Mitochondrial ribosomal proteins in metastasis and their potential use as prognostic and therapeutic targets.

The mitochondrion is an essential cell organelle known as the powerhouse of the cell. Mitochondrial ribosomal proteins (MRPs) are nuclear encoded, synthesised in the cytoplasm but perform their main functions in the mitochondria, which includes translation, transcription, cell death and maintenance. However, MRPs have also been implicated in cancer, particularly advanced disease and metastasis across a broad range of cancer types, where they play a central role in cell survival and progression.

WNT5A is a putative epi-driver of prostate cancer metastasis to the bone.

Background: Current diagnostic tools are unable to distinguish low-grade indolent prostate cancer (PrCa) from that with a propensity to become metastatic and/or lethal. Recent evidence suggests that reprogramming of the transcriptome may drive the metastatic phenotype, and that this reprogramming is controlled, at least in part, by epigenetic changes to the DNA of cancer cells, including methylation. These changes, referred to as 'epigenetic drivers,' have previously been associated with cancer cell survival.

Germline Sequencing of DNA Damage Repair Genes in Two Hereditary Prostate Cancer Cohorts Reveals New Disease Risk-Associated Gene Variants.

Rare, inherited variants in DNA damage repair (DDR) genes have a recognised role in prostate cancer (PrCa) susceptibility. In addition, these genes are therapeutically targetable. While rare variants are informing clinical management in other common cancers, defining the rare disease-associated variants in PrCa has been challenging.

RUNX1 regulates promoter activity in the absence of cognate DNA binding motifs.

Runt-related transcription factor 1 (RUNX1) plays an important role in normal haematopoietic cell development and function, and its function is frequently disrupted in leukaemia. RUNX1 is widely recognised as a sequence-specific DNA binding factor that recognises the motif 5'-TG(T/C)GGT-3' in promoter and enhancer regions of its target genes. Moreover, RUNX1 fusion proteins, such as RUNX1-ETO formed by the t(8;21) translocation, retain the ability to recognise and bind to this sequence to elicit atypical gene regulatory effects on bona fide RUNX1 targets.

Decrypting seasonal patterns of key pollen taxa in cool temperate Australia: A multi-barcode metabarcoding analysis.

Pollen allergies pose a considerable global public health concern. Allergy risk can vary significantly within plant families, yet some key pollen allergens can only be identified to family level by current optical methods. Pollen information with greater taxonomic resolution is therefore required to best support allergy prevention and self-management.

Acquired copy number variation in prostate tumours: a review of common somatic copy number alterations, how they are formed and their clinical utility.

Prostate cancer is one of the most commonly diagnosed cancers in men and unfortunately, disease will progress in up to a third of patients despite primary treatment. Currently, there is a significant lack of prognostic tests that accurately predict disease course; however, the acquisition of somatic chromosomal variation in the form of DNA copy number variants may help understand disease progression. Notably, studies have found that a higher burden of somatic copy number alterations (SCNA) correlates with more aggressive disease, recurrence after surgery and metastasis.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF.

Non-coding RNA regulation of integrins and their potential as therapeutic targets in cancer.

Background: Integrins are integral to cell signalling and management of the extracellular matrix, and exquisite regulation of their expression is essential for a variety of cell signalling pathways, whilst disordered regulation is a key driver of tumour progression and metastasis. Most recently non-coding RNAs in the form of micro-RNA (miRNA) and long non-coding RNA (lncRNA) have emerged as a key mechanism by which tissue dependent gene expression is controlled. Whilst historically these molecules have been poorly understood, advances in 'omic' technologies and a greater understanding of non-coding regions of the genome have revealed that non-coding RNAs make up a large proportion of the transcriptome.

Functional genomics for curation of variants in telomere biology disorder associated genes: A systematic review.

Purpose: Patients with an underlying telomere biology disorder (TBD) have variable clinical presentations, and they can be challenging to diagnose clinically. A genomic diagnosis for patients presenting with TBD is vital for optimal treatment. Unfortunately, many variants identified during diagnostic testing are variants of uncertain significance.

Remote primary care during the COVID-19 pandemic for people experiencing homelessness: a qualitative study.

Background: The COVID-19 pandemic has caused unprecedented disruption and change to the organisation of primary care, including for people experiencing homelessness who may not have access to a phone. Little is known about whether the recent changes required to deliver services to people experiencing homelessness will help to address or compound inequality in accessing care.

Aim: To explore the experience and impact of organisational and technology changes in response to COVID-19 on access to health care for people experiencing homelessness.

Urban-rural prostate cancer disparities in a regional state of Australia.

Men living in regional and remote areas experience disparities in prostate cancer (PrCa) diagnosis, clinical characteristics and treatment modalities. We sought to determine whether such disparities exist in PrCa patients from Tasmania; a regional state of Australia with the second-highest rate of diagnosis and where over a third of residents live in outer regional and remote areas. Our study included clinicopathological data from 1526 patients enrolled in the Prostate Cancer Outcomes Registry-Tasmania.

A novel long non-coding RNA regulates the integrin, ITGA2 in breast cancer.

Purpose: ITGA2 encodes the integrin, α2 which mediates metastatic progression, and is a predictor of poor prognosis and chemoresistance in breast cancer. Decreased ITGA2 promoter methylation is implicated as a driver of increased gene expression in aggressive prostate and pancreatic tumours, however the contribution of altered methylation to ITGA2 expression changes in breast tumours has not been examined.

Methods: ITGA2 gene methylation and gene expression was examined in publicly available breast cancer datasets, and ITGA2 promoter methylation was mapped by targeted bisulphite sequencing analysis in breast tumour cell lines.

TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis.

Introduction: Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.

Exploring the experiences of changes to support access to primary health care services and the impact on the quality and safety of care for homeless people during the COVID-19 pandemic: a study protocol for a qualitative mixed methods approach.

Background: Despite high level of health care need amongst people experiencing homelessness, poor access is a major concern. This is sometimes due to organisational and bureaucratic barriers, but also because they often feel stigmatised and treated badly when they do seek health care. The COVID-19 pandemic and the required social distancing measures have caused unprecedented disruption and change for the organisation of primary care, particularly for people experiencing homelessness.

Epigenetic regulation of the ITGB4 gene in prostate cancer.

Examination of epigenetic changes at the ITGB4 gene promoter reveals altered methylation at different stages of prostate tumour progression and these changes may, in part, explain the complex patterns of gene expression of this integrin observed. Transcriptional re-programming perturbs expression of cell adhesion molecules and underpins metastatic tumour cell behaviour. Decreasing expression of the cell adhesion molecule ITGB4, which encodes the beta subunit of the integrin, alpha6 beta4 (α6β4), has been correlated with increased tumour aggressiveness and metastasis in multiple tumour types including prostate cancer.

Recurrence patterns identify aggressive form of human papillomavirus-dependent vulvar cancer.

Background: Vulvar cancer is rare and, as a result, is understudied. Treatment is predominantly surgery, irrespective of the type of vulvar cancer, and is associated with physical, emotional and sexual complications. A cluster of human papillomavirus (HPV)-dependent vulvar cancer patients was identified in Arnhem Land Northern Territory (NT), Australia, in which young Indigenous women were diagnosed at 70 times the national incidence rate.

Age estimation in a long-lived seabird (Ardenna tenuirostris) using DNA methylation-based biomarkers.

Age structure is a fundamental aspect of animal population biology. Age is strongly related to individual physiological condition, reproductive potential and mortality rate. Currently, there are no robust molecular methods for age estimation in birds.