Accurate Reconstruction of Molecular Phylogenies for Proteins Using Codon and Amino Acid Unified Sequence Alignments (CAUSA)

Based on molecular clock hypothesis, and neutral theory of molecular evolution, molecular phylogenies have been widely used for inferring evolutionary history of organisms and individual genes. Traditionally, alignments and phylogeny trees of proteins and their coding DNA sequences are constructed separately, thus often different conclusions were drawn. Here we present a new strategy for sequence alignment and phylogenetic tree reconstruction, codon and amino acid unified sequence alignment (CAUSA), which aligns DNA and protein sequences and draw phylogenetic trees in a unified manner. We demonstrated that CAUSA improves both the accuracy of multiple sequence alignments and phylogenetic trees by solving a variety of molecular evolutionary problems in virus, bacteria and mammals. Our results support the hypothesis that the molecular clock for proteins has two pointers existing separately in DNA and protein sequences. It is more accurate to read the molecular clock by combination (additive) of these two pointers, since the ticking rates of them are sometimes consistent, sometimes different. CAUSA software were released as Open Source under GNU/GPL license, and are downloadable free of charge from the website www.dnapluspro.com

A type IV modification-dependent restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300

A gene encoding a putative DNA helicase from Staphylococcus aureus USA300 was cloned and expressed in Escherichia coli. The protein was purified to over 90% purity by chromatography. The purified enzyme, SauUSI, predominantly cleaves modified DNA containing 5mC and 5-hydroxymethylcytosine. Cleavage of 5mC-modified plasmids indicated that the sites S5mCNGS (S = C or G) are preferentially digested. The endonuclease activity requires the presence of adenosine triphosphate (ATP) or dATP whereas the non-hydrolyzable γ-S-ATP does not support activity. SauUSI activity was inhibited by ethylenediaminetetraacetic acid. It is most active in Mg++ buffers. No companion methylase gene was found near the SauUSI restriction gene. The absence of a cognate methylase and cleavage of modified DNA indicate that SauUSI belongs to type IV restriction endonucleases, a group that includes EcoK McrBC and Mrr. SauUSI belongs to a family of highly similar homologs found in other sequenced S. aureus, S. epidermidis and S. carnosus genomes. More distant SauUSI orthologs can be found in over 150 sequenced bacterial/archaea genomes. Finally, we demonstrated the biological function of the type IV REase in restricting 5mC-modified plasmid DNA by transformation into clinical S. aureus strain SA564, and in restricting phage λ infection when the endonuclease is expressed in E. col

Perspective of monochromatic gamma-ray line detection with the High Energy cosmic-Radiation Detection (HERD) facility onboard China's Space Station

HERD is the High Energy cosmic-Radiation Detection instrument proposed to operate onboard China's space station in the 2020s. It is designed to detect energetic cosmic ray nuclei, leptons and photons with a high energy resolution ($\sim1\%$ for electrons and photons and $20\%$ for nuclei) and a large geometry factor ($>3\,{ m^2\,sr}$ for electrons and diffuse photons and $>2\,{ m^2\,sr}$ for nuclei). In this work we discuss the capability of HERD to detect monochromatic $\gamma$-ray lines, based on simulations of the detector performance. It is shown that HERD will be one of the most sensitive instruments for monochromatic $\gamma$-ray searches at energies between $\sim10$ to a few hundred GeV. Above hundreds of GeV, Cherenkov telescopes will be more sensitive due to their large effective area. As a specific example, we show that a good portion of the parameter space of a supersymmetric dark matter model can be probed with HERD.Comment: 9 pages, 7 figures, matches version published in Astropart.Phy

Triple crossing positivity bounds, mass dependence and cosmological scalars: Horndeski theory and DHOST

Scalars are widely used in cosmology to model novel phenomena such as the late-time cosmic acceleration. These are effective field theories with highly nonlinear interactions, including Horndeski theory/generalized galileon and beyond. We use the latest fully crossing symmetric positivity bounds to constrain these cosmological EFTs. These positivity bounds, based on fundamental principles of quantum field theory such as causality and unitarity, are able to constrain the EFT coefficients both from above and below. We first map the mass dependence of the fully crossing symmetric bounds, and find that a nonzero mass generically enlarges the positivity regions. We show that fine-tunings in the EFT construction can significantly reduce the viable regions and sometimes can be precarious. Then, we apply the positivity bounds to several models in the Horndeski class and beyond, explicitly listing the ready-to-use bounds with the model parameters, and discuss the implications for these models. The new positivity bounds are found to severely constrain some of these models, in which positivity requires the mass to be parametrically close to the cutoff of the EFT, effectively ruling them out. The examples include massive galileon, the original beyond Horndeski model, and DHOST theory with unity speed of gravity and nearly constant Newton's coupling.Comment: 45 pages, 16 figures, 1 table. To appear in JCA

Increasing cleavage specificity and activity of restriction endonuclease KpnI

Restriction enzyme KpnI is a HNH superfamily endonuclease requiring divalent metal ions for DNA cleavage but not for binding. The active site of KpnI can accommodate metal ions of different atomic radii for DNA cleavage. Although Mg2+ ion higher than 500 μM mediates promiscuous activity, Ca2+ suppresses the promiscuity and induces high cleavage fidelity. Here, we report that a conservative mutation of the metal-coordinating residue D148 to Glu results in the elimination of the Ca2+-mediated cleavage but imparting high cleavage fidelity with Mg2+. High cleavage fidelity of the mutant D148E is achieved through better discrimination of the target site at the binding and cleavage steps. Biochemical experiments and molecular dynamics simulations suggest that the mutation inhibits Ca2+-mediated cleavage activity by altering the geometry of the Ca2+-bound HNH active site. Although the D148E mutant reduces the specific activity of the enzyme, we identified a suppressor mutation that increases the turnover rate to restore the specific activity of the high fidelity mutant to the wild-type level. Our results show that active site plasticity in coordinating different metal ions is related to KpnI promiscuous activity, and tinkering the metal ion coordination is a plausible way to reduce promiscuous activity of metalloenzymes

Evidence for a New Excitation at the Interface Between a High-Tc Superconductor and a Topological Insulator

High-temperature superconductors exhibit a wide variety of novel excitations. If contacted with a topological insulator, the lifting of spin rotation symmetry in the surface states can lead to the emergence of unconventional superconductivity and novel particles. In pursuit of this possibility, we fabricated high critical-temperature (Tc ~ 85 K) superconductor/topological insulator (Bi2Sr2CaCu2O8+delta/Bi2Te2Se) junctions. Below 75 K, a zero-bias conductance peak (ZBCP) emerges in the differential conductance spectra of this junction. The magnitude of the ZBCP is suppressed at the same rate for magnetic fields applied parallel or perpendicular to the junction. Furthermore, it can still be observed and does not split up to at least 8.5 T. The temperature and magnetic field dependence of the excitation we observe appears to fall outside the known paradigms for a ZBCP