Changes in DNA copy number, whether confined to specific genes or affecting whole chromosomes, have been identified as causes of diseases and developmental abnormalities and as sources of adaptive ...potential. Here, we discuss the costs and benefits of DNA copy-number alterations. Changes in DNA copy number are largely detrimental. Amplifications or deletions of specific genes can elicit discrete defects. Large-scale changes in DNA copy number can also cause detrimental phenotypes that are due to the cumulative effects of copy-number alterations of many genes simultaneously. On the other hand, studies in microorganisms show that DNA copy-number alterations can be beneficial, increasing survival under selective pressure. As DNA copy-number alterations underlie many human diseases, we will end with a discussion of gene copy-number changes as therapeutic targets.
Exchange bias is a property of widespread technological utility, but its underlying mechanism remains elusive, in part because it is rooted in the interaction of coexisting order parameters in the ...presence of complex magnetic disorder. Here we show that a giant exchange bias housed within a spin-glass phase arises in a disordered antiferromagnet. The magnitude and robustness of the exchange bias emerges from a convolution of two energetic landscapes, namely the highly degenerate landscape of the spin glass biased by the sublattice spin configuration of the antiferromagnet. The former provides a source of uncompensated moment, whereas the latter provides a mechanism for its pinning, which leads to the exchange bias. Tuning the relative strengths of the spin-glass and antiferromagnetic order parameters reveals a principle for tailoring the exchange bias, with potential applications to spintronic technologies.Coexistence of a spin-glass phase with antiferromagnetism in an intercalated crystal produces a large exchange bias effect. This is due to the interplay of disorder and frustration.
Abstract
Background
As one of the deadliest diseases in the world, cancer is driven by a few somatic mutations that disrupt the normal growth of cells, and leads to abnormal proliferation and tumor ...development. The vast majority of somatic mutations did not affect the occurrence and development of cancer; thus, identifying the mutations responsible for tumor occurrence and development is one of the main targets of current cancer treatments.
Results
To effectively identify driver genes, we adopted a semi-local centrality measure and gene mutation effect function to assess the effect of gene mutations on changes in gene expression patterns. Firstly, we calculated the mutation score for each gene. Secondly, we identified differentially expressed genes (DEGs) in the cohort by comparing the expression profiles of tumor samples and normal samples, and then constructed a local network for each mutation gene using DEGs and mutant genes according to the protein–protein interaction network. Finally, we calculated the score of each mutant gene according to the objective function. The top-ranking mutant genes were selected as driver genes. We name the proposed method as mutations effect and network centrality.
Conclusions
Four types of cancer data in The Cancer Genome Atlas were tested. The experimental data proved that our method was superior to the existing network-centric method, as it was able to quickly and easily identify driver genes and rare driver factors.
We identify structures of the young star cluster NGC 2232 in the solar neighborhood (323.0 pc) and a newly discovered star cluster, LP 2439 (289.1 pc). Member candidates are identified using the Gaia ...DR2 sky position, parallax, and proper-motion data by an unsupervised machine-learning method, StarGO. Member contamination from the Galactic disk is further removed using the color-magnitude diagram. The four identified groups (NGC 2232, LP 2439, and two filamentary structures) of stars are coeval with an age of 25 Myr and were likely formed in the same giant molecular cloud. We correct the distance asymmetry from the parallax error with a Bayesian method. The 3D morphology shows the two spherical distributions of clusters NGC 2232 and LP 2439. Two filamentary structures are spatially and kinematically connected to NGC 2232. Both NGC 2232 and LP 2439 are expanding. The expansion is more significant in LP 2439, generating a loose spatial distribution with shallow volume number and mass density profiles. The expansion is suggested to be mainly driven by gas expulsion. With 73% of the cluster mass bound, NGC 2232 is currently experiencing a process of revirialization, However, LP 2439, with 52% of the cluster mass unbound, may fully dissolve in the near future. The different survivability traces the different dynamical states of NGC 2232 and LP 2439 prior to the onset of gas expulsion. While NGC 2232 may have been substructured and subvirial, LP 2439 may have either been virial/supervirial or experienced a much faster rate of gas removal.
Abstract
Summary
admetSAR was developed as a comprehensive source and free tool for the prediction of chemical ADMET properties. Since its first release in 2012 containing 27 predictive models, ...admetSAR has been widely used in chemical and pharmaceutical fields. This update, admetSAR 2.0, focuses on extension and optimization of existing models with significant quantity and quality improvement on training data. Now 47 models are available for either drug discovery or environmental risk assessment. In addition, we added a new module named ADMETopt for lead optimization based on predicted ADMET properties.
Availability and implementation
Free available on the web at http://lmmd.ecust.edu.cn/admetsar2/
Supplementary information
Supplementary data are available at Bioinformatics online.
We report the discovery of tidal structures around the intermediate-aged (∼700-800 Myr), nearby (∼85 pc) star cluster Coma Berenices. The spatial and kinematic grouping of stars is determined with ...the Gaia DR2 parallax and proper motion data, by a clustering analysis tool, StarGO, to map 5D parameters (X, Y, Z, ) onto a 2D neural network. Leading and trailing tails, each with an extension of ∼50 pc are revealed for the first time around this disrupting star cluster. The cluster members, totaling , are clearly mass-segregated, and exhibit a flat mass function with ∼ 0.79 0.16, in the sense of dN/dm ∝ m− , where N is the number of member stars and m is stellar mass, in the mass range of m = 0.25-2.51 M☉. Within the tidal radius of ∼6.9 pc, there are 77 member candidates with an average position, i.e., the cluster center, of R.A. = 186 8110, and decl. = 25 8112, and an average distance of 85.8 pc. Additional 120 member candidates reside in the tidal structures, i.e., outnumbering those in the cluster core. The expansion of escaping members lead to an anisotropy in the velocity field of the tidal tails. Our analysis also serendipitously uncovers an adjacent stellar group, part of which has been cataloged in the literature. We identify 218 member candidates, 10 times more than previously known. This star group is some 65 pc away from, and ∼400 Myr younger than, Coma Ber, but is already at the final stage of disruption.
Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of ...antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis.
We explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-β1 (TGF-β1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, α-smooth muscle actin (α-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, α-SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry.
Long-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-β1, CTGF, and Collagen I and III expression.
Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.
We report a synthetic route to achieving nanoscale heterostructures consisting of a metal core and monocrystalline semiconductor shell with substantial lattice mismatches between them, which cannot ...be obtained by conventional epitaxial techniques. By controlling soft acid-base coordination reactions between molecular complexes and colloidal nanostructures, we show that chemical thermodynamics can drive nanoscale monocrystalline growth of the semiconductor shell with a lattice structure incommensurate with that of the core. More complex hybrid core-shell structures with azimuthal and radial nanotailoring of structures and compositions of the monocrystalline semiconductor shell are also demonstrated.
We present the stellar population, using Gaia DR2 parallax, kinematics, and photometry, of the young (∼100 Myr), nearby (∼230 pc) open cluster, Blanco 1. A total of 644 member candidates are ...identified via the unsupervised machine learning method StarGO to find the clustering in the five-dimensional position and proper motion parameter (X, Y, Z, , δ) space. Within the tidal radius of 10.0 0.3 pc, there are 488 member candidates, 3 times more than those outside. A leading tail and a trailing tail, each of 50-60 pc in the Galactic plane, are found for the first time for this cluster, with stars further from the cluster center streaming away faster, manifest stellar stripping. Blanco 1 has a total detected mass of 285 32 M with a mass function consistent with a slope of = 1.35 0.2 in the sense of , in the mass range of 0.25-2.51 M , where N is the number of members and m is stellar mass. A minimum spanning tree (ΛMSR) analysis shows the cluster to be moderately mass segregated among the most massive members ( 1.4 M ), suggesting an early stage of dynamical disintegration.
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