Enhancer Associated Long Non-coding RNA Transcription and Gene Regulation in Experimental Models of Rickettsial Infection

Recent discovery that much of the mammalian genome does not encode protein-coding genes (PCGs) has brought widespread attention to long noncoding RNAs (lncRNAs) as a novel layer of biological regulation. Enhancer lnc (elnc) RNAs from the enhancer regions of the genome carry the capacity to regulate PCGs in cis or in trans. Spotted fever rickettsioses represent the consequence of host infection with Gram-negative, obligate intracellular bacteria in the Genus Rickettsia. Despite being implicated in the pathways of infection and inflammation, the roles of lncRNAs in host response to Rickettsia species have remained a mystery. We have profiled the expression of host lncRNAs during infection of susceptible mice with R. conorii as a model closely mimicking the pathogenesis of human spotted fever rickettsioses. RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated, respectively, in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF), and DNaseI hypersensitivity sites to identify two potentially active and highly up-regulated elncRNAs NONMMUT013718 and NONMMUT024103. Using Hi-3C sequencing resource, we further determined that genomic loci of NONMMUT013718 and NONMMUT024103 might interact with and regulate the expression of nearby PCGs, namely Id2 (inhibitor of DNA binding 2) and Apol10b (apolipoprotein 10b), respectively. Heterologous reporter assays confirmed the activity of elncRNAs as the inducers of their predicted PCGs. In the lungs of infected mice, expression of both elncRNAs and their targets was significantly higher than mock-infected controls. Induced expression of NONMMUT013718/Id2 in murine macrophages and NONMMUT024103/Apol10b in endothelial cells was also clearly evident during R. conorii infection in vitro. Finally, shRNA mediated knock-down of NONMMUT013718 and NONMMUT024103 elncRNAs resulted in reduced expression of endogenous Id2 and Apl10b, demonstrating the regulatory roles of these elncRNAs on their target PCGs. Our results provide very first experimental evidence suggesting altered expression of pulmonary lncRNAs and elncRNA-mediated regulation of PCGs involved in immunity and during host interactions with pathogenic rickettsiae

Delicate f(R) gravity models with disappearing cosmological constant and observational constraints on the model parameters

We study the $f(R)$ theory of gravity using metric approach. In particular we investigate the recently proposed model by Hu-Sawicki, Appleby $-$ Battye and Starobinsky. In this model, the cosmological constant is zero in flat space time. The model passes both the Solar system and the laboratory tests. But the model parameters need to be fine tuned to avoid the finite time singularity recently pointed in the literature. We check the concordance of this model with the $H(z)$ and baryon acoustic oscillation data. We find that the model resembles the $\Lambda$CDM at high redshift. However, for some parameter values there are variations in the expansion history of the universe at low redshift.Comment: 16 pages and 9 figures, typos corrected, few references and minor clarifications added, revised version to appera in PR

Gravitational lensing constraint on the cosmic equation of state

Recent redshift-distance measurements of Type Ia supernovae (SNe Ia) at cosmological distances suggest that two-third of the energy density of the universe is dominated by dark energy component with an effective negative pressure. This dark energy component is described by the equation of state $p_{x} = w \rho_{x}$ $(w \geq -1)$. We use gravitational lensing statistics to constrain the equation of state of this dark energy. We use $n(\Delta\theta)$, image separation distribution function of lensed quasars, as a tool to probe $w$. We find that for the observed range of $\Omega_m \sim 0.2 - 0.4$, $w$ should lie between $-0.8 \leq w \leq -0.4$ in order to have five lensed quasars in a sample of 867 optical quasars. This limit is highly sensitive to lens and Schechter parameters and evolution of galaxies.Comment: Modified results and inclusion of calculations with new set of parameter

Variable Chaplygin Gas: Constraints from CMBR and SNe Ia

We constrain the parameters of the variable Chaplygin gas model, using the location of peaks of the CMBR spectrum and SNe Ia ``gold '' data set. Equation of state of the model is $P=-A(a)/\rho$, where $A(a)=A_0 a^{-n}$ is a positive function of the cosmological scale factor $a$, $A_0$ and $n$ being constants. The variable Chaplygin gas interpolates from dust-dominated era to quintessence dominated era. The model is found to be compatible with current type Ia Supernovae data and location of first peak if the values of $\Omega_m$ and $n$ lie in the interval $[0.017,~0.117]$ and $[-1.3,~2.6]$ respectively.Comment: 9 pages,4 figure

Cosmological Constraints on a Power Law Universe

Linearly coasting cosmology is comfortably concordant with a host of cosmological observations. It is surprisingly an excellent fit to SNe Ia observations and constraints arising from age of old quasars. In this article we highlight the overall viability of an open linear coasting cosmological model.The model is consistent with the latest SNe Ia ``gold'' sample and accommodates a very old high-redshift quasar, which the standard cold-dark model fails to do.Comment: 10 pages, 2 figure

Constraints on Chaplygin quartessence from the CLASS gravitational lens statistics and supernova data

The nature of the dark components (dark matter and dark energy) that dominate the current cosmic evolution is a completely open question at present. In reality, we do not even know if they really constitute two separated substances. In this paper we use the recent Cosmic All Sky Survey (CLASS) lensing sample to test the predictions of one of the candidates for a unified dark matter/energy scenario, the so-called generalized Chaplygin gas (Cg) which is parametrized by an equation of state $p = -A/\rho_{Cg}^{\alpha}$ where $A$ and $\alpha$ are arbitrary constants. We show that, although the model is in good agreement with this radio source gravitational lensing sample, the limits obtained from CLASS statistics are only marginally compatible with the ones obtained from other cosmological tests. We also investigate the constraints on the free parameters of the model from a joint analysis between CLASS and supernova data.Comment: 7 pages, 3 figures, to appear in Astronomy & Astrophysic

Age of High Redshift Objects - a Litmus Test for the Dark Energy Models

The discovery of the quasar, the APM 08279+5255 at z = 3.91 whose age is 2-3 Gyr has once again led to ``age crisis''. The noticeable fact about this object is that it cannot be accommodated in a universe with $\Omega_m = 0.27$, currently accepted value of matter density parameter and $\omega = \mathrm{constant}$. In this work, we explore the concordance of various dark energy parameterizations ($w(z)$ models) with the age estimates of the old high redshift objects. It is alarming to note that the quasar cannot be accommodated in any dark energy model even for $\Omega_m = 0.23$, which corresponds to $1 \sigma$ deviation below the best fit value provided by WMAP. There is a need to look for alternative cosmologies or some other dark energy parameterizations which allow the existence of the high redshift objects.Comment: Latex file, Results and Discussion section is modified, more references adde

Observational constraints on the time-dependence of dark energy

One of the most important questions nowadays in physics concerns the nature of the so-called dark energy. It is also a consensus among cosmologists that such a question will not be answered on the basis only of observational data. However, it is possible to diminish the range of possibilities for this dark component by comparing different dark energy scenarios and finding which models can be ruled out by current observations. In this paper, by asssuming three distinct parametrizations for the low-redshift evolution of the dark energy equation of state (EOS), we consider the possibility of discriminating between evolving dark energy and $\Lambda$CDM models from a joint analysis involving the most recent radio sources gravitational lensing sample, namely, the Cosmic All Sky Survey (CLASS) statistical data and the recently published \emph{gold} SNe Ia sample. It is shown that this particular combination of observational data restricts considerably the dark energy parameter space, which enables possible distinctions between time-dependent and constant EOS's.Comment: 5 pages, 1 figure, to appear in Nuclear Physics