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101.
102.
Experiments are described that characterize the nature of the stimulus leading to lymphocyte-induced angiogenesis (LIA), a reaction previously shown to reflect a local in vivo graft-vs-host reaction. The studies demonstrate that circulating cells of the host animal provide the stimulation essential for activation of donor lymphocytes and that the major allogeneic stimulus in congenic lines of mice is correlated with I-region disparity, primarily associated with IA-controlled determinants. The results are readily compatible with the hypothesis that is proposed that LIA is in large part of the consequence of the release of soluble mediators or lymphokines that may act either directly on endothelial cells or indirectly by activating macrophages, which in turn generate the vascular reaction. 相似文献
103.
104.
A genetic locus controlling the electrophoretic mobility of an acid phosphatase in mouse kidney is described. This locus, called acid phosphatase-kidney (Apk), is not expressed in erythrocytes, liver, spleen, heart, lung, brain, skeletal muscle, stomach, or testes. The product of Apk hydrolyzes the substrate naphthol AS-MX phosphoric acid but is not active on a-naphthylphosphate or 4-methylumbelliferylphosphate. It is not inactivated by 50 C for 1 hr, nor is its electrophoretic mobility altered by incubation with neuraminidase. The locus is invariant among 31 inbred strains (Apk
a), with a variant allele (Apk
m) observed only in Mus musculus molossinus. Codominant expression was observed in F1 hybrids of M. m. molossinus and inbred strains. Apk was mapped on Chr 10, near the neurological mutant waltzer (v).This work was supported by Contract NO1-ES42159 from the National Institute of Environmental Health Sciences and by Grant 1-476 from the National Foundation—March of Dimes. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care. 相似文献
105.
106.
Darin Andrew Croft Federico Anaya David Auerbach Carmala Garzione Bruce J. MacFadden 《Journal of Mammalian Evolution》2009,16(3):175-198
We provide the first faunal report for the early/middle Miocene fauna of Cerdas, Bolivia (16.5–15.3 Ma; 20° 52′ S, 66° 19′ W), based primarily on new specimens collected in 2007. As many as twelve species of mammals in nine families are represented. Notoungulates include Palyeidodon obtusum (Toxodontidae), Protypotherium cf. attenuatum and Protypotherium sp. nov. (Interatheriidae), ‘Plesiotypotherium’ minus and possibly Microtypotherium choquecotense (Mesotheriidae), and Hegetotherium? sp. nov. (Hegetotheriidae). Xenarthrans include Stenotatus planus and Prozaedyus sp. (Cingulata: Dasypodidae), Peltephilidae gen. et sp. nov. (Cingulata), and Xyophorus cf. bondesioi (Pilosa: Nothrotheriidae). A new species of litoptern is also present (Macraucheniidae) as well as an unidentified rodent (Chinchillidae: Lagostominae). Two of these Cerdas species occur in Friasian sensu stricto/Colloncuran SALMA faunas of Patagonia, and perhaps one in Santacrucian SALMA faunas. Among middle latitude localities, Cerdas resembles Chucal, Chile (late early Miocene, Santacrucian SALMA) in community composition (e.g., abundant mesotheriids, few rodent species), but has no species in common; it shares one species with Quebrada Honda, Bolivia (middle Miocene, Laventan SALMA), and perhaps as many as three more. These observations indicate that Cerdas is not referable to the Santacrucian, and that the upper limit of this SALMA in the middle latitudes falls somewhere between 17.5 Ma (the top of Chucal) and 16.5 Ma (the base of Cerdas). Based on the range of dates proposed for the youngest Santacrucian intervals in Patagonia, a diachronous offset of up to 2.1 Ma may exist at this point in the SALMA sequence between middle and high latitude faunas. 相似文献
107.
Agustin Casimiro-Garcia Christopher F. Bigge Jo Ann Davis Teresa Padalino James Pulaski Jeffrey F. Ohren Patrick McConnell Christopher D. Kane Lori J. Royer Kimberly A. Stevens Bruce Auerbach Wendy Collard Christine McGregor Kun Song 《Bioorganic & medicinal chemistry》2009,17(20):7113-7125
The synthesis of a new series of phenylpropanoic acid derivatives incorporating an heteroaryl group at the α-position and their evaluation for binding and activation of PPARα and PPARγ are presented in this report. Among the new compounds, (S)-3-{4-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-phenyl}-2-1,2,3-triazol-2-yl-propionic acid (17j), was identified as a potent human PPARα/γ dual agonist (EC50 = 0.013 and 0.061 μM, respectively) with demonstrated oral bioavailability in rat and dog. 17j was shown to decrease insulin levels, plasma glucose, and triglycerides in the ZDF female rat model. In the human apolipoprotein A-1/CETP transgenic mouse model 17j produced increases in hApoA1 and HDL-C and decreases in plasma triglycerides. The increased potency for binding and activation of both PPAR subtypes observed with 17j when compared to previous analogs in this series was explained based on results derived from crystallographic and modeling studies. 相似文献
108.
Salvador Casares Eiso AB Henk Eshuis Obdulio Lopez-Mayorga Nico AJ van Nuland Francisco Conejero-Lara 《BMC structural biology》2007,7(1):22
Background
SH3 domains are small protein modules of 60–85 amino acids that bind to short proline-rich sequences with moderate-to-low affinity and specificity. Interactions with SH3 domains play a crucial role in regulation of many cellular processes (some are related to cancer and AIDS) and have thus been interesting targets in drug design. The decapeptide APSYSPPPPP (p41) binds with relatively high affinity to the SH3 domain of the Abl tyrosine kinase (Abl-SH3), while it has a 100 times lower affinity for the α-spectrin SH3 domain (Spc-SH3). 相似文献109.
P V Dimanlig S C Faber W Auerbach H P Makarenkova R A Lang 《Development (Cambridge, England)》2001,128(22):4415-4424
110.
Agonists are evaluated by a concentration-response curve (CRC), with a midpoint (EC50) that indicates potency, a high-concentration asymptote that indicates efficacy, and a low-concentration asymptote that indicates constitutive activity. A third agonist attribute, efficiency (η), is the fraction of binding energy that is applied to the conformational change that activates the receptor. We show that η can be calculated from EC50 and the asymptotes of a CRC derived from either single-channel or whole-cell responses. For 20 agonists of skeletal muscle nicotinic receptors, the distribution of η-values is bimodal with population means at 51% (including acetylcholine, nornicotine, and dimethylphenylpiperazinium) and 40% (including epibatidine, varenicline, and cytisine). The value of η is related inversely to the size of the agonist’s headgroup, with high- versus low-efficiency ligands having an average volume of 70 vs. 102 Å3. Most binding site mutations have only a small effect on acetylcholine efficiency, except for αY190A (35%), αW149A (60%), and those at αG153 (42%). If η is known, the EC50 and high-concentration asymptote can be calculated from each other. Hence, an entire CRC can be estimated from the response to a single agonist concentration, and efficacy can be estimated from EC50 of a CRC that has been normalized to 1. Given η, the level of constitutive activity can be estimated from a single CRC. 相似文献