Search results for "Notch"

Notch in T Cell Differentiation: All Things Considered.

2015

Differentiation of naive T cells into effector cells is required for optimal protection against different classes of microbial pathogen and for the development of immune memory. Recent findings have revealed important roles for the Notch signaling pathway in T cell differentiation into all known effector subsets, raising the question of how this pathway controls such diverse differentiation programs. Studies in preclinical models support the therapeutic potential of manipulating the Notch pathway to alleviate immune pathology, highlighting the importance of understanding the mechanisms through which Notch regulates T cell differentiation and function. We review these findings here, and outl…

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…

P041 Differences in NOTCH signalling between stricturing and penetrating behaviour in Crohn’s disease

2019

Re-analysis of fatigue data for welded joints using the notch stress approach

2010

Abstract Experimental fatigue data for welded joints have been collected and subjected to re-analysis using the notch stress approach according to IIW recommendations. This leads to an overview regarding the reliability of the approach, based on a large number of results (767 specimens). Evidently, there are some limitations in the approach regarding mild notch joints, such as butt joints, which can be assessed non-conservatively. In order to alleviate this problem, an increased minimum notch factor of Kw ⩾ 2.0 is suggested instead of the current recommendation of Kw ⩾ 1.6. The data for most fillet-welded joints agree quite well with the FAT 225 curve; however a reduction to FAT 200 is sugg…

Fauna Europaea: Hymenoptera - Apocrita (excl. Ichneumonoidea)

2015

Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all living European land and freshwater animals, their geographical distribution at country level (up to the Urals, excluding the Caucasus region), and some additional information. The Fauna Europaea project covers about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies. This represents a huge effort by more than 400 contributing specialists throughout Europe and is a unique (standard) reference suitable for many users in science, government, industry, nature conservation and education. Hymenoptera is one of the four largest orders of inse…

Tool Wear and Damage

2008

This chapter provides comprehensive knowledge regarding tool wear mechanisms and characterizes their physical fundamentals. Adhesion, abrasion, diffusion and oxidation are selected as predominant mechanisms controlling tool wear, depending on the mechanical and thermal conditions at the rake and flank faces. The analytical models describing the wear rate and volumetric material loss for different wear mechanisms are provided. The tool wear indicators related to crater, flank and notch wear specified in ISO 3685 are presented for both flat-faced and grooved tools. Tool life is defined and corresponding models, including the influence of cutting speed, feed and the depth of cut, are derived. …

Intraovarian regulation of gonadotropin-dependent folliculogenesis depends on notch receptor signaling pathways not involving Delta-like ligand 4 (Dl…

2013

Background In-situ hybridisation studies demonstrate that Notch receptors and ligands are expressed in granulosa cells (GCs) and in the theca layer vasculature of growing follicles. Notch signaling involves cell-to-cell interaction mediated by transmembrane receptors and ligands. This signaling pathway may represent a novel intraovarian regulator of gonadotropin-dependent follicular development to the preovulatory stage. We hypothesized that blocking Notch pathways would disrupt follicular maturation in the mouse ovary. Methods Hypophysectomized CD21 female mice were administered pregnant mare serum gonadotropin (PMSG) for 3 days to stimulate follicular development. In one experiment, a pan…

A central role for Notch in effector CD8(+) T cell differentiation.

2014

Activated CD8(+) T cells choose between terminal effector cell (TEC) or memory precursor cell (MPC) fates. We found that the signaling receptor Notch controls this 'choice'. Notch promoted the differentiation of immediately protective TECs and was correspondingly required for the clearance of acute infection with influenza virus. Notch activated a major portion of the TEC-specific gene-expression program and suppressed the MPC-specific program. Expression of Notch was induced on naive CD8(+) T cells by inflammatory mediators and interleukin 2 (IL-2) via pathways dependent on the metabolic checkpoint kinase mTOR and the transcription factor T-bet. These pathways were subsequently amplified d…

Low Density Lipoprotein Receptor-related Protein (LRP) Interacts with Presenilin 1 and Is a Competitive Substrate of the Amyloid Precursor Protein (A…

2005

Presenilin 1 (PS1) is a critical component of the gamma-secretase complex, which is involved in the cleavage of several substrates including the amyloid precursor protein (APP) and the Notch receptor. Recently, the low density receptor-related protein (LRP) has been shown to be cleaved by a gamma-secretase-like activity. We postulated that LRP may interact with PS1 and tested its role as a competitive substrate for gamma-secretase. In this report we show that LRP colocalizes and interacts with endogenous PS1 using coimmunoprecipitation and fluorescence lifetime imaging microscopy. In addition, we found that gamma-secretase active site inhibitors do not disrupt the interaction between LRP an…

Dinotrema cavernicola sp. n. (Hymenoptera, Braconidae, Alysiinae), a new species of the genus Dinotrema Foerster from caves of Spain

2014

Dinotrema cavernicola sp. n. was collected in two caves in Spain. This is the first Dinotrema species known to occur in caves. This new species is described and compared to D. affine (Fischer, 1973) and D. collybiae Munk & Peris-Felipo, 2014, species sharing a mid-longitudinal carina on the propodeum.