Regional climate-chemistry model simulations of ozone in the lower troposphere and its climatic impacts

The Purdue Regional Climate and Chemistry Model (PRCCM), a three-dimensional regional-scale coupled climate-chemistry model, has been developed to predict ozone concentrations in the lower troposphere with real-time modeled meteorological data and to investigate their climatic impacts at the regional scale with the radiative feedback process. The PRCCM performs photolysis calculation, chemistry modeling, chemical tracer transport as well as the radiation calculation simultaneously or on-line with atmospheric modeling. The PRCCM has been utilized to simulate an ozone episode during July 16–22, 1998 over the Lake Michigan region in this study. The PRCCM modeled ozone concentrations have been compared with the ground-based and airborne measurements, and have correlation coefficients of 0.742 and 0.771 with these measurements, respectively. Furthermore, the three-dimensional ozone concentrations predicted by the PRCCM have been real-time updated within the radiation code during atmospheric modeling process in order to investigate their resulting regional climatic impact in detail. For the simulation period, the increases of tropospheric ozone have been found to cause surface warming over highly polluted area but cooling over other areas. The model results also indicate their strong effects on the radiative balance and moisture distribution, which may affect regional dynamic circulation and climate. With the radiative feedback by tropospheric ozone included in the PRCCM, the model results also show improvements on meteorological predictions, e.g., 4.9% on relative humidity

Functional parameters of Dicer-independent microRNA biogenesis

Until recently, a Dicer-class RNase III enzyme was believed to be essential for microRNA (miRNA) biogenesis in all animals. The conserved vertebrate locus mir-451 defies this expectation and instead matures by direct cleavage of its pre-miRNA hairpin via the Slicer activity of Argonaute2 (Ago2). In this study, the authors used structure–function analysis to define the functional parameters of Ago2-mediated miRNA biogenesis. The data inform the design of effective Dicer-independent substrates for gene silencing and reveal novel aspects of substrate handling by Ago proteins

Widespread regulatory activity of vertebrate microRNA* species

An obligate intermediate during microRNA (miRNA) biogenesis is an ∼22-nucleotide RNA duplex, from which the mature miRNA is preferentially incorporated into a silencing complex. Its partner miRNA* species is generally regarded as a passenger RNA, whose regulatory capacity has not been systematically examined in vertebrates. Our bioinformatic analyses demonstrate that a substantial fraction of miRNA* species are stringently conserved over vertebrate evolution, collectively exhibit greatest conservation in their seed regions, and define complementary motifs whose conservation across vertebrate 3′-UTR evolution is statistically significant. Functional tests of 22 miRNA expression constructs revealed that a majority could repress both miRNA and miRNA* perfect match reporters, and the ratio of miRNA:miRNA* sensor repression was correlated with the endogenous ratio of miRNA:miRNA* reads. Analysis of microarray data provided transcriptome-wide evidence for the regulation of seed-matched targets for both mature and star strand species of several miRNAs relevant to oncogenesis, including mir-17, mir-34a, and mir-19. Finally, 3′-UTR sensor assays and mutagenesis tests confirmed direct repression of five miR-19* targets via star seed sites. Overall, our data demonstrate that miRNA* species have demonstrable impact on vertebrate regulatory networks and should be taken into account in studies of miRNA functions and their contribution to disease states

Immunization with Apoptotic Phagocytes Containing Histoplasma capsulatum Activates Functional CD8+ T Cells To Protect against Histoplasmosis ▿

We have previously revealed the protective role of CD8+ T cells in host defense against Histoplasma capsulatum in animals with CD4+ T cell deficiency and demonstrated that sensitized CD8+ T cells are restimulated in vitro by dendritic cells that have ingested apoptotic macrophage-associated Histoplasma antigen. Here we show that immunization with apoptotic phagocytes containing heat-killed Histoplasma efficiently activated functional CD8+ T cells whose contribution was equal to that of CD4+ T cells in protection against Histoplasma challenge. Inhibition of macrophage apoptosis due to inducible nitric oxide synthase (iNOS) deficiency or by caspase inhibitor treatment dampened the CD8+ T cell but not the CD4+ T cell response to pulmonary Histoplasma infection. In mice subcutaneously immunized with viable Histoplasma yeasts whose CD8+ T cells are protective against Histoplasma challenge, there was heavy granulocyte and macrophage infiltration and the infiltrating cells became apoptotic. In mice subcutaneously immunized with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled apoptotic macrophages containing heat-killed Histoplasma, the CFSE-labeled macrophage material was found to localize within dendritic cells in the draining lymph node. Moreover, depleting dendritic cells in immunized CD11c-DTR mice significantly reduced CD8+ T cell activation. Taken together, our results revealed that phagocyte apoptosis in the Histoplasma-infected host is associated with CD8+ T cell activation and that immunization with apoptotic phagocytes containing heat-killed Histoplasma efficiently evokes a protective CD8+ T cell response. These results suggest that employing apoptotic phagocytes as antigen donor cells is a viable approach for the development of efficacious vaccines to elicit strong CD8+ T cell as well as CD4+ T cell responses to Histoplasma infection