Biomedical subjects

Yuhong Wang

Publications and source records attributed to Yuhong Wang.

15 recordsLinked to original sources

PubMed2026

Ampyrone is a direct agonist of human tyrosinase and a potential therapeutic for hypopigmentation disorders.

Significant loss of pigmentation can increase visual disability, skin cancer risk, and psychosocial stress. Tyrosinase (TYR) catalyzes the first and rate-limiting step of melanin synthesis. Inhibitors of TYR are well established and are currently used in clinical settings; however, there is a dearth of direct activators of TYR. Here, using a human TYR construct, we developed high-throughput screening methods, in cell confirmatory assays employing 13C-tyrosine tracing, and computational analysis techniques, and identified ampyrone (4-aminoantipyrine) as a TYR activator. Ampyrone increased the in vitro catalytic activity of the human recombinant intramelanosomal domain of TYR (hTYR) and its hypomorphic variant, Pro406Leu (P406L), a cause of oculocutaneous albinism type 1B (OCA1B). Moreover, ampyrone induced melanin synthesis in both WT and OCA1B human melanocytes, mouse OCA2 melanocytes, as well as 3-dimensional (3D) human skin cultures. Computational studies provided additional insight into the effects of direct TYR agonists on enzyme activity. Our results identify ampyrone as a lead candidate for TYR activation, potentially supporting the development of therapies for patients with genetic and acquired diseases of hypopigmentation.

Humans↗

PubMed2006

Bubble kinematics in a sheared foam.

We characterize the kinematics of bubbles in a sheared two-dimensional foam using statistical measures. We consider the distributions of both bubble velocities and displacements. The results are discussed in the context of the expected behavior for a thermal system and simulations of the bubble model. There is general agreement between the experiments and the simulation, but notable differences in the velocity distributions point to interesting elements of the sheared foam not captured by prevalent models.

Journal Article↗

PubMed2006

A 1500-year record of lead, copper, arsenic, cadmium, zinc level in Antarctic seal hairs and sediments.

To reconstruct the profiles of heavy metal levels in the South Ocean ecosystem of Antarctica, the concentrations of lead (Pb), copper (Cu), arsenic (As), cadmium (Cd), and zinc (Zn) in seal hairs and lake sediments spanning the past 1500 years from Fildes Peninsula of King George Island and in weathering lake sediments from Nelson Island of West Antarctica were determined. The lead contents in the seal hairs and the weathering sediments show a sharp increase since the late 1800s, very likely due to anthropogenic contamination from modern industries. After the 1980s, the Pb content in seal hairs dropped by one-third, apparently due to the reduced usage of leaded gasoline in the Southern Hemisphere. Copper arises mainly from the weathering process, and its level may be substantially affected by climatic conditions. The concentrations of Cd, As, and Zn do not show any clear temporal trends.

Animals↗

PubMed2006

P and trace metal contents in biomaterials, soils, sediments and plants in colony of red-footed booby (Sula sula) in the Dongdao Island of South China Sea.

Concentrations of P and trace metals Zn, Cu, Cd, Pb and Hg in the faeces, bones, eggshells and feathers of seabirds and in the plants, soils and sediments with and without seabird influence on Dongdao Island, South China Sea, were determined and analyzed. Among the seabird biomaterials, the levels of P, Zn, Cu and Cd are the highest in the droppings and several times those in other materials; the Hg concentration is the highest in the feathers; and the Pb content is comparable among these biomaterials. These marked differences indicate different intake-bioaccumulation-elimination pathways for different trace metals. The levels of P, Zn, Cu, Cd and Hg in the plant, soil and sediment samples with the influence of seabird droppings are significantly higher than those in the samples without, and they are significantly correlated with each other. Thus, P, Zn, Cu, Cd and Hg are very likely to have a common source-predominantly bird guano-and the faeces of red-footed booby is an important vector for the flux of nutrient phosphorus and trace metals Zn, Cu, Cd and Hg from marine to island ecosystems on Dongdao Island.

Animal Structures↗

PubMed2006

Impact of boundaries on velocity profiles in bubble rafts.

Under conditions of sufficiently slow flow, foams, colloids, granular matter, and various pastes have been observed to exhibit shear localization, i.e., regions of flow coexisting with regions of solidlike behavior. The details of such shear localization can vary depending on the system being studied. A number of the systems of interest are confined so as to be quasi two-dimensional, and an important issue in these systems is the role of the confining boundaries. For foams, three basic systems have been studied with very different boundary conditions: Hele-Shaw cells (bubbles confined between two solid plates); bubble rafts (a single layer of bubbles freely floating on a surface of water); and confined bubble rafts (bubbles confined between the surface of water below and a glass plate on top). Often, it is assumed that the impact of the boundaries is not significant in the "quasistatic limit," i.e., when externally imposed rates of strain are sufficiently smaller than internal kinematic relaxation times. In this paper, we directly test this assumption for rates of strain ranging from 10(-3) to 10(-2) s(-1). This corresponds to the quoted rate of strain that had been used in a number of previous experiments. It is found that the top plate dramatically alters both the velocity profile and the distribution of nonlinear rearrangements, even at these slow rates of strain. When a top is present, the flow is localized to a narrow band near the wall, and without a top, there is flow throughout the system.

Journal Article↗

PubMed2006

Transpupillary argon laser photocoagulation and Nd:YAG laser cystotomy for peripheral iris pigment epithelium cyst.

PURPOSE: To report the use of a combination of transpupillary argon laser photocoagulation and Nd:YAG laser cystotomy in the treatment of peripheral iris pigment epithelium (IPE) cyst. DESIGN: Case report. METHODS: A 23-year-old man presented with a one-month history of blurred vision and pain in the right eye. Slit-lamp biomicroscopy and gonioscopy revealed, in the iridociliary sulcus, a large clear IPE cyst, which was demonstrated by ultrasound biomicroscopy (UBM). A combination of transpupillary photocoagulation to devitalize the epithelial lining and neodymium-doped yttrium aluminum garnet (Nd:YAG) laser cystotomy to drain the cyst was engaged. RESULTS: Laser treatment resulted in vanishing of the cyst and disappearance of the subject symptoms. Two months postoperatively, no evidence existed of the iris pigment cyst regrowth. CONCLUSIONS: The minimal invasiveness of the combination of transpupillary laser photocoagulation and cystotomy yielded a favorable result. This procedure may be an alternative to conservative regimen if IPE cyst is clearly defined and readily seen.

Adult↗

PubMed2006

Characterization and expression of serotonin transporter genes in zebrafish.

To understand the development of serotonergic neurons in vertebrates, we used zebrafish as a model system. In this study we cloned two cDNAs (complementary DNAs) coding for serotonin transporter (SERT) from the zebrafish, named serta and sertb. The serta cDNA encodes a protein of 693 amino acids and showed high level of sequence identity with rat and human SERTs. In situ hybridization showed serta to be expressed in raphe nuclei, ventral posterior tuberculum and pineal organ. The expression of serta in raphe and ventral posterior tuberculum overlapped with the location of serotonin and expression of tryptophan hydroxylase, which is a key enzyme for serotonin synthesis. In the pineal organ serta is expressed in the cells in the vicinity of tryptophan hydroxylase-positive cells. We also cloned another zebrafish serotonin transporter, sertb, and found to be expressed in the medulla oblongata and in the inner nuclear layer of retina. The existence of two sert genes in the zebrafish genome indicates the gene was duplicated in the process of evolution as can be seen in other genes in the teleosts including zebrafish. The expression of the serta cDNA in cultured cells conferred a serotonin transport activity, thus indicating the validity of the cloned cDNA. We have established the expression system of zebrafish serotonin transporter in the cell culture in the present study, which is useful for the pharmacological analysis to determine the important residues for the interaction with serotonin and inhibitors. The expression system in the cell culture can be used to determine the effective concentration of inhibitors and addictive drugs. These information might be useful to evaluate the effect of those chemicals on serotonin neuron development and behavior of the animal.

Amino Acid Sequence↗

PubMed2005

A 2,000-year record of mercury and ancient civilizations in seal hairs from King George Island, West Antarctica.

The concentrations of total mercury (Hg(T)) and three bio-essential elements (phosphor, potassium, sodium) were analyzed in Antarctic seal hairs from a lake core spanning the past 2,000 years and collected from King George Island (63 degrees 23'S, 57 degrees 00'W), West Antarctica. The Hg(T) concentration shows a significant fluctuation while the levels of the three bio-essential elements remain almost constant. The rise and fall of the Hg(T) concentration in the seal hairs are found to be closely coincided with ancient activities of gold and silver mining using Hg-amalgamation process around the world, especially in the Southern Hemisphere. Briefly, Hg(T) levels are high during five episodes of extensive gold and silver mining activities--Rome Empire and China Han Dynasty (approximately 18-300 A.D.), Maya period and China Tang (750-900 A.D.), Incas civilization and Christian Kingdom (1200-1500 A.D.), New world (1650-1800 A.D.), and modern industry period (1840 A.D.-present); they are low during four time periods of reduced gold and silver mining activities--the China Han and Rome fall (since 300 A.D.), Maya fall and Wartime period in China (1050-1250 A.D.), Pizarro coming (ca. 1532 A.D.) and Independence War of South America (1800-1830 A.D.). Two profiles of Hg(T) in other two lake cores, one affected by seal excrements and the other by penguin droppings, from the same region are similar to the one in seal hairs. The Hg concentration profile in the seal hairs is significantly correlated with the one in a peat bog of Southern Chile near King George Island. Since Hg is existent mainly at the form of methyl-mercury in seal hairs, this correlation supports a relationship and link between atmospheric mercury concentration and methyl-mercury production. Comparing with samples from American and European continents, the Antarctic seal hairs provide an archive of total mercury concentration in surface seawater of the South Ocean less affected by regional human activities, and this archive may provide a good reference for assessing the global Hg emissions, depositions and recycling in the past thousand years.

Animals↗

PubMed2005

Reconstruction of ancient genome and gene order from complete microbial genome sequences.

Microbial genome sequences provide us with the fossil records for inferring their origination and evolution. Assuming that current microbial genomes are the evolutionary results of ancient genomes or fragments and the neighboring genes in ancient genomes are more likely neighbors in current genomes, in this paper we proposed a paleontological algorithm and assembled the orthologous gene groups from 66 complete and current microbial genome sequences into a pseudo-ancient genome, which consists of continuous fragments of various sizes. We performed bootstrap resampling and correlation analyses and the results showed that the assembled ancient genome and fragments are statistically significant and the genes of the same fragment are inherently related and likely derived from common ancestors. This method provides a new computational tool for studying microbial genome structure and evolution.

Algorithms↗

PubMed2005

A novel method of detecting rCBF with laser-Doppler flowmetry without cranial window through the skull for a MCAO rat model.

BACKGROUND AND PURPOSE: In a rat model of middle cerebral artery occlusion (MCAO) with intraluminal technique, lesion volume and its reproducibility vary among laboratories. Although laser-Doppler flowmetry (LDF) is useful to optimize the reliability, conventional methods require a craniotomy and special apparatus. The purpose of this study was to evaluate a novel approach for LDF monitoring of rCBF through lateral aspect of the skull without a craniotomy. METHODS: SD rats were subjected to 45 min of MCAO using an intraluminal thread. MCAO was achieved by an examiner who had been trained 4 weeks for making the model with no LDF monitoring (Group-1, n = 12), while in the other group, the same examiner induced MCAO using a novel approach of LDF monitoring (Group-2, n = 12). rCBF was detected through an LDF probe attached to the lateral aspect of the skull. The survival rate and the infarct volume were estimated for comparison between the two groups 2 days after MCAO. RESULTS: The mortality rate was 25% in Group-1 and 0% in Group-2. The lesion volume of the cortex in Group-2 was 167.21 +/- 48.54 mm(3) (mean +/- SD), which was larger than that in Group-1 (112.77 +/- 36.03 mm(3), P = 0.026). The coefficient variation of the lesion volume was smaller in Group-2 (29%) than in Group-1 (35%), indicating better reproducibility of the lesion volume in Group-2 than in Group-1. CONCLUSIONS: The approach of LDF monitoring through the lateral aspect of skull was useful for making large consistent infarct with reducing intraanimal variability and unexpected animal death for rat MCAO model.

Animals↗

PubMed2004

Human myoglobin recognition of oxygen: dynamics of the energy landscape.

Femtosecond to nanosecond dynamics of O(2) rebinding to human WT myoglobin and its mutants, V68F and I107F, have been studied by using transient absorption. The results are compared with NO rebinding. Even though the immediate environment around the heme binding site is changed by the mutations, the picosecond geminate rebinding of oxygen is at most minimally affected. On the other hand, the V68F (E11) mutation causes drastic differences in rebinding on the nanosecond time scale, whereas the effect of the I107F (G8) mutation remains relatively small within our 10-ns time window. Unlike traditional homogeneous kinetics and molecular dynamics collisional simulations, we propose a "bifurcation model" for populations of directed and undirected dynamics on the ultrafast time scale, reflecting the distribution of initial protein conformations. The major mutation effect occurs on the time scale on which global protein conformational change is possible, consistent with transitions between the conformations of directed and undirected population playing a role in the O(2) binding. We discuss the relevance of these findings to the bimolecular function of the protein.

Biochemical Phenomena↗

PubMed2003

Preparation and reactivity of O2-sulfonated diazeniumdiolates.

We report the facile preparation of O2-sulfonated diazeniumdiolates and mechanistic investigation of their reactions with representative nucleophiles. This new class of compounds extends the range of O2-substituted diazeniumdiolates available for potential applications in research and medicine.

Alkanesulfonates↗

PubMed2003

An interactive tool for extracting exons and SNP from genomic sequence: isolation of HCN1 and HCN3 ion channel genes.

Genome Analyzer (GenoA) with a relational database back-end, was developed to extract information from mammalian genomic sequences. This data mining and visualization tool-set enables laboratory bench scientists to identify and assemble virtual cDNA from genomic exon sequences, and provides a starting point to identify potential alternative splice variants and polymorphisms in silico. The study described in this paper demonstrates the use of GenoA to study human brain hyperpolarization-activated cation channel genes HCN1 and HCN3.

Amino Acid Sequence↗

PubMed2002

Computational and experimental studies of the effect of substituents on the singlet-triplet energy gap in phenyl(carbomethoxy)carbene.

The effect of aromatic substitution on the singlet-triplet energy gap in substituted phenyl(carbomethoxy)carbene (X-Ph-C-CO(2)CH(3), PCC) has been explored by time-resolved infrared (TRIR) spectroscopy and gas-phase computational methods. The ground state of para-substituted PCC is calculated to change from the triplet state in p-NO(2)-PCC (Delta G(ST) = 6.1 kcal/mol) to the singlet state in p-NH(2)-PCC (Delta G(ST) = -2.8 kcal/mol). The absence of solvent perturbation in the TRIR spectra of p-N(CH(3))(2)-PCC (which should have electronic properties similar to p-NH(2)-PCC) and parent PCC is consistent with their ground states lying > +/-2 kcal/mol from the next available electronic state, in line with the computational results. The observation of solvent perturbation in the TRIR spectra of p-OCH(3)-PCC and p-CH(3)-PCC implies that their ground states lie < +/-1 kcal/mol from their next available electronic state. This is in agreement with our computational results, which predict a gas-phase Delta G(ST) of -0.8 and 1.6 kcal/mol for p-OCH(3)-PCC and p-CH(3)-PCC as compared to Delta G(ST) values of -3.9 and -1.3 kcal/mol from polarizable continuum model (PCM) calculations with acetonitrile as a solvent. Gas-phase computational results for the meta- and ortho-substituted PCC species are also presented, along with selected linear free energy (LFE) relationships for the para and meta species.

Journal Article↗

PubMed2002

Solvent dependence of the 2-naphthyl(carbomethoxy)carbene singlet-triplet energy gap.

The solvent dependence of the 2-naphthyl(carbomethoxy)carbene (2) singlet-triplet energy gap has been examined by time-resolved infrared (TRIR) and computational methods. The ground state of 2 changes from the triplet state in hexane to the singlet state in acetonitrile. Preferential stabilization of the singlet carbene is the result of its increased dipole moment in polar solvents. Variable-temperature TRIR experiments provide measurements of the enthalpic and entropic differences between (1)2 and (3)2 and suggest that solvent and geometry effects on the entropy of singlet and triplet carbenes can offset differences arising from spin multiplicity. B3LYP calculations using the polarizable continuum solvation model (PCM) reproduce the general trends in enthalpic differences seen experimentally.

Journal Article↗