Combining Experimental Evolution and Genomics to Understand How Seed Beetles Adapt to a Marginal Host Plant.

Genes that affect adaptive traits have been identified, but our knowledge of the genetic basis of adaptation in a more general sense (across multiple traits) remains limited. We combined population-genomic analyses of evolve-and-resequence experiments, genome-wide association mapping of performance traits, and analyses of gene expression to fill this knowledge gap and shed light on the genomics of adaptation to a marginal host (lentil) by the seed beetle . Using population-genomic approaches, we detected modest parallelism in allele frequency change across replicate lines during adaptation to lentil.

Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes.

The aPKC [atypical PKC (protein kinase C)] isoforms ι and ζ play crucial roles in the formation and maintenance of cell polarity and represent attractive anti-oncogenic drug targets in Ras-dependent tumours. To date, few isoform-specific chemical biology tools are available to inhibit aPKC catalytic activity. In the present paper, we describe the identification and functional characterization of potent and selective thieno[2,3-d]pyrimidine-based chemical inhibitors of aPKCs.

Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers.

To identify epigenetic-based biomarkers for diagnosis of ovarian cancer we performed MeDIP-Chip in A2780 and CaOV3 ovarian cancer cell lines. Validation by Sequenom massARRAY methylation analysis confirmed a panel of six gene promoters (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD & SGNE1) where hypermethylation discriminated 27 serous ovarian cancer clinical samples versus 12 normal ovarian surface epithelial cells (OSE) (ROC of 0.98).

Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer.

Objective: Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer.

Methods: The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR.

Children's exposure to metals: a community-initiated study.

In 2007, it was shown that the shipping of lead (Pb) through Esperance Port in Western Australia resulted in contamination and increased Pb concentrations in children. A clean-up strategy was implemented; however, little attention was given to other metals. In consultation with the community, a cross-sectional exposure study was designed.

Assessing urinary levoglucosan and methoxyphenols as biomarkers for use in woodsmoke exposure studies.

A major contributor to particle concentrations in urban airsheds is domestic woodsmoke and smoke arising from wildfires or management burns. Particle concentrations in urban airsheds have been associated with a wide range of health effects. There has been little research into the contribution of biomass burning to studies of human health due to the complexity of attributing effects in the presence of multiple sources of pollutants and the variability in the nature and conditions of biomass burning.

DNA methylation changes in ovarian cancer: implications for early diagnosis, prognosis and treatment.

Objective: To review epigenetic changes identified in ovarian cancer, focusing on their potential as clinical markers for detection, monitoring of disease progression and as markers of therapeutic response.

Methods: A comprehensive review of English language scientific literature on the topics of methylation and ovarian cancer was conducted.

Results: Genome-wide demethylation of normally methylated and silenced chromosomal regions, and hypermethylation and silencing of genes including tumor suppressors are common features of cancer cells.

Acid sulphate soil disturbance and metals in groundwater: implications for human exposure through home grown produce.

A significant emerging environmental problem is the disturbance and oxidation of soils with high levels of iron sulphide minerals resulting in acidification and causing the mobilization of metals into groundwater. This process is occurring in many parts of the world. In Western Australia, impacted groundwater is extracted by residents for domestic use.

Involvement of both intrinsic and extrinsic pathways in IFN-gamma-induced apoptosis that are enhanced with cisplatin.

IFN-gamma has direct anti-proliferative effects on ovarian cancer cell lines and tumour cells isolated from ovarian cancer ascites. The aim of this study was to further elucidate the mechanisms involved. An IFN-gamma-mediated cell cycle blockade was detectable in synchronised cell populations.

IFN-gamma induces apoptosis in ovarian cancer cells in vivo and in vitro.

Purpose: The purpose of this study was to compare in vitro and in vivo responses of primary human tumor cells to IFN-gamma.

Experimental Design: IFN-gamma may have therapeutic activity in patients with ovarian cancer. We showed previously that this cytokine had direct antiproliferative activity against human ovarian cancer cell lines and xenografts in nude mice.