Landomycins as glutathione-depleting agents and natural fluorescent probes for cellular Michael adduct-dependent quinone metabolism

Landomycins are angucyclines with promising antineoplastic activity produced by Streptomyces bacteria. The aglycone landomycinone is the distinctive core, while the oligosaccharide chain differs within derivatives. Herein, we report that landomycins spontaneously form Michael adducts with biothiols, including reduced cysteine and glutathione, both cell-free or intracellularly involving the benz[a]anthraquinone moiety of landomycinone. While landomycins generally do not display emissive properties, the respective Michael adducts exerted intense blue fluorescence in a glycosidic chain-dependent manner. This allowed label-free tracking of the short-lived nature of the mono-SH-adduct followed by oxygen-dependent evolution with addition of another SH-group. Accordingly, hypoxia distinctly stabilized the fluorescent mono-adduct. While extracellular adduct formation completely blocked the cytotoxic activity of landomycins, intracellularly it led to massively decreased reduced glutathione levels. Accordingly, landomycin E strongly synergized with glutathione-depleting agents like menadione but exerted reduced activity under hypoxia. Summarizing, landomycins represent natural glutathione-depleting agents and fluorescence probes for intracellular anthraquinone-based angucycline metabolism

Solstice: An Electronic Journal of Geography and Mathematics, Volume XI, Number 2

This document was delivered over the internet.The purpose of Solstice is to promote interaction between geography and mathematics. Articles in which elements of one discipline are used to shed light on the other are particularly sought. Also welcome, are original contributions that are purely geographical or purely mathematical. These may be prefaced (by editor or author) with commentary suggesting directions that might lead toward the desired interaction. Contributed articles will be refereed by geographers and/or mathematicians. Invited articles will be screened by suitable members of the editorial board. IMaGe is open to having authors suggest, and furnish material for, new regular features.Peer 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of 2000SolsticeVol11.pdf : Solstice, 2000, Numbers 1 and 2. Contains attachments.Description of SolsticeVolXINo2.pdf : Cover of Journa

Landomycins as Glutathione-Depleting Agents and Natural Fluorescent Probes for Cellular Michael Adduct-Dependent Quinone Metabolism

Landomycins are angucyclines with promising antineoplastic activity produced by Streptomyces bacteria. The aglycone landomycinone is the distinctive core, while the oligosaccharide chain differs within derivatives. Herein, we report that landomycins spontaneously form Michael adducts with biothiols, including reduced cysteine and glutathione, both cell-free or intracellularly involving the benz[a]anthraquinone moiety of landomycinone. While landomycins generally do not display emissive properties, the respective Michael adducts exerted intense blue fluorescence in a glycosidic chain-dependent manner. This allowed label-free tracking of the short-lived nature of the mono-SH-adduct followed by oxygen-dependent evolution with addition of another SH-group. Accordingly, hypoxia distinctly stabilized the fluorescent mono-adduct. While extracellular adduct formation completely blocked the cytotoxic activity of landomycins, intracellularly it led to massively decreased reduced glutathione levels. Accordingly, landomycin E strongly synergized with glutathione-depleting agents like menadione but exerted reduced activity under hypoxia. Summarizing, landomycins represent natural glutathione-depleting agents and fluorescence probes for intracellular anthraquinone-based angucycline metabolism

Developing a sustainability science approach for water systems

We convened a workshop to enable scientists who study water systems from both social science and physical science perspectives to develop a shared language. This shared language is necessary to bridge a divide between these disciplines’ different conceptual frameworks. As a result of this workshop, we argue that we should view socio-hydrological systems as structurally co-constituted of social, engineered, and natural elements and study the “characteristic management challenges” that emerge from this structure and reoccur across time, space, and socioeconomic contexts. This approach is in contrast to theories that view these systems as separately conceptualized natural and social domains connected by bi-directional feedbacks, as is prevalent in much of the water systems research arising from the physical sciences. A focus on emergent characteristic management challenges encourages us to go beyond searching for evidence of feedbacks and instead ask questions such as: What types of innovations have successfully been used to address these challenges? What structural components of the system affect its resilience to hydrological events and through what mechanisms? Are there differences between successful and unsuccessful strategies to solve one of the characteristic management challenges? If so, how are these differences affected by institutional structure and ecological and economic contexts? To answer these questions, social processes must now take center stage in the study and practice of water management. We also argue that water systems are an important class of coupled systems with relevance for sustainability science because they are particularly amenable to the kinds of systematic comparisons that allow knowledge to accumulate. Indeed, the characteristic management challenges we identify are few in number and recur over most of human history and in most geographical locations. This recurrence should allow us to accumulate knowledge to answer the above questions by studying the long historical record of institutional innovations to manage water systems

Social science in a water observing system

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95008/1/wrcr12336.pd

Riparian thermal conditions across a mixed rural and urban landscape

Riparian corridors have the potential to function as thermal refuges, moderating extremes of local temperature variation. However, although demonstrated at individual sites, and over short periods, the consistency of this effect at wider temporal and spatial scales is poorly understood. The aim of this study is to assess the temperature differences between riparian corridors and adjacent non-riparian habitats and to explore the influence of environmental characteristics on these differences. Air temperature was monitored hourly at 20 paired locations (riparian and non-riparian) for two consecutive years. Urban index and canopy cover were characterised by calculating the percentage of impervious surface area and tree canopy cover within a 100 m radius from the centre of each sampling site. Canopy cover reduced summer thermal stresses in both urban and rural areas whereas high urban index tended to increase the daily thermal indices. Rivers had a significant mitigating effect on the urban riparian thermal condition, particularly in extreme hot weather. Riparian corridors were generally 1 °C cooler than non-riparian locations in summer and could be up to 3 °C cooler at some sites in extreme hot weather. Furthermore, riparian corridors at some sites were warmer than non-riparian locations in winter. These findings suggest that the proximity of rivers can modify riparian thermal environments, potentially reducing the heat stress of riparian corridors across landscapes

Seasonal effects of a hydropeaking dam on a downstream benthic macroinvertebrate community

Peer Reviewe