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51.
Role of cryptic genes in microbial evolution 总被引:24,自引:1,他引:23
Cryptic genes are phenotypically silent DNA sequences, not normally
expressed during the life cycle of an individual. They may, however, be
activated in a few individuals of a large population by mutation,
recombination, insertion elements, or other genetic mechanisms. A
consideration of the microbial literature concerning biochemical evolution,
physiology, and taxonomy provides the basis for a hypothesis of microbial
adaptation and evolution by mutational activation of cryptic genes.
Evidence is presented, and a mathematical model is derived, indicating that
powerful and biologically important mechanisms exist to prevent the loss of
cryptic genes. We propose that cryptic genes persist as a vital element of
the genetic repertoire, ready for recall by mutational activation in future
generations. Cryptic genes provide a versatile endogenous genetic reservoir
that enhances the adaptive potential of a species by a mechanism that is
independent of genetic exchange.
相似文献
52.
Poissonnier-Durieux S Ettaoussi M Pérès B Boutin JA Audinot V Bennejean C Delagrange P Caignard DH Renard P Berthelot P Lesieur D Yous S 《Bioorganic & medicinal chemistry》2008,16(18):8339-8348
A series of naphthalenic analogues of melatonin were prepared and evaluated as melatonin receptor MT(2) selective ligands. Activity and MT(2) selectivity can be modulated with suitable variations of the C-3 phenyl and the acyl group on the C-1 side chain. Surprisingly, in contrast with what had been previously described in other series (2-benzylindoles, 2-benzylbenzofurans and 3-phenyltetralins), the presence of a C-3 phenyl with a functional group on the meta position seems to be primordial for MT(2) affinity and selectivity. Indeed, N-[2-(3-(3-hydroxymethylphenyl)-7-methoxynaphth-1-yl)ethyl]acetamide (21) is one of the best MT(2) selective ligands described until now and behaves as an antagonist. 相似文献
53.
Lefoix M Coudert G Routier S Pfeiffer B Caignard DH Hickman J Pierré A Golsteyn RM Léonce S Bossard C Mérour JY 《Bioorganic & medicinal chemistry》2008,16(9):5303-5321
We describe here an efficient synthesis of new 5-azaindolocarbazoles designed for cytotoxic and Chk1 inhibiting properties. The synthesis of ‘symmetrical’ and ‘dissymmetrical’ structures is discussed. Concerning the dissymmetrical 5-azaindolocarbazoles derivatives, with both an indole moiety and a 5-azaindole moiety, the synthesis was achieved using two very efficient key steps. The first one is a Stille reaction with a 3-trimethylstannyl-5-azaindole derivative and the second one a photochemical step leading to the proposed polycyclic structure. Various pharmacomodulations were performed to investigate the structure–activity relationships (SAR). Several substituents such as OBn, OH, and methylenedioxy groups were successfully introduced on the indole moiety of the 5-azaindolocarbazole. Compounds with or without substituents on the nitrogen atom of the maleimide were prepared, as well as derivatives with glucopyranosyl substituent on the nitrogen atom of the indole moiety. The cytotoxicity of these new compounds was evaluated on two cell lines (L1210, HT29). Several compounds showed cytotoxicity in the sub-micromolar range. Among the most cytototoxic was the 1,3-dioxolo[4,5-b]-6-(2-dimethylaminoethyl)-1H-pyrido[3′,4′:4,5]pyrrolo[3,2-i]pyrrolo[3,4-g]carbazole-5,7(6H,12H)-dione (35, IC50 = 195 nM on L1210). The compounds were also investigated for their Chk1 inhibiting activity. Compounds without any substitution on the maleimide moiety were the most potent. This is the case of compounds 45–47 with IC50 of, respectively, 72, 27, and 14 nM toward Chk1. Compound 46, which exhibits moderate cytotoxicity, appears to be a good candidate for development in a multi-drug anticancer therapy. 相似文献
54.
Phosphostim-activated gamma delta T cells kill autologous metastatic renal cell carcinoma 总被引:7,自引:0,他引:7
Viey E Fromont G Escudier B Morel Y Da Rocha S Chouaib S Caignard A 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(3):1338-1347
Metastatic renal cell carcinoma, inherently resistant to conventional treatments, is considered immunogenic. Indeed, partial responses are obtained after treatment with cytokines such as IL-2 or IFN-alpha, suggesting that the immune system may control the tumor growth. In this study, we have investigated the ability of the main subset of peripheral gammadelta lymphocytes, the Vgamma9Vdelta2-TCR T lymphocytes, to induce an effective cytotoxic response against autologous primary renal cell carcinoma lines. These gammadelta T cells were expanded ex vivo using a Vgamma9Vdelta2 agonist, a synthetic phosphoantigen called Phosphostim. From 11 of 15 patients, the peripheral Vgamma9Vdelta2 T cells were amplified in vitro by stimulating PBMCs with IL-2 and Phosphostim molecule. These expanded Vgamma9Vdelta2 T cells express activation markers and exhibit an effector/memory phenotype. They display a selective lytic potential toward autologous primary renal tumor cells and not against renal NC. The lytic activity involves the perforin-granzyme pathway and is mainly TCR and NKG2D receptor dependent. Furthermore, an increased expression of MHC class I-related molecule A or B proteins, known ligands of NKG2D, are detected on primary renal tumor cells. Interestingly, from 2 of the 11 positive cultures in response to Phosphostim, expanded-Vgamma9Vdelta2 T cells present an expression of killer cell Ig-like receptors, suggesting their prior recruitment in vivo. Unexpectedly, on serial frozen sections from three tumors, we observe a gammadelta lymphocyte infiltrate that was mainly composed of Vgamma9Vdelta2 T cells. These results outline that Vgamma9Vdelta2-TCR effectors may represent a promising approach for the treatment of metastatic renal cell carcinoma. 相似文献
55.
Fontana A Benito EJ Martín MJ Sánchez N Alajarín R Vaquero JJ Alvarez-Builla J Lambel-Giraudet S Leonce S Pierré A Caignard D 《Bioorganic & medicinal chemistry letters》2002,12(18):2611-2614
Several new pyridazino[1',6':1,2]pyrido[3,4-b]indol-5-inium derivatives were synthesised from beta-carboline derivatives and their cytotoxic activity and effect on the cell cycle were evaluated against L1210 cancer cells. 相似文献
56.
Lisowski V Fabis F Pierré A Caignard DH Renard P Rault S 《Journal of enzyme inhibition and medicinal chemistry》2002,17(6):403-407
Diazepine analogs of thieno[2,3-b]pyrrolizin-8-ones were synthesized by aromatization of 2-hydroxypyrrolo[1,2-a]thieno[3,2-e][1,4]diazepines. These compounds were evaluated in vitro for their antiproliferative activity against the L1210 leukemia cell line. The activity of these compounds was in the micromolar range, the best result being for the mixture of the isomers 5 and 6 which showed a 0.35 microM IC50 against cell growth. 相似文献
57.
58.
liane Schermer Marie‐Claude Bel‐Venner David Fouchet Aurlie Siberchicot Vincent Boulanger Thomas Caignard Michel Thibaudon Gilles Oliver Manuel Nicolas Jean‐Michel Gaillard Sylvain Delzon Samuel Venner 《Ecology letters》2019,22(1):98-107
In many perennial wind‐pollinated plants, the dynamics of seed production is commonly known to be highly fluctuating from year to year and synchronised among individuals within populations. The proximate causes of such seeding dynamics, called masting, are still poorly understood in oak species that are widespread in the northern hemisphere, and whose fruiting dynamics dramatically impacts forest regeneration and biodiversity. Combining long‐term surveys of oak airborne pollen amount and acorn production over large‐scale field networks in temperate areas, and a mechanistic modelling approach, we found that the pollen dynamics is the key driver of oak masting. Mechanisms at play involved both internal resource allocation to pollen production synchronised among trees and spring weather conditions affecting the amount of airborne pollen available for reproduction. The sensitivity of airborne pollen to weather conditions might make oak masting and its ecological consequences highly sensitive to climate change. 相似文献
59.
Blanc-Delmas E Lebegue N Wallez V Leclerc V Yous S Carato P Farce A Bennejean C Renard P Caignard DH Audinot-Bouchez V Chomarat P Boutin J Hennuyer N Louche K Carmona MC Staels B Pénicaud L Casteilla L Lonchampt M Dacquet C Chavatte P Berthelot P Lesieur D 《Bioorganic & medicinal chemistry》2006,14(22):7377-7391
A series of 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles has been synthesized and tested for PPARgamma agonist activity. SAR were developed and revealed that 6-acyl-2(3H)-benzothiazolone derivatives with 1,3-dicarbonyl group were the most potent. IP administration of compound 22 exhibited comparable levels of glucose and triglyceride correction to PO administration of rosiglitazone in the ob/ob mouse studies. 相似文献
60.
Ethan DH Kim Ashish Sabharwal Adrian R Vetta Mathieu Blanchette 《Algorithms for molecular biology : AMB》2010,5(1):34