• Title/Summary/Keyword: Biophysics

Search Result 564, Processing Time 0.028 seconds

Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population

  • Yee, Jaeyong;Kim, Yongkang;Park, Taesung;Park, Mira
    • Genomics & Informatics
    • /
    • v.14 no.4
    • /
    • pp.181-186
    • /
    • 2016
  • Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait.

Cholinergic and Neurokinergic Agonist-induced $Ca^{2+}$ Responses in Rat von Ebner's Gland Acinar Cells

  • Chung, Ki-Myung;Kim, Sang-Hee;Cho, Young-Kyung;Roper, Stephen D.;Kim, Kyung-Nyun
    • International Journal of Oral Biology
    • /
    • v.31 no.3
    • /
    • pp.99-105
    • /
    • 2006
  • Von Ebner's glands (vEG) are minor salivary glands associated with circumvallate and foliate papilla. The secretions of vEG consist of microenvironment of the taste buds in the circumvallate and foliate papillae, and thus saliva from vEG plays a role in the perception of taste. The $Ca^{2+}$ signaling system in rat vEG acinar cell was examined using the $Ca^{2+}$-sensitive fluorescent indicator Fura-2. Agonist-induced increase in intracellular $Ca^{2+}\;([Ca^{2+}]_i)$ was stimulated by carbachol (CCh) and substance P (SP), but not by norepinephrine (NE), and recovered to control levels by their receptor antagonists dose-dependently. The effects were also observed in $Ca^{2+}$-free medium, suggesting mobilization from intracellular $Ca^{2+}$ store. These results in the vEG acinar cell indicate that 1) $[Ca^{2+}]_i$ is at least regulated by muscarinic and neurokininergic (NK1) receptors; 2) the increases in $[Ca^{2+}])i$ activated by CCh and SP are mainly mediated by discharge of cytosolic calcium pool.

Disulfide Bond as a Structural Determinant of Prion Protein Membrane Insertion

  • Shin, Jae Yoon;Shin, Jae Il;Kim, Jun Seob;Yang, Yoo Soo;Shin, Yeon-Kyun;Kim, Kyeong Kyu;Lee, Sangho;Kweon, Dae-Hyuk
    • Molecules and Cells
    • /
    • v.27 no.6
    • /
    • pp.673-680
    • /
    • 2009
  • Conversion of the normal soluble form of prion protein, PrP ($PrP^C$), to proteinase K-resistant form ($PrP^{Sc}$) is a common molecular etiology of prion diseases. Proteinase K-resistance is attributed to a drastic conformational change from ${\alpha}$-helix to ${\beta}$-sheet and subsequent fibril formation. Compelling evidence suggests that membranes play a role in the conformational conversion of PrP. However, biophysical mechanisms underlying the conformational changes of PrP and membrane binding are still elusive. Recently, we demonstrated that the putative transmembrane domain (TMD; residues 111-135) of Syrian hamster PrP penetrates into the membrane upon the reduction of the conserved disulfide bond of PrP. To understand the mechanism underlying the membrane insertion of the TMD, here we explored changes in conformation and membrane binding abilities of PrP using wild type and cysteine-free mutant. We show that the reduction of the disulfide bond of PrP removes motional restriction of the TMD, which might, in turn, expose the TMD into solvent. The released TMD then penetrates into the membrane. We suggest that the disulfide bond regulates the membrane binding mode of PrP by controlling the motional freedom of the TMD.

T7 RNA Polymerase Is Expressed in Plants in a Nicked but Active Form (T7 RNA polymerase 유전자의 담배식물에서의 발현)

  • Caviedes, Miguel A.;Thornburg, Robert W.;Park, Sang-Gyu
    • Applied Biological Chemistry
    • /
    • v.40 no.4
    • /
    • pp.271-276
    • /
    • 1997
  • We have prepared several chimeric constructs containing the bacteriophage T7 RNA polymerase gene under control of the wound-inducible potato proteinase inhibitor II (pin2) promoter and have transformed Nicotiana tabacum plants with these constructs. Southern blot analyses indicate that either one or two copies of the gene constructs are present in the transgenic plants. Northern blot analyses indicate that mRNA encoding T7 RNA polymerase is expressed in a wound-inducible manner. We purified T7 RNA polymerase and prepared antiserum. This antiserum was used for Western blot analyses to demonstrate that a protein which is cross reactive with T7 RNA polymerase is produced. The molecular mass of this protein is 80 kDa, a size which is consistant with the nicked form of the polymerase as is often seen when expressed in E. coli. RNA polymerase assays were used to indicate that the nicked form of T7 RNA polymerase is active and capable of incorporating labeled nucleotides into transcripts in vitro. Analysis of transgenic plants did indeed show that wound-inducible activation of the T7 RNA polymerase permits the establishment of a genetic system to overexpress genes in plants using T7 RNA polymerase(Received March 20, 1997; accepted May 2, 1997)

  • PDF

Relaxant Effect of Spermidine on Acethylcholine and High $K^+$-induced Gastric Contractions of Guinea-Pig

  • Kim, Young-Chul;Sim, Jae-Hoon;Choi, Woong;Kim, Chan-Hyung;You, Ra-Young;Xu, Wen-Xie;Lee, Sang-Jin
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.12 no.2
    • /
    • pp.59-64
    • /
    • 2008
  • In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current ($VDCC_L$). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current ($I_{Ba}$), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner ($IC_{50}=1.1{\pm}0.11mM$). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high $K^+$-induced contraction: Spermidine (5 mM) significantly reduced high $K^+$ (50 mM)-induced contraction to 37${\pm}$4.7% of the control (p<0.05), and inhibitory effect of spermidine on $I_{Ba}$ was also observed at a wide range of test potential in current/voltage (I/V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by $Ca^{2+}$-induced $Ca^{2+}$ release (CICR), was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of $VDCC_L$ and $Ca^{2+}$ releasing mechanism in guinea-pig stomach.

Simultaneous Biocatalytic Synthesis of Panose During Lactate Fermentation in Kimchi

  • Han, Nam-Soo;Jung, Yoon-Seung;Eom, Hyun-Ju;Koh, Young-Ho;Robyt, John F.;Seo, Jin-Ho
    • Journal of Microbiology and Biotechnology
    • /
    • v.12 no.1
    • /
    • pp.46-52
    • /
    • 2002
  • As a functional additive for intestinal microflora, panose ($6^2-{\alpha}$-D-glucopyranosylmaltose) was synthesized during kimchi fermentation using the glucose transferring reaction of glucansucrase from Leuconostoc mesenteroides. For the glucose transferring reaction, sucrose and maltose were added ($2\%$ each, w/v) to dongchimi-kimchi as the glucosyl donor and acceptor molecule, respectively. After five days of incubation at $10^{\circ}C$, referring to the initial phase for the production of lactic acid in kimchi, over $60\%$ (w/v) of the total sugars were converted into panose and other branched oligosaccharides. Thereafter, the kimchi was stored at $4^{\circ}C$ and the amount of panose remained at a constant level for three weeks, thereby indicating the stability of panose to microbial degradation during the period of kimchi consumption. The use of maltose as the acceptor molecule in the kimchi also facilitated a lower viscosity in the kimchi-juice by preventing the synthesis of a dextran-like polymer which caused an unfavorable taste. Accordingly, the application of this new method of simultaneous biocatalytic synthesis of oligosaccharides during lactate fermentation should facilitate the extensive development of new function-added lactate foods.

Buffering Contribution of Mitochondria to the $[Ca^{2+}]_i$ Increase by $Ca^{2+}$ Influx through Background Nonselective Cation Channels in Rabbit Aortic Endothelial Cells

  • Kim, Young-Chul;Lee, Sang-Jin;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.9 no.1
    • /
    • pp.29-35
    • /
    • 2005
  • To prove the buffering contribution of mitochondria to the increase of intracellular $Ca^{2+}$ level ($[Ca^{2+}]_i$) via background nonselective cation channel (background NSCC), we examined whether inhibition of mitochondria by protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) affects endothelial $Ca^{2+}$ entry and $Ca^{2+}$ buffering in freshly isolated rabbit aortic endothelial cells (RAECs). The ratio of fluorescence by fura-2 AM ($R_{340/380}$) was measured in RAECs. Biological state was checked by application of acetylcholine (ACh) and ACh ($10{\mu}M$) increased $R_{340/380}$ by $1.1{\pm}0.15$ ($mean{\pm}S.E.$, n=6). When the external $Na^+$ was totally replaced by $NMDG^+$, $R_{340/380}$ was increased by $1.19{\pm}0.17$ in a reversible manner (n=27). $NMDG^+$-induced $[Ca^{2+}]_i$ increase was followed by oscillatory decay after $[Ca^{2+}]_i$ reached the peak level. The increase of $[Ca^{2+}]_i$ by $NMDG^+$ was completely suppressed by replacement with $Cs^+$. When $1{\mu}M$ CCCP was applied to bath solution, the ratio of $[Ca^{2+}]_i$ was increased by $0.4{\pm}0.06$ (n=31). When $1{\mu}M$ CCCP was used for pretreatment before application of $NMDG^+$, oscillatory decay of $[Ca^{2+}]_i$ by $NMDG^+$ was significantly inhibited compared to the control (p<0.05). In addition, $NMDG^+-induced$ increase of $[Ca^{2+}]_i$ was highly enhanced by pretreatment with $2{\mu}M$ CCCP by $320{\pm}93.7$%, compared to the control ($mean{\pm}S.E.$, n=12). From these results, it is concluded that mitochondria might have buffering contribution to the $[Ca^{2+}]_i$ increase through regulation of the background NSCC in RAECs.

Acetylcholine Induces Hyperpolarization Mediated by Activation of $K_{(ca)}$ Channels in Cultured Chick Myoblasts

  • Lee, Do-Yun;Han, Jae-Hee;Park, Jae-Yong
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.9 no.1
    • /
    • pp.37-43
    • /
    • 2005
  • Our previous report demonstrated that chick myoblasts are equipped with $Ca^{2+}$-permeable stretchactivated channels and $Ca^{2+}-activated$ potassium channels ($K_{Ca}$), and that hyperpolarization-induced by $K_{Ca}$ channels provides driving force for $Ca^{2+}$ influx through the stretch-activated channels into the cells. Here, we showed that acetylcholine (ACh) also hyperpolarized the membrane of cultured chick myoblasts, suggesting that nicotinic acetylcholine receptor (nAChR) may be another pathway for $Ca^{2+}$ influx. Under cell-attatched patch configuration, ACh increased the open probability of $K_{Ca}$ channels from 0.007 to 0.055 only when extracellular $Ca^{2+}$ was present. Nicotine, a nAChR agonist, increased the open probability of $K_{Ca}$ channels from 0.008 to 0.023, whereas muscarine failed to do so. Since the activity of $K_{Ca}$ channel is sensitive to intracellular $Ca^{2+}$ level, nAChR seems to be capable of inducing $Ca^{2+}$ influx. Using the $Ca^{2+}$ imaging analysis, we were able to provide direct evidence that ACh induced $Ca^{2+}$ influx from extracellular solution, which was dramatically increased by valinomycin-mediated hyperpolarization. In addition, ACh hyperpolarized the membrane potential from $-12.5{\pm}3$ to $-31.2{\pm}5$ mV by generating the outward current through $K_{Ca}$ channels. These results suggest that activation of nAChR increases $Ca^{2+}$ influx, which activates $K_{Ca}$ channels, thereby hyperpolarizing the membrane potential in chick myoblasts.

Exploration of the Gene-Gene Interactions Using the Relative Risks in Distinct Genotypes (유전자형별 상대 위험도를 이용한 유전자-유전자간 상호작용 탐색)

  • Jung, Ji-Won;Yee, Jae-Yong;Lee, Suk-Hoon;Pa, Mi-Ra
    • The Korean Journal of Applied Statistics
    • /
    • v.24 no.5
    • /
    • pp.861-869
    • /
    • 2011
  • One of the main objects of recent genetic studies is to understand genetic factors that induce complex diseases. If there are interactions between loci, it is difficult to find such associations through a single-locus analysis strategy. Thus we need to consider the gene-gene interactions and/or gene-environment interactions. The MDR(multifactor dimensionality reduction) method is being used frequently; however, it is not appropriate to detect interactions caused by a small fraction of the possible genotype pairs. In this study, we propose a relative risk interaction explorer that detects interactions through the calculation of the relative risks between the control and disease groups from each genetic combinations. For illustration, we apply this method to MDR open source data. We also compare the MDR and the proposed method using the simulated data eight genetic models.

An ESR Study of Amino Acid and Protein Free Radicals in Solution Part Ⅴ. an ESR Study of Gamma-Irradiated Lysozyme in Frozen Aqueous Solutions

  • Sun Joo Hong;L. H. Pitte
    • Journal of the Korean Chemical Society
    • /
    • v.16 no.1
    • /
    • pp.40-45
    • /
    • 1972
  • An electron spin resonance study has been made on lysozyme in. frozen aqueous solutions irradiated with $_{60}Co$ r-rays in air at $77^{circ}K.$ Water resonances are dominant when the concentration and the temperature are both below 20% and $130^{circ}K$ respectively. More solute radicals are produced in the solution of higher concentration. Majority of the solute radicals results from direct hit of the radiation. The same types of radicals are induced at $77^{circ}K$ whether the substances are irradiated in the dry state or in frozen aqueous solution. Based on these results, it is assumed that the number of ESR centers produced by the secondary intermolecular radical reacions and stabilized in aqueous solutions may depend on the concentration of the solution, and the presence of water may facilitate the secondary radical reactions occuring in the solute molecules after heat treatment. Majority of the solute radicals above around $193^{circ}K$ are believed to react with oxygen to form peroxytype radicals. However, when the solution is subiected to heat-treatment at $265^{circ}K$ after irradiation at $195^{circ}K$ the peroxy-type resonance was not observed, suggestin that an appreciable amount of oxygen is condensed into the ice, at $77^{circ}K.$ in addition to the oxygen that has already been dissolved in solution and react with solute free radicals during the process of heat-treatment. When the solution contains $H_2O_2$, no water resonance but $HO_2$, type resonance was observed probably indicating that the radiation-induced OH radicals are trapped in $H_2O_2$ aggregates and react readily with $H_2O_2$ molecules to poroduce $HO_2$ type radicals even at $77^{circ}K.$.

  • PDF