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Biomedical subjects

W Kim

Publications and source records attributed to W Kim.

At least 55 records · Page 3Linked to original sources

Q2 Dependence of quadrupole strength in the gamma*p --> Delta(+)(1232) --> p pi(0) transition.

Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the Q2 dependence of the magnetic (M1+), electric (E1+), and scalar (S1+) multipoles in the gamma*p-->Delta(+)-->p pi(0) transition. We report new experimental values for the ratios E(1+)/M(1+) and S(1+)/M(1+) over the range Q2 = 0.4-1.8 GeV2, extracted from precision p(e,e(')p)pi(0) data using a truncated multipole expansion. Results are best described by recent unitary models in which the pion cloud plays a dominant role.

Journal Article↗

Second-generation intramedullary supracondylar nail for distal femoral fractures.

The objective of this study was to review the use of intramedullary supracondylar (IMSC) nails for distal femoral fractures. We reviewed 24 fractures treated with second-generation IMSC nails. The fractures consisted of 18 type A1, one type A2, two type C1, one type C2, and two type C3 fractures. The relationships between clinical results and fracture type, approaches, and patient age were retrospectively reviewed. All fractures healed clinically and radiographically. Twenty-one patients maintained gait performance equivalent to that before injury. Average operating time was 108 min +/- 43 min. ROM in the knee of all patients was -5 degrees +/- 6 degrees in extension and 102 degrees +/- 38 degrees in flexion. Extension lag was influenced by surgical approach. The final knee arc was inversely correlated to patient age (R: 0.49, P<0.05). There were three varus/valgus deformities, two cases with loosening, and two with breakage of the distal locking screws, but no failure of the nail itself. Second-generation IMSC nailing for distal femur fractures was satisfactory in patients younger than 60 years of age.

Adult↗

Human kinesin superfamily member 4 is dominantly localized in the nuclear matrix and is associated with chromosomes during mitosis.

In a previous study, we identified the human counterpart of murine kinesin superfamily member 4 (KIF4), a microtubule-based motor protein [Oh, Hahn, Torrey, Shin, Choi, Lee, Morse and Kim (2000) Biochim. Biophys. Acta 1493, 219-224]. As an initial step to understand the function(s) of human KIF4, its subcellular localization in HeLa cells was examined by using immunocytochemical and subcellular fractionation methods, and it was found that most KIF4 is localized in the nucleus. Since murine KIF4 is known to transport cytoplasmic vesicles, dominant nuclear localization of the human counterpart was somewhat surprising. Subsequent subnuclear fractionation revealed predominant association of KIF4 with the nuclear matrix. These results clearly indicate that human KIF4 is, at least, a nuclear protein. In further confirmation of this conclusion, the hexapeptide PKLRRR (amino acids 773-778) in the molecule was found to function as a nuclear localization signal. During the mitotic phase of the cell cycle, human KIF4 was associated with the chromosomes, suggesting that human KIF4 might be a microtubule-based mitotic motor, with DNA as its cargo.

Adenocarcinoma↗

Cysteinyl-tRNA synthetase is not essential for viability of the archaeon Methanococcus maripaludis.

The methanogenic archaea Methanocaldococcus jannaschii and Methanothermobacter thermautotrophicus contain a dual-specificity prolyl-tRNA synthetase (ProCysRS) that accurately forms both prolyl-tRNA (Pro-tRNA) and cysteinyl-tRNA (Cys-tRNA) suitable for in vivo translation. This intriguing enzyme may even perform its dual role in organisms that possess a canonical single-specificity cysteinyl-tRNA synthetase (CysRS), raising the question as to whether this latter aminoacyl-tRNA synthetase is indeed required for cell viability. To test the postulate that all synthetase genes are essential, we disrupted the cysS gene (encoding CysRS) of Methanococcus maripaludis. The knockout strain was viable under normal growth conditions. Biochemical analysis showed that the pure M. maripaludis ProCysRS was capable of forming Cys-tRNA, implying that the dual-specificity enzyme compensates in vivo for the loss of CysRS. The canonical CysRS has a higher affinity for cysteine than ProCysRS, a reason why M. maripaludis may have acquired cysS by a late lateral gene transfer. These data challenge the notion that all twenty aminoacyl-tRNA synthetases are essential for the viability of a cell.

Amino Acyl-tRNA Synthetases↗

Distinct retrieval and retention mechanisms are required for the quality control of endoplasmic reticulum protein folding.

Proteins destined for the secretory pathway must first fold and assemble in the lumen of endoplasmic reticulum (ER). The pathway maintains a quality control mechanism to assure that aberrantly processed proteins are not delivered to their sites of function. As part of this mechanism, misfolded proteins are returned to the cytosol via the ER protein translocation pore where they are ubiquitinated and degraded by the 26S proteasome. Previously, little was known regarding the recognition and targeting of proteins before degradation. By tracking the fate of several mutant proteins subject to quality control, we demonstrate the existence of two distinct sorting mechanisms. In the ER, substrates are either sorted for retention in the ER or are transported to the Golgi apparatus via COPII-coated vesicles. Proteins transported to the Golgi are retrieved to the ER via the retrograde transport system. Ultimately, both retained and retrieved proteins converge at a common machinery at the ER for degradation. Furthermore, we report the identification of a gene playing a novel role specific to the retrieval pathway. The gene, BST1, is required for the transport of misfolded proteins to the Golgi, although dispensable for the transport of many normal cargo proteins.

Animals↗

Quasiparticle states around a nonmagnetic impurity in a d-density-wave state of high-T(c) cuprates.

The electronic structure around a single nonmagnetic impurity in the d-density-wave (DDW) ordering is studied. It is found that a single subgap resonance peak appears in the local density of states around the impurity. In the unitary limit, the position of this resonance peak shifts away from the Fermi energy in accord with the chemical potential. This result is dramatically different from the case of the pure superconducting state for which the impurity resonant energy is approximately pinned at the Fermi level. This can be used to probe the existence of the DDW ordering in cuprates.

Journal Article↗

Photoproduction of the rho(0) meson on the proton at large momentum transfer.

The differential cross section, d sigma/dt, for rho(0) meson photoproduction on the proton above the resonance region was measured up to a momentum transfer -t = 5 GeV2 using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The rho(0) channel was extracted from the measured two charged-pion cross sections by fitting the pi(+)pi(-) and p pi(+) invariant masses. The low momentum transfer region shows the typical diffractive pattern expected from Reggeon exchange. The flatter behavior at large -t cannot be explained solely in terms of QCD-inspired two-gluon exchange models. The data indicate that other processes, like quark interchange, are important to fully describe rho photoproduction.

Journal Article↗

Mitochondrial protein phylogeny joins myriapods with chelicerates.

The animal phylum Arthropoda is very useful for the study of body plan evolution given its abundance of morphologically diverse species and our profound understanding of Drosophila development. However, there is a lack of consistently resolved phylogenetic relationships between the four extant arthropod subphyla, Hexapoda, Myriapoda, Chelicerata and Crustacea. Recent molecular studies have strongly supported a sister group relationship between Hexapoda and Crustacea, but have not resolved the phylogenetic position of Chelicerata and Myriapoda. Here we sequence the mitochondrial genome of the centipede species Lithobius forficatus and investigate its phylogenetic information content. Molecular phylogenetic analysis of conserved regions from the arthropod mitochondrial proteome yields highly resolved and congruent trees. We also find that a sister group relationship between Myriapoda and Chelicerata is strongly supported. We propose a model to explain the apparently parallel evolution of similar head morphologies in insects and myriapods.

Animals↗

Quantum interference and ballistic transmission in nanotube electron waveguides.

The electron transport properties of well-contacted individual single-walled carbon nanotubes are investigated in the ballistic regime. Phase coherent transport and electron interference manifest as conductance fluctuations as a function of Fermi energy. Resonance with standing waves in finite-length tubes and localized states due to imperfections are observed for various Fermi energies. Two units of quantum conductance 2G(0) = 4e(2)/h are measured for the first time, corresponding to the maximum conductance limit for ballistic transport in two channels of a nanotube.

Electron Transport↗

Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression.

TEL is a transcriptional repressor that is a frequent target of chromosomal translocations in a large number of hematalogical malignancies. These rearrangements fuse a potent oligomerization module, the SAM domain of TEL, to a variety of tyrosine kinases or transcriptional regulatory proteins. The self-associating property of TEL-SAM is essential for cell transformation in many, if not all of these diseases. Here we show that the TEL-SAM domain forms a helical, head-to-tail polymeric structure held together by strong intermolecular contacts, providing the first clear demonstration that SAM domains can polymerize. Our results also suggest a mechanism by which SAM domains could mediate the spreading of transcriptional repression complexes along the chromosome.

Amino Acid Sequence↗

Evidence for alternate splicing within the mRNA transcript encoding the DNA damage response kinase ATR.

Proper cellular response to genotoxic insult often requires the activity of one or more members of a family of high-molecular weight protein kinases referred to as phosphatidylinositol-3 kinase (PIK)-like proteins. While catalytic activity is an indispensable part of PIK-like protein function, little is currently known about factors that control their activity and/or functions. This deficiency stems, in large part, from our lack of knowledge concerning functionally significant subdomains within the large non-catalytic domain of these proteins. We have determined that the transcript encoding the PIK-like protein ATR undergoes alternate splicing within the region of the mRNA encoding its non-catalytic domain. This conclusion is based on the sequencing of a human expressed sequence tag clone encoding a portion of the ATR cDNA, and is supported by the results of reverse transcriptase-polymerase chain reaction (RT-PCR) assays conducted on total and polyA+ RNA, as well as sequencing of cloned RT-PCR products. Cloning and sequencing of a segment of human genomic DNA indicated that this event arises from splicing of a single 192 bp exon within the ATR gene. Analysis of several human tissues indicated that alternate ATR transcripts are differentially expressed, suggesting that this region of the ATR protein may be of functional importance.

Alternative Splicing↗

Immunostimulation of rat primary astrocytes decreases intracellular ATP level.

In this study we investigated the effect of immunostimulation on intracellular ATP level in rat glial cells. Rat primary astrocytes or C6 glioma cells were treated for 48 h with IFN-gamma, LPS or IFN-gamma plus LPS. These treatments increased NO production from the cells and a synergistic increase in NO production was observed with IFN-gamma plus LPS. Intracellular ATP level was decreased to about half the control level at the highest concentration of IFN-gamma (100 U/ml) plus LPS (1 microg/ml) without affecting cell viability. The level of intracellular ATP was inversely correlated with the extent of NO production from the glial cells. The increase in NO production is at least 6 h ahead of the initiation of ATP depletion, and NOS inhibitor N(G)-nitro-L-arginine (NNA) or Nomega-nitro-L-arginine methyl ester (L-NAME) inhibited NO production and ATP depletion. Exogenous addition of peroxynitrite generator 3-morpholinosydnonimine (SIN-1) and to a lesser extent NO generator S-nitroso-N-acetylpenicillamine (SNAP) depleted intracellular ATP level in a dose-dependent manner. The results from the present study imply that immunostimulation of rat glial cells decreases the intracellular ATP level without affecting cell viability. Considering the role of astrocytes as an essential regulator of the extracellular environment in the brain, the immunostimulation-induced decrease in intracellular ATP level may participate in the pathogenesis of various neurological diseases.

Adenosine Triphosphate↗

Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women.

BACKGROUND: Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. METHODS AND RESULTS: In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). CONCLUSIONS: CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.

Chemokine CCL2↗

Mutational analyses of Aquifex pyrophilus DNA ligase define essential domains for self-adenylation and DNA binding activity.

We constructed nine deletion mutants of NAD+-dependent DNA ligase from Aquifex pyrophilus to characterize the functional domains. All of DNA ligase deletion mutants were analyzed in biochemical assays for NAD+-dependent self-adenylation, DNA binding, and nick-closing activity. Although the mutant lsub1 (91-362) included the active site lysine (KxDG), self-adenylation was not shown. However, the mutants lsub6 (1-362), lsub7 (1-516), and lsub9 (1-635) showed the same adenylation activity as that of wild type. The lsub5 (91-719), which has the C-terminal domain (487-719) as to lsub4 (91-486), showed minimal adenylation activity. These results suggest that the presence of N-terminal 90 residues is essential for the formation of an enzyme-AMP complex, while C-terminal domain (487-719) appears to play a minimal role in adenylation. It was found that the presence of C-terminal domain (487-719) is indispensable for DNA binding activity of lsub5 (91-719). The mutant lsub9 (1-635) showed reduced DNA binding activity compared to that of wild type, suggesting the contribution of the domain (636-719) for the DNA binding activity. Thus, we concluded that the N-terminal 90 residues and C-terminal domain (487-719) of NAD+-dependent DNA ligase from A. pyrophilus are mutually indispensable for binding of DNA substrate.

Adenosine Monophosphate↗