102,909 research outputs found
Synthesis of photoactivable probes for the study of glycosphingolipid-protein interactions
No full textSYNTHESIS OF PHOTOACTIVABLE PROBES FOR THE STUDY OF GLYCOSPHINGOLIPID-PROTEIN INTERACTIONS
Giuseppina Brasile,1 Federica Compostella,1 Laura Mauri,2Sandro Sonnino2 and Fiamma Ronchetti1
Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano
1Via Saldini 50, 20133-Milano, Italy; 2Via Fratelli Cervi 93, 20190- Segrate (Milano), Italy
E-mail:[email protected]
It is widely accepted that glycosphingolipids (GSLs) at the level of the plasma membrane can affect the biological functions of protein molecules, such as cell surface receptors or transporters. The interactions between GSLs and proteins belonging to specific membrane microdomains, called lipid rafts, could be responsible for the modulation of the functional properties of membrane proteins participating in signal transduction. GSL-protein interactions can be investigated by cell photolabelling experiments using radioactive photoactivable GSLs, which yield, when illuminated, a very reactive intermediate that covalently binds to the molecules in the environment, i.e. proteins.1,2
In this context, we have designed a fatty acid probe with two nitrophenylazide photoactivable groups, one at position 2 and the other at the end of the acyl chain. The conjugation of the fatty acid to a radioactive sphingoglycolipid generates a species to be used for photolabelling experiments. In this way, the simultaneous identification of the proteins belonging to both the leaflets of the plasma membrane, the cytoplasmatic and the extracellular one, will be realized.
Herein we describe a general synthetic strategy to obtain not commercially available α,ω-diamino acids, the synthetic precursors of the labelled fatty acids, which we have applied to the synthesis of a C-18 derivative. Furthermore, it will be described the preparation of a photolabelled radioactive GSL as a case study.
1. Aureli M., Prioni S., Mauri L. Loberto N., Casellato R., Ciampa M.G., Chigorno V., Prinetti, A.; Sonnino S. J. Lipid Res. 2010, 51, 798-808
2. Mauri L., Prioni S., Loberto N., Chigorno V., Prinetti A., Sonnino S. Glycoconj. J. 2004, 20, 11-23
Complex climate-induced changes in soil development as markers for the Little Ice Age in the Northern Apennines (Italy)
No full textIn the Northern Apennines the effects of the Little Ice Age (LIA) on the mountain landscape are poorly known. A pedosedimentary sequence on the northern slope of Mt. Cusna (Tuscan-Aemilian Apennines) and its geomorphological setting were investigated in order to assess the influence of the LIA on the soils and the geomorphological processes. The upper portion of the described sequence could be interpreted as colluvial deposits burying an old paleosurface. The LIA climatic effects acted on the sequence in two distinct phases: in a first moment, partial denudation of the surfaces allowed direct daily and seasonal freeze-thaw cycles (i.e. frost action) to produce ice-related relict microscopic pedofeatures in the soil horizons constituting the paleosurface, and absent on modern surfaces. Afterwards, a slope instability phase, possibly caused by the change to wetter conditions, promoted the widespread colluvial deposits, which were later partially reworked by frost insolifluction lobes. The triggering of these events seems to be influenced by the presence of pastoral communities, too: charcoals found on the paleosurface point to the use of fire events for clearance practices and, possibly, later pasture exploitation of the surfaces. In this light, the environmental history recorded by the Mt. Cusna pedosedimentary sequence highlights how LIA was fundamental inshaping the modern landscape of the N Apennines and suggests a complex relationship between climate and human forcing on mountain environments
Holocene environmental history at the treeline in the Northern Apennines, Italy: a micromorphological approach
No full textThe aim of this work is to investigate paleoenvironment at treeline quotas through the help of soil micromorphology. It also assesses how the micromorphological approach can provide information in paleoenvironmental studies where paleosols are available as proxy archives. Nine soil profiles are described across the treeline, between 1723 and 1860 m, on Mt Cusna slope (2121 m a.s.l., Northern Apennines, Italy). Undisturbed samples from selected soil horizons are collected in Kubiëna boxes. From field observations, all the profiles appear to be composed of two main pedogenetic units: the upper one, composed of a recent soil of colluvial origin, and the deeper one, consisting of an underlying more developed buried paleosol. Thin sections give detailed information about the nature and the origin of both pedological units. Four principal phases of paleosol development are detected. A first period of temperate climate with forest cover and contrasted seasons is followed by a phase of change and then by a successive decrease of forest cover. In a last phase, the soil experiences frost action under the effect of a colder climate. The final deposition of colluvium seems to be very recent (historical time). Moreover, multiple colluvial layers are identified. Colluvial material of different origins could be identified as part of dismantled soils similar to the preexisting paleosol. In conclusion, with the help of soil micromorphology, it is possible to assess the existence of past stable forest at least 100 m above the present treeline. The micromorphological approach represents a powerful tool in multidisciplinary paleoenvironmental studies due to its high level of resolution in outlining the individual and successive phases of soil evolution
San Giacomo di Compostella e la Puglia. L’affresco del giovane pellegrino salvato dal Santo a Lizzano
No full textIn ambito iacobeo, il Libro II del Codice Callistino o Liber Sancti Iacobi contiene 22 miracoli compiuti da san Giacomo Maggiore o di Compostella, finalizzati a mostrare il potere del santo e in particolare la protezione dei pellegrini durante il viaggio dai pericoli della strada, dalle malattie, dalla malvagità degli osti.
Tra i miracoli compiuti da san Giacomo il prodigio legato alla salvezza del giovane impiccato è sicuramente il più noto e diffuso, sia nei racconti sia nelle testimonianze iconografiche.
Un’immagine del miracolo dell’impiccato è visibile in Puglia, a Lizzano, nel Tarantino, nella chiesa dell’Annunziata ˗ santuario mariano e meta di pellegrinaggio ˗ che accoglie un dipinto parietale raffigurante l’episodio del giovane pellegrino salvato da san Giacomo e sostenuto sulla forca.In the Jacobean context, Book II of the Callistine Code or Liber Sancti Iacobi contains 22 miracles performed by Saint James the Greater or of Compostella, aimed at showing the power of the saint and in particular the protection of pilgrims during the journey from the dangers of the road, from diseases , from the wickedness of the hosts.
Among the miracles performed by Saint James, the miracle linked to the salvation of the hanged young man is certainly the best known and most widespread, both in stories and in iconographic evidence.
An image of the miracle of the hanged man is visible in Puglia, in Lizzano, in the Tarantino area, in the church of the Annunziata ˗ Marian sanctuary and pilgrimage destination ˗ which houses a wall painting depicting the episode of the young pilgrim saved by Saint James and supported on the gallows
2 -O-Alkyl Derivatives and 5 -Analogues of 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) as Potential Hsp90 Inhibitors
No full textSome selective preparations of AICAR-related compounds modified at the 2- or 5-position of the ribose moiety are reported herein. In particular, 5-azido, 5-amino, 5-O-benzyl and a series of 2-O-alkylated AICAR derivatives have been synthesized. These compounds were derived from appropriately functionalized inosines by opening the pyrimidine ring at the hypoxanthine residue. The target derivatives were designed with the purpose of studying the effect of AICAR structural modifications on its ability to inhibit Hsp90, one of the biological targets for the development of anticancer agents. Nevertheless, the development of AICAR-like compounds is an appealing objective also because of their potential therapeutic application in the field of metabolic studies
CDF Monte Carlo Production on LCG Grid via LcgCAF Portal
No full textThe improvements of the luminosity of the Tevatron
Collider require large increases in computing requirements for
the CDF experiment which has to be able to increase proportionally
the amount of Monte Carlo data it produces. This is,
in turn, forcing the CDF Collaboration to move beyond the use
of dedicated resources and to exploit Grid resources. CDF has
been running a set of CDF Analysis Farm (CAFs), which are
submission portals to dedicated pools, and LcgCAF is basically
a reimplementation of the CAF model in order to access Grid
resources by using the LCG/EGEE Middleware components. By
mean of LcgCAF CDF users can submit analysis jobs with the
same mechanism adopted for the dedicated farms and at the
same time the Grid resources are accessed without any specic
software requirements for the sites. This is obtained using Parrot
for the experiment code distribution and Frontier for the run
condition database availability on the worker nodes. Currently
many sites in Italy and in Europe are accessed through this
portal in order to produce Monte Carlo data and in one year of
operations we expect about 100,000 Grid jobs submitted by the
CDF users. We review here the setup used to submit jobs and
retrieve the output, including the Grid components CDF-specic
conguration. The batch and interactive monitor tools developed
to allow users to verify the jobs status during their lifetimes in the
Grid environment are described. We analyze the efciency and
typical failure modes of the current Grid infrastructure reporting
the performances of different parts of the used system
Photoactivable probes for the study of glycosphingolipid-protein interactions in lipid-rich membrane domains
No full textLipid-rafts are membrane microdomains particularly enriched in glycosphingolipids (GSLs) involved in the information transduction process across the membrane.
The great interest for such domains is due to the observation that some membrane associated proteins are highly concentrated in lipid rafts, even if the overall protein content of these membrane areas is very low. It has been assumed that the trapping of certain proteins in lipid rafts might be somehow functional to their biological role, i.e. their involvement in signal transduction processes.
GSL-protein interactions can be investigated by cell photolabelling experiments using radioactive photoactivable GSLs, which yield, when illuminated, a very reactive intermediate that covalently binds to the molecules in the environment, i.e. proteins.
In this context, we have designed a fatty acid probe with two nitrophenylazide photoactivable groups, one at position 2 and the other at the end of the acyl chain. The conjugation of the fatty acid to a radioactive glycosphingolipid generates a species to be used for photolabelling experiments allowing the simultaneous identification of the proteins belonging to the cytoplasmatic and the extracellular leaflets of the membrane. Herein we describe a general synthetic strategy to obtain not commercially available α,ω-diamino acids, the synthetic precursors of the labelled fatty acids, which we have applied to the synthesis of a C-18 derivative. Furthermore, it will be described the preparation of a photolabelled radioactive GSL as a case study
Synthesis of an Analog of the Repeating Unit of Capsular Polysaccharide of Streptococcus Pneumoniae Type 19F
No full textA practical route to long-chain non-natural α,ω-diamino acids
No full textAn efficient method for the synthesis of long-chain α,ω-diamino acids, starting from natural α-amino acids, has been developed. The long-chain skeleton has been generated through condensation between a protected aldehyde, derived from l-aspartic acid, and an ylide obtained from an ω-hydroxy-alkyl phosphonium salt. After conversion of the ω-hydroxy group into an amine, catalytic hydrogenation produced the N, N′-protected α,ω-diamino acid. The present route to α,ω-diamino acids allows the modulation of the chain length depending on the length of the ylide used for the Wittig olefination reaction
CD1A-BINDING GLYCOSPHINGOLIPIDS STIMULATING HUMAN AUTOREACTIVE T-CELLS: SYNTHESIS OF A FAMILY OF SULFATIDES DIFFERING IN THE ACYL CHAIN MOIETY
No full textNative sulfatide (a mixture of 3-sulfated β-D-galactopyranosylceramides with different fatty acids at the ceramide moiety) is an antigen presented by CD1a proteins. Herein the preparation of four sulfatides, which are constituents of the natural mixture and bear palmitic, stearic, behenic or nervonic fatty acid chains, is described. Azidosphingosine was stereoselectively synthesized through a CuCN-catalyzed allylic alkylation of a hexenitol dimesylate derived from D-xylose; β-glycosylation of azidosphingosine with a suitable D-galactosyl trichloroacetimidate led, after reduction of the azido group, to the galactosylsphingosine skeleton, which was derivatized with the different fatty acids. Final regioselective 3-sulfation gave the desired sulfatides, which were tested for activation of sulfatide-specific and CD1a-restricted T-cell clones
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