Mutation in Archain 1, a Subunit of COPI Coatomer Complex, Causes Diluted Coat Color and Purkinje Cell Degeneration

Intracellular trafficking is critical for delivering molecules and organelles to their proper destinations to carry out normal cellular functions. Disruption of intracellular trafficking has been implicated in the pathogenesis of various neurodegenerative disorders. In addition, a number of genes involved in vesicle/organelle trafficking are also essential for pigmentation, and loss of those genes is often associated with mouse coat-color dilution and human hypopigmentary disorders. Hence, we postulated that screening for mouse mutants with both neurological defects and coat-color dilution will help identify additional factors associated with intracellular trafficking in neuronal cells. In this study, we characterized a mouse mutant with a unique N-ethyl-N-nitrosourea (ENU)–induced mutation, named nur17. nur17 mutant mice exhibit both coat-color dilution and ataxia due to Purkinje cell degeneration in the cerebellum. By positional cloning, we identified that the nur17 mouse carries a T-to-C missense mutation in archain 1 (Arcn1) gene which encodes the δ subunit of the coat protein I (COPI) complex required for intracellular trafficking. Consistent with this function, we found that intracellular trafficking is disrupted in nur17 melanocytes. Moreover, the nur17 mutation leads to common characteristics of neurodegenerative disorders such as abnormal protein accumulation, ER stress, and neurofibrillary tangles. Our study documents for the first time the physiological consequences of the impairment of the ARCN1 function in the whole animal and demonstrates a direct association between ARCN1 and neurodegeneration

Focal adhesion quantification - A new assay of material biocompatibility? : Review

The development of novel synthetic biomaterials is necessitated by the increasing demand for accelerated healing of tissues following surgical intervention. Strict testing of such materials is necessary before application. Currently, before any material can be marketed, approval by regulatory organisations such as the FDA is required. Presently, in vitro testing is performed as a prerequisite to in vivo evaluation. The in vitro techniques currently employed do not reflect the progress in our understanding of extra and intra-cellular processes, with far more sensitive in vitro evaluations now available. Obtaining quantifiable data is increasingly relevant to evaluating events occurring in vivo. Quantifying cell adhesion to surfaces provides some of this data as an initial assessment method. Major developments in this field are occurring but many investigators still use less than optimal methods for assessing biomaterials. The relevance of using cell adhesion assays to help determine biomaterial biocompatibility is reviewed. Additionally, current in vitro methods of evaluating biomaterials are discussed in the context of novel testing concepts developed by the authors

A Quantitative Method of Measuring Cell-Substrate Adhesion Areas

Variability in measurements of the \u27cell adhesion strength\u27 of fibroblasts to substrates using mechanical disruption techniques causes difficulty in determining precisely the position, in the cytoskeleton-focal adhesion-matrix -substrate interface, where failure has occurred. In the present study, a quantitative in vitro procedure for measuring the total area and percentage of fibroblast adhesion to biomaterials, using the scanning electron microscope (SEM), is described. The amount of adhesion ofL929 and Balb/c3T3 fibroblasts to discs of stainless steel, commercially pure titanium, and polyethylene terepthalate (Thermanox) was quantified. Cells were fixed, stained with heavy metals, dehydrated and embedded in resin. The resin blocks were removed from the substrate and sputter coated. The samples were examined in a field emission SEM using backscattered electron imaging. Demonstration that the cells had been removed with their adhesion sites, was by immunocytochemical labelling of vinculin within the focal adhesions of the embedded ~lis. Quantification of cell adhesion was performed by measuring the total area of each cell (imaged at 15 kV) and the area of their adhesion sites (imaged at 4kV) using an image analysis system. The in vitro results show (under static conditions, with the materials, roughnesses and cell types used) that roughness does not affect the total area of adhesion. The procedure could be applied to any cells that form focal adhesions, such as osteoblasts and may be developed to assess connective tissue adhesion to implant surfaces from in vivo experiments

Potential mode of clutch size determination and follicle development in Eudyptes penguins

It has long been held that Eudyptes penguins will only ever develop a maximum of two mature yolky follicles to match their invariant two-egg clutch, an idea inferred largely from egg removal studies. Combining our own data with those from a previous but rarely cited study and by applying these to a simple developmental model, we show that macaroni penguins (Eudyptes chrysolophus) develop up to four large, yolky vitellogenic follicles, and they do so despite the fact that they will never lay more than two eggs or rear more than one chick, a tactic that seems maladaptive given their realized reproductive success. We discuss these results within the context of the usual pattern of reproductive investment in Eudyptes penguins and suggest a broader significance to modes of clutch size determination among all penguins (order Sphenisciformes)

The 2010 Hans Cloos lecture : the contribution of urban geology to the development, regeneration and conservation of cities

Urban geology began to develop in the 1950s, particularly in California in relation to land-use planning, and led to Robert Legget publishing his seminal book “Cities and geology” in 1973. Urban geology has now become an important part of engineering geology. Research and practice has seen the evolution from single theme spatial datasets to multi-theme and multi-dimensional outputs for a wide range of users. In parallel to the development of these new outputs to aid urban development, regeneration and conservation, has been the growing recognition that city authorities need access to extensive databases of geo-information that are maintained in the long-term and renewed regularly. A further key advance has been the recognition that, in the urban environment, knowledge and understanding of the geology need to be integrated with those of other environmental topics (for example, biodiversity) and, increasingly, with the research of social scientists, economists and others. Despite these advances, it is suggested that the value of urban geology is not fully recognised by those charged with the management and improvement of the world’s cities. This may be because engineering geologists have failed to adequately demonstrate the benefits of urban geological applications in terms of cost and environmental improvement, have not communicated these benefits well enough and have not clearly shown the long-term contribution of geo-information to urban sustainability. Within this context future actions to improve the situation are proposed

Fur seals at Macquarie Island: post-sealing colonisation, trends in abundance and hybridisation of three species

© Springer-Verlag 2009Commercial sealers exterminated the original fur seal population at Macquarie Island in the early 1800s. The first breeding record since the sealing era was not reported until March 1955. Three species of fur seal now occur at Macquarie Island, the Antarctic (Arctocephalus gazella), subantarctic (A. tropicalis) and New Zealand (A. forsteri) fur seal. Census data from 54 breeding seasons in the period 1954–2007 were used to estimate population status and growth for each species. Between the 1950s and 1970s, annual increases in pup production for the species aggregate were low. Between 1986 and 2007, pup production of Antarctic fur seals increased by about 8.8% per year and subantarctic fur seals by 6.8% per year. The New Zealand fur seal, although the most numerous fur seal species on Macquarie Island, has yet to establish a breeding population, due to the absence of reproductively mature females. Hybridisation among species is significant, but appears to be declining. The slow establishment and growth of fur seal populations on Macquarie Island appears to have been affected by its distance from major population centres and hence low immigration rates, asynchronous colonisation times of males and females of each species, and extensive hybridisation.Simon David Goldsworthy, Jane McKenzie, Brad Page, Melanie L. Lancaster, Peter D. Shaughnessy, Louise P. Wynen, Susan A. Robinson, Kristian J. Peters, Alastair M. M. Baylis and Rebecca R. McIntos