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

Effects of Speed and Visual-Target Distance on Toe Trajectory During the Swing Phase of Treadmill Walking

Toe trajectory during swing phase is a precise motor control task that can provide insights into the sensorimotor control of the legs. The purpose of this study was to determine changes in vertical toe trajectory during treadmill walking due to changes in walking speed and target distance. For each trial, subjects walked on a treadmill at one of five speeds while performing a dynamic visual acuity task at either a far or near target distance (five speeds two targets distances = ten trials). Toe clearance decreased with increasing speed, and the vertical toe peak just before heel strike increased with increasing speed, regardless of target distance. The vertical toe peak just after toe-off was lower during near-target visual acuity tasks than during far-target tasks, but was not affected by speed. The ankle of the swing leg appeared to be the main joint angle that significantly affected all three toe trajectory events. The foot angle of the swing leg significantly affected toe clearance and the toe peak just before heel strike. These results will be used to enhance the analysis of lower limb kinematics during the sensorimotor treadmill testing, where differing speeds and/or visual target distances may be used

A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

Factorization of correlations in two-dimensional percolation on the plane and torus

Recently, Delfino and Viti have examined the factorization of the three-point density correlation function P_3 at the percolation point in terms of the two-point density correlation functions P_2. According to conformal invariance, this factorization is exact on the infinite plane, such that the ratio R(z_1, z_2, z_3) = P_3(z_1, z_2, z_3) [P_2(z_1, z_2) P_2(z_1, z_3) P_2(z_2, z_3)]^{1/2} is not only universal but also a constant, independent of the z_i, and in fact an operator product expansion (OPE) coefficient. Delfino and Viti analytically calculate its value (1.022013...) for percolation, in agreement with the numerical value 1.022 found previously in a study of R on the conformally equivalent cylinder. In this paper we confirm the factorization on the plane numerically using periodic lattices (tori) of very large size, which locally approximate a plane. We also investigate the general behavior of R on the torus, and find a minimum value of R approx. 1.0132 when the three points are maximally separated. In addition, we present a simplified expression for R on the plane as a function of the SLE parameter kappa.Comment: Small corrections (final version). In press, J. Phys.

Intrinsic symmetry groups of links with 8 and fewer crossings

We present an elementary derivation of the "intrinsic" symmetry groups for knots and links of 8 or fewer crossings. The standard symmetry group for a link is the mapping class group \MCG(S^3,L) or \Sym(L) of the pair $(S^3,L)$. Elements in this symmetry group can (and often do) fix the link and act nontrivially only on its complement. We ignore such elements and focus on the "intrinsic" symmetry group of a link, defined to be the image $\Sigma(L)$ of the natural homomorphism \MCG(S^3,L) \rightarrow \MCG(S^3) \cross \MCG(L). This different symmetry group, first defined by Whitten in 1969, records directly whether $L$ is isotopic to a link $L'$ obtained from $L$ by permuting components or reversing orientations. For hyperbolic links both \Sym(L) and $\Sigma(L)$ can be obtained using the output of \texttt{SnapPea}, but this proof does not give any hints about how to actually construct isotopies realizing $\Sigma(L)$. We show that standard invariants are enough to rule out all the isotopies outside $\Sigma(L)$ for all links except $7^2_6$, $8^2_{13}$ and $8^3_5$ where an additional construction is needed to use the Jones polynomial to rule out "component exchange" symmetries. On the other hand, we present explicit isotopies starting with the positions in Cerf's table of oriented links which generate $\Sigma(L)$ for each link in our table. Our approach gives a constructive proof of the $\Sigma(L)$ groups.Comment: 72 pages, 66 figures. This version expands the original introduction into three sections; other minor changes made for improved readabilit

Optimization of carbon and energy utilization through differential translational efficiency.

Control of translation is vital to all species. Here we employ a multi-omics approach to decipher condition-dependent translational regulation in the model acetogen Clostridium ljungdahlii. Integration of data from cells grown autotrophically or heterotrophically revealed that pathways critical to carbon and energy metabolism are under strong translational regulation. Major pathways involved in carbon and energy metabolism are not only differentially transcribed and translated, but their translational efficiencies are differentially elevated in response to resource availability under different growth conditions. We show that translational efficiency is not static and that it changes dynamically in response to mRNA expression levels. mRNAs harboring optimized 5'-untranslated region and coding region features, have higher translational efficiencies and are significantly enriched in genes encoding carbon and energy metabolism. In contrast, mRNAs enriched in housekeeping functions harbor sub-optimal features and have lower translational efficiencies. We propose that regulation of translational efficiency is crucial for effectively controlling resource allocation in energy-deprived microorganisms

Mantle to surface degassing of alkalic magmas at Erebus volcano, Antarctica

International audienceContinental intraplate volcanoes, such as Erebus volcano, Antarctica, are associated with extensional tectonics, mantle upwelling and high heat flow. Typically, erupted magmas are alkaline and rich in volatiles (especially CO2), inherited from low degrees of partial melting of mantle sources. We examine the degassing of the magmatic system at Erebus volcano using melt inclusion data and high temporal resolution open-path Fourier transform infrared (FTIR) spectroscopic measurements of gas emissions from the active lava lake. Remarkably different gas signatures are associated with passive and explosive gas emissions, representative of volatile contents and redox conditions that reveal contrasting shallow and deep degassing sources. We show that this unexpected degassing signature provides a unique probe for magma differentiation and transfer of CO2-rich oxidised fluids from the mantle to the surface, and evaluate how these processes operate in time and space. Extensive crystallisation driven by CO2 fluxing is responsible for isobaric fractionation of parental basanite magmas close to their source depth. Magma deeper than 4 kbar equilibrates under vapour-buffered conditions. At shallower depths, CO2-rich fluids accumulate and are then released either via convection-driven, open-system gas loss or as closed-system slugs that ascend and result in Strombolian eruptions in the lava lake. The open-system gases have a reduced state (below the QFM buffer) whereas the closed-system gases preserve their deep oxidised signatures (close to the NNO buffer)