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61.
Hu LY Ryder TR Rafferty MF Cody WL Lotarski SM Miljanich GP Millerman E Rock DM Song Y Stoehr SJ Taylor CP Weber ML Szoke BG Vartanian MG 《Bioorganic & medicinal chemistry letters》1999,9(6):907-912
Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown utility in several models of stroke and pain. We are especially interested in small molecule N-type calcium channel blockers for therapeutic use. Herein, we report a series of N,N-dialkyl-dipeptidylamines with potent functional activity at N-type VSCCs and in vivo efficacy. The synthesis, SAR, and pharmacological evaluation of this series are discussed. 相似文献
62.
The alcohol dehydrogenase (Adh) region from five planitibia subgroup
species of Hawaiian picture-wing Drosophila has been cloned. A total of 15
kb of DNA in and around the Adh gene has been compared among the five
species. Genetic distances were calculated to determine evolutionary
relationships. These distances agree with previous distances determined by
protein polymorphism and DNA hybridization techniques and can be
interpreted in terms of specific island colonization and speciation
(founder) events over the past 5 Myr. Examination of the restriction maps
of the cloned Adh region from the five species shows many instances of
small deletions, insertion of a transposable element in D. heteroneura, and
the existence of a highly variable region on the 3' side of the Adh gene.
Clustering relationships and rates of DNA change are calculated and
compared with the relationship found for other species of Drosophila.
相似文献
63.
In search for an alternative for nutritional antimicrobials in piglet feeding, the effects of adding whole Cuphea seeds, as a natural source of medium chain fatty acids (MCFA), with known antimicrobial effects, and an exogenous lipase to a weaner diet were studied. The foregut flora, the gut morphology, some digestive parameters and the zootechnical performance of weaned piglets were investigated. Thirty newly weaned piglets, initial weight 7.0 ± 0.4 kg, were divided according to litter, sex and weight in two groups (control diet; Cuphea+lipase diet). The Cuphea seeds (lanceolata and ignea) (50 g kg?1) were substituted for soybean oil (15 g kg?1), Alphacell (25 g kg?1) and soy protein isolate (10 g kg?1) in the control diet. Also 500 mg kg?1 microbial lipase was added to the Cuphea diet. The piglets were weighted individually on days 0, 3, 7, 14 and 16. Feed intake was recorded per pen during days 0 to 3, 3 to 7, 7 to 14 and 14 to 16. On day 7 five piglets of each experimental group were euthanized for counting the gastric and small intestinal gut flora and for gut morphology at two sites of the small intestine (proximal, distal). The results indicate a trend towards improved performances parameters by feeding Cuphea + lipase. The enzymic released MCFA (1.7 g kg?1 fresh gastric contents) tended to decrease the number of Coliforms in the proximal small intestine, but increased the number in the stomach and distal small intestine. With Cuphea, the number of Streptococci was significantly lower in small intestine, but not in the stomach, while the number of Lactobacilli was significantly lower in the distal small intestine and tended to be lower in the stomach and proximal small intestine. No differences between the diets were noted for the total anaerobic microbial load in the stomach or in the gut. Feeding Cuphea+lipase resulted in a significantly greater villus height (distal small intestine) and a lesser crypt depth (proximal and distal small intestine) and greater villus/crypt ratio depth (proximal and distal small intestine). The intra-epithelial lymphocyte (IEL) counts per 100 enterocytes were significantly decreased in the proximal small intestine and tended to decrease in the distal small intestine by feeding the Cuphea+lipase diet. Both phenomena are indicative for a more healthy and better functional state of the mucosa. Present results are in line with foregoing research, showing that manipulation of the gut ecosystem by the enzymic in situ released MCFA in the stomach and foregut can result in improved performances of the piglets, which makes the concept a potential alternative for in-feed nutritional antibiotics. 相似文献
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Margaret M. Schweri Phil Skolnick Michael F. Rafferty Kenner C. Rice Aaron J. Janowsky Steven M. Paul 《Journal of neurochemistry》1985,45(4):1062-1070
Saturable and stereoselective binding sites for [3H]threo-(+/-)-methylphenidate were characterized in rat brain membranes. The highest density of [3H]threo-(+/-)-methylphenidate binding sites was found in the synaptosomal fraction of corpus striatum. Scatchard analysis revealed a single class of noninteracting binding sites with an apparent dissociation constant (KD) of 235 nM and a maximum number of binding sites (Bmax) of 13.4 pmol/mg protein. Saturable, high-affinity binding of [3H]threo-(+/-)-methylphenidate to striatal synaptosomal membranes was dependent on the presence of sodium ions. A good correlation (r = 0.88; p less than 0.001) was observed between the potencies of various psychotropic drugs in displacing [3H]threo-(+/-)-methylphenidate from these sites and their potencies as inhibitors of [3H]3,4-dihydroxyphenylethylamine ( [3H]dopamine) uptake into striatal synaptosomes. A good correlation (r = 0.85; p less than 0.001) was also observed between the potencies of a series of ritalinic acid esters in inhibiting [3H]threo-(+/-)-methylphenidate binding to striatal synaptosomal membranes and their potencies as motor stimulants in mice. These observations suggest that the binding sites for [3H]threo-(+/-)-methylphenidate described here are associated with a dopamine uptake or transport complex, and that these sites may mediate the motor stimulant properties of ritalinic acid esters such as methylphenidate. 相似文献
67.
Phylogenetic screening of the human genome: identification of differentially hybridizing repetitive sequence families 总被引:1,自引:0,他引:1
The phi-screen, a method of phylogenetic screening, can be employed to
detect repetitive sequence families that differentially hybridize between
closely related species. Such differences may involve sequence divergence
or variations in copy number, including total presence versus absence of a
family of repeated DNA. We present the results of a phi-screen comparing
the human genome to that of the prosimian, Galago crassicaudatus. Three
human repetitive families that are divergent or not present in galago have
been detected. One of these families is described in detail; it is similar
among the anthropoids but is present in a lower copy number and/or
divergent form in prosimians. The family is clearly related to the
transposon-like human element (THE) described by Paulson et al. (1985).
THEs have long terminal repeats reminiscent of retroviruses but are unique
in that they have no sequence similarity to known mammalian retroviruses.
The sequence of a solo long terminal repeat, found unassociated with THE
internal sequence, is presented. This family member, THE p2, is bordered by
a 5-bp target-site repeat and is interrupted by the insertion of an Alu
element. A solo THE element sequenced by Wiginton et al. (1986) contains an
insertion of Alu at precisely the same position as does THE p2.
相似文献
68.
Nicole E. Rafferty Paul J. CaraDonna Laura A. Burkle Amy M. Iler Judith L. Bronstein 《Ecology and evolution》2013,3(9):3183-3193
Concern regarding the biological effects of climate change has led to a recent surge in research to understand the consequences of phenological change for species interactions. This rapidly expanding research program is centered on three lines of inquiry: (1) how the phenological overlap of interacting species is changing, (2) why the phenological overlap of interacting species is changing, and (3) how the phenological overlap of interacting species will change under future climate scenarios. We synthesize the widely disparate approaches currently being used to investigate these questions: (1) interpretation of long‐term phenological data, (2) field observations, (3) experimental manipulations, (4) simulations and nonmechanistic models, and (5) mechanistic models. We present a conceptual framework for selecting approaches that are best matched to the question of interest. We weigh the merits and limitations of each approach, survey the recent literature from diverse systems to quantify their use, and characterize the types of interactions being studied by each of them. We highlight the value of combining approaches and the importance of long‐term data for establishing a baseline of phenological synchrony. Future work that scales up from pairwise species interactions to communities and ecosystems, emphasizing the use of predictive approaches, will be particularly valuable for reaching a broader understanding of the complex effects of climate change on the phenological overlap of interacting species. It will also be important to study a broader range of interactions: to date, most of the research on climate‐induced phenological shifts has focused on terrestrial pairwise resource–consumer interactions, especially those between plants and insects. 相似文献
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70.
Association of heparan sulfate proteoglycan and laminin with the cytoskeleton in rat liver 总被引:1,自引:0,他引:1
Rats were injected with 35SO4 and after 2 h their livers were removed and used to prepare a detergent-insoluble cytoskeleton fraction. Spectrin, cytokeratins, and actin were major protein components of the isolated cytoskeletons. The cytoskeleton fraction accounted for approximately 14% of the total trichloroacetic acid-insoluble 35SO4 radioactivity incorporated into the liver. The cytoskeleton-associated radioactivity was present in a single species of macromolecule. This molecule was not present to a significant extent in the detergent-soluble fraction containing the cell supernatant and dissolved membrane proteins. Further characterization revealed the cytoskeleton-associated molecule was a heparan sulfate proteoglycan: it was eluted from a Sepharose CL-4B column under denaturing conditions at Kav = 0.4; following mild alkaline hydrolysis the radioactivity was eluted at a Kav = 0.7; when this material was subjected to nitrous acid hydrolysis all of the radioactivity was eluted near the column included volume. The isolated cytoskeletons contained attached nuclei. Pure nuclei isolated without associated cytoskeletal elements contained less than 1% of the total liver trichloroacetic acid-insoluble 35SO4 radioactivity and no detectable heparan sulfate proteoglycan. These results suggested that other matrix proteins might be associated with the liver cytoskeleton. When the subcellular distribution of laminin was monitored by immunostaining proteins transferred to nitrocellulose, laminin was detected exclusively in the cytoskeleton fraction. These results provide evidence for an association between extracellular connective tissue proteins and intracellular structural proteins. 相似文献