Rop/helix-loop-helix similarity.
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Amino Acid Sequence↗
Biomedical subjects
T J Gibson
Publications and source records attributed to T J Gibson.
Protruding domain of tomato bushy stunt virus coat protein is a hitherto unrecognized class of jellyroll conformation.
The capsid protein of tomato bushy stunt virus (TBSV) has two antiparallel beta-sheet domains with the so-called jellyroll conformation. Contrary to previous analyses, we note that these domains are non-superimposable topologies. The TBSV shell (S) domain topology is common to many other proteins but the protruding (P) domain is a unique conformation so far found in no other protein. The TBSV capsid P domain did not arise from the S domain by a gene duplication event as previously assumed. It is proposed instead that the P domain was acquired from an as yet unidentified cellular protein. The four possible unique jellyroll topologies that might occur in proteins are discussed and illustrated.
Capsid↗
Metabolic complexity in the RNA world and implications for the origin of protein synthesis.
A model is presented for the evolution of metabolism and protein synthesis in a primitive, acellular RNA world. It has been argued previously that the ability to perform metabolic functions logically must have preceded the evolution of a message-dependent protein synthetic machinery and that considerable metabolic complexity was achieved by ribo-organisms (i.e., organisms in which both genome and enzymes are comprised of RNA). The model proposed here offers a mechanism to account for the gradual development of sophisticated metabolic activities by ribo-organisms and explains how such metabolic complexity would lead subsequently to the synthesis of genetically encoded polypeptides. RNA structures ancestral to modern ribosomes, here termed metabolosomes, are proposed to have functioned as organizing centers that coordinated, using base-pairing interactions, the order and nature of adaptor-mounted substrate/catalyst interactions in primitive metabolic pathways. In this way an ancient genetic code for metabolism is envisaged to have predated the specialized modern genetic code for protein synthesis. Thus, encoded amino acids initially would have been used, in conjunction with other encoded metabolites, as building blocks for biosynthetic pathways, a role that they retain in the metabolism of contemporary organisms. At a later stage the encoded amino acids would have been condensed together on similar RNA metabolosome structures to form the first genetically determined, and therefore biologically meaningful, polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic Code↗
Catalytic RNA and the origin of genetic systems.
The recent discovery of catalytic RNA molecules has provoked enormous interest in the origin of life and has given rise to new speculations about how living systems developed on the primitive earth. Here we outline why the discovery of catalytic RNA molecules has profound evolutionary implications, and then go on to discuss models for the emergence of metabolic complexity and protein synthesis in a primitive 'RNA world', emphasizing the constraints imposed on such models by genetical arguments.
Biological Evolution↗
A model for the tertiary structure of the 28 residue DNA-binding motif ('zinc finger') common to many eukaryotic transcriptional regulatory proteins.
Many eukaryotic transcriptional activator proteins, including the Xenopus 5S RNA gene activator protein TFIIIA and the HeLa cell protein Sp1, have an approximately 30 amino acid repeating motif which binds to short, specific DNA sequences. Over 150 of these sequences are now known. Based on the observed distribution of amino acid residues, a series of constraints and predictions can be proposed for the structure of the motif. A compatible three-dimensional structural model has been developed by a combination of interactive model building and refinement by molecular dynamics. The model structure consists of a two-stranded beta-hairpin stabilizing a C-terminal alpha-helix by both zinc ligands and hydrophobic interactions. Four of the residue positions on the helix N-terminus and exposed face are predicted to provide base specific ligands. Further implications of the model for DNA binding are discussed.
Amino Acid Sequence↗
Lorist2, a cosmid with transcriptional terminators insulating vector genes from interference by promoters within the insert: effect on DNA yield and cloned insert frequency.
Transcription terminators have been included in a phage-lambda-replicon-based cosmid vector, Lorist2, to insulate vector genes against transcriptional interference from cloned insert DNA. DNA yields of recombinant clones containing Escherichia coli genomic DNA inserts are more even for Lorist2 than with its progenitor LoristB. However, the terminators provide only a partial reduction in the over-representation of r X DNA-containing clones generally observed in cosmid libraries of Caenorhabditis elegans DNA, suggesting that causes other than transcriptional readthrough into the vector contribute to this problem.
Animals↗
Lorist6, a cosmid vector with BamHI, NotI, ScaI and HindIII cloning sites and altered neomycin phosphotransferase gene expression.
Four new features have been included in a phage-lambda-replicon-based cosmid vector, Lorist6. A ScaI restriction site allows insertion of blunt-ended DNA, partially digested with AluI or any other restriction enzyme which creates blunt ends after cleavage. NotI and BamHI sites enable construction of libraries using double digestion with NotI + Sau3AI. The promoter of the neo gene has been substituted by a promoter derived from the tet gene of pBR322, increasing expression of the resistance gene product. A transcriptional terminator has been placed downstream from the neo gene to prevent transcription into insert DNAs.
Cloning, Molecular↗
Severity of injuries in road crashes. A comparison of injured occupants of forward control vehicles and conventional passenger cars.
Light vans are being used increasingly as substitutes for conventional passenger cars in Australia. These "forward control" vans are not required to meet the same safety standards as passenger cars. A study group of 258 injured occupants of light vans was identified from the records of the Motor Accidents Board of Victoria. A comparison group of 3468 injured occupants of conventional cars was also identified. Both groups had been injured in accidents occurring in Victoria between 1980 and 1983. The injuries received by the van occupants were compared with those received by the car occupants. Van occupants injured in frontal crashes were more likely to have sustained leg injury, and were more likely to have sustained serious injury than were car occupants who were injured in frontal crashes. Forward control vans were found to lack protection for occupants in frontal crashes.
Accidents, Traffic↗
Coding content and expression of the EBV B95-8 genome in the region from base 62,248 to base 82,920.
The DNA sequence of a 20,672-base region of the EBV B95-8 genome from the BamHI site separating fragments BamHI-F and BamHI-Q to the EcoRI site separating fragments EcoRI-G2 and EcoR1-F has been determined. S1 mapping and northern blotting with probes from M13 recombinants have been used to search for RNAs from this region. Five mRNAs have been identified and correlated with five open reading frames in the DNA sequence. Two of these open reading frames encode ribonucleotide reductase subunits. A further two open reading frames are present including one for a predicted protein of 340 kDa for which no transcript has yet been detected.
Base Sequence↗
Chelation therapy for atherosclerosis.
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Arteriosclerosis↗
The BamHI F region of the B95-8 Epstein-Barr virus genome.
The BamHI F region of the B95-8 Epstein-Barr virus (EBV) genome has been sequenced and analysed for transcription signals and open reading frames. S1 mapping and northern blotting with probes from M13 recombinants have been used to search for mRNAs. Four rightward-reading frames encoding basic proteins appear to be expressed by 3'-coterminal early mRNAs. Two leftward-reading frames appear to be expressed by 3'-coterminal early mRNAs.
Base Sequence↗
Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination.
Two methods for increasing the length of DNA sequence data that can be read off a polyacrylamide gel are described. We have developed a rapid way to pour a buffer concentration gradient gel that, by altering the vertical band separation on an autoradiograph, allows more sequence to be obtained from a gel. We also show that the use of deoxyadenosine 5'-(alpha-[35S]thio)triphosphate as the label incorporated in dideoxynucleotide sequence reactions increases the sharpness of the bands on an autoradiograph and so increases the resolution achieved.
Autoradiography↗
A study of repeated administration of fenbufen in patients with chronic rheumatic disorders and renal impairment.
Male and female patients suffering from rheumatoid arthritis with normal renal function or with renal impairment were treated in hospital with 300 mg of fenbufen 8 hourly for fourteen days. Concentrations of fenbufen and its principal metabolites were measured by high pressure liquid chromatography on days 0, 7, 10 and 14 and also four days after discontinuation of the drug. Renal impairment does not produce cumulation of either fenbufen or its major metabolites in the plasma. The metabolite profile of the drug was similar to that observed in patients with normal renal function.
Adult↗
HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis.
To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate of D-penicillamine, we studied 91 patients with rheumatoid arthritis. Seventy-one had toxic reactions to either drug or both drugs; the remaining 20 took one of the drugs for at least six months, without toxicity. Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRW3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinura and nine of 13 episodes of penicillamine-induced proteinura occurred in patients with these antigens. All 13 episodes of proteinuria in which urinary protein exceeded 2 g in 24 hours occurred in patients with DRw3. The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLA-DRw3 positive. No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications. Toxicity during aurothiomalate or penicillamine treatment for rheumatoid arthritis may be under genetic control.
Adult↗
HLA antigens in rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Treatment of cholelithiasis in patients with sickle cell anemia.
The incidence of cholelithiasis and surgical risk of cholecystectomy in patients with sickle cell anemia is reviewed. Records of all patients with sickle cell disease currently attending the Medical University of South Carolina Hematology Clinic were reviewed. An oral cholecystogram has been part of the initial evaluation for the past year. The records of 16 patients having cholecystectomy from 1968 to 1977 were reviewed with regard to diagnostic studies, preoperative preparation, morbidity, and mortality. When the status of the gallbladder is known, the incidence of cholelithiasis is 67%. The morbidity of elective cholecystectomy was high (37%); there was one death. Cholecystectomy is not recommended for the discovery of asymptomatic gallstones because of the relatively poor surgical risk and short life expectancy of these patients.
Adolescent↗