Dynamic nuclear polarization at high magnetic fields in liquids

High field dynamic nuclear polarization spectrometer for liquid samples have been constructed. ► The field dependence of the Overhauser DNP efficiency has been measured for the first time up to 9.2 T. ► High DNP enhancements for liquid samples have been observed at high magnetic fields. ► The enhancements have been compared with results from NMRD, MD and theoretical models. ► Coherent and relaxation effects within fast magnetic field changes have been analyzed

Augmenting microwave irradiation in MAS DNP NMR samples at 263 GHz

The magnetic microwave field strength and its detailed spatial distribution in magic-angle spinning (MAS) nuclear magnetic resonance (NMR) probes capable of dynamic nuclear polarization (DNP) is investigated by numerical simulations with the objective to augment the magnetic microwave amplitude by structuring the sample in the mm and sub-mm range and by improving the coupling of the incident microwave beam to the sample. As it will be shown experimentally, both measures lead to an increase of the microwave efficiency in DNP MAS NMR

DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk.

The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1. Pulse-chases combined with mutagenesis studies reveal that Ser1 strongly influences Syk stability. Furthermore, DPP9 silencing reduces Cbl interaction with Syk, suggesting that DPP9 processing is a prerequisite for Syk ubiquitination. Consistently, DPP9 inhibition stabilizes Syk, thereby modulating Syk signalling. Taken together, we demonstrate DPP9 as a negative regulator of Syk and conclude that DPP9 is a novel integral aminopeptidase of the N-end rule pathway

Sheep Updates 2005 - Part 3

This session covers seven papers from different authors: CUSTOMER 1. Benefits VIAscanR to producers and WAMMCO, Rob Davidson, Supply Development Manager, David Pethick, School of Veterinary and Biomedical Studies, Murdock University. 2. Healthy fats in lamb: how WA lambs compare with others, C. F. Engelke Animal Biology, University of Western Australia, bCSIRO Livestock Industries, Western Australia B.D. Siebert, Department of Animal Science, University of Adelaide, South Australia, K. Gregg, Centre for High-Throughput Agricultural Genetic Analysis, Murdoch University, Western Australia. A-D.G. Wright CSIRO Livestock Industries, Western Australia, P.E Vercoe Animal Biology, University of Western Australia 3. Shelf life of fresh lamb meat: lamb age & electrical stimulation, Dr Robin Jacob, Department of Agriculture, Western Australia 4. Pastures from space - An evaluation of adoption of by Australian woolgrowers, Russell Barnett, Australian Venture Consultants, Joanne Sneddon, University of Western Australia 5. Your clients can learn from ASHEEP\u27s example, Sandra Brown Department of Agriculture Western Australia 6. Lifetime Wool - Farmers attitudes affect their adoption of recommended ewe management, G. Rose Department of Agriculture Western Australia, C. Kabore, Kazresearch, Lower Templestowe Vic, J. Dart, Clear Horizons, Hastings Vic 7. Sustainable certification of Australian Merino, what will customers be looking for? Stuart Adams, i-merino / iZWool International Pty Lt

Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments