Matrigel basement membrane matrix influences expression of microRNAs in cancer cell lines.

Matrigel is a medium rich in extracellular matrix (ECM) components used for three-dimensional cell culture and is known to alter cellular phenotypes and gene expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have roles in cancer. While miRNA profiles of numerous cell lines cultured on plastic have been reported, the influence of Matrigel-based culture on cancer cell miRNA expression is largely unknown.

Receptor-Heteromer Investigation Technology and its application using BRET.

Receptor heteromerization has the potential to alter every facet of receptor functioning, leading to new pharmacological profiles with increased signaling diversity and regulation from that of the monomeric receptor, or indeed receptor homomer. An understanding of the molecular consequences of receptor heteromerization will provide new insights into the physiology and pathology mediated by receptors, expanding the possibilities for pharmacological discovery. Particularly advantageous approaches to investigate novel heteromer pharmacology utilize cell-based assay technologies that assess ligand-dependent functional responses specific to the receptor heteromer.

Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis.

Background: Although there is convincing epidemiological evidence that physical activity is associated with a reduced risk of colon cancer, it is unclear whether physical activity is differentially associated with the risks of proximal colon and distal colon cancers. We conducted a systematic review and meta-analysis to investigate this issue.

Methods: MEDLINE and EMBASE were searched for English-language cohort and case-control studies that examined associations between physical activity and the risks of proximal colon and distal colon cancers.

Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells.

The enzyme deoxyhypusine hydroxylase (DOHH) catalyzes the activation of eukaryotic translation initiation factor (eIF5A), a protein essential for cell growth. Using bioinformatic predictions and reporter gene assays, we have identified a 182-nt element within the DOHH 3'-untranslated region (3'-UTR) that contains a number of target sites for miR-331-3p and miR-642-5p. Quantitative RT-PCR studies demonstrated overexpression of DOHH mRNA and underexpression of miR-331-3p and miR-642-5p in several prostate cancer cell lines compared with normal prostate epithelial cells.

All-cause mortality and cancer incidence among adults exposed to blue asbestos during childhood.

Background: There are few data on the long-term health outcomes of exposure to asbestos in childhood. This study investigated cancer and mortality of adults exposed to blue asbestos as children.

Methods: Data linkage to relevant health registries was used to identify cancers and mortality in a cohort of adults (n = 2,460) that had lived in an asbestos mining town during their childhood (<15 years).

Proteomic characterization of the possible molecular targets of pyrrolizidine alkaloid isoline-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are distributed in plants worldwide including medicinal herbs or teas. In the present study, we investigated the effects of isoline, which is a retronecine-type PA isolated from traditional Chinese medicinal herb Ligularia duciformis, on mouse liver proteins by using proteomic approaches. Firstly, our results showed that 110mg/kg isoline increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum, and hepatic tissue pathological observation further confirmed isoline-induced liver injury.

Validation of self-reported sleep against actigraphy.

Background: Self-report remains the most practical and cost-effective method for epidemiologic sleep studies involving large population-based samples. Several validated questionnaires have been developed to assess sleep, but these tools are lengthy to administer and may be impractical for epidemiologic studies. We examined whether a 3-item sleep questionnaire, similar to those typically used in epidemiologic studies, closely corresponded with objective measures of sleep as assessed using actigraphy monitoring.

MRPS27 is a pentatricopeptide repeat domain protein required for the translation of mitochondrially encoded proteins.

Mammalian pentatricopeptide repeat domain (PPR) proteins are involved in regulation of mitochondrial RNA metabolism and translation and are required for mitochondrial function. We investigated an uncharacterised PPR protein, the supernumerary mitochondrial ribosomal protein of the small subunit 27 (MRPS27), and show that it associates with the 12S rRNA and tRNA(Glu), however it does not affect their abundance. We found that MRPS27 is not required for mitochondrial RNA processing or the stability of the small ribosomal subunit.

Associations between testosterone levels and incident prostate, lung, and colorectal cancer. A population-based study.

Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer.

Methods: This was a population-based cohort study.

Functions of the Lyn tyrosine kinase in health and disease.

Src family kinases such as Lyn are important signaling intermediaries, relaying and modulating different inputs to regulate various outputs, such as proliferation, differentiation, apoptosis, migration and metabolism. Intriguingly, Lyn can mediate both positive and negative signaling processes within the same or different cellular contexts. This duality is exemplified by the B-cell defect in Lyn-/- mice in which Lyn is essential for negative regulation of the B-cell receptor; conversely, B-cells expressing a dominant active mutant of Lyn (Lynup/up) have elevated activities of positive regulators of the B-cell receptor due to this hyperactive kinase.

The human mitochondrial transcriptome and the RNA-binding proteins that regulate its expression.

The human mitochondrial transcriptome, although produced from a small and compact genome, has revealed surprising complexity in its composition and regulation. Wide variation between individual tRNAs, mRNAs, and rRNAs indicate the importance of post-transcriptional processing, maturation, and degradation mechanisms in the regulation of mitochondrial gene expression. RNA-binding proteins play essential roles in controlling the mitochondrial transcriptome from its synthesis to its destruction and have evolved unique features to complement the unusual features of mitochondrial RNAs.

Sense of control and wellbeing decades after exposure to blue asbestos at Wittenoom, Western Australia.

Objective: The objective of this study was to examine the impact of the knowledge of past asbestos exposure on psychosocial health.

Methods: Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966. In 2007, SF-12 and Locus of Control (LOC) questionnaires were sent to 5,101 surviving Wittenoom workers and residents.

Insights into type 1 diabetes provided by genetic analyses.

Purpose Of Review: Recent identification of over 60 loci contributing to the susceptibility of developing type 1 diabetes (T1D) provides a timely opportunity to assess what is currently known of the genetics of T1D, and what these discoveries may tell us about the disease itself.

Recent Findings: The major findings will be discussed under five main themes: T1D risk gene identification, molecular mechanisms of susceptibility, shared genetic cause with other diseases, development of novel analytical methods, and understanding disease heterogeneity.

Summary: The plethora of T1D risk genes that have been identified risk overwhelming clinicians with lists of gene names and symbols that have little bearing on management, and provide a challenge for researchers to place the genetics of T1D in a more amenable clinical context.

Predictors of sickness absence in patients with a new episode of low back pain in primary care.

This study examines predictors of sickness absence in patients presenting to a health practitioner with acute/ subacute low back pain (LBP). Aims of this study were to identify baseline-variables that detect patients with a new LBP episode at risk of sickness absence and to identify prognostic models for sickness absence at different time points after initial presentation. Prospective cohort study investigating 310 patients presenting to a health practitioner with a new episode of LBP at baseline, three-, six-, twelve-week and six-month follow-up, addressing work-related, psychological and biomedical factors.

Tumor-targeted TNFα stabilizes tumor vessels and enhances active immunotherapy.

Solid tumors are intrinsically resistant to immune rejection. Abnormal tumor vasculature can act as a barrier for immune cell migration into tumors. We tested whether targeting IFNγ and/or TNFα into pancreatic neuroendocrine tumors can alleviate immune suppression.

Under-use of migrants' employment skills linked to poorer mental health.

Objective: Since the mid-1990s Australia's immigration program has focused on encouraging skilled migration. This study investigated skill usage in three longitudinal studies of immigrants to Australia and examined if there is an association with mental health status.

Methods: Three Longitudinal Surveys of Immigrants to Australia (LSIA), with multiple data collection waves, were conducted between 1994 and 2006.

A priority list of occupational carcinogenic agents for preventative action in Australia.

Objective: To develop a list of carcinogens to guide decisions on priorities for preventive action in Australian workplaces.

Approach: The following criteria provided the assessment framework to establish a list of priority carcinogens: evidence of carcinogenicity using International Agency for Research on Cancer (IARC) criteria; use in occupational circumstances; and use in Australia industry. Literature from national and international agencies relating to carcinogens and industrial practice informed the assessment.

Genetics of neuromuscular disorders.

Neuromuscular disorders affect the peripheral nervous system and muscle. The principle effect of neuromuscular disorders is therefore on the ability to perform voluntary movements. Neuromuscular disorders cause significant incapacity, including, at the most extreme, almost complete paralysis.

Deleterious GRM1 mutations in schizophrenia.

We analysed a phenotypically well-characterised sample of 450 schziophrenia patients and 605 controls for rare non-synonymous single nucleotide polymorphisms (nsSNPs) in the GRM1 gene, their functional effects and family segregation. GRM1 encodes the metabotropic glutamate receptor 1 (mGluR1), whose documented role as a modulator of neuronal signalling and synaptic plasticity makes it a plausible schizophrenia candidate. In a recent study, this gene was shown to harbour a cluster of deleterious nsSNPs within a functionally important domain of the receptor, in patients with schizophrenia and bipolar disorder.

Prognostic occupational factors for persistent low back pain in primary care.

Purpose: To reduce the socio-economic burden of persistent low back pain (LBP), factors influencing the progression of acute/subacute LBP to the persistent state must be identified at an early stage.

Methods: Prospective inception cohort study of patients attending a health practitioner for their first episode of acute/subacute or recurrent LBP. Patients were assessed at baseline addressing occupational, psychological, biomedical and demographic/lifestyle factors and followed up over 6 months.

Integrating novel signaling pathways involved in erythropoiesis.

Many extrinsic and intrinsic factors control the development of red blood cells from committed progenitors, with the Erythropoietin-receptor (Epo-R) signaling network being the primary controlling molecular hub. Although much is understood about erythroid signaling pathways, new and intriguing factors that influence different aspects of erythroid cell development are still being uncovered. New extrinsic effectors include hypoxia and polymeric IgA1 (pIgA1), and new Epo-R signaling pathway components include Lyn/Cbp and Lyn/Liar.

The impact of early emergency department allied health intervention on admission rates in older people: a non-randomized clinical study.

Background: This study sought to determine whether early allied health intervention by a dedicated Emergency Department (ED) based team, occurring before or in parallel with medical assessment, reduces hospital admission rates amongst older patients presenting with one of ten index problems.

Methods: A prospective non-randomized trial in patients aged sixty five and over, conducted in two Australian hospital EDs. Intervention group patients, receiving early comprehensive allied health input, were compared to patients that received no allied health assessment.

Including questionnaires with the invitation package appeared to increase the response fraction among women.

Objective: The Breast Cancer Environment and Employment Study (BCEES) is a case--control study that began in 2009. The study experienced a lower than expected response fraction, a trend that appears to be occurring internationally. A 32-page questionnaire was included in the initial invitation to participate, and previous research suggests that long questionnaires decrease response fractions.

Impact of the Reelin signaling cascade (ligands-receptors-adaptor complex) on cognition in schizophrenia.

Our previous neurocognitive studies of schizophrenia outlined two clusters of affected subjects--cognitively spared (CS) and cognitive deficit (CD), the latter's characteristics pointing to developmental origins and impaired synaptic plasticity. Here we investigate the contribution of polymorphisms in major regulators of these processes to susceptibility to schizophrenia and to CD in patients. We examine variation in genes encoding proteins at the gateway of Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR, and adaptor DAB1.