Search results for " ACTIVATION"
showing 10 items of 1535 documents
Regulation of the alpha-secretase ADAM10 by its prodomain and proprotein convertases.
2001
SPECIFIC AIMSTo identify the proprotein convertases responsible for maturation of the α-secretase ADAM10, we investigated the influence of PC7 and furin on ADAM10 processing and the resulting effect on amyloid precursor protein cleavage. We also examined the functional role of the ADAM10 prodomain by coexpression of a prodomain-deleted ADAM10 mutant together with its prodomain in trans.PRINCIPAL FINDINGS1. ADAM10 is proteolytically processed by PC7 and furinThe disintegrin metalloproteinase ADAM10 possesses α-secretase activity as well as a potential proprotein convertase recognition sequence (RKKR) after its prodomain. By amino-terminal sequencing of ADAM10 purified from bovine kidney plas…
Sea urchin deciliation induces thermoresistance and activates the p38 mitogen-activated protein kinase pathway.
2003
In this study, we demonstrate by a variety of approaches (ie, morphological analysis, Western blots, immunolocalization, and the use of specific antibodies) that hyperosmotic deciliation stress of sea urchin embryos induces a thermotolerant response. Deciliation is also able to activate a phosphorylation signaling cascade the effector of which might be the p38 stress-activated protein kinase because we found that the administration of the p38 inhibitor SB203580 to sea urchin deciliated gastrula embryos makes the hyperosmotic deciliation stress lethal.
Arene C‐H activation at aluminium(I) : meta selectivity driven by the electronics of SNAr chemistry
2020
The reactivity of the electron-rich anionic Al(I) (‘aluminyl’) compound K 2 [(NON)Al] 2 (NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di- tert -butyl-9,9-dimethylxanthene) towards mono- and disubstituted arenes is reported. C-H activation chemistry with n -butylbenzene gives exclusively the product of activation at the arene meta position. Mechanistically, this transformation proceeds in a single step via a concerted Meisenheimer-type transition state. Selectivity is therefore based on similar electronic factors to classical S N Ar chemistry, which implies the destabilization of transition states featuring electron-donating groups in either the ortho or the para positions. In the cases of tolu…
Memory degradation induced by attention in recurrent neural architectures
2022
This paper studies the memory mechanisms in recurrent neural architectures when attention models are included. Pure-attention models like Transformers are more and more popular as they tend to outperform models with recurrent connections in many different tasks. Our conjecture is that attention prevents the recurrent connections from transferring information properly between consecutive next steps. This conjecture is empirically tested using five different models, namely, a model without attention, a standard Loung attention model, a standard Bahdanau attention model, and our proposal to add attention to the inputs in order to fill the gap between recurrent and parallel architectures (for b…
Alpha-secretase activation--an approach to Alzheimer's disease therapy.
2006
The nonamyloidogenic pathway of processing the amyloid precursor protein (APP) involves the cleavage within the amyloid-beta peptide sequence, and thus precludes amyloid-beta formation. The identification of a member of the disintegrin and metalloproteinase family, ADAM10, as an alpha-secretase that prevents plaque formation and hippocampal deficits in vivo gave us the possibility to examine the alpha-secretase as a potential target for the therapy of Alzheimer's disease. Within the priority program Cellular Mechanisms of Alzheimer's Disease, we investigated several approaches to stimulate the alpha-secretase pathway. Two protein convertases were found to be responsible for the removal of t…
Early implant healing: promotion of platelet activation and cytokine release by topographical, chemical and biomimetical titanium surface modificatio…
2011
Abstract Objectives: Platelet releasate has been shown to promote osteogenetic cell proliferation and differentiation. Topography and chemistry of biomaterials have high impact on platelet activation. More specifically, the bioactive cell adhesive peptide sequence Arg–Gly–Asp (RGD) triggers platelet activation mediated by the αIIbβ3 integrin receptor. Accordingly, topographical, chemical and biomimetical (immobilized RGD peptide) modifications of titanium (Ti) surfaces may enhance early platelet activation and bony healing of implants. Therefore, the aim of the study was to evaluate platelet activation with subsequent platelet-derived cytokine release by accordingly modified Ti surfaces. Ma…
Onset of DNA synthesis in experimentally activated ascidian eggs
1994
DNA synthesis was studied autoradiographically in unfertilized ascidian eggs (Ascidia malaca and Ciona intestinalis) that had been artificially activated by a K+-free external medium or a Ca-ionophore. Naked eggs of A. malaca were incubated in K+-free seawater that contained [3H]-thymidine for 30 min, and naked eggs of C. intestinalis were incubated in seawater supplemented with a Ca-ionophore and [3H]-thymidine for 15 min. The observations revealed limited activation in eggs treated with K+-free seawater. Activation consisted of surface modifications and the onset of DNA synthesis. Incorporation of [3H]-thymidine was detected in female nuclei of treated eggs which had not ejected their pol…
Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cel…
2012
Summary Although allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoi…
Mechanistic Studies on the Metal-Free Activation of Dihydrogen by Antiaromatic Pentarylboroles
2013
The perfluoro- and perprotiopentaphenylboroles 1 and 2 react with dihydrogen to effect H–H bond cleavage and formation of boracyclopentene products. The mechanism of this reaction has been studied experimentally through evaluation of the kinetic properties of the slower reaction between 2 and H2. The reaction is first-order in both [borole] and [H2] with activation parameters of ΔH⧧ = 34(8) kJ/mol and ΔS⧧ = −146(25) J mol–1 K–1. A minimal kinetic isotope effect of 1.10(5) was observed, suggesting an asynchronous geometry for H–H cleavage in the rate-limiting transition state. To explain the stereochemistry of the observed products, a ring-opening/ring-closing mechanism is proposed and suppo…