Dissecting the Determinants of Neuropathogenesis of the Murine Oncornaviruses

Digitalitzat per Artypla

Analysis and modeling of broadband airgun data influenced by nonlinear internal waves

Author Posting. © Acoustical Society of America, 2004. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 116 (2004): 3404-3422, doi:10.1121/1.1819499.To investigate acoustic effects of nonlinear internal waves, the two southwest tracks of the SWARM 95 experiment are considered. An airgun source produced broadband acoustic signals while a packet of large nonlinear internal waves passed between the source and two vertical linear arrays. The broadband data and its frequency range (10–180 Hz) distinguish this study from previous work. Models are developed for the internal wave environment, the geoacoustic parameters, and the airgun source signature. Parabolic equation simulations demonstrate that observed variations in intensity and wavelet time–frequency plots can be attributed to nonlinear internal waves. Empirical tests are provided of the internal wave-acoustic resonance condition that is the apparent theoretical mechanism responsible for the variations. Peaks of the effective internal wave spectrum are shown to coincide with differences in dominant acoustic wavenumbers comprising the airgun signal. The robustness of these relationships is investigated by simulations for a variety of geoacoustic and nonlinear internal wave model parameters.This work was supported by an ONR Ocean Acoustics Graduate Traineeship Award and by ONR grants to Rensselaer, the University of Delaware, and Woods Hole Oceanographic Institution

Gene expression profiling of microglia infected by a highly neurovirulent murine leukemia virus: implications for neuropathogenesis

BACKGROUND: Certain murine leukemia viruses (MLVs) are capable of inducing progressive spongiform motor neuron disease in susceptible mice upon infection of the central nervous system (CNS). The major CNS parenchymal target of these neurovirulent retroviruses (NVs) are the microglia, whose infection is largely coincident with neuropathological changes. Despite this close association, the role of microglial infection in disease induction is still unknown. In this paper, we investigate the interaction of the highly virulent MLV, FrCasE, with microglia ex vivo to evaluate whether infection induces specific changes that could account for neurodegeneration. Specifically, we compared microglia infected with FrCasE, a related non-neurovirulent virus (NN) F43/Fr57E, or mock-infected, both at a basic virological level, and at the level of cellular gene expression using quantitative real time RT-PCR (qRT-PCR) and Afffymetrix 430A mouse gene chips. RESULTS: Basic virological comparison of NN, NV, and mock-infected microglia in culture did not reveal differences in virus expression that provided insight into neuropathogenesis. Therefore, microglial analysis was extended to ER stress gene induction based on previous experiments demonstrating ER stress induction in NV-infected mouse brains and cultured fibroblasts. Analysis of message levels for the ER stress genes BiP (grp78), CHOP (Gadd153), calreticulin, and grp58 in cultured microglia, and BiP and CHOP in microglia enriched fractions from infected mouse brains, indicated that FrCasE infection did not induce these ER stress genes either in vitro or in vivo. To broadly identify physiological changes resulting from NV infection of microglia in vitro, we undertook a gene array screen of more than 14,000 well-characterized murine genes and expressed sequence tags (ESTs). This analysis revealed only a small set of gene expression changes between infected and uninfected cells (<18). Remarkably, gene array comparison of NN- and NV-infected microglia revealed only 3 apparent gene expression differences. Validation experiments for these genes by Taqman real-time RT-PCR indicated that only single Ig IL-1 receptor related protein (SIGIRR) transcript was consistently altered in culture; however, SIGIRR changes were not observed in enriched microglial fractions from infected brains. CONCLUSION: The results from this study indicate that infection of microglia by the highly neurovirulent virus, FrCasE, does not induce overt physiological changes in this cell type when assessed ex vivo. In particular, NV does not induce microglial ER stress and thus, FrCasE-associated CNS ER stress likely results from NV interactions with another cell type or from neurodegeneration directly. The lack of NV-induced microglial gene expression changes suggests that FrCasE either affects properties unique to microglia in situ, alters the expression of microglial genes not represented in this survey, or affects microglial cellular processes at a post-transcriptional level. Alternatively, NV-infected microglia may simply serve as an unaffected conduit for persistent dissemination of virus to other neural cells where they produce acute neuropathogenic effects

Comparison of White Crappie Populations in Diked and Undiked Lake Erie Wetlands

Author Institution: School of Natural Resources, The Ohio State UniversityMost of Ohio's remaining Lake Erie wetlands are diked to enhance habitat diversity. There is concern that fish communities in these wetlands may be isolated from adjacent waters. However, little data are available with which to evaluate possible isolation. We conducted a study that examined spring length frequencies, age structure, and growth of white crappie (Pomoxis annularis) populations in 3 diked wetlands and 2 undiked, adjacent areas. If populations are not isolated then differences in population parameters between the two types of systems should not be evident. White crappies were collected in April-May 1987 using trap nets. Length frequencies of white crappies were not similar between diked wetlands and adjacent areas, and mean lengths were significantly less in the diked wetlands. Populations were not comprised of similar age classes in the 5 systems. White crappies in diked wetlands grew significantly slower than their conspecifics in the undiked areas. These data indicate that white crappies hi diked wetlands are isolated from populations in undiked areas even though up to 75% of water in diked wetlands can be exchanged each year

Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction.

Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia