Transmissible and genetic prion diseases share a common pathway of neurodegeneration

Prion diseases can be infectious, sporadic and genetic. The infectious forms of these diseases, including bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, are usually characterized by the accumulation in the brain of the transmissible pathogen, an abnormally folded isoform of the prion protein (PrP) termed PrPSc. However, certain inherited PrP mutations appear to cause neurodegeneration in the absence of PrPSc, working instead by favoured synthesis of CtmPrP, a transmembrane form of PrP. The relationship between the neurodegeneration seen in transmissible prion diseases involving PrPSc and that associated with ctmPrP has remained unclear. Here we find that the effectiveness of accumulated PrPSc in causing neurodegenerative disease depends upon the predilection of host-encoded PrP to be made in the ctmPrP form. Furthermore, the time course of PrPSc accumulation in transmissible prion disease is followed closely by increased generation of CtmPrP. Thus, the accumulation of PrPSc appears to modulate in trans the events involved in generating or metabolising CtmPrP. Together, these data suggest that the events of CtmPrP-mediated neurodegeneration may represent a common step in the pathogenesis of genetic and infectious prion diseases.     

The lipid composition of pigeon milk

Zusammenfassung Taubenmilch ist lipidhaltig und enthält zwei wesentliche Fettsäuren: Linol- und Linolensäure. Ein nicht identifizierter Faktor zusammen mit einer fett- und aminosäurehaltigen Diät ist imstande, auf Jungvögel wachstumfördernd zu wirken.     

Pigeon milk: A new source of growth factor

Crude, partially purified and purified fractions of pigeon milk injected subcutaneously in newborn mice brought about precocious opening of eyelids by 2–3 days and eruption of incisors by 3–4 days. The biological activity of pigeon milk-derived growth factor (PMGF) compared well with that of mouse epidermal growth factor (mEGF).     

The probable significance of the differential occurrence of protein in various castes of the termiteOdontotermes assmuthi (Isoptera: Termitidae)

Résumé L'évaluation de la somme de protéine contenue dans les représentants des diverses castes du termiteOdontotermes assmuthi donne les résultats suivants: 1. Les formes reproductrices potentielles, mâles et femelles, ont des quantités significatives (47,9 et 37%) que requirèrent leur activité reproductrice. 2. Les rois issus de mâles ailés n'atteignant leur pourcent maximum de protéine qu'à l'âge adulte. 3. Les reines en augmentent leur quantité (à 65,7%) en proportion de leur intense production d'ufs. 4. Les ouvriers et les soldats soumis à des tâches ardues contiennent beaucoup de protéine (33,5 et 44,5%).

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Acknowledgment. The authors are indebted to ProfessorC. J. George (C.S.I.R.) for his valuable guidance and thanks to ProfessorM. Appaswamy Rao, for the facilities provided.     

禁带区域内负的群速度

研究超声波经过两个烧结样品的行为.两个烧结样品为有序的面心立方结构,它们的结构几乎相同.研究表明:在两个有序的准均匀的介质中分别有一个禁带区域.就禁带区域而言,在两个样品中产生禁带的区域非常接近.同时在禁带出现的区域群速度为负值.我们的结果表明群速度的负值的确存在于有序介质中的禁带区域内.     

Mineral composition of pigeon milk

Summary Mineral analysis of pigeon milk indicates its major elements to be P>Ca>K>Na>Mg (in that order) and trace elements Fe>Zn>Mn>Cu. Whereas the levels of Ca, K, Mg, Na and Mn remain fairly constant in the first week, those of P, Fe, Zn and Cu fall significantly during this period. Compared to cow's and human milk, pigeon milk has definitely higher levels of trace elements. Similarly, the trace mineral content of pigeon milk exceeds that of pigeon egg albumen or yolk. Except for Fe, Mn and Cu, pigeon milk is richer than adult pigeon feed in its mineral content. The Ca:P ratio of pigeon milk increases from 0.3 to 1.1 in the first five days. It appears that the high trace mineral content of pigeon milk is one of the factors contributing to the phenomenal postnatal growth of squabs.     

The mechanism of membrane-associated steps in tail-anchored protein insertion

Tail-anchored (TA) membrane proteins destined for the endoplasmic reticulum are chaperoned by cytosolic targeting factors that deliver them to a membrane receptor for insertion. Although a basic framework for TA protein recognition is now emerging, the decisive targeting and membrane insertion steps are not understood. Here we reconstitute the TA protein insertion cycle with purified components, present crystal structures of key complexes between these components and perform mutational analyses based on the structures. We show that a committed targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is initially recruited to the membrane through an interaction with Get2. Once the targeting complex has been recruited, Get1 interacts with Get3 to drive TA protein release in an ATPase-dependent reaction. After releasing its TA protein cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP binding. This work provides a detailed structural and mechanistic framework for the minimal TA protein insertion cycle.     

The Eyes Absent proteins in development and disease

The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings.