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A versatile prion replication assay in organotypic brain slices




Methods enabling prion replication ex vivo are important for advancing prion studies. However, few such technologies exist, and many prion strains are not amenable to them. Here we describe a prion organotypic slice culture assay (POSCA) that allows prion amplification and titration ex vivo under conditions that closely resemble intracerebral infection. Thirty-five days after contact with prions, mouse cerebellar slices had amplified the abnormal isoform of prion protein, PrPSc, >105-fold. This is quantitatively similar to amplification in vivo, but fivefold faster. PrPSc accumulated predominantly in the molecular layer, as in infected mice. The POSCA detected replication of prion strains from disparate sources, including bovines and ovines, with variable detection efficiency. Pharmacogenetic ablation of microglia from POSCA slices led to a 15-fold increase in prion titers and PrPSc concentrations over those in microglia-containing slices, as well as an increase in susceptibility to infection. This suggests that the extensive microglial activation accompanying prion diseases represents an efficacious defensive reaction.


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A Plague of Rats Isnt Worth Some Ink? Bangladesh Is in Crisis

Spent much time thinking about Bangladesh lately? If the answer is no, don't worry — I was in the same boat, so to speak, until I saw these pictures.

Earlier this month, crushing rains left 20 people dead and over 20,000 stranded when overwhelming rainfall left five feet of standing water in the low-lying areas. This is on top of already taxed landscapes that flooded when melting Himalayan glaciers burst the 200 rivers that web across the country last year. Bangladesh under water is seeming like a real and permanent possibility.

The International Panel on Climate Change (IPCC) — whose claims are usually conservative — said that Bangladesh is heading to lose 17 percent of its land and 30 percent of its food production by 2050. That's like California and New York drowning, and the whole Midwest ceasing production of food.


If this happens, more than 20 million Bangladeshis will be without a patch of land to stand on. Though hardship in the country isn't entirely recent: since 1971, Bangladesh has endured over 200 disasters that have left a total of 500,000 dead and affected a total of 500 million people.

And I haven't even said anything about the plague of rats that's consuming all of their food. A plague of rats. I wish, wish there was more room for stories like this in the general consciousness — shouldn't we be hearing about this every night? Not to dwell on the gloomy, but just knowing about this makes the answer to this question pretty clear to me.

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