Targeting the Progression of Parkinson’s Disease

By the time a patient first presents with symptoms of Parkinson’s disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson’s disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease

Novel community data in ecology-properties and prospects

New technologies for monitoring biodiversity such as environmental (e)DNA, passive acoustic monitoring, and optical sensors promise to generate automated spatiotemporal community observations at unprecedented scales and resolutions. Here, we introduce ‘novel community data’ as an umbrella term for these data. We review the emerging field around novel community data, focusing on new ecological questions that could be addressed; the analytical tools available or needed to make best use of these data; and the potential implications of these developments for policy and conservation. We conclude that novel community data offer many opportunities to advance our understanding of fundamental ecological processes, including community assembly, biotic interactions, micro- and macroevolution, and overall ecosystem functioning

The stability of drystone retaining walls on highways

Surveys of the stock of masonry-faced earth-retaining walls in five local authorities showed that there was about 93 km of such walls on the 1475 km or so of trunk roads within the boundaries of these authorities. Their replacement cost was approximately £1.16 million per km of wall, while expenditure on maintenance and replacement of the whole 93 km of walls was a little over £800000 annually. Extrapolation of the data is difficult, but it would not seem unreasonable to suggest that there is a total of some 120-140 km of such walls on the trunk roads in England and Wales, and also that the total for all roads in Great Britain lies within the limits of 9000 ± 2000 km. The current stock of these walls on highways in Great Britain is therefore, by and large, performing satisfactorily and seems likely to do so for many more years. The explanation for the stability of such walls is complicated and a number of factors are involved. But current design codes preclude the use of many of these optimistic, but nevertheless real, factors. Improved methods of assessment should help ensure that the current stock on our highways is kept in good order so that this part of our national heritage is preserved for many generations to come

Deformation and failure modes of drystone retaining walls

In this paper, the factors controlling the deformation of drystone retaining walls are investigated by means of discrete element analyses. It is shown that toppling failure of unweathered drystone retaining walls is likely to occur in a brittle manner, with wall crest deflections not exceeding 1% of the backtill height until the factor of safety (based on soil strength) falls below 1.05. A compressible sub-base and weathering of the blocks will both tend to reduce the backfill height at failure to below that indicated by a limit equilibrium analysis. Bulging failure is more likely to be associated with a deterioration in block joint stiffness due to weathering than a compressible sub-base, although the latter will decrease the reduction in joint stiffness needed to cause bulging failure. Bulging is much less brittle than toppling, and the proximity to failure of bulging walls could in some circumstances be assessed on the basis of the size of the bulge

Specification for suitability testing of stress absorbing materials behind integral bridge abutments

Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:9050. 78239(553) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

The response of a reinforced soil wall to differential movement

Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:9050. 78239(565) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo