Weak mixing matrix under permutation symmetry breaking.
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Biomedical subjects
Publications and source records attributed to C Lin.
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The mitochondrial gene T-urf13 from maize (Zea mays L.) with Texas male-sterile (T) cytoplasm codes for a unique 13 kd polypeptide, T-URF13, which is implicated in cytoplasmic male sterility and sensitivity to the insecticide methomyl and to host-specific fungal toxins produced by Helminthosporium maydis race T (HmT toxin) and Phyllosticta maydis (Pm toxin). A chimeric gene coding for T-URF13 fused to the mitochondrial targeting peptide from the Neurospora crassa ATP synthase subunit 9 precursor was constructed. Expression of this gene in the yeast Saccharomyces cerevisiae yielded a polypeptide that was translocated into the membrane fraction of mitochondria and processed to give a protein the same size as maize T-URF13. Methomyl, HmT toxin and Pm toxin inhibited growth of yeast cells expressing the gene fusion on medium containing glycerol as sole carbon source and stimulated respiration with NADH as substrate by isolated mitochondria from these cells. These effects were not observed in yeast cells expressing T-URF13 without a targeting peptide. The results show that T-URF13 is sufficient to confer sensitivity to methomyl and the fungal toxins in a heterologous eukaryotic system, and suggest that mitochondrial localization of T-URF13 is critical for these functions.
Changes in gene expression occur during cold acclimation in a wide variety of plant species. Here we show that a number of the polypeptides encoded by cold-regulated (cor) genes of Arabidopsis thaliana L. (Heyn) and wheat share the unusual biochemical property that they remain soluble upon boiling in aqueous solution. Further, cDNA cloning in conjunction with Southern and Northern analyses indicate that wheat has a cor gene that is related to Arabidopsis cor47, a gene encoding a 47 kilodalton ;boiling-stable' COR polypeptide. We suggest it is likely that the boiling-stable COR polypeptides have a fundamental role in plants acclimating to cold temperatures and discuss the possibility that they may act as cryoprotectants.
Adult rats were trained in a maze for brightness discrimination (BD) or in a shuttle box for active avoidance. It was found that the pretreatment of 1-desamino-8-D-arginine-vasopressin (DDAVP) enhanced the retention of brightness discrimination and retarted the extinction of avoidance response. Neonatal daily administration for 14 d of both 9-desglycylamide-DDAVP (DGDDAVP) or 2-destyrosyl-3-desphenylalanyl-9-desglycylamide-AVP (AVP4-8), but not D-arginine-AVP4-8 (DAVP4-8) showed significant facilitation on acquisition and subsequent maintenance of BD in adult rats. The results indicate that some of synthetic arginine-vasopressin analogs may directly act on CNS and consequently affect learning behaviors in rats.
Angiotensin binding sites in membrane homogenates of rabbit iris/ciliary body and human nonpigmented ciliary epithelial (NPE) cells grown in culture were characterized using radioligand binding assays with (125I)-sarcosine1-isoleucine8-angiotensin II [(125I)-SARILE]. Scatchard analysis of the binding of (125I)-SARILE yielded linear plots with a Kd value of 0.55 +/- 0.1 nM and a Bmax of 98 +/- 23 fmol/mg protein in rabbit iris/ciliary body, and a Kd value of 0.63 +/- 0.1 nM, and a Bmax of 36.2 +/- 24 fmol/mg protein in NPE cells. Studies of the inhibition of the binding of (125I)-SARILE in rabbit iris/ciliary body were performed with a series of competing ligands, including the angiotensin receptor antagonist SARILE and the agonists angiotensin I, angiotensin II and angiotensin III. Inhibition curves for the antagonist resulted in Hill coefficients of approximately 1, consistent with the presence of a single class of binding sites with high affinity for (125I)-SARILE. Competition for the binding of (125I)-SARILE to binding sites with each of the agonists resulted in inhibition curves with Hill coefficients significantly less than 1 in the absence of GTP. However, in the presence of 100 microM GTP the Hill coefficients increased to approximately 1. The order of potencies of these agents was consistent with the pharmacologic profile of angiotensin II receptors. Thus rabbit iris/ciliary body homogenates, which include vascular tissue, contain a homogeneous population of angiotensin binding sites coupled to a guanine nucleotide binding protein. The presence of binding sites in cultured NPE cells indicates that at least some are located on the cells thought to be responsible for aqueous humor secretion.
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Myotendinous junctions are sites which are morphologically and molecularly specialized for force transmission between intracellular and extracellular structural proteins. In the present investigation, the formation of these specialized junctions is studied in chicken embryos from 9 days following fertilization to 1 day posthatching, using light and electron microscopy. Observations indicate that the first discernible event in myotendinous junction formation is the appearance of basement membrane at the incipient junction at 9-10 days postfertilization, concomitant with the aggregation of fibroblasts at the junctional regions of myogenic cells. Subsequently, subsarcolemmal densities appear at sites opposite basement membrane locations by 13 days postfertilization. Myofibrils insert into subsarcolemmal densities by day 15 and invaginations of the cell membrane are initiated at those insertions. Type I collagen fibers appear at the cell surface at day 17. Junctional structure at day 17 qualitatively resembles that of adult myotendinous junctions. Changes in junctional structure following day 17 are primarily increases in the amount of subsarcolemmal densities, myofibril-membrane associations, and amount of junctional membrane folding.
We studied the plasma pharmacokinetics and tissue penetration of Sch 39304 (SCH), a new antifungal triazole, in granulocytopenic [G(+)] and nongranulocytopenic [G(-)] rabbits. Five female New Zealand White G(-) rabbits were given a single oral dose of 2 mg of SCH per kg of body weight. Levels in plasma, determined by gas-liquid chromatography-electron capture, were obtained for 6 days. This procedure was repeated 2 weeks later with the same rabbits, which were induced and maintained G(+) with cytosine arabinoside. There were no significant differences between the pharmacokinetic parameters of G(+) and G(-) rabbits. Among all animals studied, the maximum concentration of the drug in plasma was 1.4 +/- 0.11 micrograms/ml at 4 +/- 0.5 h, the half-life was 25 +/- 1.4 h, the volume of distribution at steady state was 3.8 +/- 0.3 liters, and the area under the concentration-time curve was 44 +/- 3.4 micrograms.h/ml. SCH was detectable in plasma up to day 6. Levels of SCH in tissue were studied at steady state in six G(+) and six G(-) rabbits receiving 2 mg of the drug orally per kg per day for experimental disseminated candidiasis. Tissue SCH levels equalled or exceeded those in plasma (at steady state) at all sites examined, and these ratios were similar in both G(+) and G(-) rabbits. Thus, plasma pharmacokinetics of orally administered SCH were similar for G(+) and G(-) rabbits, and SCH achieved high levels of penetration into multiple tissues, including the liver and the central nervous system.
We reported 2 cases of Landau-Kleffner syndrome from Beijing whose clinical manifestations were very similar to ones previously reported. The onset of symptoms in these 2 cases was at 3 and 4 years of age, respectively, and both were characterised by unilateral focal epileptiform EEG discharges, without remarkable clinical seizures. One patient had normal SPECT study in addition to normal CT scan, BAER and VER results; the other had a family history of epilepsy. Since this syndrome may involve a primary brain disturbance responsible for both the epilepsy and aphasia without clear structural brain lesions, we wonder whether it can be classified as one of the benign functional partial epilepsies with genetic factors.
The effects of the artificial triglyceride-phospholipid emulsion (10% intralipid) on HDL subfraction were studied in vivo. After a 14-h fast, subjects received intralipid via a 4-h infusion. Serum lipoproteins were analyzed before and at 4 and 6 h after the start of the infusion. At 4-h the following acute changes by infusion were observed. Triglyceride, phospholipid, free cholesterol, and esterified cholesterol in chylomicrons and VLDL increased. HDL2 as well as triglyceride, phospholipid, free cholesterol and protein within the HDL2 increased, while HDL3 decreased. An increase in HDL3 triglyceride was observed. The masses of apo A-I and A-II in the HDL2 density interval rose while these parameters fell in HDL3. There were decreases of apo C-II and C-III in the HDL subfractions and elevations in chylomicrons and VLDL. The particle size of the HDL subfractions increased. However, most of these acute changes at 4 h tended to disappear by 6 h. These results suggest that there is exchange of lipids and reversible transfer of apo C-II and C-III between HDL subfractions and intralipid, and conversion of HDL3 to HDL2 followed by the reverse conversion of HDL2 to HDL3 as the synthetic emulsion is cleared from the plasma.
The requirements for activation of the transformation potential of the human c-fos proto-oncogene were investigated. Recombinant plasmids containing the Moloney murine leukemia virus long terminal repeat directing transcription of the c-fos coding region and either the authentic c-fos 3' untranslated region (UTR) or the 3' UTR from human c-myc were inefficient at inducing transformation. In contrast, a recombinant that substituted most of the c-fos 3' UTR with the 3' portion of the simian virus 40 T-antigen gene transformed cells well. This difference in transformation efficiency appeared to be due to significantly higher levels of fos mRNA and protein expressed from the transforming recombinant. This, in turn, was due to the much greater stability of its mRNA compared with those from the poorly transforming recombinants containing the c-fos or c-myc 3' UTR. Thus, the 3' UTR of the human c-fos mRNA is responsible for its rapid degradation and limits the steady-state levels of transcript and protein. Cells transformed by the activated human c-fos plasmids contained increased amounts of partially modified c-fos protein (c-Fos). This form of c-Fos turned over much more rapidly than the highly modified form of c-Fos induced by serum stimulation.
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(+)-Cyclaradine (Sch 31172) is the carbocyclic derivative of adenosine arabinoside (9-beta-D-arabinofuranosyladenine). Because it is not deaminated by deaminase in serum, as is adenosine arabinoside, (+)-cyclaradine is about 2 to 5 times more active in vitro against herpes simplex virus. (+)-Cyclaradine has in vitro activity nearly equivalent to that of phosphonoformate but is significantly less active than acycloguanosine (acyclovir; ACV), trifluorothymidine, or 9-(1,3-dihydroxy-2-propoxymethyl)guanine. The absolute ratios of in vitro activities are difficult to determine because of variability among virus strains, inoculum size, and dependence on the tissue culture cell line in which the comparative test is carried out. (+)-Cyclaradine is active against TK-, ACV-resistant mutants. In the guinea pig model of vaginal herpes simplex virus infection, (+)-cyclaradine is only slightly less active than ACV when both molecules are nearly equivalently bioavailable; thus, the large difference in activity seen in vitro is not reflected in this in vivo model system.
Both (+)-cyclaradine-5'-methoxyacetate (CM) and (+)-cyclaradine-5'-ethoxypropionate (CE) were converted to (+)-cyclaradine (C) in squirrel monkey and human sera at 37 degrees C. CE was more stable than CM. After oral administration (20 mg base equivalent per kg) of either CM or CE, no unchanged esters were observed in serum of squirrel monkeys, rabbits, or rats. Instead, C was detected, indicating conversions of CM and CE to C in vivo. In squirrel monkeys, the areas under the curve (AUCs) of C obtained from oral dosing with CM were 61% higher than those obtained from dosing with C, indicating that CM may be a good prodrug for C. In squirrel monkeys, rabbits, and rats, CE resulted in a 20 to 90% higher AUC of C than did CM, indicating that CE was better absorbed than CM.