and missing transverse energy

A search for supersymmetry with R-parity conservation in proton-proton collisions at a centre-of-mass energy of 7 TeV is presented. The data correspond to an integrated luminosity of 35 pb(-1) collected by the CMS experiment at the LHC. The search is performed in events with jets and significant missing transverse energy, characteristic of the decays of heavy, pair-produced squarks and gluinos. The primary background, from standard model multijet production, is reduced by several orders of magnitude to a negligible level by the application of a set of robust kinematic requirements. With this selection, the data are consistent with the standard model backgrounds, namely t (t) over bar, W + jet and Z + jet production, which are estimated from data control samples. Limits are set on the parameters of the constrained minimal supersymmetric extension of the standard model. These limits extend those set previously by experiments at the Tevatron and LEP colliders. (C) 2011 CMS Collaboration

A new era for understanding amyloid structures and disease

The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their intact protein precursors and how fibril formation relates to disease has remained elusive. Recent advances in structural biology techniques, including cryo-electron microscopy and solid-state NMR spectroscopy, have finally broken this impasse. The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available. The results reveal cross-β structures that are far more intricate than anticipated. Here, we describe these structures, highlighting their similarities and differences, and the basis for their toxicity. We discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention

Measurement of the underlying event activity at the LHC with root s=7 TeV and comparison with root s=0.9 TeV

A measurement of the underlying activity in events with a jet of transverse momentum in the several GeV region is performed in proton-proton collisions at s√=0.9 and 7 TeV, using data collected by the CMS experiment at the LHC. The production of charged particles with pseudorapidity |η|  0.5 GeV/c is studied in the azimuthal region transverse to that of the leading set of charged particles forming a track-jet. A significant growth of the average multiplicity and scalar-p T sum of the particles in the transverse region is observed with increasing p T of the leading track-jet, followed by a much slower rise above a few GeV/c. For track-jet p T larger than a few GeV/c, the activity in the transverse region is approximately doubled with a centre-of-mass energy increase from 0.9 to 7 TeV. Predictions of several QCD-inspired models as implemented in pythia are compared to the data

A case of mistaken identity

What went wrong between the UK media and a report on 'multi-ethnic' Britain