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21.
Alon M. Douek Mitra Amiri Khabooshan Jason Henry Sebastian-Alexander Stamatis Florian Kreuder Georg Ramm Minna-Liisa nk Donald Wlodkowic Jan Kaslin 《International journal of molecular sciences》2021,22(11)
Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgshΔex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgshΔex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgshΔex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgshΔex5−6 mutant larvae in a context-dependent manner. We expect the sgshΔex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions. 相似文献
22.
Different routes for immobilization of TiO2 on conducting substrates were compared to find active and stable photocatalysts, which could either be operated in open circuit (photocatalysis) or with applied electric potential (photoelectrocatalysis). The advantage of applying an electric potential was investigated. Polarization curves and photoelectrochemical degradation reactions served to characterize catalysts and to find a way of predicting the optimum synthesis conditions. The difference between front side (EE) and back side (SE) illumination is discussed as a function of layer thickness, as well as the influence of oxidizable substance concentration on photocurrents. Stability of catalysts was investigated in repetitive degradation experiments. 相似文献
23.
24.
Crosslinked poly(4-styrenesulfonic acid chloride) was reacted with 3-amino-4-hydroxyphenyl benzoate to give a reactive carrier after saponification and oxidation. Its binding ability was tested with α-chymotrypsin. The binding ability as well as the enzyme activity could be increased by introduction of spacers, e.g. ethylenediamine and hexamethylenediamine between the poly(styrene)-matrix and p-benzoquinone. Also crosslinked poly(vinyl alcohol) was reacted with p-benzoquinone to give a reactive carrier, which could also immobilize α-chymotrypsin. Some properties of the immobilized α-chymotrypsin as activity, pH-optimum and storage stability were investigated. 相似文献
25.
Prediction of the biologically active sites in eclosion hormone from the silkworm, Bombyx mori 总被引:1,自引:0,他引:1
Kikuchi T; Okamoto M; Geiser M; Schmitz A; Gohda K; Takai M; Morita T; Horii K; Fujita N 《Protein engineering, design & selection : PEDS》1997,10(3):217-222
The structure-activity relationship of eclosion hormone from the silkworm,
Bombyx mori, was analyzed. First, the probable active residues in silkworm
eclosion hormone and also tobacco hornworm eclosion hormone were predicted
by the average distance map method. To examine the contributions of those
residues to the activity of silkworm eclosion hormone, Gly-substituted
mutants for those predicted residues were produced by site-directed
mutagenesis and their activities were evaluated by a bioassay. Finally,
Glu12, Met24 and Phe25 were estimated to be the crucial residues for the
eclosion hormone activity. The possibility of the development of a blocker
of an eclosion hormone receptor on the basis of the present work is also
discussed.
相似文献
26.
27.
Experimental results for the electrodeposition of Ni-Zn alloys from chloride solutions, with addition of H3BO3 and without other additives, in a laboratory cell with a perforated nickel sheet cathode and with recirculating electrolyte are presented. The dependence of the zinc content in the alloy on the following operating conditions was investigated: cathodic current density, 1.0–20.0 A dm–2; temperature, 35–65°C; pH 1.5–5.5; total molarity,M
tot=M
Ni
2+
+M
Zn
2+
=1.1–2.8 M; and, molar ratio,P=M
Ni
2+
/M
Zn
2+
=1.0–15. Depending on the operating conditions the Zn content in the alloy varied over the range 22–88 mol%. In separate experiments galvanostatic polarization curves were measured in the direction of increasing and then decreasing cathodic current density in the range 0.1–20.0 A dm–2 with all other operating conditions as used for electroplating experiments. In all cases significant hysteresis effects were observed. It was found that the current efficiency for the electrodeposition of Ni-Zn alloys from chloride solutions as a function of the zinc content in the alloy showed a sharp minimum of about 55% atX
Zn=55 mol % irrespective of other operating conditions. 相似文献
28.
Tony L. Schmitz Jeremiah Couey Eric Marsh Nathan Mauntler Duke Hughes 《International Journal of Machine Tools and Manufacture》2007,47(5):841-851
This paper investigates the effect of milling cutter teeth runout on surface topography, surface location error, and stability in end milling. Runout remains an important issue in machining because commercially-available cutter bodies often exhibit significant variation in the teeth/insert radial locations; therefore, the chip load on the individual cutting teeth varies periodically. This varying chip load influences the machining process and can lead to premature failure of the cutting edges. The effect of runout on cutting force and surface finish for proportional and non-proportional tooth spacing is isolated here by completing experiments on a precision milling machine with 0.1 μm positioning repeatability and 0.02 μm spindle error motion. Experimental tests are completed with different amounts of radial runout and the results are compared with a comprehensive time-domain simulation. After verification, the simulation is used to explore the relationships between runout, surface finish, stability, and surface location error. A new instability that occurs when harmonics of the runout frequency coincide with the dominant system natural frequency is identified. 相似文献
29.
30.
Barton B Rhinow D Walter A Schröder R Benner G Majorovits E Matijevic M Niebel H Müller H Haider M Lacher M Schmitz S Holik P Kühlbrandt W 《Ultramicroscopy》2011,111(12):1696-1705
We report the implementation of an electrostatic Einzel lens (Boersch) phase plate in a prototype transmission electron microscope dedicated to aberration-corrected cryo-EM. The combination of phase plate, Cs corrector and Diffraction Magnification Unit (DMU) as a new electron-optical element ensures minimal information loss due to obstruction by the phase plate and enables in-focus phase contrast imaging of large macromolecular assemblies. As no defocussing is necessary and the spherical aberration is corrected, maximal, non-oscillating phase contrast transfer can be achieved up to the information limit of the instrument. A microchip produced by a scalable micro-fabrication process has 10 phase plates, which are positioned in a conjugate, magnified diffraction plane generated by the DMU. Phase plates remained fully functional for weeks or months. The large distance between phase plate and the cryo sample permits the use of an effective anti-contaminator, resulting in ice contamination rates of <0.6 nm/h at the specimen. Maximal in-focus phase contrast was obtained by applying voltages between 80 and 700 mV to the phase plate electrode. The phase plate allows for in-focus imaging of biological objects with a signal-to-noise of 5-10 at a resolution of 2-3 nm, as demonstrated for frozen-hydrated virus particles and purple membrane at liquid-nitrogen temperature. 相似文献