Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?

Protein homeostasis (proteostasis), the correct balance between production and degradation of proteins, is essential for the health and survival of cells. Proteostasis requires an intricate network of protein quality control pathways (the proteostasis network) that work to prevent protein aggregation and maintain proteome health throughout the lifespan of the cell. Collapse of proteostasis has been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disorder. Here, we review the evidence linking dysfunctional proteostasis to the etiology of ALS and discuss how ALS-associated insults affect the proteostasis network. Finally, we discuss the potential therapeutic benefit of proteostasis network modulation in ALS

A New Method to Measure and Map the Gas Scale-Height of Disk Galaxies

We propose a new method to measure and map the gas scale height of nearby disk galaxies. This method is applied successfully to the Australia Telescope Compact Array interferometric HI survey of the Large Magellanic Cloud (LMC); it could also be applied to a significant number of nearby disk galaxies, thanks to the next generation of interferometric facilities, such as the extended VLA and CARMA. The method consists of computing the Spectral Correlation Function (SCF) for a spectral-line map of a face-on galaxy. The SCF quantifies the correlation between spectra at different map positions as a function of their separation, and is sensitive to the properties of both the gas mass distribution and the gas velocity field. It is likely that spatial correlation properties of the gas density and velocity fields in a galactic disk are sensitive to the value of the scale height of the gas disk. A scale-free turbulent cascade is unlikely to extend to scales much larger than the disk scale height, as the disk dynamics on those larger scales should be dominated by two dimensional motions. We find a clear feature in the SCF of the LMC HI disk, on the scale of approximately 180 pc, which we identify as the disk scale height. We are also tentatively able to map variations of the scale height over the disk.Comment: 6 pages, submitted to ApJ

A Chandra X-ray Study of Cygnus A - II. The Nucleus

We report Chandra ACIS and quasi-simultaneous RXTE observations of the nearby, powerful radio galaxy Cygnus A, with the present paper focusing on the properties of the active nucleus. In the Chandra observation, the hard (> a few keV) X-ray emission is spatially unresolved with a size \approxlt 1 arcsec (1.5 kpc, H_0 = 50 km s^-1 Mpc^-1) and coincides with the radio and near infrared nuclei. In contrast, the soft (< 2 keV) emission exhibits a bi-polar nebulosity that aligns with the optical bi-polar continuum and emission-line structures and approximately with the radio jet. In particular, the soft X-ray emission corresponds very well with the [O III] \lambda 5007 and H\alpha + [N II] \lambda\lambda 6548, 6583 nebulosity imaged with HST. At the location of the nucleus there is only weak soft X-ray emission, an effect that may be intrinsic or result from a dust lane that crosses the nucleus perpendicular to the source axis. The spectra of the various X-ray components have been obtained by simultaneous fits to the 6 detectors. The compact nucleus is detected to 100 keV and is well described by a heavily absorbed power law spectrum with \Gamma_h = 1.52^{+0.12}_{-0.12} (similar to other narrow line radio galaxies) and equivalent hydrogen column N_H (nuc) = 2.0^{+0.1}_{-0.2} \times 10^{23} cm^-2. (Abstract truncated).Comment: To be published in the Astrophysical Journal, v564 January 1, 2002 issue; 34 pages, 11 figures (1 color

Focusing on ICT in Rural and Regional Education in Australia

National priorities set by an Australian ministerial taskforce provide clear guidelines to develop pedagogy that integrates ICT. Although these guidelines do not specifically address rural and regional schools needs, the two priorities: promoting pedagogic leadership and creating new learning environments, are of particular interest. But how are these priorities reflected in the realities of rural and regional schools? Focus group interviews were conducted at a selection of rural and regional schools in each state and territory across Australia. These provided teachers, parents and students with the opportunity to identify key issues in relation to ICT in their schools. Issues identified by the focus groups were; the state of equipment in schools, comparability between home and school ICT experiences for students, pedagogical approaches, leadership, professional development and availability of ICT specialist teachers

Bone turnover and metabolite responses to exercise in people with and without long-duration type 1 diabetes: a case-control study

INTRODUCTION: Exercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and matched controls. RESEARCH DESIGN AND METHODS: Participants with type 1 diabetes (n=15; age: 38.7±13.3; glycosylated hemoglobin: 60.5±6.7 mmol/mol; diabetes duration: 19.3±11.4 years) and age-matched, fitness-matched, and body mass index-matched controls (n=15) completed 45 min of incline walking (60% peak oxygen uptake). Blood samples were collected at baseline and immediately, 30 min, and 60 min postexercise. Markers of bone resorption (β-C-terminal cross-linked telopeptide of type 1 collagen, β-CTx) and formation (procollagen type-1 amino-terminal propeptide, P1NP), parathyroid hormone (PTH), phosphate, and calcium (albumin-adjusted and ionized) were measured. Data (mean±SD) were analyzed by a mixed-model analysis of variance. RESULTS: Baseline concentrations of P1NP and β-CTx were comparable between participants with type 1 diabetes and controls. P1NP did not change with exercise (p=0.20) but β-CTx decreased (p0.39). Participants with type 1 diabetes had reduced albumin and ionized calcium at all sample points (p<0.01). CONCLUSIONS: Following exercise, participants with type 1 diabetes displayed similar time-course changes in markers of bone formation and associated metabolites, but an attenuated suppression in bone resorption. The reduced albumin and ionized calcium may have implications for future bone health. Further investigation of the interactions between type 1 diabetes, differing modalities and intensities of exercise, and bone health is warranted

A reflective journal as learning process and contribution to quality and validity in interpretative phenomenological analysis

Using selected, contemporaneous illustrations from the reflective journal of a doctoral student undertaking data analysis for the first time, this article examines the relationship between journaling as a learning process when undertaking computer-assisted qualitative data analysis and establishing quality and validity in interpretative phenomenological analysis. The writing of the journal is shown both to enact some potential validity criteria (e.g. in producing an audit trail) whilst also recording and reflectively prompting the process of learning, interpretation and bracketing, thus evidencing transparency. By using a journal inside the software package and alongside the stages of the interpretative phenomenological analysis, analysis within the software package, it is argued that quality and validity become dynamic, not static constructs. These constructs are intimately linked to the researcher-learning-process and permit a critical stance to be taken

Seed production areas for the global restoration challenge

Wild-collected seed can no longer meet global demand in restoration. Dedicated Seed Production Areas (SPA) for restoration are needed and these require application of ecological, economic, and population-genetic science. SPA design and construction must embrace the ecological sustainability principles of restoration