9,409 research outputs found
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 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 (; 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 process and to the search for anomalous ZZV couplings
(V) at LEP2 and future 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 Quantum Spin Models
We conjecture that the free-fermion part of the eigenspectrum observed
recently for the Perk-Schultz spin chain Hamiltonian in a finite
lattice with is a consequence of the existence of a
special simple eigenvalue for the transfer matrix of the auxiliary
inhomogeneous 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
(), 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 case at our numerical and analytical
studies induce some conjectures for special rates of correlation functions.Comment: 25 pages and no figure
Asymmetric exclusion model with several kinds of impurities
We formulate a new integrable asymmetric exclusion process with
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 . 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
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 and the branon mass
. Prospects for the next generation of electron-positron colliders are also
considered.Comment: LaTeX, 38 pages, 7 figures. Minor changes, matches published versio
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 and continuosly varying
critical exponents.Comment: 14 pages, 11 figure
- …