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931.
Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding
protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding
of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and
single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing
of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism
of amyloid formation and detecting the variant gene in individuals at risk.
Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001 相似文献
932.
The exponential growth in the rate at which information can be communicated through an optical fibre is a key element in the 'information revolution'. However, as for all exponential growth laws, physical limits must be considered. The nonlinear nature of the propagation of light in optical fibre has made these limits difficult to elucidate. Here we use a key simplification to investigate the theoretical limits to the information capacity of an optical fibre arising from these nonlinearities. The success of our approach lies in relating the nonlinear channel to a linear channel with multiplicative noise, for which we are able to obtain analytical results. In fundamental distinction to linear channels with additive noise, the capacity of a nonlinear channel does not grow indefinitely with increasing signal power, but has a maximal value. The ideas presented here may have broader implications for other nonlinear information channels, such as those involved in sensory transduction in neurobiology. These have been often examined using additive noise linear channel models but, as we show here, nonlinearities can change the picture qualitatively. 相似文献
933.
Gene polymorphism in Netherton and common atopic disease. 总被引:13,自引:0,他引:13
A J Walley S Chavanas M F Moffatt R M Esnouf B Ubhi R Lawrence K Wong G R Abecasis E Y Jones J I Harper A Hovnanian W O Cookson 《Nature genetics》2001,29(2):175-178
Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses. 相似文献
934.
Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA 总被引:1,自引:1,他引:0
Essi Myrsky Sergio Caja Zsofi Simon-Vecsei Ilma R. Korponay-Szabo Cristina Nadalutti Russell Collighan Alexandre Mongeot Martin Griffin Markku Mäki Katri Kaukinen Katri Lindfors 《Cellular and molecular life sciences : CMLS》2009,66(20):3375-3385
Celiac disease is characterized by the presence of specific autoantibodies targeted against transglutaminase 2 (TG2) in untreated patients’ serum and at their production site in the small-bowel mucosa below the basement membrane and around the blood vessels. As these autoantibodies have biological activity in vitro, such as inhibition of angiogenesis, we studied if they might also modulate the endothelial barrier function. Our results show that celiac disease patient autoantibodies increase endothelial permeability for macromolecules, and enhance the binding of lymphocytes to the endothelium and their transendothelial migration when compared to control antibodies in an endothelial cell-based in vitro model. We also demonstrate that these effects are mediated by increased activities of TG2 and RhoA. Since the small bowel mucosal endothelium serves as a “gatekeeper” in inflammatory processes, the disease-specific autoantibodies targeted against TG2 could thus contribute to the pathogenic cascade of celiac disease by increasing blood vessel permeability. 相似文献
935.
Equilibrating metal-oxide cluster ensembles for oxidation reactions using oxygen in water. 总被引:2,自引:0,他引:2
I A Weinstock E M Barbuzzi M W Wemple J J Cowan R S Reiner D M Sonnen R A Heintz J S Bond C L Hill 《Nature》2001,414(6860):191-195
Although many enzymes can readily and selectively use oxygen in water-the most familiar and attractive of all oxidants and solvents, respectively-the design of synthetic catalysts for selective water-based oxidation processes utilizing molecular oxygen remains a daunting task. Particularly problematic is the fact that oxidation of substrates by O2 involves radical chemistry, which is intrinsically non-selective and difficult to control. In addition, metallo-organic catalysts are inherently susceptible to degradation by oxygen-based radicals, while their transition-metal-ion active sites often react with water to give insoluble, and thus inactive, oxides or hydroxides. Furthermore, pH control is often required to avoid acid or base degradation of organic substrates or products. Unlike metallo-organic catalysts, polyoxometalate anions are oxidatively stable and are reversible oxidants for use with O2 (refs 8,9,10). Here we show how thermodynamically controlled self-assembly of an equilibrated ensemble of polyoxometalates, with the heteropolytungstate anion [AIVVW11O40]6- as its main component, imparts both stability in water and internal pH-management. Designed to operate at near-neutral pH, this system facilitates a two-step O2-based process for the selective delignification of wood (lignocellulose) fibres. By directly monitoring the central Al atom, we show that equilibration reactions typical of polyoxometalate anions keep the pH of the system near 7 during both process steps. 相似文献
936.
Individual recognition in mice mediated by major urinary proteins. 总被引:25,自引:0,他引:25
J L Hurst C E Payne C M Nevison A D Marie R E Humphries D H Robertson A Cavaggioni R J Beynon 《Nature》2001,414(6864):631-634
The ability to recognize individuals is essential to many aspects of social behaviour, such as the maintenance of stable social groups, parent-offspring or mate recognition, inbreeding avoidance and the modulation of competitive relationships. Odours are a primary mediator of individuality signals among many mammals. One source of odour complexity in rodents, and possibly in humans, resides in the highly polymorphic major histocompatibility complex (MHC). The olfactory acuity of mice and rats allows them to distinguish between the urinary odours of congenic strains differing only in single genes within the MHC, although the chemical mediators or odorants are unknown. However, rodent urine also contains a class of proteins, termed major urinary proteins (MUPs), that bind and release small volatile pheromones. We have shown that the combinatorial diversity of expression of MUPs among wild mice might be as great as for MHC, and at protein concentrations a million times higher. Here we show in wild house mice (Mus domesticus) that urinary MUPs play an important role in the individual recognition mechanism. 相似文献
937.
Phot1 and phot2 mediate blue light regulation of stomatal opening. 总被引:36,自引:0,他引:36
The stomatal pores of higher plants allow for gaseous exchange into and out of leaves. Situated in the epidermis, they are surrounded by a pair of guard cells which control their opening in response to many environmental stimuli, including blue light. Opening of the pores is mediated by K(+) accumulation in guard cells through a K(+) channel and driven by an inside-negative electrical potential. Blue light causes phosphorylation and activation of the plasma membrane H(+)-ATPase that creates this potential. Thus far, no blue light receptor mediating stomatal opening has been identified, although the carotenoid, zeaxanthin, has been proposed. Arabidopsis mutants deficient in specific blue-light-mediated responses have identified four blue light receptors, cryptochrome 1 (cry1), cryptochrome 2 (cry2), phot1 and phot2. Here we show that in a double mutant of phot1 and phot2 stomata do not respond to blue light although single mutants are phenotypically normal. These results demonstrate that phot1 and phot2 act redundantly as blue light receptors mediating stomatal opening. 相似文献
938.
Gridlock signalling pathway fashions the first embryonic artery. 总被引:27,自引:0,他引:27
Arteries and veins are morphologically, functionally and molecularly very different, but how this distinction is established during vasculogenesis is unknown. Here we show, by lineage tracking in zebrafish embryos, that angioblast precursors for the trunk artery and vein are spatially mixed in the lateral posterior mesoderm. Progeny of each angioblast, however, are restricted to one of the vessels. This arterial-venous decision is guided by gridlock (grl), an artery-restricted gene that is expressed in the lateral posterior mesoderm. Graded reduction of grl expression, by mutation or morpholino antisense, progressively ablates regions of the artery, and expands contiguous regions of the vein, preceded by an increase in expression of the venous marker EphB4 receptor (ephb4) and diminution of expression of the arterial marker ephrin-B2 (efnb2). grl is downstream of notch, and interference with notch signalling, by blocking Su(H), similarly reduces the artery and increases the vein. Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision. 相似文献
939.
940.
Eugene Kouassi Joel Sango J.M. Bosson Brou Francis N. Teubissi Kern O. Kymn 《Journal of forecasting》2012,31(7):617-638
In this paper we extend the works of Baillie and Baltagi (1999, in Analysis of Panels and Limited Dependent Variables Models, Hsiao C et al. (eds). Cambridge University Press: Cambridge, UK; 255–267) and generalize certain results from the Baltagi and Li (1992, Journal of Forecasting 11 : 561–567) paper accounting for AR(1) errors in the disturbance term. In particular, we derive six predictors for the one‐way error components model, as well as their associated asymptotic mean squared error of multi‐step prediction in the presence of AR(1) errors in the disturbance term. In addition, we also provide both theoretical and simulation evidence as to the relative efficiency of our alternative predictors. The adequacy of the prediction AMSE formula is also investigated by the use of Monte Carlo methods and indicates that the ordinary optimal predictor performs well for various accuracy criteria. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献