Gene Literature Dashboard

The nucleotide sequences at and around the termini of 5 kb type 1 interruptions in three separate clones of D. melanogaster rDNA repeats have been determined, and have been compared with the sequence of the corresponding region of an insertion-free rDNA repeat. All three interrupted rDNA repeats contain a small deletion of 28S rRNA coding material at the left coding/insertion sequence junction. A second deletion was found in one of the three clones, ad other aberrations were suggested by the results of restriction enzyme digestions of unfractionated rDNA. The termini of 5 kb type 1 rDNA insertions in D. melanogaster were also compared with the corresponding regions of 28S rDNA interruptions in D. virilis: the insertion site is identical in the two species, but the termini of the two species' interruptions show no homology. I sequenced a 1.1 kb region of the 5 kb type 1 D. melanogaster rDNA interruption that covers the sequences of the 1 kb and 0.5 kb insertions. There is 98% homology between the rightmost 1 kb of the 5 kb interruption and the sequences of the shorter insertions. Data suggest that Drosophila rDNA interruptions arose as a transposable element, and that divergence had included length alterations generated by unequal crossing over.

The specific modifiers of the carboxylic groups - 1.3-dicyclohexylcarbodiimide (DCC) and 1-cyclohexyl-3-(2-morpholinyl-4-ethyl)carbodiimide methyl-p-toluenesulfonate (CMC) cause irreversible inhibition of acetylcholinesterase from human erythrocytes (AChE) and butyrycholinesterase from horse blood serum (BuChE). The rate of hydrolysis of both acetylcholine and non-charged substrates - phenylacetate and indophenylacetate - is thereby decreased. At initial steps of the reaction the irreversible inhibition obeys the kinetics of the pseudo-monomolecular reactions with the following values of bimolecular constants for the rates of DCC and CMC reactions: for AChE - 2.3 +/- 0.19; 5.1 +/- 0.23 M-1 min-1, for BuChE - 1.5 +/- 0.14 and (2.2 +/- 0.21) . 10(2) M-1 min-1 (25 degree, pH 7.5). The morpholinyl carbodiimide with a quaternary nitrogen. a more specific inhibitor of cholinesterases, which is of a mixed (Ki = (3.0 +/- 0.21) . 10(-4) M for AChE) and of competitive (Ki = (3.3 +/- 0.24) . 10(-5) M for BuChE) type. Under AChE modification by CMC at concentrations causing 50 - 70% inhibition, the substrate inhibition constants and the thermal stability of the non-inhibited part of the enzyme are increased. The role of functional groups of the catalytic and regulatory centers of cholinesterases in the chemical modification by carbodiimides is discussed.

Immune responses to several soluble antigens were compared between B6.C-H-2bm12 mutant and wild-type B6 mice by using a lymph node T-cell proliferation assay. B6.C-H-2bm12 mice failed to respond to beef insulin whereas other IA gene-controlled responses, such as response to poly(L-Tyr, L-Glu)--poly(DL-Ala, L-Lys) and collagen, were indistinguishable between mutant and wild-type mice. The responses to multideterminant antigens such as ovalbumin and purified protein derivative of tuberculin were also found to be comparable in B6.C-H-2bm12 and B6 mice, thus indicating that this mutation resulted in a selective loss of the ability to respond to a certain antigen(s)--e.g., beef insulin. Populations depleted of adherent cells have been used to examine the mechanism by which Ia molecules mediate Ir gene control of antigen recognition. We show that the nonresponsiveness to beef insulin in the mutant mouse is the result of defective antigen presentation. In addition, we find that F1 hybrids between two nonresponders--B6.C-H-2bm12 and B10.A or B10.AKM (IAk) mice--become responders to beef insulin, thus demonstrating gene complementation. These findings taken together with other serologic and biochemical studies in the B6.C-H-2bm12 present convincing genetic evidence for the direct association of the A beta polypeptide chain of the Iab molecules with the expression of immune responsiveness to beef insulin. Study of the B6.C-H-2bm12 mouse should provide new insight into the cellular and molecular mechanisms by which Ir genes determine the nature of the immune response.

A pedigree was studied in which five individuals with beta-thalassemia minor were found to have nontransfusional hemochromatosis. Three were children under the age of 10 and two were young male adults, ages 28 and 33. A 5-yr-old child without evidence of thalassemia also had hemochromatosis. Since hemochromatosis is transmitted as an HLA-linked autosomal recessive disorder, HLA haplotypes serve as markers of hemochromatosis alleles. In this pedigree, five identifiable HLA haplotypes were associated with hemochromatosis alleles. Only individuals with two hemochromatosis alleles (homozygosity) had heavy iron loads, whether beta-thalassemia minor was present or not. Individuals with beta-thalassemia minor but without a hemochromatosis allele had normal transferrin saturation. A 65-yr-old man with beta-thalassemia minor and a single hemochromatosis allele had only a minimally elevated transferrin saturation (54%). The presence of beta-thalassemia minor did not appear to accentuate the degree of iron loading expected in individuals homozygous or heterozygous for hemochromatosis alleles. Our findings suggest that nontransfusional hemochromatosis found in association with beta-thalassemia minor is due primarily to homozygosity for hemochromatosis.