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11.
Benoît Le Tallec Stéphane Koundrioukoff Therese Wilhelm Anne Letessier Olivier Brison Michelle Debatisse 《Cellular and molecular life sciences : CMLS》2014,71(23):4489-4494
Common fragile sites (CFSs) are large chromosomal regions long identified by conventional cytogenetics as sequences prone to breakage in cells subjected to replication stress. The interest in CFSs came from their key role in the formation of DNA damage, resulting in chromosomal rearrangements. The instability of CFSs was notably correlated with the appearance of genome instability in precancerous lesions and during tumor progression. Identification of the molecular mechanisms responsible for their instability therefore represents a major challenge. A number of data show that breaks result from mitotic entry before replication completion but the mechanisms responsible for such delayed replication of CFSs and relaxed checkpoint surveillance are still debated. In addition, clues to the molecular events leading to breakage just start to emerge. We present here the results of recent reports addressing these questions. 相似文献
12.
Galvin P Thompson D Ryan KB McCarthy A Moore AC Burke CS Dyson M Maccraith BD Gun'ko YK Byrne MT Volkov Y Keely C Keehan E Howe M Duffy C MacLoughlin R 《Cellular and molecular life sciences : CMLS》2012,69(3):389-404
Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues. 相似文献
13.
Enucleated oocytes have the distinctive ability to reprogram somatic nuclei back to totipotency. Here, we investigate genome-scale DNA methylation patterns after nuclear transfer and compare them to the dynamics at fertilization. We identify specific targets for DNA demethylation after nuclear transfer, such as germline-associated promoters, as well as unique limitations that include certain repetitive element classes. 相似文献
14.
Ververis K Rodd AL Tang MM El-Osta A Karagiannis TC 《Cellular and molecular life sciences : CMLS》2011,68(24):4101-4114
Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid
(Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that
histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies
such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies,
involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified
that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in
cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase
inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes.
Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors
tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained
nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight
the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination
therapies for cancer. 相似文献
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17.
F. Kaiser 《Cellular and molecular life sciences : CMLS》1965,21(10):575-575
Summary The primary glycosides, glucodigifucoside and neo-glucodigifucoside, were isolated from the extract ofDigitalis lanata leaves. They are isomeric glucosides of digiproside and differ in the position of attachment of thed-glucose residue. Digitoxigenin-allomethylosid was isolated from the leaves after enzymatic decomposition.
23. Mitteilung über Herzglykoside; unter der ausgezeichneten experimentellen Mitarbeit vonH. Gerlach. 相似文献
23. Mitteilung über Herzglykoside; unter der ausgezeichneten experimentellen Mitarbeit vonH. Gerlach. 相似文献
18.
Heterotrimeric G-proteins bind to cell-surface receptors and are integral in transmission of signals from outside the cell. Upon activation of the Galpha subunit by binding of GTP, the Galpha and Gbetagamma subunits dissociate and interact with effector proteins for signal transduction. Regulatory proteins with the 19-amino-acid GoLoco motif can bind to Galpha subunits and maintain G-protein subunit dissociation in the absence of Galpha activation. Here we describe the structural determinants of GoLoco activity as revealed by the crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's highly conserved Asp/Glu-Gln-Arg triad into the nucleotide-binding pocket of Galpha to make direct contact with the GDP alpha- and beta-phosphates. The structural organization of the GoLoco Galpha(i1) complex, when combined with supporting data from domain-swapping experiments, suggests that the Galpha all-helical domain and GoLoco-region carboxy-terminal residues control the specificity of GoLoco Galpha interactions. 相似文献
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20.
Read TD Peterson SN Tourasse N Baillie LW Paulsen IT Nelson KE Tettelin H Fouts DE Eisen JA Gill SR Holtzapple EK Okstad OA Helgason E Rilstone J Wu M Kolonay JF Beanan MJ Dodson RJ Brinkac LM Gwinn M DeBoy RT Madpu R Daugherty SC Durkin AS Haft DH Nelson WC Peterson JD Pop M Khouri HM Radune D Benton JL Mahamoud Y Jiang L Hance IR Weidman JF Berry KJ Plaut RD Wolf AM Watkins KL Nierman WC Hazen A Cline R Redmond C Thwaite JE White O Salzberg SL Thomason B Friedlander AM Koehler TM Hanna PC 《Nature》2003,423(6935):81-86
Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. 相似文献