A novel RNA helicase gene tightly linked to the Triplo-lethal locus of Drosophila.

The Triplo-lethal (Tpl) locus of Drosophila is the only known locus which is lethal when present in three copies rather than the normal two. After recovering a hybrid-dysgenesis-induced mutation of Tpl we used a rapid combination of transposon tagging, chromosome microdissection and PCR to clone the P element that had transposed into the Tpl region. That P element is located within the gene for a new and unique member of the RNA helicase family. This new helicase differs from all others known by having glycine-rich repeats at both the amino and carboxyl termini. Curiously, genetic analysis shows that the P element inserted into this gene is not responsible for the Tpl mutant phenotype. We present possible explanations for these findings.     

Role of cell-mediated immunity in the resistance to experimental sporotrichosis in mice

The in vitro activity of several new imidazoles, cloconazole, sulconazole, butoconazole, isoconazole and fenticonazole, were compared with those of amphothericin B, flucytosine, and three azoles: econazole, miconazole and ketoconazole against isolates of pathogenic Candida. A total of 186 clinical isolates of 10 species of the genus Candida and two culture collection strains were tested by an agar-dilution technique. Isoconazole was the most active azole, followed by butoconazole and sulconazole. Differences between some of the species in their susceptibility to the antifungal agents were noted. Sulconazole and cloconazole had the highest activity in vitro against 106 isolates of C. albicans. Butoconazole and isoconazole were also very active against isolates of C. albicans, and were the most active azole compounds against 80 isolates of Candida spp.     

Ribosomal protein S14 is not responsible for the Minute phenotype associated with the M(1)7C locus in Drosophila melanogaster.

Summary A locus associated with a severe Minute effect has been mapped at 7C on the X chromosome of Drosophila melanogaster. Previous work has suggested that this Minute encodes ribosomal proteins S14A and S141B. We have made a chromosomal deficiency that removes the S14 ribosomal protein genes, yet does not display the Minute phenotype. These data suggest that the S14 genes do not actually correspond to the Minute locus.     

The kinetics of generation of influenza-specific cytotoxic T-lymphocyte precursor cells

A dramatic increase in the number of restimulatable (memory) cytolytic T-cell precursors (CTLps) has been demonstrated to occur 2 to 4 days postimmunization. By 4 or at the latest 6 days following in vivo priming, the frequency of restimulatable influenza-specific CTLps has reached that characteristic of a memory response. This indicates that the proliferative events which give rise to memory CTLps occur earlier than might have been expected and in fact are completed prior to the cessation of othe primary CTL response. Such information may have important significance to future immunomodulatory efforts aimed at perturbing the establishment of T-cell memory in vivo.     

Hydrolysis of bradykinin and its higher homologues by angiotensin-converting enzyme (Short Communication)

The hydrolysis of bradykinin and its higher homologues by angiotensin-converting enzyme has been investigated by using an automated ninhydrin technique. The results show an inverse relationship of hydrolysis rate with size and charge of the peptide, which parallels the inactivation in the pulmonary circulation and offers an explanation for the selectivity of metabolism of these kinins by the lungs.     

DETERMINATION OF GUSTATORY SUCROSE THRESHOLD IN WATER BY USE OF A LINEAR SUCROSE GRADIENT

A novel experimental method was developed which allows the determination of the threshold concentration of sucrose by use of a linear sucrose gradient in water. With this method a continuous tasting of the test-liquid is possible. A panel of 15 persons experienced in taste-testing was used. Three gradients of different steepness were applied: 0 to 1.5% (w/w) sucrose in 2 min (I), 3 min (II) and 4 min (III). The results of the new method were compared with those of the standard method (DIN). With gradients I and II we found values which were significantly higher than those of the standard method (I: 0.49% (w/w); II: 0.46% (w/w); DIN: 0.31% (w/w)), whereas with gradient III the same threshold value was found as with the DIN-Method (III: 0.32% (w/w)).     

The Triplo-Lethal Locus of Drosophila: Reexamination of Mutants and Discovery of a Second-Site Suppressor

In the genome of Drosophila melanogaster there is a single locus, Triplo-lethal (Tpl), that causes lethality when present in either one or three copies in an otherwise diploid animal. Previous attempts to mutagenize Tpl produced alleles that were viable over a chromosome bearing a duplication of Tpl, but were not lethal in combination with a wild-type chromosome, as deficiencies for Tpl are. These mutations were interpreted as hypomorphic alleles of Tpl. In this work, we show that these alleles are not mutations at Tpl; rather, they are dominant mutations in a tightly linked, but cytologically distant, locus that we have named Suppressor-of-Tpl (Su(Tpl)). Su(Tpl) mutations suppress the lethality associated with three copies of the Triplo-lethal locus and are recessive lethal. We have mapped Su(Tpl) to the approximate map position 3-46.5, within the cytological region 76B-76D.     

New developments in our knowledge of the chemistry of renin.

Although the role of renin in hypertension continues to be incompletely defined, recent progress in the chemistry of renin has been considerable. Extensive purifications of hog kidney renin and the renin-like mouse submaxillary gland enzyme have been achieved. Various inhibitory peptides based on tetradecapeptide renin substrate have been useful in renin kinetic studies and in renin affinity chromatography. Classification of renin as an acid protease results from its marked inhibition by pepstatin and from the discovery that free carboxyl at the active site is essential for activity in human and hog kidney and mouse submaxillary gland enzymes. The presence of pseudorenin in all tissues has limited the use of model peptides as renin substrates in plasma and crude tissue extracts, since the proteolytic properties of the two enzymes are nearly identical. The existence of renin in multiple, chromatographically separable forms has been known. More recently inactive forms have been found in plasma, amniotic fluid, and hog and rabbit kidneys. Prolonged storage or treatment with acid, trypsin, or pepsin causes activation; in some instances the conversion is from a higher than normal molecular weight. The implications of these findings with respect to the renin-angiotensin system need much further investigation.