scholarly journals Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Antonio Junior Lepedda ◽  
Marilena Formato
Keyword(s):  
Atherosclerotic Plaque ◽  
Sulfhydryl Group ◽  
Oxidative Modification ◽  
Low Molecular Weight ◽  
Atherosclerotic Plaques ◽  
Oxidative Modifications ◽  
Protein Sulfhydryl ◽  
Sh Group ◽  
Very High

Although oxidative stress has been long associated with the genesis and progression of the atherosclerotic plaque, scanty data on its in situ effects on protein sulfhydryl group modifications are available. Within the arterial wall, protein sulfhydryls and low-molecular-weight (LMW) thiols are involved in the cell regulation of both Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) levels and are a target for several posttranslational oxidative modifications that take place inside the atherosclerotic plaque, probably contributing to both atherogenesis and atherosclerotic plaque progression towards complicated lesions. Advanced carotid plaques are characterized by very high intraplaque GSH levels, due to cell lysis during apoptotic and/or necrotic events, probably responsible for the altered equilibrium among protein sulfhydryls and LMW thiols. Some lines of evidence show that the prooxidant environment present in atherosclerotic tissue could modify filtered proteins also by protein-SH group oxidation, and demonstrate that particularly albumin, once filtered, represents a harmful source of homocysteine and cysteinylglycine inside the plaque. The oxidative modification of protein sulfhydryls, with particular emphasis to protein thiolation by LMW thiols and its association with atherosclerosis, is the main topic of this review.

Abstract 13: Inhibition of Nudt6 Stabilizes Advanced Atherosclerotic Plaques

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Hong Jin ◽  
Yuhuang Li ◽  
Ekaterina Chernogubova ◽  
Alexandra Bäcklund ◽  
Stina Sellberg ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Survival Rates ◽  
Atherosclerotic Plaques ◽  
Protein Coding ◽  
Fibrous Cap ◽  
Asymptomatic Patients ◽  
Rupture Model

Natural antisense transcripts (NATs), a non-coding RNA subclass, being transcribed in antisense direction to protein coding genes, are an intriguing novel class of targetable modulators, exerting crucial effects on gene expression. Aim of the current study was to investigate the contribution of NATs to atherosclerotic plaque vulnerability. Using laser capture micro-dissection, we isolated fibrous caps tissue of carotid artery plaques from 20 symptomatic patients with ruptured lesions vs. 20 samples from asymptomatic patients with stable lesions. A human transcriptome array (HTA; GeneChip 2.0 ) was used to profile the expression of all currently annotated RNA transcripts. Nucleoside diphosphate-linked moiety X motif 6 (NUDT6) was identified as one of the most significantly up-regulated transcripts in fibrous caps of ruptured lesions. Interestingly, NUDT6 is an established antisense RNA targeting the fibroblast growth factor 2 (FGF2). Of importance, FGF2 was among the most significantly down-regulated transcripts in ruptured lesions, corresponding to elevated NUDT6 expression. In situ hybridization in both, human and mouse carotid atherosclerotic plaques, confirmed substantially higher expression levels of NUDT6 in ruptured lesions compared to stable. In addition, in situ hybridization revealed a distinct co-localization with smooth muscle cells (SMCs) in advanced plaques. Overexpression of NUDT6 in cultured human carotid artery SMCs effectively limited FGF2 on the mRNA as well as protein level. Furthermore, reduction of NUDT6 via siRNA stimulated proliferation and blocked apoptosis in SMCs. In an inducible atherosclerotic plaque rupture model using incomplete ligation and cuff placement on common carotid arteries of male apoE -/- mice, NUDT6 inhibition with gapmeRs was able to significantly improve SMC survival rates, leading to thicker fibrous caps, and to reduce the plaque rupture rate compared to scramble-gapmeR control-treated mice (22% vs . 63%, p = 0.03). The present study presents NUDT6 as a novel crucial antisense regulator of fibrous cap stability through steering SMC survival via targeting its sense RNA transcript FGF2.

scholarly journals Protein Sulfhydryl Group Oxidation and Mixed-Disulfide Modifications in Stable and Unstable Human Carotid Plaques

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Antonio Junior Lepedda ◽  
Angelo Zinellu ◽  
Gabriele Nieddu ◽  
Elisabetta Zinellu ◽  
Ciriaco Carru ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Function ◽  
Sulfhydryl Group ◽  
Plaque Stability ◽  
Proteomic Approach ◽  
Oxidative Modifications ◽  
Protein Sulfhydryl ◽  
Unstable Plaques ◽  
Protein Sulfhydryl Groups ◽  
Human Carotid

Objectives. Oxidative stress has been implicated in the outcome of atherosclerotic plaques. However, at present, no data are available neither on the degree of plaque protein sulfhydryl groups oxidation nor on its relationship with plaque vulnerability. We investigated the entity of protein-SH oxidative modifications, focusing on low molecular weight thiols adduction, in human carotid plaque extracts in relation to plaque stability/instability.Methods. Plaque stability/instability was histologically assessed. The extent of protein-SH oxidative modifications was established by a differential proteomic approach on fluorescein-5-maleimide-labeled plaque extracts and corresponding plasma samples from 48 endarterectomized patients. The analysis on protein thiolation was performed by capillary zone electrophoresis.Results. We observed a higher protein-SH oxidation of both plasma-derived and topically expressed proteins in unstable plaques, partly due to higher levels of S-thiolation. Conversely, in plasma, none of the investigated parameters discriminated among patients with stable and unstable plaques.Conclusions. Our results suggest the presence of a more pronounced oxidative environment in unstable plaques. Identifying specific oxidative modifications and understanding their effects on protein function could provide further insight into the relevance of oxidative stress in atherosclerosis.

scholarly journals Critical Dynamics of Defects and Mechanisms of Damage-Failure Transitions in Fatigue

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2554
Author(s):  
Oleg Naimark ◽  
Vladimir Oborin ◽  
Mikhail Bannikov ◽  
Dmitry Ledon
Keyword(s):  
Fatigue Damage ◽  
Kinetic Equations ◽  
Experimental Methodology ◽  
Preliminary Deformation ◽  
Scaling Properties ◽  
In Situ Data ◽  
Number Of Cycles ◽  
Fish Eye ◽  
Very High

An experimental methodology was developed for estimating a very high cycle fatigue (VHCF) life of the aluminum alloy AMG-6 subjected to preliminary deformation. The analysis of fatigue damage staging is based on the measurement of elastic modulus decrement according to “in situ” data of nonlinear dynamics of free-end specimen vibrations at the VHCF test. The correlation of fatigue damage staging and fracture surface morphology was studied to establish the scaling properties and kinetic equations for damage localization, “fish-eye” nucleation, and transition to the Paris crack kinetics. These equations, based on empirical parameters related to the structure of the material, allows us to estimate the number of cycles for the nucleation and advance of fatigue crack.

scholarly journals A Pixel Design of a Branching Ultra-Highspeed Image Sensor

Sensors ◽  
2021 ◽  
Vol 21 (7) ◽  
pp. 2506
Author(s):  
Nguyen Hoai Ngo ◽  
Kazuhiro Shimonomura ◽  
Taeko Ando ◽  
Takayoshi Shimura ◽  
Heiji Watanabe ◽  
...  
Keyword(s):  
Image Sensor ◽  
Frame Rate ◽  
Front Side ◽  
Digital Signals ◽  
Memory Element ◽  
Image Capture ◽  
Readout Circuits ◽  
Pros And Cons ◽  
Very High

A burst image sensor named Hanabi, meaning fireworks in Japanese, includes a branching CCD and multiple CMOS readout circuits. The sensor is backside-illuminated with a light/charge guide pipe to minimize the temporal resolution by suppressing the horizontal motion of signal carriers. On the front side, the pixel has a guide gate at the center, branching to six first-branching gates, each bifurcating to second-branching gates, and finally connected to 12 (=6×2) floating diffusions. The signals are either read out after an image capture operation to replay 12 to 48 consecutive images, or continuously transferred to a memory chip stacked on the front side of the sensor chip and converted to digital signals. A CCD burst image sensor enables a noiseless signal transfer from a photodiode to the in-situ storage even at very high frame rates. However, the pixel count conflicts with the frame count due to the large pixel size for the relatively large in-pixel CCD memory elements. A CMOS burst image sensor can use small trench-type capacitors for memory elements, instead of CCD channels. However, the transfer noise from a floating diffusion to the memory element increases in proportion to the square root of the frame rate. The Hanabi chip overcomes the compromise between these pros and cons.

scholarly journals Influence of Hydrogeochemistry on Tunnel Drainage in Evaporitic Formations: El Regajal Tunnel Case Study (Aranjuez, Spain)

2021 ◽  
Vol 13 (3) ◽  
pp. 1505
Author(s):  
Ignacio Menéndez Pidal ◽  
Jose Antonio Mancebo Piqueras ◽  
Eugenio Sanz Pérez ◽  
Clemente Sáenz Sanz
Keyword(s):  
High Speed ◽  
Civil Engineering ◽  
Saturation Index ◽  
The Subject ◽  
Under Construction ◽  
Underground Flow ◽  
Very High ◽  
Over Time

Many of the large number of underground works constructed or under construction in recent years are in unfavorable terrains facing unusual situations and construction conditions. This is the case of the subject under study in this paper: a tunnel excavated in evaporitic rocks that experienced significant karstification problems very quickly over time. As a result of this situation, the causes that may underlie this rapid karstification are investigated and a novel methodology is presented in civil engineering where the use of saturation indices for the different mineral specimens present has been crucial. The drainage of the rock massif of El Regajal (Madrid-Toledo, Spain, in the Madrid-Valencia high-speed train line) was studied and permitted the in-situ study of the hydrogeochemical evolution of water flow in the Miocene evaporitic materials of the Tajo Basin as a full-scale testing laboratory, that are conforms as a whole, a single aquifer. The work provides a novel methodology based on the calculation of activities through the hydrogeochemical study of water samples in different piezometers, estimating the saturation index of different saline materials and the dissolution capacity of the brine, which is surprisingly very high despite the high electrical conductivity. The circulating brine appears unsaturated with respect to thenardite, mirabilite, epsomite, glauberite, and halite. The alteration of the underground flow and the consequent renewal of the water of the aquifer by the infiltration water of rain and irrigation is the cause of the hydrogeochemical imbalance and the modification of the characteristics of the massif. These modifications include very important loss of material by dissolution, altering the resistance of the terrain and the increase of the porosity. Simultaneously, different expansive and recrystallization processes that decrease the porosity of the massif were identified in the present work. The hydrogeochemical study allows the evolution of these phenomena to be followed over time, and this, in turn, may facilitate the implementation of preventive works in civil engineering.

scholarly journals Uric Acid Is a Genuine Metabolite of Penicillium cyclopium and Stimulates the Expression of Alkaloid Biosynthesis in This Fungus

2002 ◽  
Vol 68 (4) ◽  
pp. 1524-1533 ◽  
Author(s):  
Florian Helbig ◽  
Jörg Steighardt ◽  
Werner Roos
Keyword(s):  
Uric Acid ◽  
Low Molecular Weight ◽  
Alkaloid Production ◽  
Alkaloid Biosynthesis ◽  
Penicillium Cyclopium ◽  
Measurable Activity ◽  
Reduced Rate ◽  
Rate Limiting

ABSTRACT On searching for endogenous, low-molecular-weight effectors of benzodiazepine alkaloid biosynthesis in Penicillium cyclopium uric acid was isolated from ethanolic or autoclaved mycelial extracts of this fungus. The isolation was based on a three-step high-pressure liquid chromatography procedure guided by a microplate bioassay, and uric acid was identified by mass spectrometry and the uricase reaction. Conidiospore suspensions that were treated with this compound during the early phase of outgrowth developed emerged cultures with an enhanced rate of alkaloid production. Uric acid treatment did not increase the in vitro measurable activity of the rate-limiting biosynthetic enzyme, cyclopeptine synthetase. However, these cultures displayed a reduced rate of uptake of the alkaloid precursor l-phenylalanine into the vacuoles of the hyphal cells as assayed in situ. It is suggested that the depressed capacity of vacuolar uptake caused by the contact of outgrowing spores with uric acid liberated from hyphal cells results in an enhanced availability of the precursor l-phenylalanine in the cytoplasm and thus accounts at least in part for the increase in alkaloid production.

scholarly journals Preparation of Porous Polymers by ”in Situ Precipitation” Using Low Molecular Weight Gelators

2002 ◽  
Vol 34 (6) ◽  
pp. 474-477 ◽  
Author(s):  
Masahiro Suzuki ◽  
Yasuhiko Sakakibara ◽  
Satoshi Kobayashi ◽  
Mutsumi Kimura ◽  
Hirofusa Shirai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Porous Polymers ◽  
Low Molecular Weight ◽  
Low Molecular Weight Gelators

Investigation of Emulsion Flow in Steam-Assisted Gravity Drainage

SPE Journal ◽  
2013 ◽  
Vol 18 (03) ◽  
pp. 440-447 ◽  
Author(s):  
C.C.. C. Ezeuko ◽  
J.. Wang ◽  
I.D.. D. Gates
Keyword(s):  
Experimental Data ◽  
Numerical Simulation ◽  
Oil Recovery ◽  
Vital Role ◽  
Gravity Drainage ◽  
Steam Assisted Gravity Drainage ◽  
Emulsion Flow ◽  
Very High ◽  
Effective Representation

Summary We present a numerical simulation approach that allows incorporation of emulsion modeling into steam-assisted gravity-drainage (SAGD) simulations with commercial reservoir simulators by means of a two-stage pseudochemical reaction. Numerical simulation results show excellent agreement with experimental data for low-pressure SAGD, accounting for approximately 24% deficiency in simulated oil recovery, compared with experimental data. Incorporating viscosity alteration, multiphase effect, and enthalpy of emulsification appears sufficient for effective representation of in-situ emulsion physics during SAGD in very-high-permeability systems. We observed that multiphase effects appear to dominate the viscosity effect of emulsion flow under SAGD conditions of heavy-oil (bitumen) recovery. Results also show that in-situ emulsification may play a vital role within the reservoir during SAGD, increasing bitumen mobility and thereby decreasing cumulative steam/oil ratio (cSOR). Results from this work extend understanding of SAGD by examining its performance in the presence of in-situ emulsification and associated flow of emulsion with bitumen in porous media.

scholarly journals Asymmetric Pd-NHC*-catalyzed coupling reactions

2012 ◽  
Vol 84 (8) ◽  
pp. 1741-1748 ◽  
Author(s):  
E. Peter Kündig ◽  
Yixia Jia ◽  
Dmitry Katayev ◽  
Masafumi Nakanishi
Keyword(s):  
High Temperature ◽  
Coupling Reactions ◽  
Structural Studies ◽  
Methylene Unit ◽  
Asymmetric Coupling ◽  
New Applications ◽  
Very High

Very high asymmetric inductions result in the Pd-catalyzed intramolecular arylation of amides to give 3,3-disubstituted oxindoles when new in situ-generated chiral N-heterocyclic carbene (NHC*) ligands are employed. Structural studies show that conformational locking to minimize allylic strain is the key to understanding the function of these ligands. New applications of these ligands in the frontier area of asymmetric coupling reactions involving C(sp3)–H bonds are detailed. Highly enantioenriched fused indolines are accessible using either preformed- or in situ-generated Pd-NHC* catalysts. Remarkably, this occurs at high temperature (140–160 °C) via excellent asymmetric recognition of an enantiotopic C–H bond in an unactivated methylene unit.

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