2 documents found, page 1 of 1
A conformational switch controlling the toxicity of the prion protein
Frontzek, K; Bardelli, M; Senatore, A; Henzi, A; Reimann, RR; Bedir, S; Marino, M; Hussain, R; Jurt, S; Meisl, G; Pedotti, M; Mazzola, F; Siligardi, GPrion infections cause conformational changes of the cellular prion protein (PrPC) and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (‘H-latch’), altering the flexibility of the α2–α3 and β2–α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unabl...
The overlapping burden of the three leading causes of disability and death in s...
Reiner, RC; Welgan, CA; Troeger, CE; Baumann, MM; Weiss, DJ; Deshpande, A; Blacker, BF; Miller Petrie, MK; Earl, L; Bhatt, S; Abolhassani, HDespite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their com...