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Biomedical subjects

Fang Wu

Publications and source records attributed to Fang Wu.

9 recordsLinked to original sources

CSF proteogenomics implicates novel proteins and humoral immunity in Alzheimer's disease risk.

We profiled 2,961 cerebrospinal fluid (CSF) proteins in 1,005 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 1,066 proteins not measured in prior studies, using mass spectrometry (MS). We mapped protein quantitative trait loci (pQTLs) in CSF, compared them with brain and plasma pQTLs, and integrated them with Alzheimer's disease (AD) genome-wide association study (GWAS) data. We identified 1,417 index cis pQTLs for 654 unique genes and 130 index trans pQTLs for 94 unique genes. Cross-tissue and cross-proteomic-platform comparisons show broad consistency between MS-based CSF pQTLs and MS-based brain pQTLs as well as affinity-based CSF and plasma pQTLs. Lastly, through integrating CSF pQTLs with the largest AD GWAS, we identified 24 candidate AD causal proteins in CSF, including 10 novel and 14 previously identified in either brain, CSF, or plasma using similar approaches. These CSF AD candidate causal proteins are involved in immune response - notably humoral immunity (3 of 24) - that expands the role of the immune system in AD beyond innate immunity, as well as lysosomal function and neurovascular growth and remodeling. Together, our findings provide novel insights into AD biology and new targets for biomarker and therapeutic development.

Journal Article↗

In-phase implies large likelihood for independent codon model: distinguishing coding from non-coding sequences.

It is proven that under the independent codon model, the likelihood of a DNA coding sequence read according to the correct frame is asymptotically larger than that read with an incorrect frame. Based on this proposition, a single set of probabilities of the codon usage is enough for discriminating the six frames of coding sequences under the independent codon model. The direct coding sequence of Escherichia coli genome is taken as an example to examine the codon independency by using the mutual information and chi2 analysis. The contrast between the coding frame and the two offset frames is evident. A self-learning approach for generating training set is proposed to estimate probability parameters.

Codon↗

A novel pulsed-release system based on swelling and osmotic pumping mechanism.

A novel pulsed-release system based on bilayer coated tablets containing an osmotically active agent is presented. Hydroxypropylmethylcellulose (HPMC) and the mixture of Eudragit RS and RL were applied as the swelling layer and semipermeable outer coat, respectively. To examine the mechanism of drug release from this pulsed-release system, drug release behaviors were investigated under conditions of various osmotic pressures. Both lag time and release rate were dependent on the coating level and the osmotic pressure of the dissolution medium. The swelling of tablets and the dynamics of water uptake during the dissolution were investigated to further elucidate the mechanism of drug release. The osmotic active agent induces a continuous water influx resulting in a rapid expansion of the membrane. The subsequent formation of fractures leads to a fast drug release after an initial lag time. All the results obtained in the present study indicated that both diffusion and osmotic pumping effect were involved in drug release from the device, but the latter was more dominant.

Capsules↗

[Analysis of an inherited FVII deficiency pedigree caused by homozygosity of Thr359Met].

OBJECTIVE: To explore the gene mutation type of an inherited coagulation factor VII deficiency pedigree. METHODS: FVII:Ag, FVII:C, FVIIa were detected to classify deficiency type. FVII gene mutations were analysed in the proband and her family members by DNA directly sequencing. Biostructural pathology of the identified mutation was analysed by molecular modeling. RESULTS: Homozygosity of C-->T transition at position 11514 in exon 8 resulting in Thr359Met was identified in the proband, and heterozygosity for Thr359Met was confirmed in her parents, her son and some other family members. Thr359Met induces CRM-deficiency. It is found by computer simulated molecular model that the replacement of Thr by Met which has a larger and longer side chain might cause steric hindrance, and change the number of H-bonds. CONCLUSIONS: Homozygous missense mutation Thr359Met was found in a pedigree of hereditary FVII deficiency. This mutation might change the configuration of protein molecule and result in severe FVII deficiency.

Adolescent↗

[Stability evaluation of thymopentin in preparation process].

OBJECTIVE: To observe whether thymopentin is stable in the preparation process. METHODS: Using HPLC method, we investigated the influence of different temperature, sonification time and pH value on thymopentin. RESULTS: The optimum storage condition for preservation of thymopentin was found to be a freezing environment. Thymopentin would not be degraded in the water bath of 60 degrees C for 24 hours or in different phosphate buffer solution (PBS) (pH 2, 5, 5, 7) under 37 degrees C for 24 hours. The sonification time within 15 minutes was determined to be safe for the preparation. CONCLUSION: The experiment result indicates that thymopentin is stable during the whole preparation process.

Chromatography, High Pressure Liquid↗

Purification, characterization and preliminary crystallographic studies of a PR-10 protein from Pachyrrhizus erosus seeds.

A 16 kDa protein SPE16 was purified from the seeds of Pachyrrhizus erosus. Its N-terminal amino-acid sequence showed significant sequence homology to pathogenesis-related proteins from the PR-10 family. An activity assay indicated that SPE16 possesses ribonuclease activity as do some other PR-10 proteins. SPE16 crystals were obtained by the hanging-drop vapour-diffusion method. The space group is P2(1)2(1)2(1), with unit-cell parameters a = 53.36, b = 63.70, c = 72.96 A.

Amino Acid Sequence↗

Synapse formation in the absence of cell bodies requires protein synthesis.

Protein synthesis at distal synaptic sites is thought to play a critical role in long-term synaptic plasticity at preexisting connections. We tested whether protein synthesis in distal neuritic processes contributes to the formation of new synaptic connections by Aplysia neurons regenerating in cell culture after removing their cell bodies. Removal of either the sensory neuron (SN) or motor cell L7 cell body did not affect the formation of synaptic connections during the next 48--72 hr period. Increases in synaptic efficacy after removal of the SN cell body was accompanied by neurite growth and an increase in the number of SN varicosities contacting L7. The increases in synaptic efficacy and the number of SN varicosities were blocked by anisomycin, a protein synthesis inhibitor. The initial formation of synaptic connections was not affected by the absence of the L7 cell body. In the absence of cell bodies from both presynaptic and postsynaptic cells, synaptic efficacy increased for 48 hr and was blocked reversibly by anisomycin. These results support the idea that distal neuritic processes contain stable mRNAs and the macromolecular machinery for protein synthesis that are required for the formation of new synaptic connections.

Animals↗

[Preparation and in vitro release of tetramethylpyrazine phosphate pulsincap capsule controlled by an erodible plug].

AIM: To develop a novel pulsatile drug delivery system of which the lag-time is controlled by an erodible plug (EP) and evaluate its release characteristics in vitro. METHODS: The impermeable capsule body was prepared by fulfilling method and the drug tablet and the erodible plug were made by wet granulating compression. Tetramethylpyrazine phosphate (TMPP) pulsincap capsule was prepared by sealing the drug tablet and fillers inside the impermeable capsule body with the EP. The influence factors on the lag-time such as the EP pharmaceutical properties and the dissolution condition were investigated by dissolution testing. RESULTS: Both the composition and the weight of EP influenced the lag-time of the tetramethylpyrazine phosphate pulsincap capsule significantly. The lag-time prior to the drug release was enhanced when the content of gel-forming excipient (hydroxypropylmethylcellulose, HPMC) in the EP or the weight of EP was increased. The hardness of EP showed minor influence on the lag-time. In addition, the lag-time was shortened when the paddle speed was higher, while the pH value of the dissolution medium exhibited no significant influence on it. CONCLUSION: To meet the chronotherapeutic requirements, a pulsatile drug delivery system with a suitable lag-time can be achieved by adjusting the composition and the EP weight.

Calcium Channel Blockers↗