Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Planet formation in Binaries

Spurred by the discovery of numerous exoplanets in multiple systems, binaries have become in recent years one of the main topics in planet formation research. Numerous studies have investigated to what extent the presence of a stellar companion can affect the planet formation process. Such studies have implications that can reach beyond the sole context of binaries, as they allow to test certain aspects of the planet formation scenario by submitting them to extreme environments. We review here the current understanding on this complex problem. We show in particular how each of the different stages of the planet-formation process is affected differently by binary perturbations. We focus especially on the intermediate stage of kilometre-sized planetesimal accretion, which has proven to be the most sensitive to binarity and for which the presence of some exoplanets observed in tight binaries is difficult to explain by in-situ formation following the "standard" planet-formation scenario. Some tentative solutions to this apparent paradox are presented. The last part of our review presents a thorough description of the problem of planet habitability, for which the binary environment creates a complex situation because of the presence of two irradation sources of varying distance.Comment: Review chapter to appear in "Planetary Exploration and Science: Recent Advances and Applications", eds. S. Jin, N. Haghighipour, W.-H. Ip, Springer (v2, numerous typos corrected

The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder

In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the "zero-order region", i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON

Atomic-scale combination of germanium-zinc nanofibers for structural and electrochemical evolution

Alloys are recently receiving considerable attention in the community of rechargeable batteries as possible alternatives to carbonaceous negative electrodes; however, challenges remain for the practical utilization of these materials. Herein, we report the synthesis of germanium-zinc alloy nanofibers through electrospinning and a subsequent calcination step. Evidenced by in situ transmission electron microscopy and electrochemical impedance spectroscopy characterizations, this one-dimensional design possesses unique structures. Both germanium and zinc atoms are homogenously distributed allowing for outstanding electronic conductivity and high available capacity for lithium storage. The as-prepared materials present high rate capability (capacity of similar to 50% at 20 C compared to that at 0.2 C-rate) and cycle retention (73% at 3.0 C-rate) with a retaining capacity of 546 mAh g(-1) even after 1000 cycles. When assembled in a full cell, high energy density can be maintained during 400 cycles, which indicates that the current material has the potential to be used in a large-scale energy storage system

Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

Thermal conductivity measurement of liquids in a microfluidic device

A new microfluidic-based approach to measuring liquid thermal conductivity is developed to address the requirement in many practical applications for measurements using small (microlitre) sample size and integration into a compact device. The approach also gives the possibility of high-throughput testing. A resistance heater and temperature sensor are incorporated into a glass microfluidic chip to allow transmission and detection of a planar thermal wave crossing a thin layer of the sample. The device is designed so that heat transfer is locally one-dimensional during a short initial time period. This allows the detected temperature transient to be separated into two distinct components: a short-time, purely one-dimensional part from which sample thermal conductivity can be determined and a remaining long-time part containing the effects of three-dimensionality and of the finite size of surrounding thermal reservoirs. Identification of the one-dimensional component yields a steady temperature difference from which sample thermal conductivity can be determined. Calibration is required to give correct representation of changing heater resistance, system layer thicknesses and solid material thermal conductivities with temperature. In this preliminary study, methanol/water mixtures are measured at atmospheric pressure over the temperature range 30–50°C. The results show that the device has produced a measurement accuracy of within 2.5% over the range of thermal conductivity and temperature of the tests. A relation between measurement uncertainty and the geometric and thermal properties of the system is derived and this is used to identify ways that error could be further reduced

Relationship between a Novel Polymorphism of the C5L2 Gene and Coronary Artery Disease

C5L2 has been demonstrated to be a functional receptor of acylation-stimulating protein (ASP), which is a stimulator of triglyceride synthesis or glucose transport. However, little is known about the variations in the coding region of the C5L2 gene and their association with coronary artery disease (CAD). = 0.047, OR = 2.602, 95% CI: 1.015–6.671).The 698CT genotype of C5L2 may be a genetic maker of CAD in the Han and Uygur population in western China

Superluminal motion of a relativistic jet in the neutron star merger GW170817

The binary neutron star merger GW170817 was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a distance of 41+/-3 Mpc. The radio and X-ray afterglows of GW170817 exhibited delayed onset, a gradual rise in the emission with time as t^0.8, a peak at about 150 days post-merger, followed by a relatively rapid decline. To date, various models have been proposed to explain the afterglow emission, including a choked-jet cocoon and a successful-jet cocoon (a.k.a. structured jet). However, the observational data have remained inconclusive as to whether GW170817 launched a successful relativistic jet. Here we show, through Very Long Baseline Interferometry, that the compact radio source associated with GW170817 exhibits superluminal motion between two epochs at 75 and 230 days post-merger. This measurement breaks the degeneracy between the models and indicates that, while the early-time radio emission was powered by a wider-angle outflow (cocoon), the late-time emission was most likely dominated by an energetic and narrowly-collimated jet, with an opening angle of <5 degrees, and observed from a viewing angle of about 20 degrees. The imaging of a collimated relativistic outflow emerging from GW170817 adds substantial weight to the growing evidence linking binary neutron star mergers and short gamma-ray bursts.Comment: 42 pages, 4 figures (main text), 2 figures (supplementary text), 2 tables. Referee and editor comments incorporate

The Impact of miRNA Target Sites in Coding Sequences and in 3′UTRs

Animal miRNAs are a large class of small regulatory RNAs that are known to directly and negatively regulate the expression of a large fraction of all protein encoding genes. The identification and characterization of miRNA targets is thus a fundamental problem in biology. miRNAs regulate target genes by binding to 3′ untranslated regions (3′UTRs) of target mRNAs, and multiple binding sites for the same miRNA in 3′UTRs can strongly enhance the degree of regulation. Recent experiments have demonstrated that a large fraction of miRNA binding sites reside in coding sequences. Overall, miRNA binding sites in coding regions were shown to mediate smaller regulation than 3′UTR binding. However, possible interactions between target sites in coding sequences and 3′UTRs have not been studied. Using transcriptomics and proteomics data of ten miRNA mis-expression experiments as well as transcriptome-wide experimentally identified miRNA target sites, we found that mRNA and protein expression of genes containing target sites both in coding regions and 3′UTRs were in general mildly but significantly more regulated than those containing target sites in 3′UTRs only. These effects were stronger for conserved target sites of length 7–8 nt in coding regions compared to non-conserved sites. Combined with our other finding that miRNA target sites in coding regions are under negative selection, our results shed light on the functional importance of miRNA targeting in coding regions