Committing curriculum time to science literacy: The benefits from science based media resources

Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells

Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

BACKGROUND: AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) is the second most frequent cancer associated with AIDS, and is a frequent cause of death in HIV-infected individuals. Experimental analysis of AIDS-NHL has been facilitated by the availability of an excellent animal model, i.e., simian Acquired Immunodeficiency Syndrome (SAIDS) in the rhesus macaque consequent to infection with simian immunodeficiency virus. A recent study of SAIDS-NHL demonstrated a lymphoma-derived cell line to be sensitive to the growth inhibitory effects of the ubiquitous cytokine, transforming growth factor-beta (TGF-beta). The authors concluded that TGF-beta acts as a negative growth regulator of the lymphoma-derived cell line and, potentially, as an inhibitory factor in the regulatory network of AIDS-related lymphomagenesis. The present study was conducted to assess whether other SAIDS-NHL and AIDS-NHL cell lines are similarly sensitive to the growth inhibitory effects of TGF-beta, and to test the hypothesis that interleukin-6 (IL-6) may represent a counteracting positive influence in their growth regulation. METHODS: Growth stimulation or inhibition in response to cytokine treatment was quantified using trypan blue exclusion or colorimetric MTT assay. Intracellular flow cytometry was used to analyze the activation of signaling pathways and to examine the expression of anti-apoptotic proteins and distinguishing hallmarks of AIDS-NHL subclass. Apoptosis was quantified by flow cytometric analysis of cell populations with sub-G1 DNA content and by measuring activated caspase-3. RESULTS: Results confirmed the sensitivity of LCL8664, an immunoblastic SAIDS-NHL cell line, to TGF-beta1-mediated growth inhibition, and further demonstrated the partial rescue by simultaneous treatment with IL-6. IL-6 was shown to activate STAT3, even in the presence of TGF-beta1, and thereby to activate proliferative and anti-apoptotic pathways. By comparison, human AIDS-NHL cell lines differed in their responsiveness to TGF-beta1 and IL-6. Analysis of a recently derived AIDS-NHL cell line, UMCL01-101, indicated that it represents immunoblastic AIDS-DLCBL. Like LCL-8664, UMCL01-101 was sensitive to TGF-beta1-mediated inhibition, rescued partially by IL-6, and demonstrated rapid STAT3 activation following IL-6 treatment even in the presence of TGF-beta1. CONCLUSION: These studies indicate that the sensitivity of immunoblastic AIDS- or SAIDS-DLBCL to TGF-beta1-mediated growth inhibition may be overcome through the stimulation of proliferative and anti-apoptotic signals by IL-6, particularly through the rapid activation of STAT3

The History, Relevance, and Applications of the Periodic System in Geochemistry

Geochemistry is a discipline in the earth sciences concerned with understanding the chemistry of the Earth and what that chemistry tells us about the processes that control the formation and evolution of Earth materials and the planet itself. The periodic table and the periodic system, as developed by Mendeleev and others in the nineteenth century, are as important in geochemistry as in other areas of chemistry. In fact, systemisation of the myriad of observations that geochemists make is perhaps even more important in this branch of chemistry, given the huge variability in the nature of Earth materials – from the Fe-rich core, through the silicate-dominated mantle and crust, to the volatile-rich ocean and atmosphere. This systemisation started in the eighteenth century, when geochemistry did not yet exist as a separate pursuit in itself. Mineralogy, one of the disciplines that eventually became geochemistry, was central to the discovery of the elements, and nineteenth-century mineralogists played a key role in this endeavour. Early “geochemists” continued this systemisation effort into the twentieth century, particularly highlighted in the career of V.M. Goldschmidt. The focus of the modern discipline of geochemistry has moved well beyond classification, in order to invert the information held in the properties of elements across the periodic table and their distribution across Earth and planetary materials, to learn about the physicochemical processes that shaped the Earth and other planets, on all scales. We illustrate this approach with key examples, those rooted in the patterns inherent in the periodic law as well as those that exploit concepts that only became familiar after Mendeleev, such as stable and radiogenic isotopes

"Ochoan" Quartermaster Formation of North Texas, USA, Part II: Magnetostratigraphy and geochronology

Session no. 153 - Permian-Triassic Changes and Extinction Event: New Insights from Sedimentary, Geochemical, and Paleobiological Records and Modeling Approaches I: paper no. 153-6As part of an effort to obtain a well-dated record of paleoenvironmental change (specifically in paleotemperatures and paleoatmospheric pCO2) from terrestrial strata of the latest Ochoan Series, spanning the Permian-Triassic boundary (PTB), in the southwestern United States (westernmost Pangea), we are building a detailed magnetostratigraphic record of the Ochoan Series strata represented by the Dewey Lake/Quartermaster formations (DL/QM), in west Texas. These strata are unique in that they are the only Upper Permian sedimentary rocks from western Pangea containing volcanic ash fall deposits. They offer a unique and critical paleogeographic vantage on events across the PTB, which encompassed the most severe biotic crisis known since the emergence of metazoan life on Earth and whose cause(s) remain one of the most profound unresolved questions in earth sciences. Earlier studies showed that the red-beds of the DL/QM fms are high-fidelity recorders of the paleomagnetic field and remarkably resistant to remagnetization. Dual polarity characteristic magnetizations (ChRM) are largely carried by a mix of both specular and pigment hematite, with no discernable directional difference between the carriers, as revealed by chemical demagnetization. For these red beds, hematite cement was early acquired and is an important remanence carrier. We have collected new data from ten sites over a 3 meter interval below and above the lowest ash in the DL/QM exposed at the South Prong, Caprock Canyon, and 14 sites through the part of the Country Road 207 section that exposes a probably correlative ash. Polarity data show that the DL/QM section immediately above and below these two ash occurrences is entirely normal polarity, consistent with previous work suggesting that the PTB lies within a normal polarity chron. The interval containing another ash about 20 m above the lower ash at Caprock Canyon, is of reverse polarity. Ar/Ar and U-Pb data for these ashes are consistent with this placement for the PTB, i.e. within error of the U-Pb age of 252.4 Ma for the GSSP at Meishan, China. Given that some 14 normal polarity chrons have been recognized in the latest Permian, following the termination of the Permo-Carboniferous Reverse Superchron (PCRS), we suspect that the lower DL/QM section will eventually reveal a finer polarity record.link_to_OA_fulltex

Geochronology and regional correlation of continental Permo-Triassic sediments in West Texas

Session: A 100 Year Quest to Graduate the Geological Column With an Accurate Time Scale II Posters: abstract V51A-2512Section: Volcanology, Geochemistry, PetrologyAlthough many aspects of marine sections spanning the Permian-Triassic boundary (PTB) have been studied in great detail across a broad paleogeographic area, less is known about the timing, pace, and extent of environmental changes and extinctions across this boundary in continental environments, particularly along the Panthalassa margin. Extensive outcrops in the Ochoan Series of west Texas provide an opportunity to investigate the terrestrial record spanning the PTB. The presence of several silicic tuffs in these sections allows for precise radioisotopic dating using both U-Pb ...link_to_OA_fulltex