Characterization of HSAG elements : a middle repetitive family of genetic elements which stimulate gene amplification

Members of the HSAG family of genetic elements stimulate amplification of the pSV$sb2$DHFR vector in cis, such that HSAG-pSV$sb2$DHFR transfected cell populations generate methotrexate resistant cells at a higher frequency than pSV$sb2$DHFR transfectants. Repetitive DNA sequences such as Alu elements were found in HSAG-1, HSAG-2, and HSAG-5; HSAG-1 and HSAG-2 also contain poly purine-pyrimidine tracts. Analysis of subfragments of HSAG-1, HSAG-2, and HSAG-5 demonstrated that the interaction of multiple positive-acting elements was necessary for maximum amplification stimulatory activity. Proposed positive-acting elements include Alu-like sequences, poly purine-pyrimidine tracts, A/T rich regions and potential stem-loop structures. For HSAG-1, the native configuration of these elements gives optimal activity; transcriptional activation has also been implicated. Both transcriptional activity and the aforementioned elements have been shown to promote recombination in other systems; it is therefore suggested that the HSAG elements stimulate gene amplification by increasing recombination

Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders

An investigation into CAG repeat length variation and N/C terminal interactions in the T877A mutant androgen receptor found in prostate cancer

Peer reviewed: YesNRC publication: Ye