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D Davidson

Publications and source records attributed to D Davidson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Two enhancer domains control early aspects of the complex expression pattern of Msx1.

To understand how the complex embryonic expression pattern of the Msx1 gene is produced a transgenic analysis of 13 kb of DNA around the Msx1 locus was carried out. Most of the extensive expression pattern of the Msx1 gene was reproduced in transgenics using the LacZ gene fused to 5 kb of Msx1 5' flanking DNA. Two enhancer domains were identified which produced this pattern. The distal element produced expression in the first arch and the nasal epithelium and was restricted to 240 bp. However, the proximal element which produced expression in superficial nasal epithelium, dorsal and ventral myotome, limb mesenchyme, eye, ear, roof plate, second arch, genital ridge and epiphysis, was contained in only 78 bp.

Animals↗
PubMed1997

Monolingual and bilingual children's use of the mutual exclusivity constraint.

The use of the mutual exclusivity constraint was examined in three-year-old and six-year-old children who were either monolingual in English (N = 32) or bilingual in English/Urdu (N = 32) or in English/Greek (N = 32). Three tests of the constraint were used: disambiguation rejection, and restriction. On the disambiguation test, the mutual exclusivity bias was significantly more evident in five- and six-year-old monolingual children than in their same-age bilingual peers. Monolingual children were also more likely than bilingual children to reject a new name for a familiar object. However, using a restriction test, neither monolingual nor bilingual children readily accepted and restricted typical names for hybrid objects. Developmental differences were also found, as older (five- to six-year-old) monolingual children's responses on the tests were generally more consistent with the constraint than younger (three- to four-year-old) children's responses. Nevertheless, bilingual children did use the constraint, but not to the extent of monolingual children.

Child↗
PubMed1997

A new dimension for the human genome project: towards comprehensive expression maps.

The current Human Genome Project is largely devoted to structural characterisation of our genome. We now need international co-ordination of a second phase of genome analysis, the systematic construction of expression maps using both basic and high-resolution expression assays. Databases recording different types of expression pattern for a variety of human cell types need to be established and co-ordinated. There is a compelling need for a database of gene expression in early human development, but the scarcity of human material for study requires optimisation of research strategies and co-ordination of expression studies in early human and mouse development.

Animals↗
PubMed1997

The budget deal.

Explore the source record for details and available documents.

American Hospital Association↗
PubMed1997

Computer-aided 3-D reconstruction of serially sectioned mouse embryos: its use in integrating anatomical organization.

This paper reviews recent work on a project that uses a computer-aided approach for making 3-D reconstructions of serially sectioned mouse embryos (the digital mouse). The captured images are aligned using a warping program so that almost perfect alignment of adjacent sections is achieved with minimal deformation. The sections that are viewed on the computer screen are in fact computer-generated grey-level images with a resolution of about 10 microm. The reconstructed embryo may then be resectioned in any plane to simulate as near as possible an exact match on the computer screen to the viewer's own material. Individual anatomical domains may then be painted in different colors, and these domains may be selected by querying the textual database containing anatomical and other information. Further, it is now possible to generate 3-D images of individual anatomically-discrete components or related sets of components of a particular system in isolation from the rest of the embryo, or, if required, against a 'ghost-like' image of the intact embryo, or specific parts of an embryo. In the article, examples are given of the use of the system in interpreting the vascular, gut and paraxial mesoderm systems, while both the advantages and disadvantages of this approach are also discussed. The eventual aim will be to provide 3-D reconstructions of mouse embryos from fertilization up to 14 days postcoitum of development. When completed, this project will allow the accurate spatial mapping of gene-expression and cell lineage data onto the digital Atlas of normal mouse embryonic development.

Animals↗
PubMed1997

Naltrexone blocks acquisition of voluntary ethanol intake in rats.

The effects of naltrexone (NTX) on the acquisition of ethanol drinking was assessed in rats. NTX (0, 2.5, 5.0, or 10.0 mg/kg) was administered to rats presented with an ascending series of ethanol concentrations (2%, 4%, 6%, and 8% v/v) and water. The 2.5 and 10 mg/kg doses of NTX attenuated the acquisition of voluntary drinking of 8% ethanol, but the 5.0 mg/kg dose of NTX had no effect on ethanol intake. The acquisition paradigm was repeated in experiment 2 with naïve animals that received 0, 5.0, or 7.5 mg/kg of NTX. Neither dose of NTX affected ethanol intake, preference for alcohol, or water intake. Total fluid intake was suppressed in the NTX groups, but only on the second presentations of the 2% and 6% concentrations of ethanol. We suggest that the 2.5 and 10 mg/kg doses of NTX may have attenuated the acquisition of ethanol drinking by at least two different behavioral mechanisms.

Alcohol Drinking↗
PubMed1997

Behavioral effects and pharmacokinetics of low-dose intravenous alcohol in humans.

Alcohol has physiological effects on the human central nervous system at blood alcohol concentrations (BACs) as low as 9 mg/dl. It is unknown, however, if humans can perceive the effects of such low doses of alcohol. Furthermore, low BACs can be difficult to measure. The purpose of this experiment was to: (1) assess the ability of humans to perceive subjective effects of low BACs; (2) measure behavioral effects of low BACs on a psychomotor performance task; and (3) test the sensitivity and accuracy of the transdermal alcohol sensor (TAS) for measuring low BACs from skin. Five men and seven women were administered single-blind intravenous infusions of ethyl alcohol in 5% dextrose/water to achieve peak BACs of 0, 10, 20, and 40 mg/dl. Subjective intoxication scales and a computer administered continuous performance task (CPT) were used to assess alcohol effects. BACs were estimated from skin, blood, and breath. The only alcohol-induced sensation significantly increased during the alcohol infusions was anesthesia measured by the Alcohol Sensation Scale on the descending limb of the BAC curve. The subjective positive-reinforcing stimulant and mood effects of alcohol were not reported until subjects were administered the 40 mg/dl alcohol infusion. Other measures of subjective intoxication and sedation, and the CPT were unaffected by the alcohol infusions. The TAS provided a noninvasive method for estimating BACs that was comparable with estimates obtained from blood and breath, although delayed in time.

Adult↗
PubMed1996

Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells.

Recently we have identified angiostatin, an endogenous angiogenesis inhibitor of 38 kDa which specifically blocks the growth of endothelial cells (O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C. , Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., and Folkman, J. (1994) Cell 79, 315-328; Folkman, J. (1995) Nat. Med. 1, 27-31). Angiostatin was shown to represent an internal fragment of plasminogen containing the first four kringle structures. We now report on the inhibitory effects of individual or combined kringle structures of angiostatin on capillary endothelial cell proliferation. Recombinant kringle 1 and kringle 3 exhibit potent inhibitory activity with half-maximal concentrations (ED50) of 320 nM and 460 nM, respectively. Also, recombinant kringle 2 displays a significant inhibition, although decreased compared with both kringle 1 and kringle 3. In contrast, kringle 4 is an ineffective inhibitor of basic fibroblast growth factor-stimulated endothelial cell proliferation. Among the tandem kringle arrays, the recombinant kringle 2-3 fragment exerts inhibitory activity similar to kringle 2 alone. However, relative to kringle 2-3, a marked enhancement in inhibition is observed when individual kringle 2 and kringle 3 are added together to endothelial cells. This implies that it is necessary to open the cystine bridge between kringle 2 and kringle 3 to obtain the maximal inhibitory effect of kringle 2-3. An increased (<2-fold) inhibitory activity is observed for the kringle 1-3 fragment (ED50 = 70 nM) compared with kringle 1-4 (ED50 = 135 nM). These data indicate that the anti-proliferative activity of angiostatin on endothelial cells is shared by kringle 1, kringle 2, and kringle 3, but probably not by kringle 4 and that more potent inhibition results when kringle 4 is removed from angiostatin. Thus, in view of the variable lysine affinity of the homologous domains, it would appear that lysine binding capability does not correlate with the relative inhibitory effects of the kringle-containing constructs. However, as we also demonstrate, appropriate folding of kringle structures is essential for angiostatin to maintain its full anti-endothelial activity.

Amino Acid Sequence↗
PubMed1996

Ondansetron alters human alcohol intoxication.

There is considerable evidence that serotonin-3 (5-HT3) receptor antagonists modulate some of the behavioral effects of alcohol, and may decrease alcohol consumption. To better clarify the mechanism of action of 5-HT3 antagonists on these behaviors, we investigated the effects of the 5-HT3 antagonist, ondansetron, on several subjective and objective measures of alcohol intoxication in social drinkers. Twelve nonalcoholic, social drinkers received either 8 mg ondansetron, p.o., or placebo during one of two test sessions in a crossover, double-blind protocol. Both conditions were followed by a standard, intoxicating dose of alcohol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and alcohol pharmacokinetics were determined. To control for ondansetron effects, 10 additional subjects received either ondansetron or placebo, followed by a nonintoxicating, "placebo" dose of alcohol during a second crossover double-blind protocol. Ondansetron was found to augment certain stimulant, sedative, and discriminant effects of alcohol, without affecting psychomotor performance or alcohol pharmacokinetics. Ondansetron had minimal effects on subjects receiving placebo alcohol. These data suggest that the reductions in alcohol consumption observed in animals and humans treated with ondansetron may be mediated by increases in subjective intoxication, and/or increases in the aversive effects of alcohol.

Adult↗
PubMed1996

Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes.

Accumulating data show that the tyrosine protein kinase Zap-70 plays an essential role in T cell receptor-mediated signal transduction. However, the model of action, as well as the physiologically relevant substrates of Zap-70, have not been determined. We have attempted to identify a 120-kD tyrosine-phosphorylated protein (p120) that associates with Zap-70 in activated T lymphocytes. The results of our analyses showed that p120 is largely encoded by the c-cbl protooncogene. Furthermore, the association of Zap-70 with c-Cbl was shown to be induced by T cell receptor stimulation, implying that it required posttranslational modification of one or both of these products. FynT, but not Lck, also associated with c-Cbl in activated T cells. Finally, using a heterologous system, it was demonstrated that the ability of Zap-70 to cause tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated signals. As c-Cbl can associate with several other signaling molecules, it may couple Zap-70 to downstream effectors during T cell activation.

Animals↗
PubMed1996

The effects of decision characteristics on children's selective search of predecisional information.

In the present research, an information-board procedure was used to examine second and fifth grade children's selective search of predecisional information. Several conditions were used to facilitate children's selective search of information, including putting decisions within meaningful contexts (i.e., stories), increasing the perceptual salience of some of the dimensions on the information boards, and constraining the amount of time and the amount of information children could take when searching predecisional information. It was found that both second and fifth graders' predecisional search became more selective when the perceptual salience of some of the dimensions was increased. Children also became more selective in their searching over successive decisions. In contrast, the information constraint resulted in less selective searching, and less choosing of the best alternative for both second and fifth grader, whereas the time pressure decreased second but not fifth graders' selectivity in searching. Thus, without sufficient mastery of a search strategy, children may resort to using less sophisticated strategies, particularly under time and information pressures. These results are discussed in terms how the development of selective search and attentional strategies may impact both predecisional search behavior and the quality of children's decisions.

Attention↗
PubMed1996

Complementary tissue-specific expression of LIF and LIF-receptor mRNAs in early mouse embryogenesis.

The maintenance of pluripotential embryonic stem (ES) cells is dependent on the cytokine LIF. This report documents the mRNA expression profiles of LIF and the two components of the LIF-receptor complex, LIF-R and gp130, during early mouse embryogenesis. These mRNAs were undetectable in 1- or 2-cell embryos, but all were present by the blastocyst stage. LIF transcripts were localised in the differentiated trophectoderm, and were absent from the pluripotential inner cell mass. In contrast, LIF-R mRNA was found in the inner cell mass but not in the trophectoderm. This complementary pattern of expression is suggestive of a paracrine coupling between stem cells and differentiated progeny at the earliest stage of mammalian development. After implantation, transcripts for all components were down-regulated in the embryo. High levels of LIF-R and gp130 mRNAs were observed in the deciduum, however. These dynamic, tissue-specific expression patterns are consistent with regulatory roles for LIF or related cytokines, both in the maintenance of pluripotency in the mouse embryo, and in development of the foeto-maternal interface.

Animals↗
PubMed1996

Mutation of putative branchpoint consensus sequences in plant introns reduces splicing efficiency.

Intron lariat formation between the 5' end of an intron and a branchpoint adenosine is a fundamental aspect of the first step in animal and yeast nuclear pre-mRNA splicing. Despite similarities in intron sequence requirements and the components of splicing, differences exist between the splicing of plant and vertebrate introns. The identification of AU-rich sequences as major functional elements in plant introns and the demonstration that a branchpoint consensus sequence was not required for splicing have led to the suggestion that the transition from AU-rich intron to GC-rich exon is a major potential signal by which plant pre-mRNA splice sites are recognized. The role of putative branchpoint sequences as an internal signal in plant intron recognition/definition has been re-examined. Single nucleotide mutations in putative branchpoint adenosines contained within CUNAN sequences in four different plant introns all significantly reduced splicing efficiency. These results provide the most direct evidence to date for preferred branchpoint sequences being required for the efficient splicing of at least some plant introns in addition to the important role played by AU sequences in dicot intron recognition. The observed patterns of 3' splice site selection in the introns studied are consistent with the scanning model described for animal intron 3' splice site selection. It is suggested that, despite the clear importance of AU sequences for plant intron splicing, the fundamental processes of splice site selection and splicing in plants are similar to those in animals.

Amylases↗