Biomedical subjects

Feng Ding

Publications and source records attributed to Feng Ding.

45 records · Page 3Linked to original sources

PubMed2002

Molecular dynamics simulation of the SH3 domain aggregation suggests a generic amyloidogenesis mechanism.

We use molecular dynamics simulation to study the aggregation of Src SH3 domain proteins. For the case of two proteins, we observe two possible aggregation conformations: the closed form dimer and the open aggregation state. The closed dimer is formed by "domain swapping"-the two proteins exchange their RT-loops. All the hydrophobic residues are buried inside the dimer so proteins cannot further aggregate into elongated amyloid fibrils. We find that the open structure-stabilized by backbone hydrogen bond interactions-packs the RT-loops together by swapping the two strands of the RT-loop. The packed RT-loops form a beta-sheet structure and expose the backbone to promote further aggregation. We also simulate more than two proteins, and find that the aggregate adopts a fibrillar double beta-sheet structure, which is formed by packing the RT-loops from different proteins. Our simulations are consistent with a possible generic amyloidogenesis scenario.

Amino Acid Sequence↗

PubMed2002

In vivo stabilization of the Dnmt1 (cytosine-5)- methyltransferase protein.

The Dnmt1o form of the Dnmt1 (cytosine-5)-methyltransferase enzyme is synthesized and stored in the cytoplasm of the oocyte and is used after fertilization to maintain methylation patterns on imprinted genes. After implantation of the blastocyst, Dnmt1o is replaced by the Dnmt1 form, which has an additional 118 aa at its amino terminus. To investigate functional differences between Dnmt1o and Dnmt1, mice were generated with a mutant allele, Dnmt1(V), which synthesized Dnmt1o instead of Dnmt1 in all somatic cells. Homozygous Dnmt1(V) mice were phenotypically normal, and had normal levels of genomic methylation, indicating that Dnmt1o adopts the maintenance methyltransferase function of Dnmt1. Despite the apparent equivalence of Dnmt1o and Dnmt1 maintenance methyltransferase function in somatic cells, the Dnmt1o protein was found at high levels (with a corresponding high enzymatic activity) in Dnmt1(V) mice. In heterozygous Dnmt1(V)/+ embryonic stem cells and early embryos, equal steady-state levels of Dnmt1o and Dnmt1 proteins were produced from the Dnmt1(V) and the WT Dnmt1 alleles, respectively. However, in older embryos and adults, the Dnmt1(V) allele produced five times the steady-state level of protein of the WT Dnmt1 allele. The difference in Dnmt1o and Dnmt1 levels is due to a developmentally regulated mechanism that degrades the Dnmt1 protein. The intrinsic stability of the Dnmt1o protein is the most likely reason for its use as a maternal-effect protein; stable ooplasmic stores of Dnmt1o would be available to traffick into the nuclei of the eight-cell stage embryo and maintain methylation patterns on alleles of imprinted genes during the fourth embryonic S phase.

Animals↗

PubMed2002

Topological determinants of protein folding.

The folding of many small proteins is kinetically a two-state process that represents overcoming the major free-energy barrier. A kinetic characteristic of a conformation, its probability to descend to the native state domain in the amount of time that represents a small fraction of total folding time, has been introduced to determine to which side of the free-energy barrier a conformation belongs. However, which features make a protein conformation on the folding pathway become committed to rapidly descending to the native state has been a mystery. Using two small, well characterized proteins, CI2 and C-Src SH3, we show how topological properties of protein conformations determine their kinetic ability to fold. We use a macroscopic measure of the protein contact network topology, the average graph connectivity, by constructing graphs that are based on the geometry of protein conformations. We find that the average connectivity is higher for conformations with a high folding probability than for those with a high probability to unfold. Other macroscopic measures of protein structural and energetic properties such as radius of gyration, rms distance, solvent-accessible surface area, contact order, and potential energy fail to serve as predictors of the probability of a given conformation to fold.

Kinetics↗

PubMed2002

Dynamics of Dnmt1 methyltransferase expression and intracellular localization during oogenesis and preimplantation development.

The imprinting of mammalian genes depends on the maintenance of DNA methylation patterns during pre- and postimplantation development. Dnmt1o is a variant form of the somatically expressed Dnmt1 cytosine methyltransferase that is synthesized and stored in the oocyte cytoplasm and trafficks to the eight-cell nucleus during preimplantation development, where it maintains DNA methylation patterns on alleles of imprinted genes. Transcripts encoding Dnmt1 are present in preimplantation embryos, suggesting that Dnmt1 protein is also expressed in the preimplantation embryo, and may account for maintenance methylation at preimplantation stages other than the eight-cell embryo. However, using an antibody that detects Dnmt1, but not Dnmt1o, no Dnmt1 protein was detected on immunoblots or by immunocytochemical staining in wildtype preimplantation embryos. Moreover, Dnmt1 protein produced in the oocyte from a modified Dnmt1 allele, Dnmt1(1s/1o), trafficked to nuclei of eight-cell embryos, but not to nuclei of other stages. The highly restricted nuclear localization patterns of oocyte-derived Dnmt1o and Dnmt1 during preimplantation development add further support to the notion that DNA methyltransferases other than Dnmt1 are required for maintaining imprints during preimplantation development.

Alternative Splicing↗

PubMed2002

Direct molecular dynamics observation of protein folding transition state ensemble.

The concept of the protein transition state ensemble (TSE), a collection of the conformations that have 50% probability to convert rapidly to the folded state and 50% chance to rapidly unfold, constitutes the basis of the modern interpretation of protein engineering experiments. It has been conjectured that conformations constituting the TSE in many proteins are the expanded and distorted forms of the native state built around a specific folding nucleus. This view has been supported by a number of on-lattice and off-lattice simulations. Here we report a direct observation and characterization of the TSE by molecular dynamic folding simulations of the C-Src SH3 domain, a small protein that has been extensively studied experimentally. Our analysis reveals a set of key interactions between residues, conserved by evolution, that must be formed to enter the kinetic basin of attraction of the native state.

Computer Simulation↗

PubMed2002

Online hemodiafiltration versus acetate-free biofiltration: a prospective crossover study.

Online hemodiafiltration (online HDF) and acetate-free biofiltration (AFB) are 2 innovative renal replacement therapies. Convincing evidence has shown that both techniques are superior to conventional hemodialysis in many aspects. The aim of the present investigation was to compare online HDF and AFB in 12 stable maintenance hemodialysis patients in a prospective, randomized crossover trial. Twelve stable dialysis patients, age 49.7 +/- 11.3 years and on dialysis for 83.5 +/- 76.7 months, were treated prospectively and randomly by either AFB, predilution HDF (pre-HDF), or postdilution HDF (post-HDF) for a total of 36 weeks using exclusively F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters, and clearance for both small and larger molecular weight substances were measured at defined intervals. During the trial period inter- and intradialysis symptoms, e.g., hypotensive episodes and intradialysis arterial blood gas analyses, were recorded. Both online HDF and AFB were well accepted by the overwhelming majority of patients and also by the dialysis staff. Pretreatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between the 3 treatment groups. Potassium increased slightly in HDF patients while phosphate and beta2-microglobulin (beta2-M) decreased in all groups. After dialysis, AFB patients exhibited a significantly higher bicarbonate concentration and lower potassium level when identical potassium concentrations in dialysate were used. Patients receiving AFB manifested less intradialysis partial pressure of oxygen drop and partial pressure of carbon dioxide rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and beta2M clearance, and lower total interdialysis symptom scores than the AFB treatment method. While bone metabolism parameters did not differ between the 3 dialysis modalities, some parameters such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, and deoxypyridinoline in AFB deteriorated at the end of the crossover study. Aluminum concentration decreased progressively to about one-third of prestudy values at the end of the study with all 3 treatments. AFB was associated with a lower predialysis mean arterial pressure (MAP), a smaller drop in MAP during treatment, and similar hypotension episodes compared with the 2 HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of the trial period followed by a slight increase thereafter but still significantly lower than initial value at the end of crossover. Both online HDF and AFB share most of the features of optimal renal replacement therapy. Online HDF is superior to AFB in such aspects as increased delivered dialysis dose both for small and larger molecular weight toxins and less interdialysis symptoms. On the other hand, AFB is associated with a smaller effect on arterial blood gas values and improved intradialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level.

Adult↗

PubMed2002

[Effect of abnormal apoptosis in human decidual tissue during early gestation on pregnancy].

OBJECTIVE: To investigate the relationship between abnormal cellular apoptosis of the decidual tissue during the early stages of gestation and failure of pregnancy. METHODS: Samples of the decidual tissues of early gestation were obtained from 60 healthy women with pregnancy, and cellular apoptosis was assessed by using terminal transferase-mediated nick-end labeling (TUNEL). The expressions of Fas and FasL in the decidual tissues at different stages of gestation were examined by in situ hybridization and immunohistochemistry. RESULTS: On day 41 of normal pregnancy, evident apoptosis in the decidual tissues occurred with significantly enhanced Fas and FasL expressions, while obvious reduction in both the apoptotic cells and Fas and FasL expression was observed on day 54. In women with spontaneous abortion, increased apoptotic cells were present in the decidual tissues around day 55 of gestation when significantly enhanced Fas and FasL mRNA and protein expressions also took place, in comparison with those of healthy pregnant women on day 54. CONCLUSION: Abnormal apoptosis of the decidua during early gestation may be one of the mechanisms for spontaneous abortion, and the Fas pathway may play an important role in apoptosis induction.

Abortion, Spontaneous↗

PubMed2002

Determination of vitamin C in plasma and dialysate from uremia patients by high performance liquid chromatography with electrochemical detection.

A convenient and valid method for the determination of ascorbic acid(AA) and dehydroascorbic acid(DHAA) in plasma and dialysate from patients with uremia by high performance liquid chromatography with electrochemical detection is described. A mixture of 0.8 g/L metaphosphoric acid and 18% (volume fraction) perchloric acid was used as a protein precipitant and the extractant for AA from biosamples. It was also a good stabilizer for AA in samples. The proposed method is satisfied for routine screening of vitamin C in clinical applications with a correlation coefficient of more than 0.99 in the range of 2 mumol/L-40 mumol/L AA. The within-day precision was less than 8.9% and 10.55% for AA and DHAA, respectively. The recoveries of AA in plasma and dialysate were over 95% and 78%, respectively.

Ascorbic Acid↗

PubMed2002

[Preliminary research on environmental characteristics of oasis-desert ecotone].

Taking Minqin Oasis in the downstream of Shiyanghe Rivers as example, the shrub characteristics of sand dune, which was closely related to the vegetation of the interface between the outside of oasis and desert, was studied in this paper. The change of vegetation coverage and dune density indicated that the vegetation coverage in the ecotone was obviously higher than that in the outside of oasis and in drift desert. There existed an area outside oasis that was obviously affected by human activies and 0-600 m away from the outside of oasis. Meanwhile, the appearing position of area outside oasis was different in different place. The naked area ratio of dune in the area outside oasis was the biggest, so that the area outside oasis was the main resource of drift sand resulting in desertification of oasis. Over extracting ground water in oasis district resulted in a forming of dropping funnel of ground water there, and resulted in a fluid of ground water from desert to oasis. Ultimately, human activites aggravated those processes to some extent.

Agriculture↗