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排序方式: 共有349条查询结果,搜索用时 15 毫秒
271.
272.
Holsworth DD Jalaie M Belliotti T Cai C Collard W Ferreira S Powell NA Stier M Zhang E McConnell P Mochalkin I Ryan MJ Bryant J Li T Kasani A Subedi R Maiti SN Edmunds JJ 《Bioorganic & medicinal chemistry letters》2007,17(13):3575-3580
Novel 2,4-diaminopyrimidine-based small molecule renin inhibitors are disclosed. Through high throughput screening, parallel synthesis, X-ray crystallography, and structure based drug design, we have developed the first non-chiral, non-peptidic, small molecular template to possess moderate potency against renin. The designed compounds consist of a novel 6-ethyl-5-(1,2,3,4-tetrahydroquinolin-7-yl)pyrimidine-2,4-diamine ring system that exhibit moderate potency (IC(50): 91-650 nM) against renin while remaining 'Rule-of-five' compliant. 相似文献
273.
Yuri A. Blednov Michal Bajo Amanda J. Roberts Adriana J. Da Costa Mendy Black Stephanie Edmunds Jody Mayfield Marisa Roberto Gregg E. Homanics Amy W. Lasek Robert J. Hitzemann Robert A. Harris 《Genes, Brain & Behavior》2019,18(6)
The voltage‐gated sodium channel subunit β4 (SCN4B) regulates neuronal activity by modulating channel gating and has been implicated in ethanol consumption in rodent models and human alcoholics. However, the functional role for Scn4b in ethanol‐mediated behaviors is unknown. We determined if genetic global knockout (KO) or targeted knockdown of Scn4b in the central nucleus of the amygdala (CeA) altered ethanol drinking or related behaviors. We used four different ethanol consumption procedures (continuous and intermittent two‐bottle choice (2BC), drinking‐in‐the dark and chronic intermittent ethanol vapor) and found that male and female Scn4b KO mice did not differ from their wild‐type (WT) littermates in ethanol consumption in any of the tests. Knockdown of Scn4b mRNA in the CeA also did not alter 2BC ethanol drinking. However, Scn4b KO mice showed longer duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital and ketamine. KO mice showed slower recovery to basal levels of handling‐induced convulsions after ethanol injection, which is consistent with the increased sedative effects observed in these mice. However, Scn4b KO mice did not differ in the severity of acute ethanol withdrawal. Acoustic startle responses, ethanol‐induced hypothermia and clearance of blood ethanol also did not differ between the genotypes. There were also no functional differences in the membrane properties or excitability of CeA neurons from Scn4b KO and WT mice. Although we found no evidence that Scn4b regulates ethanol consumption in mice, it was involved in the acute hypnotic effects of ethanol and other sedatives. 相似文献
274.
275.
Lactate dehydrogenase-B (ldh-b) encodes a metabolic enzyme (LDH-B) which plays an important role in maintaining aerobic performance and in thermal acclimation and/or adaptation of fish. As the first step in understanding the effect this enzyme has on the ability of tropical coral reef fishes to cope with thermal stress, we characterized both coding and non-coding regions of ldh-b in two congeneric perciformes, Plectropomus leopardus and Plectropomus laevis. Ldh-b was 4666 and 4539bp in length in P. leopardus and P. laevis, respectively, with coding regions comprising 1005bp in both species. We report a high level of sequence homology between the coding regions of ldh-b in these two species, with 98.1% identity of nucleotides corresponding to 100% amino acid identity between the deduced protein sequences. Comparison between non-coding (intron) regions of both species revealed the presence of several indels, despite the high level of homology observed (95.9% identity of intron nucleotides). Potential regulatory motifs and elements, including twenty-six simple sequence repeat motifs (mono-, di-, tri- and tetranucleotide) and twenty-three putative microRNA elements are identified within the introns of both species, further supporting recent demonstrations that such short motifs and elements exhibit widespread positioning throughout non-coding regions of the genome. This novel characterization of ldh-b in these two coral reef fishes allows for a wide range of future studies (e.g. analytical comparisons of ldh-b and LDH-B among different fish genera from different thermal environments and habitats). 相似文献
276.
John R. Malinowski Danielle L. Laval-Martin Leland N. Edmunds Jr. 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1985,155(2):257-267
Summary The free-running circadian rhythm of cell division in the algal flagellate,Euglena gracilis (Z) was perturbed by 3-h light signals of varying intensities imposed at different circadian times (CT). Light pulses within the range of 700 to 7,500 lux were found to yield the same strong (Type 0) phase response curve (PRC) comprising both advance and delaye phase shifts as great as 15 h. Dark signals generated a PRC of reduced amplitude with very little, if any, phase advance being observed. Light perturbations of lower intensity, however, elicited quite different responses if applied at a quite specific circadian time: A 40- to 400-lux pulse given at approximately CT 0 (late subjective night) induced total arrhythmicity, and the culture reverted to asynchronous, exponential growth. Different degrees of arryhtmicity were induced by the same low-intensity perturbations (I
*) given slightly before or after this sensitive phase point (T
*), but if imposed at other circadian times, they generated normal type 0 phase resetting. The demonstration of the existence of this critical pulse (T
*,I
*) provides further evidence that the cell division cycle ofEuglena (and presumably other microorganisms) is regulated by a circadian oscillator and, in particular, by one having limit cycle dynamics.Abbreviations
LL
continuous illumination
-
DD
continuous darkness
-
LD
light-dark cycle
-
LD
x, y, light-dark cycle comprisingx h of light andy h of dark
-
t
period of a LD cycle
-
CO
circadian oscillator
-
CR
circadian rhythm
-
period of a freerunning circadian rhythm in constant conditions (taken here to be the time between onsets of cell division in a population of cells
- R
phase marker, or phase reference point (here, the onset of the division burst)
-
phase of the rhythm
-
change in phase (phase shift)
-
new phase attained after phase shift
-
CT
circadian time (CT 0 indicates the phase point of a free-running rhythm that has been normalized to 24 h which corresponds to that occurring at the onset of light in aLD:12, 12 reference cycle)
-
PRC
phase response curve (plot of phase shift engendered by a perturbation as a function of the circadian time of its application)
-
T
*,I
*)
coordinates of an annihilating (light) stimulus given at a critical circadian time (T
*, corresponding to the singularity point) and having a critical strength (I
*)
-
CDC
cell division cycle
-
average generation (doubling) time of a cell population
-
average step-size, or factorial increase in cell titer (plateau to plateau) after a phased division burst
Dedicated to Prof. Colin S. Pittendrigh on only his 65th birthday 相似文献
277.
278.
The respiration rate of the Caribbean reef coral Porites porites was shown to increase by a mean of 39% above the pre-illumination respiration rate when exposed for 3 h to light equivalent to that at 10 m depth on the reef. When exposed to a subsaturating irradiance of 140 E m-2 s-1, the respiration rate increased successively in a curvilinear form to 58% greater than the preillumination respiration rate after 80 min. It is suggested that this increase may be analogous to the elevation in respiration rate observed in cnidarians and other animals after feeding on particulate food and may represent energy expenditure in growth. If this elevated respiration rate is maintained over the whole of the daytime period, the current methodologies used for determining carbon and energy budgets in symbiotic cnidarians result in an underestimation of the 24 h energy expenditure. 相似文献
279.
M E Edmunds G I Russell R F Bing H Thurston J D Swales 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1987,184(1):107-112
The rapid fall in blood pressure after removal of the constricting clip in two-kidney one-clip (2K-1C) hypertension in the rat is not fully explained by inhibition of the renin-angiotensin system or change in sodium balance. It has been postulated that compounds released in the renal venous effluent following unclipping of 2K-1C rats have a central opiate-like action and endogenous opioids are recognized to have profound hypotensive properties. To investigate this, we removed the clip from, or performed a sham operation in, early phase (less than 6 weeks) 2K-1C hypertensive rats during an infusion of naloxone, an opioid antagonist, or vehicle alone. The infusion of naloxone did not affect the pattern of blood pressure fall in either unclipped or sham-operated rats. Both naloxone-treated and control groups were similarly normotensive at 24 hr postoperation, the MAP being significantly lower than in the sham-operated groups, which regained previously hypertensive levels. Heart rate was unchanged 24 hr postoperatively in all groups. Morphine-induced bradycardia and hypotension were significantly reduced by naloxone infusion. Thus, naloxone infusion had no effect on blood pressure or heart rate in either the sham-operated or the unclipped groups, indicating that endogenous opioids do not have a major role in the reversal of renovascular hypertension under these circumstances. 相似文献
280.
Ramesh C. Adlakha Victor R. Villanueva Régis Calvayrac Leland N. Edmunds 《Archives of biochemistry and biophysics》1980,201(2):660-668
A trimodal change in the cellular levels of three major polyamines: spermidine, N,N′-bis(3-aminopropyl)-1, 3-propanediamine (BAP) and 3,3′-diaminodipropylamine (DAD) was observed during two successive cell cycles in synchronously dividing cultures of the algal flagellate, Euglena gracilis Z photoautotrophically grown in a 24-h light-dark cycle. The intracellular levels of these three polyamines decreased as cells divided and then were enhanced as cells exited the G1 phase and proceeded through the S and G2 phases. Spermidine, BAP and DAD concentrations increased about 2.5-fold during the S phase. Putrescine and 1,3-diaminopropane levels did not vary significantly. One peak of polyamine synthesis occurred in the G1 phase prior to DNA synthesis, followed by a second more important peak during the S-G2 phases before cell division; both peaks were observed during the light period. A third minor peak was observed during the pre-G1 (or G0) phase in the dark period after mitosis had been completed. In contrast, when the cells attained the “stationary” phase of growth, there was no significant increase in the content of polyamines during the light period although spermidine and BAP increased slightly twice during the dark period (putrescine and 1,3-diaminopropane and DAD levels remained almost constant). To ascertain whether the synthesis of polyamines was merely a direct effect of the photoperiod, parallel experiments with synchronous cultures were carried out in the presence and absence of 3-(3,4-dichlorophenyl)-1, 1-dimethyl urea, a photosynthetic inhibitor. Although a slight decrease in the concentration of polyamines was observed, the three maxima of polyamines synthesis were observed as in normal cultures. These results clearly suggest that polyamine biosynthesis is closely related to DNA replication and cell division in Euglena cells. 相似文献