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Fereydoun Ala Jean-Pierre Allain Imelda Bates Kamel Boukef Frank Boulton James Brandful Elizabeth M. Dax Magdy El Ekiaby Albert Farrugia Jed Gorlin Oliver Hassall Helen Lee Andr�� Loua Kathryn Maitland Dora Mbanya Zainab Mukhtar William Murphy Ohene Opare-Sem Shirley Owusu-Ofori Henk Reesink David Roberts Oscar Torres Grace Totoe Henrik Ullum Silvano Wendel 《PLoS medicine》2012,9(9)
123.
Efficient UV stimulation of yeast integrative transformation requires damage on both plasmid strands
The nature of UV-induced pre-recombinational structures was studied using transformation of Saccharomyces cerevisiae cells with non-replicative plasmids. Transformation by double-stranded plasmids irradiated with UV was stimulated up to 50-fold, and both plasmid integration and conversion of the mutated chromosomal selective gene were found to be equally increased. The stimulation observed with such totally irradiated plasmids was not found with plasmids bearing lesions in only one strand. This effect is attributed to the formation by excision repair of recombinogenic structures consisting of a pyrimidine dimer opposite a gap. When single-stranded integrative plasmids were irradiated, their transforming potential was decreased but the proportion of transformants that arose by gene conversion, rather than by plasmid integration, was increased from 8% to 49% as a function of the UV dose. Possible reasons why single-strand UV lesions favour gene conversion are discussed. 相似文献
124.
Shirley H. Jones Ala E. Lew Wayne K. Jorgensen Stephen C. Barker 《International journal for parasitology》1997,27(12):1569-1573
Pulsed field gel electrophoresis of intact chromosomes of Babesia bovis revealed four chromosomes in the haploid genome. A telomere probe, derived from Plasmodium berghei, hybridised to eight SfiI restriction fragments of genomic B. bovis DNA digests indicating the presence of four chromosomes. A small subunit (18S) ribosomal RNA gene probe hybridised to the third chromsome only. The genome size of B. bovis is estimated to be 9.4 million base pairs. The sizes of chromosomes 1, 2, 3 and 4 are estimated to be 1.4, 2.0, 2.8 and 3.2 million base pairs, respectively. 相似文献
125.
Myroxylon balsamum (Leguminosae-Lotoideae) trunk wood contains a series of biogenetically related flavonoids, including the novel (±) -7-hydroxy-4′-methoxyisoflavanone, (±)-7,3′-dihydroxy-4′-methoxyisoflavanone and 2-(2′,4′-dihydroxyphenyl)-5,6-dimethoxybenzofuran. 相似文献
126.
Moshiri A Gonzalez E Tagawa K Maeda H Wang M Frishman LJ Wang SW 《Developmental biology》2008,316(2):214-227
Retinal ganglion cells (RGCs) are the first cell type to differentiate during retinal histogenesis. It has been postulated that specified RGCs subsequently influence the number and fate of the remaining progenitors to produce the rest of the retinal cell types. However, several genetic knockout models have argued against this developmental role for RGCs. Although it is known that RGCs secrete cellular factors implicated in cell proliferation, survival, and differentiation, until now, limited publications have shown that reductions in the RGC number cause significant changes in these processes. In this study, we observed that Math5 and Brn3b double null mice exhibited over a 99% reduction in the number of RGCs during development. This severe reduction of RGCs is accompanied by a drastic loss in the number of all other retinal cell types that was never seen before. Unlike Brn3b null or Math5 null animals, mice null for both alleles lack an optic nerve and have severe retinal dysfunction. Results of this study support the hypothesis that RGCs play a pivotal role in the late phase of mammalian retina development. 相似文献
127.
Yue EW Wayland B Douty B Crawley ML McLaughlin E Takvorian A Wasserman Z Bower MJ Wei M Li Y Ala PJ Gonneville L Wynn R Burn TC Liu PC Combs AP 《Bioorganic & medicinal chemistry》2006,14(17):5833-5849
The structure-based design and discovery of the isothiazolidinone (IZD) heterocycle as a mimic of phosphotyrosine (pTyr) has led to the identification of novel IZD-containing inhibitors of protein tyrosine phosphatase 1B (PTP1B). The structure-activity relationships (SARs) of peptidic IZD-containing inhibitors of PTP1B are described along with a novel synthesis of the aryl-IZD fragments via a Suzuki coupling. The SAR revealed the saturated IZD heterocycle (42) is the most potent heterocyclic pTyr mimetic compared to the unsaturated IZD (25), the thiadiazolidinone (TDZ) (38), and the regioisomeric unsaturated IZD (31). The X-ray crystal structures of 11c and 25 complexed with PTP1B were solved and revealed nearly identical binding interactions in the active site. Ab initio calculations effectively explain the strong binding of the (S)-IZD due to the preorganized binding of the IZD in its low energy conformation. 相似文献
128.
X-linked lympho-proliferative (XLP) is an immunodeficiency condition caused by mutation or deletion of the gene encoding the adaptor protein SAP/SH2D1A. Besides defects in T cell and NK cell function and an absence of NKT cells, XLP can also manifest as lymphomas resulting primarily from uncontrolled B cell proliferation upon acute infection by Epstein-Barr virus. While it has been demonstrated that SAP regulates the functions of T cells and NK cells through the SLAM family of immunoreceptors, its role in B cells has not been defined. Here we show that SAP forms a ternary complex with the kinase Lyn and the inhibitory IgG Fc receptor FcgammaRIIB to regulate B cell proliferation and survival. SAP binds directly and simultaneously to the Lyn SH3 domain and an Immuno-receptor Tyrosine-based Inhibitory Motif (ITIM) in FcgammaRIIB, resulting in the activation of the latter. Moreover, SAP associates with FcgammaRIIB in mouse splenic B cells and promotes its tyrosine phosphorylation. Expression of SAP in the A20 B cell line led to a marked reduction in Blnk phosphorylation, a decrease in Akt activation, and a near-complete ablation of phosphorylation of the MAP kinases Erk1/2, p38 and JNK upon colligation of FcgammaRIIB with the B cell receptor (BCR). In contrast, an XLP-causing SAP mutant was much less efficient in eliciting these effects in B cells. Furthermore, compared to A20 cells, SAP transfectants displayed a significantly reduced rate of proliferation and an increased sensitivity to activation-induced cell death. Collectively these data identify an intrinsic function for SAP in inhibitory signaling in B cells and suggests that SAP may play an important role in balancing positive versus negative immune responses. 相似文献
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