Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

Theory of preparation and relaxation of a p-orbital atomic Mott insulator

We develop a theoretical framework to understand the preparation and relaxation of a metastable Mott insulator state within the first excited band of a 1D optical lattice. The state is loaded by "lifting" atoms from the ground to the first excited band by means of a stimulated Raman transition. We determine the effect of pulse duration on the accuracy of the state preparation for the case of a Gaussian pulse shape. Relaxation of the prepared state occurs in two major stages: double-occupied sites occurring due to quantum fluctuations initially lead to interband transitions followed by a spreading of particles in the trap and thermalization. We find the characteristic relaxation times at the earliest stage and at asymptotically long times approaching equilibrium. Our theory is applicable to recent experiments performed with 1D optical lattices [T. M\"uller, S. F\"olling, A. Widera, and I. Bloch, Phys. Rev. Lett. \textbf{99}, 200405 (2007)].Comment: 27 pages, 23 figures: Edited figures, added reference

Developing the evidence base for adult social care practice: The NIHR School for Social Care Research

In a foreword to 'Shaping the Future of Care Together', Prime Minister Gordon Brown says that a care and support system reflecting the needs of our times and meeting our rising aspirations is achievable, but 'only if we are prepared to rise to the challenge of radical reform'. A number of initiatives will be needed to meet the challenge of improving social care for the growing older population. Before the unveiling of the green paper, The National Institute for Health Research (NIHR) announced that it has provided 15m pounds over a five-year period to establish the NIHR School for Social Care Research. The School's primary aim is to conduct or commission research that will help to improve adult social care practice in England. The School is seeking ideas for research topics, outline proposals for new studies and expert advice in developing research methods

Demographic and clinical characteristics of UK military veterans attending a psychological therapies service

© 2014 The Authors. Aims and method To investigate the demographic and clinical characteristics of subgroups of UK veterans attending a dedicated psychological therapies service following the Improving Access to Psychological Therapies (IAPT) treatment model. Veterans accessing a newly established service in the north-west were categorised into three groups: early service leavers, those with a physical disability, and substance and/or alcohol misusers. Anxiety, depression and social functioning were measured pre- and post-treatment. Results Veterans vary in their demographic and clinical characteristics as well as in treatment efficacy, as measured by the post-treatment scores on probable depression and anxiety. Therapy appears to be most effective in early service leavers, whereas veterans with a physical disability or a substance or alcohol misuse problem tend not to do as well in terms of symptoms of depression or anxiety. Clinical implications This study highlights the importance of targeting different veteran subgroups for dedicated psychological therapy