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61.
Atul Gupta Pijus Saha Caroline Descôteaux Valérie Leblanc Éric Asselin Gervais Bérubé 《Bioorganic & medicinal chemistry letters》2010,20(5):1614-1618
A series of estradiol–chlorambucil hybrids was synthesized as anticancer drugs for site-directed chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of estrone at position 16α of the steroid nucleus. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent breast cancer cell lines. The novel hybrids showed significant in vitro anticancer activity when compared to chlorambucil. Structure–activity relationship (SAR) reveals the influence of the length of the spacer chain between carrier and drug molecule. 相似文献
62.
Dominic Bastien Valérie Leblanc Éric Asselin Gervais Bérubé 《Bioorganic & medicinal chemistry letters》2010,20(7):2078-2081
The synthesis of two separable isomeric testosterone dimers is reported. The dimers are made from testosterone in a 5 step sequence and with 36% overall yield. The key dimerization step was performed using Hoveyda–Grubb’s metathesis catalysts on 7α-allyltestosterone with 75% yield. The synthesis led to separable isomeric dimers (trans and cis, 2:1). X-ray diffraction crystallography, performed on monocrystal of the minor isomer, confirms the cis geometry of the double bound between the two testosterone units. MTT assays showed that the cis dimer has the highest activity against prostate cancer cell lines. The novel cis dimer is more active than the antiandrogen cyproterone acetate indicating the possible therapeutic value of this molecule. 相似文献
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Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux
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Bartels CF Bükülmez H Padayatti P Rhee DK van Ravenswaaij-Arts C Pauli RM Mundlos S Chitayat D Shih LY Al-Gazali LI Kant S Cole T Morton J Cormier-Daire V Faivre L Lees M Kirk J Mortier GR Leroy J Zabel B Kim CA Crow Y Braverman NE van den Akker F Warman ML 《American journal of human genetics》2004,75(1):27-34
The homodimeric transmembrane receptor natriuretic peptide receptor B (NPR-B [also known as guanylate cyclase B, GC-B, and GUC2B]; gene name NPR2) produces cytoplasmic cyclic GMP from GTP on binding its extracellular ligand, C-type natriuretic peptide (CNP). CNP has previously been implicated in the regulation of skeletal growth in transgenic and knockout mice. The autosomal recessive skeletal dysplasia known as "acromesomelic dysplasia, type Maroteaux" (AMDM) maps to an interval that contains NPR2. We sequenced DNA from 21 families affected by AMDM and found 4 nonsense mutations, 4 frameshift mutations, 2 splice-site mutations, and 11 missense mutations. Molecular modeling was used to examine the putative protein change brought about by each missense mutation. Three missense mutations were tested in a functional assay and were found to have markedly deficient guanylyl cyclase activity. We also found that obligate carriers of NPR2 mutations have heights that are below the mean for matched controls. We conclude that, although NPR-B is expressed in a number of tissues, its major role is in the regulation of skeletal growth. 相似文献
65.
Regulation of prohibitin expression during follicular development and atresia in the mammalian ovary
Thompson WE Asselin E Branch A Stiles JK Sutovsky P Lai L Im GS Prather RS Isom SC Rucker E Tsang BK 《Biology of reproduction》2004,71(1):282-290
Prohibitin is a ubiquitous and highly conserved protein implicated as an important regulator in cell survival. Prohibitin content is inversely associated with cell proliferation, but it increases during granulosa cell differentiation as well as in earlier events of apoptosis in a temperature-sensitive granulosa cell line. In the present study, we have characterized the spatial expression patterns for prohibitin using established in vivo models for the induction of follicular development and atresia in the mammalian ovary. Comparative Western blot analyses of granulosa cell lysates from control ovaries and from ovaries primed with eCG or treated with eCG plus anti-eCG (gonadotropin withdrawal) were conducted. Prohibitin was immunolocalized in rat ovarian sections probed with antibodies against either proliferating cell nuclear antigen (PCNA) or cholesterol side-chain cleavage cytochrome P450 (P450(scc)) or in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeled sections. Additionally, porcine oocytes, zygotes, and blastocyts were also immunolocalized with prohibitin antibody. Immunolocalization revealed the presence of prohibitin in granulosa cells, theca-interstitial cells, and the oocyte. The results indicate that prohibitin protein expression in the gonadotropin-treated cells was upregulated. Immunoreactivity of prohibitin was inversely related to PCNA expression during follicular maturation and colocalized with P450(scc). Prohibitin appeared to be translocated from the cytoplasm to the nucleus in atretic follicles, germinal vesicle-stage oocytes, zygotes, and blastocysts. These results suggest that prohibitin has several functional regulatory roles in granulosa and theca-interstitial cells and in the ovum during follicular maturation and atresia. It is likely that prohibitin may play an important role in determining the fate of these cells and eventual follicular destiny. 相似文献
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Susceptibility and Adaptive Response to Bile Salts in Propionibacterium freudenreichii: Physiological and Proteomic Analysis
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Pauline Leverrier Diliana Dimova Vianney Pichereau Yanick Auffray Patrick Boyaval Gwnaël Jan 《Applied microbiology》2003,69(7):3809-3818
Tolerance to digestive stresses is one of the main factors limiting the use of microorganisms as live probiotic agents. Susceptibility to bile salts and tolerance acquisition in the probiotic strain Propionibacterium freudenreichii SI41 were characterized. We showed that pretreatment with a moderate concentration of bile salts (0.2 g/liter) greatly increased its survival during a subsequent lethal challenge (1.0 g/liter, 60 s). Bile salts challenge led to drastic morphological changes, consistent with intracellular material leakage, for nonadapted cells but not for preexposed ones. Moreover, the physiological state of the cells during lethal treatment played an important role in the response to bile salts, as stationary-phase bacteria appeared much less sensitive than exponentially growing cells. Either thermal or detergent pretreatment conferred significantly increased protection toward bile salts challenge. In contrast, some other heterologous pretreatments (hypothermic and hyperosmotic) had no effect on tolerance to bile salts, while acid pretreatment even might have sensitized the cells. Two-dimensional electrophoresis experiments revealed that at least 24 proteins were induced during bile salts adaptation. Identification of these polypeptides suggested that the bile salts stress response involves signal sensing and transduction, a general stress response (also triggered by thermal denaturation, oxidative toxicity, and DNA damage), and an alternative sigma factor. Taken together, our results provide new insights into the tolerance of P. freudenreichii to bile salts, which must be taken into consideration for the use of probiotic strains and the improvement of technological processes. 相似文献
68.
A Canadian PAV-like isolate of barley yellow dwarf virus (BYDV) was used to infect durum wheat (Triticum durum) cultivars previously identified in field trials involving artificial inoculation as highly sensitive (12 IDSN74), slightly tolerant (La Dulce), and relatively tolerant (Boohai and 12 IDSN227) to BYDV. The cultivars were inoculated in the greenhouse as seedlings, and indexed for virus accumulation by enzyme-linked immunosorbent assay (ELISA) at various intervals between 3 and 60 days thereafter. Mean ELISA values were somewhat consistent with tolerance levels for 4 durum wheat cultivars, but the use of ELISA to screen for BYDV resistance in durum wheat is not practical. The magnitude of the difference between sensitive and tolerant cultivars for the mean ELISA value is not high enough, and it may be necessary to average readings between 3 and 60 days after inoculation to obtain somewhat meaningful ELISA data. The effect of vector aphid numbers on virus titre and aerial biomass in the sensitive durum wheat cv. Karim was also evaluated. There was no significant effect on virus content in a preliminary trial, but a second trial revealed that more viruliferous aphids per plant resulted in higher ELISA values. Infestation with 32 or 50 viruliferous Rhopalosiphum padi per plant depressed biomass yield below the level observed with 1–10 aphids per plant. 相似文献
69.
Xavier Gansel Marie Dutreix Axel Hartke Philippe Boutibonnes Dr. Yanick Auffray 《Current microbiology》1993,27(5):267-271
With degenerated oligonucleotide primers for conserved regions of bacterial sigma factor proteins, a 117-bp internal DNA fragment of anrpoD-like gene ofLactoccocus lactis subsp.lactis ML3 was amplified by the polymerase chain reaction (PCR). The DNA sequence of this PCR product was determined by cycle sequencing, and the deduced amino acid sequence of this internal fragment showed an extensive homology with the known sigma factor sequences from six other microorganisms and present a 13-amino acid region corresponding to the typical RpoD box of primary sigma factors. This PCR product was used as a probe to specifically detect sigma homologs inPediococcus acidilactici, Leuconostoc lactis, Lactobacillus helveticus, Lactobacillus acidophilus, Enterococcus faecalis, Streptococcus thermophilus, andLactococcus lactis subsp.cremoris. These data are consistent with the existence of a high similarity between the primary sigma factors from diverse Gram-positive microorganisms. 相似文献
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