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I like to catch on PBS, and with a little help from TiVo, I was lucky enough to see three attention-gripping documentary shorts earlier this week. Now I just found a that says all three shorts were made by recent graduates of the Graduate School of Journalism at the University of California at Berkeley. I thought it was cool that recent graduates (a) did such good work, and (b) got a chance to have that work broadcast on free TV.
But even cooler — you can watch these documentaries (free) on your computer. So many people are trying to learn to tell stories with video today — maybe these three shorts can be instructional.
(by Xiaoli Zhou; shot in China): Broadcast version (length only 9:36) will be online July 5; a 20-minute rough cut is online now.
(by Claudine LoMonaco and and Mary Spicuzza; shot in Mexico and the U.S.): Unfortunately, the three clips online (lengths 4:36, 7:54 and 6:12) at only available in Real Video format, which looks horrible, as usual. (Why doesn’t PBS use Flash video? Or at least QuickTime! Come on, people, Real Video is so often completely unwatchable, it’s not even funny!) This story taught me some things about the U.S.-Mexico border situation that I had not realized, even though I have been following the recent political discussions pretty closely.
(by Alexis Bloom and Cassandra Herrman): The (length 26:36) will be online July 5, and there will be a QuickTime version (hooray!). The overall online package for this story is excellent; it includes two interactive pieces and transcripts of the extended interviews with several knowledgeable Zimbabweans.
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After the cells had matured, the scaffolding and the newly formed penile spongy tissue, called corpora cavernosa, was surgically implanted into the rabbits' penises.
The report was to be presented Tuesday at the American College of Chest Physicians annual meeting, in Philadelphia.
To determine whether the immunomodulatory effect of PDE5 inhibition affected T cell activation within the tumor microenvironment, we examined IL-2 production by TILs using a transgenic mouse in which expression of GFP is under an IL-2 promoter (BALB/c–IL-2p/GFP) (25). In this model, T cell stimulation activates the IL-2 promoter and results in expression of the reporter transgene, GFP, which is easily detectable by flow cytometry. C26GM-primed BALB/c–IL-2p/GFP splenocytes were adoptively transferred into tumor-bearing recipients that were either left untreated or treated with sildenafil for 9 d. Single cell suspensions of the tumor-infiltrating CD8+ T cells were analyzed by flow cytometry for GFP expression. Adoptively transferred, vaccine-primed T cells were activated in the tumor microenvironment only in the presence of PDE5 inhibition, whereas in its absence they produced no IL-2 and, hence, were bona fide anergic T cells (Fig. 4 D). To further prove that these effects were dependent on CD8+ T cells, mice were challenged with C26GM and were (a) left untreated, (b) given sildenafil, (c) given an anti-CD8+ depleting antibody, or (d) given both sildenafil and the CD8+ depleting antibody. Sildenafil treatment again demonstrated a statistically significant reduction in tumor outgrowth, an effect completely abrogated by CD8+ depletion (Fig. 4 E). These experiments demonstrate that PDE5 inhibition enhances the tumor-specific T cell response, increases intratumoral T cell infiltration and activation, and underscores the role of CD8+ T cells in sildenafil-mediated antitumor responses.
If unsuccessful, interferes with other treatments
ED can in many cases be treated by drugs taken orally, injected, or as penile suppositories. These drugs increase the efficacy of nitrous oxide, which dilates the blood vessels of corpora cavernosa. When oral drugs or suppositories fail, injections into the erectile tissue of the penile shaft are extremely effective but occasionally cause priapism.
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?2 Note that the number of functional enzymes in most species may not equal the number of gene products. For example, the major rod cell photoreceptor PDE6 exists as a heterodimer of two different gene products, PDE6A and PDE6B. The cone photoreceptor cell PDE6 consists of a homodimeric PDE6C. In some species, such as chickens, the rod enzyme may be a PDE6B homodimer. Thus, it is not clear whether each gene that contains a conserved catalytic sequence should be classified separately as a different PDE.
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The researchers found that the overall prevalence of erectile dysfunction among U.S. men was 18.4 percent. Age was a strong risk factor -- men 70 and older accounted for 70 percent of those with erectile dysfunction. In contrast, just 5 percent of men with erectile problems were between the ages of 20 and 40.
Freshly isolated MDSCs suppress the in vitro proliferation of activated lymphocytes. Interestingly, the suppressive mechanisms appear to be strain specific. In the Th1 cell prone strain C57BL/6, it is mediated by NOS2 through NO production (34), whereas, in the mixed Th1/Th2 cell BALB/c strain, suppression requires peroxynitrite formation via ARG1 and NOS2 coexpression (8) or L-arginine depletion secondary to ARG1 overexpression (35). Reductions of both ARG1 and NOS2 expression via PDE5 inhibition should affect both suppressive pathways, resulting in less MDSC-mediated immunosuppression and, therefore, enhanced antigen-specific T cell proliferation. To test this hypothesis, tumor-derived CD11b+ MDSCs were isolated from C26GM-bearing BALB/c mice. MDSC suppressive activity was determined by admixing MDSCs with CFSE-labeled HA-specific CD8+ (clone 4) or CD4+ (6.5) T cells pulsed with their relevant peptide in the presence or absence of sildenafil (Fig. 7, A and B). Although the addition of tumor-derived MDSCs significantly impaired antigen-specific T cell proliferation as demonstrated by the low percentage of CFSElow clonotypic T cells, sildenafil almost completely restored both CD4+ and CD8+ responsiveness of these antigen-specific T cells. The absence of sildenafil-mediated enhancement in T cell function in the groups lacking CD11b+ cells underscores the targeted role of sildenafil on the MDSC population. Because in a Th1 cell–prone environment MDSC suppression is only NOS2 dependent (34), we examined the role of PDE5 in MDSCs in a C57BL/6 background where NOS2–/– mice are also available. CD11b+ MDSCs were isolated from either C57BL/6-NOS2+/+ or B16GM-bearing C57BL/6-NOS2–/– B16GM melanoma-bearing mice. A suppression assay was performed by stimulating OVA-specific CD4+ T cells with the relevant peptide in the presence or absence of MDSCs obtained from either NOS2+/+ or NOS2–/– tumor-bearing mice (Fig. 7 C). Although the addition of C57BL/6-NOS2+/+ MDSCs induced considerable T cell suppression, no suppression was observed with MDSCs from NOS2–/– mice. Furthermore, although PDE5 inhibition reversed MDSC suppression in NOS2+/+ mice, sildenafil failed to augment T cell responsiveness in the NOS2–/–-derived MDSC suppression assay. These results confirm the role of NOS2 in MDSC-mediated T cell suppression (Fig. 7 C) and underscore the ability of PDE5 inhibition to reverse the two major suppressive pathways in MDSCs (ARG1 and NOS2).
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