Origins and impact of extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.

MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution.

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue.

Increased flushing frequency of a model plumbing system initially promoted the formation of viable but non culturable cells but ultimately reduced the concentration of culturable and total DNA.

is the causative agent of Legionnaires' disease, and its prevalence in potable water is a significant public health issue. Water stagnation within buildings increases the risk of However, there are limited studies investigating how stagnation arising through intermittent usage affects proliferation and the studies that are available do not consider viable but non culturable (VBNC) . This study used a model plumbing system to examine how intermittent water stagnation affects both VBNC and culturable .

Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer.

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering and to predict their metabolic wiring.

Genetic landscape of interval and screen detected breast cancer.

Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project.

Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing the most detailed somatic mutational landscape to date. We identify new driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for drug repurposing.

The composition of planktonic prokaryotic communities in a hospital building water system depends on both incoming water and flow dynamics.

In recent years, the frequency of nosocomial infections has increased. Hospital water systems support the growth of microbes, especially opportunistic premise plumbing pathogens. In this study, planktonic prokaryotic communities present in water samples taken from hospital showers and hand basins, collected over three different sampling phases, were characterized by 16S rRNA gene amplicon sequencing.

Stagnation arising through intermittent usage is associated with increased viable but non culturable and amoeba hosts in a hospital water system.

Hospital water systems are a significant source of , resulting in the potentially fatal Legionnaires' disease. One of the biggest challenges for management within these systems is that under unfavorable conditions transforms itself into a viable but non culturable (VBNC) state that cannot be detected using the standard methods. This study used a novel method (flow cytometry-cell sorting and qPCR [VFC+qPCR] assay) concurrently with the standard detection methods to examine the effect of temporary water stagnation, on spp.

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome.

Detection and quantification of viable but non-culturable from water samples using flow cytometry-cell sorting and quantitative PCR.

is a waterborne pathogen and, as the causative agent of Legionnaires' disease, a significant public health concern. Exposure to environmental stresses, and disinfection treatments, promotes the formation of resistant and potentially infectious viable but non-culturable (VBNC) . The management of engineered water systems to prevent Legionnaires' disease is hindered by the presence of VBNC that cannot be detected using the standard culture (ISO11731:2017-05) and quantitative polymerase reaction (ISO/TS12869:2019) methods.

Molecular screening and characterization of Legionella pneumophila associated free-living amoebae in domestic and hospital water systems.

Free-living amoebae are ubiquitous in the environment and cause both opportunistic and non-opportunistic infections in humans. Some genera of amoebae are natural reservoirs of opportunistic plumbing pathogens, such as Legionella pneumophila. In this study, the presence of free-living amoebae and Legionella was investigated in 140 water and biofilm samples collected from Australian domestic (n = 68) and hospital water systems (n = 72).

PrEP awareness and protective barrier negotiation among transgender people attracted to men in Aotearoa New Zealand.

Introduction: Internationally, trans women are disproportionately impacted by HIV, encounter specific barriers navigating safer sex and face inequities accessing HIV prevention, including pre-exposure prophylaxis (PrEP). Aotearoa/New Zealand (hereafter Aotearoa) was one of the first countries internationally to publicly fund PrEP in 2018, including for trans people. However, few data exist on PrEP awareness or sexual negotiation among trans populations to guide implementation.

Using DNA sequencing data to quantify T cell fraction and therapy response.

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations.

A rare case of intramuscular angioma involving the medial rectus muscle.

Benign benign vascular tumors (e.g., hemangiomas) and malformations are commonly encountered lesions in all ages of life, especially in infancy and childhood.

Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response.

Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as mitochondrial retrograde response (MRR) and is induced by mitochondrial dysfunction. MRR results in the nuclear stabilization of prosurvival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).

The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism.

IκB kinase ε (IKKε) is a key molecule at the crossroads of inflammation and cancer. Known to regulate cytokine secretion via NFκB and IRF3, the kinase is also a breast cancer oncogene, overexpressed in a variety of tumours. However, to what extent IKKε remodels cellular metabolism is currently unknown.

and Protozoan Hosts: Implications for the Control of Hospital and Potable Water Systems.

is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires' disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This review collates the literature describing interactions between and protozoan hosts in hospital and municipal potable water distribution systems.

Public Health Risks Associated with Heavy Metal and Microbial Contamination of Drinking Water in Australia.

Recently in Australia concerns have been raised regarding the contamination of municipal drinking water supplies with lead. This is of particular concern to children due to the impact of lead exposure on cognitive development and as such these findings have received much media attention. The response from legislators has been swift, and The Victorian School Building Authority has announced that all new schools and school upgrade works will only use lead-free tapware and piping systems.

Real-Time Continuous Surveillance of Temperature and Flow Events Presents a Novel Monitoring Approach for Hospital and Healthcare Water Distribution Systems.

Within hospitals and healthcare facilities opportunistic premise plumbing pathogens (OPPPs) are a major and preventable cause of healthcare-acquired infections. This study presents a novel approach for monitoring building water quality using real-time surveillance of parameters measured at thermostatic mixing valves (TMVs) across a hospital water distribution system. Temperature was measured continuously in real-time at the outlet of 220 TMVs located across a hospital over a three-year period and analysis of this temperature data was used to identify flow events.

Factors Influencing Contamination of Domestic Household Showers.

Legionnaires' disease is a potentially fatal pneumonia like infection caused by inhalation or aspiration of water particles contaminated with pathogenic spp. Household showers have been identified as a potential source of sporadic, community-acquired Legionnaires' disease. This study used qPCR to enumerate spp.

Biclustering Analysis of Co-regulation Patterns in Nuclear-Encoded Mitochondrial Genes and Metabolic Pathways.

Transcription of a large set of nuclear-encoded genes underlies biogenesis of mitochondria, regulated by a complex network of transcription factors and co-regulators. A remarkable heterogeneity can be detected in the expression of these genes in different cell types and tissues, and the recent availability of large gene expression compendiums allows the quantification of specific mitochondrial biogenesis patterns. We have developed a method to effectively perform this task.