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171.
Stefania Butini Emanuele Gabellieri Margherita Brindisi Alice Casagni Egeria Guarino Paul B. Huleatt Nicola Relitti Valeria La Pietra Luciana Marinelli Mariateresa Giustiniano Ettore Novellino Giuseppe Campiani Sandra Gemma 《Bioorganic & medicinal chemistry letters》2013,23(1):85-89
Aiming at identifying new scaffolds for BACE-1 inhibition devoid of the pharmacokinetic drawbacks of peptide-like structures, we investigated a series of novel peptidomimetics based on a 1,4-benzodiazepine (BDZ) core 1a–h and their seco-analogues 2a–d. We herein discuss synthesis, molecular modeling and in vitro studies which, starting from 1a, led to the seco-analogues (R)-2c and (S)-2d endowed with BACE-1 inhibition properties in the micromolar range both on the isolated enzyme and in cellular studies. These data can encourage to pursue these analogues as hits for the development of a new series of BACE-1 inhibitors active on whole-cells. 相似文献
172.
173.
Julien Thézé Tony Li Louis du Plessis Jerome Bouquet Moritz U.G. Kraemer Sneha Somasekar Guixia Yu Mariateresa de Cesare Angel Balmaseda Guillermina Kuan Eva Harris Chieh-hsi Wu M. Azim Ansari Rory Bowden Nuno R. Faria Shigeo Yagi Sharon Messenger Trevor Brooks Oliver G. Pybus 《Cell host & microbe》2018,23(6):855-864.e7
174.
Tandem running is a common recruitment strategy in ant species with small colony sizes. During a tandem run, an informed leader guides a usually naïve nestmate to a food source or a nest site. Some species perform tandem runs only during house hunting, suggesting that tandem running does not always improve foraging success in species known to use tandem running as a recruitment strategy, but more natural history information on tandem running under natural conditions is needed to better understand the adaptive significance of tandem recruitment in foraging. Studying wild colonies in Brazil, we for the first time describe tandem running in the ponerine ant Pachycondyla harpax (Fabricius). We asked if foragers perform tandem runs to carbohydrate- (honey) and protein-rich (cheese) food items. Furthermore, we tested whether the speed and success rate of tandem runs depend on the foraging distance. Foragers performed tandem runs to both carbohydrate food sources and protein-rich food items that exceed a certain size. The probability to perform a tandem run and the travelling speed increase with increasing foraging distances, which could help colonies monopolize more distant food sources in a competitive environment. Guiding a recruit to a food source is costly for leaders as ants are ~66% faster when travelling alone. If tandem runs break up (~23% of all tandem runs), followers do not usually discover the food source on their own but return to the nest. Our results show that tandem running to food sources is common in P. harpax, but that foragers modify their behaviour according to the type of food and its distance from the nest. Competition with other ants was intense and we discuss how tandem running in P. harpax might help colonies to build-up a critical number of ants at large food items that can then defend the food source against competitors. 相似文献
175.
Fusogenic domains in herpes simplex virus type 1 glycoprotein H 总被引:4,自引:0,他引:4
Galdiero S Falanga A Vitiello M Browne H Pedone C Galdiero M 《The Journal of biological chemistry》2005,280(31):28632-28643
Infection of eukaryotic cells by enveloped viruses requires fusion between the viral envelope and the cellular plasma or endosomal membrane. The actual merging of the two membranes is mediated by viral envelope glycoproteins, which generally contain a highly hydrophobic region termed the fusion peptide. The entry of herpesviruses is mediated by three conserved proteins: glycoproteins B, H (gH), and L. However, how fusion is executed remains unknown. Herpes simplex virus type 1 gH exhibits features typical of viral fusion glycoproteins, and its ectodomain seems to contain a putative internal fusion peptide. Here, we have identified additional internal segments able to interact with membranes and to induce membrane fusion of large unilamellar vesicles. We have applied the hydrophobicity-at-interface scale proposed by Wimley and White (Wimley, W. C., and White, S. H. (1996) Nat. Struct. Biol. 3, 842-848) to identify six hydrophobic stretches within gH with a tendency to partition into the membrane interface, and four of them were able to induce membrane fusion. Experiments in which equimolar mixtures of gH peptides were used indicated that different fusogenic regions may act in a synergistic way. The functional and structural characterization of these segments suggests that herpes simplex virus type 1 gH possesses several fusogenic internal peptides that could participate in the actual fusion event. 相似文献
176.
Marianthi Karali Maria Persico Margherita Mutarelli Annamaria Carissimo Mariateresa Pizzo Veer Singh?Marwah Concetta Ambrosio Michele Pinelli Diego Carrella Stefano Ferrari Diego Ponzin Vincenzo Nigro Diego di?Bernardo Sandro Banfi 《Nucleic acids research》2016,44(4):1525-1540
MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina. 相似文献
177.
Roger Raupp Cipriano Rafael Bueno Noleto Daniel Luis Zanella Kantek Maria Cristina da Silva Cortinhas Marta Margarete Cestari 《Cytotechnology》2016,68(4):1585-1589
Cytogenetic studies have assisted in the taxonomic classification of organisms, especially those involving species with highly similar morphologic characteristics, or so-called cryptic species. Strongylura marina and Strongylura timucu collected from Paranaguá Bay, Paraná Coast in Southern Brazil are considered cryptic species, and the identification of interspecific variations based on the number and/or morphology of its chromosomes may serve as differentiating cytotaxonomic markers. Chromosomes of the two species were subjected to different banding and staining methods (C-, Ag-, and DAPI-CMA3), as well as chromosomal mapping of major rDNA (45S), revealed with an 18S probe by fluorescence in situ hybridization (FISH). The pattern of distribution of constitutive heterochromatin showed distinct features involving the pericentromeric and telomeric bands in both species. In S. marina, chromosome 1 represents the main species-specific marker, appearing almost entirely heterochromatic. In both species, the 45S rDNA is located at terminal region of the short arm of the chromosome 6, as detected by silver nitrate staining and FISH. Despite the apparent conserved diploid number of 48 chromosomes, data on the karyotype microstructure characterize the cytogenetic profile of the genus and may allow the establishment of cytotaxonomic and evolutionary inferences for these fishes. 相似文献
178.
179.
Yunxiang Zhang Jiajie Diao Karen N. Colbert Ying Lai Richard A. Pfuetzner Mark S. Padolina Sandro Vivona Susanne Ressl Daniel J. Cipriano Ucheor B. Choi Niket Shah William I. Weis Axel T. Brunger 《The Journal of biological chemistry》2015,290(16):10518-10534
Sec1/Munc18 (SM) proteins are essential for membrane trafficking, but their molecular mechanism remains unclear. Using a single vesicle-vesicle content-mixing assay with reconstituted neuronal SNAREs, synaptotagmin-1, and complexin-1, we show that the neuronal SM protein Munc18a/nSec1 has no effect on the intrinsic kinetics of both spontaneous fusion and Ca2+-triggered fusion between vesicles that mimic synaptic vesicles and the plasma membrane. However, wild type Munc18a reduced vesicle association ∼50% when the vesicles bearing the t-SNAREs syntaxin-1A and SNAP-25 were preincubated with Munc18 for 30 min. Single molecule experiments with labeled SNAP-25 indicate that the reduction of vesicle association is a consequence of sequestration of syntaxin-1A by Munc18a and subsequent release of SNAP-25 (i.e. Munc18a captures syntaxin-1A via its high affinity interaction). Moreover, a phosphorylation mimic mutant of Munc18a with reduced affinity to syntaxin-1A results in less reduction of vesicle association. In summary, Munc18a does not directly affect fusion, although it has an effect on the t-SNARE complex, depending on the presence of other factors and experimental conditions. Our results suggest that Munc18a primarily acts at the prefusion stage. 相似文献
180.
The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people 总被引:1,自引:0,他引:1
Giacconi R Muti E Malavolta M Cipriano C Costarelli L Bernardini G Gasparini N Mariani E Saba V Boccoli G Mocchegiani E 《Molecular medicine (Cambridge, Mass.)》2007,13(7-8):388-395
Carotid artery stenosis (CS) is a well-established risk factor for stroke. Increased proinflammatory chemokines, enhanced metallothionein (MT), and altered metal homeostasis may play roles in atherosclerosis progression and plaque destabilization. MT may sequester zinc during chronic inflammation, provoke zinc deficiency, and modulate NK cell cytotoxicity. A recent investigation of older patients with diabetes and atherosclerosis showed an association between the -209 A/G MT2A polymorphism, CS, and zinc status. In this study, we evaluated the relationship between two MT2A polymorphisms (-209 and + 838 locus), metal status, and inflammatory/immune response in older patients with CS only (the CS1 group) or with CS and previous cerebrovascular episodes (transient ischemic attack or stroke) (the CS2 group). A total of 506 individuals (188 CS1, 100 CS2, and 218 healthy controls) were studied. Atherosclerotic patients (CS1 and CS2) showed increased levels of MT, MCP-1, and RANTES, reduced NK cell cytotoxicity, and altered trace element concentrations (zinc, copper, magnesium, iron). The +838 C/G MT2A polymorphism was differently distributed in CS1 and CS2 patients, who displayed the GG genotype (C-) with significantly higher frequency than elderly controls. C- carriers showed increased MCP-1 and decreased NK cell cytotoxicity, CD56+ cells, and intracellular zinc availability along with decreased zinc, copper, and magnesium content in erythrocytes and increased iron in plasma. C- carriers also showed a major incidence of soft carotid plaques. In conclusion, the +838 C/G MT2A polymorphism seems to influence inflammatory markers, zinc availability, NK cell cytotoxicity, and trace element status, all of which may promote CS development. 相似文献