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PubMed1984

Developmental effects of a temperature-sensitive RNA polymerase II mutation in Drosophila melanogaster.

Drosophila melanogaster possessing a temperature-sensitive (ts) mutation that maps to an X-linked locus ( RpII215 ) (the locus has also been called l(1)L5 and Ultrabithorax -like or Ubl ) encoding a subunit of RNA polymerase II are fertile at 22 degrees C but become sterile when shifted to 29 degrees C. Homozygous RpII215ts adult females shifted to 29 degrees C lay structurally normal eggs for 24 hr, after which increasing numbers of eggs are abnormal. Eggs left to develop at 29 degrees C die as morphologically normal late embryos or first instar larvae when produced by females maintained at 29 degrees C for less than 6 hr. However, eggs produced by females undergoing oogenesis at 29 degrees C for longer than 6 hr develop abnormally, displaying holes primarily in their ventral cuticle and possessing an abnormal pharyngeal apparatus. As exposure of females to 29 degrees C lengthens there is an increase in the severity of these defects. Some of the eggs can be rescued by either mating RpII215ts females to wild-type males or shifting the eggs to 22 degrees C. The percentage of eggs rescued decreases with increased length of oogenesis at 29 degrees C, up to 20 hr, at which point they are no longer rescuable. The terminal phenotype of eggs that fail to be rescued by the above procedure is less extreme than that of eggs for which no rescue attempt was made. Holes in the ventral cuticle are reduced or absent, but pattern formation is disrupted such that segments are often missing, incorrectly oriented or fused. Because the RpII215 locus encodes a subunit of RNA polymerase II, the developmental defects described above are most likely due to reduced or aberrant transcription during oogenesis and early embryogenesis. This postulated effect on transcription results, in part, from the maternal loading of a gene product(s) that is thermolabile in eggs.

Animals↗
PubMed1998

Developmental effects on odor learning and memory in children.

The child version of the California Odor Learning Test (COLT) was designed to assess cognitive functioning in impaired and healthy children. The COLT's rationale was based on two assumptions. First, measures of cognitive functioning are a good index of severity or extent of brain damage if compared between normal and clinical populations. Second, the cognitive-mediated tasks of verbal odor recall, recognition and identification were suitable to evaluate cognitive functioning. The focus of this study was to determine the COLT's ability to detect developmental differences in odor learning and memory. The participants were 51 healthy children who were twice administered the COLT with a weekly delay between tests. They were ascribed to two age-groups (7-10 and 11-15 years old) according to levels of cognitive development. The COLT employed 22 common odors and included two sessions. In the first session, children learned two sets of six odors. The first set was presented three times, the second one once, during a single learning episode. Following learning, children recalled the odors of the first set by name at free recall and category-cued recall. The second session included the following tasks: long-term free odor recall and category-cued odor recall, odor recognition-memory and verbal odor identification. A series of analyses of variance (ANOVAs, p < 0.05) with age as between-subject variable and repeated measurements on recall revealed significant differences between the two groups on the number of odors correctly recalled by name both at free recall, category-cued recall, recognition and identification. There were differences in false alarms at odor recognition between the two groups. Children from both groups benefited from a learning effect over odor trials. A gender effect was found for odor free recall at retest. These results suggest that the COLT has the potential to serve as a useful tool in the assessment of cognitive functioning in children.

Adolescent↗
PubMed1999

Developmental effects of urban storm water in Medaka (Oryzias latipes) and inland silverside (Menidia beryllina).

Stormwater runoff in a coastal urban area (San Diego County, CA) produced significant toxicity to early life stages of medaka (Oryzias latipes) and Menidia (M. beryllina). Exposure of embryos to lower concentrations (5 to 25%) increased the incidence of abnormal swim bladder inflation and other teratogenic responses, whereas higher concentrations resulted in mortality or failure to hatch. Comparisons of EC50s for mortality and failure to hatch with concentrations of individual chemical pollutants (including Cd, Cr, Cu, Pb, Ni, and Zn) revealed low correlations; however, the correlation with total metals was high (-0.84) and corresponded with sample exceedences of Water Quality Criteria (WQC) for Cd, Cu, Pb, and Zn. This strong association between developmental toxicity and toxic metal content of storm water compared favorably with developmental anomalies reported in other studies. Analytical chemistry data for pesticides that may have been in these samples were limited to selected pesticides found usually below detection limits. Greater toxicity of the watershed effluents sampled was generally associated with more developed land surface and less open space. Both medaka and Menidia were found to be useful for studying effects of stormwater on embryonic and early larval development. http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p227.html

Animals↗
PubMed2001

Developmental effects of selective breeding for an infantile trait: the rat pup ultrasonic isolation call.

This article describes how continued selection for divergent levels of the 10-day-old infant rat's ultrasonic vocal (USV) response to isolation affects the time course of development of that and other possible co-selected traits from 3 to 21 days postnatally. Since selective breeding for an infantile trait has not been reported before, we collected from colleagues a number of predicted outcomes that reflect the wide range of current opinion on the relationship between microevolutionary and developmental processes. After 15 generations of selective breeding, we found widely divergent USV responses between 10-day-old High USV line (300 USV/2 min) and low USV line (15 USV/2 min) pups. The developmental trajectory of USV responses at 3 and 7 days of age also was markedly altered in both these lines in comparison to the randomly bred controls, but was much less affected in 14-, 18-, or 21-day-old pups, contrary to all predictions. The development of other behavioral responses to isolation generally remained unaffected by the continued selection as did physical traits, measures of temperature regulation and classic developmental milestones. Only two traits showed evidence of co-selection: High line pups showed more urination/defecation in response to isolation from 10 days on, and more rapid ear canal opening at 10 days. These and other findings are presented and discussed in relation to the developmental and evolutionary concepts on which the different predictions were based.

Age Factors↗
PubMed1986

Developmental effects of chemicals and the heat shock response in Drosophila cells.

Exposure of prokaryotic and eukaryotic cells to heat shock (hyperthermia) or to a number of diverse environmental stresses such as teratogens, anoxia, and inhibitors of oxidative phosphorylation results in the enhanced synthesis of a number of proteins which have been previously referred to as heat shock proteins (hsps). More recently, in view of the diverse types of agents that can induce these proteins, they have also been referred to as stress proteins. This phenomenon is one of the most basic regulatory mechanisms in living organisms. Exposure of Drosophila embryos, larvae, or pupae to these types of stresses also results in a variety of developmental abnormalities in the ensuing adult. Although the function(s) of these heat shock proteins has yet to be determined, they are widely thought to play an important role in cell survival and protection following some types of environmental stress. In our laboratory, we have developed an in vitro assay for detecting agents that act as teratogens, utilizing Drosophila embryonic cultures. Drosophila embryonic cells differentiate in vitro to a number of functional cell types including myotubes and ganglia. A number of drugs that have been shown to act as teratogens in mammals have also been found to inhibit muscle and/or neuron differentiation in Drosophila embryonic cultures. We have examined, by two-dimensional gel electrophoresis, the effects of such teratogens on protein synthesis in Drosophila embryonic cells. Inhibition of muscle and/or neuron differentiation correlates well with the induction of two proteins of about 20 kilodaltons. These are identical to two of the heat shock proteins (hsp 23, 22) as shown by electrophoretic mobilities and peptide mapping by partial proteolysis. Heat shock and other treatments such as exposure to some of the metal ions and ether induces the entire set of seven major heat shock proteins in the Drosophila embryonic cells. Dose-response studies of several teratogens show a correlation between the degree of inhibition of differentiation and the level of induction of hsps. Since heat shock proteins have been suggested as possibly serving a protecting role, our present studies are aimed at identifying the role of hsps in teratogenesis and investigating the differential regulation of heat shock genes in response to different external stimuli.

Animals↗
PubMed1998

Developmental effect of polyamine depletion in Caenorhabditis elegans.

Ornithine decarboxylase (ODC) catalyses the conversion of ornithine to putrescine, an obligate precursor to the polyamines spermidine and spermine. We reported previously that homozygous odc-1 (pc13) worms have no detectable ODC activity. Despite their inability to make polyamines, these mutant worms appear normal, but with a slight reduction in total brood size, when grown in complex medium that presumably contains polyamines. We now show that when ODC-deficient worms are transferred to polyamine-free medium, they show a strong phenotype. odc-1 worms have two different fates, depending upon the developmental stage at which polyamines are removed. If the polyamines are removed at the L1 larval stage, the mutant animals develop into adult hermaphrodites that produce very few or no eggs. In contrast, if mutant larvae at the later L4 stage of development are transferred to polyamine-deficient medium, they develop and lay eggs normally. However, approx. 90% of the eggs yield embryos that, although well differentiated, arrest at early stage 3. Either maternal or zygotic expression of ODC provides partial rescue of embryonic lethality. Supplementing deficient medium with the polyamine spermidine allows ODC-deficient worms to develop as on complex medium. Together, these findings suggest that ODC activity is most critically required during oogenesis and embryogenesis and, furthermore, that exogenous polyamines can override the requirement for ODC activity.

Animals↗
PubMed1994

Housing of pregnant rats in metabolism cages: maternal and developmental effects.

The influence of the caging conditions on maternal and gestational variables was assessed for pregnant rats housed individually in two cage types. Plug-positive Sprague-Dawley females were caged either in Makrolon or in metabolism (Tecniplast) cages, and were not disturbed throughout all the gestational period. Cesarean sections were performed on gestation day 20. All live fetuses were examined for external, internal, and skeletal malformations and variations. Pregnant rats were affected by the housing system, as evidenced by a significant weight loss and reduced food consumption in the animals housed in metabolism cages. A moderate increase in the number of total skeletal defects was also observed in the fetuses of dams housed in metabolism cages. An important implication of these results would be that in maternal and developmental toxicity studies of xenobiotics, pregnant animals should not be housed in metabolism cages.

Animals↗
PubMed1998

Developmental effects on intersexual and intrasexual variation in growth and reproduction in a lizard with temperature-dependent sex determination.

The mechanisms that control growth and reproduction have received considerable attention by molecular and cellular endocrinologists, yet there has been relatively little effort to link these two aspects of physiology. On the other hand, evolutionary biologists have long commented on the relationship between growth and reproduction in many species, yet have generally neglected the mechanisms underlying such complex traits. An approach that integrates the multiple proximate levels promises to provide significant insight into the evolution of neuroendocrine control mechanisms. In this chapter, we take this approach in reviewing environmental influences on growth and reproduction in the leopard gecko, Eublepharis macularius. In this species, incubation temperature during embryonic development not only determines gonadal sex, but also underlies within-sex differences in growth, adult morphology, aggressiveness, reproductive physiology and behaviour, and brain organization. Thus, the leopard gecko is an excellent model to elucidate the developmental interactions among the environment and the endocrine and nervous systems that control growth and reproduction.

Animals↗
PubMed1988

Interactions and developmental effects of mutations in the Broad-Complex of Drosophila melanogaster.

The 2B5 region on the X chromosome of Drosophila melanogaster forms an early ecdysone puff at the end of the third larval instar. The region contains a complex genetic locus, the Broad-Complex (BR-C) composed of four groups of fully complementing (br, rbp, l(1)2Bc, and l(1)2Bd) alleles, and classes of noncomplementing (npr 1) and partially noncomplementing l(1)2Bab alleles. BR-C mutants prevent metamorphosis, including the morphogenesis of imaginal discs. Results are presented that indicate that the BR-C contains two major functional domains. One, the br domain is primarily, if not exclusively, involved in the elongation and eversion of appendages by imaginal discs. The second, the l(1)2Bc domain, is primarily involved in the fusion of discs to form a continuous adult epidermis. Nonetheless, the two domains may encode products with related functions because in some situations mutants in both domains appear to affect similar developmental processes.

Alleles↗
PubMed1996

Surface:volume relationship in cardiac myocytes studied with confocal microscopy and membrane capacitance measurements: species-dependence and developmental effects.

The quantitative analysis of the contribution of ion fluxes through membrane channels to changes of intracellular ion concentrations would benefit from the exact knowledge of the cell volume. It would allow direct correlation of ionic current measurements with simultaneous measurements of ion concentrations in individual cells. Because of various limitations of conventional light microscopy a simple method for accurate cell volume determination is lacking. We have combined the optical sectioning capabilities of fluorescence laser scanning confocal microscopy and the whole-cell patch-clamp technique to study the correlation between cell volume and membrane capacitance. Single cardiac myocytes loaded with the fluorescent dye calcein were optically sectioned to produce a series of confocal images. The volume of cardiac myocytes of three different mammalian species was determined by three-dimensional volume rendering of the confocal images. The calculated cell volumes were 30.4 +/- 7.3 pl (mean +/- SD) in rabbits (n = 28), 30.9 +/- 9.0 pl in ferrets (n = 23), and 34.4 +/- 7.0 pl in rats (n = 21), respectively. There was a positive linear correlation between membrane capacitance and cell volume in each animal species. The capacitance-volume ratios were significantly different among species (4.58 +/- 0.45 pF/pl in rabbit, 5.39 +/- 0.57 pF/pl in ferret, and 8.44 +/- 1.35 pF/pl in rat). Furthermore, the capacitance-volume ratio was dependent on the developmental stage (8.88 +/- 1.14 pF/pl in 6-month-old rats versus 6.76 +/- 0.62 pF/pl in 3-month-old rats). The data suggest that the ratio of surface area:volume of cardiac myocytes undergoes significant developmental changes and differs among mammalian species. We further established that the easily measurable parameters of cell membrane capacitance or the product of cell length and width provide reliable but species-dependent estimates for the volume of individual cells.

Animals↗
PubMed1977

Anatomical analysis of the developmental effects of aneuploidy in man--the 18-trisomy syndrome: I. Anomalies of the head and neck.

This paper describes the anatomical variations observed in the head and neck in eight infants with the 18-trisomy syndrome that were dissected and studied in detail. Of the usual muscles of facial expression, occipitofrontalis and the auricular and nasal muscles were hypolastic in all eight bodies and each subject showed extensive fusion of the muscles around the corner of the mouth. In each body there was a supernumerary muscle band that extended from the region near the corner of the mouth to the occipital attachment of trapezius. The otomandibular region in each body showed a variable spectrum of muscular, skeletal, arterial, and salivary gland variations bilaterally. Three of the bodies had infrahyoid muscle variations. The sum of these observations provides a more complete delineation of the variations that occur in the 18-trisomy syndrome. Tentative pathogenetic hypotheses for several of the defects are discussed, based on observations from human descriptive embryology. Poswillo's teratological model [1973] implicating hemorrhaging as a causal mechanism in human first and second branchial arch malformations is suggested as a possible mechanism to explain the bilateral otomandibular defects.

Chromosomes, Human, 16-18↗
PubMed1978

Anatomical analysis of the developmental effects of aneuploidy in man--the 18-trisomy syndrome: II. Anomalies of the upper and lower limbs.

We report the anatomical variations of the limbs in eight infants with the trisomy-18 syndrome that were dissected and studied in detail. In each case, the upper limbs showed defects which further define the specific influence of this aneuploidy on the development of its preaxial (radial) component, and the tendency towards reduction defects. Abnormalities included muscle variations concentrated along the radial margin of the forearm and hand, the absence of the definitive musculocutaneous nerve in all of the limbs, and reductions of the radial artery in four of the bodies. Pathogenetic mechanisms explaining the observed defects are discussed, and include: 1) a defect in peripheral nerve development; or 2) tissue necrosis. The characteristic flexion deformities of the fingers seem to be due to a displacement of the tendons of extensors digitorum and digiti minimi. The lower limbs did not show a consistent pattern of defects, except for the absence of some muscles (psoas minor, the tendon of flexor digitorum brevis to digit V), and the presence of several supernumerary muscles. These variations are discussed as possible nonspecific effects of 18-trisomy on development. The additional anatomical data from this and the first paper in this series [Bersu and Ramirez-Castro, 1977] provide a more detailed picture of the trisomy-18 phenotype which may be useful in corroborating an unconfirmed clinical diagnosis of the syndrome.

Abnormalities, Multiple↗
PubMed2001

Letter to the editor: Chronicle for an orphan trait: comment on Hofer, Shair, Masmela, & Brunelli, "Developmental effects of selective breeding for an infantile trait: the rat pup ultrasonic isolation call".

Hofer, Brunelli, Shair, and Masmela (2001) examined several behavioral and physiological measures in low, high, and unselected lines obtained from a divergent selection for ultrasound production (USP) in young rats. Although the response to selection was clear-cut, few correlated responses appeared. This surprising result could be explained by two reasons. USP has polygenic correlates in this population, and most of the chromosomal regions that are linked with these measures only contribute to a small part of the genetic variance. Therefore, correlated responses to selection might exist, but the common genetic variance between the trait under selection and the indirectly selected trait is too small to be detected by a selective breeding strategy.

Age Factors↗
PubMed1989

Developmental effects of modifiers of the vg mutant in Drosophila melanogaster.

An analysis of the modifiers affecting the expression of the vg gene was performed. We selected for weak and strong expression of the vg mutant in F2 segregating populations obtained by crossing a vestigial stock with an Oregon laboratory stock (O) and with a wild strain (B) captured near Bologna, Italy. The selection for enlarged wings was more effective in the vg B population where wild wings appeared from the 10th generation. The assay of the three major chromosomes showed that the modifiers are located on chromosomes 2 and 3. The mutant imaginal disc cell death phenotype is evident in vg/vg strains that have a wild-type wing phenotype. It is suggested that the selected modifiers do not prevent cell death but induce regenerative growth.

Animals↗
PubMed1988

Developmental effect of dimethyl sulfoxide on hypothalamo-neurohypophysial neurons in vitro.

Primary dissociated cultures were established from diencephalic tissue of 14-day-old fetal rats. Neurons exhibiting immunocytochemical staining for neurophysin appeared in these cultures after 6 days of cultivation. Addition of dimethyl sulfoxide (DMSO) to the culture medium resulted in a slight decrease in total neuronal cell mass as assessed by immunocytochemistry and radio-immunometric quantitation of neuron-specific enolase. In contrast, in DMSO-treated cultures the number of neurophysin-immunoreactive neurons was more than doubled as compared to control cultures. [3H]Thymidine labeling and autoradiography in conjunction with immunocytochemistry for neurophysin showed that this was not due to a mitogenic effect of DMSO on precursor cells. Time-course analysis of the action of DMSO revealed a 6-day time lag between the initiation of treatment and the appearance of increased numbers of neurophysin-immunoreactive cells. These findings suggest that DMSO, which has previously been reported to have a differentiation-inducing effect on malignant transformed cells, may also modulate cellular processes that control differentiation in specific types of neurons in primary culture.

Animals↗
PubMed1995

Changes in dopamine uptake and developmental effects of dopamine receptor inactivation in the sea urchin.

[3H]-dopamine ([3H]-DA) uptake was measured in the presence or absence of the catecholamine uptake inhibitor nomifensine in both unfertilized and fertilized eggs. Specific [3H]-DA uptake depended on time and [3H]-DA concentration; it was high in unfertilized eggs, declined 20-30 min after fertilization, and rose again during cleavage. Irreversible inactivation of dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) resulted in a complete loss of sensitivity of egg adenylate cyclase to dopamine stimulation. In fertilized eggs treated with EEDQ for 1 hr, restoration of adenylate cyclase activity sensitive to dopamine stimulation could be observed 4 hr after the end of treatment, thus suggesting the appearance of new dopamine receptors in cleaving eggs. Short-term EEDQ treatment on unfertilized eggs, although not impairing fertilization, resulted in cleavage inhibition; the same treatment carried out soon after fertilization, on the other hand, elicited no effect on development. On the contrary, in embryos subjected to continuous treatment with EEDQ, development was impaired independent of the stage at which the treatment was started.

Adenylyl Cyclases↗
PubMed1987

Developmental effects of isotretinoin and 4-oxo-isotretinoin: the role of metabolism in teratogenicity.

Previous observations have indicated that isotretinoin (IT), a drug in common use for therapy of cystic acne, is teratogenic in humans but possesses low embryotoxicity in pregnant mice, probably because of its shorter half-life and limited placental transfer in rodents. In human volunteers and patients, one major blood metabolite of IT is 4-oxo-isotretinoin (4-oxo-IT) which undergoes slower elimination than IT and may itself be a participant in teratogenesis. To investigate the problem of species differences displayed by IT and the role of its metabolism, embryotoxic effects of 4-oxo-IT were examined after its single or repeated intubations into pregnant ICR mice and compared with the effects of a similar regimen of IT. The two compounds were also tested for their relative ability to suppress chrondrogenesis in the in vitro cell and organ culture assays. We found that a single dose of 4-oxo-IT, 100 mg/kg, given on day 11 of gestation (plug day = day 0 of gestation) produced a moderate incidence of limb reduction defects and cleft palate (39% and 27% of surviving fetuses, respectively), while a dose of 150 mg/kg affected virtually every fetus. IT, on the other hand, produced no defects in fetuses exposed to similar dose levels. Repeated intubations with IT, however, resulted in increasing the frequencies of limb reduction defects and cleft palate to levels obtained after 4-oxo-IT administration. We found that a 3-hour interval between IT intubations was more effective in this regard than an 8-hour interval. Repeated IT intubations also uncovered sharper stage-dependency of limb and palatal defects than obtained otherwise.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗