Direct gene transfer into neurons has potential for developing gene therapy treatments for specific neurological conditions,
and for elucidating neuronal physiology. Due to the complex cellular composition of specific brain areas, neuronal type-specific
recombinant gene expression is required for many potential applications of neuronal gene transfer. One approach is to target
gene transfer to a specific type of neuron. We developed modified Herpes Simplex Virus (HSV-1) particles that contain chimeric
glycoprotein C (gC) – glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) proteins.
HSV-1 vector particles containing either gC – GDNF or gC – BDNF target gene transfer to nigrostriatal neurons, which contain
specific receptors for GDNF or BDNF. A second approach to achieve neuronal type-specific expression is to use a cell type-specific
promoter, and we have used the tyrosine hydroxylase (TH) promoter to restrict expression to catecholaminergic neurons or a
modified neurofilament heavy gene promoter to restrict expression to neurons, and both of these promoters support long-term
expression from HSV-1 vectors. To both improve nigrostriatal-neuron specific expression, and to establish that targeted gene
transfer can be followed by long-term expression, we performed targeted gene transfer with vectors that support long-term,
neuronal-specific expression. 相似文献
Magnesium-Eriochrome Black T in ethylenediamine medium gives a polarographic adsorptive wave at -0.7 V (vs. an Ag/Hg electrode). It gives a limit of detection for magnesium of 2 x 10(-8)M. It is made the basis of a method for determination of magnesium in serum, water and various salts, without any pretreatment. The method is very rapid, sensitive and convenient for serum analysis. 相似文献
In order to better understand the therapeutic mechanism of dual-function peptide 5rolGLP-HV in treatment of treat diabetes and its complication of thrombosis, the pharmacological effects and pharmacokinetic properties of 5rolGLP-HV were conducted in this study. 5rolGLP-HV was orally administered to diabetic mice, and the hypoglycemic mechanism was investigated. Thrombotic mice were applied to study the thrombus dissolving ability of 5rolGLP-HV. The concentration of rolGLP and rHV in rat plasma following single oral dose or intravenous injection of 5rolGLP-HV was measured. Treatment with 5rolGLP-HV decreased insulin resistance (2.96 ± 1.43 vs. 9.35 ± 1.51, p < 0.05) of diabetic mice. 5rolGLP-HV shortened the length of thrombus in thrombosis mice (2.92 ± 0.74 vs. 5.92 ± 1.16 cm, p < 0.01) and extended the thrombin time (15.35 ± 1.22 vs. 8.67 ± 0.89 s, p < 0.01) of normal mice. Meanwhile, 5rolGLP-HV restored the damage of pancreatic, liver, kidney, and adipose tissues induced in the diabetic mice. 5rolGLP-HV exhibited a fast absorption and slow elimination phase after digested into rolGLP-1 and rHV in vivo. These results suggested that 5rolGLP-HV had an ideal therapeutic potential in the prevention of β cell dysfunction in type 2 diabetes and delay of the thrombus. 相似文献
In this paper, we use exact matrix diagonalization to explore the many-body localization (MBL) transition of the Heisenberg Ising spin-1/2 chain with nearest neighbor couplings and disordered external fields. It demonstrates that the fidelity, magnetization and spin-spin space correlation can be used to characterize the many-body localization transition in this closed spin system which is also in agreement with previous analytical and numerical results. We test the properties for the middle third many-body eigenstates. It shows that for this model with random-field, the excited-state fidelity exhibits a pronounced drop at the transition and then gradually tends to be stable in the localized phase, the critical point and the final value of averaged fidelity are all size dependent. It demonstrates that disordered external fields drive the occurrence of the MBL transition. Moreover, we investigate the magnetization and spin-spin space correlation in this model to verify the conclusion we got and further explore the properties of ergodic phase and localized phase.