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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
3.
Genetics of the alkaline phosphatase polymorphism of the human placenta 总被引:27,自引:0,他引:27
4.
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
5.
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
7.
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
8.
9.
A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n 总被引:39,自引:0,他引:39
The instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division. Human telomeric DNA comprises approximately 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5'----3' in towards the end of the chromosome, interspersed with variant repeats in the proximal region. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase) or by recombination; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells. Here we describe an alpha thalassaemia mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13-3) to a site 50 kb distal to the alpha globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation. 相似文献
10.
木槿愈伤组织耐盐细胞系是在含NaCl的培养基上通过屡代选择产生的,在无盐培养其中进行几代继代培养后的愈伤组织,由其分化的芽以及脱分化增殖的愈伤组织均表现了耐盐性,木槿耐盐细胞由于对NaCl的反应比未经选择的细胞积累了更多的N^+,K^+,而且细胞体积较小。 相似文献