Differential binding of NAD+ to acyl glyceraldehyde-3-phosphate dehydrogenase and its role in the acyl group transfer reaction.

Enzyme protein fluorescence of di-furylacryloyl-glyceraldehyde-3-phosphate dehydrogenase (di-FA-GPDH:lambda max.excitation 290 nm, lambda max.emission 338 nm) is quenched about 28% on saturation with NAD+. Results of fluorometric titration of di-FA-GPDH with NAD+ suggest the presence of two tight and two loose coenzyme binding sites (Kdiss. 0.1 and 6.0 microM, respectively). Initial rates of the NAD(+)-dependent reaction of di-FA-GPDH with arsenate and phosphate and of mono-FA-GPDH with phosphate have been determined at varying coenzyme concentrations. The data suggest that binding of NAD+ at the tight sites does not activate the acyl group for its reaction with the acceptor (phosphate or arsenate). The group transfer reaction is dependent only on NAD+ binding to the loose sites, which carry the acyl group. The large difference in the NAD+ binding affinity to the two types of sites and their different effects on the group transfer reaction impart a sigmoidal shape to the rate versus [NAD+] plots. The sigmoidicity is abolished if the reactive SH groups at the unacylated sites are blocked by carboxymethylation.     

ABO and Rh blood groups in diabetes mellitus

The present investigation was conducted with a view to testing the hypothesis that there is some association between blood groups (ABO and Rh) and diabetes mellitus. 520 proven cases of adult diabetes mellitus from the Diabetic Clinic of Rajendra Hospital, Patiala, were studied in 1979-1980. A large sample of 6204 normal individuals studied by Jolly et al. (1969) for ABO and Rh blood groups was taken as control for comparison with the patients. There is a strong indication of an association of diabetes mellitus with blood groups, especially with A, AB and Rh-positive blood groups. The maximum differences are in the AB groups in the two series and minimum in the A group. Individuals with gene p seem to be more susceptible to this disease. Thus the association between blood groups and diabetes mellitus is not a chance finding, but implies an aetiological relationship.     

Haematocytometrical changes in chicken blood to acute 60Co gamma radiation

Newly hatched white leghorn chicks (Gallus domesticus) subjected to single whole body 2.25 Gy (225 rads) gamma radiation exposure at the dose rate of 0.50 Gy/sec (50 rads/sec), were studied for changes in a number of haematological parameters at days 1,3,5,7,14 and 28 post irradiation during development. The sudden decline and gradual recovery in total RBC and WBC counts and the level of Hb and Hct along with MCV, MCH and MCHC values evaluation indicates a high regenerative capability of leghorn chicks.     

On multiple forms of bovine seminal plasma inhibin.

Out of a possible minimum of four, three distinct molecular species of bovine seminal plasma inhibin-differing either in Mr or in pI--have been purified to homogeneity. All three molecules exhibit the same proportion of alpha-helicity and beta-form when examined for their CD-spectra in a non-aqueous solvent medium. The implication of this finding for an induced conformation at the receptor-binding site for these hormonal peptides is briefly discussed.     

Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthesis of the antitumor antibiotic sibiromycin by Streptosporangium sibiricum

The biosynthesis of the antitumor antibiotic sibiromycin by Streptosporangium sibiricum requires the construction of four units: the amino sugar from glucose; the anthranilate ring from DL-tryptophan probably via kynurenine; the aromatic methyl group from methionine; the propylidene proline from L-tyrosine with the loss of two aromatic carbons and addition of a C-1 from methionine. Retention of tritium from DL-[5-3H]tryptophan in sibiromycin suggest an NIH shift during hydroxylation of an intermediate.     

Novel multi-nucleotide polymorphisms in the human genome characterized by whole genome and exome sequencing

Genomic sequence comparisons between individuals are usually restricted to the analysis of single nucleotide polymorphisms (SNPs). While the interrogation of SNPs is efficient, they are not the only form of divergence between genomes. In this report, we expand the scope of polymorphism detection by investigating the occurrence of double nucleotide polymorphisms (DNPs) and triple nucleotide polymorphisms (TNPs), in which two or three consecutive nucleotides are altered compared to the reference sequence. We have found such DNPs and TNPs throughout two complete genomes and eight exomes. Within exons, these novel polymorphisms are over-represented amongst protein-altering variants; nearly all DNPs and TNPs result in a change in amino acid sequence and, in some cases, two adjacent amino acids are changed. DNPs and TNPs represent a potentially important new source of genetic variation which may underlie human disease and they should be included in future medical genetics studies. As a confirmation of the damaging nature of xNPs, we have identified changes in the exome of a glioblastoma cell line that are important in glioblastoma pathogenesis. We have found a TNP causing a single amino acid change in LAMC2 and a TNP causing a truncation of HUWE1.