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101.
Wayne A. Cass Nancy R. Zahniser Karen A. Flach Greg A. Gerhardt 《Journal of neurochemistry》1993,61(6):2269-2278
In vivo electrochemistry was used to investigate the mechanisms contributing to the clearance of locally applied dopamine in the dorsal striatum and nucleus accumbens of urethane-anesthetized rats. Chronoamperometric recordings were continuously made at 5 Hz using Nafion-coated carbon fiber electrodes. When a finite amount of dopamine was pressure-ejected at 5-min intervals from a micropipette adjacent to the electrode, transient and reproducible dopamine signals were detected. Substitution of L-a-methyldopamine, a substrate for the dopamine transporter but not for monoamine oxidase, for dopamine in the micropipette did not substantially alter the time course of the resulting signals. This indicates that metabolism of locally applied dopamine to 3,4-dihydroxyphenylacetic acid is not responsible for the decline in the dopamine signal. Similarly, changing the applied oxidation potential from ±0.45 to ±0.80 V, which allows for detection of 3-methoxytyramine formed from dopamine via catechol-O-methyltransferase, had little effect on signal amplitude or time course. In contrast, lesioning the dopamine terminals with 6-hydroxydopamine, or locally applying the dopamine uptake inhibitors cocaine or nomifensine before pressure ejection of dopamine, significantly increased the amplitude and time course of the dopamine signals in both regions. The effects of cocaine and nomifensine were greater in the nucleus accumbens than in the dorsal striatum. Local application of lidocaine and procaine had no effect on the dopamine signals. Initial attempts at modeling resulted in curves that were in qualitative agreement with our experimental findings. Taken together, these data indicate that (1) uptake of dopamine by the neuronal dopamine transporter, rather than metabolism or diffusion, is the major mechanism for clearing locally applied dopamine from the extracellular milieu of the dorsal striatum and nucleus accumbens, and (2) the nucleus accumbens is more sensitive to the effects of inhibitors of dopamine uptake than is the dorsal striatum. 相似文献
102.
Nancy Minugh-Purvis 《American journal of physical anthropology》1993,92(4):449-461
Reexamination of the immature Upper Pleistocene hominid maxilla from Mugharet el-'Aliya (Tangier), Morocco is undertaken in light of new evidence on the growth and development of Upper Pleistocene hominids. Metric and qualitative comparisons were made with 17 immature Upper Pleistocene maxillae, and with a recent Homo sapiens sapiens sample. No unambiguous criteria for aligning the maxilla with Neandertals were found, although one character, the degree of maxillary flexion on the zygoma, strongly suggests that this child could be a representative of H. s. sapiens. The probable lack of a canine fossa in Mugharet el-'Aliya 1, the primary criterion used previously to align it with Neandertals, cannot be accurately extrapolated to its adult form from this juvenile. The present evidence suggests that it is inappropriate to refer to this fossil as “Neandertal-like” or as a North African “neandertaloid.” Thus, the Tangier maxilla should not be cited as evidence for the presence of Neandertal facial features in North Africa during the Upper Pleistocene. © 1993 Wiley-Liss, Inc. 相似文献
103.
The Duwamish River Floating Wetlands project designed, built, and deployed constructed floating wetlands in the estuary of the urban Duwamish River in Seattle, Washington, during the 2019 and 2020 outmigration seasons for juvenile salmon. Using a “safe-to-fail” methodology and adaptive management strategies, these innovative floating wetland prototypes were custom designed to provide the native plants, invertebrates and slow water habitat that juvenile salmon require during their transition from fresh to salt water, and were monitored for these outcomes. This paper will provide insight into the prototype designs, adaptive management strategies and plant performance, and unique public-private-academic-community partnerships that supported 2 years of design and research. 相似文献
104.
Summary DNA fingerprints generated by the Jeffreys' probes, 33.6 and 33.15, indicated the presence of minisatellite-like sequences
in the red clover genome. The fingerprints generated by probe 33.6 gave less background and fewer but better defined bands
than those obtained with probe 33.15. Assay of a regenerative somaclonal variant (F49R) by DNA fingerprinting with probe 33.6
detected mutation that was unlinked to the regenerative trait. The fingerprints obtained under the applied conditions also
demonstrated genetic stability of consecutive generations of the regenerants in tissue culture. DNA fingerprints of F1 plants revealed that each polymorphic band was inherited from either one or the other parent. Both probes distinguished individual-specific
genotypes in seven cultivars of red clover. Greater variability in DNA fingerprints was detected between (V=0.899) than within
(0.417≤V≤0.548) cultivars. 相似文献
105.
Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages 总被引:21,自引:5,他引:16
Nancy A. Buchmeier Craig J. Lipps Magdalene Y. H. So Fred Heffron 《Molecular microbiology》1993,7(6):933-936
Mutations in the genes recA and recBC were constructed in the virulent Salmonella typhimurium strain 14028s. Both the recA and recBC mutants were attenuated in mice. The mutants were also sensitive to killing by macrophages in vitro. The recombination mutants were no longer macrophage sensitive in a variant line of J774 macrophage-like cells that fail to generate superoxide. This suggests that repair of DNA damage by Salmonella is necessary for full virulence in vivo and that the oxidative burst of phagocytes is one source of such DNA damage. 相似文献
106.
Adnan M. M. Mjalli Kevin T. Chapman Malcolm MacCoss Nancy A. Thornberry 《Bioorganic & medicinal chemistry letters》1993,3(12):2689-2692
Phenylalkyl ketones are potent reversible inhibitors of interleukin-1β converting enzyme (ICE). The extended alkyl chain ketones AcTyrValAlaAspCO(CH2)nPh display increased potency over the simple aryl ketone. In particular, the tetrapeptide AcTyrValAlaAspCOPh has a Ki of 10μM while AcTyrValAlaAspCO(CH2)5Ph has a Ki of 18.5nM. 相似文献
107.
Rosamarie Frieri William Fisher Rosenberger Nancy Flournoy Zhantao Lin 《Biometrics》2023,79(3):2565-2576
When there is a predictive biomarker, enrichment can focus the clinical trial on a benefiting subpopulation. We describe a two-stage enrichment design, in which the first stage is designed to efficiently estimate a threshold and the second stage is a “phase III-like” trial on the enriched population. The goal of this paper is to explore design issues: sample size in Stages 1 and 2, and re-estimation of the Stage 2 sample size following Stage 1. By treating these as separate trials, we can gain insight into how the predictive nature of the biomarker specifically impacts the sample size. We also show that failure to adequately estimate the threshold can have disastrous consequences in the second stage. While any bivariate model could be used, we assume a continuous outcome and continuous biomarker, described by a bivariate normal model. The correlation coefficient between the outcome and biomarker is the key to understanding the behavior of the design, both for predictive and prognostic biomarkers. Through a series of simulations we illustrate the impact of model misspecification, consequences of poor threshold estimation, and requisite sample sizes that depend on the predictive nature of the biomarker. Such insight should be helpful in understanding and designing enrichment trials. 相似文献
108.
Jeffries et al. (2018) investigated testing for a treatment difference in the setting of a randomized clinical trial with a single outcome measured longitudinally over a series of common follow-up times while adjusting for covariates. That paper examined the null hypothesis of no difference at any follow-up time versus the alternative of a difference for at least one follow-up time. We extend those results here by considering multivariate outcome measurements, where each individual outcome is examined at common follow-up times. We consider the case where there is interest in first testing for a treatment difference in a global function of the outcomes (e.g., weighted average or sum) with subsequent interest in examining the individual outcomes, should the global function show a treatment difference. Testing is conducted for each follow-up time and may be performed in the setting of a group sequential trial. Testing procedures are developed to determine follow-up times for which a global treatment difference exists and which individual combinations of outcome and follow-up time show evidence of a difference while controlling for multiplicity in outcomes, follow-up, and interim analyses. These approaches are examined in a study evaluating the effects of tissue plasminogen activator on longitudinally obtained stroke severity measurements. 相似文献
109.
110.
Florence W. L. Tsui Hing-Wo Tsui Samuel Mok Irena Mlinaric Neal G. Copeland Debra J. Gilbert Nancy A. Jenkins Katherine A. Siminovitch 《Genomics》1993,15(3)
Stefins or Type 1 cystatins belong to a large, evolutionarily conserved protein superfamily, the members of which inhibit the papain-like cysteine proteinases. We report here on the molecular cloning and chromosomal localization of three newly identified members of the murine stefin gene family. These genes, designated herein as mouse stefins 1, 2, and 3, were isolated on the basis of their relatively increased expression in moth-eaten viable compared to normal congenic mouse bone marrow cells. The open reading frames of the stefin cDNAs encode proteins of approximately 11.5 kDa that show between 50 and 92% identity to sequences of stefins isolated from various other species. Data from Southern analysis suggest that the murine stefin gene family encompasses at least 6 and possibly 10-20 members, all of which appear to be clustered in the genome. Analysis of interspecific backcross mice indicates that the genes encoding the three mouse stefins all map to mouse chromosome 16, a localization that is consistent with the recent assignment of the human stefin A gene to a region of conserved homology between human chromosome 3q and the proximal region of mouse chromosome 16. 相似文献