Novel microbicidal agents derived from Naja atra cardiotoxin 1 (CTX-1)

During my PhD course, I focused my research on antimicrobial peptides (AMPs), in particular on the aspects of their computational design and development. This work led to the development of a new family of AMPs that I designed, starting from the amino acid sequence of a snake venom toxin, the cardiotoxin 1 (CTX-1) of Naja atra. Naja atra atra cardiotoxin 1, produced by Chinese cobra snakes belonging to Elapidae family, is included in the three-finger toxin family and exerts high cytotoxicity and antimicrobial activity too. This toxin family is characterized by specific folding of three beta-sheet loops (“fingers”) extending from the central core and by four conserved disulfide bridges. Using as template the first loop of this toxin, different sequences of 20 amino acids linear cationic peptides have been designed in order to avoid toxic effects but to maintain and strengthen the antimicrobial activity. As a result, the sequence NCP-0 (Naja Cardiotoxin Peptide-0) was designed as ancestor and subsequently other 4 variant sequences of NCP0 were developed. These variant sequences have shown microbicidal activity towards a panel of reference strains of Gram-positive and Gram-negative bacteria, fungi and an enveloped virus. In particular, the sequence designed as NCP-3 (Naja Cardiotoxin Peptide-3) and its variants NCP-3a and NCP-3b have shown the best antimicrobial activity together with low cytotoxicity against eukaryotic cells and low hemolytic activity. Bactericidal activity has been demonstrated by minimum bactericidal concentration (MBC) assay at values below 10 μg/ml for Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ( clinical isolates), Moraxella catharralis ATCC 25238, MRSA ATCC 43400, while towards Staphylococcus aureus ATCC 25923, Enterococcus hirae ATCC 10541 and Streptococcus agalactiae ATCC 13813 the bactericidal activity was demonstrated even below 1.6 μg/ml concentration. This potent antimicrobial activity was confirmed even for unicellular fungi Candida albicans, Candida glabrata and Malassezia pachydermatis (MBC 32.26-6.4 μg/ml), and also against the fast-growing mycobacteria Mycobacterium smegmatis DSMZ 43756 and Mycobacterium fortuitum DSMZ 46621 (MBC 100 μg/ml). Moreover, NCP-3 has shown a virucidal activity on the enveloped virus Bovine Herpesvirus 1 (BoHV1) belonging to herpesviridae family. The bactericidal activity is maintained in a high salt concentration (125 and 250 mM NaCl) medium and PB +20% Mueller Hinton Medium for E. coli, MRSA and Pseudomonas aeruginosa reference strains. Considering these in vitro obtained data, we propose NCP-3 and its variants NCP-3a and NCP-3b as promising antimicrobial candidates. For this reason, the whole novel AMPs family has been protected by a national patent (n°102015000015951).

Berlin, Germany, 1748 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de la ville de Berlin : levé et dessiné par ordre et privilege privatif du Roy sous la direction du Marchall Comte de Schmettau, par Hildner approuvé par l'Academie Royale de Science â Berlin ; gravé sous la direction de G.F. Schmidt Graveur du Roy. It was published by l'Academie Royale de Science â Berlin in 1748. Scale [ca. 1:6,500]. Covers Berlin, Germany. This layer is image 1 of 4 total images of the four sheet source map, representing the northeast portion of the map. Map in French and German.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Deutsches Hauptdreiecksnetz (DHDN) 3-degree Gauss-Kruger Zone 4 coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortification, parks, cemeteries, ground cover, and more. Relief shown by hachures. Includes also view and inset engravings: Prospect du Stadt Berlin von Süden gegen Norden -- 1. Prospect des grossen Platzes von Opera Hausse 2. der Cathol. Kirche St. Hedwig 3. und einer Seite des Marggraff Henrich. Pallais -- Prospect der Neuen Schloss u Dohm Kirche -- Prospect des Neuen Königl. Printz Heinrich. Pallais den Opern Hausse gegen über.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Europe & Mediterranean Sea Region, 1705 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Toonneel des oorlogs in't zuider deel van Europa, door Carel Allard = Theatre de la guerre dans l'Europe meridionale, par Charles Allard. It was published by C. Allard in 1705. Scale [ca. 1:6,800,000]. Covers a portion of Europe and the Mediterranean Sea region. This layer is image 1 of 2 total images of the two sheet source map, representing the western portion of the map. Map in Dutch and French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the World Miller Cylindrical projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown pictorially.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Philadelphia, Pennsylvania, 1794 (Raster Image) (Image 1 of 2)

This layer is a georeferenced raster image of the historic paper map entitled: To Thomas Mifflin, governor and commander in chief of the state of Pennsylvania, this plan of the city and suburbs of Philadelphia is respectfully inscribed by the editor, 1794, A.P. Folie del. ; R. Scot & S. Allardice sculpsit. It was published in 1794. Scale [ca. 1:6,800]. This layer is image 1 of 2 total images of the two sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, selected public and private buildings, and more. Relief is shown by hachures. Includes index to points of interest, ill., and coat of arms held by two female figures. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Warsaw, Poland, 1762 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de la ville de Varsovie : dedie A. S. Mavgvste III roi de Pologne Electevr de Saxe, levé par ordre de S.E. M. le Comte Bielinksi Grand Marechal de la Covronne par M. P. Ricavd de Tirregaille Lieut. Colonel et Inginieur au Service du Roi et de la Repvblique en 1762 ; Marstalski fecit. It was published in 1762. Scale [ca. 1:6,600]. Covers Warsaw, Poland. This layer is image 1 of 4 total images, representing the southwest portion of the four sheet source map. Map in French and Polish. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Pulkovo 1942 Adjust 1958 Poland Zone II' coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortification, ground cover, and more. Relief shown by hachures. Includes index and views. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Cambridge, Massachusetts, 1854 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the city of Cambridge, Middlesex County, Massachusetts, by H.F. Walling, civil engineer ; engraved on stone by Friend & Aub. It was published by Geo. L. Dix in 1854. Scale 1:6,000. This layer is image 1 of 2 total images, representing the eastern portion of the two sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected public buildings (schools, university buildings, churches, etc.), selected property lots, building footprints, and names of property owners, selected businesses and industries, cemeteries, city ward boundaries, and more. Includes views of local buildings in margins. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Amsterdam Region, the Netherlands, 1749 (Image 1 of 3) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Kaarte van alle de dykpligtige en eenige waalpligtige landen behorende onder het Hoogreemraadschap van den Zeeburg en Diemerdyk, J. Wandelaar, delin. et sculpsit. It was published in 1749. Scale [ca. 1:6,000]. This layer is image 1 of 3 total images of the three sheet source map, representing the northern portion of the map. Covers the region east of Amsterdam, the Netherlands including portions of Gemeente Amsterdam, Gemeente Diemen, Gemeente Muiden, and Gemeente Weesp. Map in Dutch.The image inside the map neatline is georeferenced to the surface of the earth and fit to the RD_New (Rijksdriehoekstelsel), GCS Amersfoort coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, canals, cities and other human settlements, administrative boundaries, roads, propery boundaries with names of landowners, selected buildings and built-up areas, fortification, dikes, dams, windmills, shoreline features, and more. Relief shown by hachures. Depths shown by soundings.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Africa, 1811 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Africa, A. Arrowsmith. It was published by A. Arrowsmith, Soho Square. Additions to 1811. Scale [ca. 1:6,750,000]. This layer is image 1 of 4 total images of the four sheet source map, representing the northeast portion of the map. Covers also a small portion of Europe and the Middle East.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Africa Sinusoidal projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, territorial boundaries, roads, shoreline features, and more. Relief shown by hachures. Includes notes.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Perspectives in Resource Management and Climate Change Adaptation in the Southern and Eastern Mediterranean. MEDPRO Policy Paper No. 6, March 2013

This policy paper focuses on the sustainable management of some key natural resources in southern and eastern Mediterranean countries (SEMCs) under climate change and anthropogenic pressures. In a business-as-usual and even more so in a failed cooperation scenario, water resources, ecosystems and biodiversity in the region are under stress, with negative consequences for agriculture, food security, tourism and development. However, proper adaptation strategies are shown to be effective in reconciling resource conservation with GDP, trade and population growth. These need be implemented in different ways: technological, institutional, behavioural; and at different levels: regional, national and international. There is ample room for fruitful cooperation between the EU and SEMCs in this area, which can take the form of EU direct financial and technical support when resources in SEMCs are scarce, and of multilateral and bilateral cooperation programmes to improve resource efficiency. The EU could also take on the role of coordinating these different bilateral actions and, at the same time, support SEMCs to establish a structured programme focused on the communication and dissemination of emerging best practices.