University of Virginia

About: University of Virginia is a education organization based out in Charlottesville, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 52543 authors who have published 113268 publications receiving 5220506 citations. The organization is also known as: U of V & UVa.

Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex

Abstract: Mammalian Dock180 and ELMO proteins, and their homologues in Caenorhabditis elegans and Drosophila melanogaster, function as critical upstream regulators of Rac during development and cell migration. The mechanism by which Dock180 or ELMO mediates Rac activation is not understood. Here, we identify a domain within Dock180 (denoted Docker) that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro. The Docker domain is conserved among known Dock180 family members in metazoans and in a yeast protein. In cells, binding of Dock180 to Rac alone is insufficient for GTP loading, and a Dock180 ELMO1 interaction is required. We can also detect a trimeric ELMO1 Dock180 Rac1 complex and ELMO augments the interaction between Dock180 and Rac. We propose that the Dock180 ELMO complex functions as an unconventional two-part exchange factor for Rac.

microRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes

Abstract: MicroRNA-34a (miR-34a) is a transcriptional target of p53 that is down-regulated in some cancer cell lines. We studied the expression, targets, and functional effects of miR-34a in brain tumor cells and human gliomas. Transfection of miR-34a down-regulated c-Met in human glioma and medulloblastoma cells and Notch-1, Notch-2, and CDK6 protein expressions in glioma cells. miR-34a expression inhibited c-Met reporter activities in glioma and medulloblastoma cells and Notch-1 and Notch-2 3'-untranslated region reporter activities in glioma cells and stem cells. Analysis of human specimens showed that miR-34a expression is down-regulated in glioblastoma tissues as compared with normal brain and in mutant p53 gliomas as compared with wild-type p53 gliomas. miR-34a levels in human gliomas inversely correlated to c-Met levels measured in the same tumors. Transient transfection of miR-34a into glioma and medulloblastoma cell lines strongly inhibited cell proliferation, cell cycle progression, cell survival, and cell invasion, but transfection of miR-34a into human astrocytes did not affect cell survival and cell cycle status. Forced expression of c-Met or Notch-1/Notch-2 transcripts lacking the 3'-untranslated region sequences partially reversed the effects of miR-34a on cell cycle arrest and cell death in glioma cells and stem cells, respectively. Also, transient expression of miR-34a in glioblastoma cells strongly inhibited in vivo glioma xenograft growth. Together, these findings represent the first comprehensive analysis of the role of miR-34a in gliomas. They show that miR-34a suppresses brain tumor growth by targeting c-Met and Notch. The results also suggest that miR-34a could serve as a potential therapeutic agent for brain tumors.

Monolithic germanium/silicon avalanche photodiodes with 340 GHz gain-bandwidth product

Abstract: Significant progress has been made recently in demonstrating that silicon photonics is a promising technology for low-cost optical detectors, modulators and light sources1,2,3,4,5,6,7,8,9,10,11,12. It has often been assumed, however, that their performance is inferior to InP-based devices. Although this is true in most cases, one of the exceptions is the area of avalanche photodetectors, where silicon's material properties allow for high gain with less excess noise than InP-based avalanche photodetectors and a theoretical sensitivity improvement of 3 dB or more. Here, we report a monolithically grown germanium/silicon avalanche photodetector with a gain–bandwidth product of 340 GHz, a keff of 0.09 and a sensitivity of −28 dB m at 10 Gb s−1. This is the highest reported gain–bandwidth product for any avalanche photodetector operating at 1,300 nm and a sensitivity that is equivalent to mature, commercially available III–V compound avalanche photodetectors. This work paves the way for the future development of low-cost, CMOS-based germanium/silicon avalanche photodetectors operating at data rates of 40 Gb s−1 or higher. A monolithically grown Ge/Si avalanche photodetectors (APD) with a gain–bandwidth product of 340 GHz, the highest value for any APDs operating at 1,300 nm, and a sensitivity equivalent to commercially available III-V compound APDs is reported. The excellent performance paves the way to achieving low-cost, CMOS-based, Ge/Si APDs operating at data rates of 40 Gb s−1 or higher, where the performance of III-V APDs is severely limited.