Interplay between Thyroid Hormones and Stearoyl-CoA Desaturase 1 in the Regulation of Lipid Metabolism in the Heart

Stearoyl-CoA desaturase 1 (SCD1), an enzyme that is involved in the biosynthesis of monounsaturated fatty acids, induces the reprogramming of cardiomyocyte metabolism. Thyroid hormones (THs) activate both lipolysis and lipogenesis. Many genes that are involved in lipid metabolism, including Scd1, are regulated by THs. The present study used SCD1 knockout (SCD1^−/−) mice to test the hypothesis that THs are important factors that mediate the anti-steatotic effect of SCD1 downregulation in the heart. SCD1 deficiency decreased plasma levels of thyroid-stimulating hormone and thyroxine and the expression of genes that regulate intracellular TH levels (i.e., Slc16a2 and Dio1-3) in cardiomyocytes. Both hypothyroidism and SCD1 deficiency affected genomic and non-genomic TH pathways in the heart. SCD1 deficiency is known to protect mice from genetic- or diet-induced obesity and decrease lipid content in the heart. Interestingly, hypothyroidism increased body adiposity and triglyceride and diacylglycerol levels in the heart in SCD1^−/− mice. The accumulation of triglycerides in cardiomyocytes in SCD1^−/− hypothyroid mice was caused by the activation of lipogenesis, which likely exceeded the upregulation of lipolysis and fatty acid oxidation. Lipid accumulation was also observed in the heart in wildtype hypothyroid mice compared with wildtype control mice, but this process was related to a reduction of triglyceride lipolysis and fatty acid oxidation. We also found that simultaneous SCD1 and deiodinase inhibition increased triglyceride content in HL-1 cardiomyocytes, and this process was related to the downregulation of lipolysis. Altogether, the present results suggest that THs are an important part of the mechanism of SCD1 in cardiac lipid utilization and may be involved in the upregulation of energetic metabolism that is associated with SCD1 deficiency.     

Methemoglobin Is an Endogenous Toll-Like Receptor 4 Ligand—Relevance to Subarachnoid Hemorrhage

Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and may be responsible for important complications of SAH. Signaling by Toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NFκB) in microglia plays a critical role in neuronal damage after SAH. Three molecules derived from erythrocyte breakdown have been postulated to be endogenous TLR4 ligands: methemoglobin (metHgb), heme and hemin. However, poor water solubility of heme and hemin, and lipopolysaccharide (LPS) contamination have confounded our understanding of these molecules as endogenous TLR4 ligands. We used a 5-step process to obtain highly purified LPS-free metHgb, as confirmed by Fourier Transform Ion Cyclotron Resonance mass spectrometry and by the Limulus amebocyte lysate assay. Using this preparation, we show that metHgb is a TLR4 ligand at physiologically relevant concentrations. metHgb caused time- and dose-dependent secretion of the proinflammatory cytokine, tumor necrosis factor α (TNFα), from microglial and macrophage cell lines, with secretion inhibited by siRNA directed against TLR4, by the TLR4-specific inhibitors, Rs-LPS and TAK-242, and by anti-CD14 antibodies. Injection of purified LPS-free metHgb into the rat subarachnoid space induced microglial activation and TNFα upregulation. Together, our findings support the hypothesis that, following SAH, metHgb in the subarachnoid space can promote widespread TLR4-mediated neuroinflammation.     

Microfluidic characterization and continuous separation of cells and particles using conducting poly(dimethyl siloxane) electrode induced alternating current-dielectrophoresis

This paper presents a poly(dimethyl siloxane) (PDMS) polymer microfluidic device using alternating current (ac) dielectrophoresis (DEP) for separating live cells from interfering particles of similar sizes by their polarizabilities under continuous flow and for characterizing DEP behaviors of cells in stagnant flow. The ac-DEP force is generated by three-dimensional (3D) conducting PDMS composite electrodes fabricated on a sidewall of the device main channel. Such 3D PDMS composite electrodes are made by dispersing microsized silver (Ag) fillers into PDMS gel. The sidewall AgPDMS electrodes can generate a 3D electric field that uniformly distributes throughout the channel height and varies along the channel lateral direction, thereby producing stronger lateral DEP effects over the entire channel. This allows not only easy observation of cell/particle lateral motion but also using the lateral DEP force for manipulation of cells/particles. The former feature is used to characterize the frequency-dependent DEP behaviors of Saccharomyces cerevisiae (yeast) and Escherichia coli (bacteria). The latter is utilized for continuous separation of live yeast and bacterial cells from similar-size latex particles as well as live yeast cells from dead yeast cells. The separation efficiency of 97% is achieved in all cases. The demonstration of these functions shows promising applications of the microfluidic device.     

Recent development and new ideas in the field of dispersive multilayer optics

A dispersive-mirror-based laser permits a dramatic simplification of high-power femtosecond and attosecond systems and affords promise for their further development toward shorter pulse durations, higher peak powers, and higher average powers with user-friendly systems. The result of the continuous development of dispersive mirrors permits pulse compression down to almost single cycle pulses of 3?fs duration. These design approaches together with the existing modern deposition technology pave the way for the manufacture of dielectric multilayer coatings able to compress pulses of tens of picoseconds duration down to a few femtoseconds.     

Analysis of dynamic matching networks for the ICRF system at ASDEX Upgrade

The ICRF (Ion Cyclotron Range of Frequencies) system, used to heat the plasma of ASDEX Upgrade, consists of RF generators, 3 dB hybrids, coaxial transmission lines, matching networks and inductive loop antennas. The maximum power achievable by the generator strongly depends on the amplitude and phase of the reflection coefficient. Hence, matching of the antenna input impedance to the generator output impedance is essential for the ICRF heating system. The coupling between the ICRF antennas and the plasma is subject to relatively fast variations (few ms). The changes are caused by the modification of plasma edge conditions, such as L–H mode transitions, gas puffing or ELMs (Edge Localized Modes). These variations change the impedance of the ICRF antennas. For optimal operation of the ICRF system, a continuous, and fast matching is therefore preferable. A MATLAB^® based simulation tool has been developed to analyse matching networks for the ICRF system at ASDEX Upgrade. The program is highly flexible, and can solve the matching calculations for different conditions and configurations of the system. The results are presented in a Smith chart.     

Coupling global methylation and gene expression profiles reveal key pathophysiological events in liver injury induced by a methyl-deficient diet

Scope : A methyl‐deficient diet induces liver injury similar to human nonalcoholic steatohepatitis, one of the main risk factors for the development of hepatocellular carcinoma. Previous studies have demonstrated that this diet perturbs DNA methylation by causing a profound loss of global cytosine methylation, predominantly at heavily methylated repetitive sequences. However, whether methyl deficiency affects the methylation status of gene promoters has not been explored. Methods and results : Mouse gene expression and CpG island microarrays were used to characterize the gene expression and CpG island methylation profiles in the livers of C57BL/6J mice fed a methyl‐deficient diet. We detected 164 genes that were differentially expressed and exhibited an inverse relationship between the gene expression and the extent of CpG island methylation. Furthermore, these genes were associated with altered lipid and glucose metabolism, DNA damage and repair, apoptosis, the development of fibrosis, and liver tissue remodeling. Although there were both increased and decreased levels of CpG island methylation, the number of hypomethylated genes was substantially greater than the number of hypermethylated genes. Conclusion : The results this study demonstrate that pairing methylation profiles with gene expression profiles is a powerful approach to identify dysregulated high‐priority fundamental pathophysiological pathways associated with disease development.     

Dynamic compositional modeling of pedestrian crash counts on urban roads in Connecticut

Uncovering the temporal trend in crash counts provides a good understanding of the context for pedestrian safety. With a rareness of pedestrian crashes it is impossible to investigate monthly temporal effects with an individual segment/intersection level data, thus the time dependence should be derived from the aggregated level data. Most previous studies have used annual data to investigate the differences in pedestrian crashes between different regions or countries in a given year, and/or to look at time trends of fatal pedestrian injuries annually. Use of annual data unfortunately does not provide sufficient information on patterns in time trends or seasonal effects. This paper describes statistical methods uncovering patterns in monthly pedestrian crashes aggregated on urban roads in Connecticut from January 1995 to December 2009. We investigate the temporal behavior of injury severity levels, including fatal (K), severe injury (A), evident minor injury (B), and non-evident possible injury and property damage only (C and O), as proportions of all pedestrian crashes in each month, taking into consideration effects of time trend, seasonal variations and VMT (vehicle miles traveled). This type of dependent multivariate data is characterized by positive components which sum to one, and occurs in several applications in science and engineering. We describe a dynamic framework with vector autoregressions (VAR) for modeling and predicting compositional time series. Combining these predictions with predictions from a univariate statistical model for total crash counts will then enable us to predict pedestrian crash counts with the different injury severity levels. We compare these predictions with those obtained from fitting separate univariate models to time series of crash counts at each injury severity level. We also show that the dynamic models perform better than the corresponding static models. We implement the Integrated Nested Laplace Approximation (INLA) approach to enable fast Bayesian posterior computation.     

Functional peroxides and peroxy oligoesters on the basis of pyromellitic dianhydride

A series of peroxy oligomers has been synthesized on the basis of pyromellitic dianhydride and tetrachloroanhydride of pyromellitic acid by condensation with polyethylene glycols and tert-butylhydroperoxide. The resulting oligoesters contain two types of functional groups: carboxylic – which can participate in ionic reactions and peroxide – able to initiate certain radical processes. Concentrations of these groups depend on the method of synthesis, the nature of starting monomers, and the molecular mass of polyethylene glycol. Structures of oligoesters have been determined by IR and ¹H-NMR spectroscopy. The oligoesters are able to form three-dimensional networks when heated to 400 K. A mechanism of the network formation is proposed. These materials can be used as curing agents for unsaturated polyesters and also for epoxy + unsaturated polyester resin compositions. Electronic Publication     

前驱体对激光熔覆复合溶胶凝胶制备陶瓷涂层的影响

目的研究不同前驱体配比下,激光熔覆复合溶胶凝胶在3Cr13不锈钢表面制备的陶瓷涂层的性能,并对强化机理进行分析。方法通过溶胶凝胶法制备均匀的前驱体,即Ti O2和C(微米石墨和碳纳米管),利用激光熔覆技术,在3Cr13不锈钢基体表面制备出高性能的涂层。采用光学显微镜、X射线衍射仪、扫描电镜和能谱仪对涂层组织和相成分进行分析,采用维氏硬度计对涂层的硬度进行测试,采用HT-600型高温摩擦磨损试验机测试基体和熔覆层在常温下的磨损性能。结果通过溶胶凝胶法,制备出均匀的Ti O2和C混合粉末。激光熔覆后,在覆层中均匀分布着Ti C和Cr7C3强化相。改变前驱体配比,当C和Ti O2的摩尔比增大时,涂层组织明显细化,且涂层中无气孔,显微硬度也有较大提高。当n(TiO2)∶n(C)=1∶8时,次表面显微硬度达到810HV0.2,涂层硬度从上到下呈现递减的趋势,且涂层的耐磨性最好,为基体的4.5倍。结论增大C和Ti O2两者摩尔比,可以提高熔覆层的显微硬度和耐磨性。在熔池中,Ti C密度较小,涂层中硬质颗粒从上到下依次减少,与之对应,硬度也依次递减。同时,碳纳米管的加入将对涂层起到细晶强化的效果。Ti与碳纳米管和微米石墨结合生成微米级和亚微米级Ti C,提高了形核率,Cr7C3以亚微米级Ti C为非均质核心,形核长大,生成均匀分布的Cr7C3强化相。