Defence Of The Ancients Download

Defense of the Ancients (shorted to DotA) is a custom map for Warcraft III, based on the "Aeon of Strife" map for StarCraft. The objective of the scenario is to destroy the opponents' "Ancient". The two teams' ancients are heavily guarded structures at opposing corners of the map. Players use powerful units known as heroes, and are assisted by allied heroes and AI-controlled units called "creeps". As in role-playing games, players level up their hero and use gold to buy equipment during the game.

Controlled release of chromatin from the nuclei of inflammatory cells is a process that entraps and kills microorganisms in the extracellular environment. Now termed ETosis, it is important for innate immunity in vertebrates. Paradoxically, however, in mammals, it can also contribute to certain pathologies. Here we show that ETosis occurs in several invertebrate species, including, remarkably, an acoelomate. Our findings reveal that the phenomenon is primordial and predates the evolution of the coelom. In invertebrates, the released chromatin participates in defence not only by ensnaring microorganisms and externalizing antibacterial histones together with other haemocyte-derived defence factors, but crucially, also provides the scaffold on which intact haemocytes assemble during encapsulation; a response that sequesters and kills potential pathogens infecting the body cavity. This insight into the early origin of ETosis identifies it as a very ancient process that helps explain some of its detrimental effects in mammals.

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The ancients used bloodletting extensively in infectious and other diseases. When recent work on iron and bacterial infection is taken into account, it is possible to argue that bloodletting, which reduced plasma iron and transferrin saturation, might have been of value in increasing resistance to infection by bacteria or plasmodia. Galen's bloodletting methods are summarized, and their probable effect on plasma iron is considered. The ancient physicans who had no specific remedies for infection whatsoever, may well have been justified in making responsible use of bloodletting, both for the treatment and for the prophylaxis of infectious disease.

As invertebrates depend on the innate activities of blood cells for defence and possess the key structures and protein homologues necessary to execute inflammation, we hypothesized that ETosis could be an important primordial defence strategy. For animals in lower taxa, especially those with an open circulatory system, we theorized that chromatin externalized by ETosis would represent a powerful way to contain infectious agents gaining entry into the body cavity and could play a role in the encapsulation of foreign materials by the haemocytes. For these studies, the shore crab, Carcinus maenas, was used as the main experimental animal because it possesses large populations of haemocytes that can be separated on Percoll and manipulated easily in vitro16. To investigate if ETosis occurs more widely across the invertebrates, comparative studies were also made on a distantly related protostome, the blue mussel, Mytilus edulis, and a cnidarian, specifically the sea anemone, Actinia equina. Mussel haemocytes are avidly phagocytic and display a strong respiratory burst17,18. Sea anemones, while not possessing a dedicated coelomic immune system, nevertheless, contain phagocytes within the mesoglea that are known to undergo a respiratory burst19 and express ROS-relevant genes20. Therefore, we performed a study to ascertain if immune cells from these invertebrates exhibit ETosis.

The findings reported here confirm that invertebrate defence cells are indeed capable of ETosis and at least in crab, the process contributes to encapsulation reactions mounted against non-self agents. That an acoelomate invertebrate also undergoes an ETotic-type response shows for the first time that chromatin release is an ancient and evolutionary conserved mechanism.

A role for extracellular chromatin released by haemocytes actively participating in defence has not previously been demonstrated in any invertebrate. One study on the wax moth, Galleria mellonella, reported that injection of purified endogenous nucleic acids simultaneously with pathogenic bacteria prolonged larval survival40. The present findings suggest that the injected bacteria were not only killed by AMPs and other immune molecules but also trapped on the externally introduced chromatin and then confined within haemocyte nodules, and thus unable to establish a lethal infection.

As members of the Cnidaria lack a coelom and true circulatory system, chromatin released through ETosis must be an ancient defence process that predates the development of an organized immune system within the mesoderm. In plants, extracellular DNA in root-cap slime of pea, Pisum sativum, confers protection against fungal infections45, but whether the DNA is extruded in a controlled, NADPH oxidase or ROS-dependent manner, as in vertebrate immune cells, has yet to be established. Moreover, as the chromatin is discharged to the external environment (that is, the soil), rather than within the tissues, it is uncertain if the deployment of chromatin in pea root genuinely represents ETosis. Therefore, at present, it is unknown when ETosis arose in eukaryote evolution, but the present study sheds new light on how early multicellular animals might have protected themselves against prokaryote competitors in their environment.

In conclusion, the InEPTs described here confirm that extracellular chromatin is a primordial defence process that effectively protects against infection and, accordingly, has been conserved through evolution. In higher animals, the advantages of externalized chromatin as an anti-infective strategy remain, but the more complex vasculature of vertebrates and the presence of an adaptive immune system mean that exposed chromatin can be problematic. The phylogenetic history of ETosis as a primitive host defence strategy accounts for its paradoxical effects in higher vertebrates.

How to cite this article: Robb, C. T. et al. Invertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon. Nat. Commun. 5:4627 doi: 10.1038/ncomms5627 (2014).

Emma F Harding, Alice G Russo, Grace J H Yan, Paul D Waters, Peter A White, Ancient viral integrations in marsupials: a potential antiviral defence, Virus Evolution, Volume 7, Issue 2, December 2021, veab076,

The New York Public Library. "Wall Street, the site of an ancient wall of defence [i.e. defense] against the Indians" The New York Public Library Digital Collections. 1869. -06df-a3d9-e040-e00a18064a99

The New York Public Library. "Wall Street, the site of an ancient wall of defence [i.e. defense] against the Indians" New York Public Library Digital Collections. Accessed January 7, 2024. -06df-a3d9-e040-e00a18064a99

An international team of researchers from the University of Haifa, Flinders University in Australia, the Israel Antiquities Authority and The Hebrew University uncovered and analysed the oldest known coastal defence system anywhere in the world, constructed by ancient settlers from boulders sourced in riverbeds from 1-2km near their village.

"Many of the fundamental human questions and the decision-making relating to human resilience, coastal defence, technological innovation and decisions to ultimately abandon long-standing settlements remain relevant." says Dr. Galili.

Harbour defence-works using chains in a limen kleistos[1] could be used both to stop the enemy from entering the port and to trap the enemy once inside the port, as mentioned by Dio Cassius (Hist, 51, 9) at Paraetonium (Egypt):

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