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951.
We have recently reported the synthesis of a platinum(II) complex, made of estradiol, the female sex hormone, and a cisplatin analog, an anticancer drug, linked together by an eleven carbon atoms chain. The novel estradiol-Pt(II) hybrid molecule was synthesized in nine chemical steps with 10% overall yield. This new compound has been tested in vitro on estrogen-dependent (MCF-7) and -independent (MDA-MD-231) (ER(+) and ER(-)) cell lines. Interestingly, the biological activity was quite significant, more potent than that of cisplatin, the compound currently used in chemotherapy. The estrogen receptor binding affinity (ERBA) of this compound was very similar to that of 17beta-estradiol (E(2)) on both estrogen receptors (ERs), alpha and beta. In order to further study this type of molecule, we have decided to synthesize several analogs with the same estrogenic scaffold but with various chain lengths separating the estradiol from the toxic part of the molecule. This was planned in order to study the effect of the length of the linking chain on the biological activity of the hybrids. Four E(2)-Pt(II) hybrid molecules having 6-14 carbon atoms linking chain have been synthesized using a new synthetic methodology. They are synthesized in only eight chemical steps with 21% overall yield. The 17beta-estradiol-linked platinum(II) complexes have been tested for their receptor binding affinity as well as for their cytocidal activity on several breast cancer cell lines. The synthesis and biological results are reported herein. 相似文献
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954.
Two new turtles from the Lower Eocene of Saint-Papoul (Aude, France). Among the fossil turtles from of the Lower Eocene of Saint-Papoul (Aude, France), two new taxa of freshwater Testudinoidea are described. The first is a new species of the genus Palaeoemys, known before in the Lutetian of Germany. The second taxon is a new genus, also described on material of Pépieux-Cesseras and Eygalayes. To cite this article: S. Hervet, C. R. Palevol 2 (2003). 相似文献
955.
Hunter syndrome (mucopolysaccharidosis-II) is caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. The assay of this sulfatase requires the use of α-l-iduronate glycosides containing a sulfate at the 2-position. We report a simple, three-step procedure for the introduction of sulfate at the 2-position starting with the methyl ester of α-l-iduronate glycosides. The procedure involves protection of the 2- and 4-hydroxyl groups of the iduronate moiety as the dibutyl stannylene acetal, selective sulfation with sulfur trioxide-trimethylamine, and deprotection of the methyl ester to afford the desired 2-sulfate in 61% overall yield. 相似文献
956.
Banas SM Rouch C Kassis N Markaki EM Gerozissis K 《Cellular and molecular neurobiology》2009,29(2):157-168
Early changes in neuroendocrine pathways are essential in the development of metabolic pathologies. Thus, it is important
to have a better understanding of the signals involved in their initiation. Long-term consumption of high-fat diets induces
insulin resistance, obesity, diabetes. Here, we have investigated early neural and endocrine events in the hypothalamus and
hippocampus induced by a short-term high fat, low carbohydrate diet in adult male Wistar rats. The release of serotonin, which
is closely associated with the actions of insulin and leptin, was measured, by electrochemical detection following reverse-phase
liquid chromatography (HPLC), in the extracellular space of the medial hypothalamus and the dorsal hippocampus in samples
obtained from non-anesthetized animals, by microdialysis. The high-fat diet had a specific effect on the hypothalamus. Serotonin
release induced by food intake was reduced after 1 week, and effectively ceased after 6 weeks of the diet. After 1 week, there
was an increased gene expression of the insulin receptor and the insulin receptor substrates IRS1 and IRS2, as measured by
real-time PCR. After 6 weeks of diet, insulin gene expression increased. Leptinemia increased in all cases. This new data
support the concept that high-fat diets, in addition to have peripheral effects, cause a rapid alteration in specific central
mechanisms involved in energy and glucose homeostasis. The changes in the gene expression of insulin and signaling elements
represent possible adaptations aimed at counterbalancing the reduced responsiveness of the serotonergic system to nutritional
signals and maintaining homeostasis.
Sophie M. Banas and Claude Rouch have contributed equally to this work. 相似文献
957.
Annika?C.?DahlbergEmail author Sophie?B.?Trygger 《Human ecology: an interdisciplinary journal》2009,37(1):79-94
Indigenous medicine is important to rural livelihoods, but lay knowledge and use of medicinal plants has not been extensively
studied. Research in KwaZulu-Natal, South Africa, showed that medicinal plants were frequently used by villagers and contributed
to their ability to cope with health problems. Knowledge of plants and household remedies was extensive and varied in that
households often held different knowledge. Villagers mainly relied on common species, and were generally aware of alternative
species for a certain ailment. People were flexible in their use of indigenous and western health care, which were both perceived
as beneficial. Improved cooperation between health care systems could improve health standards. Extraction of medicinal plants
has been described as unsustainable in the region—a situation not found in the study area. It is argued that conservation
policies aimed to restrict access should be differential and potentially not include local consumption, since this may be
ecologically unnecessary and entail local hardships. 相似文献
958.
Alexander D. Dergunov Anne Ponthieux Maxim V. Mel’kin Daniel Lambert Sophie Visvikis-Siest Gerard Siest 《Molecular and cellular biochemistry》2009,325(1-2):41-51
Sixteen patients differing widely in plasma triglyceride content were divided into three groups by their apolipoprotein E (apoE) phenotype—E33 homozygotes, E23, and E34 heterozygotes. The plasma lipid and apoE distribution between individual lipoproteins was followed by capillary isotachophoresis (CITP) of plasma samples pre-stained with lipid fluorescent probe NBD-C6-ceramide and by fluorescein-labeled apoE, respectively. Among 12 peaks visualized by ceramide staining, an individual peak with very low density lipoproteins (VLDL) was identified. The VLDL cholesterol and apoE content determined by CITP directly in whole plasma were significantly related to their content as determined by conventional analysis with isolated VLDL. The ceramide distribution among lipoprotein pools was insensitive to apoE phenotype (49–53 : 7–11 : 39–43% for HDL, VLDL, and IDL/LDL, respectively) while the preferential binding of apoE to VLDL was observed in E34 patients compared to E33 (62 : 19 : 20 vs. 70 : 9 : 22%). In a study of apoE/F displacement from lipoproteins at plasma titration by apoC-III in vitro, apoE was found to bind more tightly to VLDL from E34 compared to E33 patients as evidenced by both the increased non-displaceable apoE pool, the increased VLDL sorbtion capacity for apoE, and the decreased displacement parameter in a “container” model of lipoprotein binding. Two different types of apoE package in a whole lipoprotein profile were observed. ApoE structure in a particular lipoprotein may underlie the phenotype-sensitive apoE distribution and apoC-III interference in hypertriglyceridemia. 相似文献
959.
Claudine Dherin Emeric Gueneau Mathilde Francin Marcela Nunez Simona Miron Sascha Emilie Liberti Lene Juel Rasmussen Sophie Zinn-Justin Bernard Gilquin Jean-Baptiste Charbonnier Serge Boiteux 《Molecular and cellular biology》2009,29(3):907-918
Mlh1 is an essential factor of mismatch repair (MMR) and meiotic recombination. It interacts through its C-terminal region with MutL homologs and proteins involved in DNA repair and replication. In this study, we identified the site of yeast Mlh1 critical for the interaction with Exo1, Ntg2, and Sgs1 proteins, designated as site S2 by reference to the Mlh1/Pms1 heterodimerization site S1. We show that site S2 is also involved in the interaction between human MLH1 and EXO1 or BLM. Binding at this site involves a common motif on Mlh1 partners that we called the MIP-box for the Mlh1 interacting protein box. Direct and specific interactions between yeast Mlh1 and peptides derived from Exo1, Ntg2, and Sgs1 and between human MLH1 and peptide derived from EXO1 and BLM were measured with Kd values ranging from 8.1 to 17.4 μM. In Saccharomyces cerevisiae, a mutant of Mlh1 targeted at site S2 (Mlh1-E682A) behaves as a hypomorphic form of Exo1. The site S2 in Mlh1 mediates Exo1 recruitment in order to optimize MMR-dependent mutation avoidance. Given the conservation of Mlh1 and Exo1 interaction, it may readily impact Mlh1-dependent functions such as cancer prevention in higher eukaryotes. 相似文献
960.
Marie-Pierre Forquin Hugo Duvergey Caroline Proux Valentin Loux Jerome Mounier Sophie Landaud Jean-Yves Coppée Jean-Fran?ois Gibrat Pascal Bonnarme Isabelle Martin-Verstraete Tatiana Vallaeys 《Applied and environmental microbiology》2009,75(19):6406-6409
Multilocus sequence typing with nine selected genes is shown to be a promising new tool for accurate identifications of Brevibacteriaceae at the species level. A developed microarray also allows intraspecific diversity investigations of Brevibacterium aurantiacum showing that 13% to 15% of the genes of strain ATCC 9174 were absent or divergent in strain BL2 or ATCC 9175.Brevibacteriaceae play a major part in the cheese smear community (6, 11). The classification and typing of cheese-related Brevibacteriaceae have been based mainly on molecular methods such as amplified ribosomal DNA restriction enzyme analysis, pulsed-field gel electrophoresis, and ribotyping (8, 10, 12). Recently, the original Brevibacterium linens group was split into two species on the basis of their physiological and biochemical characteristics, the sugar and polyol composition of their teichoic acids, and their 16S rRNA sequence and DNA-DNA hybridization levels. One species remains B. linens and is represented by type strain ATCC 9172. The other, represented by type strain ATCC 9175, has been renamed Brevibacterium aurantiacum. Regarding this new classification, the taxonomic position of cheese-related isolates has to be revisited and potential relationships between phylogenetic affiliation and the potential occurrence of given metabolic characteristics redefined (7). The unfinished genome sequence of B. aurantiacum ATCC 9174 has recently been released by the Joint Genome Institute (http://genome.jgi-psf.org/draft_microbes/breli/breli.home.html). The development of focused phylogenetic approaches using multiple markers in conjunction with whole-genome screening techniques such as comparative genomic hybridization (CGH) has proven to be useful for the detailed characterization of pathogenic species, including food pathogens (3, 5, 9). However, only a few technological species have been investigated at an intraspecies level (2). Our intention was thus to develop modern tools to facilitate the typing of strains of technological interest, for which Brevibacteriaceae could be used as a case study. 相似文献