Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation

We have generated lines of transgenic mice that express a mutant prion protein (PrP) containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia. These mice develop a neurological illness with prominent ataxia at 65 or 240 days of age, depending on whether the transgene array is, respectively, homozygous or hemizygous. Starting from birth, mutant PrP is converted into a protease-resistant and detergent-insoluble form that resembles the scrapie isoform of PrP, and this form accumulates dramatically in many brain regions throughout the lifetime of the mice. As PrP accumulates, there is massive apoptosis of granule cells in the cerebellum. Our analysis provides important insights into the molecular pathogenesis of inherited prion disorders in humans.

Abrogation of disease development in plants expressing animal antiapoptotic genes

An emerging topic in plant biology is whether plants display analogous elements of mammalian programmed cell death during development and defense against pathogen attack. In many plant–pathogen interactions, plant cell death occurs in both susceptible and resistant host responses. For example, specific recognition responses in plants trigger formation of the hypersensitive response and activation of host defense mechanisms, resulting in restriction of pathogen growth and disease development. Several studies indicate that cell death during hypersensitive response involves activation of a plant-encoded pathway for cell death. Many susceptible interactions also result in host cell death, although it is not clear how or if the host participates in this response. We have generated transgenic tobacco plants to express animal genes that negatively regulate apoptosis. Plants expressing human Bcl-2 and Bcl-xl, nematode CED-9, or baculovirus Op-IAP transgenes conferred heritable resistance to several necrotrophic fungal pathogens, suggesting that disease development required host–cell death pathways. In addition, the transgenic tobacco plants displayed resistance to a necrogenic virus. Transgenic tobacco harboring Bcl-xl with a loss-of-function mutation did not protect against pathogen challenge. We also show that discrete DNA fragmentation (laddering) occurred in susceptible tobacco during fungal infection, but does not occur in transgenic-resistant plants. Our data indicate that in compatible plant–pathogen interactions apoptosis-like programmed cell death occurs. Further, these animal antiapoptotic genes function in plants and should be useful to delineate resistance pathways. These genes also have the potential to generate effective disease resistance in economically important crops.

Ediacaran biota from Sonora, Mexico.

The Ediacaran biota is the earliest diverse community of macroscopic animals and protoctists. Body and trace fossils in the Clemente Formation of northwestern Sonora extend downward the geologic range of Ediacaran forms. Taxa present in the Clemente Formation include cf. Cyclomedusa plana, Sekwia sp., an erniettid (bearing an air mattress-like "pneu" body construction), and the trace fossils Lockeia ichnosp. and Palaeophycus tubularis. The trace fossils confirm the presence of sediment-dwelling animals in this shallow marine community. The body fossils are headless, tailless, and appendageless. Some may be body fossils of animals but others may be fossils of large protoctists. These body and trace fossils, recovered from thinly bedded sandstones and siltstones, occur 75 meters lower in the Sonoran stratigraphic section than a distinctive Clemente Formation oolite. The stratigraphic position of the fossils below this oolite permits long-distance correlation between fossiliferous Proterozoic strata of Mexico and the United States. Correlations utilizing both the Clemente Formation oolite and a trace fossil (Vermiforma antiqua) confirm the antiquity (600 million years or more) of this body fossil-rich community of macroscopic eukaryotes. The recently discovered body fossils are the oldest known remains of the Ediacaran biota.