Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis A virus (HAV) mutants containing large deletions within the first pyrimidine-rich tract (pY1; nucleotides [nt] 99 to 138) of the 5' nontranslated RNA (5'NTR) replicate well in cultured cells, while those with pY1 deletions which extend in a 3' direction to include nt 140 to 144 (CUUGU) have a temperature-sensitive (ts) replication phenotype (D.R. Shaffer, E.A. Brown, and S.M. Lemon, J. Virol. 68:5568-5578, 1994). To characterize this replication defect, the ts mutant delta 131-144 was grown under one-step conditions at the nonpermissive temperature (37 degrees C). A shift to the permissive temperature (31 degrees C) for the first 18 h of the viral replication cycle did not enhance virus yields, indicating that temperature sensitivity is not due to a defect in viral entry or uncoating. Similarly, absence of increased yield with a late shift to 31 degrees C between 54 and 72 h suggested that the ts defect does not involve viral assembly. Although monocistronic RNA transcripts containing the delta 99-144 deletion directed translation 22 to 58% less efficiently than the standard 5'NTR in transfected BS-C-1 cells, this difference was present at both 31 and 37 degrees C. In addition, there were no temperature-dependent differences in the abilities of bicistronic transcripts containing either ts or non-ts 5'NTR sequences within the intercistronic space to direct translation of a downstream reporter gene. Thus, ts mutations do not confer a demonstrable temperature-related defect in cap-independent translation. In contrast, an RNase protection assay showed that synthesis of viral plus-strand RNA was markedly delayed in BS-C-1 cells infected with ts virus at 37 degrees C. Analysis of the nucleotide sequence surrounding the deletion in a non-ts revertant derived from delta 116-144 virus revealed that a single U-to-G transversion at nt 114 (CUUUU-->CUUGU) had restored the sequence normally present between nt 140 and 144. These results indicate that ts mutants of HAV with deletions extending downstream from the pY1 domain to nt 140 to 144 are defective in RNA synthesis and that the single-stranded RNA segment containing nt 140 to 144 plays a critical role in replication of HAV RNA.
 ...
PMID:Temperature-sensitive hepatitis A virus mutants with deletions downstream of the first pyrimidine-rich tract of the 5' nontranslated RNA are impaired in RNA synthesis. 766 51

Wood lemmings (Myopus schisticolor) were captured during their autumnal migration in September and October. The animals were maintained at 12 degrees C and under 12L:12D photoperiod. Basal metabolic rate and thermogenic capacity of the wood lemming were studied. Basal metabolic rate was 3.54 ml O2.g-1.h-1, which is 215-238% of the expected value. The high basal metabolic rate seems to be typical of rodents living in high latitudes. The body temperature of the wood lemming was high (38.0-38.8 degrees C), and did not fluctuate much during the 24-h recording. The high basal metabolic rate and the high body temperature are discussed with regard to behavioural adaptation to a low-quality winter diet. Thermogenic capacity, thermal insulation and non-shivering thermogenesis of the wood lemming displayed higher values than expected: 53.0 mW.g-1, 0.53 mW.g-1.degrees C-1 and 53.2 mW.g-1, respectively. Brown adipose tissue showed typical thermogenic properties, although its respiratory property was fairly low, but mitochondrial protein content was high compared to other small mammals. The 24-h recording of body temperature and motor activity did not reveal whether the wood lemming is a nocturnal animal. Possibly, the expression of a circadian rhythm was masked by peculiar feeding behaviour. It is concluded that the wood lemming is well adapted to living in cold-temperature climates.
 ...
PMID:Metabolism, thermogenesis and daily rhythm of body temperature in the wood lemming, Myopus schisticolor. 815 Oct 13

Mutations in the 5' nontranslated RNA (5'NTR) of an attenuated, cell culture-adapted hepatitis A virus (HAV), HM175/P16, enhance growth in cultured African green monkey kidney (BS-C-1) cells but not in fetal rhesus monkey kidney (FRhK-4) cells (S. P. Day, P. Murphy, E. A. Brown, and S. M. Lemon, J. Virol. 66: 6533-6540, 1992). To determine whether these mutations enhance cap-independent translation directed by the HAV internal ribosomal entry site (IRES), we compared the translational activities of the 5'NTRs of wild-type and HM175/P16 viruses in two stably transformed cell lines (BT7-H and FRhK-T7) which constitutively express cytoplasmic bacteriophage T7 RNA polymerase and which are derived from BS-C-1 and FRhK-4 cells, respectively. Translational activity was assessed by monitoring expression of a reporter protein, chloramphenicol acetyltransferase (CAT), following transfection with plasmid DNAs containing bicistronic T7 transcriptional units of the form luciferase-5'NTR-CAT. In both cell types, transcripts containing the 5'NTR of HM175/P16 expressed CAT at levels that were 50- to 100-fold lower than transcripts containing the IRES elements of Sabin type 1 poliovirus or encephalomyocarditis virus, confirming the low activity of the HAV IRES. However, in BT7-H cells, transcripts containing the 5'NTR of wild-type virus. This translational enhancement was due to additive effects of a UU deletion at nucleotides 203 and 204 and a U-to-G substitution at nucleotide 687 of HM175/P16. These mutations did not enhance translation in FRhK-T7 or Huh-T7 cells (a T7 polymerase-expressing cell line derived from human hepatoblastoma cells) or in vitro in rabbit reticulocyte lysates. These results demonstrate that mutations in the 5'NTR of a cell culture-adapted HAV enhance viral replication by facilitating cap-independent translation in a cell-type-specific fashion and support the concept that picornaviral host range is determined in part by differences in cellular translation initiation factors.
 ...
PMID:Mutations within the 5' nontranslated RNA of cell culture-adapted hepatitis A virus which enhance cap-independent translation in cultured African green monkey kidney cells. 855 62

Long-range carbon atom topomerization in a 1,3-diyne has been demonstrated for the first time. 1-Phenyl-4-p-tolyl-1,3-butadiyne, (13)C-enriched at C-1, was synthesized and subjected to flash vacuum pyrolysis. At 800 degrees C and 0.01 Torr, this resulted in nearly complete (13)C label equilibration between C-1 and C-2, as seen by NMR analysis. Pyrolysis at 900 degrees C further led to ca. 35% of the label migrating about equally to C-3 and C-4. These results demonstrate that both intrabond and interbond atom exchange processes are operative, with the former having a lower activation barrier. DFT and Moller-Plesset calculations support a mechanism that passes through Brown rearrangement (1,2-shift), closure to trialene (bicyclo[1.1.0]-1,3-butadiene), bond-shift isomerization to exchange C-2 and C-3, and ring opening. The resulting vinylidene can rearrange to a butadiyne with the isotopic label at C-3 or C-4. Consistent with earlier calculations, trialene is predicted to have alternating peripheral bonds, with a weak central sigma bond and significant diradical character. Trialene is predicted [(B3LYP/6-311+G(2d,p)] to lie 64.6 kcal/mol above butadiyne, with barriers of 2.2 and 4.4 kcal/mol, respectively, for ring opening or bond-shift isomerization. Other potential rearrangement mechanisms which pass through tetrahedrene (E(rel) = 167.2 kcal/mol) or 1,2,3-cyclobutatriene (E(rel) = 161.1 kcal/mol) lie at much higher energies.
 ...
PMID:Beyond the Roger Brown rearrangement: long-range atom topomerization in conjugated polyynes. 1203 81

The planar and stereostructures of JBIR-108 isolated from Streptomyces gramineus IR087Pi-4 were determined partly by spectral analysis, and these structural assignments were confirmed and completed by the total synthesis of both 1-epimers. The key stereocenters in JBIR-108 were constructed via a Corey-Bakshi-Shibata (CBS) reduction (C-1), vinylogous Mukaiyama aldol reaction (C-7), and Brown crotylation (C-14 and C-15). Although it was difficult to determine the stereochemistries at the C-1 and C-7 positions in the natural product using the modified Mosher's method, the synthesis of two possible C-1 diastereomers enabled the identification of the configurations at the hitherto unknown stereocenters.
...
PMID:Total Synthesis and Structure Determination of JBIR-108-A 2-Hydroxy-2-(1-hydroxyethyl)-2,3-dihydro-3(2H)-furanone Isolated from Streptomyces gramineus IR087Pi-4. 2543 51