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91.
María Prez-Caro Csar Cobaleda Ins Gonzlez-Herrero Carolina Vicente-Dueas Camino Bermejo-Rodríguez Margarita Snchez-Beato Alberto Orfao Beln Pintado Teresa Flores Manuel Snchez-Martín Rafael Jimnez Miguel A Piris Isidro Snchez-García 《The EMBO journal》2009,28(1):8-20
In human cancers, all cancerous cells carry the oncogenic genetic lesions. However, to elucidate whether cancer is a stem cell-driven tissue, we have developed a strategy to limit oncogene expression to the stem cell compartment in a transgenic mouse setting. Here, we focus on the effects of the BCR-ABLp210 oncogene, associated with chronic myeloid leukaemia (CML) in humans. We show that CML phenotype and biology can be established in mice by restricting BCR-ABLp210 expression to stem cell antigen 1 (Sca1)+ cells. The course of the disease in Sca1-BCR-ABLp210 mice was not modified on STI571 treatment. However, BCR-ABLp210-induced CML is reversible through the unique elimination of the cancer stem cells (CSCs). Overall, our data show that oncogene expression in Sca1+ cells is all that is required to fully reprogramme it, giving rise to a full-blown, oncogene-specified tumour with all its mature cellular diversity, and that elimination of the CSCs is enough to eradicate the whole tumour. 相似文献
92.
Comparison of the three-dimensional structure of hyperthermophilic and mesophilic β-glycosidases shows differences in secondary
structure composition. The enzymes from hyperthermophilic archaea have a significantly larger number of β-strands arranged
in supernumerary β-sheets compared to mesophilic enzymes from bacteria and other organisms. Amino acid replacements designed
to alter the structure of the supernumerary β-strands were introduced by site directed mutagenesis into the sequence encoding
the β-glycosidase from Sulfolobus solfataricus. Most of the replacements caused almost complete loss of activity but some yielded enzyme variants whose activities were
affected specifically at higher temperatures. Far-UV CD spectra recorded as a function of temperature for both wild type β-glycosidase
and mutant V349G, one of the mutants with reduced activity at higher temperatures, were similar, showing that the protein
structure of the mutant was stable at the highest temperatures assayed. The properties of mutant V349G show a difference between
thermostability (stability of the protein structure at high temperatures) and thermophilicity (optimal activity at high temperatures). 相似文献
93.
Polybrominated diphenyl ethers (PBDEs) are widely used as additive flame-retardants and have been detected in human blood,
adipose tissue, and breast milk. Developmental and long-term exposures to these chemicals may pose a human health risk, especially
to children. We have previously demonstrated that polychlorinated biphenyls (PCBs), which are structurally similar to PBDEs
and cause neurotoxicity, perturb intracellular signaling events including calcium homeostasis and protein kinase C translocation,
which are critical for neuronal function and development of the nervous system. The objective of the present study was to
test whether environmentally relevant PBDE congeners 47 and 99 are also capable of disrupting Ca2 + homeostasis. Calcium buffering was determined by measuring 45Ca2 + -uptake by microsomes and mitochondria, isolated from adult male rat brain (frontal cortex, cerebellum, hippocampus, and hypothalamus).
Results show that PBDEs 47 and 99 inhibit both microsomal and mitochondrial 45Ca2 + -uptake in a concentration-dependent manner. The effect of these congeners on 45Ca2 + -uptake is similar in all four brain regions though the hypothalamus seems to be slightly more sensitive. Among the two preparations,
the congeners inhibited 45Ca2 + -uptake in mitochondria to a greater extent than in microsomes. These results indicate that PBDE 47 and PBDE 99 congeners
perturb calcium signaling in rat brain in a manner similar to PCB congeners, suggesting a common mode of action of these persistent
organic pollutants.
The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory
of the US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily
reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement
or recommendation for use.
These results will be presented at the 21th Biennial Meeting of International Society for Neurochemistry and American Society
for Neurochemistry in Cancun, Mexico (August 19–24, 2007).
Special issue article in honor of Dr. Frode Fonnum. 相似文献
94.
95.
96.
Patrick Mavingui Margarita Flores Xianwu Guo Guillermo Dvila Xavier Perret William J. Broughton Rafael Palacios 《Journal of bacteriology》2002,184(1):171-176
Bacterial genomes are usually partitioned in several replicons, which are dynamic structures prone to mutation and genomic rearrangements, thus contributing to genome evolution. Nevertheless, much remains to be learned about the origins and dynamics of the formation of bacterial alternative genomic states and their possible biological consequences. To address these issues, we have studied the dynamics of the genome architecture in Rhizobium sp. strain NGR234 and analyzed its biological significance. NGR234 genome consists of three replicons: the symbiotic plasmid pNGR234a (536,165 bp), the megaplasmid pNGR234b (>2,000 kb), and the chromosome (>3,700 kb). Here we report that genome analyses of cell siblings showed the occurrence of large-scale DNA rearrangements consisting of cointegrations and excisions between the three replicons. As a result, four new genomic architectures have emerged. Three consisted of the cointegrates between two replicons: chromosome-pNGR234a, chromosome-pNGR234b, and pNGR234a-pNGR234b. The other consisted of a cointegrate of the three replicons (chromosome-pNGR234a-pNGR234b). Cointegration and excision of pNGR234a with either the chromosome or pNGR234b were studied and found to proceed via a Campbell-type mechanism, mediated by insertion sequence elements. We provide evidence showing that changes in the genome architecture did not alter the growth and symbiotic proficiency of Rhizobium derivatives. 相似文献
97.
Gutiérrez ME García AF Africa de Madariaga M Sagrista ML Casadó FJ Mora M 《Life sciences》2003,72(21):2337-2360
This paper describes the use of complex liposomes as real membrane models to evaluate the potential benefits of several antioxidants in relation to lipid peroxidation. The xanthine oxidase/Fe(3+)-ADP-EDTA and the Fe(2+)/H2O2 systems have been used to generate hydroxyl radicals and the water soluble azo-compound 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) to generate carbon centered radicals (A*) by thermal decomposition. The antioxidant behavior of the rosemary and citrus plant extracts and vitamin-E and vitamin-E acetate alpha-tocopherols have been analyzed. The order of effectiveness in avoiding radical chain reactions has been established by using the colorimetric thiobarbituric acid reaction and the fluorescent probe DPH-PA. ESR spectroscopy has been used to carry out the pursuit of the oxidation processes on the basis of the identification of the radical species resulting from the oxidant system and the ability of the antioxidants to act as scavengers for hydroxyl and AAPH-derived radicals. The modification of the main transition temperature for the lipid mixture and the splitting of the calorimetric peak in the presence of the antioxidants were demonstrated by differential scanning calorimetry. The results obtained showed that the phenols-containing plant extracts and alpha-tocopherols perturb the phase behavior of the BBE lipid bilayer and have a fluidifying effect that could favor the known antioxidant capability and scavenging characteristics of these compounds. 31P-NMR results could be interpreted as, after the incorporation of these antioxidants, those lipid molecules interacting with antioxidants give rise to lamellar phase spectral components with resonance position at lower fields or to isotropic signals in accordance with a higher motion of their phosphate groups. 相似文献
98.
Margarita Puigserver Marie‐Josphe Chrtiennot‐Dinet Elisabeth Nezan 《Journal of phycology》2003,39(4):762-774
Five species belonging to the family Prymnesiaceae (one Prymnesium and four Chrysochromulina) have been identified in cultures obtained from water collected in the Bay of Banyuls‐sur‐Mer (Mediterranean Sea, France) using LM, SEM, and TEM. Two are described as new species, Chrysochromulina lanceolata sp. nov. and C. pseudolanceolata sp. nov. Both species are large and lanceolate with an acute posterior and two anterior arms. They are easily detectable with LM but difficult to distinguish to species level with live cells, without experience. EM reveals two completely different scale patterns in the two species. Cells of C. lanceolata are 21–38 μm long, 7–12 μm wide, and 3–7 μm thick. They possess two subequal flagella (30–51 and 29–44 μm), and the haptonema is shorter than the flagella (23–37 μm). The cell body is covered by plate and spine scales. Cells of C. pseudolanceolata sp. nov. are slightly smaller (15–18 × 6–8 μm) with more rounded extremities, two subequal flagella (19–26 and 17–24 μm), and the haptonema is longer than the flagella (about 35 μm). Three types of plate scales are observed in this species. Other findings are C. alifera Parke et Manton and C. throndsenii Eikrem (a new record for the Mediterranean Sea). Prymnesium faveolatum Fresnel, a new toxic species recently described, is illustrated with both LM and SEM. 相似文献
99.
Margarita Torrent Blanca Llompart Sabine Lasserre-Ramassamy Immaculada Llop-Tous Miriam Bastida Pau Marzabal Ann Westerholm-Parvinen Markku Saloheimo Peter B Heifetz M Dolors Ludevid 《BMC biology》2009,7(1):5-14
Background
Protein bodies (PBs) are natural endoplasmic reticulum (ER) or vacuole plant-derived organelles that stably accumulate large amounts of storage proteins in seeds. The proline-rich N-terminal domain derived from the maize storage protein γ zein (Zera) is sufficient to induce PBs in non-seed tissues of Arabidopsis and tobacco. This Zera property opens up new routes for high-level accumulation of recombinant proteins by fusion of Zera with proteins of interest. In this work we extend the advantageous properties of plant seed PBs to recombinant protein production in useful non-plant eukaryotic hosts including cultured fungal, mammalian and insect cells. 相似文献100.
Margarita Kirkova Elina Tzvetanova Stefani Vircheva Rositsa Zamfirova Beata Grygier Marta Kubera 《Cell biochemistry and function》2010,28(6):497-502
In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14‐day treatment with fluoxetine (10 mg kg?1 day?1, i.p.), the endogenous antioxidant non‐enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug‐protective effect against the melanoma‐induced oxidative changes (increased LP and decreased total glutathione (GSH)‐level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose‐dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma‐induced oxidative changes in mice spleen. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献