The structure of protein molecules : in celebration of the International Year of Crystallography, 2014

Many people, including laymen, are aware of the double helical nature of the DNA molecule. A few may actually realise that it was the technique of X-ray crystallography that was the key to solving this structure. Even fewer will understand the uses and applications of crystallography to the most diverse of biological materials; proteins. In this review we discuss the application of a number of methodologies required to progress from a cloned gene to protein expression and purification, crystallisation conditions and eventually to X-ray structure determination. We provide our own experience in the field as examples of the procedures required. Protein crystallographers worldwide are contributing to our understanding of how enzymes work, how our immune system defends us against viruses and are using structural information to design novel pharmaceutical reagents.peer-reviewe

Surveying mobile populations: lessons from recent longitudinal surveys of Indigenous Australians

Geographically mobile populations are notoriously difficult to survey, especially in a cross-cultural context. In broad terms, it is difficult to ensure that respondents are representative of the underlying population and that data obtained are relevant to them. At a practical level, the problem can be as basic as not having any well-formed notion of what defines a household. Consequently, the resulting analysis of households is at best imprecise and, at worst, conceptually confused. Longitudinal data add a time dimension to surveys and the resulting analysis is potentially sensitive to the initial experience of individual respondents. This paper documents the lessons for the design and conduct of longitudinal data collection from three recent surveys of an exceptionally mobile population, Indigenous Australians. Since high levels of mobility characterise many unemployed and younger Australians, the lessons described here have wider application for general longitudinal surveys

Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(−/−);SMN2(tg/0);SMN1(SC)). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms

Development of a Geographic Information System for Natural Resources and Recreational Facilities

unpublishednot peer reviewedOpe

Dysfunctional stem and progenitor cells impair fracture healing with age

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly

ALMA Resolves 30 Doradus: Sub-parsec Molecular Cloud Structure Near the Closest Super-Star Cluster

We present ALMA observations of 30 Doradus -- the highest resolution view of molecular gas in an extragalactic star formation region to date (~0.4pc x 0.6pc). The 30Dor-10 cloud north of R136 was mapped in 12CO 2-1, 13CO 2-1, C18O 2-1, 1.3mm continuum, the H30alpha recombination line, and two H2CO 3-2 transitions. Most 12CO emission is associated with small filaments and clumps (<1pc, ~1000 Msun at the current resolution). Some clumps are associated with protostars, including "pillars of creation" photoablated by intense radiation from R136. Emission from molecular clouds is often analyzed by decomposition into approximately beam-sized clumps. Such clumps in 30 Doradus follow similar trends in size, linewidth, and surface density to Milky Way clumps. The 30 Doradus clumps have somewhat larger linewidths for a given size than predicted by Larson's scaling relation, consistent with pressure confinement. They extend to higher surface density at a given size and linewidth compared to clouds studied at 10pc resolution. These trends are also true of clumps in Galactic infrared-dark clouds; higher resolution observations of both environments are required. Consistency of clump masses calculated from dust continuum, CO, and the virial theorem reveals that the CO abundance in 30 Doradus clumps is not significantly different from the LMC mean, but the dust abundance may be reduced by ~2. There are no strong trends in clump properties with distance from R136; dense clumps are not strongly affected by the external radiation field, but there is a modest trend towards lower dense clump filling fraction deeper in the cloud.Comment: accepted to Ap

The Eating and Drinking Ability Classification System for cerebral palsy:a study of reliability and stability over time

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAIM: This study evaluated the inter-observer reliability and stability over time of the Eating and Drinking Ability Classification System (EDACS) for children and young people with cerebral palsy (CP). METHOD: Case records for 97 children with CP were examined to collect retrospective data about eating and drinking abilities at four time-points with a minimum of 2 years between each time-point. Sex, Gross Motor Function Classification System (GMFCS) level, presence of feeding tube and orthopaedic issues were recorded from case records. One speech and language therapist (SaLT1) classified eating and drinking ability using EDACS for all cases at all time-points; SaLT2 assigned EDACS levels for 50 cases at time-point 1; SaLT3 assigned EDACS levels for 24 cases at all time-points. Inter-observer reliability and stability over time were assessed using the Intraclass Correlation Coefficient (ICC). Associations between EDACS levels and functioning recorded with other Functional Classification Systems (FCSs) were calculated using Kendall's tau (τ). RESULTS: Out of 97 children, 48 were male, 48 had feeding tubes, and 83 had orthopaedic issues. ICC for EDACS levels recorded by SaLT1 across all time-points was 0.97 (95% CI 0.96-0.98); changes in EDACS levels occurred infrequently and never by more than one level. ICC between SaLT1 and SaLT2 at time-point 1 was 0.8 (95% CI 0.67-0.89); ICC between SaLT1 and SaLT3 across all time-points was 0.95 (95% CI 0.92-0.98). Association between GMFCS and EDACS was moderate (τ= 0.58). INTERPRETATION: Retrospective use of EDACS to classify children's eating and drinking abilities appears reliable; EDACS appeared stable over 6 or more years in 86% of the cases.British Academy of Childhood Disability and Royal College of Paediatrics and Child Health Polani Priz