University of Nottingham

About: University of Nottingham is a education organization based out in Nottingham, Nottingham, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 54772 authors who have published 119600 publications receiving 4227408 citations. The organization is also known as: The University of Nottingham & University College, Nottingham.

Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets

Abstract: The ubiquitin-proteasome system (UPS) and ubiquitin-like protein (UBL) conjugation pathways are integral to cellular protein homeostasis. The growing recognition of the fundamental importance of these pathways to normal cell function and in disease has prompted an in-depth search for small-molecule inhibitors that selectively block the function of these pathways. However, our limited understanding of the molecular mechanisms and biological consequences of UBL conjugation is a significant hurdle to identifying drug-like inhibitors of enzyme targets within these pathways. Here, we highlight recent advances in understanding the role of some of these enzymes and how these new insights may be the key to developing novel therapeutics for diseases including immuno-inflammatory disorders, cancer, infectious diseases, cardiovascular disease and neurodegenerative disorders.

The Electromagnetic Counterpart of the Binary Neutron Star Merger LIGO/Virgo GW170817. I. Discovery of the Optical Counterpart Using the Dark Energy Camera

Abstract: We present the Dark Energy Camera (DECam) discovery of the optical counterpart of the first binary neutron star merger detected through gravitational-wave emission, GW170817. Our observations commenced 10.5 hr post-merger, as soon as the localization region became accessible from Chile. We imaged 70 deg(2) in the i and z bands, covering 93% of the initial integrated localization probability, to a depth necessary to identify likely optical counterparts (e.g., a kilonova). At 11.4 hr post-merger we detected a bright optical transient located $10\buildrel{\prime\prime}\over{.} 6$ from the nucleus of NGC 4993 at redshift z = 0.0098, consistent (for ${H}_{0}=70$ km s(−)(1) Mpc(−)(1)) with the distance of 40 ± 8 Mpc reported by the LIGO Scientific Collaboration and the Virgo Collaboration (LVC). At detection the transient had magnitudes of $i=17.3$ and $z=17.4$, and thus an absolute magnitude of ${M}_{i}=-15.7$, in the luminosity range expected for a kilonova. We identified 1500 potential transient candidates. Applying simple selection criteria aimed at rejecting background events such as supernovae, we find the transient associated with NGC 4993 as the only remaining plausible counterpart, and reject chance coincidence at the 99.5% confidence level. We therefore conclude that the optical counterpart we have identified near NGC 4993 is associated with GW170817. This discovery ushers in the era of multi-messenger astronomy with gravitational waves and demonstrates the power of DECam to identify the optical counterparts of gravitational-wave sources.

A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule

Abstract: Mutations in the seven clustered rpf genes cause downregulated synthesis of extracellular enzymes and reduced virulence of Xanthomonas campestris pathovar campestris (Xcc). The phenotype of mutants in one of the genes, rpfF, can be restored by a diffusible extracellular factor (DSF) produced by all Xcc strains tested, apart from rpfF and rpfB mutants. DSF accumulates in early stationary phase (when synthesis of enzymes is maximal), but levels decline subsequently. Addition of DSF to exponentially-growing wild-type bacteria does not cause precocious enzyme synthesis. rpfB and rpfF are expressed throughout growth, but the rate increases in early stationary phase. RpfB is predicted to be a long-chain fatty acyl CoA ligase, and RpfF shows some relatedness to enoyl CoA hydratases. The properties of DSF suggest that it may be a fatty-acid derivative, and certain lipid preparations possess DSF activity at higher concentrations. These include lipid extracts and acid-hydrolysed lipoplysaccharide and lipid A from Xcc, and purified dodecanoic and hydroxydodecanoic acid. DSF production is confined to certain xanthomonads. We propose a model for the DSF system, which represents a novel mechanism for regulating virulence factor synthesis in response to physiological or environmental changes.

A spin-valve-like magnetoresistance of an antiferromagnet-based tunnel junction

Abstract: Spin-valve structures used in modern hard-drive read heads and magnetic random access memories comprise two ferromagnetic electrodes. It is now shown that antiferromagnets can be used as electrodes in spin valves. The results open a wide range of new possibilities for the choice of materials for spintronics devices.