Biomedical subjects

Kang Chen

Publications and source records attributed to Kang Chen.

27 records · Page 2Linked to original sources

PubMed2004

The polyproline II conformation in short alanine peptides is noncooperative.

The finding that short alanine peptides possess a high fraction of polyproline II (PII) structure (Phi=-75 degrees, Psi=+145 degrees ) at low temperature has broad implications for unfolded states of proteins. An important question concerns whether or not this structure is locally determined or cooperative. We have monitored the conformation of alanine in a series of model peptides AcGGAnGGNH2 (n=1-3) over a temperature range from -10 degrees C to +80 degrees C. Use of 15N-labeled alanine substitutions makes it possible to measure 3JalphaN coupling constants accurately over the full temperature range. Based on a 1D next-neighbor model, the cooperative parameter sigma of PII nucleation is evaluated from the coupling constant data. The finding that sigma is close to unity (1 +/- 0.2) indicates a noncooperative role for alanine in PII structure formation, consistent with statistical surveys of the Protein Data Bank that suggest that most PII structure occurs in isolated residues. Lack of cooperativity in these models implies that hydration effects that influence PII conformation in water are highly localized. Using a nuclear Overhauser effect ratio strategy to define the alanine Psi angle, we estimate that, at 40 degrees C, the time-averaged alanine conformation (Phi=-80 degrees, Psi=+170 degrees ) deviates from canonical PII structure, indicating that PII melts at high temperature. Thus, the high-temperature state of short alanine peptides seems to be an unfolded ensemble with higher distribution in the extended beta structure basin, but not a coil.

Alanine↗

PubMed2004

[The toxic effect of N-methyl-N- nitrosourea on retina in rats].

PURPOSE: To observe the toxic effect of N-methyl-N-nitrosourea (MNU) on photoreceptor cells within retina of SD rats. METHODS: At 50 days of age, 100 female rats received a single intraperitoneal injection of MNU at different doses of 50 mg/kg, 60 mg/kg, 70 mg/kg and 80 mg/kg body weight, respectively. Each group had 6 rats and 4 untreated rats were used as normal control. At 24, 48 and 72 hours and 7 days after the administration of MNU, the animals were sacrificed and both eyes were enucleated immediately and processed for histological examination. RESULTS: It was found that all doses of MNU could sequentially damage the central and peripheral retina. The first evidence of retinapathy 24 hours after the application of MNU was pyknosis and disruption of photoreceptor cells nuclei and the disorientation of the photoreceptor outer segments; loss of photoreceptor cell deteriorated significantly at 48 hours or 72 hours; the outer nuclear layer and photoreceptor layer were almost completely lost at 7 days. CONCLUSION: The results demonstrated that MNU could selectively damage the photoreceptor cells in the retina of the rats, which was dose-dependent and time-dependent.

Animals↗

PubMed2003

Mycobacterial heat shock protein 65 enhances antigen cross-presentation in dendritic cells independent of Toll-like receptor 4 signaling.

Heat shock proteins (HSP) have been shown to enhance antigen processing and presentation through their association with antigenic peptides and delivery of these moieties into major histocompatibility complex class I pathways. In this study, mycobacterial Hsp65 is demonstrated to have the ability to help cross-present an exogenous protein by dendritic cells (DC) to CD8 T cells without the need for complex formation between Hsp65 and the protein. This ability of Hsp65 to enhance cross-presentation is independent of its weak stimulatory effect on DC, the latter seen only after prolonged incubation. When the effect of lipopolysaccharide contamination is abrogated, Hsp65 is unable to activate Toll-like receptor (TLR)4 in the presence of CD14 and MD2. This accounts for the inability of Hsp65 to drive maturation of DC and shows that Hsp65 is not a potent stimulator of DC. Thus, Hsp65 enhances the cross-presentation of a soluble, free antigen by DC, independent of TLR4 signaling and up-regulation of costimulatory molecules.

Antigen Presentation↗

PubMed2003

Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures.

Febrile (fever-induced) seizures are the most common form of childhood seizures, affecting 3%-5% of infants and young children. Here we show that the activity-dependent, retrograde inhibition of GABA release by endogenous cannabinoids is persistently enhanced in the rat hippocampus following a single episode of experimental prolonged febrile seizures during early postnatal development. The potentiation of endocannabinoid signaling results from an increase in the number of presynaptic cannabinoid type 1 receptors associated with cholecystokinin-containing perisomatic inhibitory inputs, without an effect on the endocannabinoid-mediated inhibition of glutamate release. These results demonstrate a selective, long-term increase in the gain of endocannabinoid-mediated retrograde signaling at GABAergic synapses in a model of a human neurological disease.

Action Potentials↗

PubMed2003

The pentapeptide GGAGG has PII conformation.

Most of what we know about proteins reflects their native folded structure. Much less is understood about the structure of unfolded proteins, which tends to be referred to as "random coil", lacking extended alpha-helix or beta-strand structure. Recent work suggests that unfolded proteins might adopt significant population of PII structure, an extended left-handed helix found in collagen and proline-rich peptides. A series of short peptides AcGGXGGNH2 has been adopted as a model for studying unfolded protein structure because of the minimal steric effect imposed by flanking glycines. Peptide AcGGAGGNH2 makes possible a host-guest conformation analysis of the middle residue alanine. NMR experiments reveal that the Phi and Psi dihedral angles of the central alanine are -73 degrees and 125 degrees , respectively, placing the alanine in the PII region of the Ramachandran plot. Circular dichroism shows a typical PII spectrum with a strong negative absorbance at 190 nm. Temperature experiments show the alanine structure shifts to increasing beta-strand at high temperature. Because the alanine side chain most closely represents unsubstituted peptide backbone, these results have significant implications for the conformational entropy of unfolded polypeptide chains.

Alanine↗

PubMed2003

Cluster randomization trial of sequence mass screening for colorectal cancer.

PURPOSE: Colorectal cancer is a major cause of death worldwide. To reduce the incidence and mortality from rectal cancer, an individual quantitative risk-assessment model (hereafter referred to as the Attributive Degree Value) and reverse passive hemagglutination fecal occult blood test were used in a randomized, controlled, population-based trial that was conducted in Jiashan County, People's Republic of China. METHODS: All residents of Jiashan County aged 30 years or older were enrolled in the study, and 21 townships in the county were randomized to either a screening (n = 10 townships) or control (n = 11 townships) group. Participants in the screened group submitted a one-article-per-slide stool sample and completed a structured risk-assessment questionnaire from which their attributive degree value was computed. According to study protocol, 4,299 participants were defined as high risk and underwent diagnostic evaluation with 60-cm flexible sigmoidoscopy and, in some cases, an additional screening with colonoscopy. RESULTS: From 1989 to 1996, cumulative mortality from colon cancer was 90 (95 percent confidence interval, 83-97) per 100,000 in the screened group and 83 (95 percent confidence interval, 76-90) per 100,000 in the control group (log-rank P = 1.49, P = 0.222). Mortality from rectal cancer during this time was 110 (95 percent confidence interval, 102-118) per 100,000 in the screened group, which differed significantly from the control group mortality rate of 161 (95 percent confidence interval, 152-170) per 100,000 (log-rank P = 0.003). CONCLUSION: Mass screening with a reverse passive hemagglutination fecal occult blood test along with an individual attributive degree value score was effective in reducing mortality from rectal cancer but not in reducing mortality from colon cancer or the incidence of colorectal cancer.

Adult↗

PubMed2002

Self-assembling morphology induced by nanoscale rods in a phase-separating mixture.

A symmetric binary mixture containing mobile nanoscale rods is quenched from a one-phase state into an unstable phase-separating region. Incorporating the motion of rods, the system undergoes spinodal decomposition to form a dropletlike structure. The rod-rod interaction and the preferential adsorption of one of the two immiscible phases onto the mobile rods play an important role in driving the system to self-assemble into this special structure. Within each cluster of the wetting phase, the rods align parallel to each other as in a nematic liquid crystal, while the rod orientations between these clusters are randomly distributed. However, an interconnected structure is recovered in the presence of hydrodynamic interaction. In the present phase-separating mixture with rods, the growth dynamics is examined in detail, and our simulations reveal a crossover from a rod-mobility-dependent to an independent regime. The system always exhibits slowing-down growth behavior where the well-known diffusive Lifshitz-Slyozov mechanism and hydrodynamic effects are both suppressed.

Journal Article↗

PubMed2002

Postsynaptic effects of GABAergic synaptic diversity: regulation of neuronal excitability by changes in IPSC variance.

GABAergic synaptic inputs to principal cells are heterogeneous in terms of their anatomical, molecular and physiological properties. Whether diversity in GABAergic synaptic inputs affects the efficacy of GABAergic inhibition is not understood. Here we show that alterations in the heterogeneity of IPSC populations arriving at single cells can significantly modify the effects of GABAergic inputs on neuronal excitability. The effects of IPSC diversity were examined in a computational model that incorporated experimentally measured values for spontaneous IPSCs and CA1 pyramidal cell electrophysiological properties. The simulations showed that increased variance in the conductance or decay of IPSCs could potently modulate the firing rate of the postsynaptic cells. The actual direction of the IPSC variance-induced modulation in postsynaptic cell discharges depended on the mean IPSC conductance and mean decay time constant around which the variance was introduced, as well as on the degree of depolarization and firing of the postsynaptic cell. Further analysis of the underlying mechanisms determined that these effects of IPSC variance on neuronal excitability were entirely predicted from the non-linear actions of IPSCs on action potential generation. The variance effects on neuronal excitability could be strong enough to overcome even large changes in mean IPSC conductance, demonstrating that increased mean synaptic conductance (or increased mean IPSC or IPSP) alone does not necessarily imply a more effective inhibition, a finding which has important implications for epilepsy research. These data show that the degree of heterogeneity of the GABAergic synaptic inputs to principal cells can powerfully modulate the efficacy of GABAergic inhibition. The results indicate the functional importance of the diversity of interneurons in cortical and hippocampal circuits, and suggest that plastic changes in GABAergic synaptic diversity may modulate neuronal excitability under both normal and pathological conditions.

Cerebral Cortex↗

PubMed2002

H-channels in epilepsy: new targets for seizure control?

Hyperpolarization-activated cation channels (h-channels) are key regulators of neuronal excitation and inhibition, and have a rich diversity of subunit composition, distribution, modulation and function. Recent results indicate that the behavior of h-channels can be altered significantly by seizures. The activity-dependent, short-term and long-term plasticity of h-channels can, in turn, modulate neuronal excitability. The reciprocal interactions between neuronal activity and h-channels indicate that these ion channels could be promising novel targets for anti-epileptic therapies.

Anticonvulsants↗