HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.</div

Community assembly of the native C. elegans microbiome is influenced by time, substrate and individual bacterial taxa

Summary Microbiome communities are complex assemblages of bacteria. The dissection of their assembly dynamics is challenging because it requires repeated sampling of both host and source communities. We used the nematode Caenorhabditis elegans as a model to study these dynamics. We characterized microbiome variation from natural worm populations and their substrates for two consecutive years using 16S rDNA amplicon sequencing. We found conservation in microbiome composition across time at the genus, but not amplicon sequencing variant (ASV) level. Only three ASVs were consistently present across worm samples (Comamonas ASV10859, Pseudomonas ASV7162 and Cellvibrio ASV9073). ASVs were more diverse in worms from different rather than the same substrates, indicating an influence of the source community on microbiome assembly. Surprisingly, almost 50% of worm-associated ASVs were absent in corresponding substrates, potentially due to environmental filtering. Ecological network analysis revealed strong effects of bacteria–bacteria interactions on community composition: While a dominant Erwinia strain correlated with decreased alpha-diversity, predatory bacteria of the Bdellovibrio and like organisms associated with increased alpha-diversity. High alpha-diversity was further linked to high worm population growth, especially on species-poor substrates. Our results highlight that microbiomes are individually shaped and sensitive to dramatic community shifts in response to particular competitive species

Humidity-Induced Degradation of Lithium-Stabilized Sodium-Beta Alumina Solid Electrolytes

Sodium-beta alumina is a solid-state electrolyte with outstanding chemical, electrochemical, and mechanical properties. Sodium polyaluminate is successfully employed in established Na–S and Na–NiCl 2 cell systems. It is a promising candidate for all-solid-state sodium batteries. However, humidity affects the performance of this solid electrolyte. In this work, the effect of humidity on disk-shaped samples of Li-stabilized sodium-beta alumina stored in three different environments is quantified. We used impedance analysis and additional characterizations to investigate the consequences of the occurring degradation, namely ion exchange and subsequent buildup of surface layers. Sodium-beta alumina’s ionic conductivity gradually deteriorates up to two orders of magnitude. This is due to layers developed superficially during storage, while its fracture strength of 240 MPa remains unaffected. Changes in microstructure, composition, and cycle life of Na|BASE|Na cells highlight the importance of proper storage conditions: In just one week of improper storage, the critical current density collapsed from the maximum of 9.1 mA cm −2 , one of the highest values reported for sodium-beta alumina, to 1.7 mA cm −2 at 25 °C. The results validate former observations regarding sodium-beta alumina’s moisture sensitivity and suggest how to handle sodium-beta alumina used in electrochemical cell systems

Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Computing Zernike polynomials of arbitrary degree using the discrete Fourier transform

The conventional representation of Zernike polynomials R_n^m(rho) gives unacceptable results for large values of the degree n. We present an algorithm for the computation of Zernike polynomials of arbitrary degree n. The algorithm has the form of a discrete cosine transform which comes with advantages over other methods in terms of computation time, accuracy and transparancy. As an application we consider the effect of NA-scaling on the lower-order aberrations of an optical system in the presence of a very high order aberration

Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy

Rapid evolution is central to the current antibiotic crisis. Sustainable treatments must thus take account of the bacteria’s potential for adaptation. We identified cellular hysteresis as a principle to constrain bacterial evolution. Cellular hysteresis is a persistent change in bacterial physiology, reminiscent of cellular memory, which is induced by one antibiotic and enhances susceptibility toward another antibiotic. Cellular hysteresis increases bacterial extinction in fast sequential treatments and reduces selection of resistance by favoring responses specific to the induced physiological effects. Fast changes between antibiotics are key, because they create the continuously high selection conditions that are difficult to counter by bacteria. Our study highlights how an understanding of evolutionary processes can help to outsmart human pathogens.Antibiotic resistance has become one of the most dramatic threats to global health. While novel treatment options are urgently required, most attempts focus on finding new antibiotic substances. However, their development is costly, and their efficacy is often compromised within short time periods due to the enormous potential of microorganisms for rapid adaptation. Here, we developed a strategy that uses the currently available antibiotics. Our strategy exploits cellular hysteresis, which is the long-lasting, transgenerational change in cellular physiology that is induced by one antibiotic and sensitizes bacteria to another subsequently administered antibiotic. Using evolution experiments, mathematical modeling, genomics, and functional genetic analysis, we demonstrate that sequential treatment protocols with high levels of cellular hysteresis constrain the evolving bacteria by (i) increasing extinction frequencies, (ii) reducing adaptation rates, and (iii) limiting emergence of multidrug resistance. Cellular hysteresis is most effective in fast sequential protocols, in which antibiotics are changed within 12 h or 24 h, in contrast to the less frequent changes in cycling protocols commonly implemented in hospitals. We found that cellular hysteresis imposes specific selective pressure on the bacteria that disfavors resistance mutations. Instead, if bacterial populations survive, hysteresis is countered in two distinct ways, either through a process related to antibiotic tolerance or a mechanism controlled by the previously uncharacterized two-component regulator CpxS. We conclude that cellular hysteresis can be harnessed to optimize antibiotic therapy, to achieve both enhanced bacterial elimination and reduced resistance evolution

On the evolution of eccentric and inclined protoplanets embedded in protoplanetary disks

Young planets embedded in their protoplanetary disk interact gravitationally with it leading to energy and angular momentum exchange. This interaction determines the evolution of the planet through changes to the orbital parameters. We investigate changes in the orbital elements of a 20 Earth--mass planet due to the torques from the disk. We focus on the non-linear evolution of initially non-vanishing eccentricity $e$ and/or inclination $i$. We treat the disk as a two- or three-dimensional viscous fluid and perform hydrodynamical simulations with an embedded planet. We find rapid exponential decay of the planet orbital eccentricity and inclination for small initial values of $e$ and $i$, in agreement with linear theory. For larger values of $e > 0.1$ the decay time increases and the decay rate scales as $\dot{e} \propto e^{-2}$, consistent with existing theoretical models. For large inclinations ($i$ > 6 deg) the inclination decay rate shows an identical scaling $di/dt \propto i^{-2}$. We find an interesting dependence of the migration on the eccentricity. In a disk with aspect ratio $H/r=0.05$ the migration rate is enhanced for small non-zero eccentricities ($e < 0.1$), while for larger values we see a significant reduction by a factor of $\sim 4$. We find no indication for a reversal of the migration for large $e$, although the torque experienced by the planet becomes positive when $e \simeq 0.3$. This inward migration is caused by the persisting energy loss of the planet. For non gap forming planets, eccentricity and inclination damping occurs on a time scale that is very much shorter than the migration time scale. The results of non linear hydrodynamic simulations are in very good agreement with linear theory for small $e$ and $i$.Comment: accepted for Astronomy & Astrophysics, 16 pages, 16 figures, animations under: http://www.tat.physik.uni-tuebingen.de/~kley/publ/paper/eccp.htm