Complex Transposon Insertion as a Novel Cause of Pompe Disease

Pompe disease (OMIM#232300) is an autosomal recessive lysosomal storage disorder caused by mutations in the GAA gene. According to public mutation databases, more than 679 pathogenic variants have been described in GAA, none of which are associated with mobile genetic elements. In this article, we report a novel molecular genetic cause of Pompe disease, which could be hardly detected using routine molecular genetic analysis. Whole genome sequencing followed by comprehensive functional analysis allowed us to discover and characterize a complex mobile genetic element insertion deep in the intron 15 of the GAA gene in a patient with infantile onset Pompe disease.     

Sintering kinetics of ZrO2 nanopowders modified by group IV elements

The sintering behavior of tetragonal zirconia nanopowders modified by the group IV elements at the initial sintering stage was investigated. It was found that different additives SiO₂, SnO₂, and GeO₂ have a significant influence on the densification kinetics of 3Y-TZP nanopowders obtained by coprecipitation during sintering as it depends on the amount of additives (0-5 wt%). The shrinkage of zirconia-based specimens during the nonisothermal sintering was analyzed using the dilatometric data. The constant rate of heating technique was applied in order to determine the dominant mass transfer mechanism at the initial stage of sintering in modified zirconia nanopowders. It was found that there was a change in the mass transfer mechanism and diffusion activation energy in 3Y-TZP as a result of the additives. The dominant sintering mechanism in 3Y-TZP changed from the volume diffusion to the grain boundary diffusion due to the addition of SiO₂ and SnO₂ and the sintering activation energy increased in these cases. However, GeO₂ additive activated the viscous flow mechanism in sintering process of 3Y-TZP nanopowders which led to acceleration of the densification due to the decrease in the diffusion activation energy.     

Mechanisms of molecular interactions in polybase–polyacid complex formed by copolymers of N,N‐dimethylaminoethylmethacrylate with alkylmethacrylates and methacrylic acid with ethylacrylate

Mechanisms of molecular interaction in the blends of a polybase, a copolymer of N,N‐dimethylaminoethylmethacrylate with methylmethacrylate and butylmethacrylate (PDMAEMA–MMA/BMA), with a polyacid, a copolymer of methacrylic acid with ethylacrylate (PMAA‐co‐EA), and plasticizer, triethylcitrate (TEC), have been investigated with FTIR Spectroscopy and potentiometry. To evaluate the strengths of hydrogen and ionic bonds in the polyelectrolyte complexes, quantum‐chemical calculations were performed. According to this analysis, the energy of ionic and hydrogen bonding diminishes in the order: multi‐component complexes involving protonated aminogroup of DMAEMA (ammonium cation) in the presence of chlorine counterion with ionized or unchanged carboxyl groups and water molecules (690–520 kJ/mol) > ternary H‐bonded acid‐base complexes associated with molecule of water (520–420 kJ/mol) > binary ionic complex of carboxylate anion and ammonium cation (404 kJ/mol) > H‐bonded complex of carboxylate and ammonium ions (257 kJ/mol) > binary H‐bonded complex of uncharged carboxyl group with ammonium cation (114 kJ/mol) > ternary H‐bonded complex of uncharged carboxyl group, aminogroup and water molecule (43 kJ/mol) > binary H‐bonded complex between nonionized carboxyl and amino groups (26 kJ/mol). Proton‐donating capability of functional groups in the studied polyelectrolyte blends diminishes in the order: HN⁺(CH₃)₂ ? > HOOC? > HO? . The proton‐donating capacity can be significantly improved in the presence of Cl^? ions, the effect of which may be appreciably inhibited if Na⁺ cations are available in the blend or solution. Proton‐accepting capability weakens in the order: uncharged aminogroup > carboxylate anion > uncharged carboxyl group > hydroxyl group. The results of quantum chemical calculations facilitate interpretation of FTIR spectra. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Confinement effects on the kinetics of formation of sequential semi-interpenetrating polymer networks

Summary Peculiarities of formation kinetics of sequential semi-interpenetrating polymer networks based on crosslinked polyurethane with different cross-linking density and linear polystyrene and polybutylmethacrylate have been studied. Polyurethane networks were synthesized differing in molecular mass M_c of the chains between cross-links. Monomeric styrene and butyl methacrylate were introduced into these networks by swelling them in monomers up to equilibrium. The kinetics of polymerization of monomers in swollen networks was investigated. The experimental data show the dependence of the kinetic parameters of polymerization on M_c, this dependence being different for various monomers. Sharp discrepancy in molecular mass distribution of polymers formed in various matrices has been observed. The differences in dependencies of reaction kinetics and molecular mass distribution are supposed to be connected to various dependence of the chain growth and termination of various monomers on the density of network, i.e. on the confinements imposed by the intranetwork space.     

Effect of boiling and frying on the content of essential polyunsaturated fatty acids in muscle tissue of four fish species

Frozen samples of common fish species, sea trout (Salmo trutta), from Norway and Siberia, herring (Clupea harengus pallasi), rock sole (Lepidopsetta bilineata) and cod (Gadus morhua maris-albi), collected from a wholesale market in Krasnoyarsk city (Siberia, Russia) were analyzed. Special attention was paid to long-chain essential polyunsaturated fatty acids: eicosapentaenoic, 20:5ω3 (EPA) and docosahexaenoic, 22:6ω3 (DHA). Heat-treatment (cooking and frying) did not in general significantly decrease the contents of EPA and DHA compared to raw fish species, except for a modest reduction in Norwegian trout during frying. Boiled trout appeared to be a more valuable fish dish for obtaining the officially recommended appropriate daily intake of EPA + DHA for humans. Herring and sole had intermediate values, while boiled cod had a comparatively low value.     

NSOM the fourth dimension: Integrating nanometric spatial and femtosecond time resolution

Photonic devices are becoming the cornerstone of next generation systems for computing and information processing. This paper reports on the first steps in the development of methods to understand these devices with nanometric (10^?7 cm) spatial and femtosecond (10^?15 s) time resolution. The basis of this achievement is the dramatic developments that have occurred in the past few years in a new area of optics called near-field optics. Near-field optics is a form of lensless optics with a resolution that is subwavelength and which is independent of the wavelength of the light being employed. We report in this paper the transmission of pulses with tens of femtosecond duration through subwavelength, near-field optical elements. We also report on a femtosecond near-field optical light source with cross-correlating capabilities and on the growth of GaAs in the tip of micropipettes for use as an ultra-fast electro-optical switch which can cross-correlate optical, electrical, and electro-optical effects. These developments are especially relevant in the investigation of photonic devices since such devices can alter their characteristics as a function of size in the mesoscopic regime from just below lens-based optical resolutions to dimensions that approach atomic scales of ～1 nm (10^?7 cm). In view of the fact that these devices and the processes that govern them also exhibit ultrafast speeds, the combination of state of the art femtosecond laser spectroscopy with the unique features of near-field optics is a critical step in advancing our next generation understandings of such materials and structures so that their full potential in information processing can be achieved.     

Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo

Nanocomposites （NCs） consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin （HP） have been fabricated in order to improve the efficiency of cancer treatment by combining photothermal and photodynamic therapies （PDT ＋ PTT） in vivo. In addition to the long-wavelength plasmon resonance near 810-830 nm, the fabricated NCs exhibited a 400-nm absorbance peak corresponding to bound HP, generated singlet oxygen under 633-nm excitation near the 632.5-nm Q-band, and produced heat under a 808-nm near-infrared （NIR） laser irradiation. These modalities were used for a combined PDT ＋ PTT treatment of large （about 3 cm3） solid tumors in vivo with a xenorafted tumor rat model. NCs were directly injected into tumors and irradiated simultaneously with 633-nm and 808-nm lasers to stimulate the combined photodynamic and photothermal activities of NCs. The efficiency of the combined therapy was evaluated by optical coherence tomography, histological analysis, and by measurements of the tumor volume growth during a 21-day period. The NC-mediated PDT led to weak changes in tissue histology and to a moderate 20% decrease in the tumor volume. In contrast, the combined PDT ＋ PTT treatment resulted in the large-area tumor necrosis and led to dramatic decrease in the tumor volume.     

Conjugates of Methylene Blue with Cycloalkaneindoles as New Multifunctional Agents for Potential Treatment of Neurodegenerative Disease

The development of multi-target-directed ligands (MTDLs) would provide effective therapy of neurodegenerative diseases (ND) with complex and nonclear pathogenesis. A promising method to create such potential drugs is combining neuroactive pharmacophoric groups acting on different biotargets involved in the pathogenesis of ND. We developed a synthetic algorithm for the conjugation of indole derivatives and methylene blue (MB), which are pharmacophoric ligands that act on the key stages of pathogenesis. We synthesized hybrid structures and performed a comprehensive screening for a specific set of biotargets participating in the pathogenesis of ND (i.e., cholinesterases, NMDA receptor, mitochondria, and microtubules assembly). The results of the screening study enabled us to find two lead compounds (4h and 4i) which effectively inhibited cholinesterases and bound to the AChE PAS, possessed antioxidant activity, and stimulated the assembly of microtubules. One of them (4i) exhibited activity as a ligand for the ifenprodil-specific site of the NMDA receptor. In addition, this lead compound was able to bypass the inhibition of complex I and prevent calcium-induced mitochondrial depolarization, suggesting a neuroprotective property that was confirmed using a cellular calcium overload model of neurodegeneration. Thus, these new MB-cycloalkaneindole conjugates constitute a promising class of compounds for the development of multitarget neuroprotective drugs which simultaneously act on several targets, thereby providing cognitive stimulating, neuroprotective, and disease-modifying effects.