Robert Frederickson

β-Amyloid of Alzheimer's Disease Induces Reactive Gliosis That Inhibits Axonal Outgrowth

Pathological lesions in the brains of patients with Alzheimers disease (AD) are characterized by dense deposits of the protein beta-amyloid. The link between the deposition of beta-amyloid in senile plaques and AD-associated pathology is, at present, controversial since there have been conflicting reports on whether the 39-43 amino acid beta-amyloid sequence is toxic or trophic to neurons. In this report, we show that beta-amyloid peptide when presented as an insoluble substrate which mimics its conformation in vivo can induce cortical glial cells in vitro and in vivo to locally deposit chondroitin sulfate containing proteoglycan. In vitro the proteoglycan-containing matrix deposited by glia on beta-amyloid blocks the usual ability of the peptide to allow cortical neurons to adhere and grow. Chondroitin sulfate-containing proteoglycan was also found in senile plaques of human AD tissue. We suggest that an additional effect of beta-amyloid in the brain, which compounds the direct effects of beta-amyloid on neurons, is mediated by the stimulation of astroglia to become reactive. Once in the reactive state, glial cells deposit large amounts of growth-inhibitory molecules within the neuropil which could impair neuronal process survival and regeneration leading to neurite retraction and/or dystrophy around senile plaques in AD.

Artificial antigen presenting cells

When introducing foreign genes into plants, scientists must also introduce a resistance gene to herbicide or antibiotics—this allows the cells with the incorporated transgenes to be regenerated on selectable media. However, while it has not ben demonstrated that marker genes can “escape” to weedy relatives or gut bacteria, their safety has nonetheless become a flash point in the debate over safety of GM foods. Since marker genes are only needed during the plant transformation process, it should be possible to remove marker genes from crops after the transgenic material has been selected, which would improve the public acceptance of genetically engineered crops. On page 442, Meyer and colleagues describe a vector that mediates deletion of marker genes from transgenic tobacco. They placed the marker gene, which confers resistance to kanamycin, between bacteriophage lambda sequences called Attachment P regions, which mediate intrachromosomal recombination. They also included a gene called tms2, which inhibits growth in the presence of certain hormones, and therefore can be used to select transformants in which the marker gene was deleted through intrachromosomal recombination. In and out

Human stem cells become more established

When introducing foreign genes into plants, scientists must also introduce a resistance gene to herbicide or antibiotics—this allows the cells with the incorporated transgenes to be regenerated on selectable media. However, while it has not ben demonstrated that marker genes can “escape” to weedy relatives or gut bacteria, their safety has nonetheless become a flash point in the debate over safety of GM foods. Since marker genes are only needed during the plant transformation process, it should be possible to remove marker genes from crops after the transgenic material has been selected, which would improve the public acceptance of genetically engineered crops. On page 442, Meyer and colleagues describe a vector that mediates deletion of marker genes from transgenic tobacco. They placed the marker gene, which confers resistance to kanamycin, between bacteriophage lambda sequences called Attachment P regions, which mediate intrachromosomal recombination. They also included a gene called tms2, which inhibits growth in the presence of certain hormones, and therefore can be used to select transformants in which the marker gene was deleted through intrachromosomal recombination. In and out

Protein production in ciliates

One of the more elusive goals of bioremediation has been finding organisms that can destroy the high levels of explosives found in soils around munitions sites. Certain microbes can denitrify nitrate explosives in the lab, but have failed to thrive on sites. To get around this problem, Bruce and colleagues transferred this degradative ability from microbe to plants, which are more easily harvested and sustained in the field (pp. 491 and 491). They engineered tobacco plants that express pentaerythritol tetranitrate reductase, a microbial enzyme capable of removing nitrates from TNT and GTN. The transgenic plants can withstand exposure to higher levels of explosives and break them down into harmless components.

Test run for kidney replacement

One of the more elusive goals of bioremediation has been finding organisms that can destroy the high levels of explosives found in soils around munitions sites. Certain microbes can denitrify nitrate explosives in the lab, but have failed to thrive on sites. To get around this problem, Bruce and colleagues transferred this degradative ability from microbe to plants, which are more easily harvested and sustained in the field (pp. 491 and 491). They engineered tobacco plants that express pentaerythritol tetranitrate reductase, a microbial enzyme capable of removing nitrates from TNT and GTN. The transgenic plants can withstand exposure to higher levels of explosives and break them down into harmless components.

Chemical genetics and tissue engineering

expressing transgenes in chloroplast genomes (transplastomics) is viewed as a way of preventing the transgenes’ spread to weedy relatives. Now on page 333, Staub et al. show that human somatotropin, a therapeutic protein used to treat disorders such as hypopituitary dwarfism and HIV wasting syndrome, can be produced at high levels and in an active form in tobacco chloroplasts. Given that there are no known plastid-encoded proteins that contain disulfide bonds, it was particularly encouraging that the recombinant somatotropin was appropriately disulfide bonded.

Delivering PNAs to the nucleus

expressing transgenes in chloroplast genomes (transplastomics) is viewed as a way of preventing the transgenes’ spread to weedy relatives. Now on page 333, Staub et al. show that human somatotropin, a therapeutic protein used to treat disorders such as hypopituitary dwarfism and HIV wasting syndrome, can be produced at high levels and in an active form in tobacco chloroplasts. Given that there are no known plastid-encoded proteins that contain disulfide bonds, it was particularly encouraging that the recombinant somatotropin was appropriately disulfide bonded.

Sampling kinases in single cells

expressing transgenes in chloroplast genomes (transplastomics) is viewed as a way of preventing the transgenes’ spread to weedy relatives. Now on page 333, Staub et al. show that human somatotropin, a therapeutic protein used to treat disorders such as hypopituitary dwarfism and HIV wasting syndrome, can be produced at high levels and in an active form in tobacco chloroplasts. Given that there are no known plastid-encoded proteins that contain disulfide bonds, it was particularly encouraging that the recombinant somatotropin was appropriately disulfide bonded.

Cryopreservation by vitrification

expressing transgenes in chloroplast genomes (transplastomics) is viewed as a way of preventing the transgenes’ spread to weedy relatives. Now on page 333, Staub et al. show that human somatotropin, a therapeutic protein used to treat disorders such as hypopituitary dwarfism and HIV wasting syndrome, can be produced at high levels and in an active form in tobacco chloroplasts. Given that there are no known plastid-encoded proteins that contain disulfide bonds, it was particularly encouraging that the recombinant somatotropin was appropriately disulfide bonded.

A “cool” new system for gene expression

When introducing foreign genes into plants, scientists must also introduce a resistance gene to herbicide or antibiotics—this allows the cells with the incorporated transgenes to be regenerated on selectable media. However, while it has not ben demonstrated that marker genes can “escape” to weedy relatives or gut bacteria, their safety has nonetheless become a flash point in the debate over safety of GM foods. Since marker genes are only needed during the plant transformation process, it should be possible to remove marker genes from crops after the transgenic material has been selected, which would improve the public acceptance of genetically engineered crops. On page 442, Meyer and colleagues describe a vector that mediates deletion of marker genes from transgenic tobacco. They placed the marker gene, which confers resistance to kanamycin, between bacteriophage lambda sequences called Attachment P regions, which mediate intrachromosomal recombination. They also included a gene called tms2, which inhibits growth in the presence of certain hormones, and therefore can be used to select transformants in which the marker gene was deleted through intrachromosomal recombination. In and out