DNA tumor virus oncoproteins and retinoblastoma gene mutations share the ability to relieve the cells requirement for cyclin D1 function in G1

The retinoblastoma gene product (pRB) participates in the regulation of the cell division cycle through complex formation with numerous cellular regulatory proteins including the potentially oncogenic cyclin D1. Extending the current view of the emerging functional interplay between pRB and D-type cyclins, we now report that cyclin D1 expression is positively regulated by pRB. Cyclin D1 mRNA and protein is specifically downregulated in cells expressing SV40 large T antigen, adenovirus E1A, and papillomavirus E7/E6 oncogene products and this effect requires intact RB-binding, CR2 domain of E1A. Exceptionally low expression of cyclin D1 is also seen in genetically RB-deficient cell lines, in which ectopically expressed wild-type pRB results in specific induction of this G1 cyclin. At the functional level, antibody-mediated cyclin D1 knockout experiments demonstrate that the cyclin D1 protein, normally required for G1 progression, is dispensable for passage through the cell cycle in cell lines whose pRB is inactivated through complex formation with T antigen, E1A, or E7 oncoproteins as well as in cells which have suffered loss-of-function mutations of the RB gene. The requirement for cyclin D1 function is not regained upon experimental elevation of cyclin D1 expression in cells with mutant RB, while reintroduction of wild-type RB into RB-deficient cells leads to restoration of the cyclin D1 checkpoint. These results strongly suggest that pRB serves as a major target of cyclin D1 whose cell cycle regulatory function becomes dispensable in cells lacking functional RB. Based on available data including this study, we propose a model for an autoregulatory feedback loop mechanism that regulates both the expression of the cyclin D1 gene and the activity of pRB, thereby contributing to a G1 phase checkpoint control in cycling mammalian cells

Topical Issues for Particle Acceleration Mechanisms in Astrophysical Shocks

Particle acceleration at plasma shocks appears to be ubiquitous in the universe, spanning systems in the heliosphere, supernova remnants, and relativistic jets in distant active galaxies and gamma-ray bursts. This review addresses some of the key issues for shock acceleration theory that require resolution in order to propel our understanding of particle energization in astrophysical environments. These include magnetic field amplification in shock ramps, the non-linear hydrodynamic interplay between thermal ions and their extremely energetic counterparts possessing ultrarelativistic energies, and the ability to inject and accelerate electrons in both non-relativistic and relativistic shocks. Recent observational developments that impact these issues are summarized. While these topics are currently being probed by astrophysicists using numerical simulations, they are also ripe for investigation in laboratory experiments, which potentially can provide valuable insights into the physics of cosmic shocks.Comment: 13 pages, no figures. Invited review, accepted for publication in Astrophysics and Space Science, as part of the HEDLA 2006 conference proceeding

Towards laboratory produced relativistic electron-positron pair plasmas

We review recent experimental results on the path to producing electron-positron pair plasmas using lasers. Relativistic pair-plasmas and jets are believed to exist in many astrophysical objects and are often invoked to explain energetic phenomena related to Gamma Ray Bursts and Black Holes. On earth, positrons from radioactive isotopes or accelerators are used extensively at low energies (sub-MeV) in areas related to surface science positron emission tomography and basic antimatter science. Experimental platforms capable of producing the high-temperature pair-plasma and high-flux jets required to simulate astrophysical positron conditions have so far been absent. In the past few years, we performed extensive experiments generating positrons with intense lasers where we found that relativistic electron and positron jets are produced by irradiating a solid gold target with an intense picosecond laser pulse. The positron temperatures in directions parallel and transverse to the beam both exceeded 0.5 MeV, and the density of electrons and positrons in these jets are of order 1016 cm-3 and 1013 cm-3, respectively. With the increasing performance of high-energy ultra-short laser pulses, we expect that a high-density, up to 1018 cm-3, relativistic pair-plasma is achievable, a novel regime of laboratory-produced hot dense matter. © 2011 Elsevier B.V