Search results for "Teas"

2019

Phobalysin P (PhlyP, for photobacterial lysin encoded on a plasmid) is a recently described small β-pore forming toxin of Photobacterium damselae subsp. damselae (Pdd). This organism, belonging to the family of Vibrionaceae, is an emerging pathogen of fish and various marine animals, which occasionally causes life-threatening soft tissue infections and septicemia in humans. By using genetically modified Pdd strains, PhlyP was found to be an important virulence factor. More recently, in vitro studies with purified PhlyP elucidated some basic consequences of pore formation. Being the first bacterial small β-pore forming toxin shown to trigger calcium-influx dependent membrane repair, PhlyP ha…

2020

We report that several viruses from the human enterovirus group B cause massive vimentin rearrangements during lytic infection. Comprehensive studies suggested that viral protein synthesis was triggering the vimentin rearrangements. Blocking the host cell vimentin dynamics with β, β'-iminodipropionitrile (IDPN) did not significantly affect the production of progeny viruses and only moderately lowered the synthesis of structural proteins such as VP1. In contrast, the synthesis of the nonstructural proteins 2A, 3C, and 3D was drastically lowered. This led to attenuation of the cleavage of the host cell substrates PABP and G3BP1 and reduced caspase activation, leading to prolonged cell surviva…

A Microscopic Description of SARS-CoV-2 Main Protease Inhibition with Michael Acceptors. Strategies for Improving Inhibitors Design

2020

The irreversible inhibition of the main protease of SARS-CoV-2 by a Michael acceptor known as N3 has been investigated using multiscale methods. The noncovalent enzyme–inhibitor complex was simulated using classical molecular dynamics techniques and the pose of the inhibitor in the active site was compared to that of the natural substrate, a peptide containing the Gln–Ser scissile bond. The formation of the covalent enzyme–inhibitor complex was then simulated using hybrid QM/MM free energy methods. After binding, the reaction mechanism was found to be composed of two steps: (i) the activation of the catalytic dyad (Cys145 and His41) to form an ion pair and (ii) a Michael addition where the …

Intestinal CD36. A lipid-sensor involved in the processing of chylomicrons in rodents

2011

International audience; CD36 is a multifunctional glycoprotein which binds nanomolar concentrations of long-chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. Despite of its implication in oleoylethanolamide (OEA) and chylomicron synthesis, CD36 function in small intestine remains incompletely understood. Our in vivo data demonstrated that CD36 gene deletion in mice did not affect intestinal LCFA uptake. CD36 protein disappeared early from the luminal side of intestinal villi during the post-prandial period but only when the diet contained lipids. This drop was significant 1 h after a lipid supply and was associated with ubiquitination of CD36. Using CHO…

Direct pathway cloning and expression of the radiosumin biosynthetic gene cluster

2023

Radiosumins are a structurally diverse family of low molecular weight natural products that are produced by cyanobacteria and exhibit potent serine protease inhibition. Members of this family are dipeptides characterized by the presence of two similar non-proteinogenic amino acids. Here we used a comparative bioinformatic analysis to identify radiosumin biosynthetic gene clusters from the genomes of 13 filamentous cyanobacteria. We used direct pathway cloning to capture and express the entire 16.8 kb radiosumin biosynthetic gene cluster from Dolichospermum planctonicum UHCC 0167 in Escherichia coli. Bioinformatic analysis demonstrates that radiosumins represent a new group of chorismate-der…

The N-terminal domain of the light-harvesting chlorophyll a/b-binding protein complex (LHCII) is essential for its acclimative proteolysis.

2000

AbstractVariations in the amount of the light-harvesting chlorophyll a/b-binding protein complex (LHCII) is essential for regulation of the uptake of light into photosystem II. An endogenous proteolytic system was found to be involved in the degradation of LHCII in response to elevated light intensities and the proteolysis was shown to be under tight regulation [Yang, D.-H. et al. (1998) Plant Physiol. 118, 827–834]. In this study, the substrate specificity and recognition site towards the protease were examined using reconstituted wild-type and mutant recombinant LHCII. The results show that the LHCII apoprotein and the monomeric form of the holoprotein are targeted for proteolysis while t…

Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease in…

2011

Abstract Background Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce. Methods Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after…

Enzymatic modification of low-density lipoprotein in the arterial wall: a new role for plasmin and matrix metalloproteinases in atherogenesis.

2004

Objective— Functionally interactive proteases of the plasminogen/plasmin and the matrix metalloproteinase (MMP) system degrade and reorganize the extracellular matrix of the vessel wall in atherosclerosis. Here we investigated whether such proteases are able to confer atherogenic properties onto low density lipoprotein by nonoxidative modification. Methods and Results— Similar to the recently described enzymatically-modified low-density lipoprotein (E-LDL), native LDL exposed to plasmin or matrix MMP-2 or MMP-9 and cholesterylester-hydrolase (CEH) showed extensive deesterification, with ratios of free cholesterol to total cholesterol rising to 0.8 compared with 0.2 in native LDL. When the …

Liver cirrhosis associated with heterozygous alpha-1-antitrypsin deficiency type Pi MS and autoimmune features.

1995

Patients with homozygous protease inhibitor (Pi) type ZZ or a few rare M-like types may develop liver cirrhosis due to intracellular storage of alpha-antitrypsin (AAT), whereas some patients with heterozygous Pi MZ or SZ normally present with transient abnormal liver function tests in childhood. We report a 42-year-old obese patient who developed liver cirrhosis in association with heterozygous Pi MS (AAT) deficiency. Immunohistological and electron microscope examination showed storage of AAT in the hepatocytes. Interestingly, autoimmune features in this patient suggest that abnormal immune responses may contribute to the pathology of chronic liver disease.

High density of tryptase-positive mast cells in human colorectal cancer: a poor prognostic factor related to protease-activated receptor 2 expression

2013

Tryptase(+) mast cells (MCs), abundant in the invasive front of tumours, contribute to tissue remodelling. Indeed, protease-activated receptor- 2 (PAR-2) activation by MC-tryptase is considered an oncogenic event in colorectal cancer (CRC). Recently, we have suggested NHERF1 as a potential new marker in CRC. In this study, we aimed to determine the distribution of tryptase(+) MCs and PAR-2 and to examine the relationship between PAR-2 and NHERF1, investigating their reputed usefulness as tumour markers. We studied a cohort of 115 CRC specimens including primary cancer (C) and adjacent normal mucosa (NM) by immunohistochemical double staining, analyzing the protein expression of MC-tryptase,…