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991.
Grieco P Franco R Bozzuto G Toccacieli L Sgambato A Marra M Zappavigna S Migaldi M Rossi G Striano S Marra L Gallo L Cittadini A Botti G Novellino E Molinari A Budillon A Caraglia M 《Journal of cellular biochemistry》2011,112(1):341-353
Urotensin II (UT-II) is a potent vasoconstrictor peptide and its receptor (UTR) was correlated with human cortico-adrenal carcinoma proliferation. In this study, we have evaluated the correlation between UTR expression and prognosis of human prostate adenocarcinoma and the involvement of this receptor in the regulation of biological properties on both in vivo and in vitro models. UTR mRNA and protein, evaluated by real-time PCR and Western blotting, respectively, were expressed at high levels only in androgen-dependent LNCaP cells. In order to investigate UTR changes occurring in human prostate tumorigenesis, we have also evaluated the expression of UTR in vivo in 195 human prostate tissue samples. UTR was always expressed at low intensity in hyperplastic tissues and at high intensity in well-differentiated carcinomas (Gleason 2-3). Moreover, we have evaluated the effects of an antagonist of UTR, urantide on migration and invasion of LNCaP cells. Urantide induced a dose-dependent decrease of motility and invasion of LNCaP cells whose characteristic ameboid movement seems to be advantageous for their malignancy. These effects were paralleled by down-regulating the autophosphorylation of focal adhesion kinase and the integrin surface expression on LNCaP cells. The effects on cell motility and invasion were likely due to the inhibition of RhoA activity induced by both urantide and shRNA UTR. These data suggest that UTR can be considered a prognostic marker in human prostate adenocarcinoma patients. 相似文献
992.
Disruption of CD40/CD40L interaction influences the course of Cryptococcus neoformans infection 总被引:2,自引:0,他引:2
Pietrella D Lupo P Perito S Mosci P Bistoni F Vecchiarelli A 《FEMS immunology and medical microbiology》2004,40(1):63-70
CD40 signaling has been implicated in various pathogenic processes such as chronic inflammatory disease, graft-versus-host disease, autoimmune disease and cancer. We previously demonstrated in an in vitro system that the CD40/CD40L pathway mediates late interleukin (IL) 12 production in response to Cryptococcus neoformans. The purpose of this study was to examine the course of C. neoformans infection in the absence of CD40/CD40L costimulation. We compared infection in mice genetically lacking CD40L (CD40L(-/-)) and in the wild-type counterpart. The animals were injected intratracheally with C. neoformans and monitored for clearance of the organism and the development of cellular immune response. CD40L(-/-) mice exhibited an exacerbation of infection, evaluated as scarce inflammatory response in the lung, that mirrored an increase of fungal burden. This correlated with impairment of nitrite production and antimicrobial activity by macrophages against C. neoformans and unrelated microorganisms such as Candida albicans. Moreover, IL-12 production by splenic macrophages was diminished in CD40L(-/-) mice and interferon-gamma production by CD4 and CD8 T cells was decreased. CD4 T cells retained the ability to express a costimulatory molecule, CTLA-4, but showed a decrease in CD28 expression. This latter molecule is implicated in a positive effect on proliferation, cytokine production and survival of T cells. Collectively these data demonstrate that absence of CD40L correlates with (i) reduced antimicrobial activity of natural effector cells; (ii) reduction of the magnitude of T cell response; and (iii) increase of fungal growth in the brain. These findings suggest that disruption of CD40/CD40L may be deleterious for development of an efficient immune response to C. neoformans and may identify potential molecular targets for novel immunotherapeutic approaches 相似文献
993.
Ferlin MG Marzano C Dalla Via L Chilin A Zagotto G Guiotto A Moro S 《Bioorganic & medicinal chemistry》2005,13(15):4733-4739
A new class of water soluble 3H-pyrrolo[3,2-f]quinoline derivatives has been synthesized and investigated as potential anticancer drugs. Water solubility profiles have been used to select the most promising derivatives. The novel compound 10, having two (2-diethylamino-ethyl) side chains linked through positions 3N and 9O, presents a suitable water solubility profile, and it was shown to exhibit cell growth inhibitory properties when tested against the in-house panel of cell lines, in particular those obtained from melanoma. 相似文献
994.
995.
Small hydroxyethylene-based peptidomimetics inhibiting both HIV-1 and C. albicans aspartic proteases
Tossi A Benedetti F Norbedo S Skrbec D Berti F Romeo D 《Bioorganic & medicinal chemistry》2003,11(22):4719-4727
We have extended a highly flexible method for rapidly assembling aspartic protease inhibitors to produce symmetric and asymmetric monohydroxyethylene peptidomimetics. This method is based on the prior synthesis of the central non-cleavable peptide-bond isostere [NH(2)-P(1)psiP1'-NH(2); psi=hydroxyethylene isostere, HNCH(Bz)CHOHCH(2)CH(Bz)NH], with the possibility of accurately controlling its stereochemistry (S,S,S or S,R,S), and subsequently adding appropriate flanking units, chosen from commercially available amino acids, aromatic carboxylic acids, or phenoxyacetic acid (Poa) derivatives. The method was used to make asymmetric inhibitors of general formula Kyn-Xaa-PhepsiPhe-dmPoa, (Kyn=kynurenic acid, Xaa=Val, Thr or D-thienylglycine, M(r)=716-754) and symmetric inhibitors of formula xPoa-PhepsiPhe-xPoa (xPoa=Poa or dimethyl-, hydroxy-, formyl- or acetyl-Poa, M(r)=553-609), with logP(o/w) values ranging from 4.1 to 7.6. Inhibition of HIV-PR did not depend on the stereochemistry of the hydroxyl group, while it depended markedly on the substituents present on the Poa residues, with dmPoa being preferred over Poa or its more hydrophilic derivatives. Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa. 相似文献
996.
Sebastiana Angelaccio Florian Dworkowski Angela Di Bello Teresa Milano Guido Capitani Stefano Pascarella 《Proteins》2014,82(10):2831-2841
Serine hydroxymethyltransferase (SHMT) is a pyridoxal‐5′‐phosphate (PLP)‐dependent enzyme belonging to the fold type I superfamily, which catalyzes in vivo the reversible conversion of l ‐serine and tetrahydropteroylglutamate (H4PteGlu) to glycine and 5,10‐methylenetetrahydropteroylglutamate (5,10‐CH2‐H4PteGlu). The SHMT from the psychrophilic bacterium Psychromonas ingrahamii (piSHMT) had been recently purified and characterized. This enzyme was shown to display catalytic and stability properties typical of psychrophilic enzymes, namely high catalytic activity at low temperature and thermolability. To gain deeper insights into the structure–function relationship of piSHMT, the three‐dimensional structure of its apo form was determined by X‐ray crystallography. Homology modeling techniques were applied to build a model of the piSHMT holo form. Comparison of the two forms unraveled the conformation modifications that take place when the apo enzyme binds its cofactor. Our results show that the apo form is in an “open” conformation and possesses four (or five, in chain A) disordered loops whose electron density is not visible by X‐ray crystallography. These loops contain residues that interact with the PLP cofactor and three of them are localized in the major domain that, along with the small domain, constitutes the single subunit of the SHMT homodimer. Cofactor binding triggers a rearrangement of the small domain that moves toward the large domain and screens the PLP binding site at the solvent side. Comparison to the mesophilic apo SHMT from Salmonella typhimurium suggests that the backbone conformational changes are wider in psychrophilic SHMT. Proteins 2014; 82:2831–2841. © 2014 Wiley Periodicals, Inc. 相似文献
997.
Stefano R. Montanari Jean‐Paul A. Hobbs Morgan S. Pratchett Line K. Bay Lynne Van Herwerden 《Molecular ecology》2014,23(11):2757-2770
Christmas Island is located at the overlap of the Indian and Pacific Ocean marine provinces and is a hot spot for marine hybridization. Here, we evaluate the ecological framework and genetic consequences of hybridization between butterflyfishes Chaetodon guttatissimus and Chaetodon punctatofasciatus. Further, we compare our current findings to those from a previous study of hybridization between Chaetodon trifasciatus and Chaetodon lunulatus. For both species groups, habitat and dietary overlap between parental species facilitate frequent heterospecific encounters. Low abundance of potential mates promotes heterospecific pair formation and the breakdown of assortative mating. Despite similarities in ecological frameworks, the population genetic signatures of hybridization differ between the species groups. Mitochondrial and nuclear data from C. guttatissimus × C. punctatofasciatus (1% divergence at cyt b) show bidirectional maternal contributions and relatively high levels of introgression, both inside and outside the Christmas Island hybrid zone. In contrast, C. trifasciatus × C. lunulatus (5% cyt b divergence) exhibit unidirectional mitochondrial inheritance and almost no introgression. Back‐crossing of hybrid C. guttatissimus × C. punctatofasciatus and parental genotypes may eventually confound species‐specific signals within the hybrid zone. In contrast, hybrids of C. trifasciatus and C. lunulatus may coexist with and remain genetically distinct from the parents. Our results, and comparisons with hybridization studies in other reef fish families, indicate that genetic distance between hybridizing species may be a factor influencing outcomes of hybridization in reef fish, which is consistent with predictions from terrestrially derived hybridization theory. 相似文献
998.
David Papo Massimiliano Zanin José Angel Pineda-Pardo Stefano Boccaletti Javier M. Buldú 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1653)
Many physical and biological systems can be studied using complex network theory, a new statistical physics understanding of graph theory. The recent application of complex network theory to the study of functional brain networks has generated great enthusiasm as it allows addressing hitherto non-standard issues in the field, such as efficiency of brain functioning or vulnerability to damage. However, in spite of its high degree of generality, the theory was originally designed to describe systems profoundly different from the brain. We discuss some important caveats in the wholesale application of existing tools and concepts to a field they were not originally designed to describe. At the same time, we argue that complex network theory has not yet been taken full advantage of, as many of its important aspects are yet to make their appearance in the neuroscience literature. Finally, we propose that, rather than simply borrowing from an existing theory, functional neural networks can inspire a fundamental reformulation of complex network theory, to account for its exquisitely complex functioning mode. 相似文献
999.
Stefano Romano Patrizia Paganin Cristiano Varrone Silvia Tabacchioni Luigi Chiarini 《Archives of microbiology》2014,196(2):97-107
In this study, we evaluated the effectiveness of lake sediment as inoculum for hydrogen production through dark fermentation in a repeated batch process. In addition, we investigated the effect of heat treatment, applied to enrich hydrogen-producing bacteria, on the bacterial composition and metabolism. Denaturing gradient gel electrophoresis and molecular cloning, both performed using the 16S rDNA gene as target gene, were used to monitor the structure of the bacterial community. Hydrogen production and bacterial metabolism were analysed via gas chromatography and high-performance liquid chromatography. Both treated and non-treated inocula were able to produce high amounts of hydrogen. However, statistical analysis showed a clear difference in their bacterial composition and metabolism. The heat treatment favoured the growth of different Clostridia sp., in particular of Clostridium bifermentans, allowing the production of a constant amount of hydrogen over prolonged time. These cultures showed both butyrate and ethanol fermentation types. Absence of heat treatment allowed species belonging to the genera Bacillus, Sporolactobacillus and Massilia to outgrow Clostridia sp. with a reduction in hydrogen production and a significant metabolic change. Our data indicate that lake sediment harbours bacteria that can efficiently produce hydrogen over prolonged fermentation time. Moreover, we could show that the heat treatment stabilizes the bacterial community composition and the hydrogen production. 相似文献
1000.
Linda Avesani Matilde Merlin Elisa Gecchele Stefano Capaldi Annalisa Brozzetti Alberto Falorni Mario Pezzotti 《Transgenic research》2014,23(2):281-291
The 65-kDa isoform of human glutamic acid decarboxylase (hGAD65) is a major diabetes autoantigen that can be used for the diagnosis and (more recently) the treatment of autoimmune diabetes. We previously reported that a catalytically-inactive version (hGAD65mut) accumulated to tenfold higher levels than its active counterpart in transgenic tobacco plants, providing a safe and less expensive source of the protein compared to mammalian production platforms. Here we show that hGAD65mut is also produced at higher levels than hGAD65 by transient expression in Nicotiana benthamiana (using either the pK7WG2 or MagnICON vectors), in insect cells using baculovirus vectors, and in bacterial cells using an inducible-expression system, although the latter system is unsuitable because hGAD65mut accumulates within inclusion bodies. The most productive of these platforms was the MagnICON system, which achieved yields of 78.8 μg/g fresh leaf weight (FLW) but this was substantially less than the best-performing elite transgenic tobacco plants, which reached 114.3 μg/g FLW after six generations of self-crossing. The transgenic system was found to be the most productive and cost-effective although the breeding process took 3 years to complete. The MagnICON system was less productive overall, but generated large amounts of protein in a few days. Both plant-based systems were therefore advantageous over the baculovirus-based production platform in our hands. 相似文献