Birth/birth-death processes and their computable transition probabilities with biological applications

Birth-death processes track the size of a univariate population, but many biological systems involve interaction between populations, necessitating models for two or more populations simultaneously. A lack of efficient methods for evaluating finite-time transition probabilities of bivariate processes, however, has restricted statistical inference in these models. Researchers rely on computationally expensive methods such as matrix exponentiation or Monte Carlo approximation, restricting likelihood-based inference to small systems, or indirect methods such as approximate Bayesian computation. In this paper, we introduce the birth(death)/birth-death process, a tractable bivariate extension of the birth-death process. We develop an efficient and robust algorithm to calculate the transition probabilities of birth(death)/birth-death processes using a continued fraction representation of their Laplace transforms. Next, we identify several exemplary models arising in molecular epidemiology, macro-parasite evolution, and infectious disease modeling that fall within this class, and demonstrate advantages of our proposed method over existing approaches to inference in these models. Notably, the ubiquitous stochastic susceptible-infectious-removed (SIR) model falls within this class, and we emphasize that computable transition probabilities newly enable direct inference of parameters in the SIR model. We also propose a very fast method for approximating the transition probabilities under the SIR model via a novel branching process simplification, and compare it to the continued fraction representation method with application to the 17th century plague in Eyam. Although the two methods produce similar maximum a posteriori estimates, the branching process approximation fails to capture the correlation structure in the joint posterior distribution

NCP activates chloroplast transcription by controlling phytochrome-dependent dual nuclear and plastidial switches.

Phytochromes initiate chloroplast biogenesis by activating genes encoding the photosynthetic apparatus, including photosynthesis-associated plastid-encoded genes (PhAPGs). PhAPGs are transcribed by a bacterial-type RNA polymerase (PEP), but how phytochromes in the nucleus activate chloroplast gene expression remains enigmatic. We report here a forward genetic screen in Arabidopsis that identified NUCLEAR CONTROL OF PEP ACTIVITY (NCP) as a necessary component of phytochrome signaling for PhAPG activation. NCP is dual-targeted to plastids and the nucleus. While nuclear NCP mediates the degradation of two repressors of chloroplast biogenesis, PIF1 and PIF3, NCP in plastids promotes the assembly of the PEP complex for PhAPG transcription. NCP and its paralog RCB are non-catalytic thioredoxin-like proteins that diverged in seed plants to adopt nonredundant functions in phytochrome signaling. These results support a model in which phytochromes control PhAPG expression through light-dependent double nuclear and plastidial switches that are linked by evolutionarily conserved and dual-localized regulatory proteins

Phytochrome activates the plastid-encoded RNA polymerase for chloroplast biogenesis via nucleus-to-plastid signaling.

Light initiates chloroplast biogenesis by activating photosynthesis-associated genes encoded by not only the nuclear but also the plastidial genome, but how photoreceptors control plastidial gene expression remains enigmatic. Here we show that the photoactivation of phytochromes triggers the expression of photosynthesis-associated plastid-encoded genes (PhAPGs) by stimulating the assembly of the bacterial-type plastidial RNA polymerase (PEP) into a 1000-kDa complex. Using forward genetic approaches, we identified REGULATOR OF CHLOROPLAST BIOGENESIS (RCB) as a dual-targeted nuclear/plastidial phytochrome signaling component required for PEP assembly. Surprisingly, RCB controls PhAPG expression primarily from the nucleus by interacting with phytochromes and promoting their localization to photobodies for the degradation of the transcriptional regulators PIF1 and PIF3. RCB-dependent PIF degradation in the nucleus signals the plastids for PEP assembly and PhAPG expression. Thus, our findings reveal the framework of a nucleus-to-plastid anterograde signaling pathway by which phytochrome signaling in the nucleus controls plastidial transcription

Solvent content of protein crystals from diffraction intensities by Independent Component Analysis

An analysis of the protein content of several crystal forms of proteins has been performed. We apply a new numerical technique, the Independent Component Analysis (ICA), to determine the volume fraction of the asymmetric unit occupied by the protein. This technique requires only the crystallographic data of structure factors as input.Comment: 9 pages, 2 figures, 1 tabl

An HST/COS legacy survey of high-velocity ultraviolet absorption in the Milky Way's circumgalactic medium and the Local Group

To characterize the absorption properties of this circumgalactic medium (CGM) and its relation to the LG we present the so-far largest survey of metal absorption in Galactic high-velocity clouds (HVCs) using archival ultraviolet (UV) spectra of extragalactic background sources. The UV data are obtained with the Cosmic Origins Spectrograph (COS) onboard the Hubble Space Telescope (HST) and are supplemented by 21 cm radio observations of neutral hydrogen. Along 270 sightlines we measure metal absorption in the lines of SiII, SiIII, CII, and CIV and associated HI 21 cm emission in HVCs in the velocity range |v_LSR|=100-500 km s^-1. With this unprecedented large HVC sample we were able to improve the statistics on HVC covering fractions, ionization conditions, small-scale structure, CGM mass, and inflow rate. For the first time, we determine robustly the angular two point correlation function of the high-velocity absorbers, systematically analyze antipodal sightlines on the celestial sphere, and compare the absorption characteristics with that of Damped Lyman alpha absorbers (DLAs) and constrained cosmological simulations of the LG. Our study demonstrates that the Milky Way CGM contains sufficient gaseous material to maintain the Galactic star-formation rate at its current level. We show that the CGM is composed of discrete gaseous structures that exhibit a large-scale kinematics together with small-scale variations in physical conditions. The Magellanic Stream clearly dominates both the cross section and mass flow of high-velocity gas in the Milky Way's CGM. The possible presence of high-velocity LG gas underlines the important role of the local cosmological environment in the large-scale gas-circulation processes in and around the Milky Way (abridged).Comment: 37 pages, 25 figures, 8 tables, accepted for publication in A&

Paraoxonase 2 overexpression inhibits tumor development in a mouse model of ovarian cancer.

Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue. Using a mouse xenograft model of OC, we demonstrate that overexpression of PON2 prevents tumor formation. Mechanistically, PON2 decreases OC cell proliferation by inhibiting insulin like growth factor-1 (IGF-1) expression and signaling. Intriguingly, PON2 reduces c-Jun-mediated transcriptional activation of IGF-1 gene by decreasing mitochondrial superoxide generation. In addition, PON2 impairs insulin like growth factor-1 receptor (IGF-1R) signaling in OC cells by altering cholesterol homeostasis, which resulted in reduced caveolin-1/IGF-1R interaction and IGF-1R phosphorylation. Taken together, we report for the first time that PON2 acts as a tumor suppressor in the early stage of OC by reducing IGF-1 production and its signaling, indicating PON2 activation might be a fruitful strategy to inhibit early stage ovarian tumor