Pharmacological And Genetic Reversal Of Age-Dependent Cognitive Deficits Attributable To Decreased Presenilin Function

Alzheimer\u27s disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced

Surface rupture displacement on the Greendale Fault during the Mw 7.1 Darfield (Canterbury) earthquake, New Zealand, and its impact on man-madestructures.

Surface rupture of the previously unrecognised Greendale Fault extended west-east for ~30 km across alluvial plains west of Christchurch, New Zealand, during the Mw 7.1 Darfield (Canterbury) earthquake of September 2010. Surface rupture displacement was predominantly dextral strike-slip, averaging ~2.5 m, with maxima of ~5 m. Vertical displacement was generally less than 0.75 m. The surface rupture deformation zone ranged in width from ~30 to 300 m, and comprised discrete shears, localised bulges and, primarily, horizontal dextral flexure. About a dozen buildings, mainly single-storey houses and farm sheds, were affected by surface rupture, but none collapsed, largely because most of the buildings were relatively flexible and resilient timber-framed structures and also because deformation was distributed over a relatively wide zone. There were, however, notable differences in the respective performances of the buildings. Houses with only lightly-reinforced concrete slab foundations suffered moderate to severe structural and non-structural damage. Three other buildings performed more favourably: one had a robust concrete slab foundation, another had a shallow-seated pile foundation that isolated ground deformation from the superstructure, and the third had a structural system that enabled the house to tilt and rotate as a rigid body. Roads, power lines, underground pipes, and fences were also deformed by surface fault rupture and suffered damage commensurate with the type of feature, its orientation to the fault, and the amount, sense and width of surface rupture deformation

Strike-slip ground-surface rupture (Greendale Fault) associated with the 4th September 2010 Darfield Earthquake, Canterbury, New Zealand

This paper provides a photographic tour of the ground-surface rupture features of the Greendale Fault, formed during the 4th September 2010 Darfield Earthquake. The fault, previously unknown, produced at least 29.5 km of strike-slip surface deformation of right-lateral (dextral) sense. Deformation, spread over a zone between 30 and 300 m wide, consisted mostly of horizontal flexure with subsidiary discrete shears, the latter only prominent where overall displacement across the zone exceeded about 1.5 m. A remarkable feature of this event was its location in an intensively farmed landscape, where a multitude of straight markers, such as fences, roads and ditches, allowed precise measurements of offsets, and permitted well-defined limits to be placed on the length and widths of the surface rupture deformation