Bioinformatics of Cellular Complex and Chromosomal Synteny

2020 ◽  
pp. 437-505
2019 ◽  
Vol 218 (2) ◽  
pp. 644-663 ◽  
Author(s):  
Lei Liu ◽  
Li Ding ◽  
Matteo Rovere ◽  
Michael S. Wolfe ◽  
Dennis J. Selkoe

Intramembrane proteolysis of transmembrane substrates by the presenilin–γ-secretase complex is preceded and regulated by shedding of the substrate’s ectodomain by α- or β-secretase. We asked whether β- and γ-secretases interact to mediate efficient sequential processing of APP, generating the amyloid β (Aβ) peptides that initiate Alzheimer’s disease. We describe a hitherto unrecognized multiprotease complex containing active β- and γ-secretases. BACE1 coimmunoprecipitated and cofractionated with γ-secretase in cultured cells and in mouse and human brain. An endogenous high molecular weight (HMW) complex (∼5 MD) containing β- and γ-secretases and holo-APP was catalytically active in vitro and generated a full array of Aβ peptides, with physiological Aβ42/40 ratios. The isolated complex responded properly to γ-secretase modulators. Alzheimer’s-causing mutations in presenilin altered the Aβ42/40 peptide ratio generated by the HMW β/γ-secretase complex indistinguishably from that observed in whole cells. Thus, Aβ is generated from holo-APP by a BACE1–γ-secretase complex that provides sequential, efficient RIP processing of full-length substrates to final products.


2008 ◽  
Vol 18 (05) ◽  
pp. 739-757 ◽  
Author(s):  
SNORRE H. CHRISTIANSEN

Given a cellular complex, we construct spaces of differential forms which form a complex under the exterior derivative, which is isomorphic to the cochain complex of the cellular complex. The construction applies in particular to subsets of Euclidean space divided into polyhedra, for which it provides, for each k, a space of k-forms with a basis indexed by the set of k-dimensional cells. In the framework of mimetic finite differences, the construction provides a conforming reconstruction operator. The construction requires auxiliary spaces of differential forms on each cell, for which we provide two examples. When the cells are simplexes, the construction can be used to recover the standard mixed finite element spaces also called Whitney forms. We can also recover the dual finite elements previously constructed by A. Buffa and the author on the barycentric refinement of a two-dimensional mesh.


1909 ◽  
Vol XVI (1) ◽  
pp. 132-183
Author(s):  
M. A. Chalusov

Role n. depressoris in the regulation of blood pressure was elucidated by the works of Ludwig and Suon and the work is on an unshakable basis, but the relationship of depressors to that central cellular complex in the brain, which they are connected to, is unclear and insufficiently justified by them, therefore, the work clarification of these relations should be recognized as worthy of attention.


2003 ◽  
Vol 50 (3) ◽  
pp. 735-742 ◽  
Author(s):  
Erik Fries ◽  
Aneta Kaczmarczyk

Inter-alpha-inhibitor is an abundant plasma protein whose physiological function is only now beginning to be revealed. It consists of three polypeptides: two heavy chains and one light chain called bikunin. Bikunin, which has antiproteolytic activity, carries a chondroitin sulphate chain to which the heavy chains are covalently linked. The heavy chains can be transferred from inter-alpha-inhibitor to hyaluronan molecules and become covalently linked. This reaction seems to be mediated by TSG-6, a protein secreted by various cells upon stimulation by inflammatory cytokines. Inter-alpha-inhibitor has been shown to be required for the stabilization of the cumulus cell-oocyte complex during the expansion that occurs prior to ovulation. Hyaluronan-linked heavy chains in the extracellular matrix of this cellular complex have recently been shown to be tightly bound to TSG-6. Since TSG-6 binds to hyaluronan, its complex with heavy chains could stabilize the extracellular matrix by cross-linking hyaluronan molecules. Heavy chains linked to hyaluronan molecules have also been found in inflamed tissues. The physiological role of these complexes is not known but there are indications that they might protect hyaluronan against fragmentation by reactive oxygen species. TSG-6 also binds to bikunin thereby enhancing its antiplasmin activity. Taken together, these results suggest that inter-alpha-inhibitor is an anti-inflammatory agent which is activated by TSG-6.


1993 ◽  
Vol 47 (1) ◽  
pp. 145-148 ◽  
Author(s):  
A.N. Dranišnikov ◽  
D. Repovš

We give 8 short proof of the classical Stallings theorem that every finite n-dimensional cellular complex embeds up to homotopy in the 2n-dimensional Euclidean space. As an application we solve a problem of M. Kreck.


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