Regulation by small RNAs via coupled degradation: mean-field and variational approaches

Regulatory genes called small RNAs (sRNAs) are known to play critical roles in cellular responses to changing environments. For several sRNAs, regulation is effected by coupled stoichiometric degradation with messenger RNAs (mRNAs). The nonlinearity inherent in this regulatory scheme indicates that exact analytical solutions for the corresponding stochastic models are intractable. Here, we present a variational approach to analyze a well-studied stochastic model for regulation by sRNAs via coupled degradation. The proposed approach is efficient and provides accurate estimates of mean mRNA levels as well as higher order terms. Results from the variational ansatz are in excellent agreement with data from stochastic simulations for a wide range of parameters, including regions of parameter space where mean-field approaches break down. The proposed approach can be applied to quantitatively model stochastic gene expression in complex regulatory networks.Comment: 4 pages, 3 figure

Detection of Prolonged Diapause of Northern Corn Rootworm in Michigan (Coleoptera: Chrysomelidae)

Prolonged diapause of northern corn rootworm, while known from other Midwestern states, has not previously been reported in Michigan. Populations of northern corn rootworm, (Diabrotica barberi) from two first-year corn fields in Genesee County, Michigan were examined for prolonged egg diapause. Pro- longed diapause was suspected in these populations due to an unusually high proportion of northern versus western corn rootworms in these fields. Eggs obtained from females collected at these sites were reared in the laboratory for two years. The presence of the prolonged diapause trait was confirmed in one population by eggs which hatched following two simulated winters (7.3%). None of the eggs m the second population hatched following the second chill period, however, some eggs in this population remained in apparent diapause at the end of two years. The potential for using observed population shifts in favor of D. barberi as an early warning of the expansion of prolonged diapause in a population is discussed

ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervious system

Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes. A particularly dramatic form of APA occurs in the developing nervous system of flies and mammals, whereby various developmental genes undergo coordinate 3' UTR extension. In Drosophila, the RNA-binding protein ELAV inhibits RNA processing at proximal polyadenylation sites, thereby fostering the formation of exceptionally long 3' UTRs. Here, we present evidence that paused Pol II promotes recruitment of ELAV to extended genes. Replacing promoters of extended genes with heterologous promoters blocks normal 3' extension in the nervous system, while extension-associated promoters can induce 3' extension in ectopic tissues expressing ELAV. Computational analyses suggest that promoter regions of extended genes tend to contain paused Pol II and associated cis-regulatory elements such as GAGA. ChIP-seq assays identify ELAV in the promoter regions of extended genes. Our study provides evidence for a regulatory link between promoter-proximal pausing and APA

The Low Quiescent X-Ray Luminosity of the Neutron Star Transient XTE J2123-058

We report on the first X-ray observations of the neutron star soft X-ray transient (SXT) XTE J2123-058 in quiescence, made by Chandra and BeppoSAX, as well as contemporaneous optical observations. In 2002, the Chandra spectrum of XTE J2123-058 is consistent with a power-law model, or the combination of a blackbody plus a power-law, but it is not well-described by a pure blackbody. Using the interstellar column density, the power-law fit gives photon index of 3.1 (+0.7,-0.6) and indicates a 0.3-8 keV unabsorbed luminosity of 9(+4,-3)E31 (d/8.5 kpc)^2 ergs/s (90% confidence errors). Fits with models consisting of thermal plus power-law components indicate that the upper limit on the temperature of a 1.4 solar mass, 10 km radius neutron star with a hydrogen atmosphere is kT_eff < 66 eV, and the upper limit on the bolometric luminosity is L_infinity < 1.4E32 ergs/s, assuming d = 8.5 kpc. Of the neutron star SXTs that exhibit short (< 1 year) outbursts, including Aql X-1, 4U 1608-522, Cen X-4, and SAX J1810.8-2609, the lowest temperatures and luminosities are found for XTE J2123-058 and SAX J1810.8-2609. From the BeppoSAX observation of XTE J2123-058 in 2000, we obtained an upper limit on the 1-10 keV unabsorbed luminosity of 9E32 ergs/s. Although this upper limit allows that the X-ray luminosity may have decreased between 2000 and 2002, that possibility is not supported by our contemporaneous R-band observations, which indicate that the optical flux increased significantly. Motivated by the theory of deep crustal heating by Brown and co-workers, we characterize the outburst histories of the five SXTs. The low quiescent luminosity for XTE J2123-058 is consistent with the theory of deep crustal heating without requiring enhanced neutron star cooling if the outburst recurrence time is >~ 70 years.Comment: 8 pages, accepted by Ap

Use of Gas Electron Multiplier (GEM) Detectors for an Advanced X-ray Monitor

We describe a concept for a NASA SMEX Mission in which Gas Electron Multiplier (GEM) detectors, developed at CERN, are adapted for use in X-ray astronomy. These detectors can be used to obtain moderately large detector area and two-dimensional photon positions with sub mm accuracy in the range of 1.5 to 15 keV. We describe an application of GEMs with xenon gas, coded mask cameras, and simple circuits for measuring event positions and for anticoincidence rejection of particle events. The cameras are arranged to cover most of the celestial sphere, providing high sensitivity and throughput for a wide variety of cosmic explosions. At longer timescales, persistent X-ray sources would be monitored with unprecedented levels of coverage. The sensitivity to faint X-ray sources on a one-day timescale would be improved by a factor of 6 over the capability of the RXTE All Sky Monitor.Comment: 10 pages, 5 figs., in X-Ray and Gamma Ray Instrumentation for Astronomy XI, SPIE conference, San Diego, Aug. 200

Fractional Variations for Dynamical Systems: Hamilton and Lagrange Approaches

Fractional generalization of an exterior derivative for calculus of variations is defined. The Hamilton and Lagrange approaches are considered. Fractional Hamilton and Euler-Lagrange equations are derived. Fractional equations of motion are obtained by fractional variation of Lagrangian and Hamiltonian that have only integer derivatives.Comment: 21 pages, LaTe

Detection of Prolonged Diapause of Northern Corn Rootworm in Michigan (Coleoptera: Chrysomelidae)

Prolonged diapause of northern corn rootworm, while known from other Midwestern states, has not previously been reported in Michigan. Populations of northern corn rootworm, (Diabrotica barberi) from two first-year corn fields in Genesee County, Michigan were examined for prolonged egg diapause. Pro- longed diapause was suspected in these populations due to an unusually high proportion of northern versus western corn rootworms in these fields. Eggs obtained from females collected at these sites were reared in the laboratory for two years. The presence of the prolonged diapause trait was confirmed in one population by eggs which hatched following two simulated winters (7.3%). None of the eggs m the second population hatched following the second chill period, however, some eggs in this population remained in apparent diapause at the end of two years. The potential for using observed population shifts in favor of D. barberi as an early warning of the expansion of prolonged diapause in a population is discussed

Chromatin remodeling — a novel strategy to control excessive alcohol drinking

Harmful excessive use of alcohol has a severe impact on society and it remains one of the major causes of morbidity and mortality in the population. However, mechanisms that underlie excessive alcohol consumption are still poorly understood, and thus available medications for alcohol use disorders are limited. Here, we report that changing the level of chromatin condensation by affecting DNA methylation or histone acetylation limits excessive alcohol drinking and seeking behaviors in rodents. Specifically, we show that decreasing DNA methylation by inhibiting the activity of DNA methyltransferase (DNMT) with systemic administration of the FDA-approved drug, 5-azacitidine (5-AzaC) prevents excessive alcohol use in mice. Similarly, we find that increasing histone acetylation via systemic treatment with several histone deacetylase (HDAC) inhibitors reduces mice binge-like alcohol drinking. We further report that systemic administration of the FDA-approved HDAC inhibitor, SAHA, inhibits the motivation of rats to seek alcohol. Importantly, the actions of both DNMT and HDAC inhibitors are specific for alcohol, as no changes in saccharin or sucrose intake were observed. In line with these behavioral findings, we demonstrate that excessive alcohol drinking increases DNMT1 levels and reduces histone H4 acetylation in the nucleus accumbens (NAc) of rodents. Together, our findings illustrate that DNA methylation and histone acetylation control the level of excessive alcohol drinking and seeking behaviors in preclinical rodent models. Our study therefore highlights the possibility that DNMT and HDAC inhibitors can be used to treat harmful alcohol abuse

X 1908+075: An X-ray Binary with a 4.4 day Period

X 1908+075 is an optically unidentified and highly absorbed X-ray source that appears in early surveys such as Uhuru, OSO-7, Ariel V, HEAO-1, and the EXOSAT Galactic Plane Survey. These surveys measured a source intensity in the range of 2-12 mCrab at 2-10 keV, and the position was localized to ~ 0.5 degrees. We use the Rossi X-ray Timing Explorer (RXTE) All Sky Monitor (ASM) to confirm our expectation that a particular Einstein IPC detection (1E 1908.4+0730) provides the correct position for X 1908+075. The analysis of the coded mask shadows from the ASM for the position of 1E 1908.4+0730 yields a persistent intensity ~ 8 mCrab (1.5-12 keV) over a 3 year interval beginning in 1996 February. Furthermore, we detect a period of 4.400 +- 0.001 days with a false alarm probability < 1.0e-7 . The folded light curve is roughly sinusoidal, with an amplitude that is 22 % of the mean flux. The X-ray period may be attributed to the scattering and absorption of X-rays through a stellar wind combined with the orbital motion in a binary system. We suggest that X 1908+075 is an X-ray binary with a high mass companion star.Comment: 6 pages, two-column,"emulateapj" style, submitted to Ap