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Biomedical subjects

S Waddell

Publications and source records attributed to S Waddell.

12 recordsLinked to original sources
PubMed2001

A "no-hybrids" screen for functional antagonizers of human p53 transactivator function: dominant negativity in fission yeast.

We have developed a functional "no-hybrids" screen in the fission yeast Schizosaccharomyces pombe based on the transcription transactivator activity of human p53. The screen can be used to identify antagonizers and modulators of p53 activity. Expression of functional full-length human p53 is conditionally lethal to the screen reporter strains. Co-expression of specific inhibitory proteins promotes cell survival and growth. We have validated the "no-hybrids" system by (a) successful modeling of human wild-type p53 interaction with SV40 large T antigen, Mdm2 and a panel of tumor-derived human p53 mutants, (b) demonstrating the screening system's efficiency through identification of a dominant negative fragment of p53 itself in a library screen context and (c) using Drosophila p53 to demonstrate that the system can detect evolutionarily distant p53 homologues based on their transactivator activity. The "no-hybrids" screen will be of utility in searches for p53 function-modulators of both cellular and viral origin.

Animals↗
PubMed2001

What can we teach Drosophila? What can they teach us?

A number of single gene mutations dramatically reduce the ability of fruit flies to learn or to remember. Cloning of the affected genes implicated the adenylyl cyclase second-messenger system as key in learning and memory. The expression patterns of these genes, in combination with other data, indicates that brain structures called mushroom bodies are crucial for olfactory learning. However, the mushroom bodies are not dedicated solely to olfactory processing; they also mediate higher cognitive functions in the fly, such as visual context generalization. Molecular genetic manipulations, coupled with behavioral studies of the fly, will identify rudimentary neural circuits that underly multisensory learning and perhaps also the circuits that mediate more-complex brain functions, such as attention.

Animals↗
PubMed2001

Fas-acting memory.

Genetic and behavioral analysis points to a role for fasciclin II in controlling odor memory and alcohol sensitivity in Drosophila.

Animals↗
PubMed2001

Flies, genes, and learning.

Flies can learn. For the past 25 years, researchers have isolated mutants, engineered mutants with transgenes, and tested likely suspect mutants from other screens for learning ability. There have been notable surprises-conventional second messenger systems co-opted for intricate associative learning tasks, two entirely separate forms of long-term memory, a cell-adhesion molecule that is necessary for short-term memory. The most recent surprise is the mechanistic kinship revealed between learning and addictive drug response behaviors in flies. The flow of new insight is likely to quicken with the completion of the fly genome and the arrival of more selective methods of gene expression.

Animals↗
PubMed2000

The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory.

Mutations in the amnesiac gene in Drosophila affect both memory retention and ethanol sensitivity. The predicted amnesiac gene product, AMN, is an apparent preproneuropeptide, and previous studies suggest that it stimulates cAMP synthesis. Here we show that, unlike other learning-related Drosophila proteins, AMN is not preferentially expressed in mushroom bodies. Instead, it is strongly expressed in two large neurons that project over all the lobes of the mushroom bodies, a finding that suggests a modulatory role for AMN in memory formation. Genetically engineered blockade of vesicle recycling in these cells abbreviates memory as in the amnesiac mutant. Moreover, restoration of amn gene expression to these cells reestablishes normal olfactory memory in an amn deletion background. These results indicate that AMN neuropeptide release onto the mushroom bodies is critical for normal olfactory memory.

Animals↗
PubMed1998

Defining the minimal requirements for papilloma viral E6-mediated inhibition of human p53 activity in fission yeast.

The majority of human anogenital carcinomas show evidence of papillomavirus infection. To facilitate viral replication, viruses disable key cellular responses which would otherwise precipitate cell suicide. An obligate factor in one such response is the p53 tumour suppressor protein. p53 gene mutation is an infrequent event in anogenital cancer, apparently due to the action of HPV E6 protein, which inhibits wild-type p53 function by stimulating the degradation of p53 protein. p53 is required for the apoptotic response that is triggered in untransformed cells following inappropriate cell-cycling. E6 directed inhibition of p53 function thus facilitates the survival of transformed cells. We have developed a genetically tractable model that reports E6 protein-mediated human p53 inactivation in the fission yeast Schizosaccharomyces pombe. Functional dissection of the requirements for E6 directed inhibition in this system reveal an absolute requirement for the presence of both E6 protein and the human E3 ubiquitin ligase, E6-AP. Using a defined set of E6 mutants we show that degradation of p53 protein rather than E6/p53 association is likely required for E6-mediated inhibition. This S. pombe based system represents a candidate screen for novel antiviral agents that act by disrupting the E6/E6-AP/p53 interaction.

DNA-Binding Proteins↗
PubMed1995

Ty1-copia group retrotransposon sequences in amphibia and reptilia.

We have isolated sequences belonging to Ty1-copia group retrotransposons from the genomes of an amphibian (Pyxicephalus adspersa) and three reptiles (Conolophus subscristatus, Amblyrynchus cristatus and Pytas mucosus). Two different sequences were found in the amphibian (Tpa1 and Tpa2). Each is present in several copies per genome and absent from the genomes of two other amphibian species. The C. subcristatus sequence Tcs1 is present in multiple copies in both its host genome (Galapagos land iguana) and the genome of the related Galapagos marine iguana (A. cristatus). There is little or no polymorphism in Tcs1 insertions between different individual animals, suggesting that this sequence is not transposing rapidly in either iguana genome. The P. mucosus sequence Tpm1 shows a discontinuous distribution in snake species, suggesting that it has either been lost from many lineages during vertical germline transmission or has been transferred horizontally in some snake species. Phylogenetic comparisons of all these sequences with each other and with other members of this retrotransposon group from other animals and plants show that sequences within a particular vertebrate species are most closely related to each other, consistent with a vertical transmission model for their evolution.

Amino Acid Sequence↗
PubMed1995

Some effects of homelessness on the psychological functioning of preschoolers.

The developmental consequences of homelessness have only recently begun to be investigated. This study examined the effects of homelessness on the self-concept, behavioral symptoms, and emotional development of preschoolers. Self-concept was examined using the Pictorial Scale of Perceived Competence and Acceptance for Young Children and teachers rated behavioral symptoms using the Child Behavior Checklist. Emotional development was also examined. Results showed that homeless preschoolers have lower self-concepts and display more deviant behaviors on the Child Behavior Checklist than housed preschoolers of the same socioeconomic status. Recognition and understanding of emotion, however, were similar in both groups.

Child Behavior Disorders↗
PubMed1989

Vasovagal syncope.

To return to the patient's syncopal episode, it is clearer now that he probably did have a vasovagal reaction. An hour had elapsed since administration of morphine, making that etiology unlikely. The patient showed no evidence of heart block or acute ischemia. While nitrate induced hypotension may have contributed to his faint, that would not have explained his bradycardia. Worth noting is the fact that he developed nausea and lost consciousness as an arterial puncture was about to be performed. Had he been asked, the patient might have recalled other incidents of vasovagal fainting. A combination of factors may cause a brief syncopal episode in the ICU. Sorting out the causes of vasovagal syncope may be difficult if not impossible, and a syncopal episode may set a chain of events into motion that further complicates the situation. The patient with an acute, especially inferior MI who received intravenous medications is particularly prone to vagal-like reactions. Patients with nausea or extreme anxiety should be watched carefully and their symptoms treated.

Diagnosis, Differential↗
PubMed1988

Singleness of action in the interactions of feeding with other behaviors in Hermissenda crassicornis.

Singleness of action in the interactions of feeding behavior with other behaviors was studied in Hermissenda crassicornis. In Experiment 1 withdrawal of the oral veil from a tactile stimulus was inhibited during feeding elicited by application of a mussel homogenate to hungry animals. Rolling-over behavior was also inhibited during feeding. When animals were satiated, thereby abolishing the feeding response to mussel homogenate, withdrawal occurred in the presence of the food stimulus; however, rolling-over behavior was still inhibited. In Experiments 2 and 3 it was demonstrated that spontaneous locomotion was also inhibited in hungry animals by food stimuli; however, satiated animals ignored the food stimulus and continued to locomote. Both biting behavior and the suppressive effect of food stimuli on locomotion were also observed in dissected anterior ends of Hermissenda, suggesting that the mechanisms underlying the interaction of feeding with other behaviors may be accessible to study in the nervous system of reduced preparations.

Animals↗