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J Parish

Publications and source records attributed to J Parish.

5 recordsLinked to original sources
PubMed2000

The human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway.

The human papillomavirus (HPV) E2 protein regulates viral gene expression and is also required for viral replication. HPV-transformed cells often contain chromosomally integrated copies of the HPV genome in which the viral E2 gene is disrupted. We have shown previously that re-expression of the HPV 16 E2 protein in HPV 16-transformed cells results in cell death via apoptosis. Here we show that the HPV 16 E2 protein can induce apoptosis in both HPV-transformed and non-HPV-transformed cell lines. E2-induced apoptosis is abrogated by a trans-dominant negative mutant of p53 or by overexpression of the HPV 16 E6 protein, but is increased by overexpression of wild-type p53. We show that mutations that block the DNA binding activity of E2 do not impair the ability of this protein to induce apoptosis. In contrast, removal of both N-terminal domains from the E2 dimer completely blocks E2-induced cell death. Heterodimers formed between wild-type E2 and N-terminally deleted E2 proteins also fail to induce cell death. Our data suggest that neither the DNA binding activity of E2 nor other HPV proteins are required for the induction of apoptosis by E2 and that E2-induced cell death occurs via a p53-dependent pathway.

Animals↗
PubMed1999

BMP/GDF-signalling interactions during synovial joint development.

The synovial joint arises from an initial condensation of cells that subsequently develops into distinct skeletal structures, separated by the joint. Bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs) have a fundamental role during skeletogenesis, including joint formation. Development of the joint appears to be dependent on the differential expression/activity of the related BMP and GDF subfamilies. Gdf-5 is expressed in the developing joints and is necessary for the formation of some joints. In contrast, recent data has shown that antagonism of the BMP family is crucial for joint formation. Here, we review mechanisms of how BMP signalling may be antagonised/modified. We also describe the expression of Bmp-2 and Bmp-4 together with two BMP antagonists, chordin and noggin, during chick joint development. Finally, we discuss possible mechanisms of how a joint forms and the evidence that the joint is a 'signalling centre' that may coordinate the development of adjacent skeletal structures.

Animals↗
PubMed1999

Mechanisms of GDF-5 action during skeletal development.

Mutations in GDF-5, a member of the TGF-beta superfamily, result in the autosomal recessive syndromes brachypod (bp) in mice and Hunter-Thompson and Grebe-type chondrodysplasias in humans. These syndromes are all characterised by the shortening of the appendicular skeleton and loss or abnormal development of some joints. To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP. This resulted in up to a 37.5% increase in length of the skeletal elements, which was predominantly due to an increase in the number of chondrocytes. By injecting virus at different stages of development, we show that GDF-5 can increase both the size of the early cartilage condensation and the later developing skeletal element. Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner. We did not detect changes in proliferation. However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis. In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes. Thus, here we show two mechanisms of how GDF-5 may control different stages of skeletogenesis. Finally, our data show that levels of GDF-5 expression/activity are important in controlling the size of skeletal elements and provides a possible explanation for the variation in the severity of skeletal defects resulting from mutations in GDF-5.

Amino Acid Sequence↗
PubMedDate not supplied

Status and trends of Ontario's Sydenham River ecosystem in relation to aquatic species at risk.

The Sydenham River in southwestern Ontario is located in the Mixedwood Plains Ecozone, which supports the greatest diversity of flora and fauna in Canada. The river historically supported a rich aquatic community that included 80 fishes and 34 species of freshwater mussels. Fourteen aquatic species native to the river (8 fishes, 5 mussels and 1 turtle) have been designated as endangered, threatened, or of special concern by the Committee on the Status of Species at Risk in Canada (COSEWIC). A multi-agency Recovery Team was formed in 1999 to ensure the continued survival of these and other rare species in the river. The Sydenham River Recovery Team is the first in Canada to adopt an ecosystem approach to recovery planning for aquatic species. Information on land use patterns, water quality trends, the physical condition of the river, and the distributions of aquatic species at risk was synthesized to gain an understanding of the overall health of the river and its major anthropogenic stresses. Seven of the species at risk have declined in distribution or abundance, and three may be extirpated. The main threat to fishes and mussels is heavy loadings of sediment, nutrients, and possibly pesticides to the river via tile drainage and overland runoff from agricultural lands. A strategy that incorporates four overall approaches (management, stewardship, research and monitoring, and awareness and outreach) was developed to recover and protect this globally significant freshwater ecosystem.

Animals↗