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P J Webster

Publications and source records attributed to P J Webster.

12 recordsLinked to original sources
PubMed1997

Translational repressor bruno plays multiple roles in development and is widely conserved.

oskar (osk) mRNA is tightly localized to the posterior pole of the Drosophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced expression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localization process, ensuring that Osk protein is only expressed after the mRNA has reached the posterior. An ovarian protein, Bruno (Bru), has been implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the expression cloning of an RNA-binding protein, and the identification of previously described mutants in the arrest (aret)-locus as mutants in Bru. The mutant phenotype, along with the binding properties of the protein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesis as well as early in embryogenesis. Genetic experiments provide further evidence that Bru functions in the translational repression of osk. Intriguingly, we find that Bru interacts physically with Vasa (Vas), an RNA helicase that is a positive regulator of osk translation. Bru belongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for the molecular mechanism of Bru function are discussed.

Amino Acid Sequence↗
PubMed1994

Drosophila virilis oskar transgenes direct body patterning but not pole cell formation or maintenance of mRNA localization in D. melanogaster.

The Drosophila melanogaster gene oskar is required for both posterior body patterning and germline formation in the early embryo; precisely how oskar functions is unknown. The oskar transcript is localized to the posterior pole of the developing oocyte, and oskar mRNA and protein are maintained at the pole through early embryogenesis. The posterior maintenance of oskar mRNA is dependent upon the presence of oskar protein. We have cloned and characterized the Drosophila virilis oskar homologue, virosk, and examined its activity as a transgene in Drosophila melanogaster flies. We find that the cis-acting mRNA localization signals are conserved, although the virosk transcript also transiently accumulates at novel intermediate sites. The virosk protein, however, shows substantial differences from oskar: while virosk is able to rescue body patterning in a D. melanogaster oskar- background, it is impaired in both mRNA maintenance and pole cell formation. Furthermore, virosk induces a dominant maternal-effect lethality when introduced into a wild-type background, and interferes with the posterior maintenance of the endogenous oskar transcript in early embryogenesis. Our data suggest that virosk protein is unable to anchor at the posterior pole of the early embryo; this defect could account for all of the characteristics of virosk mentioned above. Our observations support a model in which oskar protein functions both by nucleating the factors necessary for the activation of the posterior body patterning determinant and the germ cell determinant, and by anchoring these factors to the posterior pole of the embryo. While the posterior body patterning determinant need not be correctly localized to provide body patterning activity, the germ cell determinant may need to be highly concentrated adjacent to the cortex in order to direct pole cell formation.

Amino Acid Sequence↗
PubMed1993

Multiple RNA regulatory elements mediate distinct steps in localization of oskar mRNA.

Pattern formation in the early development of many organisms relies on localized cytoplasmic proteins, which can be prelocalized as mRNAs. The Drosophila oskar gene, required both for posterior body patterning and germ cell determination, encodes one such mRNA. Localization of oskar mRNA is an elaborate process involving movement of the transcript first into the oocyte from adjacent interconnected nurse cells and then across the length of the oocyte to its posterior pole. We have mapped RNA regulatory elements that direct this localization. Using a hybrid lacZ/oskar mRNA, we identify several elements within the oskar 3' untranslated region that affect different steps in the process: the early movement into the oocyte, accumulation at the anterior margin of the oocyte and finally localization to the posterior pole. This use of multiple cis-acting elements suggests that localization may be orchestrated in a combinatorial fashion, thereby allowing localized mRNAs with ultimately different destinations to employ common mechanisms for shared intermediate steps.

Animals↗
PubMed1992

The cost of treating small cell lung cancer.

OBJECTIVE: To determine the cost of treating small cell lung cancer (SCLC) and to assess quality-adjusted survival in these patients. DESIGN: Retrospective analysis. SETTING: Westmead Hospital, a tertiary referral institution. PATIENTS: Consecutive sample of 31 patients with histologically proved SCLC, treated between January 1987 and December 1987. MAIN OUTCOME MEASURES: The cost of investigation, hospitalisation, chemotherapy, radiotherapy and follow-up of patients overall and for those with limited and extensive disease respectively. Quality-adjusted survival was based on a Q-TWiST analysis. RESULTS: The median overall cost per patient was $14,413 (range, $1188-$39,598) for all patients and for limited disease and extensive disease was $18,234 (range, $1914-$39,598) and $13,177 (range, $1188-$32,798) respectively. The two major costs were hospitalisation (42%) and chemotherapy (18%). Radiotherapy accounted for 11% of all costs. The Q-TWiST analysis suggests that for patients with limited disease, quality-adjusted survival is similar to absolute survival. CONCLUSIONS: The treatment of SCLC at our institution was expensive but the cost may be reduced by reduction in the duration of hospitalisation, the use of less expensive combination drug regimens, or the use of "true" outpatient chemotherapy. Despite intensive therapy, patients with limited disease maintained a reasonable quality of life.

Aged↗
PubMed1992

Conserved classes of homeodomains in Schistosoma mansoni, an early bilateral metazoan.

Genes containing a homeobox can be divided into classes based on the distinctive peptide sequences of their diverged homeodomains. Many of these classes, including Antennapedia, engrailed and paired, are strongly conserved in higher multicellular animals, but have not previously been found in platyhelminths, the flatworms which represent the most primitive bilateral metazoans. We have screened cDNA libraries of the platyhelminth Schistosoma mansoni using a degenerate oligonucleotide derived from the third helix of the homeodomain, and have identified numerous schistosome homeobox-containing sequences, including members of the Antennapedia, engrailed and paired classes. The schistosome homeodomain sequences are more similar to the higher animals sequences in their respective classes than they are to each other, indicating that the establishment of these three distinctive classes is at least as ancient as the flatworms. Our data suggest that the ancestral functions of the Antennapedia, engrailed and paired classes involve fundamental features of all bilateral metazoan development. The putative full-length coding sequence of the S. mansoni en homologue is presented.

Amino Acid Sequence↗
PubMed1987

Tissue effects of an ultrasonic scalpel for clinical surgical use.

The effects of a new ultrasonic scalpel were studied in laboratory animals. Tissue heat conduction from the tip of the ultrasonic blade was measured. Tissue damage was assessed by light microscopy of histochemically stained sections. The ultrasonic scalpel incised nonfibrous tissue effectively, with minimal heat conduction, and the incisions healed with no evidence of fibrosis nor of tissue destruction.

Animals↗
PubMed1976

A review of macromolecular transport and secretion at the cellular level.

This is a review of current information concerning mechanisms involved in transport and secretion of macromolecules in exocrine glands. Emphasis has been placed on information available for pancreatic acinar cells. The review was prompted by the availability of considerable amounts of new information developed during the past several years. Exportable proteins in the pancreatic acinar cells are synthesized on ribosomes attached to the endoplasmic reticulum. Following synthesis, nascent proteins are transported from ribosomes attached to the endoplasmic reticulum into intracisternal spaces bound by the endoplasmic reticulum. The proteins are then carried to the Golgi complex by transitional elements. Zymogen granules are formed in the Golgi complex and migrate to the cell apex. Appropriate stimulation leads to fusion of the zymogen granule membrane and apical plasmalemma followed by a break in the membrane and consequent release of the granule content into the ductules. The extact molecular events involved in the process of secretion are not known. The roles of cAMP and cGMP in pancreatic secretion are supported by indirect evidence only. The role of calcium in secretion is apparent, but further investigation is needed to delineate the exact mechanism of its action. Membrane depolarization and associated ionic fluexes seem to play a significant role.

Animals↗