sources, and the Human Genome project had slightly higher success rates, but these represented a total of only 4% of the submitted R01 applications.For R29 awards, the success rates for unamended competing proposals for fiscal years 1993 and 1994 were 23.1% and 19.0%, respectively. In general, the distribution patterns for R29 and R01 applications were similar, but the success rate for R29 grants was a little higher. The total pool of these relatively low-cost R29 applications was much smaller, however.There has been a progressive deterioration over the past 10 years ( Fig. 1) in the funding of unsolicited, competing, unamended R01 applications for new (Type 1) and renewal (Type 2) applications. The data on renewal applications indicate that two out of three established investigators cannot continue their ongoing research programs. They are also deterred from propos-ing highly imaginative but speculative ideas that might lead to major scientific breakthroughs (2).Debates for the budget for fiscal year 1996 have begun, and further cuts in the NIH budget have been proposed. The NIH has shown itself to be an excellent financial investment, as measured by improved health care for our citizens as well as the progress of our biotechnology industry (3). Our political leaders must have the understanding and courage to protect government expenditures that have proved to be invaluable for this country and for mankind. p. 1261). They suggest that the RAC reduce its role in the supervision of human gene therapy and specifically suggest that the RAC end protocolby-protocol review and review of Phase I follow-up studies. We believe that separate issues are involved in these two suggestions that require further public discussion.With regard to protocol-by-protocol review, it should first be pointed out that an accelerated review process not requiring a wait for a quarterly meeting of RAC already speeds the approval of replicative protocols.For instance, at its recent June meeting, the RAC reviewed nine new protocols while it heard about the approval of three accelerated reviews and four minor modifications. The relative number of accelerated approvals compared to full RAC review could certainly be increased. Second, we believe that substantial safety issues, particularly regarding long-term potential effects of gene therapy experiments, remain sufficiently important to merit discussion in a public setting. It has not yet been 5 years since the approval of the first human
Neuronal nitric oxide synthase (nNOS) is one of two constitutive enzyme variants responsible for the production of nitric oxide (NO) from L‐arginine in mammalian cells. In somatic cells, this membrane‐associated protein has been shown to be activated by Ca2+ and to interact with Plasma Membrane Calcium ATPase 4 (PMCA4), the major calcium efflux pump in murine sperm (Wennemuth et. al. 2003), which negatively regulates it. NO is an important second messenger, and is required for a variety of sperm functions, including motility and fertilizing ability (Ramya et. al. 2011). Recently, the DeLeon lab has shown the expression of PMCA4 in the murine epididymis. However, no work has been done on the expression of nNOS in the extratesticular pathway of any mammalian species. Therefore, we set out to investigate the expression pattern of nNOS in the post‐testicular pathway and its role in sperm maturation. Here, we show the presence of nNOS in all three regions of the murine epididymis (caput, corpus, and cauda), including the basal and apical regions of the cells, via immunofluorescence for the first time. Western blotting results confirmed the expression of nNOS throughout the epididymis, and showed differential expression of nNOS, with highest expression in the corpus. Furthermore, preliminary immunofluorescence results suggest that the process of capacitation, in which the sperm experience a major influx of calcium, may influence the localization of nNOS. Experiments to isolate epididymosomes and determine if they are able to deliver nNOS to sperm are in progress.
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