Pathways of ion–molecular interactions of nucleogenic phenyl cations with the nucleophilic centers of picolines

Background

The nuclear-chemical method brought unique opportunity for synthesis of unknown and hardly available organic compounds. Presence of tritium labeling allows one-step preparation of radioactive markers for the investigation of chemical and biological processes.

Methods

The ion–molecular reactions of nucleogenic phenyl cations with 4-picoline have been carried out. The phenyl cations were generated by spontaneous tritium β-decay within the tritium-labeled benzene. Both additions to the nitrogen and substitutions about the aromatic ring were able to be studied simultaneously.

Results

Unusual substitutions on both the α- and β-positions of the ring system have been revealed.

Conclusion

By unknown direct phenylation of nitrogen atom tritium-labeled N-phenylpicolinium derivatives, perspective biological markers have been synthesized.     

Molecular characterization of infectious bronchitis virus isolates from Russia and neighbouring countries: identification of intertypic recombination in the S1 gene

Infectious bronchitis virus (IBV) isolates recovered in Russia, Ukraine, and Kazakhstan between 2007 and 2010 were subjected to molecular characterization and compared with those isolated a decade ago. The IBV genome was detected in 202 out of 605 field samples from chickens with various clinical signs. Partial sequencing of the S1 gene revealed 153 vaccine strains and 49 field isolates of several genetic groups. Massachusetts, 793/B and D274 remained the predominant IBV genotypes along with QX, whereas B1648, Italy-02, Arkansas and variants accounted for about 12% of the total number. Three IBVs contained recombinant S1 gene sequences comprising genome fragments of QX-type field isolates and vaccine strains H120 (UKR/02/2009) or 4/91 (RF/03/2010), and vaccine strains H120 and D274 (RF/01/2010). The results of the present study showed a significant decline in prevalence of variant IBVs and a further spread of QX-type isolates in commercial chicken flocks in Russia as compared with the 1998 to 2002 data.     

RNA chaperone activity of the tombusviral p33 replication protein facilitates initiation of RNA synthesis by the viral RdRp in vitro

Small plus-stranded RNA viruses do not code for RNA helicases that would facilitate the proper folding of viral RNAs during replication. Instead, these viruses might use RNA chaperones as shown here for the essential p33 replication protein of Tomato bushy stunt virus (TBSV). In vitro experiments demonstrate that the purified recombinant p33 promotes strand separation of a DNA/RNA duplex. In addition, p33 renders dsRNA templates sensitive to single-strand specific S1 nuclease, suggesting that p33 can destabilize highly structured RNAs. We also demonstrate that the RNA chaperone activity of p33 facilitates self-cleavage by a ribozyme in vitro. In addition, purified p33 facilitates in vitro RNA synthesis on double-stranded (ds)RNA templates up to 5-fold by a viral RNA-dependent RNA polymerase. We propose that the RNA chaperone activity of p33 facilitates the initiation of plus-strand synthesis as well as affects RNA recombination. Altogether, the TBSV RNA chaperone might perform similar biological functions to the helicases of other RNA viruses with much larger coding capacity.     

The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus

In adult brain the majority of AMPA glutamate receptor (GluR) subunits contain GluR2. In knock-out (KO) mice the absence of GluR2 results in consequences for synaptic plasticity including cognitive impairments. Here the morphology of dendritic spines and their synaptic contacts was analysed via three-dimensional reconstruction of serial electron micrographs from dentate gyrus (DG) of adult wild type (WT) and GluR2 KO mice. Pre-embedding immunocytochemical staining was used to examine the distribution and subcellular localization of AMPA receptor GluR1 and N -methyl- d -aspartate receptor NR1 subunits. There were no significant changes in synapse density in the DG of GluR2 KO compared with WT mice. However, in GluR2 KO mice there was a significant decrease in the percentage of synapses on mushroom spines but an increase in synapses on thin spines. There was also a large decrease in the proportion of synapses with complex perforated/segmented post-synaptic densities (PSDs) (25 vs. 78% in WT) but an increase in synapses with macular PSDs (75 vs. 22%). These data were coupled in GluR2 KO mice with significant decreases in volume and surface area of mushroom spines and their PSDs. In both GluR2 KO and WT mice, NR1 and GluR1 receptors were present in dendrites and spines but there was a significant reduction in NR1 labelling of spine membranes and cytoplasm in GluR2 KO mice, and a small decrease in GluR1 immunolabelling in membranes and cytoplasm of spines in GluR2 KO compared with WT mice. Our data demonstrate that the absence of GluR2 has a significant effect on both DG synapse and spine cytoarchitecture and the expression of NR1 receptors.     

In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 microM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion.     

Rapid emergence of transcriptional heterogeneity upon molecular stress predisposes cells to two distinct states of senescence

GeroScience - Slowing aging can reduce the risk of chronic diseases. In particular, eliminating senescent cells is a promising approach to slow aging. Previous studies found that both cells from...     

Fast block flow tracking of atrial septal defects in 4D echocardiography

We are working to develop beating-heart atrial septal defect (ASD) closure techniques using real-time 3D ultrasound guidance. The major image processing challenges are the low-image quality and the processing of information at high-frame rate. This paper presents comparative results for ASD tracking in time sequences of 3D volumes of cardiac ultrasound. We introduce a block flow technique, which combines the velocity computation from optical flow for an entire block with template matching. Enforcing adapted similarity constraints to both the previous and first frames ensures optimal and unique solutions. We compare the performance of the proposed algorithm with that of block matching and region-based optical flow on eight in vivo 4D datasets acquired from porcine beating-heart procedures. Results show that our technique is more stable and has higher sensitivity than both optical flow and block matching in tracking ASDs. Computing velocity at the block level, our technique tracks ASD motion at 2 frames/s, much faster than optical flow and comparable in computation cost to block matching, and shows promise for real-time (30 frames/s). We report consistent results on clinical intra-operative images and retrieve the cardiac cycle (in ungated images) from error analysis. Quantitative results are evaluated on synthetic data with maximum tracking errors of 1 voxel.