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Biomedical subjects

E W Tan

Publications and source records attributed to E W Tan.

10 recordsLinked to original sources
PubMed2006

Global electrosensory oscillations enhance directional responses of midbrain neurons in eigenmannia.

Eigenmannia, a genus of weakly electric fish, exhibits a specialized behavior known as the jamming avoidance response (JAR). The JAR results in a categorical difference between Eigenmannia that are in groups of conspecifics and those that are alone. Fish in groups exhibit the JAR behavior and thereby experience ongoing, global synchronous 20- to 50-Hz electrosensory oscillations, whereas solitary fish do not. Although previous work has shown that these ongoing signals do not significantly degrade electrosensory behavior, these oscillations nevertheless elicit short-term synaptic depression in midbrain circuits. Because short-term synaptic depression can have profound effects on the transmission of information through synapses, we examined the differences in intracellularly recorded responses of midbrain neurons in awake, behaving fish to moving electrosensory images under electrosensory conditions that mimic solitary fish and fish in groups. In solitary conditions, moving objects elicited Gaussian or sinusoidal postsynaptic potentials (PSPs) that commonly exhibited preferential responses to a direction of motion. Surprisingly, when the same stimulus was presented in the presence of the global oscillations, directional selectivity was increased in all neurons tested. The magnitudes of the differences in PSP amplitude for preferred and nonpreferred directions were correlated with a measure of short-term synaptic depression in both conditions. The electrosensory consequences of the JAR appear to result in an enhancement of the representation of direction of motion in midbrain neurons. The data also support a role for short-term synaptic depression in the generation and modulation of directional responses.

Animals↗
PubMed1999

Mandarin and English single word processing studied with functional magnetic resonance imaging.

The cortical organization of language in bilinguals remains disputed. We studied 24 right-handed fluent bilinguals: 15 exposed to both Mandarin and English before the age of 6 years; and nine exposed to Mandarin in early childhood but English only after the age of 12 years. Blood oxygen level-dependent contrast functional magnetic resonance imaging was performed while subjects performed cued word generation in each language. Fixation was the control task. In both languages, activations were present in the prefrontal, temporal, and parietal regions, and the supplementary motor area. Activations in the prefrontal region were compared by (1) locating peak activations and (2) counting the number of voxels that exceeded a statistical threshold. Although there were differences in the magnitude of activation between the pair of languages, no subject showed significant differences in peak-location or hemispheric asymmetry of activations in the prefrontal language areas. Early and late bilinguals showed a similar pattern of overlapping activations. There are no significant differences in the cortical areas activated for both Mandarin and English at the single word level, irrespective of age of acquisition of either language.

Adolescent↗
PubMed1999

Processing of visually presented sentences in Mandarin and English studied with fMRI.

Comprehension of visually presented sentences in fluent bilinguals was studied with functional magnetic resonance imaging (fMRI) using a set of conceptually similar sentences in two orthographically and phonologically distinct languages, Mandarin and English. Responses were monitored during scanning. Sentence comprehension in each language was compared to fixation in nine subjects and Tamil-like pseudo-word strings in five subjects. Spatially congruent activations in the prefrontal, temporal, and superior parietal regions and in the anterior supplementary motor area were observed for both languages and in both experiments at the individual and group levels of analysis. Proficient bilinguals exposed to both languages early in life utilize common neuroanatomical regions during the conceptual and syntactic processing of written language irrespective of their differences in surface features.

Adolescent↗
PubMed1997

Synthesis and in vitro evaluation of two progressive series of bifunctional polyhydroxybenzamide catechol-O-methyltransferase inhibitors.

Two progressive series of molecules with two polyhydroxybenzamide substructures were synthesized and tested as potential inhibitors of catechol-O-methyltransferase (COMT). These compounds were designed for the purpose of enhanced enzyme binding with duplicated substructures separated by a linker section of various lengths. Our results show that potency and mode of inhibition observed with the "bifunctional" compounds were a reflection of their bifunctional nature. Furthermore, potency and mode of inhibition were dependent on the length of the linker section. Of the assayed compounds, the optimum linker was found to be diaminopropane. For example, N,N'-1,3-propanediylbis(3,4-dihydroxybenzamide) and N,N'-1,3-propanediylbis(3,4,5-trihydroxybenzamide) demonstrated strong inhibitory action against COMT, with apparent Ki values of 0.3 and 6.0 microM, respectively.

Animals↗
PubMed1996

Physical characterization of incense aerosols.

Experiments were performed to study the physical characteristics of smoke aerosols generated by burning three types of stick incense in a 4 m3 clean room. Sidestream cigarette smoke was also examined under the same conditions to provide a comparison. Among the parameters measured were (a) masses of aerosol, carbon monoxide and nitrogen oxides generated by burning the incense or cigarettes, (b) rates of decay of the particles from the air, and (c) estimates of count median particle size during a 7 h period post-burning. There was variability among the types of incense studied with respect to many of the parameters. Also, as a general trend, the greater the initial particulate mass concentration, the more rapid the rate of decay of the smoke. In relation to the quantity of particulate generated, cigarette smoke was found to produce proportionally larger quantities of carbon monoxide and nitrogen oxides than did incense. Due to the fact that burning incense was found to generate large quantities of particulate (an average of greater than 45 mg/g burned, as opposed to about 10 mg/g burned for the cigarettes), it is likely, in cases in which incense is habitually burned in indoor settings, that such a practice would produce substantial airborne particulate concentrations.

Aerosols↗
PubMed1992

Identification of an isoprenylated cysteine methyl ester hydrolase activity in bovine rod outer segment membranes.

Proteins from eucaryotic cells which have a carboxyl-terminal CAAX motif are posttranslationally modified by isoprenylation. The pathway involves the linkage of an all-trans-farnesyl (C15) or an all-trans-geranylgeranyl (C20) moiety to the cysteine residue followed by proteolysis which generates the modified cysteine as the carboxyl-terminal residue. Carboxylmethylation of the modified cysteine residue completes the pathway. This latter methylation reaction is the only potentially reversible reaction in the pathway and thus of possible regulatory significance. A specific esterase is required to reverse the methylation. It is demonstrated here that simple isoprenylated cysteine derivatives, such as N-acetyl-S-farnesyl-L-cysteine methyl ester (L-AFCM) and N-acetyl-S-geranylgeranyl-L-cysteine methyl ester (L-AGGCM), are substrates for a rod outer segment (ROS) membrane esterase activity. The KM and Vmax values for L-AFCM and L-AGGCM are 186 microM and 2.2 nmol mg-1 min-1 and 435 microM and 4.8 nmol mg-1 min-1, respectively. The enzyme(s) is stereoselective rather than stereospecific because D-AFCM is enzymatically hydrolyzed with KM and Vmax values of 157 microM and 0.46 nmol mg-1 min-1, respectively. The enzyme(s) does not process N-acetyl-L-cysteine methyl ester, demonstrating that the isoprenyl moiety is required for substrate activity. Ebelactone B is a potent mechanism-based inactivator of the enzyme with a KI = 42 microM and a kinh = 3.7 x 10(-3) s-1. Importantly, L-AFCM, L-AGGCM, and ebelactone B all inhibit the demethylation of the endogenous ROS substrates, showing that the same enzymatic activity is involved in the processing of the synthetic and physiological substrates.

Amino Acid Sequence↗
PubMed1992

Prenylated protein methyltransferases do not distinguish between farnesylated and geranylgeranylated substrates.

Proteins that are post-translationally modified by prenylation can be either farnesylated (C-15) or geranylgeranylated (C-20) by separate prenyltransferase enzymes. Prenylated proteins are also methylated at their C-terminal residue by S-adenosylmethionine-linked methylation. In this paper we show that the methylation of farnesylated and geranyl-geranylated substrates can be accounted for by the presence of a single enzyme. It is demonstrated that the Km and Vmax. values for the retinal rod outer segment methyltransferase, measured with small molecule farnesylated and geranylgeranylated substrates, are identical. These substrates mutually inhibit each other's methylation, with KI values being equal to their Km values. The Km for S-adenosylmethionine was measured to be the same with either farnesylated or geranylgeranylated substrates. Competitive inhibitors of the methyltransferase containing either a geranylgeranyl or a farnesyl group equally block the methylation of synthetic geranylgeranylated and farnesylated substrates of the enzyme. Importantly, these inhibitors are also equipotent at inhibiting the methylation of the physiological substrates of the rod outer segment methyltransferase. These substrates are both farnesylated and geranylgeranylated. One of these substrates had previously been identified as the farnesylated gamma subunit of transducin. Therefore it appears that the same enzymic activity can methylate both farnesylated and geranylgeranylated substrates.

Alkyl and Aryl Transferases↗
PubMed1991

Identifying the recognition unit for G protein methylation.

Signal transducing G proteins, such as transducin, are prenylated and methylated at carboxyl-terminal cysteine residues. The methylation of transducin occurs by means of a membrane bound S-adenosyl methionine-dependent methyltransferase. This methyltransferase accepts the simple modified amino acid N-acetyl-S-farnesyl-L-cysteine (AFC) as a substrate. This means that the enzyme does not require peptide sequences of transducin in a putative substrate. Moreover, small structural changes in the AFC structural unit all lead to molecules incapable of being substrates. For example, neither N-acetyl-S-farnesylhomocysteine (AFHC) nor the saturated form of AFC are substrates. Interestingly, substitution of the N-acetyl moiety of AFC with a hydrogen atom leads to S-farnesylthiopropionic acid (FTP), which is an excellent substrate for the methyltransferase. The methyltransferase shows great specificity for the the FTP pharmacophore. So far, alterations in this structure have not led to active substrates. For example, removal of a methylene group of FTP, producing S-farnesylthioacetic acid (FTA), abolished substrate activity. FTA is a potent competitive inhibitor of the enzyme. FTP is thus the ultimately simplified substrate for the methyltransferase and does not contain any remnants of the peptide structure of transducin.

Animals↗
PubMed1991

Methylation and demethylation reactions of guanine nucleotide-binding proteins of retinal rod outer segments.

Retinal transducin was previously shown to be farnesylated on its gamma subunit. This farnesylation reaction on a cysteine residue near the carboxyl terminus is followed by peptidase cleavage at the cysteine. Thus the modified cysteine becomes the carboxyl terminus. It is shown here that the free carboxyl group can be methylated by an S-adenosyl-L-methionine-dependent methyltransferase associated with the rod outer segment membranes. This process can be inhibited by S-adenosyl-L-homocysteine and sinefungin. Moreover, synthetic N-acetyl-S-farnesyl-L-cysteine, but not N-acetyl-L-cysteine, is a substrate for the enzyme. Rapid demethylation of N-acetyl-S-farnesyl-L-cysteine methyl ester can be observed in the membranes. Transducin is also enzymatically demethylated by the rod outer segment membranes. Moreover, the 23- to 29-kDa small G proteins are methylated and demethylated in this system. These data suggest that methylation/demethylation may play a regulatory role in visual signal transduction.

Acetylcysteine↗