Search results for "Creta"

Chilamnestocoris mixtus gen. et spec. nov., the first burrower bug (Hemiptera: Pentatomoidea: Cydnidae) in Upper Cretaceous Burmese amber

2018

The beast burrowed, the fluid followed – Crustacean burrows as methane conduits

2015

Abstract An extensive pockmark field with associated methane-seep carbonates has recently been reported from the late Albian (Lower Cretaceous) Ubidepea Mudstone of the Black Flysch Group in the Basque Country, northern Spain, but the exact pathways of the migrating methane-rich fluids remained elusive. Here we provide petrographic, stable carbon and oxygen isotope evidence that abundant crustacean burrows in the surrounding mudstone, preserved as the trace fossil Thalassinoides, and the seep carbonates themselves have acted as long-lasting fluid conduits in this system. The Thalassinoides infill generations show a diagenetic parasequence often starting with a distinctive lining, followed b…

The origin and timing of multiphase cementation in carbonates: Impact of regional scale geodynamic events on the Middle Jurassic Limestones diagenesi…

2009

The Middle Jurassic carbonates of the eastern part of the Paris Basin display surprisingly low values of porosity and permeability (Φ < 15‰ and K < 0.5 mD). The main objective of this study is to determine the causes and timing of the cementation that altered the petrophysical properties of these carbonates thereby destroying their potential as oil reservoirs; a fate that did not befall their equivalents in deeper, central parts of the Paris Basin. Using petrographic and geochemical analyses (stable O and C isotopes, Sr isotopes, major elements), we identify six calcitic spar stages, two dolomite stages, and several episodes of fracturing and stylolitization ordered in paragenetic sequence.…

Holo-APP and G-protein-mediated signaling are required for sAPPa-induced activation of the Akt survival pathway

2014

International audience; Accumulating evidence indicates that loss of physiologic amyloid precursor protein (APP) function leads to reduced neuronal plasticity, diminished synaptic signaling and enhanced susceptibility of neurons to cellular stress during brain aging. Here we investigated the neuroprotective function of the soluble APP ectodomain sAPPa (soluble APPa), which is generated by cleavage of APP by a-secretase along the non-amyloidogenic pathway. Recombinant sAPPa protected primary hippocampal neurons and SH-SY5Y neuroblastoma cells from cell death induced by trophic factor deprivation. We show that this protective effect is abrogated in neurons from APP-knockout animals and APP-de…

Notch inhibition restores TRAIL-mediated apoptosis via AP1-dependent upregulation of DR4 and DR5 TRAIL receptors in MDA-MB-231 breast cancer cells.

2013

Notch is a family of transmembrane receptors whose activation through proteolytic cleavage by γ-secretase targets genes which participate in cell development, differentiation and tumorigenesis. Notch signaling is constitutively activated in various cancers, including breast cancer and its upregulation is usually related with poor clinical outcomes. Therefore, targeting Notch signaling with γ-secretase inhibitors (GSIs) is considered a promising strategy for cancer treatment. We report that the γ-secretase inhibitor-I (GSI-I) sensitizes human breast cancer cells to apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The antiproliferative GSI-I/TRAIL synergi…

FACIES HETEROGENEITY AND SEDIMENTARY PROCESSES ALONG A TECTONICALLY-CONTROLLED CARBONATE SLOPE: A CASE STUDY FROM THE CRETACEOUS OF WESTERN SICILY (I…

2020

Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aβ42

2005

Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate whether Abeta42 reduction is a common property of ROCK inhibitors, we tested commercially available compounds in cell lines that were previously used to demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that two ROCK inhibitors reduced total Abeta secretion in a dose-dependent m…

α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure

2001

Disintegrin metalloproteases from different organisms form the ADAM (a disintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain. The proteolytic process is referred to as ectodomain shedding, which is activated by phorbol esters and inhibited by hydroxamic acid-based inhibitors. We have shown that the disintegrin metalloprotease ADAM 10 has both constitutive and regulated alpha-secretase activity. Expression of a dominant n…

Presenilin is the molecular target of acidic γ-secretase modulators in living cells.

2012

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain an…

Activation of α-secretase cleavage

2011

Alpha-secretase-mediated cleavage of the amyloid precursor protein (APP) releases the neuroprotective APP fragment sαAPP and prevents amyloid β peptide (Aβ) generation. Moreover, α-secretase-like cleavage of the Aβ transporter 'receptor for advanced glycation end products' counteracts the import of blood Aβ into the brain. Assuming that Aβ is responsible for the development of Alzheimer's disease (AD), activation of α-secretase should be preventive. α-Secretase-mediated APP cleavage can be activated via several G protein-coupled receptors and receptor tyrosine kinases. Protein kinase C, mitogen-activated protein kinases, phosphatidylinositol 3-kinase, cAMP and calcium are activators of rece…