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11.
The subcellular fate and activity in inhibiting the hepatitis B virus of free and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-phosphorothioate oligonucleotides were studied. Their internalization and subcellular fate were monitored with confocal microscopy. A fraction of the internalized free oligonucleotides escaped into the cytoplasm and nucleus of Hep G2 cells but were not active antiviral agents. Covalently attaching the oligonucleotides to the HPMA copolymers via nondegradable dipeptide GG spacers resulted in sequestering the oligonucleotides in vesicles after internalization. Conjugation of the oligonucleotides to an HPMA copolymer via a lysosomally cleavable tetrapeptide GFLG spacer resulted in release of the oligonucleotide in the lysosome and subsequent translocation into the cytoplasm and nucleus of the cells. The HPMA copolymer-oligonucleotide conjugate possessed antiviral activity, indicating that phosphorothioate oligonucleotides released from the carrier in the lysosome were able to escape into the cytoplasm and nucleus and remain active. The Hep G2 cells appeared to actively internalize the phosphorothioate oligonucleotides as oligonucleotide-HPMA copolymer conjugates were internalized to a greater extent than unconjugated polymers. 相似文献
12.
A comparative study of two modifications of enzymic reduction of ethyl N-{2-{4-[(2-oxo-cyclohexyl)methyl]phe- noxy}ethyl} carbamate (1), an insect juvenile hormone bioanalog, was performed using Saccharomyces cerevisiae in two bioreactors of different size, 250-ml shake-flask and 1-l fermenter. The two major products of this reduction were obtained in 45–49% (w/w) yields but with > 99% enantiomeric purity. Their absolute configurations were assigned as ethyl (1S,2S)-N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl}carbamate (2a) and ethyl (1R,2S)-N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl}carbamate (3a). 相似文献
13.
Combination of modeling and experiment in structure analysis of intercalated layer silicates 总被引:1,自引:0,他引:1
A strategy for the structure analysis of intercalated layer silicates based on a combination of modeling (i.e. force field calculations) and experiment is presented. Modeling in conjunction with experiment enables us to analyze the disordered intercalated structures of layer silicates where conventional diffraction analysis fails. Experiment plays a key role in the modeling strategy and in corroboration of the modeling results. X-ray powder diffraction and IR spectroscopy were found to be very useful complementary experiments to molecular modeling. Molecular mechanics and molecular dynamics simulations were carried out in the Cerius2 and Materials Studio modeling environments. An overview is given of the structures of layer silicates, especially smectites intercalated with various inorganic and organic guest species. Special attention is paid to the ordering of guests in the interlayer space, as it is important for the practical applications of these intercalates, where the interlayer porosity, photofunctions, etc. must be controlled. Figure Structure of montmorillonite intercalated with octadecylamine via ion-dipole interaction with the maximum concentration of guests corresponding to the monolayer arrangement of guests with basal spacing 33.3 A. The Na cations remaining in the interlayer are visualized as pink balls 相似文献
14.
We have synthesized N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cell penetrating peptide Tat conjugates and evaluated their subcellular distribution in A2780 human ovarian carcinoma cells by confocal fluorescence microscopy and subcellular fractionation. Our data indicate the transport of these conjugates by a single Tat molecule to both the cytoplasm and nucleus via a nonendocytotic and concentration independent process. The uptake was observed to occur within 3 min, as confirmed by live cell microscopy. In contrast, HPMA copolymers lacking the Tat peptide were internalized solely by endocytosis. For the first time, Tat-mediated cytoplasmic delivery of a polymer bound anticancer drug, doxorubicin, was also demonstrated. These findings establish the feasibility of overcoming major cellular and subcellular obstacles to intracellular macromolecular delivery and hold great promise for the development of polymer-based systems for the cytoplasmic delivery of therapeutic molecules. 相似文献
15.
Xianjun Dong Pavla Navratilova David Fredman ?yvind Drivenes Thomas S. Becker Boris Lenhard 《Nucleic acids research》2010,38(4):1071-1085
Using a comparative genomics approach to reconstruct the fate of genomic regulatory blocks (GRBs) and identify exonic remnants that have survived the disappearance of their host genes after whole-genome duplication (WGD) in teleosts, we discover a set of 38 candidate cis-regulatory coding exons (RCEs) with predicted target genes. These elements demonstrate evolutionary separation of overlapping protein-coding and regulatory information after WGD in teleosts. We present evidence that the corresponding mammalian exons are still under both coding and non-coding selection pressure, are more conserved than other protein coding exons in the host gene and several control sets, and share key characteristics with highly conserved non-coding elements in the same regions. Their dual function is corroborated by existing experimental data. Additionally, we show examples of human exon remnants stemming from the vertebrate 2R WGD. Our findings suggest that long-range cis-regulatory inputs for developmental genes are not limited to non-coding regions, but can also overlap the coding sequence of unrelated genes. Thus, exonic regulatory elements in GRBs might be functionally equivalent to those in non-coding regions, calling for a re-evaluation of the sequence space in which to look for long-range regulatory elements and experimentally test their activity. 相似文献
16.
Tomaz Henrique Araújo Flavio Pavla de Faria Eduardo Katchburian Edna Freymüller Haapalainen 《Acta zoologica》2010,91(4):440-446
Araújo, T.H., Faria, F.P., Katchburian, E. and Freymüller, E. (2009). Ultrastructural changes in skeletal muscle of the tail of the lizard Hemidactylus mabouia immediately following autotomy. —Acta Zoologica (Stockholm) 91 : 440–446. Although autotomy and subsequent regeneration of lizard tails has been extensively studied, there is little information available on ultrastructural changes that occur to the muscle fibers at the site of severance. Thus, in the present study, we examine the ultrastructure of the musculature of the remaining tail stump of the lizard Hemidactylus mabouia immediately after autotomy. Our results show that exposed portions of the skeletal muscle fibers of the stump that are unprotected by connective tissue bulge to produce large mushroom‐like protrusions. These exposed portions show abnormal structure but suffer no leakage of cytoplasmic contents. Many small and large vesicular structures appeared between myofibrils in the interface at this disarranged region (distal) and the other portion of the fibers that remain unchanged (proximal). These vesicles coalesce, creating a gap that leads to the release of the mushroom‐like protrusion. So, our results showed that after the macroscopic act of autotomy the muscular fibers release part of the sarcoplasm as if a second and microscopic set of autotomic events takes place immediately following the macroscopic act of autotomy. Presumably these changes pave the way for the formation of a blastema and the beginning of regeneration. 相似文献
17.
Karel Královec Zbyněk Roček Pavla Žáková Vladimíra Mužáková 《Journal of morphology》2010,271(9):1078-1093
We use histological techniques and computer‐aided three‐dimensional reconstructions made from serial histological sections to describe the ontogeny of the ethmoidal endocranium of discoglossid frog Discoglossus pictus. We identify a pattern of development for the suprarostral cartilage that differs from previous findings and probably represents the ancestral anuran pattern. The nasal cartilages, including the inferior prenasal cartilage, are de novo adult structures. The only larva‐derived structures of the adult nasal capsules are the posterior aspects of the solum nasi and septum nasi. We also identify patterns of development for the ethmoid plate and postnasal wall that occur during early in ontogenesis. These patterns are associated with development events during metamorphic climax. The pattern of timing of chondrification of the anterior nasal cartilages more closely coincides with that of the neobatrachian species than that recorded for the pelobatid frog Spea. In addition, this study supports a sister taxon relationship between Discoglossus and Alytes. J. Morphol. 271:1078‐1093, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
18.
Pokorna B Mandl M Borilova S Ceskova P Markova R Janiczek O 《Applied and environmental microbiology》2007,73(11):3752-3754
Wide ranges of growth yields on sulfur (from 2.4 x 10(10) to 8.1 x 10(11) cells g(-1)) and maximum sulfur oxidation rates (from 0.068 to 1.30 mmol liter(-1) h(-1)) of an Acidithiobacillus ferrooxidans strain (CCM 4253) were observed in 73 batch cultures. No significant correlation between the constants was observed. Changes of the Michaelis constant for sulfur (from 0.46 to 15.5 mM) in resting cells were also noted. 相似文献
19.
Simerská P Monti D Cechová I Pelantová H Macková M Bezouska K Riva S Kren V 《Journal of biotechnology》2007,128(1):61-71
An extracellular alpha-d-galactosidase from Talaromyces flavus CCF 2686 with extremely broad and unusual acceptor specificity is produced exclusively in the presence of the specific inducer--6-deoxy-D-glucose (quinovose). The procedure for the preparation of this very expensive substance has been modified and optimized. Surprisingly, any of other common alpha-D-galactosidase inducers or substrates, e.g., D-galactose, melibiose and raffinose, did not stimulate its production. The crude alpha-D-galactosidase preparation was purified by anion-exchange chromatography and three isoenzymes with different substrate specificities were identified. The main isoenzyme (alphaGal1) was further purified by cation-exchange chromatography and fully characterized. When compared with other alpha-galactosidases and also with other isoenzymes produced by T. flavus, it showed a markedly different regioselectivity and also negligible hydrolytic activity towards melibiose. Moreover, it was active on polymeric substrates (locust bean gum, guar gum) and significantly inhibited by alpha-D-galactopyranosyl azide, D-galactose, D-xylose, melibiose, methyl alpha- and beta-D-galactopyranoside and lactose. 相似文献
20.
Spíchal L Krystof V Paprskárová M Lenobel R Styskala J Binarová P Cenklová V De Veylder L Inzé D Kontopidis G Fischer PM Schmülling T Strnad M 《The Journal of biological chemistry》2007,282(19):14356-14363
Cytokinins are a class of plant hormones that regulate the cell cycle and diverse developmental and physiological processes. Several compounds have been identified that antagonize the effects of cytokinins. Based on structural similarities and competitive inhibition, it has been assumed that these anticytokinins act through a common cellular target, namely the cytokinin receptor. Here, we examined directly the possibility that various representative classical anticytokinins inhibit the Arabidopsis cytokinin receptors CRE1/AHK4 (cytokinin response 1/Arabidopsis histidine kinase 4) and AHK3 (Arabidopsis histidine kinase 3). We show that pyrrolo[2,3-d]pyrimidine and pyrazolo[4,3-d]pyrimidine anticytokinins do not act as competitors of cytokinins at the receptor level. Flow cytometry and microscopic analyses revealed that anticytokinins inhibit the cell cycle and cause disorganization of the microtubular cytoskeleton and apoptosis. This is consistent with the hypothesis that they inhibit regulatory cyclin-dependent kinase (CDK) enzymes. Biochemical studies demonstrated inhibition by selected anti-cytokinins of both Arabidopsis and human CDKs. X-ray determination of the crystal structure of a human CDK2-anticytokinin complex demonstrated that the antagonist occupies the ATP-binding site of CDK2. Finally, treatment of human cancer cell lines with anticytokinins demonstrated their ability to kill human cells with similar effectiveness as known CDK inhibitors. 相似文献