ALBERT

Notes: Summary The present investigation analyzes intercellular junctions in tissues with different developmental capacities. The distribution of junctions was studied inDrosophila embryos, in imaginal disks, and in cultures of disk cells that were no longer able to differentiate any specific pattern of the adult epidermis. The first junctions —primitive desmosomes andclose membrane appositions — already appear in blastoderm.Gap junctions are first detected in early gastrulae and later become more and more frequent.Zonulae adhaerentes are formed around 6 h after fertilization, whileseptate junctions appear in the ectoderm of 10-h-old embryos. Inwing disks of all stages studied (22–120 h), three types of junctions are found: zonulae adhaereentes, gap junctions, and septate junctions. Gap junctions, which are rare and small at 22 h, increase in number and size during larval development. The other types of junctions are found between all cells of a wing disk throughout development. All types of junctions that are found in normal wing disks are also present in theimaginal disk tissues cultured in vivo for some 15 years and in thevesicles of imaginal disk cells grown in embryonic primary cultures in vitro. However, gap junctions are smaller and in the vesicles less frequent than in wing disks of mature larvae. Thus gap junctions, which allow small molecules to pass between the cells they connect, are present in the early embryo, when the first developmental decisions take place, and in all imaginal disk tissues studied, irrespective of whether or not these are capable of forming normal patterns.

Notes: Summary The lineages of cells on the second-leg basitarsus ofDrosophila melanogaster were analyzed by examining gynandromorphs andMinute mosaics. Bracts lie proximal to bristles on the adult basitarsus, yet bract precursor cells were found to originate lateral to bristle precursor cells. In 6 of the 8 longitudinal rows of bristles on this segment, the bract cells arise ventral to the bristle cells; in the others they arise dorsally. The lateral cell origins are interpreted as reflecting a pattern of lateral cell movements associated with evagination of the leg disc. An unusual discrepancy was observed in the relative frequencies of male vs. female bracts and bristles in gynandromorphs. The discrepancy suggests that there is a cell-autonomous sexual difference in either the time at which cells begin moving during evagination or the speed with which they move. On the basis of the results, it is reasoned that the bristle pattern of the basitarsus does not originate in its final form. Prior to evagination, the bristle cells of each row are apparently closer together than in the final pattern, and the rows are farther apart. Evidence is presented which suggests that the bristle cells of each row may originally be arranged in a jagged line which is later straightened by cell movements. The two locations where the anterior/posterior compartment boundary of the second leg passes through the basitarsus were found to vary relative to the bristle pattern. If this boundary is assumed to be a fixed line of positional values, then the extent of the observed variability — which is estimated to be ± 1 or 2 cell diameters — provides a measure of the precision of patterning around the circumference.

Notes: Summary The mature labial disc, when implanted into a larva of the same age, undergoes metamorphosis along with the host and produces one lateral half of the medi- and distiproboscis. On the basis of results obtained from transplanted disc halves (including the separate peripodial membrane) a tentative fate map of the labial disc was constructed, which shows most of the presumptive mediproboscis to be located in the dorsal, and most of the presumptive distiproboscis in the ventral part of the disc. The distal protion of the peripodial membrane also contains imaginal anlagen, viz. part of the mediproboscis, prementum, and labellar cap anlagen. The involvement of this part of the peripodial membrane was checked by a careful histological analysis of labial disc development during the first ten hours after prepupation. The results were compared with the situation described forCalliphora imaginal discs. In addition, a detailed morphological analysis was made of the proboscis of the homoeotic mutantproboscipedia (pb). At 27°C,pb changes the distiproboscis into a “telopodite” (leg segments distal to the coxa); the (unchanged) prementum may therefore correspond to the coxa. At 15° C, the tarsus of this homoeotic “telopodite” is replaced to a greater or lesser extent by an arista. The present analysis thus confirms (a) the fundamental morphological correspondence of the medi- and distiproboscis with the labium of other insects, and (b) the fundamental developmental correspondence of the labial, antennal, and leg discs.

Notes: Summary A temperature-sensitive period during early embryogenesis for three stocks carrying thetuh-3 gene suggests that it is a homoeotic mutation involved in the initial determination of the eye-antennal disc rather in maintenance of the determination.

Notes: Summary The development of the adult abdomen ofDrosophila melanogaster was analyzed by histology, microcautery, and genetic strategies. Eight nests of diploid histoblasts were identified in the newly hatched larva among the polytene epidermal cells of each abdominal segment: pairs of anterior dorsal, posterior dorsal, and ventral histoblast nests and a pair of spiracular anlagen. The histoblasts do not divide during larval life but begin dividing rapidly 3 h after pupariation, doubling every 3.6 h. Initially they remain confined to their original area, but 15 h after pupariation the nests enlarge, and histoblasts replace adjacent epidermis cell by cell. The histoblasts cover half the abdomen by 28 h after pupariation and the rest by 36 h. Polytene epidermal cells of the intersegmental margin are replaced last. Cautery of the anterior dorsal nest caused deletion of the whole corresponding hemitergite, whereas cautery of the posterior dorsal nest caused the deletion of the macrochaetae of the posterior of the hemitergite. Cautery of the ventral nest deleted the hemisternite and the pleura, whereas cautery of the spiracular anlagen deleted the spiracle. Results of cautery also revealed that no macrochaetae formed on the tergite in the absence of adjacent microchaetae. Clonal analysis revealed that there were no clonal restrictions within a hemitergite at pupariation. Cautery of polytene epidermal cells other than those of the intersegmental margin failed to affect tergite development. However, cautery of polytene epidermal cells of the intersegmental margin adjacent to either dorsal histoblast nest caused mirror-image duplications of the anterior or posterior of the hemitergite in 10% of the hemitergites. Forty percent of the damaged presumptive hemitergites formed complete hemitergites, indicating extensive pattern regulation and regeneration. Pattern duplication and regeneration were accounted for in terms of intercalation and a model of epimorphic pattern regulation (French et al., 1976). Histoblasts in adjacent segments normally develop independently, but if they are enabled to interact by deleting the polytene epidermal cells of the intersegmental margin, they undergo intercalation which results in duplication or regeneration. The possible role of the intersegmental margin cells of insects in development was analyzed.

Notes: Zusammenfassung Die Methode von Alsop (1966) für den Durchgang von schräg einfallenden Oberflächenwellen durch eine vertikale Diskontinuität wird durch Verwendung eines neuen Funktionals, das auf der Diskontinuitätsfläche stationär sein soll, verbessert Das modifizierte Funktional hat die Dimension eines Energieflusses und wird durch diejenige Spannungs- und Verschiebungsdiskontinuität charakterisiert, die durch das Oberflächenwellenfeld auf der Diskontinuitätsfläche erzeugt wird. Modellrechnungen für SV-Wellen und Lovewellen zeigen, daß die neue Version von Alsoos Verfahren in jeder Hinsicht konsistentere Ergebnisse als die bisherige liefert.

Notes: Summary sev LY3,the only existing allele at thesev locus (1–33,2±0,2), behaves as strongly hypomorph or even as amorph. Ommatidia in asev compound eye have only seven receptor cells, the position of the R7 pattern element being vacant. Various criteria showing that the missing cell is R7 have been verified. These include (i) anatomical characteristics ofsev ommatidia; (ii) behaviour of central R cells insev rdgB double mutants; (iii) medullary projection of central R cell axons; and (iv) mitotic pattern ofsev imaginal discs. The analysis of morphogeneticsev-sev + mosaics has shown thatsev is expressed autonomously by R7 cells, indicating that thesev phenotype is not due to asev genotype of ommatidial pattern elements other than R7. The study of third instarsev imaginal discs has not brought any direct evidence for death of clustered presumptive R7 cells; however, clonal analysis of the developingsev compound eye has given evidence of developmental parameters comparable to those ofsev +, therefore favouring the hypothesis that R7 cells die insev mutants. On the other hand,sev + seems to be required for the determination of the R7 cells, since thesev phenotype cannot be uncovered during the last mitoses of heterozygous mutant cells.

Notes: Summary These experiments examined whether inDrosophila immature imaginal disc tissue and tissues from embryonic stages can influence pattern regulation in a disc fragment in the same way as can mature imaginal discs. Immature imaginal discs, or the cells of whole embryos, were mixed with a test fragment (presumptive notum) from a mature wing disc. The immature tissues in each mixture were genetically marked and had been heavily irradiated (25 Kr gamma) prior to mixing to prevent growth and maturation during subsequent culture in vivo. Alteration of the regulative behavior of the test fragment (that is, regeneration of wing) thus provided an assay for the communication of positional information by the immature tissues. The results suggest that this capacity arises well before competence to metamorphose, as early as the 16th hour of embryonic development, whereas prior to 16 h, essentially no stimulation of regeneration occurred. It is suggested that the imaginal disc (or presumptive disc) cells of the embryo may have been responsible for this early stimulatory capacity.

Notes: Summary The ontogeny of allozyme patterns has been studied in embryos ofDrosophilamelanogaster, which are doubly heterozygous for alleles specifying the slow and fast forms of alcohol dehydrogenase (ADH) and α-glycerophosphate dehydrogenase (GPDH). The ontogeny of esterase-2 was studied in embryos and young larvae of the flour mothEphestia kühniella, which are heterozygous for two of the three existing esterase-2 alleles. In freshly laidDrosophila eggs only the maternal enzyme forms are present and during the first 15 hours of development the staining of these forms becomes progressively fainter. After 16 and 17 h, the paternal and hybrid bands of ADH and GPDH respectively become obvious. Before hatching, the intensity distribution in the three-banded pattern of reciprocal hybrids is asymmetric in favour of the persisting maternal enzyme form. InEphestia embryos, however, there is no persistence of the maternal esterases. In all reciprocal heterozygotes a three-banded pattern suddenly appears 96 h after egg deposition, indicating synchronous activation of both parental alleles. The relative intensity distribution in the hybrid patterns approaches that of the mature larvae stepwise and in an allele-specific manner. This result and the fact that the various heterozygous types exhibit unequal total activities suggest that the Esterase-2 alleles have different activities, which are fixed late in embryogenesis.

Notes: Summary TheDrosophila chorion is produced normally in isolated follicles in Robb's chemically defined culture medium. The complex architecture of the shell developed in vitro from follicles as young as early stage 10 is completely normal morphologically. In addition, the time required for in vitro development closely approximates that observed for in vivo development. Comparisons of insect culture media developed by Robb, Grace, Schneider, and Echalier show large variations in their ability to supportDrosophila chorion development.

Notes: Summary The bristle pattern of the second-leg basitarsus inDrosophila melanogaster was studied as a function of the number and size of the cells on this segment in well-fed and starved wild-type flies, in triploid flies, and in two mutants (dachs andfour-jointed) that have abnormally short basitarsi. The second-leg basitarsi of well-fed, wild-type flies from 22 otherDrosophila species were studied in a similar manner. There are typically 8 longitudinal rows of evenly-spaced bristles on the second-leg basitarsus, and in each row the number of bristles was consistently found to vary in proportion to the estimated number of cells along the segment, and the interval between bristles was found to vary in proportion to the average cell diameter on the segment. These correlations are interpreted to mean that the spacing of the bristles within each row is controlled developmentally, whereas the number of bristles is not. The interval between bristles is evidently measured either as a fixed number of cells or as a distance which indirectly depends upon cell diameter.

Notes: Summary Salivary gland cells of members of theDrosophila melanogaster group (from four different subgroups) were examined electron microscopically and histochemically during the late larval period of development. The secretory product, which is supposed to be utilized as ‘glue’ at the time of puparium formation, appears, by analogy to Palade and Jamieson's results, to be synthesized partially in the rough endoplasmic reticulum (RER) and partially in the Golgi complex. The latter is also the usual site of the packaging of the product into secretory granules, except in the case of one of the secretory granule components ofD. lucipennis. The phylogenetic relationships among the subgroups, implied by the morphological appearance of the secretory granules, fit well with the existing phylogenetic relationships within the group. The secretory granules of each species have their own morphological features; granules of species of the same subgroup share some of these features. Secretion occurs from the cells via exocytosis during which the morphology of the secretory granules changes. Light microscope examination of PAS (Periodic Acid-Schiff reaction) stained glands shows a strong positive reaction in most species, with the exception of the species of thesuzukii subgroup which show a weak, or a negative reaction (D. rajasekari). Electron histochemical localization of polysaccharides in the secretory granules was possible inD. melanogaster and the species of theananassae subgroup.

Notes: Summary Immature ovaries ofDrosophila mercatorum were injected into young larvae and into adult males ofD. mercatorum, D. melanogaster, D. hydei, D. virilis, andZaprionius vittiger. These homo- and heteroplastic transplantations allow normal vitellogenesis to occur in the donor ovary. By SDS gel electrophoresis, we identified the major species-specific yolk proteins of mature eggs (stage 14) which were exclusively of donor-specific origin. Other experiments withD. hydei andZ. vittiger showed that, when females were used as hosts, the host-specific yolk proteins became incorporated into the donor eggs. When two immature ovaries, one ofD. mercatorum and one ofD. hydei, were co-cultured in males, again only the donor-specific yolk proteins were found in the mature eggs implying that these yolk proteins were not released into the host hemolymph. A parthenogenetic strain ofD. mercatorum was used to demonstrate the ability of transplanted immature ovaries to produce viable eggs which can give rise to fertile adults. The role of the species-specific yolk proteins is discussed with respect to the dual origin of these proteins during normal vitellogenesis, i.e., an autonomous synthesis within the ovary itself in addition to the well-known production by the fat body. Further experiments with pupae as hosts indicate that even in the absence of juvenile hormone and in the presence of high doses of ecdysone, vitellogenesis can proceed within the donor ovary. Based on these experiments, a new hyopthesis on the hormonal control of vitellogenesis inDrosophila is presented. We propose that yolk proteins derived from the fat body are controlled by juvenile hormone, whereas the independent and autonomous vitellogenesis within the ovary itself is controlled by endogenously synthesized ecdysone.

Notes: Summary We estimate the number of blastoderm cells which generate the thoracic imaginal discs ofDrosophila. At hatching the wing disc is twice the size of the haltere disc, but the results suggest that both discs develop from a similar number of blastoderm cells. Two homeotic mutations, which transform the haltere into wing, affect embryonic growth but not the primordial number. All the segmental primordia may be of similar size and each may be similarly subdivided into a larger anterior, and a smaller posterior polyclone.

Notes: Summary Pairs of eye-antennal discs, attached to the cephalic ganglia, were cultured in vitro with a concentration of β-ecdysone optimal for imaginal differentiation. The eye-antennal discs fused to form a vesicle inside which the antennae were partially everted, and on the inner surface of which imaginal structures differentiated. The epithelium of the discs was continuous, and an integrated pattern of bristles and hairs differentiated in vitro. In particular, the median ocellus, a unified structure derived partially from each disc, differentiated normally.

Notes: Summary l(1)su(f)mad-ts (mad) is a new temperature-sensitive (ts) lethal mutant ofDrosophila melanogaster which produces duplicated legs after temperature pulse treatment during larval development. The ts-lethality was studied in temperature experiments and genetic mosaics. Temperature pulses given during two distinct TSPs of larval development result in two different types of leg pattern duplication. “Total” differ from “partial” duplications with respect to the affected leg compartments and the orientation of the planes of symmetry which are perpendicular to the dorso-ventral and the proximo-distal leg axes in total and partial duplications, respectively. Genetic mosaic studies indicate (i) disc autonomy of leg pattern duplication, (ii) clonal separation of the anlagen of the two pattern copies, and (iii) clonal restriction along the antero-posterior compartment border in the two pattern copies of totally duplicated legs. The results suggest thatmad leg pattern duplication is caused by a change in positional information rather than by cell death and subsequent regeneration. Our data are compatible with the assumption that during normal development the leg disc cells acquire information about their position within the disc with respect to the different leg axes independently and at different times.

Notes: Summary Two possible mechanisms are considered for the occurrence of experimentally or genetically induced duplications of bristles: extra cell division of a bristle mother cell versus determination of more than one mother cell. From a clonal analysis it appears that duplications induced by actinomycin-D arise by the latter mechanism, whereas those found in the mutantspl seem to arise by the former mechanism.

Notes: Summary The effects of short-term treatment with either placebo or two serotonin antagonists, cyproheptadine and metergoline, on oral glucose tolerance and insulin secretion have been evaluated in normal subjects and in patients with chemical diabetes. Placebo treatment was not associated with any significant change in the parameters examined. Glucose tolerance in chemical diabetics was significantly improved both after cyproheptadine and metergoline; fasting plasma glucose was also reduced by metergoline. Treatment with the latter drug was also associated with a significant decrease in incremental glucose area in healthy subjects, which was not affected by cyproheptadine. Basal and glucose-stimulated insulin secretion were not affected by either drug in any subjects. Cyproheptadine and metergoline improve glucose metabolism in chemical diabetes probably by reducing insulin resistance. This may depend either on decreased secretion of counter-regulatory hormones or on a direct pharmacological action of the drugs on glucose utilization, possibly mediated by their common antiserotoninergic properties.

Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.

Notes: Summary The acute haemodynamic effects of injected diazoxide (Hyperstat® Schering) have been studied in 8 hypertensive subjects. Aortic blood pressure was measured and cardiac output and peripheral conductance were assessed continuously using a simulation model. In six of the patients pulmonary artery end-diastolic pressure was also measured. Blood pressure fell in all subjects 5–10 min after injection of the drug cardiac output increased in all patients studied. However, the initial change in cardiac output differed, as it decreased in two subjects and did not change in one. The largest initial increases in cardiac output were seen in the subjects with the highest pulmonary artery end-diastolic pressure. Patients with an initial decrease in cardiac output were those with the least compliant (stiffest) aortas. We consider that the responsiveness of the baroreceptors determines the size of the increase in cardiac output immediately after reduction of blood pressure by diazoxide. Thus in a patient with a stiff aorta, particularly at low cardiac filling pressure, diazoxide might cause a fall in blood pressure to an unacceptable level.

Notes: Abstract Sepiapterin synthase, the enzyme system responsible for the synthesis of sepiapterin from dihydroneopterin triphosphate, has been partially purified from extracts of the heads of young adult fruit flies (Drosophila melanogaster). The sepiapterin synthase system consists of two components, termed “enzyme A” (MW 82,000) and “enzyme B” (MW 36,000). Some of the properties of the enzyme system are as follows: NADPH and a divalent cation, supplied most effectively as MgCl2, are required for activity; optimal activity occurs at pH 7.4 and 30 C; the K m for dihydroneopterin triphosphate is 10 µm; and a number of unconjugated pterins, including biopterin and sepiapterin, are inhibitory. Dihydroneopterin cannot be used as substrate in place of dihydroneopterin triphosphate. Evidence is presented in support of a proposed reaction mechanism for the enzymatic conversion of dihydroneopterin triphosphate to sepiapterin in which enzyme A catalyzes the production of a labile intermediate by nonhydrolytic elimination of the phosphates of dihydroneopterin triphosphate, and enzyme B catalyzes the conversion of this intermediate, in the presence of NADPH, to sepiapterin. An analysis of the activity of sepiapterin synthase during development in Drosophila revealed the presence of a small amount of activity in eggs and young larvae and a much larger amount in late pupae and young adults. Sepiapterin synthase activity during development corresponds with the appearance of sepiapterin in the flies. Of a variety of eye color mutants of Drosophila melanogaster tested for sepiapterin synthase activity, only purple (pr) flies contained activity that was significantly lower than that found in the wild-type flies (22% of the wild-type activity). Further studies indicated that the amount of enzyme A activity is low in purple flies, whereas the amount of enzyme B activity is equal to that present in wild-type flies.

Notes: Abstract Four glycolytic enzymes in Drosophila melanogaster have been genetically and/or cytogenetically mapped. The structural gene for aldolase (Ald) has been genetically mapped to 3-91.5 and cytogenetically localized to 97A-B. Tpi, the structural gene for triosephosphate isomerase, has been genetically mapped to 3-101.3 and cytogenetically localized to 99B-E. Utilizing closer-flanking markers than the previous mapping, Pgk, the structural gene for 3-phosphoglycerate kinase, has been mapped to 2-5.9; cytogenetically it was found to lie in the interval between 22D and 23E3. The cytogenetic location of Pgm, the structural gene for phosphoglucomutase which has been located genetically at 3-43.4, was determined to be in 72D1-5.

Notes: Abstract NADP-malic enzyme (NADP-ME) (E.C. 1.1.1.40) is situated in the cytosol of Drosophila melanogaster. Both the tissue activity and CRM level of NADP-ME parallel changes in the dosage of a gene, Men +, located in region 87C2-3 to 87D1-2 of the third chromosome. The tissue activity of NADP-ME is very high in early third instar larvae, providing about 33% of the NADPH at this life stage. The tissue activity declines during pupal development but increases as the adult ages. The concentration of NADP-ME CRM and tissue activity are coordinately increased in third instar larvae by dietary carbohydrate and decreased by dietary lipid.

Notes: Abstract Isoelectrofocusing of abdominal extracts of Drosophila melanogaster revealed the existence of two forms of sucrase (E.C. 3.2.1.26). One form exhibited an isoelectric point of 4.63±0.02 while the other form exhibited an isoelectric point of 4.83±0.02. The localization of the structural gene for sucrase is proposed on the basis of enzyme determinations in a series of duplication- and deletion-bearing aneuploids. We suggest that the sucrase structural gene lies between 31CD and 31EF on the left arm of chromosome 2 and that the two forms of abdominal sucrase derive from a common protein coded for by a single sucrase gene designated Sucr +.

Notes: Abstract Genetic and cytogenetic locations of the structural genes for the NAD-dependent malate dehydrogenases have been studied. The mitochondrial form (mMDH) is coded for by a gene (Mdh) found at 62.6 on the third chromosome and included in Df(3R)P14, which includes 90C2–91A3 in the salivary gland chromosomes. Based on its inclusion within several J (Jammed; 2–41.0) deficiencies, the structural gene (cMdh) for the cytoplasmic form (cMDH) was determined to lie in region 31B-E, confirming the earlier finding of Grell. Flies lacking any cMDH activity (cMdhn-γ10069/ Df(2L)J-der-27) were both viable and fertile.

Notes: Abstract When adult Drosophila are placed on medium containing 0.5% acetone, their level of alcohol dehydrogenase activity drops rapidly. At the same time, the proportion of activity in the various electrophoretic forms of the enzyme shifts; most of the activity becomes localized in what is ordinarily a minor form of the enzyme. Moreover, the loss of enzyme activity occurs in vivo as well, as shown by sensitivity to ethanol poisoning, insensitivity to pentenol treatment, and inability to utilize ethanol as an energy source. These observations are discussed in light of a model advanced for the origin of the multiple forms of alcohol dehydrogenase in Drosophila.

Notes: Abstract Several in vitro properties of partially purified form II RNA polymerase from Drosophila melanogaster embryo nuclei are described. The enzyme preparation is free from contaminating RNase, protein kinase, and polyphosphate kinase activities and can be used to study the incorporation of γ-32P-labeled nucleoside triphosphates. The enzyme exhibits a biphasic heat inactivation pattern which is probably related to differential lability of its two subforms. However, a considerable protection against heat inactivation is provided by the nucleoside triphosphates present in the in vitro reaction system such that the enzyme catalyzes RNA synthesis in a nearly linear mode for over 2 hr at 30 C. Two initiation inhibitors, rifamycin AF/013 and polyriboinosinic acid (poly[I]), were tested against this enzyme. Rifamycin AF/013 was found unsuitable for critical studies because of the high concentrations necessary for total inhibition (200 µg/ml) and particularly because of the obligate use of solvents which secondarily have a destabilizing effect on native DNA. Poly[I] was found to effectively block initiation at very low concentrations (1 µg/ml). The enzyme rapidly forms poly[I]-resistant preinitiation complexes on both double- and single-stranded DNA. These complexes decay with a half-life of 2.5–3 min. RNA synthesis from poly[I]-resistant complexes amounts to 10% of the total potential synthesis on both double- and single-stranded DNA. Enzyme-DNA saturation experiments indicate that the form II enzyme discriminates two types of sites on Drosophila DNA, tight binding and weak binding, from which RNA synthesis proceeds slowly and rapidly, respectively. The tight-binding sites appear to be analogous to those sites with which the enzyme is able to form poly[I]-resistant complexes.

Notes: Abstract Allozyme frequency data from natural populations of Drosophila buzzatii were analyzed for genotype-environment relationships. Allele frequency and heterozygosity at six loci polymorphic throughout eastern Australia and a number of environmental factors (both means and variabilities) were examined by a variety of multivariate techniques. Significant genotype-environment associations were found for five of the six loci, and after correcting for geographic location significant associations remained for Est-2 and Adh-1 gene frequencies and heterozygosities and for Pgm gene frequencies. The results are discussed in relation to selection and gene flow and provide the basis for laboratory studies to disentangle confounded effects of (1) environmental means and environmental variabilities and (2) allele frequency and heterozygosity, and thus to further test for and determine the nature of any natural selection at particular allozyme loci.

Notes: Abstract A locus has been found, an allele of which causes a modification of some allozymes of the enzyme esterase 6 in Drosophila melanogaster. There are two alleles of this locus, one of which is dominant to the other and results in increased electrophoretic mobility of affected allozymes. The locus responsible has been mapped to 3-56.7 on the standard genetic map (Est-6 is at 3-36.8). Of 13 other enzyme systems analyzed, only leucine aminopeptidase is affected by the modifier locus. Neuraminidase incubations of homogenates altered the electrophoretic mobility of esterase 6 allozymes, but the mobility differences found are not large enough to conclude that esterase 6 is sialylated.

Notes: Summary As a test of the hypothesis that adult temperature stress is an important component of natural selection maintaining the α-gpdh polymorphism, we have looked for differential survival among genotypes subjected to (i) heat shock and (ii) cold shock. Factorial ANOVAR, taking account of genotype, sex and temperature-stress indicated that genotype did not contribute to the variance of survival proportion per vial. We have not therefore found evidence to support our hypothesis. Incidental to the above was a significant sex-temperature interaction. Thus, adult females showed higher survival than males under heat stress, while under cold stress, there was no indication of a survival difference between the sexes.

Notes: Abstract Comparative studies of oviposition site preference (OSP) inDrosophila suggest that choice of oviposition site is an important adaptive behavior which influences individual fitness and the potential of populations for speciation. OSP has been investigated under conditions which provided females with a choice of standard medium or medium containing ethanol for oviposition. OSP is an extremely labile behavior in the laboratory, but a technique has been developed which minimizes variation between replicates and allows the detection of OSP differences between semispecies of a single species. An analysis of the OSP of 14Drosophila species shows that this behavior is not correlated with phylogenetic relationships. OSP with respect to ethanol may be correlated with the presence of ethanol in the environment and the activity of alcohol dehydrogenase in the species tested.

Notes: Abstract An alternative explanation to the pheromonal control of mating through chemoreceptor saturation proposed by Averhoff and Richardson (1974) is offered for the apparent rise in heterogamic mating in their experiments, after several generations of full-sib mating. In a multiple-choice mating between two genotypic strains differing in their level of sexual vigor, there is a sequence from heterogamic to homogamic mating. It is proposed that, by reducing mating speed, inbreeding changes the rate of this sequence but not its pattern, so the apparent level of heterogamic mating will increase during inbreeding, for a fixed observation period. This hypothesis was tested using the Kence-Bryant model of mating success.

Notes: Abstract Two alcohol dehydrogenase genotypes (Adh F /Adh F andAdh S /Adh S ) exhibit different behavioral responses when presented with a choice between ethanol and nonethanol environments at the larval stage but not at the adult stage. The larval preferences are correlated with alcohol dehydrogenase activity, which also differs between genotypes. Since ethanol is important in the ecology of this species, the preference may be related to microhabitat selection in nature.

Notes: Abstract Selection for the wing vibration component of courtship in the Oregon-R stock ofD. melanogaster was practiced for 44 generations. Selection was successful, indicating that there is genetic variation for the trait in the Oregon-R stock. The mean realized heritability of the trait, based on the first 11 generations of selection, was 15%. Biometrical analysis showed that there is some additive genetic variance for the trait with the possibility of some ambidirectional dominance. No maternal effects for the trait were found.

Notes: Abstract It is shown that minority mating advantages, so commonly observed inDrosophila, would be selectively advantageous in a heterotic system. When an allele is below the equilibrium frequency maintained by heterosis, females mating with that homozygote produce offspring of highest mean fitness.

Notes: Abstract Using Hirsch-Hadler phototaxis mazes, selection for photopositive and photonegative behavior was carried out for 21 generations inDrosophila ananassae. The chromosomes that are important in influencing photomaze behavior inD. ananassae are different from what has been observed for other members of themelanogaster species group, and the differences cannot be entirely attributed to the chromosome rearrangements which have occurred during the evolution of these related species.

Notes: Abstract Experiments on frequency-dependent fitness often consist of forming pairwise mixtures of distinguishable types at several frequency combinations. These mixtures are allowed to undergo competition, after which the performance of each type is enumerated. A statistical method for analyzing such experiments is described in this article. This method, suggested previously for other purposes, is superior to the statistical procedures now commonly employed. It involves the maximum likelihood estimation of parameters for two logistic regression models: one which assumes that fitness is frequency-dependent, the other that fitness is constant over changing frequency. Estimators for both models can be calculated without difficulty using an iterative numerical algorithm implemented in a Fortran computer program available from the authors. Fitting both models allows for the construction of a likelihood ratio statistical test for whichever model is more appropriate. The method is illustrated by application to publishedDrosophila data from differential mating success experiments.

Notes: Summary Pinocytotic activity has been analyzed in Drosophila oocytes following either in vivo or in vitro exposure to horseradish peroxidase. The enzyme tracer gains access to the yolk spheres only when supplied to the oocyte in vivo. In oocytes cultured in vitro, peroxidase remains restricted to the residual coated vesicles and to the tubular profiles formed in excess in the cortical ooplasm. In an attempt to induce peroxidase uptake by oocytes cultured in vitro, various incubations were tested. Among these, hemolymph from both sexes is capable of promoting peroxidase uptake up to a level comparable to that detectable in vivo. On the other hand, fat body extracts fail to promote such cellular activity. Finally, the juvenile hormone analogue ZR-515 is shown to be the only factor required to promote pinocytotic activity under the experimental conditions tested. The observations are interpreted to indicate that vitellogenin has no inductive role on pinocytosis but simply acts by adhering to the forming coated vesicles which in turn are produced by the oolemma in response to the action of juvenile hormone.

Notes: Summary The differentiation of muscles in primary cultures of cells fromDrosophila melanogaster embryos was investigated. In early cultures, and in the absence of exogenous ecdysone, two main classes of muscle were found. Comparison, by light and electron microscopy, of one of these classes (the “myotube” class) with muscles from third instar larvae shows that this class corresponds to the muscles of the body wall of the larva. When α- or β-ecdysone is added to the cultures, these undergo a number of metamorphic changes. Most of the larval muscles disappear, and two new types of muscle form. Ultrastructural and light microscopic examination of these two types indicates that they correspond to the two classes of skeletal muscle (fibrillar and tubular) found in adult flies.

Notes: Summary The pathway of adult sensory nerves has been analysed in three experimental situations: (i) in flies with grossly abnormal thoracic morphology resulting from X-irradiation early during development, (ii) in flies which had been subjected to surgical operations late in the larval period, (iii) in homoeotic mutants. The results provide experimental support for a simple mechanism in which developing adult axons join the nearest larval nerve and are guided by it up to the central nervous system. In particular, experimental interference with normal development can result in nerves from different segments, or from dorsal and ventral appendages, joining each other and entering the central nervous system together.

Notes: Abstract A new method is presented for the determination of higher mode dispersion over small distances, using two stations. From an intermediate focus earthquake it has been possible to measure the dispersion of the first and second Rayleigh modes in the period range 25–35 sec and 25–70 sec respectively. Using the almost linear array of Italian long-period stations TRI, BLZ, OLB an estimate of the average errors is also made.

Notes: Summary The phase velocity curve of Rayleigh-waves is determined for a profile crossing the area of GDR from south to north. Two different methods of seismogram processing are used which are discussed in detail. The phase velocities found are checked for compatibility. An inversion of a common phase velocity curve is done by using hedgehog procedure.

Notes: Abstract AP-wave velocity model for the upper mantle beneath eastern and southern Africa is proposed. The top 250 km of the model is characterized by relatively low velocities similar to those deduced for the upper mantle beneath the western United States of America. At greater depths, the velocities gradually change to normal mantle values.

Notes: Abstract The displacement produced in a semi-infinite, homogeneous, isotropic elastic medium by the application of shearing traction over a circular portion of the half-space has been evaluated in exact form by Cagniard's Technique (Cagniard, 1962;Gakenheimer andMiklowitz, 1969).

Notes: Summary Five regions of the compound eye have been found to be preferential boundaries for clones of labelledMinute + cells, and to act restrictively on the growth of cell clones after a given developmental stage. One of these regions is topographically related to the line of pattern inversion existing at the level of the equator. The results of experiments showing independency of origin of restriction lines and line of pattern inversion are reported.

Notes: Summary Females homozygous for a newly isolated mutation induced by ethyl methane sulphonate,fs(1)K10, lay abnormally shaped eggs in which the dorsal appendages of the chorion are enlarged and fused ventrally. The eggs are usually not fertilized and development is never normal beyond the blastoderm stage. The mutant was mapped to the tip of the X-chromosome with a meiotic position of 1–0.5 and a cytological location between 2B17 and 3A3. Using germ line mosaics constructed by transplantation of pole cells, it was shown that the abnormal morphology and the sterility are obtained only when the germ line is homozygous for the mutant.

Notes: Summary The embryonic organization of the sexually dimorphic genital disc was studied in genetic mosaics resulting (a) from early loss of a chromosome or (b) from mitotic recombination. (a) Early Loss of a Chromosome. Three types of mosaics were produced — purely female mosaics, purely male mosaics, and gynandromorphs. They show that the genital disc arises from a group of cells in the ventral region of the embryo somewhat larger than that giving rise to a single foreleg (Table 2). Within this group of cells three regions can be distinguished that are present in both sexes: an anterior, a medial, and a posterior one, with distances of only 3–4 sturts between adjacent regions. The anterior region gives rise to the female genitalia, the medial region to the male genitalia, and the posterior region forms the analia of both sexes and the parovaria of the female (Figs. 2 and 3). The relative positions of the three regions were deduced from sturt distances (Tables 1 and 5), and from frequencies of mosaicism (Table 2). (b) Mitotic recombination was induced at the blastoderm stage in order to produce twin spots in the external genitalia and analia of purely male and female flies. Clone sizes indicate that these structures arise from a small number of precursor cells (Table 4). Clones overlapped right and left sides, but no clones were found extending over analia and genitalia. However, within either the analia or the genitalia of each sex, no clonal restrictions could be observed, and the clones comprised structures that were up to 12 sturts apart. A comparison of clone sizes and sturt distances in the foreleg and in the genital disc indicates that equal gynandromorph distances involve equal numbers of cells in different regions on the ellipsoid egg (Fig. 5). The results obtained from all mosaics provide a consistent picture of the embryonic organization of the genital disc. This becomes apparent in the summarized fate maps (Fig. 4), where the map derived from normal gynandromorphs can be produced by a simple superposition of the male and the female maps. The data are also discussed with respect to mechanisms of sexual differentiation in the genital disc.

Notes: Summary Mutations of the bithorax complex result in segmental transformations in the thorax and abdomen ofDrosophila. The haltere discs from larvae homozygous forbx 3 orpbx are transformed so that the discs contain cells that will produce wing cuticle as well as cells that produce haltere cuticle. The pattern regulation behavior of these discs has been examined. The fate maps of the two discs were established, and then the regulative behavior of a number of fragments from both types of mutant discs was established by culturing the fragments in vivo prior to metamorphosis. The most important conclusion from this work is that the cells producing, haltere cuticle and wing cuticle within the same disc share the same positional information and that they communicate during pattern regulation.

Notes: Summary The inhibitory effect of activated charcoal 50 g suspended in water on the absorption of digoxin, phenytoin and aspirin was studied in six healthy volunteers in a cross-over manner. The absorption of digoxin and phenytoin were almost completely prevented (about 98%) when activated charcoal was ingested immediately after the drug. The total absorption of aspirin was inhibited by 70%, with clear postponement of absorption and partial release of aspirin from the charcoal in the gut: The peak serum concentration of aspirin was reduced by 95% by charcoal. When activated charcoal was ingested 1 hour after the drugs the inhibition of absorption was considerably less. However, since the absorption of larger doses of the drugs is often slow, the administration of an adequate dose of activated charcoal will be of definite value in the treatment of acute intoxication, even if delayed for several hours.

Notes: Summary The absorption of tetracycline in man under the influence of concomitantly administered EDTA, milk and a combination of EDTA and milk has been investigated. Urinary excretion of the drug was measured for 30 h. The inhibitory effect of milk could be counteracted by simultaneous ingestion of EDTA, which resulted in almost equivalent urinary excretion of tetracycline compared to experiments done in the fasting state. Administration of EDTA alone, in a neutral dosage form, did not significantly change absorption of the drug, which contradicted previous findings. The possible use of EDTA during tetracycline therapy is discussed.

Notes: Summary In order to study the intestinal interactions of doxycycline (DC) with Fe++ and charcoal, two groups of healthy volunteers were given either 200 mg or 100 mg DC in capsules at 2 p. m. and 9 p. m., and blood samples for fluorimetric assay of DC were collected for 24 h starting at 8.30 a. m. on the following morning. A 24-h-urine was also collected. The test was subsequently repeated at one-week intervals, when the volunteers also ingested either ferrous sulphate (80 mg Fe++) or charcoal (4.0 g) immediately after the zero-time sample of DC and at 3, 8 and 12 h. Charcoal completely adsorbed DC in vitro in an artificial small intestinal fluid. Ferrous sulphate or charcoal did not modify the serum level or urinary excretion of DC after the 200 mg+200 mg dose, but ferrous sulphate did reduce the 24-h urinary excretion of DC after the 100 mg+100 mg dose. The serum half-life and AUC of DC were reduced by ferrous sulphate given after the 100 mg+100 mg dose of DC. Charcoal did not modify any parameter, even after the 100 mg+100 mg dose of DC. The results do not support existence of important enteral cycling of DC. Although oral ferrous sulphate can lower the serum level and shorten the serum half-life of DC, the acute experiment suggested that a therapeutic serum level of DC can be maintained despite treatment with iron in the doses used in iron-deficiency, and charcoal in the doses used in diarrhoeic states, if the drugs are administered several hours apart.

Notes: Summary The plasma concentrations of citalopram, a potent serotonin reuptake inhibitor, and its demethylated metabolite have been determined by a specific fluorescence coupling technique during single dose experiments in volunteers and in clinical tests. Citalopram was found to have linear kinetics within the dose range investigated, which were characterized by fairly rapid absorption and slow elimination (biological half-life 1–21/2 days). Steady state levels in the range 120–340 nM (i.e. slightly above those associated with pharmacodynamic activity in animals) were attained within a week. A drug/metabolite ratio of 2–3 was recorded.

Notes: Summary Penta-acetyl-gitoxin (PAG) shows species-specific deacylation to 16-acetyl-gitoxin (16-AG; I and III) or gitoxin (II and IV) by homogenates of liver and intestinal mucosa of man (I), rabbit (II), guinea-pig (III) and rat (IV), whereas it is degraded into tri- and tetra-acetates by homogenates of guinea-pig myocardium as well as by human blood and serum. The identity of the principal and chloroform-extractable metabolites in human urine after PAG administration with 16-AG has been demonstrated by mass spectrometry.

Notes: Summary The selective β1-adrenoceptor agonist H 80/62 was administered intravenously and orally to healthy subjects and its effects on systolic time intervals, arterial blood pressure and heart rate were studied. Side-effects were noted too, and continuous ECG-recordings were made in order to study its arrhythmogenic effect. After i.v. administration of H 80/62 20 µg/kg body weight there was shortening of total electromechanical systole, the pre-ejection period and of the left ventricular ejection time, systolic blood pressure tended to increase, and diastolic blood pressure and heart rate were essentially unchanged. When administered orally as a sustained-release preparation in doses between 20 and 40 mg the haemodynamic effects were qualitatively the same as after i.v. administration, but in some studies there was a slight increase in heart rate. During exercise the systolic blood pressure and heart rate were identical after H 80/62 and placebo. The effect of the drug was maximal immediately after cessation of the i.v. infusion and basal values were regained within 60 min. After oral administration of a sustained-release formulation the effect was maximal after one hour and persisted for at least five to seven hours. The drug was well tolerated on repeated administration. The incidence of ventricular extrasystoles was possibly increased in one subject out of eight (11 ventricular extrasystoles during 18 h). The results of this Phase I study of H 80/62 warrant further evaluation of the drug in man.

Notes: Summary Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, ‘Medicoal’ was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charchoal may therefore be useful in the treatment of tricyclic antide-pressant poisoning even if a delay of several hours ensues before medical help is sought.

Notes: Summary Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal failure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 8 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.

Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.

Notes: Abstract Three of the major protein species present in the hemolymph of Drosophila melanogaster larvae just prior to pupation are absent from second instar larvae but accumulate rapidly during the third instar. This article describes the purification and characterization of one of these, larval serum protein (LSP) 2, using an immunological assay. It is a homohexamer of molecular weight about 450,000, with a polypeptide molecular weight of 78,000–83,000. Fast and slow electrophoretic variants of this protein map between the markers vin and gs, at 36–37 on chromosome 3.

Notes: Abstract Only one molecular form of trehalase (E.C. 3.2.1.28) was detectable in adult Drosophila melanogaster by polyacrylamide gel electrophoresis and isoelectric focusing. An examination of duplication- and deletion-bearing aneuploids exhibiting do sage sensitivity indicated that the enzyme is encoded by a gene, Treh +, located between 55B and 55E of the second chromosome. The tissue-specific soluble and particulate forms of trehalase appear to be manifestations of a single protein encoded by a single gene.

Notes: Abstract Glutamine-dependent CPSase, ATCase, and DHOase from Drosophila, the first three enzymes in pyrimidine biosynthesis, show coordinate variation in activity throughout development. The three activities were highest in first instar larvae and decreased as development proceeded. The three activities cosediment in sucrose gradients as a single peak with a relative sedimentation coefficient of approximately 30S. CPSase, ATCase, and DHOase copurify during (NH4) 2SO4 fractionation and during DEAE-cellulose and hydroxylapatite chromatography.

Notes: Abstract It has been shown that crude extracts of Drosophila melanogaster adults contain three distinctly different enzymes which catalyze the oxidation of d-sorbitol into d-fructose. These include (1) a soluble NAD-dependent sorbitol dehydrogenase (NAD-SoDHs), (2) a mitochondrial NAD-dependent sorbitol dehydrogenase (NAD-SoDHm), and (3) a soluble NADP-dependent sorbitol dehydrogenase (NADP-SoDH). Developmental studies have shown that the activities of all three of these enzymes are lowest during the larval stages while highest levels are seen during or shortly prior to the adult period. With respect to NAD-SoDHs, studies of tissue distribution in adults have shown that highest activity is associated with thoracic musculature in both sexes and with organs of the male reproductive system. The developmental profile of this enzyme reveals a significant increase in activity at between 40 and 60 hr after hatching. This time interval corresponds closely to that during which the paternally derived NAD-SoDHs gene is expressed. An additional increase in activity is seen in male pupae at 160 hr and in female adults at 210 hr. The rapid increase in males takes place immediately following the developmental period during which the testes attach to their respective duct systems. NADP-SoDH activity is concentrated among organs of the thorax and abdomen in both sexes. Males show significantly higher levels of this enzyme during the late pupal and early adult periods. In contrast to the patterns of distribution seen for NAD-SoDHs and NADP-SoDH, 91–92% of the total NAD-SoDHm activity in adults is localized to the thoracic musculature. The developmental profile of this enzyme reveals a significant increase in activity during the late pupal and early adult periods, when flight muscle mitochondria are known to be proliferating and undergoing structural maturation.

Notes: Abstract Among the progeny of Drosophila flies heterozygous for two noncomplementing Adh-negative alleles, two individuals were found that had recovered appreciable alcohol dehydrogenase activity, thereby surviving the ethanol medium used as a screen. The most likely explanation is that these Adh-positive flies are the product of intracistronic recombination within the Adh locus. Judging by the distribution of outside markers, one of the crossovers would have been a conventional reciprocal exchange while the other appears to have been an instance of nonreciprocal recombination. The enzymes produced in strains derived from the original survivors can be easily distinguished from wild-type enzymes ADH-S and ADH-F on the basis of their sensitivity to denaturing agents. None of various physical and catalytic properties tested revealed differences between the enzymes of the survivor strains except that in one of them the level of activity is 55–65% of the other. Quantitative immunological determinations of ADH gave estimates of enzyme protein which are proportional to the measured activity levels. These results are interpreted to indicate that different amounts of ADH protein are being accumulated in the two strains.

Notes: Abstract It is shown that the gene controlling the synthesis of the organ-specific S-esterase of Drosophila virilis ejaculatory bulbs is located on the second chromosome (at approximate position 192.1±map units). The cells of the genital imaginal disks are determined for the synthesis of S-esterase 10–12 hr after the second molt. The organ-specific esterase can be detected after adult emergence only. It is preceded by an increase in RNA content and by enhancement of RNA synthesis in the cells of the ejaculatory bulbs. Interstock differences were found in the level of the activity of S-esterase, which is under the control of the X chromosome, as well as in the time of expression of enzyme activity, which is controlled by the fifth chromosome. It is suggested that the specific phenotypic expression of this enzyme depends on the system of genes with regulatory expression at both the transcriptional and posttranscriptional levels. The genetic control of the synthesis of the S-esterase described is a convenient model for studying mechanisms of gene activity regulation in eukaryotes.

Notes: Abstract Starch and polyacrylamide gel electrophoresis were used to ascertain the substrate specificities of alcohol-oxidizing enzymes in 13 Drosophila species. The substrates used were a variety of long- and short-chain aliphatic alcohols, one aromatic alcohol, and benzaldehyde. Only one enzyme (product of a single-gene locus) showed significant NAD+-dependent alcohol dehydrogenase activity with short-chain aliphatic alcohols. The 13 species, belonging to four different Drosophila groups, all showed a similar complement of alcohol-oxidizing enzymes, although differences in electrophoretic mobility and in levels of activity existed from species to species. These findings are relevant to the adaptation of Drosophila to alcohol environments.

Notes: Abstract There is an association among resource utilization divergence, habitat selection, and taxonomic divergence in the genusDrosophila. Given permissive conditions of temperature, humidity, and light intensity, an enormous variety of resources is used in a diversity of habitats. These resources are considered in the cosmopolitan and endemic Australian fauna, providing evidence for habitat selection in the laboratory and field. Lek behavior in picture-winged species of subgenusHirtodrosophila, a case of parallel evolution with lek behavior in subgenusDrosophila in Hawaii, is discussed in detail. Other examples of habitat selection discussed concern behavioral reactions of larvae to alcohol and other metabolites and the avoidance by adults of extreme physical environments. Evolutionary strategies involved in habitat selection are considered at various taxonomic levels inDrosophila. These considerations show that it is essential to relate results from laboratory studies to natural environments in order to explore the genetics of habitat selection.

Notes: Summary Intercellular bridges have been detected in ovarian follicle cells of Drosophila melanogaster. These bridges occur widely between follicle cells of previtellogenic chambers, while, in vitellogenic chambers, they become restricted to the columnar follicle cells. Usually, only one bridge is detectable between adjacent follicle cells, but a single cell may form two cytoplasmic continuities. The fine structure of the intercellular bridges is similar to that previously described in the development of Drosophila. The bridge wall consists of two layers of which the more external is more electron dense and thinner than the inner one. The role played by the intercellular bridges in the determination of a synchronous differentiation of the linked follicle cells is discussed in relation to the known behaviour of these cells in the secretion of the egg covering precursors.

Notes: Summary The nucleotide sequence ofDrosophila melanogaster 5S RNA has been determined and appears to be homogeneous both in the KC cell line and in the insect at different developmental stages. Experimental evidence on the conformation of this molecule is in agreement with a general class of 5S RNA models.

Notes: Summary Injection of α-ecdysone into the larval haemolymph of late third instar larvae ofD. virilis induces both the extrusion of secretory proteins and the inactivation of the enzyme glutamine-fructose-6-phosphate-aminotransferase (E.C. 2.6.16) in the salivary glands. In the presence of actinomycin D or cycloheximide the hormone is ineffective. If before adding these inhibitors RNA synthesis is allowed to proceed for 1.5h, or protein synthesis for 2h after ecdysone injection, however, the protein extrusion and the enzyme inactivation do occur. It is proposed that ecdysone controls these two cytoplasmic events at the transcriptional level by the activation of specific Correlations with puff activities are discussed.

Notes: Summary 1. The developmental potentials of dissociated cells of the different regions of the male foreleg disc ofDrosophila melanogaster were analysed. To this end, various amounts of foreleg disc material were dissociated together with an excess of heavily irradiated wing discs (“feeding layer”), and the reaggregates were cultured for 10 days in the abdomens of adult hosts prior to metamorphosis. 2. The foreleg disc cells were in most cases unable to regenerate missing structures in a circular direction within the leg segments. Instead they strongly tended to adopt the specifications of more distal leg segments (distal transformation), irrespective of the region of origin of the ancestor cells within the disc. 3. The distal transformation occurred mainly, if not exclusively, during an early phase (“initial phase”) in the reaggregates. 4. The extent of distal transformation was most pronounced in those series in which the foreleg cells were initially least diluted by the “feeding layer” cells. 5. Cells of the lower lateral quadrant were very poor both in proliferative activity and in the extent of distal transformation, compared to cells of the three remaining quadrants. In the experiments with a low initial dilution of the foreleg cells, cells of the lower medial quadrant underwent distal transformation much more distinctly than cells of the upper medial and the upper lateral quadrants. 6. Allotypic structures occurred exclusively in reaggregates of the upper medial and upper lateral quadrants. In these implants, however, the frequency of transdetermination was extremely high. 7. Two alternative mechanisms are discussed which could have led to the general occurrence of distal transformation. They differ in the basic assumption of whether or not the “feeding layer” cells were able to interact with the leg cells to influence their regulative behaviour. In addition, interactions among the leg cells themselves seemed to stimulate proliferation to varying degrees and may account for the observed differences in the degree of distal transformation.

Notes: Summary Three-hundred and twenty fertile,pal-induced Y-chromosome mosaic males and females were obtained. Fractional analysis of the sons of 55 somatically mosaic flies that were also germinally mosaic tentatively suggests that the number of functional primordial germ cells inDrosophila melanogaster is variable and that it is seldom greater than 24. From the observed 0.17 frequency of germinal mosaicism it was estimated that the average number of pole cells at the end of blastoderm formation is 45. At present, the germ cells afford the only opportunity to compare genetic estimates of the number of blastoderm or primordial cells with available histological counts. The good agreement between them suggests that both the fractional and the mosaic frequency methods for estimating primordial or blastoderm cell numbers of various larval and imaginal anatomical structures provide reasonably close approximations of the actual values.

Notes: Summary 1. Histological analyses were made of imaginal discs and histoblasts during the larval development ofDrosophila melanogaster to determine the number of cells, the patterns of cell division and the growth dynamics in these adult primordia. Histological studies were also made of the imaginal rings which are the primordia of the adult salivary gland, fore-and hindgut, the anlage cells of the midgut and several larval and embryonic tissues. 2. In the newly-hatched larva, the immature eye-antenna, wing, haltere, leg and genital discs contain about 70, 38, 20, 36–45 and 64 cells respectively. These numbers include cells destined to form cuticular elements as well as peripodial, tracheal and nerve cells and probably the progenitors of adepithelial cells. The number of cells counted in the various imaginal disc anlagen is 1.5 to 4 times higher than the numbers deduced from genetic mosaic analyses by other investigators and reasons for these differences are given. 3. About 12 h after fertilization, mitosis ceases in all tissues of the embryo except the nervous system. After the larva hatches, mitosis resumes in most of the imaginal anlagen and in some larval tissues. The time of resumption of mitosis in the imaginal anlagen was determined after treating the larvae with colchicine for 2 h. 4. Among the imaginal discs, the eye disc is the first to begin cell division, at about 13–15 h after the hatching of the larva (first instar) followed by the wing (15–17 h), the haltere (18–20 h), the antenna, leg, and genitalia (24–26 h, early second instar), and finally the labial and dorsal prothoracic discs (52–54 h, early third instar). The cell doubling time for various discs was calculated from cell counts and the times agree closely with the doubling times deduced from clonal analyses by other workers: e.g., 7.5 h for the cells of the wing disc. 5. The imaginal ring of the hindgut first shows cell division early in the second instar. The imaginal rings of the foregut and salivary glands, the anlage cells of the midgut and the cells of the segmental lateral tracheal branches begin to divide early in the third instar. 6. The histoblasts which are the anlagen of the integument of the adult abdomen do not increase in number from the time of larval hatching until about 5 h after pupation when they begin to divide. Their behaviour contrasts with that of the histoblasts of the other dipterans such asCalliphora, Musca andDacus, which begin to divide during the second instar. 7. The histoblasts are an integral part of the larval abdominal epidermis and, unlike imaginal disc cells, secrete cuticle during larval life. Each hemisegment consists of an anterior dorsal, a posterior dorsal, and a ventral histoblast nest containing about 13, 6 and 12 cells respectively. The 62 histoblasts in each larval segment represent about 7–8% of the total number of cells that form the integument of that segment. 8. The number of cells in a particular type of histoblast nest was constant for both male and female larvae and among the different abdominal segments, except that the anterior dorsal group of the first and the seventh segments contains fewer cells than those of the other segments. Although the male and female adultDrosophila lack the first abdominal sternite and the male lacks the seventh abdominal tergite and sternite, the ventral histoblast nests of the first and the dorsal and ventral nests of the seventh abdominal segments are present in the larval stages as well as in the prepupa and have the same morphology and cell number as similar nests in the rest of the abdominal segments. 9. The cells of the imaginal discs increase in volume about six-fold and their nuclei increase in volume three-fold between the time of hatching and the initiation of mitosis. The histoblasts increase in volume about 60-fold and their nuclei increase in volume about 25-fold between larval hatching and pupariation. 10. Prior to each cell division, the nuclei of the columnar cells of the disc epithelium and of the histoblasts appear to migrate toward the apical surface of the epithelium. The cells round up and shift toward the apical region where mitosis occurs. After cytokinesis, the daughter cells move back to deeper positions in the epithelium. Because the nuclei of the non-dividing cells continue to lie deep in the epithelium, this intermitotic migration of nuclei gives these epithelia a pseudostratified appearance. 11. Analyses of the growth of larval cells and of organs confirmed the observations of earlier investigators that cell division occurs only in a few larval tissues, whereas growth in the rest of the larval tissues is by cell enlargement and polyteny. During larval life, cell division was detected only in the central nervous system, gonads, prothoracic glands, lymph glands and haemocytes. Each tissue began mitosis at a characteristic stage in larval life. The larval cells that did not divide, grew enormously, e.g., epidermal cells increased in volume 150-fold and their nuclei increased in volume 80-fold. 12. The adepithelial cells, which give rise to some of the imaginal muscles, were first identified between the thick side of the imaginal dise epithelium and the basement membrane at the beginning of the third larval instar (50–52 h). The origin of these precursors of mesodermal structures was analysed and evidence is presented that the adepithelial cells come from the disc epithelium. The question of the origin of the mesoderm of cyclorrhaphan Diptera is reviewed and it is suggested that the imaginal disc ectoderm may become segregated from the rest of the embryo before gastrulation has occurred, that is before the mesoderm has been established.

Notes: Summary A new computation method is described which determines the focal coordinates, theP n-andP G-velocity, the focal time and the Moho-depth in the case of near earthquakes. The method is provided especially for areas where the crustal parameters are insufficiently known. It presumes that the standard error ofP n-andP G-arrival times is a minimum. The problem turns out to represent the solution of a set of at least seven equations with seven unknown parameters. Four of these unknowns can be separated in advance. This leads to a considerable simplification. The three remaining unknowns are the focal coordinates. Their best fitting values are found by the gradient method. An example is presented which shows how errors can arise if the initial trial coordinate is chosen at an unfavourable position.

Notes: Summary An attempt has been made to interpret the striking difference, in focal properties, between the intermediate and shallow earthquakes in Central Greece and an observed time sequence of these shocks by a lithospheric model. This model consists of a lithospheric slab descending from the Ionian to the Aegean and a back-arc expanding Aegean lithosphere. Thrust faulting near the top surface of the slab, caused by the sinking of the slab, triggers spreading and normal faulting in the back-arc Aegean region.

Notes: Summary Mean travel-time residuals of P waves for the period 1964–1970 at stations in North America and Europe are well separated into large domains of positive and negative values. The spatial distribution of residuals in North America is in good agreement with the structure of the upper mantle obtained from Rayleigh wave dispersion and is in accord with magnitude anomalies and heat flow data. A systematic variation of residuals in time is found to be sensitive to major changes in the nature of the earthquake source distribution, as for example aftershocks, as well as to changes in methods of detection of first arrivals. Residuals at neighboring stations are correlated up to distances of the order of 2°. Half year mean residuals at stations within 2° distance from the epicenters of strong earthquakes have a sudden jump 1.5 years before the occurrence of an earthquake. A formal algorithm based on this pattern permits prediction of the times of all 16 earthquakes with magnitudeM≥7.5 occurring during the interval 1966–1972. Although the average duration of the alarm periods is about half the total time interval of the catalog, so that the algorithm has no practical importance, these results are statistically significant on a 99% level of confidence.

Notes: Summary The derivatives of 110 mosaic genital discs of gynandromorphs have been analysed microscopically. It has been found that theanalia of both sexes are homologous and derive from a single primordium (see Fig. 1a). Whether male or female anal plates are formed depends on the genetic constitution of the cells. This is analogous to the development of male sex combs versus female transversal rows on the forelegs of gynandromorphs. In contrast, the data for thegenitalia (see Fig. 1 b) are best explained if it is assumed that there are two genital primordia in everyDrosophila embryo: a male primordium that will only develop into genitalia if populated by XY (or XO) nuclei, and a female primordium that will only do so if populated by XX nuclei. This model, as depicted in Figure 2, is compatible with all our gynandromorph data and also with observations onMusca andCalliphora where in fact two separate genital primordia are found.

Notes: Summary The females produced in the crossesD. melanogaster×D. simulans andD. melanogaster×D. mauritiana are sterile and have reduced ovaries. Normal and fertile ovaries were produced when genetically marked pole cells ofD. melanogaster were transplanted into eggs which gave rise to the hybrid females. These results eliminate the possibility that the sterility of these hybrids is due to the somatic component, i.e. the follicular cells of the ovaries, or to other physiological causes. The results also suggest that the control of gonadal morphogenesis is dependent mainly on the germ line.

Notes: Summary The generalogical relationships of photoreceptor cells within the compound eye ofDrosophila have been studied using cell labelling, with either3H-thymidine or recessive mutations, during the third larval stage. It has been found that photoreceptor and secondary pigment cells arise from different precursor cells. Under the present experimental conditions, precursors of receptor cells give rise to about 8 elements which differentiate as R cells of two different groups. One of the cells differentiates as R7 and the remaining as any one of the R1 to R6. The last cells behave initially as equivalent, and can differentiate within the same or within different, but neighbouring, ommatidia. The class of R1 to R6 cell in which each one of these elements differentiates, seems to depend on the time of its origin. The implications of these findings for the formation of the ommatidial pattern are discussed.

Notes: Summary We report on the size distribution of clones marked by mitotic recombination induced by several different doses of X-rays applied to 72 h oldDrosophila larvae. The results indicate that the radiation significantly reduces the number of cells which undergo normal proliferation in the imaginal wing disc. We estimate that 1000 r reduces by 40–60% the number of cells capable of making a normal contribution to the development of the adult wing. Part of this reduction is due to severe curtailment in the proliferative ability of cells which nevertheless remain capable of adult differentiation; this effect is possibly due to radiation-induced aneuploidy. Cytological evidence suggests that immediate cell death also occurs as a result of radiation doses as low as 100 r. The surviving cells are stimulated to undergo additional proliferation in response to the X-ray damage so that the result is the differentiation of a normal wing.

Notes: Summary Plasma-levels of thioridazine, mesoridazine, sulphoridazine and two other metabolites were determined in ten older chronic psychotic patients on thioridazine therapy. The plasma-level before the morning dose of thioridazine was the most reliable parameter for clinical studies. An intra-individual relationship between lower doses of thioridazine and plasma-levels was found. The percentage contribution of psychoactive compounds to the total sum of “thioridazine plus metabolites” ranged from 43–74%. The mean “early disappearance half-life” of thioridazine was 5 hours, and its mean “late disapperance half-life” was 26 hours.

Notes: Summary The influence of genetic and environmental factors on the metabolism of a single oral dose of ethanol 1.2 ml per kg body weight was analysed in 19 identical and 21 fraternal healthy, adult, un-selected male twin pairs. The heritability values of the rates of absorption, degradation and elimination of ethanol were 0.57, 0.41 and 0.46 respectively. Environmental factors, such as daily alcohol intake and smoking, increased the rate of elimination of blood alcohol. Intrasubject variation in ethanol metabolism was studied by repeated tests in 11 male volunteers at intervals of at least 2 months, under the same conditions as in the twins; the coefficients of variation for parameters of metabolism was about 8%. The results demonstrate both genetic control of ethanol absorption, degradation and elimination and the appreciable influence of environmental factors. The almost total genetic control of ethanol metabolism postulated by Vesell et al. (1971) could not be confirmed.

Notes: Summary The absorption and elimination of orally administered14C-phenylbutazone and the role of oxidation in its metabolism have been studied. The main routes of excretion of14C-phenylbutazone and its metabolites were investigated in 3 patients with rheumatoid arthritis, and in 1 patient with a T-tube in the common bile duct. Up to 9 days after an oral dose of14C-phenylbutazone 600 mg (30 µCi) 63% of the radioactivity was found in the urine and 14% had appeared in the faeces. The cumulative excretion of radioactivity in bile amounted to 9.5% of the dose in 4 days. Only 1% of the radioactivity in the urine and bile was due to unchanged phenylbutazone. The role of oxidative metabolism of phenylbutazone in healthy human subjects was studied by gas chromatography. In 3 subjects given a single dose of phenylbutazone 600 mg, only 8.3% of the dose was excreted in urine as oxidized metabolites after 5 days. However, in 5 patients who had taken phenylbutazone for more than 5 weeks, these metabolites accounted for 23.4% of the dose. These results suggest that oxidative metabolism becomes more important after continued administration of the drug. After a single dose of phenylbutazone, the side-chain oxidized metabolite (II) was the major free derivative excreted in urine, but the ring oxidized metabolite, oxyphenbutazone (I), was much more important than the former in plasma. However, after prolonged treatment there was little difference between the concentration of the two metabolites in plasma. This finding suggests that side-chain oxidation is increased relative to ring oxidation on prolonged treatment with phenylbutazone. A third derivative containing hydroxyl groups both in the phenyl ring and in the side-chain (metabolite III) was found in urine in experiments with phenylbutazone, but in only one out of 3 volunteers given repeated doses of oxyphenbutazone.

Notes: Summary Antiserum to fentanyl was obtained in rabbits repeatedly injected with carboxyfentanyl conjugated to bovine serum albumin. Using the antiserum, a highly sensitive radioimmunoassay has been developed, based on the dextran-coated charcoal method. It proved possible to assay the drug directly in plasma, in amounts as small as 30 picogram in 0.5 ml. The antibody was highly specific for fentanyl and no cross-reaction was observed with its major metabolites. This sensitive and specific radioimmunoassay method was employed to determine fentanyl in plasma from six volunteers after an intravenous bolus of 0.2 mg, and in plasma from dogs treated both intravenously and subcutaneously with 0.02 mg/kg. The plasma level of fentanyl could be followed for up to 6 h after a therapeutic dose in dogs and man.

Notes: Summary Plasma levels of thioridazine and four of its metabolites were determined in a series of fifteen young acute schizophrenics. Consistent individually different metabolic patterns were detected in a group of patients who had the same value for the sum of thioridazine plus metabolites. The apparent volume of distribution and half life were calculated. Clinical evolution tended to correlate best with the level of mesoridazine.

Notes: Summary The aim of the present investigation was to estimate the ratio of the intravenous doses ofβ-methyl-digoxin and digoxin required to produce identical serum glycoside concentrations in man. 20 patients on intravenous maintenance therapy were changed fromβ-methyl-digoxin to the identical dose of digoxin or vice versa. Each drug was given for 7 days. Serum concentrations 13% higher were found during administration ofβ-methyl-digoxin. Assuming a half life of 60 h after with drawal, the dose of digoxin producing the same minimum serum concentration was estimated to be 1.16 times higher than that ofβ-methyl-digoxin. 18 healthy volunteers received 0.4 mg β-methyldigoxin, and 23 the same dose of digoxin, as an intravenous infusion over 2 h. The serum concentrations and urinary glycoside excretion were measured over a period of 32 hrs. During the first hour after the infusion the serum concentration of digoxin declined more rapidly than that ofβ-methyl-digoxin. Thereafter, the ratio of the serum concentrations did not change appreciably up to the end of the investigation. The area under the serum concentration/time curve was about 13% greater forβ-methyl-digoxin than for digoxin; this difference was not significant. The average renal clearance was 96±9 ml forβ-methyl-digoxin, 151±13 ml for digoxin. Since the total body clearance of digoxin is only about 1.16 times higher than that ofβ-methyl-digoxin, the lower renal clearance ofβ-methyl-digoxin must partly be compensated by higher extrarenal clearance. From the ratios of the areas under the serum concentration/time curves after single doses of β-methyldigoxin and digoxin, and the minimum serum concentrations during maintenance therapy, it was concluded that the dose of digoxin to produce the same average serum concentrations would be about 1.15 times higher than that ofβ-methyl-digoxin. In comparison with the large variations in individual dosage of digoxin andβ-methyl-digoxin, this difference is too small to be of practical importance.

Notes: Summary Changes in catecholamine, c-AMP and lactate concentrations in the coronary circulation of man, during smoking, were studied in 12 patients. The heart rate increased from 63±2 beats/min (control) to 74±3 (smoking) (P〈0.01), falling to 70±2 (10 min after smoking) (0.05〉P〉0.01), whilst coronary sinus c-AMP concentrations rose from 11±0.7 nmol/l (smoking) to 11.9±0.8 nmol/l (after smoing) (0.05〉P〉0.01; one tailed ‘t’ test). There was no significant change in blood pressure, catecholamine or lactate concentrations. The study was repeated in eight of the patients following intravenous oxprenolol. Coronary sinus catecholamine concentrations increased from 4.1±0.7 nmol/l (control) to 5.5±1.1 nmol/l (after smoking) (0.05〉P〉0.01; one tailed ‘t’ test), but heart rate and c-AMP concentrations remained unchanged, confirming that smoking-induced tachycardia is a result of a β-adrenergic mechanism, at least part of which is due to a release of cardiac catecholamines. Arterial lactate concentrations increased only following oxprenolol from 0.74±0.07 mmol/l (control) to 0.83±0.09 mmol/l (smoking).

Notes: Summary Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.

Notes: Abstract Allozyme polymorphisms at seven loci have been studied in nine natural populations of Drosophila melanogaster from the Saône and Rhône valleys sampled in 1973 and 1974. A great deal of polymorphism was observed; an individual was on the average heterozygous at 20.2% of its loci. The populations were genetically very homogeneous throughout the region sampled. The number of ovariolae per female varied from one group of populations to another depending on their geographical separation. Yet the number of ovariolae remained constant from one year to the next. The results show that migration alone cannot explain the homogeneity of the allozyme frequencies. It seems reasonable to conclude that selection plays a major role in maintaining the homogeneity of populations living in proximal biotopes.

Notes: Abstract The activities of the enzymes aspartate transcarbamylase (ATCase) and dihydroorotase (DHOase) were determined in adult females from a wild-type strain and from eight different alleles of the X-linked mutation rudimentary (r) of Drosophila melanogaster. The alleles chosen span the genetic map of the r locus. The characteristics of the DHOase-catalyzed reaction which converts carbamyl aspartate to dihydroorotate are briefly described. Of all of the r strains tested, only one, r 9, has wild-type levels of aspartate transcarbamylase and dihydroorotase activities. The other seven show either intermediate or very low levels of activity for both enzymes. The lowered ATCase and DHOase activities observed in mutants which do not map in the region of the structural gene for these enzymes are interpreted in light of recent evidence that ATCase and DHOase are part of a three-enzyme complex.

Notes: Abstract An improved thin-layer chromatography technique is described for the separation of fluorescent compounds found in extracts of heads of Drosophila melanogaster. Eighteen to twenty fluorescent spots are resolved, two of which are xanthurenic acid and 3-hydroxykynurenine, and the remaining spots are presumably pteridines. Of these, nine have been identified and quantitated directly on the chromatograms with a fluorometer. One of the spots present on the chromatogram apparently has not been described previous to this work. Characteristics of this substance, termed “quench spot,” are presented, several of which indicate that it may be a pteridine or pteridine derivative.

Notes: Abstract Several points of biochemical similarity between white and scarlet mutants suggest that both are defective in the transport of xanthommatin precursors. In both, accumulation of 3-hydroxykynurenine is negligible during larval life and occurs at only a slow rate during adult development. Larvae of both mutants also excrete 3H-3-hydroxykynurenine and 3H-kynurenine rapidly, which probably accounts for the normal levels of kynurenine during larval life. 3-Hydroxykynurenine levels are abnormal in all white mutants which were studied, although in two alleles which are strongly pigmented (w sat and w col) accumulation is enhanced rather than diminished. In w a, larval accumulation is normal but accumulation during adult development is greatly diminished, suggesting that this mutation has a tissue-specific effect. Similar levels were found in zeste females. Of the 11 other eye color mutants tested, abnormal levels of 3-hydroxykynurenine were found in eight. In four of these (claret, light, lightoid, and pink), larval accumulation is negligible, suggesting that these have defects in the kynurenine transport system like scarlet and white. In three others, however (brown, karmoisin, and rosy), accumulation during larval life is enhanced. In cardinal accumulation is normal during larval life but is excessive during adult development. This evidence supports the suggestion that the cd mutation blocks the final step of xanthommatin synthesis.

Notes: Abstract The suppressible eye color mutant purple (pr) of Drosophila melanogaster is known to be unable to synthesize a wild-type complement of pteridine eye pigments. This study measures the reduced levels of drosopterins, sepiapterin, and an unidentified presumed pteridine in pr and pr bw. Pteridine analyses in double mutants combining pr with one of three other eye color mutants sepia, Henna-recessive3, and prune2, suggest that the metabolic block in pr occurs prior to sepiapterin biosynthesis. Measurements of GTP and GTP cyclohydrolase in pr showed wild-type levels and indicate the metabolic block in pr to be at one of the steps converting dihydroneopterin triphosphate to sepiapterin. Quantitation of pteridines in suppressed purple [su(s) 2; pr and pr; su(pr) e3] shows restoration of pteridines to wild-type or nearly wild-type levels.