MSH2-deficient prostate tumours have a distinct immune response and clinical outcome compared to MSH2-deficient colorectal or endometrial cancer.

Background: Recent publications have shown patients with defects in the DNA mismatch repair (MMR) pathway driven by either MSH2 or MSH6 loss experience a significant increase in the incidence of prostate cancer. Moreover, this increased incidence of prostate cancer is accompanied by rapid disease progression and poor clinical outcomes.

Methods And Results: We show that androgen-receptor activation, a key driver of prostate carcinogenesis, can disrupt the MSH2 gene in prostate cancer.

Preparation of fluorescent in situ hybridisation probes without the need for optimisation of fragmentation.

DNA-fluorescence in situ hybridisation (DNA-FISH) allows visualisation of chromosome organisation and rearrangement. FISH probes are pools of short fluorescently labelled DNA fragments that are often produced from template plasmids that contain large genomic inserts. For effective sample penetration and target hybridisation it is critical that probe fragments are between 200 and 500bp.

Periprostatic fat tissue transcriptome reveals a signature diagnostic for high-risk prostate cancer.

Evidence suggests that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. In this study, we investigated the adipose transcriptional profiles of low- and high-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue from patients categorised as having prostate cancer with either a low or high risk of progression based on tumour characteristics at prostatectomy and profiled by RNA sequencing.

Molecular Pathways: Targeting DNA Repair Pathway Defects Enriched in Metastasis.

The maintenance of a pristine genome, free from errors, is necessary to prevent cellular transformation and degeneration. When errors in DNA are detected, DNA damage repair (DDR) genes and their regulators are activated to effect repair. When these DDR pathways are themselves mutated or aberrantly downregulated, cancer and neurodegenerative disorders can ensue.

Reliability of indicators of sheep welfare assessed by a group observation method.

Assessments of animal-based outcomes form the core of routine veterinary clinical examinations and are being increasingly used as indicators of animal welfare. A method of group observation that did not require gathering and handling of individual sheep, was used to assess eight animal-based indicators of sheep welfare: demeanour, skin irritation, wool loss, excessive panting, coughing, lameness, and cleanliness of the ventral abdominal and 'breech' (perineum/gluteal/caudal hindlimb) areas. The inter-observer reliability of two or three observers who independently assessed these indicators was tested on 2406 adult sheep and growing lambs across 36 farms and the intra-observer reliability of an experienced, veterinary assessor--the 'test standard observer'--was assessed on 88 adult sheep during four on-farm assessments.

The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9].

Despite 12 yr since the discovery of SRY, little is known at the molecular level about how SRY and the SRY-related protein, SOX9 [SRY-related high-mobility group (HMG) box 9], initiate the program of gene expression required to commit the bipotential embryonic gonad to develop into a testis rather than an ovary. Analysis of SRY and SOX9 clinical mutant proteins and XX mice transgenic for testis-determining genes have provided some insight into their normal functions. SRY and SOX9 contain an HMG domain, a DNA-binding motif.

Sex with two SOX on: SRY and SOX9 in testis development.

Although gonads are not required for development or survival, defects in gonadal development undoubtedly have a profound influence on affected individuals. Recent complementary studies in the fields of cytology, biochemistry and molecular genetics have revealed that normal gonad development involves an exquisitely regulated network of gene expression and protein-protein interactions. The initial event of gonadogenesis, in both males and females, involves the formation of a bipotential primordium.