Cell density-induced changes in lipid composition and intracellular trafficking

Cell density is one of the extrinsic factors to which cells adapt their physiology when grown in culture. However, little is known about the molecular changes which occur during cell growth and how cellular responses are then modulated. In many cases, inhibitors, drugs or growth factors used for in vitro studies change the rate of cell proliferation, resulting in different cell densities in control and treated samples. Therefore, for a comprehensive data analysis, it is essential to understand the implications of cell density on the molecular level. In this study, we have investigated how lipid composition changes during cell growth, and the consequences it has for transport of Shiga toxin. By quantifying 308 individual lipid species from 17 different lipid classes, we have found that the levels and species distribution of several lipids change during cell growth, with the major changes observed for diacylglycerols, phosphatidic acids, cholesterol esters, and lysophosphatidylethanolamines. In addition, there is a reduced binding and retrograde transport of Shiga toxin in high density cells which lead to reduced intoxication by the toxin. In conclusion, our data provide novel information on how lipid composition changes during cell growth in culture, and how these changes can modulate intracellular trafficking.     

What are the memory sources of dreaming?

Investigators since Freud have appreciated that memories of the people, places, activities and emotions of daily life are reflected in dreams but are typically so fragmented that their predictability is nil. The mechanisms that translate such memories into dream images remain largely unknown. New research targeting relationships between dreaming, memory and the hippocampus is producing a new theory to explain how, why and when we dream of waking life events.     

A new species of Exitomelita (Amphipoda: Melitidae) from a deep-water wood fall in the northern Norwegian Sea

The recently erected amphipod genus Exitomelita (Tandberg et al., 2012) has so far been found only associated with the deep-water hydrothermal vent field “Loki's Castle” in the Norwegian-Greenland Sea. There it was found on the black smoker chimney walls as well as within fields of the tubeworm Sclerolinum contortum in sulphide- and methane-rich sediments surrounding the vent field. A new species has now been found in a large wood fall of pine at 2800 m depth close to this vent field. This group of amphipods is apparently confined to reduced habitats, and our data support the theory that the vent fauna in this area is closely related to fauna found on cold seeps and wood falls in the northernmost Atlantic and Arctic Oceans. Here we present morphological and molecular data and a short discussion of the habitat of the new species, in addition to a comparison with the previously described species of Exitomelita.http://www.zoobank.org/urn:lsid:zoobank.org:pub:2B0B3CC2-AB6A-4006-83BB-182280CB22B8     

The ether lipid precursor hexadecylglycerol protects against Shiga toxins

Shiga toxin-producing Escherichia coli bacteria cause hemorrhagic colitis and hemolytic uremic syndrome in humans. Currently, only supportive treatment is available for diagnosed patients. We show here that 24-h pretreatment with an ether lipid precursor, the alkylglycerol sn-1-O-hexadecylglycerol (HG), protects HEp-2 cells against Shiga toxin and Shiga toxin 2. Also the endothelial cell lines HMEC-1 and HBMEC are protected against Shiga toxins after HG pretreatment. In contrast, the corresponding acylglycerol, dl-α-palmitin, has no effect on Shiga toxicity. Although HG treatment provides a strong protection (~30 times higher IC₅₀) against Shiga toxin, only a moderate reduction in toxin binding was observed, suggesting that retrograde transport of the toxin from the plasma membrane to the cytosol is perturbed. Furthermore, endocytosis of Shiga toxin and retrograde sorting from endosomes to the Golgi apparatus remain intact, but transport from the Golgi to the endoplasmic reticulum is inhibited by HG treatment. As previously described, HG reduces the total level of all quantified glycosphingolipids to 50–70 % of control, including the Shiga toxin receptor globotriaosylceramide (Gb3), in HEp-2 cells. In accordance with this, we find that interfering with Gb3 biosynthesis by siRNA-mediated knockdown of Gb3 synthase for 24 h causes a similar cytotoxic protection and only a moderate reduction in toxin binding (to 70 % of control cells). Alkylglycerols, including HG, have been administered to humans for investigation of therapeutic roles in disorders where ether lipid biosynthesis is deficient, as well as in cancer therapy. Further studies may reveal if HG can also have a therapeutic potential in Shiga toxin-producing E. coli infections.     

Dissolved organic carbon trends resulting from changes in atmospheric deposition chemistry

Several hypotheses have been proposed to explain recent, widespread increases in concentrations of dissolved organic carbon (DOC) in the surface waters of glaciated landscapes across eastern North America and northern and central Europe. Some invoke anthropogenic forcing through mechanisms related to climate change, nitrogen deposition or changes in land use, and by implication suggest that current concentrations and fluxes are without precedent. All of these hypotheses imply that DOC levels will continue to rise, with unpredictable consequences for the global carbon cycle. Alternatively, it has been proposed that DOC concentrations are returning toward pre-industrial levels as a result of a gradual decline in the sulphate content of atmospheric deposition. Here we show, through the assessment of time series data from 522 remote lakes and streams in North America and northern Europe, that rising trends in DOC between 1990 and 2004 can be concisely explained by a simple model based solely on changes in deposition chemistry and catchment acid-sensitivity. We demonstrate that DOC concentrations have increased in proportion to the rates at which atmospherically deposited anthropogenic sulphur and sea salt have declined. We conclude that acid deposition to these ecosystems has been partially buffered by changes in organic acidity and that the rise in DOC is integral to recovery from acidification. Over recent decades, deposition-driven increases in organic matter solubility may have increased the export of DOC to the oceans, a potentially important component of regional carbon balances. The increase in DOC concentrations in these regions appears unrelated to other climatic factors.