Individual medicine

Research objective: Establish the genetic variants database of 04 genes CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in Kinh Vietnamese. Identification of genotype and allele frequencies of 04 genes CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in Kinh Vietnamese. Perform in silico functional analysis of novel variants.

27p extraenglish 24-05-2021 27 4   Download

Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities.

5p caothientrangnguyen 09-05-2020 11 2   Download

To establish stable cell lines that produce recombinant multisubunit proteins, it is usually necessary to cotransfect cells with several independent gene constructs. Here, we show that a stepwise fusion of individually transfected cells, results in a fused cell-line that secretes a complete multisubunit protein. Functional expression of recombinant multisubunit proteins may require a defined expression ratio between each protein subunit. The cell-fusion technology described allows a predefined expression level of each subunit.

6p system191 01-06-2013 35 4   Download

By replacing specific amino acids at positions 112, 147 and 152 of the human aldosterone synthase (CYP11B2) with the corresponding residues from human, mouse or rat 11b-hydroxylase (CYP11B1), we have been able to investigate whether these residues belong to structural determinants of individual enzymatic activities. When incubated with 11-deoxycorticosterone (DOC), the 11b-hydroxylation activity of the mutants was most effectively increased by combining D147E and I112P (sixfold increase).

10p research12 01-06-2013 36 4   Download

When theaand bchains were separated from human oxyhemoglobin (HbO2), each individual chain was oxidized easily to the ferric form, their rates being almost the same with a very strong acid-catalysis. In the HbO2tetramer, on theother hand, bothchains become considerably resistant to autoxidation over a wide range of pH values (pH 5±11).

10p research12 29-04-2013 42 4   Download

Eur. J. Biochem. 269, 5950–5955 (2002) Ó FEBS 2002 doi:10.1046/j.1432-1033.2002.03323.x The most active factor VIIa (FVIIa) variants identified to date carry concurrent substitutions at positions 158, 296and 298 with the intention of generating a thrombin-mimicking motif, optionally combined with additional replacements within the protease domain [Persson, E., Kjalke, M. & Olsen, O. H. (2001)Proc. Natl Acad. Sci. USA98, 13583– 13588]. Here we have characterized variants of FVIIa mutatedat one or twoof these positions toassess the relative importance of the individual replacements.

6p tumor12 22-04-2013 36 2   Download

The aimof this workwas to elucidate the roles of individual residues within the flexible second binding loop of human cystatin A in the inhibition of cysteine proteases. Four recombinant variants of the inhibitor, each with a single mutation, L73G, P74G, Q76G or N77G, in the most exposed part of this loopwere generated by PCR-based site-directed mutagenesis. The binding of these variants to papain, cathepsin L, and cathepsin B was characterized by equilibrium and kinetic methods.

10p tumor12 22-04-2013 34 2   Download

Opacity-associated (Opa) proteins are outer membrane proteins which play a critical role in the adhesion of patho-genicNeisseriaspp. to epithelial and endothelial cells and polymorphonuclear neutrophils. The adherence is mainly mediated by the CD66-epitope-containing members of the carcinoembryonic-antigen family of human cell-adhesion molecules (CEACAM). For the analysis of the specific in-teractions of individual Opa proteins with their receptors, pure protein is needed in its native conformation. ...

9p tumor12 22-04-2013 34 2   Download

Reconstitution of membrane proteins allows their study in a membrane environment that can be manipulated at will. Because membrane proteins have diverse biophysical pro-perties, reconstitution methods have so far been developed for individual proteins on an ad hoc basis. We developed a postinsertion reconstitution method for CCR5, a G protein coupled receptor, with seven transmembraneahelices and small ecto- and endodomains.

12p tumor12 22-04-2013 38 2   Download

The beneficial influence of dietary curcumin, capsaicin and their combina-tion on the susceptibility of low-density lipoprotein (LDL) to oxidation was examined in an animal study. Individually, both dietary curcumin and capsaicin significantly inhibited thein vivo iron-induced LDL oxidation, as well as copper-induced oxidation of LDLin vitro. The protective effect of the combination of curcumin and capsaicin on LDL oxidation was greater than that of individual compounds.

10p tumor12 20-04-2013 48 5   Download

The kinetic properties of glycine oxidase fromBacillus sub-tiliswere investigated using glycine, sarcosine, andD-proline as substrate. The turnover numbers at saturating substrate andoxygen concentrationswere 4.0 s )1 ,4.2s )1 ,and3.5 s )1 , respectively, with glycine, sarcosine, andD-proline as sub-strate. Glycine oxidase was converted to a two-electron reduced form upon anaerobic reduction with the individual substrates and its reductive half-reaction was demonstrated tobe reversible.

9p tumor12 20-04-2013 38 4   Download

Multi-protein complexes are emerging as important entities of biological activity inside cells that serve to create func-tional diversity by contextual combination of gene products and, at the same time, organize the large number of different proteins into functional units. Many a time, when studying protein complexes rather than individual proteins, the bio-logical insight gained has been fundamental, particularly in cases in which proteins with no previous functional anno-tation couldbe placed intoa functional context derived from their
molecular environment. ...

9p tumor12 20-04-2013 38 2   Download

We report experiments to investigate the role of the physio-logically relevant protein tyrosine kinase Lck in the ordered phosphorylation of the T-cell receptorfchain. Six synthetic peptides were designed based on the sequences of the immunoreceptor tyrosine-based activation motifs (ITAMs) of thefchain. Preliminary 1 H-NMRstudies of recombinant f chain suggested that it is essentially unstructured and therefore that peptide mimics would serve as useful models for investigating individual ITAM tyrosines....

8p fptmusic 16-04-2013 26 1   Download

HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8–2.3 A˚ resolution, and the inhibitory activity of the compounds characterized inorder toevaluate the effects of the individual modifications. ...

13p fptmusic 16-04-2013 44 3   Download

The small heat shock proteins function as molecular chaperones, an activ-ity often requiring reversible oligomerization and which protects against irreversible protein denaturation. An abundantly produced small heat shock protein termed p26 is thought to contribute to the remarkable stress resistance exhibited by encysted embryos of the crustacean,Artemia francis-cana. Three novel sequence motifs termed G, R and TS were individually deleted from p26 by site-directed mutagenesis.

14p fptmusic 12-04-2013 44 4   Download

In humans, thromboxane (TX) A2 signals through two receptor isoforms, thromboxane receptor (TP)aand TPb, which are transcriptionally regula-ted by distinct promoters, Prm1 and Prm3, respectively, within the single TP gene. The aim of the current study was to investigate the ability of the endogenous peroxisome proliferator-activated receptor (PPAR)c ligand 15-deoxy-D 12,14 -prostaglandin J2 (15d-PGJ2) to regulate expression of the human TP gene and to ascertain its potential effects on the individual TPa and TPbisoforms....

20p fptmusic 12-04-2013 37 3   Download

Ech hydrogenase fromMethanosarcina barkeriis a member of a distinct group of membrane-bound [NiFe] hydrogenases with sequence similarity to energy-conserving NADH:quinone oxidoreductase (complex I). The sequence of the enzyme predicts the binding of three [4Fe-4S] clusters, one by subunit EchC and two by subunit EchF. Previous studies had shown that two of these clusters could be fully reduced under 10 5 Pa of H2at pH 7 giving rise to two distinct S½ electron paramagnetic resonance (EPR) signals, designated as the g¼1.89 and theg¼1.92 signal....

13p fptmusic 12-04-2013 36 2   Download

Oxysterol binding protein (OSBP) and its homologs have been shown to regulate lipid metabolism and vesicular transport. However, the exact molecular function of individual OSBP homologs remains uncharacterized. Here we demonstrate that the yeast OSBP homolog, Osh6p, bound phos-phatidic acid and phosphoinositides via its N-terminal half containing the conserved OSBP-related domain (ORD). Using a green fluorescent protein fusion chimera, Osh6p was found to localize to the cytosol and patch-like or punctate structures in the vicinity of the plasma membrane....

13p fptmusic 12-04-2013 52 3   Download

Members of atRNA Gly 1 multigene family from the silkwormBombyx mori have been classified based on their transcriptions in homologous nuclear extracts, into three groups of highly, moderately and poorly transcribed genes. Because all these gene copies have identical coding sequences and consequently identical promoter elements (the A and B boxes), the flanking sequences modulate their expression levels. Here we demonstrate the inter-action of transcription factor TFIIIB with these genes and its role in regu-lating differential transcriptions....

15p fptmusic 12-04-2013 37 2   Download

The structural changes produced by the minor-groove binding ligand DAPI (4¢,6-diamidine-2-phenylindole) on individual strands of trinucleotide repeat sequences were detectedby electrophoreticband-shift analysis andrelated to their effects on DNA replication in vitro. Among the 20 possible single-stranded trinucleotide repeats, only theT-rich strand of the AATÆATT triplet exhibits an observable fluorescence band and a change in electrophoretic mobility due to the drug binding.

7p fptmusic 12-04-2013 45 4   Download