Gating-like Motions and Wall Porosity in a DNA Nanopore Scaffold Revealed by Molecular Simulations

Recently developed synthetic membrane pores composed of folded DNA enrich the current range of natural and engineered protein pores and of nonbiogenic channels. Here we report all-atom molecular dynamics simulations of a DNA nanotube (DNT) pore scaffold to gain fundamental insight into its atomic structure, dynamics, and interactions with ions and water. Our multiple simulations of models of DNTs that are composed of a six-duplex bundle lead to a coherent description. The central tube lumen adopts a cylindrical shape while the mouth regions at the two DNT openings undergo gating-like motions which provide a possible molecular explanation of a lower conductance state observed in our previous experimental study on a membrane-spanning version of the DNT (ACS Nano 2015, 9, 1117-26). Similarly, the central nanotube lumen is filled with water and ions characterized by bulk diffusion coefficients while the gating regions exhibit temporal fluctuations in their aqueous volume. We furthermore observe that the porous nature of the walls allows lateral leakage of ions and water. This study will benefit rational design of DNA nanopores of enhanced stability of relevance for sensing applications, of nanodevices with tunable gating properties that mimic gated ion channels, or of nanopores featuring defined permeation behavior

Galaxy And Mass Assembly (GAMA) : The mechanisms for quiescent galaxy formation at z<1

© 2016 The Authors. One key problem in astrophysics is understanding how and why galaxies switch off their star formation, building the quiescent population that we observe in the local Universe. From the Galaxy And Mass Assembly and VIsible MultiObject Spectrograph Public Extragalactic Redshift surveys, we use spectroscopic indices to select quiescent and candidate transition galaxies.We identify potentially rapidly transitioning post-starburst (PSB) galaxies and slower transitioning green-valley galaxies. Over the last 8Gyr, the quiescent population has grown more slowly in number density at high masses (M * > 10 11 M ⊙ ) than at intermediate masses (M * > 10 10.6 M ⊙ ). There is evolution in both the PSB and green-valley stellar mass functions, consistent with higher mass galaxies quenching at earlier cosmic times.At intermediatemasses (M * > 10 10.6 M ⊙ ), we find a green-valley transition time-scale of 2.6 Gyr. Alternatively, at z ~ 0.7, the entire growth rate could be explained by fast-quenching PSB galaxies, with a visibility time-scale of 0.5 Gyr. At lower redshift, the number density of PSBs is so low that an unphysically short visibility window would be required for them to contribute significantly to the quiescent population growth. The importance of the fast-quenching route may rapidly diminish at z 10 11 M ⊙ ), there is tension between the large number of candidate transition galaxies compared to the slow growth of the quiescent population. This could be resolved if not all high-mass PSB and green-valley galaxies are transitioning from star forming to quiescent, for example if they rejuvenate out of the quiescent population following the accretion of gas and triggering of star formation, or if they fail to completely quench their star formation

Discovery of a ~1 Hz quasi-periodic oscillation in the low-mass X-ray binary 4U 1746-37

We have discovered a ~1 Hz quasi-periodic oscillation (QPO) in the persistent X-ray emission and during type I X-ray bursts of the globular cluster source, dipper and low-mass X-ray binary (LMXB) 4U 1746-37. The QPO properties resemble those of QPOs found recently in the LMXB dippers 4U 1323-62, and EXO 0748-676, which makes 4U 1746-37 the third source known to exhibit this type of QPOs. We present evidence for X-ray spectral changes in this source similar to those observed in LMXBs referred to as atoll sources. We detect two states, a low intensity and spectrally hard state, and a higher intensity and spectrally soft state. This may explain the different spectral characteristics reported for 4U 1746-37 earlier. The high intensity state resembles the banana branch state of atoll sources. The QPOs are only seen in the low intensity state, and are absent when the source is in the banana branch. This strongly suggests that either the accretion disk or an extended central source change shape between the low intensity state and the banana branch. Twelve bursts were detected, of which 5 took place while the source was on the banana branch and 7 when the source was in the low intensity state. The bursts occurring on the banana branch had an e-folding time ~3 times longer than those which occurred in the low intensity state. Whereas previously detected dips showed only a decrease in count rate of ~15%, we found in one observation a dip in which the count rate dropped from ~200 counts per second to ~20 counts per second. This dip lasted only ~250 seconds, during which clear spectral hardening occured. This is the first time strong evidence for spectral changes during a dip are reported for this source.Comment: 17 pages, accepted for publication in Ap

An Extended and More Sensitive Search for Periodicities in RXTE/ASM X-ray Light Curves

We present the results of a systematic search in approximately 14 years of Rossi X-ray Timing Explorer All-Sky Monitor data for evidence of periodicities not reported by Wen et al. (2006). Two variations of the commonly used Fourier analysis search method have been employed to achieve significant improvements in sensitivity. The use of these methods and the accumulation of additional data have resulted in the detection of the signatures of the orbital periods of eight low-mass X-ray binary systems and of ten high-mass X-ray binaries not listed in the tables of Wen et al.Comment: 20 pages, 22 figures, in emulateapj format; submitted to ApJ

Absorption-Line Probes of Gas and Dust in Galactic Superwinds

We discuss moderate resolution spectra of the NaD absorption-line in a sample of 32 far-IR-bright starburst galaxies. In 18 cases, the line is produced primarily by interstellar gas, and in 12 of these it is blueshifted by over 100 km/s relative to the galaxy systemic velocity. The absorption-line profiles in these outflow sources span the range from near the galaxy systemic velocity to a maximum blueshift of 400 to 600 km/s. The outflows occur in galaxies systematically viewed more nearly face-on than the others. We therefore argue that the absorbing material consists of ambient interstellar gas accelerated along the minor axis of the galaxy by a hot starburst-driven superwind. The NaD lines are optically-thick, but indirect arguments imply total Hydrogen column densities of N_H = few X 10^{21} cm^{-2}. This implies that the superwind is expelling matter at a rate comparable to the star-formation rate. This outflowing material is very dusty: we find a strong correlation between the depth of the NaD profile and the line-of-sight reddening (E(B-V) = 0.3 to 1 over regions several-to-ten kpc in size). The estimated terminal velocities of superwinds inferred from these data and extant X-ray data are typically 400 to 800 km/s, are independent of the galaxy rotation speed, and are comparable to (substantially exceed) the escape velocities for $L_*$ (dwarf) galaxies. The resulting loss of metals can establish the mass-metallicity relation in spheroids, produce the observed metallicity in the ICM, and enrich a general IGM to 10$^{-1}$ solar metallicity. If the outflowing dust grains survive their journey into the IGM, their effect on observations of cosmologically-distant objects is significant.Comment: 65 pages, including 16 figures. ApJ, in pres

A human cancer-associated truncation of MBD4 causes dominant negative impairment of DNA repair in colon cancer cells

MBD4 binds to methylated DNA and acts as a thymine DNA glycosylase in base excision repair. Deficiency of MBD4 in mice enhances mutation at CpG sites and alters apoptosis in response to DNA damage, but does not increase tumorigenesis in mismatch repair-deficient mice. However, in humans, frameshift mutation of MBD4, rather than deletion, is what occurs in up to 43% of microsatellite unstable colon cancers. There is no murine equivalent of this mutation. We now show that recombinant truncated MBD4 (MBD4tru) inhibits glycosylase activities of normal MBD4 or Uracil DNA glycosylase in cell-free assays as a dominant negative effect. Furthermore, overexpression of MBD4tru in Big Blue (lacI)-transfected, MSI human colorectal carcinoma cells doubled mutation frequency, indicating that the modest dominant negative effect on DNA repair can occur in living cells in short-term experiments. Intriguingly, the whole mutation spectrum was increased, not only at CpG sites, suggesting that truncated MBD4 has a more widespread effect on genomic stability. This demonstration of a dominant negative effect may be of significance in tumour progression and acquisition of drug resistance

Wnt signaling is boosted during intestinal regeneration by a CD44-positive feedback loop

Enhancement of Wnt signaling is fundamental for stem cell function during intestinal regeneration. Molecular modules control Wnt activity by regulating signal transduction. CD44 is such a positive regulator and a Wnt target gene. While highly expressed in intestinal crypts and used as a stem cell marker, its role during intestinal homeostasis and regeneration remains unknown. Here we propose a CD44 positive-feedback loop that boosts Wnt signal transduction, thus impacting intestinal regeneration. Excision of Cd44 in Cd44$^{fl/fl}$;VillinCreER$^{T2}$ mice reduced Wnt target gene expression in intestinal crypts and affected stem cell functionality in organoids. Although the integrity of the intestinal epithelium was conserved in mice lacking CD44, they were hypersensitive to dextran sulfate sodium, and showed more severe inflammation and delayed regeneration. We localized the molecular function of CD44 at the Wnt signalosome, and identified novel DVL/CD44 and AXIN/CD44 complexes. CD44 thus promotes optimal Wnt signaling during intestinal regeneration

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis

Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here