Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype

Development and characterisation of a 3D multi-cellular in vitro model of normal human breast: a tool for cancer initiation studies.

Multicellular 3-dimensional (3D) in vitro models of normal human breast tissue to study cancer initiation are required. We present a model incorporating three of the major functional cell types of breast, detail the phenotype and document our breast cancer initiation studies. Myoepithelial cells and fibroblasts were isolated and immortalised from breast reduction mammoplasty samples. Tri-cultures containing non-tumorigenic luminal epithelial cells HB2, or HB2 overexpressing different HER proteins, together with myoepithelial cells and fibroblasts were established in collagen I. Phenotype was assessed morphologically and immunohistochemically and compared to normal breast tissue. When all three cell types were present, polarised epithelial structures with lumens and basement membrane production were observed, akin to normal human breast tissue. Overexpression of HER2 or HER2/3 caused a significant increase in size, while HER2 overexpression resulted in development of a DCIS-like phenotype. In summary, we have developed a 3D tri-cellular model of normal human breast, amenable to comparative analysis after genetic manipulation and with potential to dissect the mechanisms behind the early stages of breast cancer initiation

Is EC class predictable from reaction mechanism?

We thank the Scottish Universities Life Sciences Alliance (SULSA) and the Scottish Overseas Research Student Awards Scheme of the Scottish Funding Council (SFC) for financial support.Background: We investigate the relationships between the EC (Enzyme Commission) class, the associated chemical reaction, and the reaction mechanism by building predictive models using Support Vector Machine (SVM), Random Forest (RF) and k-Nearest Neighbours (kNN). We consider two ways of encoding the reaction mechanism in descriptors, and also three approaches that encode only the overall chemical reaction. Both cross-validation and also an external test set are used. Results: The three descriptor sets encoding overall chemical transformation perform better than the two descriptions of mechanism. SVM and RF models perform comparably well; kNN is less successful. Oxidoreductases and hydrolases are relatively well predicted by all types of descriptor; isomerases are well predicted by overall reaction descriptors but not by mechanistic ones. Conclusions: Our results suggest that pairs of similar enzyme reactions tend to proceed by different mechanisms. Oxidoreductases, hydrolases, and to some extent isomerases and ligases, have clear chemical signatures, making them easier to predict than transferases and lyases. We find evidence that isomerases as a class are notably mechanistically diverse and that their one shared property, of substrate and product being isomers, can arise in various unrelated ways. The performance of the different machine learning algorithms is in line with many cheminformatics applications, with SVM and RF being roughly equally effective. kNN is less successful, given the role that non-local information plays in successful classification. We note also that, despite a lack of clarity in the literature, EC number prediction is not a single problem; the challenge of predicting protein function from available sequence data is quite different from assigning an EC classification from a cheminformatics representation of a reaction.Publisher PDFPeer reviewe

Multi-static, multi-frequency scattering from zooplankton

Abstract: Inversion of multi-frequency acoustic backscattering cm be used to estkate size-abundances of zooplankton, given a valid model for backscattering for the zooplankters. me physical properties of the scatterers, density and compressibility (or compressional-wave sound speed), are usually assigned fixed values in the scattering model.~ese properties wotid be of interest if they could be mew~~in~it~, e.g.to exm~e~hange$in liPid contents over seasons. Extension of currently-favored backscattering models to multi-static configurations looks promising as a method to directly measure these relevant physical properties simultaneously with size-abundance estimation

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

BACKGROUND: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas. METHODS: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed. RESULTS: Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis. CONCLUSIONS: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR

Impact of mobile devices on clinical laboratory data

Recent advancements in mobile wireless devices (smart phones and tablets) have given these products the potential to drastically alter the practice of healthcare. The project described determined how these devices would assist in improving diagnosis, treatment, and therapeutic outcomes in the delivery of healthcare. Also, it seeks to determine if the healthcare community feels these devices will make healthcare more cost effective and affordable. To cover multiple aspects of healthcare, several groups have been targeted: clinical laboratory; emergency, dental, rehabilitation, and surgical medicine; hospital administration; diagnostic imaging technology; public health; and veterinary medicine. This presentation will focus on our current results pertaining to the clinical laboratory. A questionnaire was distributed to clinical laboratory personnel both domestic and international. Questionnaire data was analyzed. The respondents concluded the use of mobile wireless devices have and will improve the dissemination of laboratory data in the coming years. The devices will assist in direct clinical assessment of reported test results even directly to the patient. Additionally, responders noted such devices should allow greater and improved access to medical literature that is web-based such as test procedures, treatment protocols, and guidelines. Also, responders reported these devices should improve laboratory work productivity and efficiency. In the future, the project will to continue monitor the impact of mobile devices in these areas of health care in order to help define the effect of mobile wireless devices to improve future healthcare delivery and practice

Lesbian and bisexual women's experiences of sexuality-based discrimination and their appearance concerns

Lesbian and bisexual women frequently experience sexuality-based discrimination, which is often based on others' judgements about their appearance. This short article aims to explore whether there is a relationship between lesbian and bisexual women's experiences of sexuality-based discrimination and their satisfaction with the way that they look. Findings from an online survey suggest that discrimination is negatively related to appearance satisfaction for lesbian women, but not for bisexual women. It is argued that this difference exists because lesbian appearance norms are more recognisable and distinctive than bisexual women's appearance norms

Occurrence and mechanisms of formation of a dramatic thin layer of marine snow in a shallow Pacific fjord

Huge accumulations of diatom-dominated marine snow (aggregates \u3e0.5 mm in diameter) were observed in a layer approximately 50 cm thick persisting over a 24 h period in a shallow fjord in the San Juan Islands, Washington, USA. The layer was associated with the 22.4 σt density surface. A second thin layer of elevated phytoplankton concentration located at a density discontinuity 1.5 to 2 m above the marine snow layer occurred within a dense diatom bloom near the surface. At the end of the study period, isopycnals shoaled and the 2 layers merged. More than 80% of the diatom bloom consisted of Thalassiosira spp. (50 to 59%), Odontella longicruris (5 to 14%), Asterionellopsis glacialis, and Thalassionema nitzschioides. A much higher proportion of O. longicruris occurred in marine snow (about 53%) than among suspended cells suggesting that this species differentially aggregated. Most zooplankton avoided the mucus-rich aggregate layer. The layer of marine snow was formed when sinking aggregated diatoms reached neutral buoyancy at the 22.4 isopycnal, probably due to the presence of low salinity mucus resistant to salt exchange in the interstices of the aggregates. Rates of turbulent kinetic energy dissipation throughout the water column rarely exceeded 10-8 m2 s-3 and aggregates below the thin layer were largely detrital in composition indicating that small-scale shears due to turbulence did not erode the layer of marine snow. The accumulation of marine snow and phytoplankton in persistent, discrete layers at density discontinuities results in habitat partitioning of the pelagic zone, impacts the distribution and interactions of planktonic organisms as well as the intensity and location of biological processes in the water column, and helps maintain species diversity