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M Han

Publications and source records attributed to M Han.

At least 145 records · Page 8Linked to original sources
PubMed1996

Effects of temperature and humidity on the performance of polymer-coated surface acoustic wave vapor sensor arrays.

The influences of temperature and atmospheric humidity on the performance of an array of eight polymer-coated 158-MHz surface acoustic wave vapor sensors were investigated. Sensitivities to the seven organic vapors examined all exhibited negative Arrhenius temperature dependencies, with responses increasing by factors of 1.5-4.4 on going from 38 to 18 degrees C. The magnitudes of the temperature effects, while generally similar, differed sufficiently among certain sensor-vapor combinations to cause marked changes in vapor response patterns. In addition, it was found that operating identically coated sensors at different temperatures could provide a means for discriminating certain vapors. The changes in sensor responses with temperature agreed reasonably well with those expected assuming ideal vapor sorption behavior and indicated that changes in the moduli of the sensor coatings were not important mediating factors. Responses to relative humidity (RH) from 0 to 85% RH were important even for the nonpolar sensor coatings. Significant changes in the sensitivities to the organic vapors were observed as a function of atmospheric humidity for several sensor-vapor combinations, which, in turn, affected the patterns of responses obtained from the sensor array. Results indicate that small changes in temperature or humidity have a larger effect on baseline stabilities than on the responses to the vapors. Monte Carlo simulations of sensor responses show that the ability to discriminate vapors in binary and ternary mixtures using a four-sensor array remains high regardless of the operating temperature and ambient humidity, provided that temperature-or humidity-induced changes in the response patterns are taken into account.

Acoustics↗
PubMed1996

Control and integration of cell signaling pathways during C. elegans vulval development.

Vulval development in the Caenorhabditis elegans hermaphrodite represents a simple, genetically tractable system for studying how cell signaling events control cell fate decisions. Current models suggest that proper specification of vulval cell fates relies on the integration of multiple signaling systems, including one that involves a receptor tyrosine kinase (RTK)-->Ras-->mitogen activated protein kinase (MAPK) cascade and one that involves a LIN-12/Notch family receptor. In this review, we first discuss how genetic strategies are being used to identify and analyze components that control vulval cell fate decisions. We then describe the different signaling systems that have been elucidated and how they relate to one another. Finally, we highlight several recently characterized genes that encode positive regulators, negative regulators or potential targets of the RTK-->Ras-->MAPK cascade involved in vulval induction.

Animals↗
PubMed1996

A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans.

Sex myoblast migration in the Caenorhabditis elegans hermaphrodite represents a simple, genetically amenable model system for studying how cell migration is regulated during development. Two separable components of sex myoblast guidance have been described: a gonad-independent mechanism sufficient for the initial anterior migration to the mid-body region, and a gonad-dependent mechanism required for precise final positioning (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041-1052). Here, we demonstrate a role for a Ras-mediated signal transduction pathway in controlling sex myoblast migration. Loss-of-function mutations in let-60 ras, ksr-1, lin-45 raf, let-537/mek-2 or sur-1/mpk-1 cause defects in sex myoblast final positions that resemble those seen in gonad-ablated animals, while constitutively active let-60 ras(G13E) trans-genes allow fairly precise positioning to occur in the absence of the gonad. A mosaic analysis demonstrated that let-60 ras is required within the sex myoblasts to control proper positioning. Our results suggest that gonadal signals normally stimulate let-60 ras activity in the sex myoblasts, thereby making them competent to sense or respond to positional cues that determine the precise endpoint of migration. let-60 ras may have additional roles in sex myoblast guidance as well. Finally, we have also investigated genetic interactions between let-60 ras and other genes important for sex myoblast migration, including egl-15, which encodes a fibroblast growth factor receptor tyrosine kinase (D. L. DeVore, H. R. Horvitz and M. J. Stern (1995) Cell 83, 611-623). Since mutations reducing Ras pathway activity cause a different phenotype than those reducing egl-15 activity and since constitutive Ras activity only partially suppresses the migration defects of egl-15 mutants, we argue that let-60 ras and egl-15 do not act together in a single linear pathway.

Animals↗
PubMed1996

Availability of liposomes as drug carriers to the brain.

Phospholipid vesicles, also known as liposomes, were examined for their ability to act as a drug carrier to the brain. 9-Amino-1,2,3,4-tetrahydroacridine (THA), a centrally acting acetylcholinesterase inhibitor, was used as a model drug. THA was encapsulated in dehydration-rehydration vesicles (DRV) composed of egg yolk phosphatidylcholine, cholesterol and dipalmitoyl-phosphatidic acid (molar ratio, 10/10/1) and injected into the heart of mice. The toxicity and side effects of THA were reduced by encapsulation in liposomes. The THA concentration in the mouse brain after injection of THA-encapsulated DRV at a dose of 2 mg/kg remained higher than that of free THA at the same dose. Effective concentration of THA in the brain was also prolonged by the use of liposomes, although accumulation of THA in the spleen and kidney was observed. We, therefore, concluded that liposomes are useful as carriers of drugs to the brain.

Animals↗
PubMed1996

The effects of acute and chronic exercise on sleep. A meta-analytic review.

Studies attempting to ascertain the effects of acute and chronic exercise on measures of sleep have yielded conflicting results and interpretations. Methodological differences among studies may explain this lack of consensus; however, small sample sizes and subsequently low statistical power may also have contributed. In an attempt to resolve these issues, this review used meta-analytical techniques to: (a) re-examine the effects of exercise on sleep; and (b) examine possible moderators of these effects. Studies meeting the selection criteria were included in the analysis. Analyses of moderating factors were performed for stage 4 sleep and rapid eye movement (REM) sleep. The results indicated that acute and chronic exercise increased slow wave sleep (SWS) and total sleep time but decreased sleep onset latency and REM sleep. Moderating variables influencing the magnitude and direction of these effects were related to characteristics of the individual (e.g. sex, age, fitness level) and the exercise (e.g. time of day exercise was completed, type of exercise, exercise duration). Mechanisms which have been suggested to explain the relationship between exercise and sleep are discussed and directions for further research are provided.

Exercise↗
PubMed1996

In vitro expansion of murine hematopoietic progenitor cells by leukemia inhibitory factor, stem cell factor, and interleukin-1 beta.

Murine hematopoietic progenitor cells were markedly expanded in the presence of leukemia inhibitory factor (LIF), interleukin (IL)-1 beta and/or stem cell factor (SCF), although SCF+IL-1 beta +IL-3, LIF+SCF+IL-3, and SCF+IL-1 beta showed an appreciable effect on the in vitro expansion of hematopoietic progenitor cells as well. In the presence of LIF+SCF+IL-1 beta, highly proliferative potential colony-forming units (CFU-HPP) and colony forming units of mixed lineages (CFU-Mix) were more efficiently expanded than colony forming units granulocytes/macrophage (CFU-GM) and burst-forming units of erythroid lineage (BFU-E) compared with the colony formations of freshly obtained bone marrow cells. The cell yield on day 5 in the presence of LIF+SCF+IL-1 beta was comparable to that in SCF+IL-1 beta and SCF+IL-1 beta +IL-3. Nevertheless, colony formations were marked in LIF+SCF+IL-1 beta, thus suggesting that this combination can generate hematopoietic progenitor cells that possess greater potential for CFU-HPP, CFU-Mix, CFU-GM, and BFU-E colony formations. Hematopoietic cells expanded in the presence of LIF+SCF+IL-1 beta showed increased mRNA expressions of IL-1 beta, IL-3, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage (GM)-CSF, interferon gamma (IFN-gamma), and LIF compared with those of nontreated hematopoietic cells. Furthermore, LIF+SCF+IL-1 beta induced increased IL-3 and GM-CSF mRNA expression in hematopoietic cells but induced decreased macrophage inflammatory protein 1 alpha (MIP1 alpha) mRNA expression as compared with SCF+IL-1 beta +IL-3. These results suggest that the balance between stimulatory and inhibitory cytokines plays an important role in in vitro expansion of hematopoietic progenitor cells.

Animals↗
PubMed1996

Increased expression of PDGF and c-myc genes in lungs and pulmonary arteries of pulmonary hypertensive rats induced by hypoxia.

The role of growth factors and proto-oncogene in pulmonary vascular structural remodelling is not well known. The present study examined gene expression of platelet-derived growth factor (PDGF)-A and -B chain and proto-oncogene, c-myc, in lung tissue and pulmonary artery of rats exposed to hypoxia and compared to those levels of gene expression in normal rats. Normal lungs and pulmonary artery expressed PDGF-A chain transcript of 1.7 kb and PDGF-B chain transcript of 3.5 Kb. The c-myc transcript of 2.2 kb was expressed as well. After hypoxic exposure for 7 and 14 days mRNA levels of PDGF-B chain and c-myc were elevated significantly compared with those of control rats. PDGF-A chain mRNA increased after hypoxia for 7 days, and then declined. These results suggest that activation of autocrine and/or paracrine is important in proliferation mechanism of pulmonary artery smooth muscle cells in hypoxic pulmonary hypertensive rats.

Animals↗
PubMed1995

The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction.

Vulval induction in C. elegans is controlled by a highly conserved signaling pathway similar to the RTK-Ras-MAPK cascade in mammals. By screening for suppressors of the Multivulva phenotype caused by an activated let-60 ras allele, we isolated mutations in a gene, ksr-1, that acts as a positive modifier of vulval induction and is required for at least two other let-60 ras-mediated processes. Although ksr-1 mutations do not perturb vulval induction in an otherwise wild-type background, they have very strong effects on vulval induction in genetic backgrounds where Ras pathway activity is constitutively activated or compromised, suggesting that ksr-1 activity is required for maximal stimulation of vulval fates by the Ras pathway. Genetic epistasis analysis suggests that ksr-1 acts downstream of or in parallel to let-60 ras. We cloned ksr-1 and have shown that it encodes a novel putative protein kinase related to the Raf family of Ser/Thr kinases.

Amino Acid Sequence↗
PubMed1995

Neurosteroid analogues. 3. The synthesis and electrophysiological evaluation of benz[e]indene congeners of neuroactive steroids having the 5 beta-configuration.

A series of 7-(2-hydroxyethyl)benz[e]indene analogues of 3 alpha-hydroxy-5 beta-pregnan-20-one (7), a neuroactive steroid known to be a positive allosteric modulator of GABAA receptor function, was prepared. Electrophysiological measurements carried out on cultured rat hippocampal neurons were used to evaluate the modulatory effects of the analogues on GABAA receptor function. Analogues were tested for their ability to potentiate 1 microM GABA-mediated chloride currents and for their ability to directly gate chloride currents at this ligand-gated ion channel. Active analogues typically enhanced GABA-mediated currents at concentrations below those required to directly gate chloride currents. The dose-response relationships for potentiation of 1 microM GABA-mediated chloride currents were studied for [3S-(3 alpha, 3a alpha, 5a beta, 7 beta, 9a alpha, 9b beta)]-1- [dodecahydro-7-(2-hydroxyethyl)-3a-methyl-1H-benz[e]inden-3- yl]ethanone (3), steroid 7, 3 alpha-hydroxy-5 alpha-pregnan-20-one (5), and the analogous 7 alpha-(2-hydroxyethyl)benz[e]indene analogue of steroid 5 (compound 1). Compound 3 was the most active potentiator (EC50 = 0.017 microM) of GABA-mediated current. The direct gating actions of compound 3 were not observed at a concentration of 1 microM, but were observed at a concentration of 10 microM.

Animals↗
PubMed1995

sur-2, a novel gene, functions late in the let-60 ras-mediated signaling pathway during Caenorhabditis elegans vulval induction.

We describe here a new gene acting downstream of let-60 ras in the vulval signaling pathway of Caenorhabditis elegans. The sur-2 (suppressor of ras) gene is defined by eight mutations identified in a genetic screen for suppressors of the Multivulva phenotype of let-60(n1046), an activated let-60 ras mutation. sur-2 mutations result in pleiotropic, incompletely penetrant phenotypes that include a Vulvaless phenotype in hermaphrodites, defects in development of the male tail, gonadal abnormalities, and larval lethality, indicating a role for the sur-2 gene product in multiple developmental events. Genetic epistasis analyses suggest that sur-2 is required late in the vulval signaling pathway, downstream of let-60 Ras, and is likely to act downstream of the Raf/MAP Kinase cascade. We cloned the sur-2 gene by DNA-mediated transformation and have shown that it encodes a novel protein. We also show that a sur-2::lacZ transgene is expressed in the vulval precursor cells at the time of vulval determination.

Amino Acid Sequence↗
PubMed1995

Ras farnesyltransferase inhibitors suppress the phenotype resulting from an activated ras mutation in Caenorhabditis elegans.

Attachment of Ras protein to the membrane, which requires farnesylation at its C terminus, is essential for its biological activity. A promising pharmacological approach of antagonizing oncogenic Ras activity is to develop inhibitors of farnesyltransferase. We use Caenorhabditis elegans vulval differentiation, which is controlled by a Ras-mediated signal transduction pathway, as a model system to test previously identified farnesyltransferase inhibitors. We show here that two farnesyltransferase inhibitors, manumycin and gliotoxin, suppress the Multivulva phenotype resulting from an activated let-60 ras mutation, but not the Multivulva phenotype resulting from mutations in the lin-1 gene or the lin-15 gene, which act downstream and upstream of let-60 ras, respectively, in the signaling pathway. These results are consistent with the idea that the suppression of the Multivulva phenotype of let-60 ras by the two inhibitors is specific for Ras protein and that the mutant Ras protein might be more sensitive than wild-type Ras to the farnesyltransferase inhibitors. This work suggests that C. elegans vulval development could be a simple and effective in vivo system for evaluation of farnesyltransferase inhibitors against Ras-activated tumors.

Alkyl and Aryl Transferases↗
PubMed1995

Optimal coating selection for the analysis of organic vapor mixtures with polymer-coated surface acoustic wave sensor arrays.

A method for determining the optimal set of polymer sensor coatings to include in a surface acoustic wave (SAW) sensor array for the analysis of organic vapors is described. The method combines an extended disjoint principal components regression (EDPCR) pattern recognition analysis with Monte Carlo simulations of sensor responses to rank the various possible coating selections and to estimate the ability of the sensor array to identify any set of vapor analytes. A data base consisting of the calibrated responses of 10 polymer-coated SAW sensors to each of six organic solvent vapors from three chemical classes was generated to demonstrate the method. Responses to the individual vapors were linear over the concentration ranges examined, and coatings were stable over several months of operation. Responses to binary mixtures were additive functions of the individual component responses, even for vapors capable of strong hydrogen bonding. The EDPCR-Monte Carlo method was used to select the four-sensor array that provided the least error in identifying the six vapors, whether present individually or in binary mixtures. The predicted rate of vapor identification (87%) was experimentally verified, and the vapor concentrations were estimated within 10% of experimental values in most cases. The majority of errors in identification occurred when an individual vapor could not be differentiated from a mixture of the same vapor with a much lower concentration of a second component. The selection of optimal coating sets for several ternary vapor mixtures is also examined. Results demonstrate the capabilities of polymer-coated SAW sensor arrays for analyzing of solvent vapor mixtures and the advantages of the EDPCR-Monte Carlo method for predicting and optimizing performance.

Acoustics↗
PubMed1995

MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events.

Activated Ras initiates a cascade of sequential phosphorylation events, including the protein kinases Raf, MEK, and MAP kinase. The Let-60 Ras-mediated signal transduction pathway controls vulval induction in Caenorhabditis elegans. Both Lin-45 Raf and Sur-1 MAP kinase have been determined to be essential factors during vulval induction; however, the C. elegans mek gene has not been identified. In this paper, we have cloned a C. elegans mek gene, mek-2, and demonstrated that the MEK-2 protein possesses the biochemical properties of MAP kinase kinases: The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase (ERK1), and MEK-2 itself can be phosphorylated and activated by immunoprecipitated mammalian Raf. The mek-2 gene plays a key role in the let-60 ras-mediated vulval induction pathway, as loss-of-function mutations in the gene (ku114 and h294) significantly reduce the signal transmitted through Ras. mek-2(ku114) completely suppressed the Multivulva (Muv) phenotype of a hyperactive let-60 ras mutation, and animals homozygous for mek-2(ku114) also displayed a partial larval lethal phenotype. Animals homozygous for mek-2(h294) exhibited a highly penetrant sterile and Vulvaless phenotype. Microinjection of a gain-of-function mek-2 mutation resulted in Muv and other mutant phenotypes, whereas microinjection of a dominant-negative mutation not only suppressed the Muv phenotype of an activated let-60 ras mutation but also caused an egg-laying defective phenotype in otherwise wild type animals. Our results demonstrate that mek-2 acts between lin-45 raf and sur-1/mpk-1 in a signal transduction pathway used in the control of vulval differentiation and other developmental events.

Amino Acid Sequence↗