Two routes of chlorophyllide synthesis that are differentially regulated by light in barley (Hordeum vulgare L.).

NADPH-protochlorophyllide oxidoreductase (POR; EC 1.6.99.1) catalyzes the only known light-dependent step in chlorophyll synthesis of higher plants, the reduction of protochlorophyllide (Pchlide) to chlorophyllide. In barley, two distinct immunoreactive POR proteins were identified. In contrast to the light-sensitive POR enzyme studied thus far (POR-A), levels of the second POR protein remained constant in seedlings during the transition from dark growth to the light and in green plants. The existence of a second POR-related protein was verified by isolating and sequencing cDNAs that encode a second POR polypeptide (POR-B) with an amino acid sequence identity of 75% to the POR-A. In the presence of NADPH and Pchlide, the in vitro-synthesized POR-A and POR-B proteins could be reconstituted to ternary enzymatically active complexes that reduced Pchlide to chlorophyllide only after illumination. Even though the in vitro activities of the two enzymes were similar, the expression of their genes during the light-induced transformation of etiolated to green seedlings was distinct. While the POR-A mRNA rapidly declined during illumination of dark-grown seedlings and soon disappeared, POR-B mRNA remained at an approximately constant level in dark-grown and green seedlings. Thus these results suggest that chlorophyll synthesis is controlled by two light-dependent POR enzymes, one that is active only transiently in etiolated seedlings at the beginning of illumination and the other that also operates in green plants.

Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.

Mast cells are multifunctional bone marrow-derived cells found in mucosal and connective tissues and in the nervous system, where they play important roles in tissue inflammation and in neuroimmune interactions. Very little is known about endogenous molecules and mechanisms capable of modulating mast cell activation. Palmitoylethanolamide, found in peripheral tissues, has been proposed to behave as a local autacoid capable of downregulating mast cell activation and inflammation. A cognate N-acylamide, anandamide, the ethanolamide of arachidonic acid, occurs in brain and is a candidate endogenous agonist for the central cannabinoid receptor (CB1). As a second cannabinoid receptor (CB2) has been found in peripheral tissues, the possible presence of CB2 receptors on mast cells and their interaction with N-acylamides was investigated. Here we report that mast cells express both the gene and a functional CB2 receptor protein with negative regulatory effects on mast cell activation. Although both palmitoylethanolamide and anandamide bind to the CB2 receptor, only the former downmodulates mast cell activation in vitro. Further, the functional effect of palmitoylethanolamide, as well as that of the active cannabinoids, was efficiently antagonized by anandamide. The results suggest that (i) peripheral cannabinoid CB2 receptors control, upon agonist binding, mast cell activation and therefore inflammation; (ii) palmitoylethanolamide, unlike anandamide, behaves as an endogenous agonist for the CB2 receptor on mast cells; (iii) modulatory activities on mast cells exerted by the naturally occurring molecule strengthen a proposed autacoid local inflammation antagonism (ALIA) mechanism; and (iv) palmitoylethanolamide and its derivatives may provide antiinflammatory therapeutic strategies specifically targeted to mast cells ("ALIAmides").

Rapid alteration of thalamocortical axon morphology follows peripheral damage in the neonatal rat.

The effect of day of birth (postnatal day 0; P0) infraorbital nerve section on the morphology of individual thalamocortical axons in rat somatosensory cortex was examined on P3. Thalamic fibers were labeled in fixed brains with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate, and individual photo-converted thalamocortical fibers were reconstructed. In normal animals on P3, axon arbor terminal formation within layer IV has commenced and terminal arbor width is comparable to that of a cortical "barrel." After infraorbital nerve section, the average width of thalamocortical terminal arbors is significantly greater than is the average arbor width of normal rats of the same age; however, neither the number of branches per terminal arbor nor total arbor length differs between groups. These observations suggest that the role of the periphery in guiding terminal arbor formation is exerted both very rapidly and at the level of the single thalamic axon. Further, these results indicate a close association between individual axon terminal arbor morphology and pattern formation in the rat somatosensory cortex.

Valutazione della risposta immunitaria cellulare e fenotipizzazione linfocitaria nel suino in corso di infezione naturale da virus della PRRS (“Porcine Reproductive and Respiratory Syndrome”) e dopo stimolazione di PBMC (“Peripheral Blood Mononuclear Cells”) in vitro con Peptide Killer (KP)

SUMMARY The Porcine Reproductive and Respiratory Syndrome (PRRS) virus is one of the most spread pathogens in swine herds all over the world and responsible for a reproductive and respiratory syndrome that causes severe heath and economical problems. This virus emerged in late 1980’s but although about 30 years have passed by, the knowledge about some essential facets related to the features of the virus (pathogenesis, immune response, and epidemiology) seems to be still incomplete. Taking into account that the development of modern vaccines is based on how innate and acquire immunity react, a more and more thorough knowledge on the immune system is needed, in terms of molecular modulation/regulation of the inflammatory and immune response upon PRRSV infection. The present doctoral thesis, which is divided into 3 different studies, is aimed to increase the knowledge about the interaction between the immune system and the PRRS virus upon natural infection. The objective of the first study entitled “Coordinated immune response of memory and cytotoxic T cells together with IFN-γ secreting cells after porcine reproductive and respiratory syndrome virus (PRRSV) natural infection in conventional pigs” was to evaluate the activation and modulation of the immune response in pigs naturally infected by PRRSV compared to an uninfected control group. The course of viremia was evaluated by PCR, the antibody titres by ELISA, the number of IFN-γ secreting cells (IFN- SC) by an ELISPOT assay and the immunophenotyping of some lymphocyte subsets (cytotoxic cells, memory T lymphocytes and cytotoxic T lymphocytes) by flow cytometry. The results showed that the activation of the cell-mediated immune response against PRRSV is delayed upon infection and that however the levels of IFN-γ SC and lymphocyte subsets subsequently increase over time. Furthermore, it was observed that the course of the different immune cell subsets is time-associated with the levels of PRRSV-specific IFN-γ SC and this can be interpreted based on the functional role that such lymphocyte subsets could have in the specific production/secretion of the immunostimulatory cytokine IFN-γ. In addition, these data support the hypothesis that the age of the animals upon the onset of infection or the diverse immunobiological features of the field isolate, as typically hypothesized during PRRSV infection, are critical conditions able to influence the qualitative and quantitative course of the cell-mediated immune response during PRRSV natural infection. The second study entitled “Immune response to PCV2 vaccination in PRRSV viremic piglets” was aimed to evaluate whether PRRSV could interfere with the activation of the immune response to PCV2 vaccination in pigs. In this trial, 200 pigs were divided into 2 groups: PCV2-vaccinated (at 4 weeks of age) and PCV2-unvaccinated (control group). Some piglets of both groups got infected by PRRSV, as determined by PRRSV viremia detection, so that 4 groups were defined as follows: PCV2 vaccinated - PRRSV viremic PCV2 vaccinated - PRRSV non viremic PCV2 unvaccinated - PRRSV viremic PCV2 unvaccinated - PRRSV non viremic The following parameters were evaluated in the 4 groups: number of PCV2-specific IFN-γ secreting cells, antibody titres by ELISA and IPMA. Based on the immunological data analysis, it can be deduced that: 1) The low levels of antibodies against PCV2 in the PCV2-vaccinated – PRRSV-viremic group at vaccination (4 weeks of age) could be related to a reduced colostrum intake influenced by PRRSV viremia. 2) Independently of the viremia status, serological data of the PCV2-vaccinated group by ELISA and IPMA does not show statistically different differences. Consequently, it can be be stated that, under the conditions of the study, PRRSV does not interfere with the antibody response induced by the PCV2 vaccine. 3) The cell-mediated immune response in terms of number of PCV2-specific IFN-γ secreting cells in the PCV2-vaccinated – PRRSV-viremic group seems to be compromised, as demonstrated by the reduction of the number of IFN-γ secreting cells after PCV2 vaccination, compared to the PCV2-vaccinated – PRRSV-non-viremic group. The data highlight and further support the inhibitory role of PRRSV on the development and activation of the immune response and highlight how a natural infection at early age can negatively influence the immune response to other pathogens/antigens. The third study entitled “Phenotypic modulation of porcine CD14+ monocytes, natural killer/natural killer T cells and CD8αβ+ T cell subsets by an antibody-derived killer peptide (KP)” was aimed to determine whether and how the killer peptide (KP) could modulate the immune response in terms of activation of specific lymphocyte subsets. This is a preliminary approach also aimed to subsequently evaluate such KP with a potential antivural role or as adjuvant. In this work, pig peripheral blood mononuclear cells (PBMC) were stimulated with three KP concentrations (10, 20 and 40 g/ml) for three time points (24, 48 and 72 hours). TIME POINTS (hours) KP CONCENTRATIONS (g/ml) 24 0-10-20-40 48 0-10-20-40 72 0-10-20-40 By using flow cytometry, the qualitative and quantitative modulation of the following immune subsets was evaluated upon KP stimulation: monocytes, natural killer (NK) cells, natural killer T (NKT) cells, and CD4+ and CD8α/β+ T lymphocyte subsets. Based on the data, it can be deduced that: 1) KP promotes a dose-dependent activation of monocytes, particularly after 24 hours of stimulation, by inducing a monocyte phenotypic and maturation shift mainly involved in sustaining the innate/inflammatory response. 2) KP induces a strong dose-dependent modulation of NK and NKT cells, characterized by an intense increase of the NKT cell fraction compared to NK cells, both subsets involved in the antibody-dependent cell cytotoxicity (ADCC). The increase is observed especially after 24 hours of stimulation. 3) KP promotes a significant activation of the cytotoxic T lymphocyte subset (CTL). 4) KP can modulate both the T helper and T cytotoxic phenotype, by inducing T helper cells to acquire the CD8α thus becoming doube positive cells (CD4+CD8+) and by inducing CTL (CD4-CD8+high) to acquire the double positive phenotype (CD4+CD8α+high). Therefore, KP may induce several effects on different immune cell subsets. For this reason, further research is needed aimed at characterizing each “effect” of KP and thus identifying the best use of the decapeptide for vaccination practice, therapeutic purposes or as vaccine adjuvant. RIASSUNTO Il virus della PRRS (Porcine Reproductive Respiratory Syndrome) è uno dei più diffusi agenti patogeni negli allevamenti suini di tutto il mondo, responsabile di una sindrome riproduttiva e respiratoria causa di gravi danni ad impatto sanitario ed economico. Questo virus è emerso attorno alla fine degli anni ’80 ma nonostante siano passati circa una trentina di anni, le conoscenze su alcuni punti essenziali che riguardano le caratteristiche del virus (patogenesi, risposta immunitaria, epidemiologia) appaiono ancora spesso incomplete. Considerando che lo sviluppo dei vaccini moderni è basato sui principi dell’immunità innata e acquisita è essenziale una sempre più completa conoscenza del sistema immunitario inteso come modulazione/regolazione molecolare della risposta infiammatoria e immunitaria in corso di tale infezione. Questo lavoro di tesi, suddiviso in tre diversi studi, ha l’intento di contribuire all’aumento delle informazioni riguardo l’interazione del sistema immunitario, con il virus della PRRS in condizioni di infezione naturale. L’obbiettivo del primo studio, intitolato “Associazione di cellule memoria, cellule citotossiche e cellule secernenti IFN- nella risposta immunitaria in corso di infezione naturale da Virus della Sindrome Riproduttiva e Respiratoria del Suino (PRRSV)” è stato di valutare l’attivazione e la modulazione della risposta immunitaria in suini naturalmente infetti da PRRSV rispetto ad un gruppo controllo non infetto. I parametri valutati sono stati la viremia mediante PCR, il titolo anticorpale mediante ELISA, il numero di cellule secernenti IFN- (IFN- SC) mediante tecnica ELISPOT e la fenotipizzazione di alcune sottopopolazioni linfocitarie (Cellule citotossiche, linfociti T memoria e linfociti T citotossici) mediante citofluorimetria a flusso. Dai risultati ottenuti è stato possibile osservare che l’attivazione della risposta immunitaria cellulo-mediata verso PRRSV appare ritardata durante l’infezione e che l’andamento, in termini di IFN- SC e dei cambiamenti delle sottopopolazioni linfocitarie, mostra comunque degli incrementi seppur successivi nel tempo. E’ stato inoltre osservato che gli andamenti delle diverse sottopopolazioni immunitarie cellulari appaiono temporalmente associati ai livelli di IFN- SC PRRSV-specifiche e ciò potrebbe essere interpretato sulla base del ruolo funzionale che tali sottopopolazioni linfocitarie potrebbero avere nella produzione/secrezione specifica della citochina immunoattivatrice IFN-. Questi dati inoltre supportano l’ipotesi che l’età degli animali alla comparsa dell’infezione o, come tipicamente ipotizzato nell’infezione da PRRSV, le differenti caratteristiche immunobiologiche dell’isolato di campo, sia condizioni critiche nell’ influenzare l’andamento qualitativo e quantitativo della risposta cellulo-mediata durante l’infezione naturale da PRRSV. Il secondo studio, dal titolo “Valutazione della risposta immunitaria nei confronti di una vaccinazione contro PCV2 in suini riscontrati PRRSV viremici e non viremici alla vaccinazione” ha avuto lo scopo di valutare se il virus della PRRS potesse andare ad interferire sull’attivazione della risposta immunitaria indotta da vaccinazione contro PCV2 nel suino. In questo lavoro sono stati arruolati 200 animali divisi in due gruppi, PCV2 Vaccinato (a 4 settimane di età) e PCV2 Non Vaccinato (controllo negativo). Alcuni suinetti di entrambi i gruppi, si sono naturalmente infettati con PRRSV, come determinato con l’analisi della viremia da PRRSV, per cui è stato possibile creare quattro sottogruppi, rispettivamente: PCV2 vaccinato - PRRSV viremico PCV2 vaccinato - PRRSV non viremico PCV2 non vaccinato - PRRSV viremico PCV2 non vaccinato - PRRSV non viremico Su questi quattro sottogruppi sono stati valutati i seguenti parametri: numero di cellule secernenti IFN- PCV2 specifiche, ed i titoli anticorpali mediante tecniche ELISA ed IPMA. Dall’analisi dei dati immunologici derivati dalle suddette tecniche è stato possibile dedurre che:  I bassi valori anticorpali nei confronti di PCV2 del gruppo Vaccinato PCV2-PRRSV viremico già al periodo della vaccinazione (4 settimane di età) potrebbero essere messi in relazione ad una ridotta assunzione di colostro legata allo stato di viremia da PRRSV  Indipendentemente dallo stato viremico, i dati sierologici del gruppo vaccinato PCV2 provenienti sia da ELISA sia da IPMA non mostrano differenze statisticamente significative. Di conseguenza è possibile affermare che in questo caso PRRSV non interferisce con la risposta anticorpale promossa dal vaccino PCV2.  La risposta immunitaria cellulo-mediata, intesa come numero di cellule secernenti IFN- PCV2 specifiche nel gruppo PCV2 vaccinato PRRS viremico sembra essere compromessa, come viene infatti dimostrato dalla diminuzione del numero di cellule secernenti IFN- dopo la vaccinazione contro PCV2, comparata con il gruppo PCV2 vaccinato- non viremico. I dati evidenziano ed ulteriormente sostengono il ruolo inibitorio del virus della PRRSV sullo sviluppo ed attivazione della risposta immunitaria e come un infezione naturale ad età precoci possa influenzare negativamente la risposta immunitaria ad altri patogeni/antigeni. Il terzo studio, intitolato “Modulazione fenotipica di: monociti CD14+, cellule natural killer (NK), T natural killer (NKT) e sottopopolazioni linfocitarie T CD4+ e CD8+ durante stimolazione con killer peptide (KP) nella specie suina” ha avuto come scopo quello di stabilire se e come il Peptide Killer (KP) potesse modulare la risposta immunitaria in termini di attivazione di specifiche sottopopolazioni linfocitarie. Si tratta di un approccio preliminare anche ai fini di successivamente valutare tale KP in un potenziale ruolo antivirale o come adiuvante. In questo lavoro, periferal blood mononuclear cells (PBMC) suine sono state stimolate con KP a tre diverse concentrazioni (10, 20 e 40 g/ml) per tre diversi tempi (24, 48 e 72 ore). TEMPI DI STIMOLAZIONE (ore) CONCENTRAZIONE DI KP (g/ml) 24 0-10-20-40 48 0-10-20-40 72 0-10-20-40 Mediante la citometria a flusso è stato dunque possibile analizzare il comportamento qualitativo e quantitativo di alcune sottopopolazioni linfocitarie sotto lo stimolo del KP, tra cui: monociti, cellule Natural Killer (NK), cellule T Natural Killer (NKT) e linfociti T CD4 e CD8+. Dai dati ottenuti è stato possibile dedurre che: 1) KP promuove un’attivazione dei monociti dose-dipendente in particolare dopo 24 ore di stimolazione, inducendo uno “shift” fenotipico e di maturazione monocitaria maggiormente coinvolto nel sostegno della risposta innata/infiammatoria. 2) KP induce una forte modulazione dose-dipendente di cellule NK e NKT con un forte aumento della frazione delle cellule NKT rispetto alle NK, sottopopolazioni entrambe coinvolte nella citotossicità cellulare mediata da anticorpi (ADCC). L’aumento è riscontrabile soprattutto dopo 24 ore di stimolazione. 3) KP promuove una significativa attivazione della sottopopolazione del linfociti T citotossici (CTL). 4) Per quanto riguarda la marcatura CD4+/CD8+ è stato dimostrato che KP ha la capacità di modulare sia il fenotipo T helper che T citotossico, inducendo le cellule T helper ad acquisire CD8 diventando quindi doppio positive (CD4+CD8+) ed inducendo il fenotipo CTL (CD4-CD8+high) ad acquisire il fenotipo doppio positivo (CD4+CD8α+high). Molti dunque potrebbero essere gli effetti che il decapeptide KP potrebbe esercitare sulle diverse sottopopolazioni del sistema immunitario, per questo motivo va evidenziata la necessità di impostare e attuare nuove ricerche che portino alla caratterizzazione di ciascuna “abilità” di KP e che conducano successivamente alla scoperta del migliore utilizzo che si possa fare del decapeptide sia dal punto di vista vaccinale, terapeutico oppure sotto forma di adiuvante vaccinale.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 1 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 1 of 8 total images of the seven sheet source map. Covers portions of eastern Asia, Siberia, Russia, Pacific Islands, and western portions of Canada and the United States including Alaska. The image inside the map neatline is georeferenced to the surface of the earth and fit to a non-standard 'World Mercator' projection, with the central meridian at 180 degrees west. 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. Note: The central meridian of this map is not the same as the Prime Meridian and may wrap the International Date Line or overlap itself when displayed in GIS software. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 2 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 2 of 8 total images of the seven sheet source map. Covers portions of Europe, Northern Africa, and Asia. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'World Mercator' projection. 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 by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 3 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 3 of 8 total images of the seven sheet source map. Covers portions of South America, the South Pacific and the South Atlantic. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'World Mercator' projection. 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 by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 5 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 5 of 8 total images of the seven sheet source map. Covers portions of North America, northern South America, and the western coasts of Europe and Africa. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'World Mercator' projection. 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 by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 4 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 4 of 8 total images of the seven sheet source map. Covers portions of Southern Africa, Southeast Asia, Western Australia, and the Indian Ocean. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'World Mercator' projection. 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 by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 6 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 6 of 8 total images of the seven sheet source map. Covers portions of Australia, Southeast Asia, and the South Pacific Ocean. The image inside the map neatline is georeferenced to the surface of the earth and fit to a non-standard 'World Mercator' projection, with the central meridian at 180 degrees west. 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. Note: The central meridian of this map is not the same as the Prime Meridian and may wrap the International Date Line or overlap itself when displayed in GIS software. This map shows features such as drainage, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 8 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 8 of 8 total images of the seven sheet source map. Covers portions of eastern Asia. The original map sheet contains multiple maps on one sheet. Because the map images are non-contiguous and possibly at differing scales, each map image was georeferenced separately. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Mercator' projection. 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 by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1790 (Image 7 of 8) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the world on Mercators projection : exhibiting all the new discoveries to the present time, with the tracks of the most distinguished navigators since the year 1700 carefully collected from the best charts, maps, voyages, &c. extant and regulated from the accurate astronomical observations made in three voyages performed under the command of Captn. James Cook in the years 1768, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 & 80, compiled and published by A. Arrowsmith, geographer; by permission of Simon McTavish Esq[r] is correctly delineated the discoveries of Mr. McKenzie laid down from his original journal in the year 1789. It was published by A. Arrowsmith, April 1, 1790. Scale [ca. 1:20,000,000]. This layer is image 7 of 8 total images of the seven sheet source map. Covers portions of Australia and Southeast Asia. The original map sheet contains multiple maps on one sheet. Because the map images are non-contiguous and possibly at differing scales, each map image was georeferenced separately. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Mercator' projection. 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 by hachures. Depths shown by soundings. Includes routes, locations, and dates of James Cook's voyages. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1853 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Planisphere : elémentaire et illustré indiquant la description géographique des parties connues de la terre, l'époque des grandes découvertes des navigateurs les colonies Européennes, les principaux parcours des paquebots, l'époque des départs, la durée du trajet, &c[a]., dreseé par Vuillemin, géographie ; gravé par Langevin. It was published by Fatout in 1853. Scale [ca. 1:50,000,000]. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the the 'World Mercator' projection. 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. Shows voyage routes of exploration and discovery. Relief shown pictorially and by spot heights. Includes historical notes, explanations, and ill. of sea vessels and scenes of exploration. Includes insets at lower margin: Costumes des différentes races qui peuplent la terre -- [Chart of Mt. heights in Europe] -- Hauteur des principales montagnes du monde -- [Chart of Mt. heights in Asia] -- Tableau faisant voir que le Planisphère n'est que le développement figure du globe sur une surface plane -- Longueurs sources et embouchures des principaux fleuves du monde -- Costumes des différentes races qui peuplent la terre. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

World Map Showing Routes of Exploration and Discovery, 1850 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: The world, on Mercator's projection, by David H. Burr. It was published by J. Haven, 86 State St. in 1850. Scale [ca. 1:74,000,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to a non-standard 'Mercator' projection with the central meridian at 90 degrees west. 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. "Showing the different routes to California, and distance by each, routes of different navigators, route of the contemplated Pacific R. Road, distances to China, Europe, & c." This map shows features such as drainage, cities and other human settlements, shoreline features, and more. Relief shown by abbreviated form lines. Includes historical notes, ship ill., tables of distances, "Nicaragua route" distances, and text on "Pacific Railroad." Insets: Map of the Nicaragua route -- Map of the proposed rail road from St. Louis to the bay of St. Francisco. This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection and the Harvard University Library as part of the Open Collections Program at Harvard University project: Organizing Our World: Sponsored Exploration and Scientific Discovery in the Modern Age. Maps selected for the project correspond to various expeditions and represent a range of regions, originators, ground condition dates, scales, and purposes.

Railway map of routes to the White Mountains, New Hampshire 1859 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Railway map of routes to the White Mountains, by Harvey Boardman. It was published in 1859 by J.H. Bufford's Lith. Scale not given. Covers New Hampshire, Vermont, Massachusetts, Connecticut, Rhode Island, and portions of Maine, New York, and the province of Quebec, Canada. The image inside the map neatline is georeferenced to the surface of the earth and fit to the USA Contiguous Albers Equal Area Conic projection (Meters). 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, railroad stations, drainage, selected cities, towns, villages, and points of interest (hotels, houses, etc.), state boundaries, and more. Relief shown by hachures. Includes text on routes in margins. This layer is part of a selection of digitally scanned and georeferenced historic maps of New England 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, scales, and purposes.