Gene silencing by siRNA microhydrogels via polymeric nanoscale condensation

The first attempt to prepare biologically active siRNA-based microhydrogels is reported. The self-assembled microhydrogels were fabricated using sense/antisense complementary hybridization between single-stranded linear and Y-shaped trimeric siRNAs. The siRNA microhydrogels were condensed using a popular cationic polymer such as LPEI to form compact, stable siRNA/polymeric nanoparticles that exhibited superb cellular uptake efficiency and gene silencing activity.     

Selectivity between N-1 and N-7 nucleosides: regioselective synthesis of BMK-Y101, a potent cdk7 and 9 inhibitor

BMK-Y101 is a new pyrrolo[2,3-d]pyrimidine-based potent cdk7 and 9 inhibitor, which is characterized by an intriguing structural feature of N-1 nucleoside, departing from previously reported N-7 nucleoside Cdk inhibitor, xylocydine. Though N-1 nucleosides have appeared in the literature, they have often been considered as kinetic products and thus intermediates of N-7 glycosylation. In the course of the synthetic studies of xylocydine derivatives, we have developed a highly regioselective method to obtain the N-1 nucleoside. The origin of the selectivity is apparently based on the reactivity of the silylated nucleobase and the stability of the resulting N-1 nucleoside. The choice of BSA as a silylating agent was critical in securing the N-1 nucleoside, BMK-Y101. On the other hand, proper selection of reaction conditions promoting transglycosylation provides an efficient route to N-7 nucleosides.     

Synergistic induction of cancer cell migration regulated by Gβγ and phosphatidylinositol 3-kinase

Phosphatidylinositol 3-kinase (PI3K) is essential for both G protein-coupled receptor (GPCR)- and receptor tyrosine kinase (RTK)-mediated cancer cell migration. Here, we have shown that maximum migration is achieved by full activation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) in the presence of Gβγ and PI3K signaling pathways. Lysophosphatidic acid (LPA)- induced migration was higher than that of epidermal growth factor (EGF)-induced migration; however, LPA-induced activation of Akt was lower than that stimulated by EGF. LPA-induced migration was partially blocked by either Gβγ or RTK inhibitor and completely blocked by both inhibitors. LPA-induced migration was synergistically increased in the presence of EGF and vice versa. In correlation with these results, sphingosine-1-phosphate (S1P)-induced migration was also synergistically induced in the presence of insulin-like growth factor-1 (IGF-1). Finally, silencing of P-Rex1 abolished the synergism in migration as well as in Rac activation. Moreover, synergistic activation of MMP-2 and cancer cell invasion was attenuated by silencing of P-Rex1. Given these results, we suggest that P-Rex1 requires both Gβγ and PI3K signaling pathways for synergistic activation of Rac, thereby inducing maximum cancer cell migration and invasion.     

Mössbauer study of Fe‐doped CuGeO3 system Cu0.9Ge0.9Fe0.2O3

The Fe‐doped system Cu_0.9Ge_0.9Fe_0.2O₃ has been investigated by means of X‐ray diffractometry, Mössbauer spectroscopy and superconducting quantum interference device. The structure of this system is orthorhombic and the lattice constants are a=4.784 Å, b=8.472 Å and c=2.904 Å, respectively. Magnetic measurements confirm that the spin‐Peierls transition appears in our sample at about 12 K, which is near to the spin‐Peierls transition temperature (T _sp) 14 K of pure CuGeO₃ system. The Mössbauer spectrum shows the superposition of two Zeeman sextets and a broad central line due to Fe³⁺ ions from room temperature to 4.2 K. The Mössbauer parameters show a discontinuity near T _sp. The jump of the magnetic hyperfine field at temperatures lower than T _sp means increasing of the superexchange interaction among the magnetic ions. The jump of the quadrupole splitting and the isomer shift values could be interpreted as due to decrement in symmetry of lattice sites and spontaneous thermal contraction.     

Self-Assembled Peptidyl Aggregates for the Fluorogenic Recognition of Mitochondrial DNA G-Quadruplexes

The selective monitoring of G-quadruplex (G4) structures in living cells is important to elucidate their functions and reveal their value as diagnostic or therapeutic targets. Here we report a fluorogenic probe ( CV2 ) able to selectively light-up parallel G4 DNA over antiparallel topologies. CV2 was constructed by conjugating the excimer-forming CV dye with a peptide sequence (l -Arg-l -Gly-glutaric acid) that specifically recognizes G4s. CV2 forms self-assembled, red excimer-emitting nanoaggregates in aqueous media, but specific binding to G4s triggers its disassembly into rigidified monomeric dyes, leading to a dramatic fluorescence enhancement. Moreover, selective permeation of CV2 stains G4s in mitochondria over the nucleus. CV2 was employed for tracking the folding and unfolding of G4s in living cells, and for monitoring mitochondrial DNA (mtDNA) damage. These properties make CV2 appealing to investigate the possible roles of mtDNA G4s in diseases that involve mitochondrial dysfunction.     

Constituent analysis of metal and metal oxide in reduced SIMFuel using bromine-ethyl acetate

Journal of Radioanalytical and Nuclear Chemistry - We demonstrated that bromine in ethyl acetate can selectively separate metallic contents in lanthanide metal-oxide mixtures for analysis, which...     

Regularity of Non-Newtonian Fluids

In this paper, we consider a non-Newtonian fluids with shear dependent viscosity in a bounded domain ${\Omega \subset \mathbb{R}^n, n = 2, 3}$ . For the power-law model with the viscosity as in (1.4), we show the global in time existence of a weak solution for ${q \geq \frac{11}{5}}$ when n = 3 (see Theorem 1.1), and the local in time existence of a weak solution for ${2 > q > \frac{3n}{n+2}}$ , when n = 2,3 (see Theorem 1.2).     

Synthesis of tri-, hexa-, and nonasaccharide subunits of the atypical O-antigen polysaccharide of the lipopolysaccharide from Danish Helicobacter pylori strains

Synthesis of trisaccharide repeating unit, -->3)-alpha-D-Rhap-(1-->2)-alpha-D-Manp3CMe-(1-->3)-alpha-L-Rha p-(1-->, and its dimeric hexa- and trimeric nonasaccharide subunits of the atypical O-antigen polysaccharide of the lipopolysaccharide from Danish H. pylori strains D1, D3, and D6 has been accomplished. Successful synthesis of the hexasaccharide and the nonasaccharide was possible by dimerization and trimerization of the suitably protected trisaccharide repeating unit, in which three monosaccharide moieties were arranged in a proper order by placing the sterically demanding 3-C-methyl-D-mannose moiety in between D- and L-rhamnoses. Key steps include the coupling of three monosaccharide moieties and dimerization and trimerization of the trisaccharide unit by glycosylations employing the 2'-carboxybenzyl glycoside method. Also presented is a method for the synthesis of the novel branched sugar, 3-C-methyl-D-mannose moiety by elaboration of its equatorial hydroxyl and axial methyl groups at C-3' in the disaccharide stage.     

Lysophosphatidic acid induces cell migration through the selective activation of Akt1

Akt plays pivotal roles in many physiological responses including growth, proliferation, survival, metabolism, and migration. In the current studies, we have evaluated the isoform-specific role of akt in lysophosphatidic acid (LPA)-induced cell migration. Ascites from ovarian cancer patients (AOCP) induced mouse embryo fibroblast (MEF) cell migration in a dose-dependent manner. On the other hand, ascites from liver cirrhosis patients (ALCP) did not induce MEF cell migration. AOCP-induced MEF cell migration was completely blocked by pre-treatment of cells with LPA receptor antagonist, Ki16425. Both LPA- and AOCP-induced MEF cell migration was completely attenuated by PI3K inhibitor, LY294002. Furthermore, cells lacking Akt1 displayed defect in LPA-induced cell migration. Re-expression of Akt1 in DKO (Akt1-/-Akt2-/-) cells restored LPA-induced cell migration, whereas re-expression of Akt2 in DKO cells could not restore the LPA-induced cell migration. Finally, Akt1 was selectively phosphorylated by LPA and AOCP stimulation. These results suggest that LPA is a major factor responsible for AOCP-induced cell migration and signaling specificity of Akt1 may dictate LPA-induced cell migration.