Correlation of structural elements and infectivity of the HET-s prion

Prions are believed to be infectious, self-propagating polymers of otherwise soluble, host-encoded proteins. This concept is now strongly supported by the recent findings that amyloid fibrils of recombinant prion proteins from yeast, Podospora anserina and mammals can induce prion phenotypes in the corresponding hosts. However, the structural basis of prion infectivity remains largely elusive because acquisition of atomic resolution structural properties of amyloid fibrils represents a largely unsolved technical challenge. HET-s, the prion protein of P. anserina, contains a carboxy-terminal prion domain comprising residues 218-289. Amyloid fibrils of HET-s(218-289) are necessary and sufficient for the induction and propagation of prion infectivity. Here, we have used fluorescence studies, quenched hydrogen exchange NMR and solid-state NMR to determine the sequence-specific positions of amyloid fibril secondary structure elements of HET-s(218-289). This approach revealed four beta-strands constituted by two pseudo-repeat sequences, each forming a beta-strand-turn-beta-strand motif. By using a structure-based mutagenesis approach, we show that this conformation is the functional and infectious entity of the HET-s prion. These results correlate distinct structural elements with prion infectivity.     

Liver esterase abnormalities in hereditary neurological diseases of mice

Zusammenfassung Alle von uns in Mäusen untersuchten vererblichen neurologischen Erkrankungen stellen entweder primäre oder sekundäre gesamtkörperliche Prozesse dar. Verschiedene allelische Substitutionen produzieren spezifische Leber-Esterase-Isozym-Defekte.

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This work was supported in part by NIH research grant No. NB 06448 from the National Institute of Neurological Diseases nad Stroke, a grant from the National Foundation for Neuromuscular Diseases, Inc., a grant from the Health Research Fund, United Fund of Schenectedy County, Inc., and an allocation from NIH General Research Support Grant No. RR 05545 from the Division of Research Resources to The Jackson Laboratory.

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The principles of laboratory animal care as promulgated by the National Society for Medical Research are observed in this Laboratory.     

Die Wirkung von Demecolceinamiden an Zellenin vitro

Summary A series of demecolceinamids was examinedin vitro on chicken fibroblasts, leucocytes, and different bacteria. It was found that with increasing length of the side chain on ring C the antimitotic activity is decreasing while the antibacterial effect is increasing.     

Reduction of body fat stores by inhibition of prolactin secretion

Summary Reductions of prolactin secretion by bromocriptine treatment for 24 days reduced fat stores (abdominal and epididymal fat depots) in hamsters by 25–49% compared with control animals. However, body weights and food consumption were not affected. These results further substantiate an important role for prolactin in regulation of fat metabolism and indicate that bromocriptine might be used to decrease fat stores.     

o-Allyloxy-phenoxy-propanolamine,eine neue Gruppe adrenergischer β-Rezeptoren-Blocker

Summary The synthesis of a new class of adrenergic-receptor blocking agents based upon ao-allyloxy-phenoxy-propanolamine structure is described. The structure activity relationships were studied, and the structural elements responsible for an optimal pharmacological effect are discussed.     

Apoptosis in development

Essential to the construction, maintenance and repair of tissues is the ability to induce suicide of supernumerary, misplaced or damaged cells with high specificity and efficiency. Study of three principal organisms--the nematode, fruitfly and mouse--indicate that cell suicide is implemented through the activation of an evolutionarily conserved molecular programme intrinsic to all metazoan cells. Dysfunctions in the regulation or execution of cell suicide are implicated in a wide range of developmental abnormalities and diseases.