Cytotoxicity of albebetin oligomers depends on cross-β-sheet formation

AbstractPrefibrillar cytotoxicity was suggested as a common amyloid characteristic. We showed two types of albebetin prefibrillar oligomers are formed during incubation at pH 7.3. Initial round-shaped oligomers consist of 10–15 molecules determined by atomic force microscopy, do not bind thioflavin-T and do not affect viability of granular neurons and SH-SY5Y cells. They are converted into ca. 30–40-mers possessing cross-β-sheet and reducing viability of neuronal cells. Neither monomers nor fibrils possess cytotoxicity. We suggest that oligomeric size is important for stabilising cross-β-sheet core critical for cytotoxicity. As albebetin was used as a carrier-protein for drug delivery, examination of amyloidogenicity is required prior polypeptide biomedical applications

Cs7Sm11[TeO3]12Cl16 and Rb7Nd11[TeO3]12Br16, the new tellurite halides of the tetragonal Rb6LiNd11[SeO3]12Cl16 structure type

The authors thank the Russian Foundation for Basic Researches for the support of this work under Grants No. 14-03-00604_a and 12-03-92604-KO_a. The X-ray study of compound II was made possible due to M.V. Lomonosov Moscow State University Programm of Development. PL thanks the University of St Andrews and EPSRC for DTA Studentships to CB and LJD.Two new rare-earth – alkali – tellurium oxide halides were synthesized by a salt flux technique and characterized by single-crystal X-ray diffraction. The structures of the new compounds Cs7Sm11[TeO3]12Cl16 (I) and Rb7Nd11[TeO3]12Br16 (II) (both tetragonal, space group I4/mcm) correspond to the sequence of [MLn11(TeO3)12] and [M6×16] layers and bear very strong similarities to those of known selenite analogs. We discuss the trends in similarities and differences in compositions and structural details between the Se and Te compounds; more members of the family are predicted.PostprintPeer reviewe

Lynx1 and Aβ1–42 bind competitively to multiple nicotinic acetylcholine receptor subtypes

AbstractLynx1 regulates synaptic plasticity in the brain by regulating nicotinic acetylcholine receptors (nAChRs). It is not known to which extent Lynx1 can bind to endogenous nAChR subunits in the brain or how this interaction is affected by Alzheimer's disease pathology. We apply affinity purification to demonstrate that a water-soluble variant of human Lynx1 (Ws-Lynx1) isolates α3, α4, α5, α6, α7, β2, and β4 nAChR subunits from human and rat cortical extracts, and rat midbrain and olfactory bulb extracts, suggesting that Lynx1 forms complexes with multiple nAChR subtypes in the human and rodent brain. Incubation with Ws-Lynx1 decreases nicotine-mediated extracellular signal–regulated kinase phosphorylation in PC12 cells and striatal neurons, indicating that binding of Ws-Lynx1 is sufficient to inhibit signaling downstream of nAChRs. The effect of nicotine in PC12 cells is independent of α7 or α4β2 nAChRs, suggesting that Lynx1 can affect the function of native non-α7, non-α4β2 nAChR subtypes. We further show that Lynx1 and oligomeric β-amyloid1–42 compete for binding to several nAChR subunits, that Ws-Lynx1 prevents β-amyloid1–42–induced cytotoxicity in cortical neurons, and that cortical Lynx1 levels are decreased in a transgenic mouse model with concomitant β-amyloid and tau pathology. Our data suggest that Lynx1 binds to multiple nAChR subtypes in the brain and that this interaction might have functional and pathophysiological implications in relation to Alzheimer's disease

The Concept of the "Field" in Early Soviet Ethnography : A Northern Perspective

Peer reviewedPublisher PD

THE INTERMEDIATE STATE OF THE PROTEIN MOLECULES IN OBTAINING THE ARTIFICIAL PROTEINS

Detected and investigated has been the new state of the protein molecules - the state of the globule, and its model has been offered. It has been shown, that it is the kinetic intermediate state on the way of the protein coagulation. The artificial protein albebetin, to be constructed for the preset spatial structure, not observed in the nature proteins, has been obtained. To analyze it, the new methods, allowing to evaluate the commonstructural characteristics of the protein has been used, utilizing the nanogram quantities of the material, worked in the acellular system of tranlation. It has been shown, that albebetin possesses the secondary structure near to the preset one and compact, ralatively stable spatial structure, not opposing to the preset one.Available from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

Abstract

An internet traffic caching system based on a Zipf-like distribution (ZBS) is invented. New system construction consists of three parts: a kernel for storing popular documents, an accessory part for unpopular documents and a management part for keeping requests ’ statistic. A documents replacement algorithm based on a metric function that uses Zipf-like distribution is a part of the new ZBS system. Key words: elements of cache construction, replacement algorithm based on Zipf-like distribution, document lifetime