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Biomedical subjects

H Cheng

Publications and source records attributed to H Cheng.

At least 19 recordsLinked to original sources
PubMed2002

Direct determination of the timing of sea level change during termination II.

An outcrop within the last interglacial terrace on Barbados contains corals that grew during the penultimate deglaciation, or Termination II. We used combined 230Th and 231Pa dating to determine that they grew 135.8 +/- 0.8 thousand years ago, indicating that sea level was 18 +/- 3 meters below present sea level at the time. This suggests that sea level had risen to within 20% of its peak last-interglacial value by 136 thousand years ago, in conflict with Milankovitch theory predictions. Orbital forcing may have played a role in the deglaciation, as may have isostatic adjustments due to large ice sheets. Other corals in the same outcrop grew during oxygen isotope (delta18O) substage 6e, indicating that sea level was 38 +/- 5 meters below present sea level, about 168.0 thousand years ago. When compared to the delta18O signal in the benthic V19-30/V19-28 record at that time, the coral data extend to the previous glacial cycle the conclusion that deep-water temperatures were colder during glacial periods.

Animals↗
PubMed2002

Quantitative trait locus mapping in chickens by selective DNA pooling with dinucleotide microsatellite markers by using purified DNA and fresh or frozen red blood cells as applied to marker-assisted selection.

Many large, half-sib sire families are an integral component of chicken genetic improvement programs. These family structures include a sufficient number of individuals for mapping quantitative trait loci (QTL) at high statistical power. However, realizing this statistical power through individual or selective genotyping is yet too costly to be feasible under current genotyping methodologies. Genotyping costs can be greatly reduced through selective DNA pooling, involving densitometric estimates of marker allele frequencies in pooled DNA samples. When using dinucleotide microsatellite markers, however, such estimates are often confounded by overlapping "shadow" bands and can be confounded further by differential amplification of alleles. In the present study a shadow correction procedure provided accurate densitometric estimates of allele frequency for dinucleotide microsatellite markers in pools made from chicken purified DNA samples, fresh blood samples, and frozen-thawed blood samples. In a retrospective study, selective DNA pooling with thawed blood samples successfully identified two QTL previously shown by selective genotyping to affect resistance in chickens to Marek's disease. It is proposed that use of selective DNA pooling can provide relatively low-cost mapping and use in marker-assisted selection of QTL that affect production traits in chickens.

Alleles↗
PubMed2001

A high-resolution absolute-dated late Pleistocene Monsoon record from Hulu Cave, China.

Oxygen isotope records of five stalagmites from Hulu Cave near Nanjing bear a remarkable resemblance to oxygen isotope records from Greenland ice cores, suggesting that East Asian Monsoon intensity changed in concert with Greenland temperature between 11,000 and 75,000 years before the present (yr. B.P.). Between 11,000 and 30,000 yr. B.P., the timing of changes in the monsoon, as established with 230Th dates, generally agrees with the timing of temperature changes from the Greenland Ice Sheet Project Two (GISP2) core, which supports GISP2's chronology in this interval. Our record links North Atlantic climate with the meridional transport of heat and moisture from the warmest part of the ocean where the summer East Asian Monsoon originates.

Journal Article↗
PubMed2001

Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise.

Reactive oxygen species produced during vigorous exercise may permeate into cell nuclei and induce oxidative DNA damage, but the supporting evidence is still lacking. By using a 42 km marathon race as a model of massive aerobic exercise, we demonstrated a significant degree of unrepaired DNA base oxidation in peripheral immunocompetent cells, despite a concurrent increase in the urinary excretion of 8-hydroxy-2'-deoxyguanosine. Single cell gel electrophoresis with the incorporation of lesion-specific endonucleases further revealed that oxidized pyrimidines (endonuclease III-sensitive sites) contributed to most of the postexercise nucleotide oxidation. The oxidative DNA damage correlated significantly with plasma levels of creatinine kinase and lipid peroxidation metabolites, and lasted for more than 1 week following the race. This phenomenon may be one of the mechanisms behind the immune dysfunctions after exhaustive exercise.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Site-specific antibody of (Na(+) + K(+))-ATPase augments cardiac myocyte contraction without inactivating enzyme activity.

(Na(+) + K(+))-ATPase regulates both excitability and contractility of the heart. Little is known about the molecular basis of the enzyme that underlies its cardiac regulatory functions. Here we demonstrate that the (833)KRQPRNPKTDKLVNE(847) region, which resides in the alpha-subunit of rat (Na(+) + K(+))-ATPase, directly participates in the regulation of cardiac contraction. A site-specific antibody (SSA95) against this peptide sequence markedly increased intracellular Ca(2+) transients and contraction (EC(50) = 11.4 nM) in intact rat heart cells without inactivating the (Na(+) + K(+))-ATPase. These novel findings establish the first link between a precise structural region of the (Na(+) + K(+))-ATPase and cardiac positive inotropy.

Amino Acid Sequence↗
PubMed2001

Human T cell leukemia virus type 1 Tax associates with a molecular chaperone complex containing hTid-1 and Hsp70.

Tax, an oncogenic viral protein encoded by human T cell leukemia virus type 1 (HTLV-1), induces cellular transformation of T lymphocytes by modulating a variety of cellular gene expressions [1]. Identifying cellular partners that interact with Tax constitutes the first step toward elucidating the molecular basis of Tax-induced transformation. Here, we report a novel Tax-interacting protein, hTid-1. hTid-1, a human homolog of the Drosophila tumor suppressor protein Tid56, was initially characterized based on its interaction with the HPV-16 E7 oncoprotein [2]. hTid-1 and Tid56 are members of the DnaJ family [2,3], which contains a highly conserved signature J domain that regulates the activities of heat shock protein 70 (Hsp70) by serving as cochaperone [4-6]. In this context, the molecular chaperone complex is involved in cellular signaling pathways linked to apoptosis, protein folding, and membrane translocation and in modulation of the activities of tumor suppressor proteins, including retinoblastoma, p53, and WT1[7-12]. We find that expression of hTid-1 inhibits the transformation phenotype of two human lung adenocarcinoma cell lines. We show that Tax interacts with hTid-1 via a central cysteine-rich domain of hTid-1 while a signature J domain of hTid-1 mediates its binding to Hsp70 in HEK cells. Importantly, Tax associates with the molecular chaperone complex containing both hTid-1 and Hsp70 and alters the cellular localization of hTid-1 and Hsp70. In the absence of Tax, expression of the hTid-1/Hsp70 molecular complex is targeted to perinuclear mitochondrial clusters. In the presence of Tax, hTid-1 and its associated Hsp70 are sequestered within a cytoplasmic "hot spot" structure, a subcellular distribution that is characteristic of Tax in HEK cells.

Binding Sites↗
PubMed2001

Tetracycline-regulated gene expression mediated by a novel chimeric repressor that recruits histone deacetylases in mammalian cells.

Regulated gene expression will provide important platforms from which gene functions can be investigated and safer means of gene therapy may be developed. Histone deacetylases have recently been shown to play an important role in regulating gene expression. Here we investigated whether a more tightly controlled expression could be achieved by using a novel chimeric repressor that recruits histone deacetylases to a tetracycline-responsive promoter. This chimeric repressor was engineered by fusing the tetracycline repressor (TetR) with an mSin3-interacting domain of human Mad1 and was shown to bind the tetO(2) element with high affinity, and its binding was efficiently abrogated by doxycycline. The chimeric repressor was shown to directly interact with mSin3 of the histone deacetylase complex. This inducible system was further simplified by using a single vector that contained both a chimeric repressor expression cassette and a tetracycline-responsive promoter. When transiently introduced into mammalian cells, the chimeric repressor system exhibited a significantly lower basal level of luciferase activity (up to 25-fold) than that of the TetR control. When stably transfected into HEK 293 cells, the chimeric repressor system was shown to exert a tight control of green fluorescent protein expression in a doxycycline dose- and time-dependent fashion. Therefore, this novel chimeric repressor provides an effective means for more tightly regulated gene expression, and the simplified inducible system may be used for a broad range of basic and clinical studies.

Base Sequence↗
PubMed2001

Modulation of specific intestinal epithelial progenitors by enteric neurons.

The proglucagon-derived peptide glucagon-like peptide 2 (GLP-2), a product of a subset of gut epithelial cells, is pursued clinically for its ability to stimulate gut epithelial growth and repair. Here we show that although specific epithelial progenitors respond to GLP-2 administration, the epithelium does not express the GLP-2 receptor. Rather, enteric neurons express the receptor, respond to GLP-2, and transmit a signal (which can be blocked by the voltage-gated sodium channel inhibitor tetrodotoxin) back to the epithelium. Thus the nervous system is a key component of a feedback loop regulating epithelial growth and repair.

Animals↗
PubMed2001

A novel[2 + 3]cycloaddition reaction: singlet oxygen mediated formation of 1,3-dipole from iminodiacetic acid dimethyl ester and its addition to maleimides.

Sensitized photolysis of iminodiacetic acid methyl ester and maleimides follows a [2 + 3] cycloaddition pathway yielding pyrrolidine derivatives. This is similar to the photochemical reaction between C(60) and amines. A series of pyrrolidine derivatives are prepared by the method including multipyrrolidines from bis- and tris-maleimide starting materials. The yields range from 13% to 85%. The reaction is highly stereoselective. All the isolated products have the 1,3-dimethoxycarbonyl groups in the cis configuration. Various sensitizers may be used with slightly different yields. A plausible mechanism is proposed that involves the singlet oxygen abstraction of two alpha hydrogen atoms from the iminodiacetate and formation of a 1,3-dipole with a structure similar to the classical thermally generated 1,3-dipole.

Journal Article↗
PubMed2001

RyR3 amplifies RyR1-mediated Ca(2+)-induced Ca(2+) release in neonatal mammalian skeletal muscle.

The neonatal mammalian skeletal muscle contains both type 1 and type 3 ryanodine receptors (RyR1 and RyR3) located in the sarcoplasmic reticulum membrane. An allosteric interaction between RyR1 and dihydropyridine receptors located in the plasma membrane mediates voltage-induced Ca(2+) release (VICR) from the sarcoplasmic reticulum. RyR3, which disappears in adult muscle, is not involved in VICR, and the role of the transiently expressed RyR3 remains elusive. Here we demonstrate that RyR1 participates in both VICR and Ca(2+)-induced Ca(2+) release (CICR) and that RyR3 amplifies RyR1-mediated CICR in neonatal skeletal muscle. Confocal measurements of intracellular Ca(2+) in primary cultured mouse skeletal myotubes reveal active sites of Ca(2+) release caused by peripheral coupling between dihydropyridine receptors and RyR1. In myotubes lacking RyR3, the peripheral VICR component is unaffected, and RyR1s alone are able to support inward CICR propagation in most cells at an average speed of approximately 190 microm/s. With the co-presence of RyR1 and RyR3 in wild-type cells, unmitigated radial CICR propagates at 2,440 microm/s. Because neonatal skeletal muscle lacks a well developed transverse tubule system, the RyR3 reinforcement of CICR seems to ensure a robust, uniform, and synchronous activation of Ca(2+) release throughout the cell body. Such functional interplay between RyR1 and RyR3 can serve important roles in Ca(2+) signaling of cell differentiation and muscle contraction.

Animals↗
PubMed2001

Solvent extraction for separating micellar-solubilized contaminants and anionic surfactants.

Decontamination of contaminant-laden surfactant solutions is critical to successful implementation of surfactant-enhanced aquifer remediation (SEAR). Solvent extraction was studied for removing micellar-solubilized contaminants having low equivalent alkyl carbon numbers (EACNs) from surfactant solutions. Factors influencing the solvent extraction of micellar-solubilized contaminant were studied, including surfactant concentration, solution salinity, solvent solubilization, and solvent/solution volumetric ratio. A model was developed to quantify the impacts of these factors on contaminant removal. The good agreement between experimental results and model predictions corroborates assumptions made in the model development. From these results, it is concluded that extracting solvents must have much higher EACNs than that of the contaminant to reduce the micellar solubilization of the solvents, which can significantly reduce contaminant removal efficiency. However, the highest EACN solvent is not necessarily the best one for contaminant removal due to other constraints (e.g., molecular weight and viscosity). Increasing the total surfactant concentration or salinity of an anionic surfactant solution increases its contaminant solubilization capacity but reduces the contaminant removal efficiency by solvent extraction. Continuous column extraction operated at a low column surface loading rate allowed contaminant partitioning to approach equilibrium conditions, and multistage column extraction was able to improve the contaminant removal efficiency while minimizing solvent requirement.

Anions↗
PubMed2001

Separation of radioactive metabolites in cultured tea cells fed with [14C]phenylalanine using high-speed counter-current chromatography.

Separation of radioactive metabolites in cultured tea cells fed with [14C]phenylalanine was conducted using high-speed counter-current chromatography. Among seven components obtained our studies focused two metabolites, i.e. (-)-epicatechin and D,L-catechin. The specific radioactivity of (-)-epicatechin was 212.01 KBq/mg, amounting to 8.5% of the total radioactivity of ethyl acetate extract while that of D,L-catechin was 1.0006 MBq/mg or 5.4% of the total.

Carbon Radioisotopes↗
PubMed2001

Prostaglandin F2alpha added to extended boar semen at processing elicits in vitro myometrial contractility after 72 hours of storage.

Improved fertility will maximize productivity of the swine industry. Myometrial contractility is an essential component in the fertilization process because it is the mechanism by which spermatozoa are transported to the site of fertilization. In the present study, we evaluated the potential use of PGF2alpha supplementation to the extended pig semen in regard to inducing myometrial contractility of sows. Extended boar semen (80 mL) was supplemented with PGF2alpha (5 mg) for 72 h at 17 +/- 1 degrees C. Cumulative doses of 0.1, 1, 10 and 100 microL of the mixture were tested on uterine strips obtained from diestrus sows. An increase in myometrial contractility was recorded with PGF2alpha supplementation when compared to extended semen or extender treatment alone after 72 h of incubation. Addition of PGF2alpha to the extended boar semen at the time of the experiment did not differ from the 72 h treated group. The results from this study support that PGF2alpha preparations can be added to extended doses of boar semen at processing to enhance myometrial contractility at the time of insemination for up to 72 h.

Animals↗
PubMed2001

Rat glutathione S-transferase M4-4: an isoenzyme with unique structural features including a redox-reactive cysteine-115 residue that forms mixed disulphides with glutathione.

Although the existence of the rat glutathione S-transferase (GST) M4 (rGSTM4) gene has been known for some time, the corresponding protein has not as yet been purified from tissue. A recombinant rGSTM4-4 was thus expressed in Escherichia coli from a chemically synthesized rGSTM4 gene. The catalytic efficiency (k(cat)/K(m)) of rGSTM4-4 for the 1-chloro-2,4-dinitrobenzene (CDNB) conjugation reaction was 50-180-fold less than that of the well-characterized homologous rGSTM1-1, and the pH optimum for the same reaction was 8.5 for rGSTM4-4 as opposed to 6.5 for rGSTM1-1. Molecular-modelling studies predict that key substitutions in the helix alpha4 region of rGSTM4-4 account for this pK(a) difference. A notable structural feature of rGSTM4-4 is the Cys-115 residue in place of the Tyr-115 of other Mu-class GSTs. The thiol group of Cys-115 is redox-reactive and readily forms a mixed disulphide even with GSH; the S-glutathiolated form of the enzyme is catalytically active. A mutated rGSTM4-4 (C115Y) had 6-10-fold greater catalytic efficiency than the wild-type rGSTM4-4. Trp-45, a conserved residue among Mu-class GSTs, is essential in rGSTM4-4 for both enzyme activity and binding to glutathione affinity matrices. Antibodies directed against either the unique C-terminal undecapeptide or tridecapeptide of rGSTM4 reacted with rat and mouse liver GSTs to reveal an orthologous mouse GSTM4-4 present at low basal levels but which is inducible in mouse liver. This subclass of rodent Mu GSTs with redox-active Cys-115 residues could have specialized physiological functions in response to oxidative stress.

Amino Acid Sequence↗
PubMed2001

Sparks and puffs in oligodendrocyte progenitors: cross talk between ryanodine receptors and inositol trisphosphate receptors.

Investigating how calcium release from the endoplasmic reticulum (ER) is triggered and coordinated is crucial to our understanding of how oligodendrocyte progenitor cells (OPs) develop into myelinating cells. Sparks and puffs represent highly localized Ca(2+) release from the ER through ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP(3)Rs), respectively. To study whether sparks or puffs trigger Ca(2+) waves in OPs, we performed rapid high-resolution line scan recordings in fluo-4-loaded OP processes. We found spontaneous and evoked sparks and puffs, and we have identified functional cross talk between IP(3)Rs and RyRs. Local events evoked using the IP(3)-linked agonist methacholine (MeCh) showed significantly different morphology compared with events evoked using the caffeine analog 3,7-dimethyl-1-propargylxanthine (DMPX). Pretreatment with MeCh potentiated DMPX-evoked events, whereas inhibition of RyRs potentiated events evoked by low concentrations of MeCh. Furthermore, activation of IP(3)Rs but not RyRs was critical for Ca(2+) wave initiation. Using immunocytochemistry, we show OPs express the specific Ca(2+) release channel subtypes RyR3 and IP(3)R2 in patches along OP processes. RyRs are coexpressed with IP(3)Rs in some patches, but IP(3)Rs are also found alone. This differential distribution pattern may underlie the differences in local and global Ca(2+) signals mediated by these two receptors. Thus, in OPs, interactions between IP(3)Rs and RyRs determine the spatial and temporal characteristics of calcium signaling, from microdomains to intracellular waves.

Aniline Compounds↗
PubMed2001

HSP22, a new member of the small heat shock protein superfamily, interacts with mimic of phosphorylated HSP27 ((3D)HSP27).

Most of the members of the superfamily of mammalian small heat shock or stress proteins are abundant in muscles where they play a role in muscle function and maintenance of muscle integrity. One member of this protein superfamily, human HSP27, is rapidly phosphorylated on three serine residues (Ser(15), Ser(78), and Ser(82)) during cellular response to a number of extracellular factors. To understand better the role of HSP27, we performed a yeast two-hybrid screen of a human heart cDNA library for HSP27-interacting proteins. By using the triple aspartate mutant, a mimic of phosphorylated HSP27, as "bait" construct, a protein with a molecular mass of 21.6 kDa was identified as an HSP27-binding protein. Sequence analysis revealed that this new protein shares an overall sequence identity of 33% with human HSP27. This protein also contains the alpha-crystallin domain in its C-terminal half, a hallmark of the superfamily of small stress proteins. Thus, the new protein itself is a member of this protein superfamily, and consequently we designated it HSP22. According to the two-hybrid data, HSP22 interacts preferentially with the triple aspartate form of HSP27 as compared with wild-type HSP27. HSP22 is expressed predominantly in muscles. In vitro, HSP22 is phosphorylated by protein kinase C (at residues Ser(14) and Thr(63)) and by p44 mitogen-activated protein kinase (at residues Ser(27) and Thr(87)) but not by MAPKAPK-2.

Amino Acid Sequence↗