Hot and crispy : CRISPR-Cas systems in the hyperthermophile Sulfolobus solfataricus

The CRISPR (clustered regularly interspaced short palindromic repeats) and Cas (CRISPR-associated) genes are widely spread in bacteria and archaea, representing an intracellular defence system against invading viruses and plasmids. In the system, fragments from foreign DNA are captured and integrated into the host genome at the CRISPR locus. The locus is transcribed and the resulting RNAs are processed by Cas6 into small crRNAs (CRISPR RNAs) that guide a variety of effector complexes to degrade the invading genetic elements. Many bacteria and archaea have one major type of effector complex. However, Sulfolobus solfataricus strain P2 has six CRISPR loci with two families of repeats, four cas6 genes and three different types of effector complex. These features make S. solfataricus an important model for studying CRISPR-Cas systems. In the present article, we review our current understanding of crRNA biogenesis and its effector complexes, subtype I-A and subtype III-B, in S. solfataricus. We also discuss the differences in terms of mechanisms between the subtype III-B systems in S. solfataricus and Pyrococcus furiosus.PostprintPeer reviewe

The density profile of equilibrium and non-equilibrium dark matter halos

We study the diversity of the density profiles of dark matter halos based on a large set of high-resolution cosmological simulations of 256^3 particles. The cosmological models include four scale-free models and three representative cold dark matter models. The simulations have good force resolution, and there are about 400 massive halos with more than 10^4 particles within the virial radius in each cosmological model. Our unbiased selection of all massive halos enables to quantify how well the bulk of dark matter halos can be described by the Navarro, Frenk & White (NFW) profile which was established for equilibrium halos. We find that about seventy percent of the halos can be fitted by the NFW profile with a fitting residual dvi_{max} less than 30% in Omega_0=1 universes. This percentage is higher in lower density cosmological models. The rest of the halos exhibits larger deviations from the NFW profile for more significant internal substructures. There is a considerable amount of variation in the density profile even for the halos which can be fitted by the NFW profile (i.e. dvi_{max}<0.30). The distribution of the profile parameter, the concentration $c$, can be well described by a lognormal function with the mean value \bar c slightly smaller (15%) than the NFW result and the dispersion \sigma_c in \ln c about 0.25. The more virialized halos with dvi_{max}<0.15 have the mean value \bar c in good agreement with the NFW result and a slightly smaller dispersion \sigma_c (about 0.2). Our results can alleviate some of the conflicts found recently between the theoretical NFW profile and observational results. Implications for theoretical and observational studies of galaxy formation are discussed.Comment: The final version accepted for publication in ApJ; one figure and one paragraph added to demonstrate that all the conclusions of the first version are solid to the resoltuion effects; 19 pages with 6 figure

Targeting the Nrf2-Heme Oxygenase-1 Axis after Intracerebral Hemorrhage.

BACKGROUND: Injury to cells adjacent to an intracerebral hemorrhage (ICH) is likely mediated at least in part by toxins released from the hematoma that initiate complex and interacting injury cascades. Pharmacotherapies targeting a single toxin or pathway, even if consistently effective in controlled experimental models, have a high likelihood of failure in a variable clinical setting. Nuclear factor erythroid-2 related factor 2 (Nrf2) regulates the expression of heme oxygenase-1 (HO-1) and multiple other proteins with antioxidant and antiinflammatory effects, and may be a target of interest after ICH. METHODS: Studies that tested the effect of HO and Nrf2 in models relevant to ICH are summarized, with an effort to reconcile conflicting data by consideration of methodological limitations. RESULTS: In vitro studies demonstrated that Nrf2 activators rapidly increased HO-1 expression in astrocytes, and reduced their vulnerability to hemoglobin or hemin. Modulating HO-1 expression via genetic approaches yielded similar results. Systemic treatment with small molecule Nrf2 activators increased HO-1 expression in perivascular cells, particularly astrocytes. When tested in mouse or rat ICH models, Nrf2 activators were consistently protective, improving barrier function and attenuating edema, inflammation, neuronal loss and neurological deficits. These effects were mimicked by selective astrocyte HO-1 overexpression in transgenic mice. CONCLUSION: Systemic treatment with Nrf2 activators after ICH is protective in rodents. Two compounds, dimethyl fumarate and hemin, are currently approved for treatment of multiple sclerosis and acute porphyria, respectively, and have acceptable safety profiles over years of clinical use. Further development of these drugs as ICH therapeutics seems warranted

Kondo correlation and spin-flip scattering in spin-dependent transport through a quantum dot coupled to ferromagnetic leads

We investigate the linear and nonlinear dc transport through an interacting quantum dot connected to two ferromagnetic electrodes around Kondo regime with spin-flip scattering in the dot. Using a slave-boson mean field approach for the Anderson Hamiltonian having finite on-site Coulomb repulsion, we find that a spin-flip scattering always depresses the Kondo correlation at arbitrary polarization strength in both parallel and antiparallel alignment of the lead magnetization and that it effectively reinforces the tunneling related conductance in the antiparallel configuration. For systems deep in the Kondo regime, the zero-bias single Kondo peak in the differential conductance is split into two peaks by the intradot spin-flip scattering; while for systems somewhat further from the Kondo center, the spin-flip process in the dot may turn the zero-bias anomaly into a three-peak structure.Comment: 4 pages, 2 figure

Supersolidity and phase diagram of softcore bosons in a triangular lattice

We study the softcore extended Bose Hubbard model in a two-dimensional triangular lattice by using the quantum Monte Carlo methods. The ground state phase diagram of the system exhibits a very fruitful structure. Except the Mott insulating state, four kinds of solid states with respect to the commensurate filling factors $\rho=1/3,2/3$ and $\rho=1$ are identified. Two of them (CDW II and CDW III) are newly predicted. In incommensurate fillings, superfluid, spuersolid as well as phase separation states are detected . As in the case for the hardcore bosons, a supersolid phase exists in $1/3<\rho<2/3$ while it is unstable towards the phase separation in $\rho<1/3$. However, this instability is refrained in $2/3<\rho<1$ due to the softening of the bosons and then a supersolid phase survives.Comment: 4 pages, 5 figure

The Power Spectrum, Bias Evolution, and the Spatial Three-Point Correlation Function

We calculate perturbatively the normalized spatial skewness, $S_3$, and full three-point correlation function (3PCF), $\zeta$, induced by gravitational instability of Gaussian primordial fluctuations for a biased tracer-mass distribution in flat and open cold-dark-matter (CDM) models. We take into account the dependence on the shape and evolution of the CDM power spectrum, and allow the bias to be nonlinear and/or evolving in time, using an extension of Fry's (1996) bias-evolution model. We derive a scale-dependent, leading-order correction to the standard perturbative expression for $S_3$ in the case of nonlinear biasing, as defined for the unsmoothed galaxy and dark-matter fields, and find that this correction becomes large when probing positive effective power-spectrum indices. This term implies that the inferred nonlinear-bias parameter, as usually defined in terms of the smoothed density fields, might depend on the chosen smoothing scale. In general, we find that the dependence of $S_3$ on the biasing scheme can substantially outweigh that on the adopted cosmology. We demonstrate that the normalized 3PCF, $Q$, is an ill-behaved quantity, and instead investigate $Q_V$, the variance-normalized 3PCF. The configuration dependence of $Q_V$ shows similarly strong sensitivities to the bias scheme as $S_3$, but also exhibits significant dependence on the form of the CDM power spectrum. Though the degeneracy of $S_3$ with respect to the cosmological parameters and constant linear- and nonlinear-bias parameters can be broken by the full configuration dependence of $Q_V$, neither statistic can distinguish well between evolving and non-evolving bias scenarios. We show that this can be resolved, in principle, by considering the redshift dependence of $\zeta$.Comment: 41 pages, including 12 Figures. To appear in The Astrophysical Journal, Vol. 521, #