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991.
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
992.
993.
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
994.
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
995.
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
996.
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
997.
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
998.
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
999.
Filippo Menolascina Gianfranco Fiore Emanuele Orabona Luca De Stefano Mike Ferry Jeff Hasty Mario di Bernardo Diego di Bernardo 《PLoS computational biology》2014,10(5)
We describe an innovative experimental and computational approach to control the expression of a protein in a population of yeast cells. We designed a simple control algorithm to automatically regulate the administration of inducer molecules to the cells by comparing the actual protein expression level in the cell population with the desired expression level. We then built an automated platform based on a microfluidic device, a time-lapse microscopy apparatus, and a set of motorized syringes, all controlled by a computer. We tested the platform to force yeast cells to express a desired fixed, or time-varying, amount of a reporter protein over thousands of minutes. The computer automatically switched the type of sugar administered to the cells, its concentration and its duration, according to the control algorithm. Our approach can be used to control expression of any protein, fused to a fluorescent reporter, provided that an external molecule known to (indirectly) affect its promoter activity is available. 相似文献
1000.
Stefano Luccioli Eshel Ben-Jacob Ari Barzilai Paolo Bonifazi Alessandro Torcini 《PLoS computational biology》2014,10(9)
It has recently been discovered that single neuron stimulation can impact network dynamics in immature and adult neuronal circuits. Here we report a novel mechanism which can explain in neuronal circuits, at an early stage of development, the peculiar role played by a few specific neurons in promoting/arresting the population activity. For this purpose, we consider a standard neuronal network model, with short-term synaptic plasticity, whose population activity is characterized by bursting behavior. The addition of developmentally inspired constraints and correlations in the distribution of the neuronal connectivities and excitabilities leads to the emergence of functional hub neurons, whose stimulation/deletion is critical for the network activity. Functional hubs form a clique, where a precise sequential activation of the neurons is essential to ignite collective events without any need for a specific topological architecture. Unsupervised time-lagged firings of supra-threshold cells, in connection with coordinated entrainments of near-threshold neurons, are the key ingredients to orchestrate population activity. 相似文献