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Feng Ding

Publications and source records attributed to Feng Ding.

At least 37 records · Page 2Linked to original sources
PubMed2005

Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader-Willi syndrome mouse models.

Prader-Willi syndrome (PWS) is a neurobehavioral disorder caused by the lack of paternal expression of imprinted genes in the human chromosome region 15q11-13. Recent studies of rare human translocation patients narrowed the PWS critical genes to a 121-kb region containing PWCR1/HBII-85 and HBII-438 snoRNA genes. The existing mouse models of PWS that lack the expression of multiple genes, including Snrpn, Ube3a, and many intronic snoRNA genes, are characterized by 80%-100% neonatal lethality. To define the candidate region for PWS-like phenotypes in mice, we analyzed the expression of several genetic elements in mice carrying the large radiation-induced p(30PUb) deletion that includes the p locus. Mice having inherited this deletion from either parent develop normally into adulthood. By Northern blot and RT-PCR assays of brain tissue, we found that Pwcr1/MBII-85 snoRNAs are expressed normally, while MBII-52 snoRNAs are not expressed when the deletion is paternally inherited. Mapping of the distal deletion breakpoint indicated that the p30PUb deletion includes the entire MBII-52 snoRNA gene cluster and three previously unmapped EST sequences. The lack of expression of these elements in mice with a paternal p30PUb deletion indicates that they are not critical for the neonatal lethality observed in PWS mouse models. In addition, we identified MBII-436, the mouse homolog of the HBII-436 snoRNA, confirmed its imprinting status, and mapped it outside of the p30PUb deletion. Taking together all available data, we conclude that the lack of Pwcr1/MBII-85 snoRNA expression is the most likely cause for the neonatal lethality in PWS model mice.

Animals↗
PubMed2005

Scaling behavior and structure of denatured proteins.

An ensemble of random-coil conformations with no persistent structures has long been accepted as the classical model of denatured proteins due to its consistency with the experimentally determined scaling of protein sizes. However, recent NMR spectroscopy studies on proteins at high chemical denaturant concentrations suggest the presence of significant amounts of native-like structures, in contrast to the classical random-coil picture. To reconcile these seemingly controversial observations, we examine thermally denatured states of experimentally characterized proteins by using molecular dynamics simulations. For all studied proteins, we find that denatured states indeed have strong local conformational bias toward native states while a random-coil power law scaling of protein sizes is preserved. In addition, we explain why experimentally determined size of the protein creatine kinase does not follow general scaling. In simulations, we observe that this protein exhibits a stable intermediate state, the size of which is consistent with the reported experimental observation.

Computer Simulation↗
PubMed2005

Simple but predictive protein models.

The traditional approach to computational biophysics studies of molecular systems is brute force molecular dynamics simulations under the conditions of interest. The disadvantages of this approach are that the time and length scales that are accessible to computer simulations often do not reach biologically relevant scales. An alternative approach, which we call intuitive modeling, is hypothesis-driven and based on tailoring simplified protein models to the systems of interest. Using intuitive modeling, the length and time scales that can be achieved using simplified protein models exceed those of traditional molecular-dynamic simulations. Here, we describe several recent studies that signify the predictive power of simplified protein models within the intuitive-modeling approach.

Computer Simulation↗
PubMed2005

Comparisons between oral pulse alfacalcidol therapy and daily therapy in maintenance hemodialysis patients with secondary hyperparathyroidism: a randomized, controlled, and multicenter study.

OBJECTIVE: To investigate the efficacy and safety of 1alpha-(OH)-D3 high-dose pulse therapy or daily low-dose therapy in secondary hyperthyroidism in maintenance hemodialysis patients in China. METHODS: Maintenance hemodialysis patients of both gender with intact parathyroid hormone (iPTH) level above 200 pg/mL were randomly divided into a pulse group and a daily group. They were treated for 20 weeks, with 2 microg oral Alfacalcidol twice weekly or thrice weekly in the pulse group, and 0.5 microg oral Alfacalcidol per day in the daily group. The therapeutic end point was parathyroid hormone level < 200 pg/ mL. The iPTH levels during the study were monitored, and parameters representative of calcium and phosphate metabolism and side effects were also observed. RESULTS: One hundred and fifty-eight patients were initially enrolled, 91 in the pulse therapy group and 67 in the daily therapy group. There was no significant difference in age, hemodialysis duration, proportion of diabetic nephropathy and systemic diseases, proportion of patients who had received active vitamin D therapy previously, mean initial iPTH level (pulse group 570.47 +/- 295.86 pg/mL; daily group 498.33 +/- 207.84 pg/mL), serum calcium, serum phosphate, alkaline phosphatase (AKP), and albumin between two groups. In the pulse therapy group there were more patients with iPTH levels of 500 to approximately 1,000 pg/mL and > 1,000 pg/mL, so stratified analysis according to iPTH level was used. In therapeutic end point, iPTH levels in both groups were significantly lower compared with those before therapy (pulse group 261.29 +/- 234.97 pg/mL, P < .01; daily group 262.17 +/- 274.82 pg/mL, P < .01). After 4 weeks, the ratio of reaching end point in the pulse group was 35.2%, which was significantly higher than that (19.4%) in the daily group (P < .05). More obvious change was seen in the 200 to approximately 500 pg/mL subgroup by stratified analysis (P < .05), whereas there was no significant difference between the 500 to approximately 1,000 pg/mL and > 1,000 pg/mL subgroup (P > .05). At therapeutic end point, the total ratio of reaching end point did not differ between the two groups, and there were no obvious differences between each subgroup. In the iPTH 200 to approximately 500 pg/mL subgroup, mean iPTH%/week in the pulse group was significantly higher than that in the daily group, and no obvious difference was seen in other subgroups. AKP levels decreased significantly in both groups at therapeutic end point (pulse group 98.42 +/- 54.52 vs. 74.21 +/- 30.68 IU/L, P < .01; daily group 103.3 +/- 68.04 vs. 75.40 +/- 34.12 IU/L, P < .01). On the 4th week, AKP level in pulse group (82.39 +/- 35.23 IU/L) was significantly lower than the initial level (98.42 +/- 54.52 IU/L, P < .05), whereas in the daily group there was no difference between each week. The mean serum calcium, phosphate, and [Ca2+] x [P3+] levels in both groups did not change greatly. Nine patients in the pulse group (9.9%) and 8 patients in the daily group (11.9%) suffered hypercalcemia at least once. Persistent hypercalcemia occurred in 8 patients in the pulse group (8.8%) and 9 patients in the daily group (13.4%), but the difference in proportion did not show statistical significance. The serum phosphate in the daily group was higher after the therapy (1.74 +/- 0.36 vs. 1.89 +/- 0.36 mmol/L, P < .05), whereas that in the pulse group remained unchanged. At therapeutic end point, [Ca2+] x [P3+] level in the daily group was higher than that before the therapy (48.04 +/- 11.71 vs. 55.46 +/- 12.66, P < .05), whereas in the pulse group there was no significant difference. Side effects for both groups were minimal and well tolerated. CONCLUSIONS: Alfacalcidol [1alpha-(OH)-D3] has good and safe effects on secondary hyperparathyroidism in maintenance hemodialysis patients. The efficacy and early effects of pulse therapy are superior to those of daily therapy in moderate hyperparathyroidism patients.

Administration, Oral↗
PubMed2005

Use of ascorbate-rich dialysate to attenuate oxidative stress in maintenance hemodialysis patients.

BACKGROUND: Oxidative stress exists in uremic milieu, particularly in maintenance hemodialysis (MHD) patients, and accounts for certain long-term complications. Yet little is known about whether supplementation of ascorbic acid (vitamin C, or vitC) via extracorporeal circuit has substantial effects on minifying oxidative impairment. SUBJECTS AND METHODS: The entire experiment consisted of three sections: 1) Practicing ascorbate dialysate among 8 MHD patients in a single dialysis session, compared with a conventional hemodialysis session and another one with intravenous injection of vitC. In each session, oxidative stress markers--namely, plasma total ascorbic acid (TAA), ratio of dehydroascorbic acid (DHAA) to TAA (DHAA/TAA), vitamin E (vitE), and malondialdehyde (MDA)--in both plasma and erythrocytes were measured. 2) A relatively long-term application of ascorbate dialysate in 12 of 23 MHD patients, who were randomly allocated to experimental group (n = 12), and control group (n = 11). Oxidative stress markers and main hematological and biochemical indices were determined at the beginning and end of the period. 3) Application of ascorbate dialysate in 10 MHD patients with intravenous iron treatment, performed in similar procedures as section 1. In addition to determining the aforementioned oxidative stress markers, area under the curve (AUC0-180 min) of ratio of plasma MDA to cholesterol (MDA:Cho) was calculated to evaluate the extent of lipoperoxidation. RESULTS: 1) Plasma TAA gradually decreased during dialysis, whereas a mild increase appeared in MDA. A protruding TAA concentration peak, as well as an extreme DHAA/TAA reduction, followed the injection of vitC, but soon a precipitous fall in DHAA/TAA ensued. Stable plasma TAA and slightly raised vitE were observed when applying ascorbate dialysate. 2) Plasma TAA augmented (27.4 +/- 13.3 vs. 16.8 +/- 9.5 mg/dL, P < .05) and plasma low-density lipoprotein (oxLDL) became two-thirds of baseline data (32.6 +/- 25.2 vs. 83.8 +/- 56.5 micromol/L, P < .05) in the experimental group, whereas oxLDL in the control group reduced quantitatively but not significantly in statistics. (3) As iron sucrose was infused, the decline of TAA and ascending of MDA would be abated not only by intravenous drop of vitC, but also by ascorbate dialysate; however, TAA or MDA curve manifested totally distinguished in the two modalities. AUC0-180 min in ascorbate dialysate group was significantly less than that in control group (400.25 +/- 28.54 vs. 487.25 +/- 109.82). CONCLUSION: Plasma ascorbic acid diminished a great deal during hemodialysis, and at the same time oxidative stress formed and intensified, which will be exacerbated by a remedy of frequent intravenous iron. Ascorbate supplementation, by means of either infusion or extracorporeal circuit, can lessen the loss and therefore attenuate oxidative stress. The latter pattern takes the advantage of retaining the approximate internal balance instead of exquisite change in vivo due to administration of intravenous vitC.

Ascorbic Acid↗
PubMed2004

Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model.

We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein--Trp-cage--from a fully extended conformation. We demonstrate the ability of the Trp-cage model to consistently reach conformations within 2-angstroms backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp-cage conformations in simulations can be <1 angstroms. Our findings suggest that, at least in the case of Trp-cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp-cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein.

Algorithms↗
PubMed2004

Molecular dynamics study of the catalyst particle size dependence on carbon nanotube growth.

The molecular dynamics method, based on an empirical potential energy surface, was used to study the effect of catalyst particle size on the growth mechanism and structure of single-walled carbon nanotubes (SWNTs). The temperature for nanotube nucleation (800-1100 K), which occurs on the surface of the cluster, is similar to that used in catalyst chemical vapor deposition experiments, and the growth mechanism, which is described within the vapor-liquid-solid model, is the same for all cluster sizes studied here (iron clusters containing between 10 and 200 atoms were simulated). Large catalyst particles, which contain at least 20 iron atoms, nucleate SWNTs that have a far better tubular structure than SWNTs nucleated from smaller clusters. In addition, the SWNTs that grow from the larger clusters have diameters that are similar to the cluster diameter, whereas the smaller clusters, which have diameters less than 0.5 nm, nucleate nanotubes that are approximately 0.6-0.7 nm in diameter. This is in agreement with the experimental observations that SWNT diameters are similar to the catalyst particle diameter, and that the narrowest free-standing SWNT is 0.6-0.7 nm.

Journal Article↗
PubMed2004

New insights into FAK signaling and localization based on detection of a FAT domain folding intermediate.

Mounting evidence suggests that the focal adhesion targeting (FAT) domain, an antiparallel four-helix bundle, exists in alternative conformations that may modulate phosphorylation, ligand binding, and the subcellular localization of focal adhesion kinase (FAK). In order to characterize the conformational dynamics of the FAT domain, we have developed a novel method for reconstructing the folding pathway of the FAT domain by using discrete molecular dynamics (DMD) simulations, with free energy constraints derived from NMR hydrogen exchange data. The DMD simulations detect a folding intermediate, in which a cooperative unfolding event causes helix 1 to lose helical character while separating from the helix bundle. The conformational dynamic features of helix 1 in the intermediate state of the FAT domain are likely to facilitate Y926 phosphorylation, yet interfere with paxillin binding. The presence of this intermediate state in vivo may promote FAK signaling via the ERK/MAPK pathway and by release of FAK from focal adhesions.

Focal Adhesion Protein-Tyrosine Kinases↗
PubMed2004

Multiple folding pathways of the SH3 domain.

Experimental observations suggest that proteins follow different folding pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the c-Crk SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature-the temperature for which the c-Crk SH3 domain undergoes a rapid folding transition with minimal kinetic barriers-and observe that below this temperature the model protein may undergo a folding transition by multiple folding pathways via only one or two intermediates. Our findings suggest the hypothesis that the SH3 domain, a protein fold for which only two-state folding kinetics was observed in previous experiments, may exhibit intermediate states under conditions that strongly stabilize the native state.

Animals↗
PubMed2004

[Determination of iohexol by high performance liquid chromatography].

A fast, sensitive and reproducible method for the determination of iohexol by high performance liquid chromatography with narrow-bore column was developed. The method involved one step deproteinization of plasma by perchloric acid and a simple, isocratic elution system of 7% (v/v) methane solution. The linearity of the method ranged from 0.5 to 500 mg/L of iohexol with a correlation coefficient of more than 0.999 8. Minimum detection limit was 154 pg of the agent in plasma. Retention time for the contrast medium in the elution system was (3.46 +/- 0.02) min and a single run was less than 5 min. The relative standard deviation of iohexol in peak area was less than 4.3% for run to run within a day and 11.4% for day to day operations. The recoveries of iohexol in plasma were over 91.51% at low, middle and high concentrations.

Chromatography, High Pressure Liquid↗
PubMed2003

Folding of Cu, Zn superoxide dismutase and familial amyotrophic lateral sclerosis.

Cu, Zn superoxide dismutase (SOD1) has been implicated in the familial form of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). It has been suggested that mutant mediated SOD1 misfolding/aggregation is an integral part of the pathology of ALS. We study the folding thermodynamics and kinetics of SOD1 using a hybrid molecular dynamics approach. We reproduce the experimentally observed SOD1 folding thermodynamics and find that the residues which contribute the most to SOD1 thermal stability are also crucial for apparent two-state folding kinetics. Surprisingly, we find that these residues are located on the surface of the protein and not in the hydrophobic core. Mutations in some of the identified residues are found in patients with the disease. We argue that the identified residues may play an important role in aggregation. To further characterize the folding of SOD1, we study the role of cysteine residues in folding and find that non-native disulfide bond formation may significantly alter SOD1 folding dynamics and aggregation propensity.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Mechanism for the alpha-helix to beta-hairpin transition.

The aggregation of alpha-helix-rich proteins into beta-sheet-rich amyloid fibrils is associated with fatal diseases, such as Alzheimer's disease and prion disease. During an aggregation process, protein secondary structure elements-alpha-helices-undergo conformational changes to beta-sheets. The fact that proteins with different sequences and structures undergo a similar transition on aggregation suggests that the sequence nonspecific hydrogen bond interaction among protein backbones is an important factor. We perform molecular dynamics simulations of a polyalanine model, which is an alpha-helix in its native state and observe a metastable beta-hairpin intermediate. Although a beta-hairpin has larger potential energy than an alpha-helix, the entropy of a beta-hairpin is larger because of fewer constraints imposed by the hydrogen bonds. In the vicinity of the transition temperature, we observe the interconversion of the alpha-helix and beta-sheet states via a random coil state. We also study the effect of the environment by varying the relative strength of side-chain interactions for a designed peptide-an alpha-helix in its native state. For a certain range of side-chain interaction strengths, we find that the intermediate beta-hairpin state is destabilized and even disappears, suggesting an important role of the environment in the aggregation propensity of a peptide.

Amino Acid Sequence↗
PubMed2003

Effect of continuous hemofiltration on hemodynamics, lung inflammation and pulmonary edema in a canine model of acute lung injury.

OBJECTIVE: This study examined whether continuous hemofiltration favorably affects cardiopulmonary variables, lung inflammation, and lung fluid balance in a canine model of oleic acid induced acute lung injury. METHODS: Eleven pentobarbital-anesthetized dogs were randomly divided into a control (mechanical ventilation, MV) group (n=6) and a MV plus hemofiltration (HF) group (n=5). All animals received an intravenous injection of oleic acid (0.09 ml/kg) to induce acute lung injury. Continuous arterial-venous hemofiltration (blood flow 100 ml/min, ultrafiltration rate at 50-65 ml kg(-1) h(-1)) was started after establishment of oleic acid induced acute lung injury and continued for 4 h. Hemodynamics, lung mechanics, gas exchange, lung fluid balance, lung histology, and the level of plasma cytokines were assessed. RESULTS: After 240 min of HF treatment there was a significant increase in cardiac output, reduction in pulmonary arterial pressure, and improvement in both oxygenation and lung mechanics. Also, in the HF group the lung wet-to-dry weight ratio was significantly reduced. Histologically, HF reduced edema and inflammatory cell infiltration in the lung. There was also a significantly greater decrease in plasma IL-6 and IL-8 levels in the HF group than in group receiving MV alone. CONCLUSIONS: In a canine model of acute lung injury continuous HF improved cardiopulmonary function, reduced pulmonary edema, decreased lung permeability and inflammation, and decreased the plasma concentration of proinflammatory cytokines.

Albumins↗
PubMed2003

Conservation of Dnmt1o cytosine methyltransferase in the marsupial Monodelphis domestica.

Imprinted genes have been identified in both eutherian mammals and in marsupials. In eutherian species, there is a conservation of the imprinting process, both in terms of the genes imprinted and the epigenetic inheritance mechanism. In the mouse, the inheritance of gametic methylation patterns depends on an oocyte-derived isoform of the Dnmt1 (cytosine-5)-methyltransferase protein, Dnmt1o, which functions during preimplantation development to maintain methylation patterns on imprinted alleles. To determine if this component of genomic imprinting is also found in marsupials, Dnmt1 isoforms were examined in somatic cells and germ cells of the South American opossum Monodelphis domestica. There is a Dnmt1o protein in Monodelphis oocytes that is synthesized, as in the mouse, from a different transcript than the somatic Dnmt1 protein. Thus, an essential component of imprinting in eutherian mammals is found in a marsupial species, suggesting that marsupials and eutherian mammals imprint their genes with the same methylation-dependent mechanism.

Amino Acid Sequence↗
PubMed2003

Molecular diagnosis of Down's syndrome.

OBJECTIVE: To establish a new diagnostic method for Down's syndrome using polymerase chain reaction (PCR). METHODS: DNA extracted from five healthy individuals and five Down's syndrome patients was amplified in six specific tetranucleotide repeat loci on chromosome 21 using PCR. An accurate diagnosis was made by analyzing allelic distribution at each locus. RESULTS: All Down's syndrome patients were identified as having at least two loci with three alleles, while none of the healthy individuals had three alleles. In addition, when two alleles were identified for a particular locus in the Down's syndrome samples, it was more likely that the intensity ratio between the two alleles was close to 2:1. CONCLUSION: The molecular method can provide a fast, accurate, and economical alternation for the traditional cytogenetic diagnostic method for Down's syndrome.

Cytogenetic Analysis↗