The role of 44-methylgambierone in ciguatera fish poisoning: Acute toxicity, production by marine microalgae and its potential as a biomarker for Gambierdiscus spp.

Ciguatera fish poisoning (CFP) is prevalent around the tropical and sub-tropical latitudes of the world and impacts many Pacific island communities intrinsically linked to the reef system for sustenance and trade. While the genus Gambierdiscus has been linked with CFP, it is commonly found on tropical reef systems in microalgal assemblages with other genera of toxin-producing, epiphytic and/or benthic dinoflagellates - Amphidinium, Coolia, Fukuyoa, Ostreopsis and Prorocentrum. Identifying a biomarker compound that can be used for the early detection of Gambierdiscus blooms, specifically in a mixed microalgal community, is paramount in enabling the development of management and mitigation strategies. Following on from the recent structural elucidation of 44-methylgambierone, its potential to contribute to CFP intoxication events and applicability as a biomarker compound for Gambierdiscus spp. was investigated. The acute toxicity of this secondary metabolite was determined by intraperitoneal injection using mice, which showed it to be of low toxicity, with an LD50 between 20 and 38 mg kg-1. The production of 44-methylgambierone by 252 marine microalgal isolates consisting of 90 species from 32 genera across seven classes, was assessed by liquid chromatography-tandem mass spectrometry. It was discovered that the production of this secondary metabolite was ubiquitous to the eight Gambierdiscus species tested, however not all isolates of G. carpenteri, and some species/isolates of Coolia and Fukuyoa

Identification and structure elucidation of epoxyjanthitrems from Lolium perenne infected with the endophytic fungus Epichloë festucae var. lolii and determination of the tremorgenic and anti-insect activity of epoxyjanthitrem I.

Epoxyjanthitrems I-IV (1-4) and epoxyjanthitriol (5) were isolated from seed of perennial ryegrass (Lolium perenne) infected with the endophytic fungus Epichloë festucae var. lolii. Although structures for epoxyjanthitrems I-IV have previously been proposed in the literature, this is the first report of a full structural elucidation yielding NMR (Nuclear magnetic resonance) assignments for all five epoxyjanthitrem compounds, and additionally, it is the first isolation of epoxyjanthitriol (5). Epoxyjanthitrem I induced tremors in mice and gave a dose dependent reduction in weight gain and feeding for porina (Wiseana cervinata), a common pasture pest in New Zealand. These data suggest that epoxyjanthitrems are involved in the observed effects of the AR37 endophyte on livestock and insect pests

How mohallas were formed: Typology of mohallas from the viewpoint of spatial formation and the urbanization process in Varanasi, India

The Japanese version of this paper was published in Volume 73, Number 623, pages 153‐160, https://doi.org/10.3130/aija.73.153 of the Journal of Architecture and Planning (Transactions of AIJ) . The authors have obtained permission for secondary publication of the English version in another journal from the editor of the Journal of Architecture and Planning (Transactions of AIJ) . This paper is based on the translation of the Japanese version, with some slight modifications. Correction following the first Japanese version publication: In order to clarify the argument, Figure 9 has been added and the section discussing block formation has been omitted.This paper focuses upon some mohallas in Varanasi's old urban area. The mohalla is a traditional neighborhood unit common in North Indian cities. Mohallas were elemental components of the city in the Mughal period as administrative tax units as well as autonomous organizations. Currently, however, they have lost their administrative meaning, and their geographical extent and boundaries are becoming unclear. Based on field surveys, this paper reveals features of the spatial formation of mohallas such as size, boundary form, distribution of facilities, and street pattern, and links them to the historical urbanization process of the city. Mohallas in Varanasi can be broadly classified into two types. One has a linear or tree shape along streets, and the other has a broad territorial shape. The spatial features of those two types are different in various aspects and reflect the degree of urbanization at the time when the mohallas were established

Lagunamides A and B : cytotoxic and antimalarial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula

Lagunamides A (1) and B (2) are new cyclic depsipeptides isolated from the marine cyanobacterium Lyngbya majuscula obtained from Pulau Hantu Besar, Singapore. The planar structural characterization of these molecules was achieved by extensive spectroscopic analysis, including 2D NMR experiments. In addition to Marfey's method and (3)J(H-H) coupling constant values, a modified method based on Mosher's reagents and analysis using LC-MS was deployed for the determination of the absolute configuration. Lagunamides A and B displayed significant antimalarial properties, with IC(50) values of 0.19 and 0.91 muM, respectively, when tested against Plasmodium falciparum. Lagunamides A and B also possessed potent cytotoxic activity against P388 murine leukemia cell lines, with IC(50) values of 6.4 and 20.5 nM, respectively. Furthermore, these cyanobacterial compounds exhibited moderate antiswarming activities when tested against Pseudomonas aeruginosa PA0

Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula

Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar, Singapore. The complete structural characterization of the molecule was achieved by extensive NMR spectroscopic analysis as well as chemical manipulations. Several methods, including the advanced Marfey's method, a modified method based on derivatization with Mosher's reagents and analysis using LC-MS, and the use of (3)J(H-H) coupling constant values, were utilized for the determination of its absolute configuration. Compound 1 is related to the aurilide-class of molecules and it differs mainly in the macrocyclic structure by having a 27 membered ring system due to additional methylene carbon in the polyketide moiety. Lagunamide C displayed potent cytotoxic activity against a panel of cancer cell lines, such as P388, A549, PC3, HCT8, and SK-OV3 cell lines, with IC(50) values ranging from 2.1nM to 24.4nM. Compound 1 also displayed significant antimalarial activity with IC(50) value of 0.29muM when tested against Plasmodium falciparum. In addition, lagunamide C exhibited weak anti-swarming activity when tested at 100ppm against the Gram-negative bacterial strain, Pseudomonas aeruginosa PA0

Acute Toxicity of Gambierone and Quantitative Analysis of Gambierones Produced by Cohabitating Benthic Dinoflagellates

Understanding the toxicity and production rates of the various secondary metabolites produced by Gambierdiscus and cohabitating benthic dinoflagellates is essential to unravelling the complexities associated with ciguatera poisoning. In the present study, a sulphated cyclic polyether, gambierone, was purified from Gambierdiscus cheloniae CAWD232 and its acute toxicity was determined using intraperitoneal injection into mice. It was shown to be of low toxicity with an LD50 of 2.4 mg/kg, 9600 times less toxic than the commonly implicated Pacific ciguatoxin-1B, indicating it is unlikely to play a role in ciguatera poisoning. In addition, the production of gambierone and 44-methylgambierone was assessed from 20 isolates of ten Gambierdiscus, two Coolia and two Fukuyoa species using quantitative liquid chromatography–tandem mass spectrometry. Gambierone was produced by seven Gambierdiscus species, ranging from 1 to 87 pg/cell, and one species from each of the genera Coolia and Fukuyoa, ranging from 2 to 17 pg/cell. The production of 44-methylgambierone ranged from 5 to 270 pg/cell and was ubiquitous to all Gambierdiscus species tested, as well as both species of Coolia and Fukuyoa. The relative production ratio of these two secondary metabolites revealed that only two species produced more gambierone, G. carpenteri CAWD237 and G. cheloniae CAWD232. This represents the first report of gambierone acute toxicity and production by these cohabitating benthic dinoflagellate species. While these results demonstrate that gambierones are unlikely to pose a risk to human health, further research is required to understand if they bioaccumulate in the marine food web