Ex Vivo Expansion of Human Outgrowth Endothelial Cells Leads to IL-8-Mediated Replicative Senescence and Impaired Vasoreparative Function

Harnessing outgrowth endothelial cells (OECs) for vasoreparative therapy and tissue-engineering requires efficient ex-vivo expansion. How such expansion impacts on OEC function is largely unknown. In this study, we show that OECs become permanently cell-cycle arrested after ex-vivo expansion, which is associated with enlarged cell size, ß-galactosidase activity, DNA damage, tumour suppressor pathway activation and significant transcriptome changes. These senescence hallmarks were coupled with low telomerase activity and telomere shortening, indicating replicative senescence. OEC senescence limited their regenerative potential by impairing vasoreparative properties in-vitro and in-vivo. Integrated transcriptome-proteome analysis identified inflammatory signalling pathways as major mechanistic components of the OEC senescence programme. In particular, IL8 was an important facilitator of this senescence; depletion of IL8 in OECs significantly extended ex-vivo lifespan, delayed replicative senescence and enhanced function. While the ability to expand OEC numbers prior to autologous or allogeneic therapy remains a useful property, their replicative senescence and associated impairment of vasorepair needs to be considered. The current study also suggests that modulation of the senescence-associated secretory phenotype (SASP) could be used to optimise OEC therapy.

Voyage(s) to Sarajevo: Jean-Luc Godard and the Image of War

This essay discusses Jean-Luc Godard’s artistic response to the Bosnian War (1992-95), and its representations in the Western mass media. For Godard, the reluctance of Europe’s advanced liberal democracies to intervene meaningfully in Bosnia – their insistence that 'humanitarianism' rather than protective intervention was the order of the day – was tantamount to supporting Serbian fascism, and – a fortiori – regressing to a policy of appeasement reminiscent of the days of the Munich Agreement. Although Godard's stance set him against some of his former compatriots on the left, speculating on his ideological motivations is beside the point. Rather, it is is in his filmmaking, in his vision of cinema, and how it relates to other histories of the image, that Godard’s sensibility can be most keenly felt and understood. As the essay points out, even his recent contribution to Jean-Michel Frodon's compilation film, Bridges of Sarajevo/Les ponts de Sarajevo (2014, 114 mn.), persists in posing questions about how the past continues to shape the present, and how Sarajevo and its contemporary history still delineates the identity of Europe. 

The Climate of War: Violence, Warfare and Climatic Reductionism

National security agencies and other interested parties now often regard conflict as the inevitable consequence of climate change. This inclination to reduce war to the vicissitudes of climate is not new however. Here I examine some of the earlier ways in which violence was attributed to climatic conditions, particularly in the United States, and trace links between these older advocates of climatic determinism and the recent writings of those insisting that climate change will usher in a grim world of chronic warfare. It ends by drawing attention to the writings of some critics who are troubled by the ease with which climatic reductionism is capturing the public imagination.

Review of Mark F. Chingono. The State, Violence and Development. The Political Economy of War in Mozambique, 1975–1992.

Book review of: Mark F. Chingono. The State, Violence and Development. The Political Economy of War in Mozambique, 1975–1992. Avebury (Aldershot, Brookfield USA, Hong Kong, Singapore, Sydney), 1996. 291 pp. Foreword by Keith Hart. Tables. Appendix. Selected Bibliography. Index. £42.00. $71.95. Cloth.

Holidays in the Danger Zone: Entanglements of War and Tourism

A timely, and uniquely historical, look at how war turns soldiers, and all of us, into tourists. Holidays in the Danger Zone exposes the mundane and everyday entanglements between two seemingly opposed worlds—warfare and tourism. Debbie Lisle shows how a tourist sensibility shapes the behavior of soldiers in warespecially the experiences of Western military forces in “exotic” settings. This includes not only R&R but also how battlefields themselves become landscapes of leisure and tourism. It further explores how a military sensibility shapes the development of tourism in the postwar context, from “Dark Tourism” (engaging with displays of conflict and atrocity) to exhibitions of conflict in museums and at memorial sites, as well as in advertising, film, journals, guidebooks, blogs, and photography. Focused on how war and tourism reinforce prevailing modes of domination, Holidays in the Danger Zone critically examines the long historical arc of the war-tourism nexus from nineteenth-century imperialism to World War I and World War II, from the Cold War to globalization and the War on Terror.

Effect of light on ex situ production of symbiotic corals

The increasing interest in coral culture for biotechnological applications, to supply the marine aquarium trade, or for reef restoration programs, has prompted researchers to optimize coral culture protocols, with emphasis to ex situ production. When cultured ex situ, the growth performance of corals can be influenced by several physical, chemical and biological parameters. For corals harbouring zooxanthellae, light is one of such key factors, as it can influence the photosynthetic performance of these endosymbionts, as well as coral physiology, survival and growth. The economic feasibility of ex situ coral aquaculture is strongly dependent on production costs, namely those associated with the energetic needs directly resulting from the use of artificial lighting systems. In the present study we developed a versatile modular culture system for experimental coral production ex situ, assembled solely using materials and equipment readily available from suppliers all over the world; this approach allows researchers from different institutions to perform truly replicated experimental set-ups, with the possibility to directly compare experimental results. Afterwards, we aimed to evaluate the effect of contrasting Photosynthetically Active Radiation (PAR) levels, and light spectra emission on zooxanthellae photochemical performance, through the evaluation of the maximum quantum yield of PSII (Fv/Fm) (monitored non-invasively and non-destructively through Pulse Amplitude Modulation fluorometry, PAM), chlorophyll a content (also determined non-destructively by using the spectral reflectance index Normalized Difference Vegetation Index, NDVI), photosynthetic and accessory pigments, number of zooxanthellae, coral survival and growth. We studied two soft coral species, Sarcophyton cf. glaucum and Sinularia flexibilis, as they are good representatives of two of the most specious genera in family Alcyoniidae, which include several species with interest for biotechnological applications, as well as for the marine aquarium trade; we also studied two commercially important scleractinian corals: Acropora formosa and Stylophora pistillata. We used different light sources: hydrargyrum quartz iodide (HQI) lamps with different light color temperatures, T5 fluorescent lamps, Light Emitting Plasma (LEP) and Light Emitting Diode (LED). The results achieved revealed that keeping S. flexibilis fragments under the same light conditions as their mother colonies seems to be photobiologically acceptable for a short-term husbandry, notwithstanding the fact that they can be successfully stocked at lower PAR intensities. We also proved that low PAR intensities are suitable to support the ex situ culture S. cf. glaucum in captivity at lower production costs, since the survival recorded during the experiment was 100%, the physiological wellness of coral fragments was evidenced, and we did not detect significant differences in coral growth. Finally, we concluded that blue light sources, such as LED lighting, allow a higher growth for A. formosa and S. pistillata, and promote significant differences on microstructure organization and macrostructure morphometry in coral skeletons; these findings may have potential applications as bone graft substitutes for veterinary and/or other medical uses. Thus, LED technology seems to be a promising option for scleractinian corals aquaculture ex situ.

Do the psychological impacts of war cause poverty?: Evidence from Mozambique

This paper evaluates the extent to which war-related psychological distress causes poverty. The endogeneous nature of mental distress is addressed by using exposure to the civil war in Mozambique as an instrument. It is found that exposure to war has a significant and positive long-lasting impact on mental distress. Furthermore, the causal impact of war-related psychological distress on income and wealth is shown to be significant, negative, and nonnegligible. One standard deviation increase in mental distress decreases income by half a standard deviation. These findings are robust to alternative specifications, including the use of an alternative database on the incidence of PTSD in Mozambique.

Melan-A/MART-1-specific CD4 T cells in melanoma patients: identification of new epitopes and ex vivo visualization of specific T cells by MHC class II tetramers.

Over the past decade, many efforts have been made to identify MHC class II-restricted epitopes from different tumor-associated Ags. Melan-A/MART-1(26-35) parental or Melan-A/MART-1(26-35(A27L)) analog epitopes have been widely used in melanoma immunotherapy to induce and boost CTL responses, but only one Th epitope is currently known (Melan-A51-73, DRB1*0401 restricted). In this study, we describe two novel Melan-A/MART-1-derived sequences recognized by CD4 T cells from melanoma patients. These epitopes can be mimicked by peptides Melan-A27-40 presented by HLA-DRB1*0101 and HLA-DRB1*0102 and Melan-A25-36 presented by HLA-DQB1*0602 and HLA-DRB1*0301. CD4 T cell clones specific for these epitopes recognize Melan-A/MART-1+ tumor cells and Melan-A/MART-1-transduced EBV-B cells and recognition is reduced by inhibitors of the MHC class II presentation pathway. This suggests that the epitopes are naturally processed and presented by EBV-B cells and melanoma cells. Moreover, Melan-A-specific Abs could be detected in the serum of patients with measurable CD4 T cell responses specific for Melan-A/MART-1. Interestingly, even the short Melan-A/MART-1(26-35(A27L)) peptide was recognized by CD4 T cells from HLA-DQ6+ and HLA-DR3+ melanoma patients. Using Melan-A/MART-1(25-36)/DQ6 tetramers, we could detect Ag-specific CD4 T cells directly ex vivo in circulating lymphocytes of a melanoma patient. Together, these results provide the basis for monitoring of naturally occurring and vaccine-induced Melan-A/MART-1-specific CD4 T cell responses, allowing precise and ex vivo characterization of responding T cells.

Captain Lewis Warrington and others : memorial of Lewis Warrington, Captain in the U.S. Navy, (in behalf of himself and the officers and crew of the U.S. sloop-of-war Peacock); praying that the one half of the proceeds of the Epervier and goods which went into the officers and crew of said vessel, it having been decreed to them by the United States court as captors. April 26, 1848.--

Caption title.

Important state papers : declaration of war, Washington, June 18, 4 o'clock, P.M.

Message to the Senate and House of Representatives of the United States / James Madison -- Report : the Committee on Foreign relations, to whom was referred the message of the President of the United States of the 1st of June, 1812 -- An Act, declaring war between the United Kingdom of Great Britain and Ireland and the dependencies thereof, and the United States of America and their territories -- Address of the Senate to the people of the Commonwealth of Massachusetts.

Letter from the acting Secretary of War, transmitting information relative to the claims of the State of Massachusetts for payment of the expenses of the militia ordered out by the executive authority of the state, during the late war. --

15th Congress, 1st session, 1817-1818, House. Doc. 81.