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161.
Lander?Goenechea Gerhard?von der?EmdeEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2004,190(11):907-922
Mormyrid fish use active electrolocation to detect and analyze objects. The electrosensory lateral line lobe in the brain receives input from electroreceptors and an efference copy of the command to discharge the electric organ. In curarized fish, we recorded extracellularly from neurons of the electrosensory lateral line lobe while stimulating in the periphery with either a local point stimulus or with a more natural whole-body stimulus. Two classes of neurons were found: (1) three types of E-cells, which were excited by a point stimulus; and (2) two types of I-cells, which were inhibited by point stimulus and responded with excitation to the electric organ corollary discharge. While all neurons responded to a point stimulus, only one out of two types of I-units and two of the three types of E-units changed their firing behavior to a whole-body stimulus or when an object was present. In most units, the responses to whole-body stimuli and to point stimuli differed substantially. Many electrosensory lateral line lobe units showed neural plasticity after prolonged sensory stimulation. However, plastic effects during whole body stimulation were often unlike those occurring during point stimuli, suggesting that under natural conditions electrosensory lateral line lobe network effects play an important role in shaping neural plasticity. 相似文献
162.
Neel DA Brown ML Lander PA Grese TA Defauw JM Doti RA Fields T Kelley SA Smith S Zimmerman KM Steinberg MI Jadhav PK 《Bioorganic & medicinal chemistry letters》2005,15(10):2553-2557
Syntheses and SAR studies of 3,3-bisaryloxindole analogues provided potent mineralocorticoid receptor (MR) antagonists that were selective over other steroid nuclear hormone receptors. 相似文献
163.
Norman BH Lander PA Gruber JM Kroin JS Cohen JD Jungheim LN Starling JJ Law KL Self TD Tabas LB Williams DC Paul DC Dantzig AH 《Bioorganic & medicinal chemistry letters》2005,15(24):5526-5530
Structure–activity relationship (SAR) studies on the tricyclic isoxazole series of MRP1 modulators have resulted in the identification of potent and selective inhibitors containing cyclohexyl-based linkers. These studies ultimately identified compound 21b, which reverses drug resistance to MRP1 substrates, such as doxorubicin, in HeLa-T5 cells (EC50 = 0.093 μM), while showing no inherent cytotoxicity. Additionally, 21b inhibits ATP-dependent, MRP1-mediated LTC4 uptake into membrane vesicles prepared from the MRP1-overexpressing HeLa-T5 cells (EC50 = 0.064 μM) and shows selectivity (1115-fold) against the related transporter, P-glycoprotein, in HL60/Adr and HL60/Vinc cells. Finally, when dosed in combination with the oncolytic MRP1 substrate vincristine, 21b showed tumor regression and growth delay in MRP1-overexpressing tumors in vivo. 相似文献
164.
Sabeti PC Walsh E Schaffner SF Varilly P Fry B Hutcheson HB Cullen M Mikkelsen TS Roy J Patterson N Cooper R Reich D Altshuler D O'Brien S Lander ES 《PLoS biology》2005,3(11):e378
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5), they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome. 相似文献
165.
Natarajan P Lander GC Shepherd CM Reddy VS Brooks CL Johnson JE 《Nature reviews. Microbiology》2005,3(10):809-817
Virus structures are megadalton nucleoprotein complexes with an exceptional variety of protein-protein and protein-nucleic-acid interactions. Three-dimensional crystal structures of over 70 virus capsids, from more than 20 families and 30 different genera of viruses, have been solved to near-atomic resolution. The enormous amount of information contained in these structures is difficult to access, even for scientists trained in structural biology. Virus Particle Explorer (VIPER) is a web-based catalogue of structural information that describes the icosahedral virus particles. In addition to high-resolution crystal structures, VIPER has expanded to include virus structures obtained by cryo-electron microscopy (EM) techniques. The VIPER database is a powerful resource for virologists, microbiologists, virus crystallographers and EM researchers. This review describes how to use VIPER, using several examples to show the power of this resource for research and educational purposes. 相似文献
166.
167.
Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. 总被引:33,自引:18,他引:15
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Homozygosity mapping is a powerful strategy for mapping rare recessive traits in children of consanguineous marriages. Practical applications of this strategy are currently limited by the inability of conventional linkage analysis software to compute, in reasonable time, multipoint LOD scores for pedigrees with inbreeding loops. We have developed a new algorithm for rapid multipoint likelihood calculations in small pedigrees, including those with inbreeding loops. The running time of the algorithm grows, at most, linearly with the number of loci considered simultaneously. The running time is not sensitive to the presence of inbreeding loops, missing genotype information, and highly polymorphic loci. We have incorporated this algorithm into a software package, MAPMAKER/HOMOZ, that allows very rapid multipoint mapping of disease genes in nuclear families, including homozygosity mapping. Multipoint analysis with dozens of markers can be carried out in minutes on a personal workstation. 相似文献
168.
Paul Dijkstra AD. H. M. C. Schapendonk KO. Groenwold Marinus Jansen Siebe C. Van De Geijn 《Global Change Biology》1999,5(5):563-576
Winter wheat was grown at ambient and elevated (ambient plus 350 μL L–1) CO2 concentrations in open top chambers and in field-tracking sun-lit climatized enclosures (elevated is 718 μL L–1). There was no significant effect of CO2 concentration on sheath, leaf and root biomass and leaf area in the early spring (January to April). 24-h canopy CO2 exchange rate (CCER) was not significantly affected either. However, elevated CO2 concentration increased CCER at midday, decreased evapotranspiration rate and increased instantaneous water-use-efficiency during early spring. Leaf, sheath and root nitrogen concentration per unit dry weight decreased and nonstructural carbohydrate concentration increased under elevated CO2, and N-uptake per unit ground area decreased significantly (– 22%) towards the end of this period. These results contrast with results from the final harvest, when grain yield and biomass were increased by 19% under elevated CO2. N concentration per dry weight was reduced by 5%, but N-uptake per unit ground area was significantly higher (+ 11%) for the elevated CO2 treatment. 24-h and midday-CCER increased significantly more in late spring (period of 21 April to 30 May) (respectively by + 40% and 53%) than in the early spring (respectively 5% and 19%) in response to elevated CO2. Midday evapotranspiration rate was reduced less by elevated CO2 in the late spring (– 13%) than in early spring (– 21%). The CO2 response of midday and 24-h CCER decreased again (+ 27% and + 23% resp.) towards the end of the growing season. We conclude that the low response to CO2 concentration during the early spring was associated with a growth-restriction, caused by low temperature and irradiance levels. The reduction of nitrogen concentration, the increase of nonstructural carbohydrate, and the lower evapotranspiration indicated that CO2 did have an effect towards the end of early spring, but not on biomass accumulation. Regression analysis showed that both irradiance and temperature affected the response to CO2. 相似文献
169.
Ca2+, annexins, and GTP modulate exocytosis from maize root cap protoplasts 总被引:3,自引:0,他引:3
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Protoplasts isolated from root cap cells of maize were shown to secrete fucose-rich polysaccharides and were used in a patch-clamp study to monitor changes in whole-cell capacitance. Ca2+ was required for exocytosis, which was measured as an increase in cell capacitance during intracellular dialysis with Ca2+ buffers via the patch pipette. Exocytosis was stimulated significantly by small increases above normal resting [Ca2+]. In the absence of Ca2+, protoplasts decreased in size. In situ hybridization showed significant expression of the maize annexin p35 in root cap cells, differ-entiating vascular tissue, and elongating cells. Dialysis of protoplasts with maize annexins stimulated exocytosis at physiological [Ca2+], and this could be blocked by dialysis with antibodies specific to maize annexins. Dialysis with milli-molar concentrations of GTP strongly inhibited exocytosis, causing protoplasts to decrease in size. GTPgammaS and GDPbetaS both caused only a slight inhibition of exocytosis at physiological Ca2+. Protoplasts were shown to internalize plasma membrane actively. The results are discussed in relation to the regulation of exocytosis in what is usually considered to be a constitutively secreting system; they provide direct evidence for a role of annexins in exocytosis in plant cells. 相似文献
170.
CEES GRASHOFF † PAUL DIJKSTRA † SANDERINE NONHEBEL ‡ AD H.C.M. SCHAPENDONK† SIEBE C. VAN DE GEIJN† 《Global Change Biology》1995,1(6):417-428
The effect of elevated [CO2] on the productivity of spring wheat, winter wheat and faba bean was studied in experiments in climatized crop enclosures in the Wageningen Rhizolab in 1991–93. Simulation models for crop growth were used to explore possible causes for the observed differences in the CO2 response. Measurements of the canopy gas exchange (CO2 and water vapour) were made continuously from emergence until harvest. At an external [CO2] of 700 μmol mol?1 Maximum Canopy CO2 Exchange Rate (CCERmax) at canopy closure was stimulated by 51% for spring wheat and by 71% for faba bean. At the end of the growing season, above ground biomass increase at 700 μmol mol?1 was 58% (faba bean), 35% (spring wheat) and 19% (winter wheat) and the harvest index did not change. For model exploration, weather data sets for the period 1975-88 and 1991–93 were used, assuming adequate water supply and [CO2] at 350 and 700 μmol mol?1. For spring wheat the simulated responses (35–50%) were at the upper end of the experimental results. In agreement with experiments, simulations showed smaller responses for winter wheat and larger responses for faba bean. Further model explorations showed that this differential effect in the CO2 response may not be primarily due to fundamental physiological differences between the crops, but may be at least partly due to differences in the daily air temperatures during comparable stages of growth of these crops. Simulations also showed that variations between years in CO2 response can be largely explained by differences in weather conditions (especially temperature) between growing seasons. 相似文献