Impact from the deep.
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Biological Evolution↗
Biomedical subjects
Peter D Ward
Publications and source records attributed to Peter D Ward.
Climbing a triassic Mount Everest: into thinner air.
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Altitude↗
Hypoxia, global warming, and terrestrial late Permian extinctions.
A catastrophic extinction occurred at the end of the Permian Period. However, baseline extinction rates appear to have been elevated even before the final catastrophe, suggesting sustained environmental degradation. For terrestrial vertebrates during the Late Permian, the combination of a drop in atmospheric oxygen plus climate warming would have induced hypoxic stress and consequently compressed altitudinal ranges to near sea level. Our simulations suggest that the magnitude of altitudinal compression would have forced extinctions by reducing habitat diversity, fragmenting and isolating populations, and inducing a species-area effect. It also might have delayed ecosystem recovery after the mass extinction.
Altitude↗
Abrupt and gradual extinction among Late Permian land vertebrates in the Karoo basin, South Africa.
The Karoo basin of South Africa exposes a succession of Upper Permian to Lower Triassic terrestrial strata containing abundant terrestrial vertebrate fossils. Paleomagnetic/magnetostratigraphic and carbon-isotope data allow sections to be correlated across the basin. With this stratigraphy, the vertebrate fossil data show a gradual extinction in the Upper Permian punctuated by an enhanced extinction pulse at the Permian-Triassic boundary interval, particularly among the dicynodont therapsids, coinciding with negative carbon-isotope anomalies.
Animals↗
Role of phospholipase C-beta in the modulation of epithelial tight junction permeability.
The results presented in this study establish an association between phospholipase C-beta (PLC-beta) and tight junction permeability across Madin-Darby canine kidney (MDCK) cell monolayers, an in vitro model for epithelial tissue. These results further show that PLC-beta modulates tight junction permeability by affecting actin filament organization. Hexadecylphosphocholine (HPC) inhibited PLC-beta and increased tight junction permeability in MDCK cells. Interestingly, the analogs of HPC, a series of alkylphosphocholines containing various lengths of linear alkyl chains, inhibited PLC-beta and increased tight junction permeability with a wide range of potency. The potency of alkylphosphocholines as enhancers of tight junction permeability significantly correlated (p < 0.05) with their potency as PLC-beta inhibitors. U73122, a steroid derivative that is structurally unrelated to alkylphosphocholines, inhibited PLC-beta and increased tight junction permeability with potencies that fit into the correlation observed for the alkylphosphocholine series. U73122 and HPC induced disorganization of actin filaments in MDCK cell monolayers. The potencies to cause disorganization of actin filaments were consistent with the potencies of these agents as inhibitors of PLC-beta and enhancers of tight junction permeability. Furthermore, ATP, an activator of PLC-beta, attenuated U73122-induced increase in tight junction permeability as well as disorganization of actin filaments. These results provide strong evidence that PLC-beta inhibition leads to increased tight junction permeability across MDCK cell monolayers through disorganization of actin filaments.
Animals↗
Phospholipase C-gamma modulates epithelial tight junction permeability through hyperphosphorylation of tight junction proteins.
Phospholipase C-gamma (PLC-gamma) is stimulated by epidermal growth factor via activation of the epidermal growth factor receptors. The PLC inhibitor, 3-nitrocoumarin (3-NC), selectively inhibited PLC-gamma in Madin-Darby canine kidney cells without affecting the activity of PLC-beta. In contrast, inhibitors of PLC-beta, hexadecylphosphocholine and, had no effect on the activity of PLC-gamma. Inhibition of PLC-gamma by 3-NC was associated with an increase in tight junction permeability across Madin-Darby canine kidney cell monolayers, as evidenced by 3-NC-induced decrease in transepithelial electrical resistance and increase in mannitol flux over a concentration range that was inhibitory to PLC-gamma. An analog of 3-NC, 7-hydroxy-3-NC (7-OH-3-NC), which was inactive as an inhibitor of PLC-gamma, also had no effect on tight junction permeability. Treatment with 3-NC caused punctate disruption in the cortical actin filaments. The PLC-gamma inhibitor, 3-NC, but not the inactive analog, 7-OH-3-NC, caused hyperphosphorylation of the tight junction proteins, occludin, ZO-1, and ZO-2. The serine/threonine kinase inhibitor, staurosporine (50-200 nm), significantly attenuated 3-NC-induced hyperphosphorylation of ZO-2. This corresponded with attenuation by staurosporine of 3-NC-induced increase in tight junction permeability, suggesting a relationship between ZO-2 phosphorylation and tight junction permeability.
Actins↗