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1.
Franois Ancien Fabrizio Pucci Marianne Rooman 《International journal of molecular sciences》2021,22(9)
Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality. 相似文献
2.
Luc Rochette Loubna Mazini Gabriel Malka Marianne Zeller Yves Cottin Catherine Vergely 《International journal of molecular sciences》2020,21(23)
The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs is a major goal in repair medicine. Stem cells are classified by their potential to differentiate into functional cells. Compared with other sources, adipose-derived stem cells (ADSCs) have the advantage of being abundant and easy to obtain. ADSCs are considered to be tools for replacing, repairing, and regenerating dead or damaged cells. The capacity of ADSCs to maintain their properties depends on the balance of complex signals in their microenvironment. Their properties and the associated outcomes are in part regulated by reactive oxygen species, which mediate the oxidation-reduction state of cells as a secondary messenger. ADSC therapy has demonstrated beneficial effects, suggesting that secreted factors may provide protection. There is evidence that ADSCs secrete a number of cytokines, growth factors, and antioxidant factors into their microenvironment, thus regulating intracellular signaling pathways in neighboring cells. In this review, we introduce the roles of ADSCs in the protection of cells by modulating inflammation and immunity, and we develop their potential therapeutic properties. 相似文献
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The continuing progression of Moore's Law has enabled the miniaturisation and dramatic cost reduction in electronics over the last ten years. For a truly pervasive communications environment the challenges of hiding key hardware technologies from the user are rapidly being overcome. This paper reviews the status of these hardware technology developments in the pervasive space and briefly discusses other contributing factors that will enable the pervasive vision to be realised. 相似文献
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Kringlebotn J.T. Morkel P.R. Reekie L. Archambault J.-L. Payne D.N. 《Photonics Technology Letters, IEEE》1993,5(10):1162-1164
We report a 7.6-mW single-frequency fiber laser operating at 1545 nm, using for the first time an Er3+:Yb3+ doped fiber and a fiber grating output coupler. The laser did not exhibit self-pulsation, which is a typical problem in short three-level fiber lasers, and had a relative intensity noise (RIN) level below -145.5 dB/Hz at frequencies above 10 MHz. The linewidth of the laser was limited by the relaxation oscillation sidebands in the optical spectrum and was typically less than 1 MHz 相似文献
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Faulkner D.W. Payne D.B. Stern J.R. Ballance J.W. 《Lightwave Technology, Journal of》1989,7(11):1741-1751
Some of the options for optical technology within the local loop environment are examined. In particular, passive shared access networks have been considered in some detail. These networks show great promise for delivering existing telephone services to small to medium business customers (4-30 lines) economically by the early 1990s. Extending fiber to the home will also be possible by virtue of a similar passive network infrastructure for customers requiring new broadband services beyond the single telephone line. For one-line plain old telephone service (POTS) customers, an intermediate approach of terminating the fiber network at the final network distribution point, with copper retained for the final leg, may be used prior to the provision of broadband services. A key feature of the passive optical network architecture is the use of wavelength-division multiplexing (WDM) as an upgrade strategy, allowing graceful upgrading from telephone services to multichannel high-definition television (HDTV) on gigabit/second bearers and full two-way switched broadband services employing wavelength routing across the network 相似文献
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MS Payne S Wu RD Fallon G Tudor B Stieglitz IM Turner MJ Nelson 《Canadian Metallurgical Quarterly》1997,36(18):5447-5454
Nitrile hydratase from Pseudomonas putida NRRL-18668 has been purified and characterized. The purified enzyme catalyzes the hydration of 2(S)-(4'-chlorophenyl)-3-methylbutyronitrile at least fifty times faster than that of 2(R)-(4'-chlorophenyl)-3-methylbutyronitrile. This enzyme is a member of the class of nitrile hydratase that contains cobalt. Visible absorption and CD spectra suggest the cobalt exists as a non-corrin low-spin Co3+ ion in a tetragonally-distorted octahedral ligand field. Chemical reduction of the native enzyme results in a species with the EPR signature of a low-spin Co2+ complex. Like the other cobalt-containing nitrile hydratases, this enzyme is relatively stable, maintaining its activity below 35 degrees C, and it shows a broad activity optimum between pH 7.2 and 7.8. The structural genes for this enzyme have been cloned and sequenced. The deduced amino acid sequences for the alpha and beta subunits show 48-63% and 35-41% homology, respectively, to other sequenced nitrile hydratases. In particular, the cysteine residues in the alpha subunit that have been suggested to coordinate the metal ion in the iron-containing nitrile hydratases [Brennan, B. A., Cummings, J. G., Chase, D. B., Turner, I. M., Jr., & Nelson, M. J. (1996) Biochemistry 35, 10068-10077] are conserved in this enzyme, suggesting that this nitrile hydratase, like the enzyme from Rhodococcus rhodochrous J1, is a member of a newly described class of metalloenzymes with Co3+-thiolate ligation [Brennan, B. A., Alms, G., Nelson, M. J., Durney, L. T., & Scarrow, R. C. (1996) J. Am. Chem. Soc. 118, 9194-9195]. 相似文献
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