A pathway analysis of genome-wide association study highlights novel type 2 diabetes risk pathways.

Genome-wide association studies (GWAS) have been widely used to identify common type 2 diabetes (T2D) variants. However, the known variants just explain less than 20% of the overall estimated genetic contribution to T2D. Pathway-based methods have been applied into T2D GWAS datasets to investigate the biological mechanisms and reported some novel T2D risk pathways. However, few pathways were shared in these studies. Here, we performed a pathway analysis using the summary results from a large-scale meta-analysis of T2D GWAS to investigate more genetic signals in T2D. Here, we selected PLNK and VEGAS to perform the gene-based test and WebGestalt to perform the pathway-based test. We identified 8 shared KEGG pathways after correction for multiple tests in both methods. We confirm previous findings, and highlight some new T2D risk pathways. We believe that our results may be helpful to study the genetic mechanisms of T2D

Magic wavelengths for the 6s^2\,^1S_0-6s6p\,^3P_1^o transition in ytterbium atom

The static and dynamic electric-dipole polarizabilities of the 6s^2\,^1S_0 and 6s6p\,^3P_1^o states of Yb are calculated by using the relativistic ab initio method. Focusing on the red detuning region to the 6s^2\,^1S_0-6s6p\,^3P_1^o transition, we find two magic wavelengths at 1035.7(2) nm and 612.9(2) nm for the 6s^2\,^1S_0-6s6p\,^3P_1^o, M_J=0 transition and three magic wavelengthes at 1517.68(6) nm, 1036.0(3) nm and 858(12) nm for the 6s^2\,^1S_0-6s6p\,^3P_1^o, M_J=\pm1 transitions. Such magic wavelengths are of particular interest for attaining the state-insensitive cooling, trapping, and quantum manipulation of neutral Yb atom.Comment: 13 pages, 3 figure

Interconnecting bilayer networks

A typical complex system should be described by a supernetwork or a network of networks, in which the networks are coupled to some other networks. As the first step to understanding the complex systems on such more systematic level, scientists studied interdependent multilayer networks. In this letter, we introduce a new kind of interdependent multilayer networks, i.e., interconnecting networks, for which the component networks are coupled each other by sharing some common nodes. Based on the empirical investigations, we revealed a common feature of such interconnecting networks, namely, the networks with smaller averaged topological differences of the interconnecting nodes tend to share more nodes. A very simple node sharing mechanism is proposed to analytically explain the observed feature of the interconnecting networks.Comment: 9 page

Building KCNQ1/KCNE1 Channel Models and Probing their Interactions by Molecular-Dynamics Simulations

The slow delayed rectifier (IKs) channel is composed of KCNQ1 (pore-forming) and KCNE1 (auxiliary) subunits, and functions as a repolarization reserve in the human heart. Design of IKs-targeting anti-arrhythmic drugs requires detailed three-dimensional structures of the KCNQ1/KCNE1 complex, a task made possible by Kv channel crystal structures (templates for KCNQ1 homology-modeling) and KCNE1 NMR structures. Our goal was to build KCNQ1/KCNE1 models and extract mechanistic information about their interactions by molecular-dynamics simulations in an explicit lipid/solvent environment. We validated our models by confirming two sets of model-generated predictions that were independent from the spatial restraints used in model-building. Detailed analysis of the molecular-dynamics trajectories revealed previously unrecognized KCNQ1/KCNE1 interactions, whose relevance in IKs channel function was confirmed by voltage-clamp experiments. Our models and analyses suggest three mechanisms by which KCNE1 slows KCNQ1 activation: by promoting S6 bending at the Pro hinge that closes the activation gate; by promoting a downward movement of gating charge on S4; and by establishing a network of electrostatic interactions with KCNQ1 on the extracellular surface that stabilizes the channel in a pre-open activated state. Our data also suggest how KCNE1 may affect the KCNQ1 pore conductance

Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenase-2 (COX-2) has recently been considered to promote lymphangiogenesis by up-regulating vascular endothelial growth factor-C (VEGF-C) in breast and lung cancer. However, the impact of COX-2 on lymphangiogenesis of gastric cancer remains unclear. This study aims to test the expression of COX-2 and VEGF-C in human gastric cancer, and to analyze the correlation with lymphatic vessel density (LVD), clinicopathologic features and survival prognosis.</p> <p>Methods</p> <p>Using immunohistochemistry, COX-2, VEGF-C and level of LVD were analyzed in 56 R0-resected primary gastric adenocarcinomas, while paracancerous normal mucosal tissues were also collected as control from 25 concurrent patients. The relationships among COX-2 and VEGF-C expression, LVD, and clinicopathologic parameters were analyzed. The correlations of COX-2, VEGF-C and level of LVD with patient prognosis were also evaluated by univariate tests and multivariate Cox regression.</p> <p>Results</p> <p>The expression rates of COX-2 and VEGF-C were 69.64% and 55.36%, respectively, in gastric carcinoma. Peritumoral LVD was significantly higher than that in both normal and intratumoral tissue (<it>P </it>< 0.05). It was significantly correlated with lymph node metastasis and invasion depth (<it>P </it>= 0.003, <it>P </it>= 0.05). VEGF-C was significantly associated with peritumoral LVD (<it>r </it>= 0.308, <it>P </it>= 0.021). However, COX-2 was not correlated with VEGF-C (<it>r </it>= 0.110, <it>P </it>= 0.419) or LVD (<it>r </it>= 0.042, <it>P </it>= 0.758). Univariate analysis showed that survival time was impaired by higher COX-2 expression and higher peritumoral LVD. Multivariate survival analysis showed that age, COX-2 expression and peritumoral LVD were independent prognostic factors.</p> <p>Conclusions</p> <p>Although COX-2 expression was associated with survival time, it was not correlated with VEGF-C and peritumoral LVD. Our data did not show that overexpression of COX-2 promotes tumor lymphangiogenesis through an up-regulation of VEGF-C expression in gastric carcinoma. Age, COX-2 and peritumoral LVD were independent prognostic factors for human gastric carcinoma.</p

Synchronization of chaotic delayed systems via intermittent control and its adaptive strategy

In this paper the problem of synchronization for delayed chaotic systems is considered based on aperiodic intermittent control. First, delayed chaotic systems are proposed via aperiodic adaptive intermittent control. Next, to cut down the control gain, a new generalized intermittent control and its adaptive strategy is introduced. Then, by constructing a piecewise Lyapunov auxiliary function and making use of piecewise analysis technique, some effective and novel criteria are obtained to ensure the global synchronization of delayed chaotic systems by means of the designed control protocols. At the end, two examples with numerical simulations are provided to verify the effectiveness of the theoretical results proposed scheme

Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility.

Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation

High sensitivity HI image of diffuse gas and new tidal features in M51 observed by FAST

We observed the classical interacting galaxy M51 with FAST and obtain high sensitivity HI image with column density down to 3.8 $\times$ 10$^{18}$ cm$^{-2}$. In the image we can see a diffuse extended envelope around the system and several new tidal features. We also get a deeper look at M51b's probable gas, which has an approximated velocity range of 560 to 740 km s$^{-1}$ and a flux of 7.5 Jy km s$^{-1}$. Compared to the VLA image, we observe more complete structures of the Southeast Tail, Northeast Cloud and Northwest Plume, as well as new features of the Northwest Cloud and Southwest Plume. M51's most prominent tidal feature, the Southeast Tail, looks very long and broad, in addition with two small detached clouds at the periphery. Due to the presence of optical and simulated counterparts, the Northwest cloud appears to be the tail of M51a, while the Northwest Plume is more likely a tidal tail of M51b. The large mass of the Northwest Plume suggests that M51b may have been as gas-rich as M51a before the interaction. In addition, the formation process of the Northeast Cloud and Southwest Plume is obscured by the lack of optical and simulated counterparts. These novel tidal features, together with M51b's probable gas, will inspire future simulations and provide a deeper understanding of the evolution of this interacting system.Comment: 11 pages, 9 figures, accepted for publication in MNRA