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151.
152.
Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. 总被引:55,自引:0,他引:55
Previously we demonstrated that transgenic mice expressing mutant basal epidermal keratin genes exhibited a phenotype resembling a group of autosomal dominant human skin disorders known as epidermolysis bullosa simplex (EBS). EBS diseases affect approximately 1: 50,000 and are of unknown etiology, although all subtypes exhibit blistering arising from basal cell cytolysis. We now demonstrate that two patients with spontaneous cases of Dowling-Meara EBS have point mutations in a critical region in one (K14) of two basal keratin genes. To demonstrate function, we engineered one of these point mutations in a cloned human K14 cDNA, and showed that a K14 with an Arg-125----Cys mutation disrupted keratin network formation in transfected keratinocytes and perturbed filament assembly in vitro. Since we had previously shown that keratin network perturbation is an essential component of EBS diseases, these data suggest that the basis for the phenotype in this patient resides in this point mutation. 相似文献
153.
M Morgan Conn Joe Kappock Dale Drueckhammer Richard Cammack Dennis Hall Tony Cass Jon D Stewart Graham RL Cousins Jeremy KM Sanders Sabine Flitsch Philip AS Lowden Richard Newman 《Current opinion in chemical biology》1999,3(6):631
A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in chemical biology. 相似文献
154.
Michael H. Paller 《Journal of Aquatic Ecosystem Stress and Recovery (Formerly Journal of Aquatic Ecosystem Health)》2002,9(3):149-158
Fish assemblages were sampled by electrofishingover a two- to ten-year period in undisturbedand anthropogenically disturbed South Carolinacoastal plain streams. Jaccard similarity,Bray–Curtis similarity, and Spearman rankcorrelations among samples collected from thesame sites over time were significantly greaterat undisturbed sites than at disturbed sites,suggesting greater fish assemblage persistenceand stability at the undisturbed sites. TheIndex of Biotic Integrity (IBI) also exhibitedsignificantly less variation over time atundisturbed sites than at disturbed sites.Physical habitat structure changed more overtime at disturbed sites than at undisturbedsites, and this variability was directlyrelated to temporal variability in fishassemblage structure. Comparisons betweenmultiple and single pass electrofishing samplessuggested that only a small proportion of thetemporal variability observed at the studysites was caused by inefficient sampling.Assessment of temporal variation in fishassemblage structure can serve as an indicatorof environmental disturbance and facilitate thedistinction of substantive ecological changefrom normal background variation. 相似文献
155.
I. M. Häfliger N. Wiedemar T. Švara J. Starič V. Cociancich K. Šest M. Gombač T. Paller J. S. Agerholm C. Drögemüller 《Animal genetics》2020,51(3):382-390
The pulmonary hypoplasia and anasarca syndrome (PHA) is a congenital lethal disorder, which until now has been reported in cattle and sheep. PHA is characterized by extensive subcutaneous fetal edema combined with hypoplasia or aplasia of the lungs and dysplasia of the lymphatic system. PHA is assumed to be of genetic etiology. This study presents the occurrence of PHA in two different cattle breeds and their genetic causation. Two PHA cases from one sire were observed in Slovenian Cika cattle. Under the assumption of monogenic inheritance, genome-wide homozygosity mapping scaled down the critical regions to 3% of the bovine genome including a 43.6 Mb-sized segment on chromosome 6. Whole-genome sequencing of one case, variant filtering against controls and genotyping of a larger cohort of Cika cattle led to the detection of a likely pathogenic protein-changing variant perfectly associated with the disease: a missense variant on chromosome 6 in ADAMTS3 (NM_001192797.1: c.1222C>T), which affects an evolutionary conserved residue (NP_001179726.1: p.(His408Tyr)). A single PHA case was found in Danish Holstein cattle and was whole-genome sequenced along with its parents. However, as there was no plausible private protein-changing variant, mining for structural variation revealed a likely pathogenic trisomy of the entire chromosome 20. The identified ADAMTS3 associated missense variant and the trisomy 20 are two different genetic causes, which shows a compelling genetic heterogeneity for bovine PHA. 相似文献
156.
157.
M. S. Paller 《The Journal of membrane biology》1994,142(1):127-135
Because membrane fluidity is an important determinant of membrane function, the lateral diffusion rate (D
L
) of the membrane protein Na,K-ATPase was determined in intact renal proximal tubule epithelial cells by the technique of fluorescence redistribution after photobleaching (FRAP). In normal cells the D
L
of Na,K-ATPase in the basal membrane was 3.31×10–10 cm2/ sec. Treatment with cytochalasin D to promote actin filament depolymerization caused a sevenfold increase in D
L
. Exposure of cells to a Ca2+-free medium or to hypoxia and reoxygenation, which have similar disruptive effects on the cytoskeleton, also caused increases in D
L
. Disruption of actin microfilament structure also increased the mobile fraction of Na,K-ATPase. Using a confocal laser microscopic technique only 14.9% of total Na,K-ATPase was observed to reside in the apical membrane domain of normal cells. Microfilament depolymerization caused this fraction to increase to 47.7%. Thus, the translocation of Na,K-ATPase from the basolateral to the apical domain induced by cytoskeletal protein dysfunction was enabled by an increased rate of lateral diffusion of Na,K-ATPase. The behavior of a variety of membrane lipids following actin depolymerization was more heterogeneous. Some lipids showed a similar increase in D
L
whereas others showed very little dependence upon the cytoskeleton for lateral restraint.This work was supported by an American Heart Association Grant-in-Aid, an extramural grant from Baxter Healthcare Corporation, and NIH Shared Instrument Grant RR-05877. We thank Dr. J. Carlos Manivel for performing the electron microscopic studies.This paper was prepared with the technical assistance of Xing-Xing Luo and Marshalleen Patten. 相似文献
158.
F. R. SCARANO FLS H. M. DUARTE G. RÔÇAS S. M. B. BARRETO E. F. AMADO F. REINERT T. WENDT A. MANTOVANI H. R. P. LIMA C. F. BARROS 《Botanical journal of the Linnean Society. Linnean Society of London》2002,140(4):391-401
The clonal tank-bromeliad Aechmea bromeliifolia (Rudge) Baker was found in four different habitats in a restinga (vegetation mosaic on sandy coastal plains), of south-eastern Brazil. These habitats (swamp forest, dry forest, dry shrubland and herbaceous marsh) lie within a few hundred metres of each other along a gradient extending inland from the coast, and differ markedly in terms of light and flood regime. We compared ramet morphology, leaf anatomy and physiology, and population parameters to examine the amplitude of trait variation of this widespread species in the studied restinga. This integrated approach allowed us to examine which variation conferred acclimation and which was merely a stress symptom. A . bromeliifolia showed site-specific differences in abundance, distribution, rosette size and shape, leaf anatomical arrangement and photochemical efficiency (potential quantum yield; F v / F m ) during the day. Most of the variation found seemed to be related to the interaction of light and flooding. The lowest number and size of ramets at the exposed, dry shrubland was matched by a marked leaf photoinhibition, which suggested poor acclimation to local levels of light intensity and limited water supply. In the other habitats, the morpho-physiological parameters measured suggested adequate foraging behaviour and site acclimation. © 2002 The Linnean Society of London, Botanical Journal of the Linnean Society, 2002, 140 , 391-401. 相似文献