High-resolution genome-wide allelotype analysis identifies loss of chromosome 14q as a recurrent genetic alteration in astrocytic tumours

Diffusely infiltrative astrocytic tumours are the most common neoplasms in the human brain. To localise putative tumour suppressor loci that are involved in low-grade astrocytomas, we performed high-resolution genome-wide allelotype analysis on 17 fibrillary astrocytomas. Non-random allelic losses were identified on chromosomal arms 10p (29%), 10q (29%), 14q (35%), 17p (53%), and 19q (29%), with their respective common regions of deletions delineated at 10p14-15.1, 10q25.1-qter, 14q212.2-qer, 17p11.2-pter and 19q12-13.4. These results suggest that alterations of these chromosomal regions play important roles in the development of astrocytoma. We also allelotyped 21 de novo glioblastoma multiforme with an aim to unveil genetic changes that are common to both types of astrocytic tumours. Non-random allelic losses were identified on 9p (67%), 10p (62%), 10q (76%), 13q (60%), 14q (50%), and 17p (65%). Allelic losses of 10p, 10q, 14q and 17p were common genetic alterations detectable in both fibrillary astrocytomas and glioblastoma multiforme. In addition, two common regions of deletions on chromosome 14 were mapped to 14q22.3-32.1 and 14q32.1-qter, suggesting the presence of two putative tumour suppressor genes. In conclusion, our comprehensive allelotype analysis has unveiled several critical tumour suppressor loci that are involved in the development of fibrillary astrocytomas and glioblastoma multiforme. Although these two types of brain tumours are believed to evolve from different genetic pathways, they do share some common genetic changes. Our results indicate that deletions of chromosome 14q is a recurrent genetic event in the development of astrocytoma and highlight the subchromosomal regions on this chromosome that are likely to contain putative tumour suppressor genes involved in the oncogenesis of astrocytic tumours

Evaluating Cloud Computing in the Proposed NASA DESDynI Ground Data System

The proposed NASA Deformation, Ecosystem Structure and Dynamics of Ice (DESDynI) mission would be a first-of-breed endeavor that would fundamentally change the paradigm by which Earth Science data systems at NASA are built. DESDynI is evaluating a distributed architecture where expert science nodes around the country all engage in some form of mission processing and data archiving. This is compared to the traditional NASA Earth Science missions where the science processing is typically centralized. What's more, DESDynI is poised to profoundly increase the amount of data collection and processing well into the 5 terabyte/day and tens of thousands of job range, both of which comprise a tremendous challenge to DESDynI's proposed distributed data system architecture. In this paper, we report on a set of architectural trade studies and benchmarks meant to inform the DESDynI mission and the broader community of the impacts of these unprecedented requirements. In particular, we evaluate the benefits of cloud computing and its integration with our existing NASA ground data system software called Apache Object Oriented Data Technology (OODT). The preliminary conclusions of our study suggest that the use of the cloud and OODT together synergistically form an effective, efficient and extensible combination that could meet the challenges of NASA science missions requiring DESDynI-like data collection and processing volumes at reduced costs

Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes

Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the surrounding normal cells, involving filamin, drives the Warburg-effect-like metabolic alteration. Moreover, using a cell-competition mouse model, we demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12-transformed cells from intestinal epithelia. These data indicate that non-cell-autonomous metabolic modulation is a crucial regulator for cell competition, shedding light on the unexplored events at the initial stage of carcinogenesis