Search results for "Activation"

Advances in immunopathogenesis of macrophage activation syndrome during rheumatic inflammatory diseases: toward new therapeutic targets?

2017

Introduction: Macrophage activation syndrome (MAS) is a severe, hyperinflammatory life-threatening syndrome, generally complicating different rheumatic diseases. Despite the severity of the disease, little is known about the pathogenic mechanisms and, thus, possible targeted therapies in the management of these patients. Areas covered: In this review, we aimed to update the current pathogenic knowledge of MAS, during rheumatic diseases, focusing mainly on immunologic abnormalities and on new possible therapeutic strategies. Expert commentary: The difficult pathogenic scenario of MAS, in which genetic defects, predisposing diseases, and triggers are mixed together with the high mortality rat…

Semiconductor-photocatalyzed sulfoxidation of alkanes.

2008

Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine

2010

Ligands containing bulky aliphatic P1 residues exhibit a high affinity towards cytosolic leucine aminopeptidase, a bizinc protease of biomedical significance. According to this specificity, a series of phosphonic and phosphinic compounds have been put forward as novel putative inhibitors of the enzyme. These phosphonic and phosphinic compounds were derivatives of methionine and norleucine as both single amino acids and dipeptides. The designed inhibitors were synthesised and tested towards the peptidase isolated from porcine kidneys using an improved separation procedure affording superior homogeneity. Unexpectedly, organophosphorus derivatives of methionine and norleucine exhibited moderat…

Molecular mechanisms of primary and secondary mucosal immunity using avian infectious bronchitis virus as a model system

2007

Although mucosal immune responses are critical for protection of hosts from clinical illness and even mortality caused by mucosal pathogens, the molecular mechanism of mucosal immunity, which is independent of systemic immunity, remains elusive. To explore the mechanistic basis of mucosal protective immunity, gene transcriptional profiling in mucosal tissues was evaluated after the primary and secondary immunization of animals with an attenuated avian infectious bronchitis virus (IBV), a prototype of Coronavirus and a well-characterized mucosal pathogen. Results showed that a number of innate immune factors including toll-like receptors (TLRs), retinoic-acid-inducible gene-1 (RIG-1), type I…

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…

Neural contribution to postactivation potentiation

2015

The current study was designed to investigate the contribution of neural factors to postactivation potentiation (PAP). Neuromuscular function (i.e. twitches, H-reflexes, motor evoked potentials, and voluntary isometric ballistic contractions) of 8 power-trained (POW) and 8 endurance-trained (END) athletes was recorded before and after a 8-second maximal isometric conditioning contraction (CC) to induce PAP, to elucidate discriminating neural factors in exploiting PAP that might arise from the former training background compared to the latter. After CC, twitch peak force and rate of force development were significantly increased, with higher potentiation in POW (29 ± 11% and 64 ± 24%) than E…

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…