Human T Lymphotropic Virus Type 1 protein Tax reduces histone levels

<p>Abstract</p> <p>Background</p> <p>Human T-Lymphotropic Virus Type-1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATLL). The virally encoded Tax protein is thought to be necessary and sufficient for T-cell leukemogenesis. Tax promotes inappropriate cellular proliferation, represses multiple DNA repair mechanisms, deregulates cell cycle checkpoints, and induces genomic instability. All of these Tax effects are thought to cooperate in the development of ATLL.</p> <p>Results</p> <p>In this study, we demonstrate that histone protein levels are reduced in HTLV-1 infected T-cell lines (HuT102, SLB-1 and C81) relative to uninfected T-cell lines (CEM, Jurkat and Molt4), while the relative amount of DNA per haploid complement is unaffected. In addition, we show that replication-dependent core and linker histone transcript levels are reduced in HTLV-1 infected T-cell lines. Furthermore, we show that Tax expression in Jurkat cells is sufficient for reduction of replication-dependent histone transcript levels.</p> <p>Conclusion</p> <p>These results demonstrate that Tax disrupts the proper regulation of replication-dependent histone gene expression. Further, our findings suggest that HTLV-1 infection uncouples replication-dependent histone gene expression and DNA replication, allowing the depletion of histone proteins with cell division. Histone proteins are involved in the regulation of all metabolic processes involving DNA including transcription, replication, repair and recombination. This study provides a previously unidentified mechanism by which Tax may directly induce chromosomal instability and deregulate gene expression through reduced histone levels.</p

Specific Heat Study of Non-Fermi Liquid Behavior in CeNi_2Ge_2: Anomalous Peak in Quasi-Particle Density-of-States

To investigate the non-Fermi liquid (NFL) behavior in a nonalloyed system CeNi_2Ge_2, we have measured the temperature and field dependences of the specific heat C on a CeNi_2Ge_2 single crystal. The distinctive temperature dependence of C/T (~a-b*T^(1/2)) is destroyed in almost the same manner for both field directions of B//c-axis and B//a-axis. The overall behavior of C(T,B) and the low-temperature upturn in magnetic susceptibility can be reproduced, assuming an anomalous peak of the quasi-particle-band density-of-states (DOS) at the Fermi energy possessing (epsilon)^(1/2) energy dependence. Absence of residual entropy around T=0 K in B~0 T has been confirmed by the magnetocaloric effect measurements, which are consistent with the present model. The present model can also be applied to the NFL behavior in CeCu_{5.9}Au_{0.1} using a ln(epsilon)-dependent peak in the DOS. Possible origins of the peak in the DOS are discussed.Comment: 4 pages, LaTeX, using jpsj.sty, to be published in J. Phys. Soc. Jpn. 66 No. 10 (1997), 7 figures available at http://494-475.phys.metro-u.ac.jp/ao/ceni2ge2.htm

A mechanism for the non-Fermi-liquid behavior in CeCu_{6-x}Au_x

We propose an explanation for the recently observed non-Fermi-liquid behavior of metallic alloys CeCu_{6-x}Au_x: near x=0.1, the specific heat c is proportional to T \ln (T_0/T) and the resistivity increases linearly with temperature T over a wide range of T. These features follow from a model in which three-dimensional conduction electrons are coupled to two-dimensional critical ferromagnetic fluctuations near the quantum critical point, x_{c}=0.1. This picture is motivated by the neutron scattering data in the ordered phase (x=0.2) and is consistent with the observed phase diagram.Comment: 4 pages, LaTeX, 3 figure

RKKY interaction and Kondo screening cloud for correlated electrons

The RKKY law and the Kondo screening cloud around a magnetic impurity are investigated for correlated electrons in 1D (Luttinger liquid). We find slow algebraic distance dependences, with a crossover between both types of behavior. Monte Carlo simulations have been developed to study this crossover. In the strong coupling regime, the Knight shift is shown to increase with distance due to correlations.Comment: 5 pages REVTeX, incl two figures, to appear in Phys.Rev.

Fluctuation Induced Non-Fermi Liquid Behavior near a Quantum Phase Transition in Itinerant Electron Systems

The signature for a non-Fermi liquid behavior near a quantum phase transition has been observed in thermal and transport properties of many metallic systems at low temperatures. In the present work we consider specific examples of itinerant ferromagnet as well as antiferromagnet in the limit of vanishing transition temperature. The temperature variation of spin susceptibility, electrical resistivity, specific heat, and NMR relaxation rates at low temperatures is calculated in the limit of infinite exchange enhancement within the frame work of a self consistent spin fluctuation theory. The resulting non-Fermi liquid behavior is due to the presence of the low lying critically damped spin fluctuations in these systems. The theory presented here gives the leading low temperature behavior, as it turns out that the fluctuation correlation term is always smaller than the mean fluctuation field term in three as well as in two space dimensions. A comparison with illustrative experimental results of these properties in some typical systems has been done. Finally we make some remarks on the effect of disorder in these systems.Comment: File RevTex, 7 Figures available on request, Abstract and text modified, To appear in Phys. Rev.

Non-Fermi liquid behavior and Griffiths phase in {\it f}-electron compounds

We study the interplay among disorder, RKKY and Kondo interactions in {\it f}-electron alloys. We argue that the non-Fermi liquid behavior observed in these systems is due to the existence of a Griffiths phase close to a quantum critical point. The existence of this phase provides a unified picture of a large class of materials. We also propose new experiments that can test these ideas.Comment: 4 pages, 1 Figure. NEW version of the original manuscript. A single framework for NFL behavior in different kinds of alloys is presented. Final version finally allowed to appear on the glorious Physical Review Letter

HTLV-1 Tax Mediated Downregulation of miRNAs Associated with Chromatin Remodeling Factors in T Cells with Stably Integrated Viral Promoter

RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type

Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

Contains fulltext : 168172.pdf (publisher's version ) (Open Access)Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow

Hall effect in the vicinity of quantum critical point in Tm1-xYbxB12

The angular, temperature and magnetic field dependences of Hall resistance roH for the rare-earth dodecaboride solid solutions Tm1-xYbxB12 have been studied in a wide vicinity of the quantum critical point (QCP) xC~0.3. The measurements performed in the temperature range 1.9-300 K on high quality single crystals allowed to find out for the first time in these fcc compounds both an appearance of the second harmonic contribution in ro2H at QCP and its enhancement under the Tm to ytterbium substitution and/or with increase of external magnetic field. When the Yb concentration x increases a negative maximum of a significant amplitude was shown to appear on the temperature dependences of Hall coefficient RH(T) for the Tm1-xYbxB12 compounds. Moreover, a complicated activation type behavior of the Hall coefficient is observed at intermediate temperatures for x>0.5 with activation energies Eg~200K and Ea~55-75K in combination with the sign inversion of RH(T) at low temperatures in the coherent regime. The density of states renormalization effects are analyzed within the variation of Yb concentration and the features of the charge transport in various regimes (charge gap formation, intra-gap manybody resonance and coherent regime) are discussed in detail in Tm1-xYbxB12 solid solutions.Comment: 38 pages including 10 figures, 70 reference

Distinct functions of HTLV-1 Tax1 from HTLV-2 Tax2 contribute key roles to viral pathogenesis

While the human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), to date, its close relative HTLV-2 is not associated with ATL or other types of malignancies. Accumulating evidence shows that HTLV-1 Tax1 and HTLV-2 Tax2 have many shared activities, but the two proteins have a limited number of significantly distinct activities, and these distinctions appear to play key roles in HTLV-1 specific pathogenesis. In this review, we summarize the functions of Tax1 associated with cell survival, cell proliferation, persistent infection as well as pathogenesis. We emphasize special attention to distinctions between Tax1 and Tax2