Pathophysiology of Arbroviral Encephalitides in Laboratory Rodents

Western equine encephalitis virus (WEEV) is an arboviral pathogen naturally found in North America. The primary disease phenotype associated with WEEV infection in susceptible hosts is a relatively long prodromal period followed by viral encephalitis. By contrast, in the current work, experimental inoculation of WEEV into the peritoneum of Syrian golden hamsters produced rapid death within approximately 96 h. It was determined that direct virus killing of lymphoid cells leads to death in WEEV-infected Syrian golden hamsters, and that inflammatory cytokines have the potential to enhance virus-induced lymphoid cell destruction. It was further concluded that WEEV retains its ability to cause encephalitis in Syrian golden hamsters, if hamsters survive the early stages of virus infection or if virus is introduced directly into the CNS. Death in WEEV-infected hamsters is associated with lymphonecrotic lesions in the absence of pathological lesions in the central nervous system (CNS). Few clinical parameters were altered by WEEV infection, with the exception of circulating lymphocyte numbers. Circulating lymphocyte numbers decreased dramatically during WEEV infection, and lymphopenia was identified as a consistent indicator of eventual death. Virus infection also increased serum concentrations of the cytokines interferon and tumor necrosis factor-alpha (TNF-alpha). Hamster peritoneal macrophages exposed to WEEV expressed TNF-alpha in a dose-responsive manner. Macrophage expression of TNF-alpha could be significantly inhibited by treatment of cells with anti-inflammatory agents flunixin meglumine (FM) or dexamethasone (Dex). Anti-inflammatory treatment also protected macrophages from cytotoxicity associated with exposure to WEEV. Treatment of WEEV-infected hamsters with either FM or Dex significantly improved survival compared to placebo-treated controls. WEEV induced cytotoxicity in hamster splenocytes exposed to WEEV in a virus dose-responsive manner. Supernatant from WEEV-exposed macrophages significantly enhanced WEEV killing of splenocytes. Hamsters that survived the early stages of WEEV infection occasionally developed signs of neurological disease and died approximately 6 to 9 d after virus inoculation. These animals had histopathological lesions in the CNS consistent with alphavirus-induced encephalitis. Inoculation of WEEV directly into the CNS caused apparent encephalitic disease. Death following CNS inoculation of WEEV was rapid and concurrent with histopathological lesions in the CNS similar to lesions seen in encephalitic hamsters following peripheral inoculation

Distances to Populous Clusters in the LMC via the K-Band Luminosity of the Red Clump

We present results from a study of the distances and distribution of a sample of intermediate-age clusters in the Large Magellanic Cloud. Using deep near-infrared photometry obtained with ISPI on the CTIO 4m, we have measured the apparent K-band magnitude of the core helium burning red clump stars in 17 LMC clusters. We combine cluster ages and metallicities with the work of Grocholski & Sarajedini to predict each cluster's absolute K-band red clump magnitude, and thereby calculate absolute cluster distances. An analysis of these data shows that the cluster distribution is in good agreement with the thick, inclined disk geometry of the LMC, as defined by its field stars. We also find that the old globular clusters follow the same distribution, suggesting that the LMC's disk formed at about the same time as the globular clusters, ~ 13 Gyr ago. Finally, we have used our cluster distances in conjunction with the disk geometry to calculate the distance to the LMC center, for which we find (m-M)o = 18.40 +/- 0.04_{ran} +/- 0.08_{sys}, or Do = 47.9 +/- 0.9 +/- 1.8 kpc.Comment: 31 pages including 5 figures and 7 tables. Accepted for publication in the August 2007 issue of A

Effects of pH on redox proxies in a Jurassic rift lake : implications for interpreting environmental records in deep time

This work was supported at the University of California, Riverside by the NSF-EAR FESD Program and the NASA Astrobiology Institute under Cooperative Agreement No. NNA15BB03A issued through the Science Mission Directorate. We thank Roger Buick (UW) for financial support of the carbon and nitrogen isotope work. EES acknowledges support from a NASA postdoctoral fellowship, as well as valuable discussions about the Newark basin with Charlotte B. Schreiber. GDL thanks the Agouron Institute for providing funding for the Waters Autospec GC-MS instrument at UCR.It is widely agreed that the Earth’s atmosphere and oceans have undergone major redox changes over the last 2.5 billion years. However, the magnitude of these shifts remains a point of debate because it is difficult to reconstruct concentrations of dissolved O2 from indirect proxies in sedimentary archives. In this study, we show that an additional complicating factor that is rarely considered may be the pH of the water column. We analyzed rock samples from the early Jurassic Towaco Formation in the Newark basin (eastern USA), comprising deposits of a rift lake that became temporarily redox stratified. New biomarker evidence points to increasingly saline aquatic conditions during the second half of the lake’s history, with a salinity stratification that induced redox stratification, including evidence for water column anoxia, and that state may also explain the disappearance of macrofauna at this time. Distinctive lipid biomarker assemblages and stable nitrogen isotope data support previous mineralogical indications that the lake was alkaline (pH ≥ 9) during its saline episode. Despite the biomarker and macrofaunal evidence for anoxia, ratios of Fe/Al and FeHR/FeT show only small to no enrichments in the anoxic horizon compared to oxic facies in the same section – counter to what is commonly observed in anoxic marine settings. Molybdenum, As, V, U and to some degree Cd show enrichments in the anoxic interval, whereas Co, Ni, Cu, Zn and Cr do not. These patterns are most parsimoniously explained by differential pH effects on the solubility of these elements. Extrapolating from these observations in lacustrine strata, we speculate that a secular increase in seawater pH over Earth’s history as recently proposed may have helped modulate the magnitude of trace metal enrichments in marine shales, although other factors such as atmospheric and oceanic redox likely dominated the observed enrichment patterns. Further, a decrease in the solubility of ferrous iron, a major O2 sink, with increasing pH may have contributed to ocean oxygenation. In summary, our results highlight the potential importance of pH in influencing global biogeochemical cycles for multiple elements and for the interpretation of ancient nitrogen isotope signatures.PostprintPeer reviewe

Optimization of Ectopic Gene Expression in Skeletal Muscle Through DNA Transfer by Electroporation.

Background Electroporation (EP) is a widely used non-viral gene transfer method. We have attempted to develop an exact protocol to maximize DNA expression while minimizing tissue damage following EP of skeletal muscle in vivo. Specifically, we investigated the effects of varying injection techniques, electrode surface geometry, and plasmid mediums. Results We found that as the amount of damage increased in skeletal muscle in response to EP, the level of β-galactosidase (β-gal) expression drastically decreased and that there was no evidence of β-gal expression in damaged fibers. Two specific types of electrodes yielded the greatest amount of expression. We also discovered that DNA uptake in skeletal muscle following intra-arterial injection of DNA was significantly enhanced by EP. Finally, we found that DMSO and LipoFECTAMINE™, common enhancers of DNA electroporation in vitro, had no positive effect on DNA electroporationin vivo. Conclusions When injecting DNA intramuscularly, a flat plate electrode without any plasmid enhancers is the best method to achieve high levels of gene expression

An improved collision efficiency model for particle aggregation

A generalized geometric model is presented which describes the collision efficiency factor of aggregation (the probability of a binary particle or aggregate collision resulting in adhesion) for systems comprised of two oppositely charged species. Application of the general model to specific systems requires calculation of the area of each species available for collision with a second species. This is in contrast to previous models developed for polymer-particle flocculation that are based on the fractional surface coverage of adsorbed polymer. The difference between these approaches is suggested as an explanation for previously observed discrepancies between theory and observation. In the current work the specific case of oppositely charged nondeformable spherical particles (heteroaggregation) is quantitatively addressed. The optimum concentration of oppositely charged particles for rapid aggregation (maximum collision efficiency) as a function of relative particle size is calculated and an excellent correlation is found with data taken from literature

In Pursuit of Love: First Templated Search for Compact Objects with Large Tidal Deformabilities in the LIGO-Virgo Data

We report results on the first matched-filtering search for binaries with compact objects having large tidal deformabilities in the LIGO-Virgo gravitational wave (GW) data. The tidal deformability of a body is quantified by the ``Love number" $\Lambda \propto \hskip 1pt (r/m)^5$, where $r/m$ is the body's (inverse) compactness. Due to its strong dependence on compactness, the $\Lambda$ of larger-sized compact objects can easily be many orders of magnitude greater than those of black holes and neutron stars, leaving phase shifts which are sufficiently large for these binaries to be missed by binary black hole (BBH) templated searches. In this paper, we conduct a search using inspiral-only waveforms with zero spins but finite tides, with the search space covering chirp masses $3 M_\odot < \mathcal{M} < 15 M_\odot$ and effective tidal deformabilities $10^2 \lesssim \tilde{\Lambda} \lesssim 10^6$. We find no statistically significant GW candidates. This null detection implies an upper limit on the merger rate of such binaries in the range $[1-300] \hskip 2pt \text{Gpc}^{-3} \text{year}^{-1}$, depending on $\mathcal{M}$ and $\tilde{\Lambda}$. While our constraints are model agnostic, we discuss the implications on beyond the Standard Model scenarios that give rise to boson stars and superradiant clouds. Using inspiral-only waveforms we recover many of the BBH signals which were previously identified with full inspiral-merger-ringdown templates. We also constrain the Love number of black holes to $\Lambda \lesssim 10^3$ at the 90\% credible interval. Our work is the first-ever dedicated template-based search for compact objects that are not only black holes and neutron stars. Additionally, our work demonstrates a novel way of finding new physics in GW data, widening the scope of potential discovery to previously unexplored parameter space.Comment: 42+11 pages, 12 figure