High resolution positioning of intron ends on the nucleosomes

High resolution sequence-directed nucleosome mapping is applied to 36,000 sequences containing splice junctions, from five different species. As it has been also shown in previous studies, the junctions are found to be preferentially located within nucleosomes. Moreover, the orientation of guanine residues at the GT- and AG-ends of introns within the nucleosomes is such that the guanines are positioned nearest to the surface of histone octamers, 3 and 4 bases upstream from the local DNA pseudo-dyads passing through minor grooves oriented outwards. Since the guanine residues are the most vulnerable to spontaneous damage within the cell (primarily, depurination and oxidation) such positioning of the splice junctions minimizes the damage that is caused by free radicals and highly reactive metabolites.     

Crystal structure of Plasmodium falciparum phosphoglycerate kinase: evidence for anion binding in the basic patch

3-Phosphoglycerate kinase (EC 2.7.2.3) is a key enzyme in the glycolytic pathway and catalyzes an important phosphorylation step leading to the production of ATP. The crystal structure of Plasmodium falciparum phosphoglycerate kinase (PfPGK) in the open conformation is presented in two different groups, namely I222 and P6₁22. The structure in I222 space group is solved using MAD and refined at 3 Å whereas that in P6₁22A is solved using MR and refined at 2.7 Å. I222 form has three monomers in asymmetric unit whereas P6₁22 form has two monomers in the asymmetric unit. In both crystal forms a sulphate ion is located at the active site where ATP binds, but no Mg²⁺ ion is observed. For the first time another sulphate ion is found at the basic patch where the 3-phosphate of 1,3-biphosphoglycerate normally binds. This was found in both chains of P6₁22 form but only in chain A of I222 form.     

Monotone dependence of the spectral bound on the transition rates in linear compartment models

For linear compartment models or Leslie-type staged population models with quasi-positive matrix the spectral bound of the matrix (the eigenvalue determining stability) is studied in the situation where particles or individuals leave a compartment or stage with some rate and enter another with the same rate. Then the matrix carries the rate with a positive sign in some off-diagonal entry and with a negative sign in the corresponding diagonal entry. Hence the matrix does not depend on the rate in a monotone way. It is shown, however, that the spectral bound is a monotone function of the rate. It is all the time strictly increasing or strictly decreasing or it is constant. A simple algebraic criterion distinguishes between the three cases. The results can be applied to linear systems and to the stability of stationary states in non-linear systems, in particular to models for the transmission of infectious diseases, and in population dynamics.     

Methyltransferase-inhibition interferes with neuronal differentiation of P19 embryonal carcinoma cells

We have analyzed the importance of substrate methylation by S-adenosylmethionine-dependent methyltransferases for neuronal differentiation of P19 embryonal carcinoma cells. We show that treatment of cells with methyltransferase inhibitor adenosine dialdehyde (AdOx) interferes with neuronal differentiation. Retinoic acid (RA) and AdOx co-treated cells had a decreased number of neurites and a flattened morphology compared with cells differentiated by RA. Also, the amount of neuronal class III tubulin (Tuj1) decreased from 76% to 9.6% with AdOx-treatment. Gene expression levels of wnt-1, brn-2, neuroD, and mash-1 were also down-regulated by AdOx-treatment. But AdOx-treatment did not up-regulate BMP-4 and GFAP genes. Treatment of RA decreased E-cadherin expression during neuronal differentiation. However, in AdOx/RA co-treated cells, E-cadherin expression was restored to the control level. Also, mRNA expression of N-cadherin decreased with AdOx-treatment. Taken together, these data show that methylation reactions might influence the cell-fate decision and neuronal differentiation of P19 cells.     

An SIRVS epidemic model with pulse vaccination strategy

The aim of this paper is to analyze an SIRVS epidemic model in which pulse vaccination strategy (PVS) is included. We are interested in finding the basic reproductive number of the model which determine whether or not the disease dies out. The global attractivity of the disease-free periodic solution (DFPS for short) is obtained when the basic reproductive number is less than unity. The disease is permanent when the basic reproductive number is greater than unity, i.e., the epidemic will turn out to endemic. Our results indicate that the disease will go to extinction when the vaccination rate reaches some critical value.     

Kinetically controlled Ferrier rearrangement of 3-O-mesyl-d-glycal derivatives

The Ferrier rearrangement, which is widely used in carbohydrate chemistry, is generally performed under acidic conditions to give an α anomer with high stereoselectivity. We have found that 3-O-mesyl-d-glycals 2-4 were smoothly reacted with alcohols in the presence of triethylamine. The present reaction was shown to proceed under kinetic control to give ∼1.3:1.0 mixture of α and β anomers, indicating that a kinetic anomeric effect does not operate.     

Id-1 induces proteasome-dependent degradation of the HBX protein

Id-1 is a member of the HLH protein family that regulates a wide range of cellular processes such as cell proliferation, apoptosis, senescence and overexpression of Id-1 was recently suggested to play roles in the development and progression of different cancers. Previously, Id-1 was shown to physically interact with the viral protein E1A. Meanwhile, Id-1 expression was found to be regulated by several of the virus-encoded proteins, suggesting that Id-1 may be a common cellular target of the viral proteins. Here, we report that Id-1 interacts with the Hepatitis-B virus (HBV)-encoded protein HBX and regulates its stability in hepatocellular carcinoma (HCC) cells. We found that in HCC cells, ectopic Id-1 expression significantly decreased the half-life of the HBX protein, indicating that HBX is destabilized by Id-1. Meanwhile, the Id-1-induced HBX degradation was found to be inhibited by treatment with proteasome inhibitor, suggesting that this process is mediated through the proteasome pathway. Interestingly, while Id-1 did not induce HBX-ubiquitination, we found that removal of all the lysine residues of the HBX protein protects it from the effect of Id-1, indicating that ubiquitination is still required for the Id-1-mediated HBX degradation. Meanwhile, we found that Id-1 binds to the proteasome subunit C8 and facilitates its interaction with the HBX protein and disruption of this interaction completely abolishes the negative effect of Id-1 on HBX protein stability. Taken together, our results demonstrated a novel function of Id-1 in regulating HBX protein stability through interaction with the proteasome.