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1.
J A Martignetti A A Aqeel W A Sewairi C E Boumah M Kambouris S A Mayouf K V Sheth W A Eid O Dowling J Harris M J Glucksman S Bahabri B F Meyer R J Desnick 《Nature genetics》2001,28(3):261-265
The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion. 相似文献
2.
Summary Following engorgement, female ixodid ticks secrete a tick salivary gland degeneration factor (TSGDF) into the hemolymph. Here we show that the arthropod ecdysteroid hormones, ecdysome and 20-hydroxyecdysone, induce degeneration of tick salivary glands maintained in organ culture. The effective dose range in vitro is 30–300 ng/ml, a range reported to be physiological for this species following repletion. In addition, infusion of 20-hydroxyecdysome in vivo induces salivary gland degeneration. We therefore propose that TSGDF may be an ecdysteroid.Acknowledgments. Some of the data reported here were presented to the annual meeting of the Canadian Society of Zoologists, 15–18 May 1983; Program of abstracts, page 53. Financial support of the Canadian National Sportsmen's Fund and NSERC Canada to W.R.K. is gratefully acknowledged. 相似文献
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Genetics of the alkaline phosphatase polymorphism of the human placenta 总被引:27,自引:0,他引:27
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Summary The concentrations of testosterone (T) and 5-dihydrotestosterone were measured in fluid collected from the rete testis of immature and adult rats. The results indicate that adult levels of T are attained in the seminiferous tubules much earlier than in the peripheral circulation.This work was performed at the Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts, USA and supported by the National Institutes of Health through grants HD12641 and HD12642. We thank Dr B.V. Caldwell for antiserum to testosterone. 相似文献
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M. D. Adams J. T. Earnhardt B. R. Martin L. S. Harris W. L. Dewey R. K. Razdan 《Cellular and molecular life sciences : CMLS》1977,33(9):1204-1205
Summary Abnormal-8-tetrahydrocannabidiol (ABN-8-THC) failed to elicit central nervous system and cardiovascular effects in laboratory animals. Abnormal-cannabidiol (ABN-CBD) was also devoid of overt behavioral effects but produced marked hypotension with only slight bradycardia in anesthesized dogs.Acknowledgment. This work was supported by NIDA (grant No. DA-00574-01 and DA-00490) and Virginia Heart Society (grant No. RR-05697) 相似文献
6.
Volatility models such as GARCH, although misspecified with respect to the data‐generating process, may well generate volatility forecasts that are unconditionally unbiased. In other words, they generate variance forecasts that, on average, are equal to the integrated variance. However, many applications in finance require a measure of return volatility that is a non‐linear function of the variance of returns, rather than of the variance itself. Even if a volatility model generates forecasts of the integrated variance that are unbiased, non‐linear transformations of these forecasts will be biased estimators of the same non‐linear transformations of the integrated variance because of Jensen's inequality. In this paper, we derive an analytical approximation for the unconditional bias of estimators of non‐linear transformations of the integrated variance. This bias is a function of the volatility of the forecast variance and the volatility of the integrated variance, and depends on the concavity of the non‐linear transformation. In order to estimate the volatility of the unobserved integrated variance, we employ recent results from the realized volatility literature. As an illustration, we estimate the unconditional bias for both in‐sample and out‐of‐sample forecasts of three non‐linear transformations of the integrated standard deviation of returns for three exchange rate return series, where a GARCH(1, 1) model is used to forecast the integrated variance. Our estimation results suggest that, in practice, the bias can be substantial. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
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Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
10.
Leung JY Chapman JA Harris JA Hale D Chung RS West AK Chuah MI 《Cellular and molecular life sciences : CMLS》2008,65(17):2732-2739
Olfactory ensheathing cells (OECs) have been shown previously to express Toll-like receptors and to respond to bacteria by translocating nuclear factor-kappaB from the cytoplasm to the nucleus. In this study, we show that OECs extended significantly more pseudopodia when they were exposed to Escherichia coli than in the absence of bacteria (p=0.019). Co-immunoprecipitation showed that E. coli binding to OECs was mediated by Toll-like receptor 4. Lyso-Tracker, a fluorescent probe that accumulates selectively in lysosomes, and staining for type 1 lysosome-associated membrane proteins demonstrated that endocytosed FITC-conjugated E. coli were translocated to lysosomes. They appeared to be subsequently broken down, as shown by transmission electron microscopy. No obvious adherence to the membrane and less phagocytosis was observed when OECs were incubated with inert fluorescent microspheres. The ability of OECs to endocytose bacteria supports the notion that OECs play an innate immune function by protecting olfactory tissues from bacterial infection. 相似文献