Podoplanin drives dedifferentiation and amoeboid invasion of melanoma

Melanoma is an aggressive skin cancer developing from melanocytes, frequently resulting in metastatic disease. Melanoma cells utilize amoeboid migration as mode of local invasion. Amoeboid invasion is characterized by rounded cell morphology and high actomyosin contractility driven by Rho GTPase signalling. Migrastatic drugs targeting actin polymerization and contractility are therefore a promising treatment option for metastatic melanoma. To predict amoeboid invasion and metastatic potential, biomarkers functionally linked to contractility pathways are needed. The glycoprotein podoplanin drives actomyosin contractility in lymphoid fibroblasts and is overexpressed in many cancers. We show that podoplanin enhances amoeboid invasion in melanoma. Podoplanin expression in murine melanoma drives rounded cell morphology, increasing motility, and invasion in vivo. Podoplanin expression is increased in a subset of dedifferentiated human melanoma, and in vitro is sufficient to upregulate melanoma-associated marker Pou3f2/Brn2. Together, our data define podoplanin as a functional biomarker for dedifferentiated invasive melanoma and a promising migrastatic therapeutic target

The Potent Respiratory System of Osedax mucofloris (Siboglinidae, Annelida) - A Prerequisite for the Origin of Bone-Eating Osedax?

Members of the conspicuous bone-eating genus, Osedax, are widely distributed on whale falls in the Pacific and Atlantic Oceans. These gutless annelids contain endosymbiotic heterotrophic bacteria in a branching root system embedded in the bones of vertebrates, whereas a trunk and anterior palps extend into the surrounding water. The unique life style within a bone environment is challenged by the high bacterial activity on, and within, the bone matrix possibly causing O2 depletion, and build-up of potentially toxic sulphide. We measured the O2 distribution around embedded Osedax and showed that the bone microenvironment is anoxic. Morphological studies showed that ventilation mechanisms in Osedax are restricted to the anterior palps, which are optimized for high O2 uptake by possessing a large surface area, large surface to volume ratio, and short diffusion distances. The blood vascular system comprises large vessels in the trunk, which facilitate an ample supply of oxygenated blood from the anterior crown to a highly vascularised root structure. Respirometry studies of O. mucofloris showed a high O2 consumption that exceeded the average O2 consumption of a broad line of resting annelids without endosymbionts. We regard this combination of features of the respiratory system of O. mucofloris as an adaptation to their unique nutrition strategy with roots embedded in anoxic bones and elevated O2 demand due to aerobic heterotrophic endosymbionts

The consequences of niche and physiological differentiation of archaeal and bacterial ammonia oxidisers for nitrous oxide emissions

The authors are members of the Nitrous Oxide Research Alliance (NORA), a Marie Skłodowska-Curie ITN and research project under the EU's seventh framework program (FP7). GN is funded by the AXA Research Fund and CGR by a Royal Society University Research Fellowship (UF150571) and a Natural Environment Research Council (NERC) Standard Grant (NE/K016342/1). The authors would like to thank Dr Robin Walker and the SRUC Craibstone Estate (Aberdeen) for access to the agricultural plots, Dr Alex Douglas for statistical advice and Philipp Schleusner for assisting microcosm construction and sampling.Peer reviewedPublisher PD

Enrichment and characterization of ammonia-oxidizing archaea from the open ocean : phylogeny, physiology and stable isotope fractionation

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 5 (2011): 1796–1808, doi:10.1038/ismej.2011.58.Archaeal genes for ammonia oxidation are widespread in the marine environment, but direct physiological evidence for ammonia oxidation by marine archaea is limited. We report the enrichment and characterization of three strains of pelagic ammonia-oxidizing archaea (AOA) from the north Pacific Ocean that have been maintained in laboratory culture for over three years. Phylogenetic analyses indicate the three strains belong to a previously identified clade of water column-associated AOA and possess 16S rRNA genes and ammonia monooxygenase subunit a (amoA) genes highly similar (98-99% identity) to those recovered in DNA and cDNA clone libraries from the open ocean. The strains grow in natural seawater-based liquid medium while stoichiometrically converting ammonium (NH4 +) to nitrite (NO2 -). Ammonia oxidation by the enrichments is only partially inhibited by allylthiourea at concentrations known to inhibit cultivated ammonia-oxidizing bacteria. The three strains were used to determine the nitrogen stable isotope effect (15εNH3) during archaeal ammonia oxidation, an important parameter for interpreting stable isotope ratios in the environment. Archaeal 15εNH3 ranged from 13- 41‰, within the range of that previously reported for ammonia-oxidizing bacteria. Despite low amino acid identity between the archaeal and bacterial Amo proteins, their functional diversity as captured by 15εNH3 is similar.This work was supported by a Woods Hole Oceanographic Institution (WHOI) Postdoctoral Scholar fellowship to AES and the WHOI Ocean Life Institute

Incorporation of dietary trans monounsaturated fatty acids into tissues of Walker 256 tumor-bearing rats

The correlation between dietary trans fatty acids and neoplasia was examined in the present study. Walker 256 tumor-bearing and control rats were fed a trans monounsaturated fatty acid (MUFA)-rich diet for 8 weeks and the incorporation of trans fatty acids by tumor tissue was examined. Also, the effect of tumor growth on trans fatty acid composition of plasma and liver, and the content of thiobarbituric acid-reactive substances (TBARS) was determined. Walker 256 tumor cells presented both trans and cis MUFAs given in the diet. The equivalent diet proportions were 0.66 for trans and 1.14 for cis. Taking into consideration the proportion of trans MUFAs in plasma (11.47%), the tumor incorporated these fatty acids in a more efficient manner (18.27%) than the liver (9.34%). Therefore, the dietary trans fatty acids present in the diet are actively incorporated by the tumor. Tumor growth itself caused marked changes in the proportion of polyunsaturated fatty acids in the plasma and liver but provoked only slight modifications in both trans and cis MUFAs. Tumor growth also reduced the unsaturation index in both plasma and liver, from 97.79 to 86.83 and from 77.51 to 69.64, respectively. This effect was partially related to an increase in the occurrence of the lipid oxidation/peroxidation process of TBARS content which was increased in both plasma (from 0.428 to 0.505) and liver (from 9.425 to 127.792) due to tumor growth