Abstract:Streptomyces lunaelactis strains have been isolated from moonmilk deposits, which are calcium carbonate speleothems used for centuries in traditional medicine for their antimicrobial properties. Genome mining revealed that these strains are a remarkable example of a Streptomyces species with huge heterogeneity regarding their content in biosynthetic gene clusters (BGCs) for specialized metabolite production. BGC 28a is one of the cryptic BGCs that is only carried by a subgroup of S. lunaelactis strains for which in silico analysis predicted the production of nonribosomal peptide antibiotics containing the non-proteogenic amino acid piperazic acid (Piz). Comparative metabolomics of culture extracts of S. lunaelactis strains either holding or not holding BGC 28a combined with MS/MS-guided peptidogenomics and 1H/13C NMR allowed us to identify the cyclic hexapeptide with the amino acid sequence (D-Phe)-(L-HO-Ile)-(D-Piz)-(L-Piz)-(D-Piz)-(L-Piz), called lunaemycin A, as the main compound synthesized by BGC 28a. Molecular networking further identified 18 additional lunaemycins, with 14 of them having their structure elucidated by HRMS/MS. Antimicrobial assays demonstrated a significant bactericidal activity of lunaemycins against Gram-positive bacteria, including multi-drug resistant clinical isolates. Our work demonstrates how an accurate in silico analysis of a cryptic BGC can highly facilitate the identification, the structural elucidation, and the bioactivity of its associated specialized metabolites.Keywords: antibiotics; cryptic metabolites; natural compounds; Anti-MRSA; moonmilk; cave microbiology; genome mining; piperazic acid; NRPS; molecular networking
[FULL] MC Cave font
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Abstract:Atmospheric CO2 concentrations can reach high levels inside natural caves, representing a hazardous condition for both humans frequenting the underground environment and its safeguard due to the corrosion of speleothems induced by the acidification of atmospheric moisture. These issues are particularly critical for the eco-sustainable management of caves protected as nature reserves and undergoing touristic exploitation. In this paper we present the results of the C6 project, which was activated in 1999 for the monitoring of air quality inside three caves protected as nature reserves in Sicily (Italy). Near-real-time and spot measurements of air temperature and CO2 concentration have been carried out since the year 2000, giving the opportunity of evaluating the gas hazard for visitors and its potential impact on the protected underground environments, as well as the influence of meteorological and hydrological conditions in driving carbon dioxide accumulations. The analysis of data acquired in the hypogeal atmosphere, and their comparison with analogous epigeal measures, indicates that carbon dioxide accumulation is controlled by a complex interaction among cave topography, meteorological dynamics, gaseous exchanges between groundwaters and the atmosphere, and human fruition. This last factor, under particular conditions, can surprisingly diminishing underground CO2 concentrations.Keywords: groundwater; evaporites; karst; monitoring system; near-real-time data; Sicily; temperature
Colossal Cave Adventure (also known as Adventure or ADVENT) is a text-based adventure game, released in 1976 by developer Will Crowther for the PDP-10 mainframe computer. It was expanded upon in 1977 by Don Woods. In the game, the player explores a cave system rumored to be filled with treasure and gold. The game is composed of dozens of locations, and the player moves between these locations and interacts with objects in them by typing one- or two-word commands which are interpreted by the game's natural language input system. The program acts as a narrator, describing the player's location and the results of the player's attempted actions. It is the first well-known example of interactive fiction, as well as the first well-known adventure game, for which it was also the namesake.
The original game, written in 1975 and 1976, was based on Crowther's maps and experiences caving in Mammoth Cave in Kentucky, the longest cave system in the world; further, it was intended, in part, to be accessible to non-technical players, such as his two daughters. Woods' version expanded the game in size and increased the number of fantasy elements present in it, such as a dragon and magic spells. Both versions, typically played over teleprinters connected to mainframe computers, were spread around the nascent ARPANET, the precursor to the Internet, which Crowther was involved in developing.
Colossal Cave Adventure is a text-based adventure game wherein the player explores a mysterious cave that is rumored to be filled with treasure and gold. The player must explore the cave system and solve puzzles by using items that they find to obtain the treasures and leave the cave. The player types in one- or two-word commands to move their character through the cave system, interact with objects in the cave, pick up items to put into their inventory, and perform other actions. The allowable commands are contextual to the location, or room, the player is in; for example, "get lamp" only has an effect if there is a lamp present. There are dozens of rooms, each of which has a name such as "Debris Room" and a description, and may contain objects or obstacles. The program acts as a narrator, describing to the player their location in the cave and the results of certain actions. If it does not understand the player's commands, it asks for the player to retype their actions.[1] The program's replies are typically in a humorous, conversational tone, much as a Dungeon Master would use in leading players in a tabletop role-playing game.[2]
Colossal Cave Adventure was originally created by William Crowther in 1975 and 1976. Crowther and his ex-wife Patricia were both programmers and cavers and had extensively explored Mammoth Cave in Kentucky, the longest cave system in the world, in the early 1970s as part of the Cave Research Foundation. In 1972, Patricia led the expedition that found a connection between Mammoth Cave and the larger Flint Ridge Cave System. In addition to caving, the pair produced vector map surveys of the cave: they transcribed the survey data of the cave from "muddy little books" into a teleprinter terminal in their house, which could send and print messages from programs running on the central computer and was connected to a PDP-1 mainframe computer at Bolt, Beranek and Newman (BBN) where William Crowther worked. This data was then fed into a program developed by the pair that generated plotting commands onto punched tape, which were then fed into a Honeywell 316 minicomputer attached to a Calcomp drum plotter at BBN to print paper maps. These maps were some of the earliest computer-drawn maps of caves.[4]
In 1975, after he and Patricia divorced, William Crowther stopped caving with the Cave Research Foundation. Driven by what he later described as an increase in spare time combined with missing his two daughters, he began working on a text-based game in Fortran on BBN's PDP-10 mainframe, interfacing through a teletype printer, that they could play.[1][3][5] He combined his memories and maps of the Mammoth Cave system, particularly a 1975 map of the Bedquilt area of the caves, including Colossal Cavern, with elements of the Dungeons & Dragons campaigns that he played with friends to design a game around exploring a cave for treasure.[1][5] Crowther wanted the game to be accessible and not intimidating to non-technical players such as his children, and so developed a natural language input system to control the game so that it would be "a thing that gave you the illusion anyway that you'd typed in English commands and it did what you said".[6] Crowther later commented that this approach allowed the game to appeal to both non-programmers and programmers alike, as in the latter case, it gave programmers a challenge of how to make "an obstinate system" perform in a manner they wanted it to.[6] This approach was also developed to allow the game to be played on a teletype printer, rather than rely on user interface elements used in programs designed for monitors.[3]
One person who discovered the game was Don Woods, a graduate student at Stanford University. Woods found the game on a PDP-10 at the Stanford Medical School and wanted to expand upon the game. He contacted Crowther to gain access to the source code by emailing "crowther" at every domain that existed on the ARPANET.[1][9] Woods built upon Crowther's code, introducing more high fantasy-related elements such as a dragon.[10][11] He changed the puzzles, adding new elements and complexities, and added new puzzles and features such as a pirate that roams the map and steals treasure from the player or objects that could exist in multiple states.[1] He also introduced a scoring system within the game and added ten more treasures to collect in addition to the five in Crowther's original version.[9] According to cavers who have played the game, much of Crowther's original version matches the Bedquilt section of Mammoth Cave with some passages removed for gameplay purposes, though Woods' additions do not as he had never been there.[1][4] According to William Mann, a caving compatriot of Crowther who played both versions when they were developed, Crowther was focused on creating the cave system as a setting for a game, while Woods was interested in making a game and not in replicating the feeling of caving.[1]
Commercial versions of the game were also released. Microsoft published a version titled Microsoft Adventure in 1979 for the Apple II Plus and TRS-80 computers, and again in 1981 for MS-DOS as a launch title for IBM PCs, one of the few software programs and the only game at launch.[19][20] The Software Toolworks released The Original Adventure for IBM PCs in 1981; endorsed by Crowther and Woods in exchange for a nominal payment, it was the only version for which they received any money.[21] Level 9 Computing released multiple versions of the game for different computer platforms under the name Colossal Adventure, beginning with a version in 1982 for the Nascom that includes an entire extra section where the player saves elves from flooding caves, as well as later versions that include pictures of the areas.[22] 2ff7e9595c
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