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51.
A new species ofSorghastrum,S. pohlianum, from Mexico is described and illustrated. A numerical analysis comparing the new species to the closest species (S. nutans andS. nudipes) was undertaken. The first three principal components explain 84% of the variation of the taxa involved. In addition there is morphological evidence to distinguish the new species from its closest relatives. It differs fromS. nutans by showing smaller inflorescences, having sterile lemmas and anthers, and having somewhat smaller but wider blades and different flowering periods. In addition, it is distinguished fromS. nudipes due to the presence of auricles > 1 mm long and inflorescence branches bearing spikelets along their entire length. 相似文献
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53.
Identification of rCop-1, a New Member of the CCN Protein Family,as a Negative Regulator for Cell Transformation 下载免费PDF全文
Rong Zhang Lidia Averboukh Weimin Zhu Hong Zhang Hakryul Jo Peter J. Dempsey Robert J. Coffey Arthur B. Pardee Peng Liang 《Molecular and cellular biology》1998,18(10):6131-6141
By using a model system for cell transformation mediated by the cooperation of the activated H-ras oncogene and the inactivated p53 tumor suppressor gene, rCop-1 was identified by mRNA differential display as a gene whose expression became lost after cell transformation. Homology analysis indicates that rCop-1 belongs to an emerging cysteine-rich growth regulator family called CCN, which includes connective-tissue growth factor, CYR61, CEF10 (v-src inducible), and the product of the nov proto-oncogene. Unlike the other members of the CCN gene family, rCop-1 is not an immediate-early gene, it lacks the conserved C-terminal domain which was shown to confer both growth-stimulating and heparin-binding activities, and its expression is lost in cells transformed by a variety of mechanisms. Ectopic expression of rCop-1 by retroviral gene transfers led to cell death in a transformation-specific manner. These results suggest that rCop-1 represents a new class of CCN family proteins that have functions opposing those of the previously identified members.Oncogenic conversion of a normal cell into a tumor cell requires multiple genetic alterations (12). Of particular interest is the fact that mutations in both ras oncogenes (3) and the p53 tumor suppressor gene cooperate in transformation of mammalian cells (11). Mutations in both ras and the p53 gene were also found at high frequencies in a variety of human cancers, including those of the colon, lung, and pancreas (2, 18). It has been proposed that both p53 and Ras function, whether directly or through other signaling molecules, to control expression of genes that are important for cell growth and differentiation (13, 17, 37). To this end, several ras target genes (10) and p53 target genes, including those encoding p21/CIP1/WAF1, an inhibitor of G1 cyclin-dependent kinase (9); Mdm-2, a negative regulator of p53 (1); GADD45, a protein involved in DNA repair (36); and Bax, which promotes apoptosis (28), have been identified. Most of these genes, except p21/CIP1/WAF1, which was cloned by subtractive hybridization, were identified by the candidate gene hypothesis. Recently, more p53 target genes have been isolated by the differential display technique, including those coding for cyclin G (31); MAP4, a microtubule-associated protein negatively regulated by p53 (29); and PAG608, a novel nuclear zinc finger protein whose overexpression promotes apoptosis (14). Functional characterizations of these genes have shed light on the role of p53 in cell cycle control and apoptosis. However, genes that mediate tumor suppression activity by p53 remain elusive.The fact that neither the inactivation of p53 nor the activation of Ras alone is able to transform primary mammalian cells (34), whereas both mutations together can do so, suggests that genes regulated by p53 and Ras cooperate in upsetting normal cell growth control cells (11). Using differential display (22), we set out to identify genes whose expression is altered by both mutant ras and p53 by comparing the mRNA expression profiles of normal rat embryo fibroblasts (REFs) and their derivatives transformed by either a constitutively inactivated or a temperature-sensitive mutant p53 in cooperation with the activated H-ras oncogene (11, 27). In this report we describe the identification and give a functional characterization of rCop-1, a gene whose expression is abolished by cell transformation. By sequence homology, rCop-1 was found to belong to an emerging cysteine-rich growth regulator family called CCN (which stands for connective-tissue growth factor [CTGF], CEF10/Cyr61, and Nov) (4). Here we show that rCop-1 may represent a novel class of CCN family proteins based on its unique cell cycle expression pattern, its lack of the C-terminal (CT) domain conserved in all CCN proteins, its loss of expression in all transformed cells analyzed, and its ability to confer cytotoxicity to the transformed cells. 相似文献
54.
Lidia Lasecka Abdelghani Bin-Tarif Anne Bridgen Nicholas Juleff Ryan A. Waters Michael D. Baron 《PloS one》2015,10(4)
Nairobi sheep disease virus (NSDV; also called Ganjam virus in India) is a bunyavirus of the genus Nairovirus. It causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%. The virus is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV). Little is currently known about the biology of NSDV. We have generated specific antibodies against the virus nucleocapsid protein (N) and polymerase (L) and used these to characterise NSDV in infected cells and to study its distribution during infection in a natural host. Due to its large size and the presence of a papain-like protease (the OTU-like domain) it has been suggested that the L protein of nairoviruses undergoes an autoproteolytic cleavage into polymerase and one or more accessory proteins. Specific antibodies which recognise either the N-terminus or the C-terminus of the NSDV L protein showed no evidence of L protein cleavage in NSDV-infected cells. Using the specific anti-N and anti-L antibodies, it was found that these viral proteins do not fully colocalise in infected cells; the N protein accumulated near the Golgi at early stages of infection while the L protein was distributed throughout the cytoplasm, further supporting the multifunctional nature of the L protein. These antibodies also allowed us to gain information about the organs and cell types targeted by the virus in vivo. We could detect NSDV in cryosections prepared from various tissues collected post-mortem from experimentally inoculated animals; the virus was found in the mucosal lining of the small and large intestine, in the lungs, and in mesenteric lymph nodes (MLN), where NSDV appeared to target monocytes and/or macrophages. 相似文献
55.
56.
Biava M Porretta GC Poce G Supino S Manetti F Forli S Botta M Sautebin L Rossi A Pergola C Ghelardini C Norcini M Makovec F Giordani A Anzellotti P Cirilli R Ferretti R Gallinella B La Torre F Anzini M Patrignani P 《Bioorganic & medicinal chemistry》2008,16(17):8072-8081
Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations. 相似文献
57.
Delos Santos NM Gardner LA White SW Bahouth SW 《The Journal of biological chemistry》2006,281(18):12896-12907
Several key amino acids within amphipathic helix 8 of the human beta1-adrenergic receptor (beta1-AR) were mutagenized to characterize their role in signaling by G protein-coupled receptors. Mutagenesis of phenylalanine at position 383 in the hydrophobic interface to histidine (F383H) prevented the biosynthesis of the receptor, indicating that the orientation of helix 8 is important for receptor biosynthesis. Mutagenesis of aspartic acid at position 382 in the hydrophilic interface to leucine (D382L) reduced the binding and uncoupled the receptor from G protein activation. Mutagenesis of the basic arginine residue at position 384 to glutamine (R384Q) or to glutamic acid (R384E) increased basal and agonist-stimulated adenylyl cyclase activities. R384Q and R384E displayed features associated with constitutively active receptors because inverse agonists markedly reduced their elevated basal adenylyl cyclase activities. Isoproterenol increased the phosphorylation and promoted the desensitization of the Gly389 or Arg389 allelic variants of the wild type beta1-AR but failed to produce these effects in R384Q and R384E, because these receptors were maximally phosphorylated and desensitized under basal conditions. In contrast to the membranous distribution of the wild type beta1-AR, R384Q and R384E were localized mostly within intracellular punctate structures. Inverse agonists restored the membranous distribution of R384Q and R384E, indicating that they recycled normally when their constitutive internalization was blocked by inverse agonists. These data combined with computer modeling of the putative three-dimensional organization of helix 8 indicated that the amphipathic character of helix 8 and side chain projections of Asp382 and Arg384 within the hydrophilic interface might serve as a tethering site for the G protein. 相似文献
58.
Atwal KS Ahmad S Ding CZ Stein PD Lloyd J Hamann LG Green DW Ferrara FN Wang P Rogers WL Doweyko LM Miller AV Bisaha SN Schmidt JB Li L Yost KJ Lan HJ Madsen CS 《Bioorganic & medicinal chemistry letters》2004,14(4):1027-1030
A series of substituted guanidine derivatives were prepared and evaluated as potent and selective inhibitors of mitochondrial F(1)F(0) ATP hydrolase. The initial thiourethane derived lead molecules possessed intriguing in vitro pharmacological profiles, though contained moieties considered non-drug-like. Analogue synthesis efforts led to compounds with maintained potency and superior physical properties. Small molecules in this series which potently and selectivity inhibit ATP hydrolase and not ATP synthase may have utility as cardioprotective agents. 相似文献
59.
Esther Vicente Silvia Pérez-Silanes Lidia M. Lima Saioa Ancizu Asunción Burguete Beatriz Solano Raquel Villar Ignacio Aldana Antonio Monge 《Bioorganic & medicinal chemistry》2009,17(1):385-389
New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 μg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4’-fluoro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 μg/mL and SI >500). 相似文献
60.
Emma del Carmen Macías-Cortés Lidia Llanes-González Leopoldo Aguilar-Faisal Juan Asbun-Bojalil 《PloS one》2015,10(3)