Interactions in vivo between the Vif protein of HIV-1 and the precursor (Pr55GAG) of the virion nucleocapsid proteins

The abnormality of viral core structure seen in vif-defective HIV-1 grown in PBMCs has suggested a role for Vif in viral morphogenesis. Using an in vivo mammalian two-hybrid assay, the interaction between Vif and the precursor (Pr55GAG) of the virion nucleocapsid proteins has been analysed. This revealed the amino-terminal (aa 1–22) and central (aa 70–100) regions of Vif to be essential for its interaction with Pr55GAG, but deletion of the carboxy-terminal (aa 158–192) region of the protein had only a minor effect on its interaction. Initial deletion studies carried out on Pr55GAG showed that a 35-amino-acid region of the protein bridging the MA(p17)–CA(p24) junction was essential for its ability to interact with Vif. Site-directed mutagenesis of a conserved tryptophan (Trp21) near the amino terminus of Vif showed it to be important for the interaction with Pr55GAG. By contrast, mutagenesis of the highly conserved YLAL residues forming part of the BC-box motif, shown to be important in Vif promoting degradation of APOBEC3G/3F, had little or no effect on the Vif–Pr55GAG interaction

A method to estimate the efficiency of gene expression from an integrated retroviral vector

BACKGROUND: Proviral gene expression is a critical step in the retroviral life cycle and an important determinant in the efficiency of retrovirus based gene therapy vectors. There is as yet no method described that can assess the efficiency of proviral gene expression while vigorously excluding the contribution from unstable species such as passively transferred plasmid and LTR circles. Here, we present a method that can achieve this. RESULTS: Proviral gene expression was detected by the activity of the puromycin resistance gene encoded in the viral vector, and quantified by comparing the growth curve of the sample under puromycin selection to that of a series of calibration cultures. Reproducible estimates of the efficiency of proviral gene expression could be derived. We confirm that contamination from unstable species such as passively transferred plasmid used in viral vector production and unintegrated viral DNA can seriously confound estimates of the efficiency of transduction. This can be overcome using a PCR based on limiting dilution analysis. CONCLUSION: A simple, low cost method was developed that should be useful in studying the biology of retroviruses and for the development of expression systems for retrovirus based gene therapy

Log-periodic route to fractal functions

Log-periodic oscillations have been found to decorate the usual power law behavior found to describe the approach to a critical point, when the continuous scale-invariance symmetry is partially broken into a discrete-scale invariance (DSI) symmetry. We classify the `Weierstrass-type'' solutions of the renormalization group equation F(x)= g(x)+(1/m)F(g x) into two classes characterized by the amplitudes A(n) of the power law series expansion. These two classes are separated by a novel ``critical'' point. Growth processes (DLA), rupture, earthquake and financial crashes seem to be characterized by oscillatory or bounded regular microscopic functions g(x) that lead to a slow power law decay of A(n), giving strong log-periodic amplitudes. In contrast, the regular function g(x) of statistical physics models with ``ferromagnetic''-type interactions at equibrium involves unbound logarithms of polynomials of the control variable that lead to a fast exponential decay of A(n) giving weak log-periodic amplitudes and smoothed observables. These two classes of behavior can be traced back to the existence or abscence of ``antiferromagnetic'' or ``dipolar''-type interactions which, when present, make the Green functions non-monotonous oscillatory and favor spatial modulated patterns.Comment: Latex document of 29 pages + 20 ps figures, addition of a new demonstration of the source of strong log-periodicity and of a justification of the general offered classification, update of reference lis

Chern-Simons Theory for Magnetization Plateaus of Frustrated J1J_1-J2J_2 Heisenberg model

The magnetization curve of the two-dimensional spin-1/2 $J_1$-$J_2$ Heisenberg model is investigated by using the Chern-Simons theory under a uniform mean-field approximation. We find that the magnetization curve is monotonically increasing for $J_2/J_1 < 0.267949$, where the system under zero external field is in the antiferromagnetic N\'eel phase. For larger ratios of $J_2/J_1$, various plateaus will appear in the magnetization curve. In particular, in the disordered phase, our result supports the existence of the $M/M_{\rm sat}=1/2$ plateau and predicts a new plateau at $M/M_{\rm sat}=1/3$. By identifying the onset ratio $J_2/J_1$ for the appearance of the 1/2-plateau with the boundary between the N\'eel and the spin-disordered phases in zero field, we can determine this phase boundary accurately by this mean-field calculation. Verification of these interesting results would indicate a strong connection between the frustrated antiferromagnetic system and the quantum Hall system.Comment: RevTeX 4, 4 pages, 3 EPS figure

Production of simian virus 40 large tumor antigen in bacteria: altered DNA-binding specificity and dna-replication activity of underphosphorylated large tumor antigen

A bacterial expression system was used to produce simian virus 40 large tumor antigen (T antigen) in the absence of the extensive posttranslational modifications that occur in mammalian cells. Wild-type T antigen produced in bacteria retained a specific subset of the biochemical activities displayed by its mammalian counterpart. Escherichia coli T antigen functioned as a helicase and bound to DNA fragments containing either site I or the wild-type origin of replication in a manner identical to mammalian T antigen. However, T antigen purified from E. coli did not efficiently bind to site II, an essential cis element within the simian virus 40 origin of replication. It therefore could not unwind origin-containing plasmids or efficiently replicate simian virus 40 DNA in vitro. The ability of protein phosphorylation to modulate the intrinsic preference of full-length T antigen for either site I or site II is discussed

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Heavy-Tailed Distribution of Cyber-Risks

With the development of the Internet, new kinds of massive epidemics, distributed attacks, virtual conflicts and criminality have emerged. We present a study of some striking statistical properties of cyber-risks that quantify the distribution and time evolution of information risks on the Internet, to understand their mechanisms, and create opportunities to mitigate, control, predict and insure them at a global scale. First, we report an exceptionnaly stable power-law tail distribution of personal identity losses per event, ${\rm Pr}({\rm ID loss} \geq V) \sim 1/V^b$, with $b =0.7 \pm 0.1$. This result is robust against a surprising strong non-stationary growth of ID losses culminating in July 2006 followed by a more stationary phase. Moreover, this distribution is identical for different types and sizes of targeted organizations. Since $b<1$, the cumulative number of all losses over all events up to time $t$ increases faster-than-linear with time according to $\mathbf{\simeq t^{1/b}}$, suggesting that privacy, characterized by personal identities, is necessarily becoming more and more insecure. We also show the existence of a size effect, such that the largest possible ID losses per event grow faster-than-linearly as $\sim S^{1.3}$ with the organization size $S$. The small value $b \simeq 0.7$ of the power law distribution of ID losses is explained by the interplay between Zipf's law and the size effect. We also infer that compromised entities exhibit basically the same probability to incur a small or large loss.Comment: 9 pages, 3 figure