Towards a transgenic model of Huntington's disease in a non-human primate

Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of human diseases. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10-15 years of the onset of the symptoms. HD is caused by the expansion of cytosine-adenine-guanine (CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin (HTT) gene. Mutant HTT with expanded polyglutamine (polyQ) is widely expressed in the brain and peripheral tissues, but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological, neurological and genetic similarities between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases. Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine-expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.     

Distribution of α-MSH -like immunoreactive cells in the nervous system, Hatschek’s pit and other tissues of amphioxus, Branchiostoma belcheri

Immunohistochemical localization of α-melanocyte-stimulating hormone (α-MSH) in the nervous system, Hatschek’s pit and other tissues of amphioxus (Branchiostoma belcheri) was performed using the antibody against synthetic α-MSH. The results revealed that α-MSH-like immunoreactive cells were distributed at the dorsal side and ventral side of the brain vesicle, the dorsal side and the surrounding of central tube in the nerve tube, the epithelial cells of Hatschek’s pit, and zones 1, 3 and 6 in endostyle and hindgut. The immunoreactive substance was also found in the primary oocytes of the small and large growth stage of ovary and early stage spermatogenic cells in testis. These findings indicate that α-MSH is an ancient and highly conserved hormone and it is extensively distributed in amphioxus. Although Hatschek’s pit in amphioxus do not have a structure of the intermediate lobe of vertebrate adenohypophysis, it has already hosted α-MSH-like endocrine cells, implying that the functional differentiation of α-MSH-like cells occurred earlier than the differentiation of the tissue structure. The results of present study provided new evidence for the endocrinology of Hatschek’s pit and the origin and evolution of vertebrate adenphypophysis.     

4-Formyl-2-（2H-benzotriazol-2-yl）-phenol： an ESIPT chromophore

In the present work, excited state intramolecular proton transfer （ESIPT） emission properties of a new benzotriazole derivative 4-formyl-2-（2H-benzotriazol-2-yl）- phenol （C1） were studied. 4-Formyl-2-（2H-benzotriazol-2- yl）-methoxy-benzene （C2）, 4-formyl-2-（2H-benzotriazol-2- yl）-phenyl acetate （C3） and 4-methyl-2-（2H-benzotriazol- 2-yl）-phenol （C4） were used as the reference molecules. ^1H NMR chemical shift of hydroxy group in C1 was located at more down field than that of C4 or p-hydroxy-benzaldehyde （C5）, respectively. C1 showed two absorption bands in the range of 260-400 nm zones in various solvents, while C2 and C3 exhibited single absorption band. The equal molar mixtures of C2/C5 or C3/C5 showed single absorption band. C2 and C3 displayed single fluorescence emission band in various solvents, while C1 exhibited dual emission bands in some strong polar solvents. Furthermore, the second emission band in these strong polar solvents showed the large Stokes shift. The results show that the second emission band of C1 was produced by ESIPT. C2 and C3 could not undergo ESIPT due to no hydroxy group. The geometry optimization calculation of enol and keto forms in the ground and excited states of C1 provided tough theoretical evidences of ESIPT.     

Assessment of urinary concentration of cotinine in Chinese pregnant women exposed to environmental tobacco smoke

Environmental tobacco smoke （ETS） is a well- known reason of many adverse health consequences in pregnant women. Exposure of ETS during pregnancy may increase the risk of some fetal diseases in pregnant women and/or birth defects in neonates. Many countries have implemented laws to control smoking and free of second hand smoke in all enclosed workplaces. In China, anti- smoking law was enforced in March 2010. We aimed to assess the exposure of pregnant women to cotinine after anti-smoking law was implemented in China. The urine samples were collected from 2,100 volunteers from Zhejiang Province, China and urinary concentration of cotinine was measured using gas chromatography and mass spectrometry. Cotinine was detected in 87 % of the pregnant women. The GM and 95th percentile concentration in pregnant women were 4.28 and 44.00 μg/L, respectively. Similarly, the GM and 95th concentration of cotinine were significantly higher in smoking group than in non-smoking group （P 〈 0.0001）. Our results indicate that pregnant women in China are at the high risk of exposure ETS. Further attempts are required to make strategies to find out the sources of ETS exposure and prevent smoking at public places especially during pregnancy.     

Distribution of a-MSH-like immunoreactive cells in the nervous system,Hatschek's pit and other tissues of amphioxus,Branchiostoma belcheri

Immunohistochemical localization of α-melanocyte-stimulating hormone （α-MSH） in the nervous system, Hatschek＇s pit and other tissues of amphioxus （Branchiostorna belcheri） was performed using the antibody against synthetic α-MSH. The results revealed that α-MSH-like immunoreactive cells were distributed at the dorsal side and ventral side of brain vesicle, the dorsal side and the surrounding of nerve tube, and in the epithelial cells of Hatschek＇s pit, the zone 1, 3, and 6 of endostyle and gut. The immunoreactive substance was also found in the primary oocytes of the small and large growth stage of ovary and early stage spermatogenic cells in testis. These findings indicate that α-MSH is an ancient and highly conserved hormone and it is extensively distributed in amphioxus. Although Hatschek＇s pit in amphioxus does not have a structure of the intermediate lobe of vertebrate adenohypophysis, it has already hosted α-MSH-like endocrine cells, implying that the functional differentiation of α-MSH-like cells occurred earlier than the differentiation of the tissue structure. The results of the present study provided a new evidence for the endocrinology of Hatschek＇s pit and for the origin and evolution of vertebrate adenohypophysis.     

Numerical simulation of hot stamping of side impact beam

Ls-DYNA software is adopted to conduct research of numerical simulation on hot stamping of side impact beam to calculate the temperature field distribution,stress field distribution,forming limit diagram(FLD) figure,etc.in the course of hot stamping so as to predict and analyze the formability of parts.ProCAST software is employed to conduct research of numerical simulation on solid quenching course concerning hot stamping to calculate temperature field distribution of tools and component of multiple stamping cycles.The results obtained from numerical simulation can provide significant reference value to hot stamping part design,formability predication and tools cooling system design.     

Investigation on preparing boron nitride by nitriding pure boron at 1200–1550 1C

Boron nitride (BN) was prepared by nitriding pure boron (B) deposited on carbon substrates by chemical vapor deposition (CVD). Thermodynamic analysis of preparing BN by nitriding CVD B at 1200–1550 1C was firstly performed. And then, the effects of nitridation conditions, including temperature, nitridation atmosphere and CVD B microstructure, on the conversion of B to BN were analyzed by scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Results show that the conversion degree of B to BN firstly increased and then slightly decreased with rising temperature. The nitridation degree was controlled by mutual actions between the nitridation of B and consumption of the effective nitrogen source (NH3). The morphology of products and the reaction mechanism between B and N were influenced by nitridation temperature. At high temperatures (1400–1500 1C), BN with highly ordered microstructure was produced. On using N2–H2 as nitridation atmosphere instead of NH3–H2– N2, no BN was obtained in the studied temperature range. The microstructure and component of BN obtained in nitridation process were little affected by the microstructure of CVD B.     

船用GPS接收机软件设计的研究

对船用ＧＰＳ接收机软件设计中的几个问题进行了分析与研究。这对软件设计的改进与正确使用的船用ＧＰＳ接收机都有实际意义。     

On the Measurement of Technological Change

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