ZFP36 proteins and mRNA targets in B cell malignancies

The ZFP36 proteins are a family of post-transcriptional regulator proteins that bind to adenine uridine rich elements (AREs) in 3’ untranslated (3’UTR) regions of mRNAs. The members of the human family, ZFP36L1, ZFP36L2 and ZFP36 are able to degrade mRNAs of important cell regulators that include cytokines, cell signalling proteins and transcriptional factors. This project investigated two proposed targets for the protein family that have important roles in B cell biology, BCL2 and CD38 mRNAs. BCL2 is an anti-apoptotic protein with key roles in cell survival and carcinogenesis; CD38 is a membrane protein differentially expressed in B cells and with a prognostic value in B chronic lymphocytic leukaemia (B-CLL), patients positive for CD38 are considered to have a poor prognosis. This project provides evidence of a functional interaction between the three ZFP36 proteins and the 3’UTR AREs of BCL2 and CD38 mRNAs. 3’UTR dual luciferase reporter assay results showed that the three ZFP36 proteins bound the 3’UTR ARE of BCL2 mRNA and CD38 mRNA. Zinc finger mutant versions of ZFP36L1 failed to bind the 3’ UTR AREs for each target, proving that intact zinc finger domains are the functional binding domains of the protein and are required for interaction with AREs. A complete ARE sequence is also needed and when mutated BCL2 3’UTR ARE was tested, lacking the adenine uridine rich core element, the BCL2 transcript was not bound by ZFP36L1 protein. For CD38 further experiments have demonstrated that down regulation of ZFP36L1 by siRNAs in HeLa cells resulted in an increase in CD38 expression as measured by immunofluorescence and flow cytometry and by Western blot analysis. These results provide further evidence that ZFP36L1 negatively regulates CD38 mRNA. Analysis of BCL2, CD38 and ZFP36L1 protein expression in primary B-CLL cells by Western blot analysis did not show an inverse relationship between the proposed targets and ZFP36L1. Protein expression analysis in B-CLL for the whole family of ZFP36 proteins showed that ZFP36L1 was heterogeneously expressed; ZFP36L2 was detected at very low levels or was undetectable and ZFP36 was low and homogeneously expressed. In cell lines representing different B cell stages, but mainly representing mature and plasma cell stages, ZFP36L2 was detected at relatively high levels but also heterogeneously and there was very low or undetectable expression of ZFP36L1 in all cells. Immunohistochemistry analysis of ZFP36L1, BCL2 and CD38 in normal lymphoid tissue and FL indicated that areas of normal lymphoid tissues associated with highest levels of BCL2 and CD38 were associated with low or undetectable levels of ZFP36L1. In FL (FL) ZFP36L1 was detected in follicular centre cells, where BCL2 is also reported to be highly expressed due to a translocation that leads to over expression of BCL2. CD38 expression was also detected within FL follicle centres with some cells showing a high level of expression within the neoplastic follicle and amongst scattered cells outside of it. Overall, the results support the hypothesis that ZFP36L1 (and also ZFP36 and ZFP36L2) negatively regulates BCL2 and CD38 mRNAs. In a wider context, the results of this project support the view that ZFP36L1, and perhaps other ZFP36 family proteins, play important roles in controlling mature B cell survival and differentiation by targeting important regulatory mRNAs in these cells

Universal behavior of the Shannon mutual information of critical quantum chains

We consider the Shannon mutual information of subsystems of critical quantum chains in their ground states. Our results indicate a universal leading behavior for large subsystem sizes. Moreover, as happens with the entanglement entropy, its finite-size behavior yields the conformal anomaly $c$ of the underlying conformal field theory governing the long distance physics of the quantum chain. We studied analytically a chain of coupled harmonic oscillators and numerically the Q-state Potts models ($Q = 2$; 3 and 4), the XXZ quantum chain and the spin-1 Fateev-Zamolodchikov model. The Shannon mutual information is a quantity easily computed, and our results indicate that for relatively small lattice sizes its finite-size behavior already detects the universality class of quantum critical behavior.Comment: 5 pages, 5 figure

Anomalous Gauge Boson Couplings in the e^+ e^- -> ZZ Process

We discuss experimental aspects related to the $\mathrm{e^+ e^-} \to \mathrm{Z}\mathrm{Z}$ process and to the search for anomalous ZZV couplings (V$= \mathrm{Z}, \gamma$) at LEP2 and future $\mathrm{e^+ e^-}$ colliders. We present two possible approaches for a realistic study of the reaction and discuss the differences between them. We find that the optimal method to study double Z resonant production and to quantify the presence of anomalous couplings requires the use of a complete four-fermion final-state calculation.Comment: 28 pages, 12 figures, final version for Phys. Rev.

The Wave Functions for the Free-Fermion Part of the Spectrum of the SUq(N)SU_q(N) Quantum Spin Models

We conjecture that the free-fermion part of the eigenspectrum observed recently for the $SU_q(N)$ Perk-Schultz spin chain Hamiltonian in a finite lattice with $q=\exp (i\pi (N-1)/N)$ is a consequence of the existence of a special simple eigenvalue for the transfer matrix of the auxiliary inhomogeneous $SU_q(N-1)$ vertex model which appears in the nested Bethe ansatz approach. We prove that this conjecture is valid for the case of the SU(3) spin chain with periodic boundary condition. In this case we obtain a formula for the components of the eigenvector of the auxiliary inhomogeneous 6-vertex model ($q=\exp (2 i \pi/3)$), which permit us to find one by one all components of this eigenvector and consequently to find the eigenvectors of the free-fermion part of the eigenspectrum of the SU(3) spin chain. Similarly as in the known case of the $SU_q(2)$ case at $q=\exp(i2\pi/3)$ our numerical and analytical studies induce some conjectures for special rates of correlation functions.Comment: 25 pages and no figure

Limits on the brane fluctuations mass and on the brane tension scale from electron-positron colliders

In the context of the brane-world scenarios with compactified large extra dimensions, we study the production of the possible massive brane oscillations (branons) in electron-positron colliders. We compute their contribution to the electroweak gauge bosons decay width and to the single-photon and single-Z processes. With LEP-I results and assuming non observation at LEP-II, we present exclusion plots for the brane tension $\tau = f^4$ and the branon mass $M$. Prospects for the next generation of electron-positron colliders are also considered.Comment: LaTeX, 38 pages, 7 figures. Minor changes, matches published versio

Asymmetric exclusion model with several kinds of impurities

We formulate a new integrable asymmetric exclusion process with $N-1=0,1,2,...$ kinds of impurities and with hierarchically ordered dynamics. The model we proposed displays the full spectrum of the simple asymmetric exclusion model plus new levels. The first excited state belongs to these new levels and displays unusual scaling exponents. We conjecture that, while the simple asymmetric exclusion process without impurities belongs to the KPZ universality class with dynamical exponent 3/2, our model has a scaling exponent $3/2+N-1$. In order to check the conjecture, we solve numerically the Bethe equation with N=3 and N=4 for the totally asymmetric diffusion and found the dynamical exponents 7/2 and 9/2 in these cases.Comment: to appear in JSTA

Exactly Solvable Interacting Spin-Ice Vertex Model

A special family of solvable five-vertex model is introduced on a square lattice. In addition to the usual nearest neighbor interactions, the vertices defining the model also interact alongone of the diagonals of the lattice. Such family of models includes in a special limit the standard six-vertex model. The exact solution of these models gives the first application of the matrix product ansatz introduced recently and applied successfully in the solution of quantum chains. The phase diagram and the free energy of the models are calculated in the thermodynamic limit. The models exhibit massless phases and our analyticaland numerical analysis indicate that such phases are governed by a conformal field theory with central charge $c=1$ and continuosly varying critical exponents.Comment: 14 pages, 11 figure