An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

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 sgsh^Δex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgsh^Δex5−6 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 sgsh^Δex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgsh^Δex5−6 mutant larvae in a context-dependent manner. We expect the sgsh^Δex5−6 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.     

Cytochemical investigation of the digestive gland of two strombidae species (Strombus gigas and Strombus pugilis) in relation to the nutrition

Strombus gigas and Strombus pugilis are threatened species and aquaculture represents a good alternative solution to the fishing. In this study, we highlighted the intracellular digestion process in the digestive gland of two Strombidae species, S. gigas and Strombuspugilis, by the cytochemical characterization of two lysosomal enzymes: acid phosphatase and arylsulfatase. In order to check the efficiency of artificial food digestion, we conducted the characterization on freshly collected, starved and artificially fed individuals of S. pugilis. TEM observations of digestive gland sections from freshly collected individuals of both species revealed the presence of acid phosphatase and arylsulfatase activity mostly located in the apical third of digestive cells. Both enzymes were also detected in artificially fed individuals. In response to the starvation, acid phosphatase is not produced anymore by digestive cells, while arylsulfatase is still present. To our knowledge, this is the first cytochemical validation of intracellular digestion of artificial food in Strombidae. This study highlights the intracellular digestion of artificial food developed for Strombidae aquaculture. Moreover, we have shown that the lysosomal activity could be used as a feed index. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.     

两种5-氨基-3-巯基-1,2,4-三唑衍生物的合成及结构表征

5-氨基-3-苄硫基-1,2,4-三唑和5-氨基-3-正丁烷硫基-1,2,4-三唑都是三唑并嘧啶磺酰胺类除草剂的中间体,以5-氨基-3-巯基-1,2,4-三唑（AMZ）、苄氯,正溴丁烷为原料,通过对AMZ的烷基化合成上述两种化合物。通过正交实验得到较好的合成工艺条件：5-氨基-3-苄硫基-1,2,4-三唑的合成,温度为60～70℃,反应时间为10min,氯仿的量为25mL时产率可达70.4%;5-氨基-3-正丁烷硫基-1,2,4-三唑的合成,温度为70～80℃,反应时间为1h,AMZ与正溴丁烷的摩尔比为1∶1.1时产率可达78.4%。通过红外光谱、核磁共振氢谱等表征了其结构。     

水厂加碱调节pH值试验研究

对于低碱度、低pH值的原水,在水处理过程中通常投加碱调节剂,以提高出水的碱度和pH值,从而增强出水的化学稳定性。本文通过烧杯搅拌试验、中试和生产性试验,对三种碱调节剂-石灰、氢氧化钠、碳酸钠进行了对比试验,以了解三种不同碱剂的投加效果,同时对三种碱剂的投加成本进行了对比分析。     

碱性处理技术在发电机内冷水系统中的应用

介绍了碱性处理技术改善发电机内冷水水质的基本原理以及该技术在吴泾第二发电有限责任公司2×600 MW机组上试验研究和成功应用的情况,提出了将氢型混床改为碱化混床运行时应考虑对系统改进和运行控制的若干建议.     

碱性离子液体碱化制备N-十六烷基化壳聚糖

合成了1-甲基-3-丁基咪唑醋酸盐([Bmim]OAc)、1-甲基-3-丁基咪唑碳酸盐([Bmim]2CO3)及1-甲基-3-丁基咪唑氢氧化物([Bmim]OH)离子液体,由FT-IR、1HNMR、13CNMR和元素分析对结构进行了确证。首先用离子液体对壳聚糖碱化,再令碱化后壳聚糖与溴代十六烷进行烷基化反应,制备高取代度的N-十六烷基化壳聚糖。用FT-IR、XRD对烷基化产物进行了表征。考察时间、温度及物料配比对N-十六烷基壳聚糖取代度的影响,得到较佳的反应条件:n([Bmim]OH)∶n(壳聚糖原料)=3∶1,40℃碱化1 h,n(溴代十六烷)∶n(碱化后壳聚糖)=2∶1,烷基化反应温度85℃,反应时间3.5 h,在该条件下十六烷基壳聚糖的取代度达到75%以上。离子液体具有重复使用性,反应后的离子液体重复使用3次后,N-十六烷基壳聚糖的取代度仍>75%。     

竹浆碱化工艺对纤维素黄酸酯性能的影响

竹浆的主要成分是纤维素、木质素和戊聚糖,将其粉碎、碱化交联,在一定的条件下与二硫化碳反应,制得竹浆纤维素黄酸酯,作为竹浆黏胶纤维的纺丝原液.分析了碱化过程中氢氧化钠的浓度和温度、碱化时间对纤维素黄酸酯酯化度的影响.     

Laboratory study of impacts of concrete fragment sizes on wetland water chemistry

This study investigated the effects of urban concrete materials, of different particle sizes, immersed in water through a laboratory-based experiment. Water was sourced from a high conservation-value wetland (Blue Mountains upland swamp). Prior to the experiment, wetland water was dilute (32.5 μS/cm), acidic (pH 5.3) and had detectable major ion concentrations of only sodium and chloride. Water was exposed to three treatments of different concrete fragment sizes (whole, crushed and fine). All treatments increased conductivity and pH and also resulted in modified ionic composition where calcium, potassium, hydroxide, carbonate and sulphate were recorded at much high levels. The extent and speed of water chemistry changes was linked to the particle size of the concrete. The results of this study support the hypothesis that concrete can be an environmentally hazardous material influencing water quality in urban catchments.