Biology subjects

Davies, P.

Publications and source records attributed to Davies, P..

4 recordsLinked to original sources

bioRxiv2018

Taking a deeper look: Quantifying the differences in fish assemblages between shallow and mesophotic temperate rocky reefs

The spatial distribution of a species assemblage is often determined by habitat and climate. In the marine environment, depth can become an important factor as degrading light leads to changes in the biological habitat structure. To date, much of the focus of ecological fish research has been based on reefs in less than 40 m with little research on the ecological role of mesophotic reefs. We deployed baited remote underwater stereo video systems (stereo-BRUVS) on temperate reefs in two depth categories: shallow (20-40m) and mesophotic (80-120m), off Port Stephens, Australia. Sites were selected using data collected by swath acoustic sounder to ensure stereo-BRUVS were deployed on reef. The sounder also provided rugosity, slope and relief data for each stereo-BRUVS deployment. Multivariate analysis indicates that there are significant differences in the fish assemblages between shallow and mesophotic reefs, primarily driven by Ophthalmolepis lineolatus and Notolabrus gymnogenis only occurring on shallow reefs and schooling species of fish that were unique to each depth category: Atypichthys strigatus on shallow reefs and Centroberyx affinis on mesophotic reefs. While shallow reefs had a greater species richness and abundance of fish when compared to mesophotic reefs, mesophotic reefs hosted the same species richness of fishery targeted species. Chrysophrys auratus (pink snapper) and Nemodactylus douglassii (grey morwong) are two highly targeted species in this region. While C. auratus was numerically more abundant on shallow reefs, mesophotic reefs provide habitat for larger fish. In comparison, N. douglassii were evenly distributed across all sites sampled. Generalized linear models revealed that depth and habitat type provided the most parsimonious model for predicting the distribution of C. auratus, while habitat type alone best predicted the distribution of N. douglassii. These results demonstrate the importance of mesophotic reefs to fishery targeted species and therefore have implications for informing the management of these fishery resources on shelf rocky reefs.

ecology↗

bioRxiv2018

CDK1 and CDK2 regulate phosphorylation-dependent NICD1 turnover and the periodicity of the segmentation clock

All vertebrates share a segmented body axis. Segments form periodically from the rostral end of the presomitic mesoderm (PSM) and this periodicity is regulated by the segmentation clock, a molecular oscillator that drives dynamic clock gene expression across the PSM with a periodicity that matches somite formation. Notch signalling is crucial to this process. Altering Notch intracellular domain (NICD) stability affects both the clock period and somite size. However, the mechanistic details of how NICD stability is regulated are unclear.\n\nWe identified a highly conserved site crucial for NICD recognition by the SCF E3 ligase, which targets NICD for degradation. We demonstrate both CDK1 and CDK2 can phosphorylate NICD in the domain where this crucial residue lies and that NICD levels vary in a cell cycle-dependent manner. Inhibiting CDK1 or CDK2 activity increases NICD levels both in vitro and in vivo, leading to a delay of clock gene oscillations.

developmental biology↗

bioRxiv2017

Phylostratigraphic analysis of tumor and developmental transcriptomes reveals relationship between oncogenesis, phylogenesis and ontogenesis

The question of the existence of cancer is inadequately answered by invoking somatic mutations or the disruptions of cellular and tissue control mechanisms. As such uniformly random events alone cannot account for the almost inevitable occurrence of an extremely complex process such as cancer. In the different epistemic realm, an ultimate explanation of cancer is that cancer is a reversion of a cell to an ancestral pre-Metazoan state, i.e. a cellular form of atavism. Several studies have suggested that genes involved in cancer have evolved at particular evolutionary time linked to the unicellular-multicellular transition. Here we used a refined phylostratigraphic analysis of evolutionary ages of the known genes/pathways associated with cancer and the genes differentially expressed between normal and cancer tissue as well as between embryonic and mature (differentiated) cells. We found that cancer-specific transcriptomes and cancer-related pathways were enriched for genes that evolved in the pre-Metazoan era and depleted of genes that evolved in the post-Metazoan era. By contrast an opposite relation was found for cell maturation: the age distribution frequency of the genes expressed in differentiated epithelial cells were enriched for post-Metazoan genes and depleted of pre-Metazoan ones. These findings support the atavism theory that cancer cells manifest the reactivation of an ancient ancestral state featuring unicellular modalities. Thus our bioinformatics analyses suggest that not only does oncogenesis recapitulate ontogenesis, and ontogenesis recapitulates phylogenesis, but also oncogenesis recapitulates phylogenesis. This more encompassing perspective may offer a natural organizing framework for genetic alterations in cancers and point to new treatment options that target the genes controlling the atavism transition.\n\nOne Sentence SummaryTracing cancer gene evolutionary ages revealed that cancer reverts to a pre-existing early Metazoan state.

cancer biology↗

bioRxiv2016

A modification-specific peptide-based immunization approach using CRM197 carrier protein: Development of a selective vaccine against pyroglutamate Aβ peptides

Strategies aimed at reducing cerebral accumulation of the amyloid-{beta} (A{beta}) peptides have therapeutic potential in Alzheimers disease (AD). A{beta} immunization has proven to be effective at promoting A{beta} clearance in animal models but adverse effects have hampered its clinical evaluation. The first anti-A{beta} immunization clinical trial, which assessed a full-length A{beta}1-42 vaccine, increased the risk of encephalitis most likely because of autoimmune pro-inflammatory T helper 1 (Th1) response against all forms of A{beta}. Immunization against less abundant but potentially more pathologically relevant A{beta} products, such as N-terminally-truncated pyroglutamate-3 A{beta} (A{beta}pE3), could provide efficacy and improve tolerability in A{beta} immunotherapy. Here, we describe a selective vaccine against A{beta}pE3 using the diphtheria toxin mutant CRM197 as carrier protein for epitope presentation. CRM197 is currently used in licensed vaccines and has demonstrated excellent immunogenicity and safety in humans. In mice, our A{beta}pE3:CRM197 vaccine triggered the production of specific anti-A{beta}pE3 antibodies that did not cross-react with A{beta}1-42, non-cyclized A{beta}E3, or N-terminally-truncated pyroglutamate-11 A{beta} (A{beta}pE11). A{beta}pE3:CRM197 antiserum strongly labeled A{beta}pE3 in insoluble protein extracts and decorated cortical amyloid plaques in human AD brains. Anti-A{beta}pE3 antibodies were almost exclusively of the IgG1 isotype, suggesting an anti-inflammatory Th2 response bias to the A{beta}pE3:CRM197 vaccine. To the best of our knowledge, this study shows for the first time that CRM197 has potential as a safe and suitable vaccine carrier for active and selective immunization against specific protein sequence modifications or conformations, such as A{beta}pE3.

neuroscience↗