RNA pseudoknots downstream of the frameshift sites of retroviruses.

RNA pseudoknot structural motifs could have implications for a wide range of biological processes of RNAs. In this study, the potential RNA pseudoknots just downstream from the known and suspected retroviral frame-shift sites were predicted in the Rous sarcoma virus, primate immunodeficiency viruses (HIV-1, HIV-2, and SIV), equine infectious anemia virus, visna virus, bovine leukemia virus, human T-cell leukemia virus (types I and II), mouse mammary tumor virus, Mason-Pfizer monkey virus, and simian SRV-1 type-D retrovirus. Also, the putative RNA pseudoknots were detected in the gag-pol overlaps of two retrotransposons of Drosophila, 17.6 and gypsy, and the mouse intracisternal A particle. For each sequence, the thermodynamic stability and statistical significance of the secondary structure involved in the predicted tertiary structure were assessed and compared. Our results show that the stem-loop structures in the pseudoknots are both thermodynamically highly stable and statistically significant relative to other such configurations that potentially occur in the gag-pol or gag-pro and pro-pol junction domains of these viruses (300 nucleotides upstream and downstream from the possible frameshift sites are included). Moreover, the structural features of the predicted pseudoknots following the frameshift site of pro-pol overlaps of the HTLV-1 and HTLV-2 retroviruses are structurally well conserved. The occurrence of eight compensatory base changes in the tertiary interaction of the two related sequences allow the conservation of their tertiary structures in spite of the sequence divergence. The results support the possible control mechanism for frameshifting proposed by Brierley et al. and Jacks et al.     

Chromosome rearrangements in Giardia lamblia

Recent studies have shown that the genome of Giardia lamblia is plastic. Clinical isolates exhibit extensive karyotypic heterogeneity and chromosome rearrangements occur frequently, in vitro. In this review, Sylvie Le Blancq looks at genome organization and the impact of DNA rearrangement events.     

Th2-like CD8 T cells: their role in protection against infectious diseases

The expression of cytolytic activity and production of interferon gamma (IFN-gamma) by CD8(+) T cells is thought to play a fundamental role in protection against infection by viruses and intracellular parasites. Fran?ois Erard and Graham Le Gros have recently shown that CD8(+) T cells activated in the presence of interleukin 4 (IL-4) can switch development to a CD8(-)CD4(-)Th2-like phenotype that is not cytolytic and that does not produce IFN-gamma. Here they speculate on whether this IL-4-induced switch is used by the host to make a more-effective response against parasite invasion, or i f it is a host mechanism used by the parasite to evade protective CD8(+) T-cell responses.     

The Circadian Clock Gene Circuit Controls Protein and Phosphoprotein Rhythms in Arabidopsis thaliana

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Design,synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors

This paper described our efforts to develop dianilinopyrimidines as novel EGFR inhibitors. All the target compounds were tested for inhibitory effects against wild type EGFR (EGFR^wt) and three tumour cells, including A549, PC-3, and HepG2. Some of the compounds performed well in antitumor activities. Especially, compound 4c 2-((2-((4-(3-fluorobenzamido)phenyl)amino)-5-(trifluoromethyl) pyrimidin-4-yl)amino)-N-methylthiophene-3-carboxamide showed higher anti-tumour activities than Gefitinib. The IC₅₀ values of compound 4c against A549, PC-3, and HepG2. reached 0.56 μM, 2.46 μM, and 2.21 μM, respectively. In addition, further studies indicated that compound 4c could induce apoptosis against A549 cells and arrest A549 cells in the G2/M phase. Molecular docking studies showed that compound 4c could closely interact with EGFR. Generally, compound 4c was the potential for developing into an anti-tumour drug.     

Defining the risks of mesenchymal stromal cell therapy

We address the issue of the potential for malignant transformation of cultured mesenchymal stromal cells (MSC) commonly used in clinical cell-therapy protocols and describe the culture conditions under which tumorigenesis is likely to be an extremely uncommon event.     

Hydration and protein folding in water and in reverse micelles: compressibility and volume changes

The partial specific volume and adiabatic compressibility of proteins reflect the hydration properties of the solvent-exposed protein surface, as well as changes in conformational states. Reverse micelles, or water-in-oil microemulsions, are protein-sized, optically-clear microassemblies in which hydration can be experimentally controlled. We explore, by densimetry and ultrasound velocimetry, three basic proteins: cytochrome c, lysozyme, and myelin basic protein in reverse micelles made of sodium bis (2-ethylhexyl) sulfosuccinate, water, and isooctane and in aqueous solvents. For comparison, we use beta-lactoglobulin (pI = 5.1) as a reference protein. We examine the partial specific volume and adiabatic compressibility of the proteins at increasing levels of micellar hydration. For the lowest water content compatible with complete solubilization, all proteins display their highest compressibility values, independent of their amino acid sequence and charge. These values lie within the range of empirical intrinsic protein compressibility estimates. In addition, we obtain volumetric data for the transition of myelin basic protein from its initially unfolded state in water free of denaturants, to a folded, compact conformation within the water-controlled microenvironment of reverse micelles. These results disclose yet another aspect of the protein structural properties observed in membrane-mimetic molecular assemblies.