Analysis of differentially expressed genes and molecular pathways in familial hypercholesterolemia involved in atherosclerosis: A systematic and bioinformatics approach

Background and Aims: Familial hypercholesterolemia (FH) is one of the major risk factor for the progression of atherosclerosis and coronary artery disease. This study focused on identifying the dysregulated molecular pathways and core genes that are differentially regulated in FH and to identify the possible genetic factors and potential underlying mechanisms that increase the risk to atherosclerosis in patients with FH. Methods: The Affymetrix microarray dataset (GSE13985) from the GEO database and the GEO2R statistical tool were used to identify the differentially expressed genes (DEGs) from the white blood cells (WBCs) of five heterozygous FH patients and five healthy controls. The interaction between the DEGs was identified by applying the STRING tool and visualized using Cytoscape software. MCODE was used to determine the gene cluster in the interactive networks. The identified DEGs were subjected to the DAVID v6.8 webserver and ClueGo/CluePedia for functional annotation, such as gene ontology (GO) and enriched molecular pathway analysis of DEGs. Results: We investigated the top 250 significant DEGs (p-value < 0.05; fold two change ≥ 1 or ≤ −1). The GO analysis of DEGs with significant differences revealed that they are involved in critical biological processes and molecular pathways, such as myeloid cell differentiation, peptidyl-lysine modification, signaling pathway of MyD88-dependent Toll-like receptor, and cell-cell adhesion. The analysis of enriched KEGG pathways revealed the association of the DEGs in ubiquitin-mediated proteolysis and cardiac muscle contraction. The genes involved in the molecular pathways were shown to be differentially regulated by either activating or inhibiting the genes that are essential for the canonical signaling pathways. Our study identified seven core genes (UQCR11, UBE2N, ADD1, TLN1, IRAK3, LY96, and MAP3K1) that are strongly linked to FH and lead to a higher risk of atherosclerosis. Conclusion: We identified seven core genes that represent potential molecular biomarkers for the diagnosis of atherosclerosis and might serve as a platform for developing therapeutics against both FH and atherosclerosis. However, functional studies are further needed to validate their role in the pathogenesis of FH and atherosclerosis

An outbreak of food poisoning in Tamil Nadu associated with Yersinia enterocolitica

An outbreak of food poisoning in a Tamil Nadu village, affecting 25 of 48 individuals who participated in a feast, was investigated. The risk of developing illness was associated with consumption of buttermilk (relative risk 3.8). None of the food items consumed during the feast was available for analysis. Toxin-producing Y. enterocolitica (serotype 3, biotype 4) was grown from 1 of 11 stool samples from affected individuals, as well as from a water sample from the source used to dilute the buttermilk. High titres of antibody of Yersinia were detected in 2 of 12 patients but in neither of the two groups of controls. Toxin production was noted in buttermilk incubated for 6 h with Y. enterocolitica. This is the first report from India of a food poisoning outbreak associated with this organism

Structural Conformers of (1,3-Dithiol-2-ylidene)ethanethioamides: The Balance Between Thioamide Rotation and Preservation of Classical Sulfur-Sulfur Hypervalent Bonds

The reaction of N-(2-phthalimidoethyl)-N-alkylisopropylamines and S2Cl2 gave 4-N-(2-phthalimidoethyl)-N-alkylamino-5-chloro-1,2-dithiol-3-thiones that quantitatively cycloadded to dimethyl or diethyl acetylenedicarboxylate to give stable thioacid chlorides, which in turn reacted with one equivalent of aniline or a thiole to give thioanilides or a dithioester. Several compounds of this series showed atropisomers that were studied by a combination of dynamic NMR, simulation of the signals, conformational analysis by DFT methods, and single crystal X-ray diffraction, showing a good correlation between the theoretical calculations, the experimental values of energies, and the preferred conformations in the solid state. The steric hindering of the crowded substitution at the central amine group was found to be the reason for the presence of permanent atropisomers in this series of compounds and the cause of a unique disposition of the thioxo group at close-to-right angles with respect to the plane defined by the 1,3-dithiole ring in the dithiafulvene derivatives, thus breaking the sulfur–sulfur hypervalent bond that is always found in this kind of compounds.Ministerio de Economıá y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

Modelling of tungsten erosion and deposition in the divertor of JET-ILW in comparison to experimental findings

The erosion, transport and deposition of tungsten in the outer divertor of JET-ILW has been studied for an HMode discharge with low frequency ELMs. For this specific case with an inter-ELM electron temperature at the strike point of about 20 eV, tungsten sputtering between ELMs is almost exclusively due to beryllium impurity and self-sputtering. However, during ELMs tungsten sputtering due to deuterium becomes important and even dominates. The amount of simulated local deposition of tungsten relative to the amount of sputtered tungsten in between ELMs is very high and reaches values of 99% for an electron density of 5E13 cm$^{-3}$ at the strike point and electron temperatures between 10 and 30 eV. Smaller deposition values are simulated with reduced electron density. The direction of the B-field significantly influences the local deposition and leads to a reduction if the E×B drift directs towards the scrape-off-layer. Also, the thermal force can reduce the tungsten deposition, however, an ion temperature gradient of about 0.1 eV/mm or larger is needed for a significant effect. The tungsten deposition simulated during ELMs reaches values of about 98% assuming ELM parameters according to free-streaming model. The measured WI emission profiles in between and within ELMs have been reproduced by the simulation. The contribution to the overall net tungsten erosion during ELMs is about 5 times larger than the one in between ELMs for the studied case. However, this is due to the rather low electron temperature in between ELMs, which leads to deuterium impact energies below the sputtering threshold for tungsten

Tritium distributions on W-coated divertor tiles used in the third JET ITER-like wall campaign

Tritium (T) distributions on tungsten (W)-coated plasma-facing tiles used in the third ITER-like wall campaign (2015–2016) of the Joint European Torus (JET) were examined by means of an imaging plate technique and β-ray induced x-ray spectrometry, and they were compared with the distributions after the second (2013–2014) campaign. Strong enrichment of T in beryllium (Be) deposition layers was observed after the second campaign. In contrast, T distributions after the third campaign was more uniform though Be deposition layers were visually recognized. The one of the possible explanations is enhanced desorption of T from Be deposition layers due to higher tile temperatures caused by higher energy input in the third campaign

Impact of ICRF on the scrape-off layer and on plasma wall interactions: From present experiments to fusion reactor

Recent achievements in studies of the effects of ICRF (Ion Cyclotron Range of Frequencies) power on the SOL (Scrape-Off Layer) and PWI (Plasma Wall Interactions) in ASDEX Upgrade (AUG), Alcator C-Mod, and JET-ILW are reviewed. Capabilities to diagnose and model the effect of DC biasing and associated impurity production at active antennas and on magnetic field connections to antennas are described. The experiments show that ICRF near-fields can lead not only to E×B convection, but also to modifications of the SOL density, which for Alcator C-Mod are limited to a narrow region near antenna. On the other hand, the SOL density distribution along with impurity sources can be tailored using local gas injection in AUG and JET-ILW with a positive effect on reduction of impurity sources. The technique of RF image current cancellation at antenna limiters was successfully applied in AUG using the 3-strap AUG antenna and extended to the 4-strap Alcator C-Mod field-aligned antenna. Multiple observations confirmed the reduction of the impact of ICRF on the SOL and on total impurity production when the ratio of the power of the central straps to the total antenna power is in the range 0.6<P$_{cen}$/P$_{total}$<0.8. Near-field calculations indicate that this fairly robust technique can be applied to the ITER ICRF antenna, enabling the mode of operation with reduced PWI. On the contrary, for the A2 antenna in JET-ILW the technique is hindered by RF sheaths excited at the antenna septum. Thus, in order to reduce the effect of ICRF power on PWI in a future fusion reactor, the antenna design has to be optimized along with design of plasmafacing components

The effect of beryllium oxide on retention in JET ITER-like wall tiles

Preliminary results investigating the microstructure, bonding and effect of beryllium oxide formation on retention in the JET ITER-like wall beryllium tiles, are presented. The tiles have been investigated by several techniques: Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray (EDX), Transmission Electron microscopy (TEM) equipped with EDX and Electron Energy Loss Spectroscopy (EELS), Raman Spectroscopy and Thermal Desorption Spectroscopy (TDS). This paper focuses on results from melted materials of the dump plate tiles in JET. From our results and the literature, it is concluded, beryllium can form micron deep oxide islands contrary to the nanometric oxides predicted under vacuum conditions. The deepest oxides analyzed were up to 2-micron thicknesses. The beryllium Deuteroxide (BeOxDy) bond was found with Raman Spectroscopy. Application of EELS confirmed the oxide presence and stoichiometry. Literature suggests these oxides form at temperatures greater than 700 °C where self-diffusion of beryllium ions through the surface oxide layer can occur. Further oxidation is made possible between oxygen plasma impurities and the beryllium ions now present at the wall surface. Under Ultra High Vacuum (UHV) nanometric Beryllium oxide layers are formed and passivate at room temperature. After continual cyclic heating (to the point of melt formation) in the presence of oxygen impurities from the plasma, oxide growth to the levels seen experimentally (approximately two microns) is proposed. This retention mechanism is not considered to contribute dramatically to overall retention in JET, due to low levels of melt formation. However, this mechanism, thought the result of operation environment and melt formation, could be of wider concern to ITER, dependent on wall temperatures

An assessment of nitrogen concentrations from spectroscopic measurements in the JET and ASDEX upgrade divertor

The impurity concentration in the tokamak divertor plasma is a necessary input for predictive scaling of divertor detachment, however direct measurements from existing tokamaks in different divertor plasma conditions are limited. To address this, we have applied a recently developed spectroscopic N II line ratio technique for measuring the N concentration in the divertor to a range of H-mode and L-mode plasma from the ASDEX Upgrade and JET tokamaks, respectively. The results from both devices show that as the power crossing the separatrix, P$_{sep}$, is increased under otherwise similar core conditions (e.g. density), a higher N concentration is required to achieve the same detachment state. For example, the N concentrations at the start of detachment increase from ≈2% to ≈9% as Psep is increased from ≈2.5 MW to ≈7 MW. These results tentatively agree with scaling law predictions (e.g. Goldston et al.) motivating a further study examining the parameters which affect the N concentration required to reach detachment. Finally, the N concentrations from spectroscopy and the ratio of D and N gas valve fluxes agree within experimental uncertainty only when the vessel surfaces are fully-loaded with N