[Bonding behavior of 4f orbital].
In this paper, the bonding behavior of 4f orbital in lanthanide coordination compounds was discussed and corresponding theory and research methods were summed up with 36 references.
English Abstract↗
Biomedical subjects
W Yang
Publications and source records attributed to W Yang.
A multidrug resistance transporter from human MCF-7 breast cancer cells.
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.
ATP Binding Cassette Transporter, Subfamily G, Mem↗
Biochemical characterization of alpha-aspartyl dipeptidase. Cloning and expression of its gene.
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Cloning, Molecular↗
Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis.
MutL and its homologs are essential for DNA mismatch repair. Mutations in genes encoding human homologs of MutL cause multiorgan cancer susceptibility. We have determined the crystal structure of a 40 kDa N-terminal fragment of E. coli MutL that retains all of the conserved residues in the MutL family. The structure of MutL is homologous to that of an ATPase-containing fragment of DNA gyrase. We have demonstrated that MutL binds and hydrolyzes ATP to ADP and Pi. Mutations in the MutL family that cause deficiencies in DNA mismatch repair and a predisposition to cancer mainly occur in the putative ATP-binding site. We provide evidence that the flexible, yet conserved, loops surrounding this ATP-binding site undergo conformational changes upon ATP hydrolysis thereby modulating interactions between MutL and other components of the repair machinery.
Adenosine Diphosphate↗
Single glycosyltransferase, core 2 beta1-->6-N-acetylglucosaminyltransferase, regulates cell surface sialyl-Lex expression level in human pre-B lymphocytic leukemia cell line KM3 treated with phorbolester.
Sialyl-Lex (sLex) antigen expression recognized by KM93 monoclonal antibody was significantly down-regulated during differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human pre-B lymphocytic leukemia cell line KM3. The sLex determinants were almost exclusively expressed on O-linked oligosaccharide chains of an O-glycosylated 150-kDa glycoprotein (gp150). A low shear force cell adhesion assay showed that TPA treatment significantly inhibited E-selectin-mediated cell adhesion. Transcript and/or enzyme activity levels of alpha1-->3-fucosyltransferase, alpha2-->3-sialyltransferase, beta1-->4-galactosyltransferase, and elongation beta1-->3-N-acetylglucosaminyltransferase did not correlate with sLex expression levels. However, transcript and enzyme activity levels of core 2 GlcNAc-transferase (C2GnT) were significantly down-regulated during TPA treatment. Following transfection and constitutive expression of full-length exogenous C2GnT transcript, C2GnT enzyme activities were maintained at high levels even after TPA treatment and down-regulation of cell surface sLex antigen expression by TPA was completely abolished. Furthermore, in the transfected cells, the KM93 reactivity of gp150 was not reduced by TPA treatment, and the inhibition of cell adhesion by TPA was also blocked. These results suggest that sLex expression is critically regulated by a single glycosyltransferase, C2GnT, during differentiation of KM3 cells.
Animals↗
Cardiovascular disease hospitalization and ambient levels of carbon monoxide.
Recent research suggests that some cases of cardiovascular mortality may be related to carbon monoxide (CO) air pollution. Clinically based studies indicate the adverse effects of CO on the cardiopulmonary system. However, little attention has been paid to the question of hospital admissions for cardiovascular illness caused by ambient CO levels. The present study assesses the association between hospital admissions for cardiovascular system illnesses and the ambient levels of CO in the Reno-Sparks, NV, area over a 6-yr period (1989-1994). Daily admissions to all three hospitals in the region and daily ambient concentrations of CO, monitored at five sites, were included. There were 32,705 total cardiovascular (CV) admissions, including 13,108 with the diagnosis of ischemic heart disease (IHD) during the study period. The average daily 1-h maximum level of CO was 3.09 ppm. After adjusting for day-of-the-week and seasonal effects and controlling for the effects of autocorrelation errors, both weighted least squares (WLS) and autoregressive integrated moving average (ARIMA) methods showed consistently positive relationships between the ambient CO level and different groups of cardiovascular admissions, although the male gender and age older than 60 groups tended to be most affected. Data suggest a positive correlation between ambient CO levels and hospital admissions for CV diseases.
Adult↗
Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity.
FKBP ligand homodimers can be used to activate signaling events inside cells and animals that have been engineered to express fusions between appropriate signaling domains and FKBP. However, use of these dimerizers in vivo is potentially limited by ligand binding to endogenous FKBP. We have designed ligands that bind specifically to a mutated FKBP over the wild-type protein by remodeling an FKBP-ligand interface to introduce a specificity binding pocket. A compound bearing an ethyl substituent in place of a carbonyl group exhibited sub-nanomolar affinity and 1,000-fold selectivity for a mutant FKBP with a compensating truncation of a phenylalanine residue. Structural and functional analysis of the new pocket showed that recognition is surprisingly relaxed, with the modified ligand only partially filling the engineered cavity. We incorporated the specificity pocket into a fusion protein containing FKBP and the intracellular domain of the Fas receptor. Cells expressing this modified chimeric protein potently underwent apoptosis in response to AP1903, a homodimer of the modified ligand, both in culture and when implanted into mice. Remodeled dimerizers such as AP1903 are ideal reagents for controlling the activities of cells that have been modified by gene therapy procedures, without interference from endogenous FKBP.
Amino Acid Sequence↗
Dynamics of the interphase mammalian Golgi complex as revealed through drugs producing reversible Golgi disassembly.
We focus on research aimed at understanding normal Golgi complex dynamics through the use of nocodazole and other drugs which cause Golgi disassembly. In vivo nocodazole binds to tubulin, produces microtubule depolymerization, and subsequent fragmentation of the Golgi complex. These processes may be traced in living cells through the application of fluorescent green protein (GFP) conjugates. The cycling of individual Golgi proteins through the endoplasmic reticulum (ER) may be probed in vivo through the use of an organelle-specific molecular trap. One such molecular trap is protein unfolding. Golgi proteins conjugated with a domain temperature sensitive in protein folding exhibit temperature-sensitive folding properties and if misfolded during protein cycling from the Golgi become trapped in the ER. The properties of individual Golgi complex subcompartments may be characterized through antibodies to multiple subcompartment-specific proteins within the same cell line. Because of the limited availability of antibodies, normally distributed epitope tagged proteins are employed to give multiple subcompartment-specific Golgi complex markers. From experiments employing these tools, new models suggesting continuous cycling of Golgi proteins are emerging. Cycling of Golgi proteins through the ER can lead to assembly of the Golgi stack at or about ER exit sites. A major future challenge will be the characterization of the protein machineries involved in Golgi protein cycling and its regulation.
Animals↗
Leader peptide efficiency correlates with signal recognition particle dependence in Saccharomyces cerevisiae.
Secretion of bovine pancreatic trypsin inhibitor (BPTI) in Saccharomyces cerevisiae was examined with four different leader peptides: the invertase signal peptide, the mfalpha1 signal peptide, a synthetic signal peptide, and a synthetic pre pro leader. BPTI secretion from a low-copy CEN plasmid varies from 1.8 to 10.4 microgram/mL among these constructs. Secretion titers correlate with dependence on signal recognition particle (SRP), with greatest secretion from the most SRP-dependent construct. Examination of co- vs post-translational translocation pathways and overall translocation efficiency by ubiquitin translocation assay (UTA) does not provide insight into the variation in BPTI secretion efficiency, perhaps due to alteration in translocation kinetics from the additional polypeptide fusion required by the assay. BPTI translocation efficiency (as measured by UTA) is found to drop markedly upon depletion of Srp54p, prior to any observable growth defect. Subsequent to stress response induction and the onset of slow growth (15-h doubling time), BPTI translocation efficiency recovers to the level observed prior to SRP depletion.
Amino Acid Sequence↗
SHP-1 phosphatase C-terminus interacts with novel substrates p32/p30 during erythropoietin and interleukin-3 mitogenic responses.
SHP-1 protein tyrosine phosphatase is a critical negative regulator of mitogenic signaling, as demonstrated by the heightened growth responses to hematopoietic growth factors in hematopoietic cells of motheaten mice, which lack functional SHP-1 expression due to mutations in the SHP-1 gene. The mitogenic signaling molecules dephosphorylated by SHP-1 have not been fully identified. We detected two proteins (p32/p30) that are hyperphosphorylated in a DA3/erythropoietin receptor (EpoR) cell line that expresses a mutant containing the SHP-1 C-terminus that suppresses the function of the endogenous phosphatase and induces hyperproliferative responses to interleukin-3 (IL-3) and Epo. Hyperphosphorylated p32/p30 are also detected in motheaten hematopoietic cells, demonstrating an association of p32/p30 hyperphosphorylation with SHP-1-deficiency and growth factor-hyperresponsiveness. The hyperphosphorylated p32/30 associate with SHP-1 via its C-terminus, because they coimmunoprecipitate with the phosphatase and the C-terminal mutant and they bind in vitro to a synthetic peptide of the mutant but not the GST fusion proteins of SHP-1 SH2 domains. Induction of p32/p30 phosphorylation by IL-3 or Epo occurs mainly at 2 to 18 hours poststimulation in the DA3/EpoR cell line, indicating p32/p30 as novel signaling molecules during cell cycle progression. These data demonstrate a function for the SHP-1 C-terminus in recruiting potential substrates p32/p30 and suggest that SHP-1 may regulates mitogenic signaling by dephosphorylating p32/p30.
Amino Acid Sequence↗
Overcoming cytoplasmic incompatibility in Drosophila.
The endocellular microbe Wolbachia pipientis infects a wide variety of invertebrate species, in which its presence is closely linked to a form of reproductive failure termed cytoplasmic incompatibility (CI). CI renders infected males unable to father offspring when mated to uninfected females. Because CI can dramatically affect fitness in natural populations, mechanisms that abate CI can have equally large impacts on fitness. We have discovered that repeated copulation by Wolbachia-infected male Drosophila simulans significantly diminishes CI. Repeated copulation does not prevent Wolbachia from populating developing spermatids, but may reduce the time during spermatogenesis when Wolbachia can express CI. This restoration of fertility in premated infected males could have important implications for Wolbachia transmission and persistence in nature and for its exploitation as an agent of biological pest control.
Animals↗
Structural basis for MutH activation in E.coli mismatch repair and relationship of MutH to restriction endonucleases.
MutS, MutL and MutH are the three essential proteins for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli. MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex. Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL. We have crystallized MutH in two space groups and solved the structures at 1.7 and 2.3 A resolution, respectively. The active site of MutH is located at an interface between two subdomains that pivot relative to one another, as revealed by comparison of the crystal structures, and this presumably regulates the nuclease activity. The relative motion of the two subdomains in MutH correlates with the position of a protruding C-terminal helix. This helix appears to act as a molecular lever through which MutS and MutL may communicate the detection of a DNA mismatch and activate MutH. With sequence homology to Sau3AI and structural similarity to PvuII endonuclease, MutH is clearly related to these enzymes by divergent evolution, and this suggests that type II restriction endonucleases evolved from a common ancestor.
Amino Acid Sequence↗
mu Opioid receptor knockout in mice: effects on ligand-induced analgesia and morphine lethality.
The mu opioid receptor gene (MOR) was mutated in mice by a gene targeting procedure. In these MOR-knockout mice, the analgesic effects of morphine, its major metabolites, morphine-6-glucuronide (M-6-G) and morphine-6-ethereal sulfate (M-6-S), and endomorphin-2, as well as morphine-induced lethality, were drastically reduced, whereas the effects of DPDPE and U50488 remained unchanged. It is concluded that analgesic effects of mu-specific opioid ligands and acute morphine lethality are mediated by the mu receptor.
Analgesics, Opioid↗
Properties of Starches Conjugated with Lysine and Poly(lysine) by the Maillard Reaction.
Native potato starch (PS), carboxymethyl potato starch (CMS), and corn starch phosphate monoester (PCS) were conjugated with lysine (Lys) and poly(lysine) (PL) by the Maillard reaction. The increased yellowness of each reaction mixture showed the development of browning, suggesting the conjugation of starch and Lys or PL. The Lys and PL contents in the conjugates were 0.12-0.68% and 2.8-4.3%, respectively. Conjugation with PL reduced the swelling and solubility of each starch. The CMS and PCS conjugates gelatinized at higher temperatures than either CMS or PCS alone and were hard to retrograde. The digestibility of each conjugate with alpha-amylase was lower than that of the original starch. The functional changes to the starches were most marked in the cases of starches with partial distortion of the internal structure as indicated for CMS and PCS.
Journal Article↗
Conformational analysis of cyclic analogues of the Saccharomyces cerevisiae alpha-factor pheromone.
Analogues of the alpha-factor mating pheromone (WHWLQLKPGQPMY) from Saccharomyces cerevisiae in which the side chains of residues 7 and 10 were joined by lactam bonds were studied by nmr and molecular modeling. These investigations were carried out to discern the effect of lactam ring size on conformation and to ascertain whether the side chain i to i + 3 cyclized tetramers [H. R. Marepalli et al. (1996) Journal of the American Chemical Society, Vol. 118, pp. 6531-6539] can be considered as conformation-constraining building blocks when introduced into a long peptide chain. Nuclear Overhauser effect constraints, temperature coefficients, and backbone torsional angles were derived from 1H-nmr spectra measured in DMSO-d6. Modeling studies using the above constraints indicate that the lactam regions of the tridecapeptides assume various combinations of type II beta-turns, gamma-turns, and gamma 1-turns, but never type I beta-turns. These investigations provide evidence that the tetrapeptide building blocks retain their preferred conformations in larger molecules and can be used to control the architecture of regions of such peptides.
Amino Acid Sequence↗
Low basal transcripts of the COL2A1 collagen gene from lymphoblasts show alternative splicing of exon 12 in the Kniest form of spondyloepiphyseal dysplasia.
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Alternative Splicing↗
Hyperglycaemic hormones inhibit protein and mRNA synthesis in in vitro-incubated ovarian fragments of the marine shrimp Penaeus semisulcatus.
The present work shows for the first time that peptides belonging to the Crustacean hyperglycaemic hormone family (CHH-family hormones) from Penaeus japonicus affect protein and mRNA synthesis in in vitro-incubated ovarian explant fragments removed from vitellogenic females of Penaeus semisulcatus. Reduced levels of protein synthesis, determined by TCA-precipitable 35S-labeled proteins, were found in the presence of crude sinus gland extracts from both P. semisulcatus and P. japonicus. A similar inhibitory effect compared to controls was found with each of the seven CHH-family peptides. Non-CHH-family peptides did not reduce protein synthesis. Crude sinus gland extracts prepared from P. semisulcatus were at least 20-fold more effective than sinus gland extracts of P. japonicus. The inhibition level was directly related to the concentration of the peptide in the incubation media, but its degree varied among the different tested peptides. The profile of proteins synthesized during in vitro incubation was analyzed using polyacrylamide gel electrophoresis under denatured and reduced conditions (SDS-PAGE), followed by autoradiography. Synthesis of several proteins was reduced, including proteins with electrophoretic mobility similar to that of vitellin. Immunoprecipitation with antiserum prepared against native ovarian vitellin confirmed the inhibitory effect of CHH-family peptides on vitellin synthesis. The crude sinus gland extract and CHH-family peptides also inhibited RNA synthesis, as determined by [3H]uridine incorporation into mRNA of ovarian fragments. It is concluded that in addition to their role in carbohydrate metabolism, CHH-family peptides may also influence ovarian physiology in crustaceans.
Amino Acid Sequence↗
Abscess formation as a complication caused by postoperative osteomyelitis of the femur.
We report an unusual case of a giant femoral abscess caused by postoperative osteomyelitis after treating a fracture of the femoral shaft. The patient ignored it until the abscess began to interfere with knee flexion, but no symptoms of inflammation such as fever, pain or abnormal laboratory values were found. Within the marrow cavity, many plasma cells produced immunoglobulins G and M, and the level of these substances in the abscess fluid connected to the bony focus were higher than the serum levels. It was concluded that the inflammation in this case signified a peculiarity in a primarily chronic process.
Abscess↗