Brain tumor related-epilepsy

Introduction Gliomas are commonly associated with the development of epilepsy; in some cases the two conditions share common pathogenic mechanisms and may influence each other. Brain tumor related-epilepsy (BTRE) complicates the clinical management of gliomas and can substantially affect daily life. State of the art The incidence of seizures is high in patients with slow growing tumors located in the frontotemporal regions. However, recent studies suggest that epileptogenesis may be more associated with tumor molecular genetic markers than tumor grade or location. Although the exact mechanism of epileptogenesis in glioma is incompletely understood, glutamate-induced excitotoxicity and disruption of intracellular communication have garnered the most attention. Clinical management Management of BTRE requires a multidisciplinary approach involving the use of antiepileptic drugs (AEDs), surgery aided by electrocorticography, and adjuvant chemoradiation. Future directions Insight into the mechanisms of glioma growth and epileptogenesis is essential to identify new treatment targets and to develop effective treatment for both conditions. Selecting AEDs tailored to act against known tumor molecular markers involved in the epileptogenesis could enhance treatment value and help inform individualized medicine in BRTE

Analysis of the repair of topoisomerase II DNA damage

A large number of anti-cancer chemotherapeutics target DNA topoisomerases. Etoposide is a specific topoisomerase II poison which causes reversible double strand DNA breaks. The focus of this project is to analyze the repair of DNA damage induced by etoposide.. Double strand DNA break repair is mediated by through either non-homologous end joining (NHEJ) or homologous recombination. NHEJ repairs through direct ligation of a double stranded break while homologous recombination utilizes a homologous template to recover the wild type sequence. A reporter cassette, RYDR-GFP, has been stably integrated into HeLa cells. This reporter contains an ultra-high affinity topoisomerase II cleavage site (RY) placed in the middle of a mutant GFP sequence. Flanking this sequence is a corresponding stretch of wild type GFP that is used as template to repair the break and restore gene function yielding GFP positive cells. Titrations with etoposide have shown that a logarithmic increase in drug concentration yields a corresponding increase in repair through homologous recombination (HR). This result demonstrates that topoisomerase II mediated damage is efficiently repaired by the process of HR. To examine NHEJ repair, a doxycycline inducible, stably integrated NHEJ HeLa cell reporter cassette was also evaluated. The data indicates that repair of topoisomerase II mediated DNA damage occurs more efficiently through the HR pathway. Collectively, the data suggests that tumor cells proficient in HR repair may effectively elude treatment by topoisomerase II targeting drugs

Pre-Hawking Radiation from a Collapsing Shell

We investigate the effect of induced massive radiation given off during the time of collapse of a massive spherically symmetric domain wall in the context of the functional Schr\"odinger formalism. Here we find that the introduction of mass suppresses the occupation number in the infrared regime of the induced radiation during the collapse. The suppression factor is found to be given by $e^{-\beta m}$, which is in agreement with the expected Planckian distribution of induced radiation. Thus a massive collapsing domain wall will radiate mostly (if not exclusively) massless scalar fields, making it difficult for the domain wall to shed any global quantum numbers and evaporate before the horizon is formed.Comment: 10 pages, 3 figures. We updated the acknowledgments as well as added a statement clarifying that we are following the methods first laid out in Phys. Rev. D 76, 024005 (2007

Non-equilibrium phase transitions in biomolecular signal transduction

We study a mechanism for reliable switching in biomolecular signal-transduction cascades. Steady bistable states are created by system-size cooperative effects in populations of proteins, in spite of the fact that the phosphorylation-state transitions of any molecule, by means of which the switch is implemented, are highly stochastic. The emergence of switching is a nonequilibrium phase transition in an energetically driven, dissipative system described by a master equation. We use operator and functional integral methods from reaction-diffusion theory to solve for the phase structure, noise spectrum, and escape trajectories and first-passage times of a class of minimal models of switches, showing how all critical properties for switch behavior can be computed within a unified framework

Observation of Single Transits in Supercooled Monatomic Liquids

A transit is the motion of a system from one many-particle potential energy valley to another. We report the observation of transits in molecular dynamics (MD) calculations of supercooled liquid argon and sodium. Each transit is a correlated simultaneous shift in the equilibrium positions of a small local group of particles, as revealed in the fluctuating graphs of the particle coordinates versus time. This is the first reported direct observation of transit motion in a monatomic liquid in thermal equilibrium. We found transits involving 2 to 11 particles, having mean shift in equilibrium position on the order of 0.4 R_1 in argon and 0.25 R_1 in sodium, where R_1 is the nearest neighbor distance. The time it takes for a transit to occur is approximately one mean vibrational period, confirming that transits are fast.Comment: 19 pages, 8 figure

Noninvasive Imaging beyond the Diffraction Limit of 3D Dynamics in Thickly Fluorescent Specimens

SummaryOptical imaging of the dynamics of living specimens involves tradeoffs between spatial resolution, temporal resolution, and phototoxicity, made more difficult in three dimensions. Here, however, we report that rapid three-dimensional (3D) dynamics can be studied beyond the diffraction limit in thick or densely fluorescent living specimens over many time points by combining ultrathin planar illumination produced by scanned Bessel beams with super-resolution structured illumination microscopy. We demonstrate in vivo karyotyping of chromosomes during mitosis and identify different dynamics for the actin cytoskeleton at the dorsal and ventral surfaces of fibroblasts. Compared to spinning disk confocal microscopy, we demonstrate substantially reduced photodamage when imaging rapid morphological changes in D. discoideum cells, as well as improved contrast and resolution at depth within developing C. elegans embryos. Bessel beam structured plane illumination thus promises new insights into complex biological phenomena that require 4D subcellular spatiotemporal detail in either a single or multicellular context

Detection of vorticity in Bose-Einstein condensed gases by matter-wave interference

A phase-slip in the fringes of an interference pattern is an unmistakable characteristic of vorticity. We show dramatic two-dimensional simulations of interference between expanding condensate clouds with and without vorticity. In this way, vortices may be detected even when the core itself cannot be resolved.Comment: 3 pages, RevTeX, plus 6 PostScript figure

Characterisation of microRNA expression in post-natal mouse mammary gland development.

BACKGROUND: The differential expression pattern of microRNAs (miRNAs) during mammary gland development might provide insights into their role in regulating the homeostasis of the mammary epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development.We measured the expression of 318 individual murine miRNAs by bead-based flow-cytometric profiling of whole mouse mammary glands throughout a 16-point developmental time course, including juvenile, puberty, mature virgin, gestation, lactation, and involution stages. In parallel whole-genome mRNA expression data were obtained. RESULTS: One third (n = 102) of all murine miRNAs analysed were detected during mammary gland development. MicroRNAs were represented in seven temporally co-expressed clusters, which were enriched for both miRNAs belonging to the same family and breast cancer-associated miRNAs. Global miRNA and mRNA expression was significantly reduced during lactation and the early stages of involution after weaning. For most detected miRNA families we did not observe systematic changes in the expression of predicted targets. For miRNA families whose targets did show changes, we observed inverse patterns of miRNA and target expression. The data sets are made publicly available and the combined expression profiles represent an important community resource for mammary gland biology research. CONCLUSION: MicroRNAs were expressed in likely co-regulated clusters during mammary gland development. Breast cancer-associated miRNAs were significantly enriched in these clusters. The mechanism and functional consequences of this miRNA co-regulation provide new avenues for research into mammary gland biology and generate candidates for functional validation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Alternative Fourier Expansions for Inverse Square Law Forces

Few-body problems involving Coulomb or gravitational interactions between pairs of particles, whether in classical or quantum physics, are generally handled through a standard multipole expansion of the two-body potentials. We discuss an alternative based on a compact, cylindrical Green's function expansion that should have wide applicability throughout physics. Two-electron "direct" and "exchange" integrals in many-electron quantum systems are evaluated to illustrate the procedure which is more compact than the standard one using Wigner coefficients and Slater integrals.Comment: 10 pages, latex/Revtex4, 1 figure

Essential and recurrent roles for hairpin RNAs in silencing \u3ci\u3ede novo sex\u3c/i\u3e chromosome conflict in \u3ci\u3eDrosophila simulans\u3c/i\u3e

Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. Here, we present data from the fruitfly Drosophila simulans that address these questions. We show that a family of de novo, protamine- derived X-linked selfish genes (the Dox gene family) is silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. We show the Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, we provide the first experimental evidence Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis