RNA processing in human mitochondria.

Mammalian mitochondrial DNA is transcribed as precursor polycistronic transcripts containing 13 mRNAs, 2 rRNAs, punctuated by 22 tRNAs. The mechanisms involved in the excision of mitochondrial tRNAs from these polycistronic transcripts have remained largely unknown. We have investigated the roles of ELAC2, mitochondrial RNase P proteins 1 and 3, and pentatricopeptide repeat domain protein 1 in the processing of mitochondrial polycistronic transcripts.

Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study.

Background: Patients with chronic lymphocytic leukaemia (CLL) are known to have increased risks of second cancer. The incidence of second cancers after CLL has not been reported in detail for Australia, a country with particularly high levels of ultraviolet radiation (UVR).

Methods: The study cohort comprised of all people diagnosed with a primary CLL between 1983 and 2005 in Australia.

Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling.

The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin.

Quantitative rt-PCR holds promise as a screening tool for patients with severe sepsis.

Objective: The aim of the present study was to determine if the quantification of bacterial 16S rDNA could be clinically useful in predicting patients at increased risk of developing septic shock.

Methods: A retrospective study of patients with positive blood cultures taken on arrival to the ED. An EDTA sample was collected simultaneously with blood cultures and assayed by polymerase chain reaction to quantitate the bacterial 16S rDNA load.

Steroid Receptor RNA Activator - A nuclear receptor coregulator with multiple partners: Insights and challenges.

Steroid Receptor RNA Activator (SRA) occupies a unique and enigmatic position within the nuclear receptor (NR) field and more broadly in transcriptional regulation. This is as a result of its transcripts having both coding and non-coding coactivator activities along with its protein product SRAP performing mixed coactivator/repressor functions. Recent publications have provided greater understanding of SRA gene product activities and how they affect not only NR function, but now more broadly, signalling pathways involved in differentiation and metabolism.

Causes of ant sting anaphylaxis in Australia: the Australian Ant Venom Allergy Study.

Objective: To determine the Australian native ant species associated with ant sting anaphylaxis, geographical distribution of allergic reactions, and feasibility of diagnostic venom-specific IgE (sIgE) testing.

Design, Setting And Participants: Descriptive clinical, entomological and immunological study of Australians with a history of ant sting anaphylaxis, recruited in 2006-2007 through media exposure and referrals from allergy practices and emergency physicians nationwide. We interviewed participants, collected entomological specimens, prepared reference venom extracts, and conducted serum sIgE testing against ant venom panels relevant to the species found in each geographical region.

G protein-coupled receptor heteromer identification technology: identification and profiling of GPCR heteromers.

Traditionally, G protein-coupled receptors (GPCRs) were thought to function as monomeric units activating linear signaling pathways to reach a single functional response. However, it is now recognized that GPCRs can exist as higher order structures, such as homomers or heteromers. The potential for unique pharmacology attributed to these GPCR complexes has opened up the possibility of a new class of targets that can be exploited for drug discovery.

Hypotheses for mechanisms linking shiftwork and cancer.

Shift work has been associated with various adverse health outcomes. In particular, there has been a recent flourish in investigating potential cancer risk associated with working night shifts and other shift schedules. Epidemiologic studies have revealed generally weak associations due to several methodological challenges such as lack of standard classifications of shift or night work.

Merkel cell carcinoma in Western Australia: a population-based study of incidence and survival.

Background: Merkel cell carcinoma (MCC) is an uncommon but aggressive cutaneous skin cancer. Even with the appropriate treatment, MCC is prone to recurrence, and metastases are common. Exposure to ultraviolet radiation has been suggested as contributing towards the development of MCC.

ParaMED Home: a protocol for a randomised controlled trial of paramedic assessment and referral to access medical care at home.

Background: In Australia approximately 25% of Emergency Department (ED) attendances are via ambulance. ED overcrowding in Australia, as in many countries, is common. Measures to reduce overcrowding include the provision of enhanced timely primary care in the community for appropriate low risk injury and illness.

Focal epilepsy of probable temporal lobe origin in a Gypsy family showing linkage to a novel locus on 7p21.3.

We aimed to characterise the phenotype and perform genetic studies in a family of Roma/Gypsy ethnicity, affected by epilepsy. The mean age at onset of epilepsy was 9 years and seizures persisted into adulthood. Antecedent febrile convulsions were rare.

Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy.

Linkage analysis of the dominant distal myopathy we previously identified in a large Australian family demonstrated one significant linkage region located on chromosome 7 and encompassing 18.6 Mbp and 151 genes. The strongest candidate gene was FLNC because filamin C, the encoded protein, is muscle-specific and associated with myofibrillar myopathy.

A universal code for RNA recognition by PUF proteins.

The design of proteins that can bind any RNA sequence of interest has many potential biological and medical applications. Here we have expanded the recognition of Pumilio and FBF homology protein (PUF) repeats beyond adenine, guanine and uracil and evolved them to specifically bind cytosine. These repeat sequences can be used to create PUF domains capable of selectively binding RNA targets of diverse sequence and structure.

Protein annotation from protein interaction networks and Gene Ontology.

We introduce a novel method for annotating protein function that combines Naïve Bayes and association rules, and takes advantage of the underlying topology in protein interaction networks and the structure of graphs in the Gene Ontology. We apply our method to proteins from the Human Protein Reference Database (HPRD) and show that, in comparison with other approaches, it predicts protein functions with significantly higher recall with no loss of precision. Specifically, it achieves 51% precision and 60% recall versus 45% and 26% for Majority and 24% and 61% for χ²-statistics, respectively.

A comparison of metropolitan vs rural major trauma in Western Australia.

Background: Metropolitan and rural Western Australia (WA) major trauma transport times are extremely different. We compared outcomes from these different systems of care.

Methods: Major trauma (Injury Severity Score, ISS>15) data from the Royal Flying Doctor Service (RFDS) and Trauma Registries, 1 July 1997-30 June 2006.

Long-term sedentary work and the risk of subsite-specific colorectal cancer.

Research suggests that sedentary behavior may increase the risk of some chronic diseases. The aims of the study were to examine whether sedentary work is associated with colorectal cancer and to determine whether the association differs by subsite. A total of 918 cases and 1,021 controls participated in a population-based case-control study of colorectal cancer in Western Australia in 2005-2007.

Quality use of medicines and health outcomes among a cohort of community dwelling older men: an observational study.

Aim: To determine the prevalence of potentially suboptimal medication use and association with adverse outcomes.

Methods: A prospective, observational cohort study of 4260 community-dwelling older men from Perth, Western Australia (mean age of 77 ± 3.6 years) was conducted.

Temporal profiling of orexin receptor-arrestin-ubiquitin complexes reveals differences between receptor subtypes.

Orexin G protein-coupled receptors (OxRs) and their cognate agonists have been implicated in a number of disorders since their recent discovery, ranging from narcolepsy to formation of addictive behavior. Bioluminescence resonance energy transfer assays of agonist-occupied OxRs provided evidence for a strong dose-dependent interaction with both trafficking proteins β-arrestin 1 and 2 that required unusually high agonist concentrations compared with inositol phosphate signaling. This appears to be reflected in functional differences in potency with respect to orexin A (OxA) and OxR2-dependent ERK1/2 phosphorylation after 90 min compared with 2 min, potentially consistent with β-arrestin-mediated versus G protein-mediated signaling, respectively.

A comparison of major trauma patients transported to trauma centres vs. non-trauma centres in metropolitan Perth.

Introduction: Some major trauma patients in metropolitan Perth (area 5000 km(2)) are initially transported to a secondary hospital (non-trauma centre), rather than directly to a tertiary hospital (trauma centre). They are subsequently transferred to a tertiary hospital. We compared outcomes from these different systems of care.

Traditional risk factors for incident cardiovascular events have limited importance in later life compared with the health in men study cardiovascular risk score.

Background And Purpose: This study aimed to determine, among older men, the risk and independent significant baseline prognostic factors for first-ever stroke and MI.

Methods: We performed a prospective cohort study of 4382 community-dwelling older men (mean age, 75.4±4.

Using time-resolved fluorescence to measure serum venom-specific IgE and IgG.

We adapted DELFIA™ (dissociation-enhanced lanthanide fluoroimmunoassay), a time resolved fluorescence method, to quantitate whole venom specific and allergenic peptide-specific IgE (sIgE), sIgG(1) and sIgG(4) in serum from people clinically allergic to Australian native ant venoms, of which the predominant cause of allergy is jack jumper ant venom (JJAV). Intra-assay CV was 6.3% and inter-assay CV was 13.

Mouse models of dominant ACTA1 disease recapitulate human disease and provide insight into therapies.

Mutations in the skeletal muscle α-actin gene (ACTA1) cause a range of pathologically defined congenital myopathies. Most patients have dominant mutations and experience severe skeletal muscle weakness, dying within one year of birth. To determine mutant ACTA1 pathobiology, transgenic mice expressing ACTA1(D286G) were created.

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study.

Context: Hypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events.

Objective: To determine whether testosterone and its associated hormones, sex hormone-binding globulin (SHBG) and LH, predict IHD events in older men.

Tests for genetic interactions in type 1 diabetes: linkage and stratification analyses of 4,422 affected sib-pairs.

Objective: Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions.