Apoptosis is a mechanism of cell death operative in the normal development and regulation of vertebrate tissues and organ cellularity. During the postnatal development of the mouse cerebellum, extensive granule neuron apoptosis occurs that may regulate the final granule cell to Purkinje cell stoichiometry observed in the adult. Cerebellar granule cells are highly sensitive to genotoxic agents such as gamma-irradiation and methylazoxymethanol during the first 2 weeks of postnatal development. We demonstrate that ionizing radiation induces extensive cerebellar granule cell death via apoptosis in vivo. In p53 null mice, however, the cerebellar granule cells do not undergo apoptosis in response to gamma-irradiation. In mice heterozygous for the p53 allele, the granule cells apoptosis is delayed, indicating an intermediate response. The developmental apoptosis of cerebellar granule cells, however, occurs similarly in wild-type and p53 null mice. Therefore, neurons undergo p53-dependent and p53-independent apoptosis, depending upon the initiating stimulus that triggers DNA fragmentation. In contrast to x-ray damage, the extensive death of cerebellar granule cells induced by methylazoxymethanol was found to be independent of the DNA fragmentation characteristic of apoptosis, and was also independent of expression of p53. Ablation of neuron progenitor cells with genotoxic agents may occur by p53-dependent apoptosis or by p53-independent mechanisms not associated with DNA fragmentation.
SummaryThe tospoviruses are a diverse, cosmopolitan and economically important genus of plant viruses. In the recent past, interest in the tospoviruses has been rekindled with the resurgence and expansion of tomato spotted wilt virus and the appearance of new tospoviruses, including impatiens necrotic spot. This renewed interest in the tospoviruses, accompanied with the many recent advances in plant virology techniques, particularly those utilising molecular biology, have resulted in a rapid growth of our understanding of these viruses. This paper provides a review of the tospoviruses, encompassing all the major aspects of their biology, including the recent changes in the classification of the genus and current knowledge on molecular biology, vector relations, control and diagnosis.
We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, β of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 ± 1 J/cm(2). Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm(2) could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.
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