Centriole movements in mammalian epithelial cells during cytokinesis

<p>Abstract</p> <p>Background</p> <p>In cytokinesis, when the cleavage furrow has been formed, the two centrioles in each daughter cell separate. It has been suggested that the centrioles facilitate and regulate cytokinesis to some extent. It has been postulated that termination of cytokinesis (abscission) depends on the migration of a centriole to the intercellular bridge and then back to the cell center. To investigate the involvement of centrioles in cytokinesis, we monitored the movements of centrioles in three mammalian epithelial cell lines, HeLa, MCF 10A, and the p53-deficient mouse mammary tumor cell line KP-7.7, by time-lapse imaging. Centrin1-EGFP and α-Tubulin-mCherry were co-expressed in the cells to visualize respectively the centrioles and microtubules.</p> <p>Results</p> <p>Here we report that separated centrioles that migrate from the cell pole are very mobile during cytokinesis and their movements can be characterized as 1) along the nuclear envelope, 2) irregular, and 3) along microtubules forming the spindle axis. Centriole movement towards the intercellular bridge was only seen occasionally and was highly cell-line dependent.</p> <p>Conclusions</p> <p>These findings show that centrioles are highly mobile during cytokinesis and suggest that the repositioning of a centriole to the intercellular bridge is not essential for controlling abscission. We suggest that centriole movements are microtubule dependent and that abscission is more dependent on other mechanisms than positioning of centrioles.</p

Oral Lichen Planus and Mutated <i>TP53</i>—A Road to Cancer?

The malignant potential of oral lichen planus (OLP) has been discussed and disputed for decades. The lesions are often characterized by strong expression of the TP53 protein in the basal layer of the mucosa. In 2002, we reported the presence of TP53 mutations in nine out of 27 OLP lesions tested. At follow-up in 2009, one case of oral squamous cell cancer (OSCC) had occurred in a different site six years later. In contrast, in another case, TP53 mutation persisted for years without malignant transformation. In a longitudinal study of eight selected patients with OSCC or different pre-malignant lesions, it was concluded that TP53 mutations could occur early or late in the development of OSCC. A follow-up in the present, almost 20 years later, revealed that one further case of OSCC had occurred in a TP53-mutated case of OLP, 21 years after the first sample was taken, again in a different site. With this second case, this small study now points towards a risk of developing OSCC in TP53-mutated OLP lesions. A review of recent literature indicates a growing consensus that OLP should be regarded as a potentially pre-malignant lesion. Several protein markers have been studied, but none proved useful for prediction of malignant progression. The great majority of published studies are retrospective, and it has been suggested that multi-centre prospective studies will be needed to reach a definitive answer on the malignant potential of OLP, and particularly, to identify contributing factors. Screening for TP53 mutations could help to identify the subgroup of OLP patients that is truly at risk of developing oral cancer

Biodiversity of benthic invertebrates and bioprospecting in Icelandic waters

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Iceland is an island in the North Atlantic Ocean, with an exclusive economic zone of 200 nautical miles that is largely unexplored with respect to chemical constituents of the marine biota. Iceland is a geothermally active area and hosts both hot and cold adapted organisms on land and in the ocean around it. In particular, the confluence of cold and warm water masses and geothermal activity creates a unique marine environment that has not been evaluated for the potential of marine natural product diversity. Marine organisms need to protect themselves from other organisms trying to overgrow, and some need to secure their place on the bottom of the ocean. Unexplored and unique areas such as the hydrothermal vent site at the sea floor in Eyjafjordur are of particular interest. In 1992 a collaborative research programme on collecting and identifying benthic invertebrates around Iceland (BIOICE) was established, with participation of Icelandic and foreign institutes, universities and taxonomists on benthic invertebrates from all over the world. Since the programme started almost 2,000 species have been identified and of those 41 species are new to science. Our recent bioprospecting project is directed towards the first systematic investigation of the marine natural product diversity of benthic invertebrates occurring in Icelandic waters, and their potential for drug-lead discovery in several key therapeutic areas.Univ Iceland, Sch Hlth Sci, Fac Pharmaceut Sci, IS-107 Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 2 ] Univ Iceland, Sch Hlth Sci, Fac Med, IS-101 Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 3 ] Landspitali Univ Hosp, Ctr Rheumatol Res, IS-101 Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 4 ] Landspitali Univ Hosp, Dept Immunol, IS-101 Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 5 ] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA Show the Organization-Enhanced name(s) [ 6 ] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA Show the Organization-Enhanced name(s) [ 7 ] Univ Iceland, Sch Engn & Nat Sci, Fac Life & Environm Sci, IS-101 Reykjavik, Icelan

Metabolic Profiling as a Screening Tool for Cytotoxic Compounds: Identification of 3-Alkyl Pyridine Alkaloids from Sponges Collected at a Shallow Water Hydrothermal Vent Site North of Iceland

Twenty-eight sponge specimens were collected at a shallow water hydrothermal vent site north of Iceland. Extracts were prepared and tested in vitro for cytotoxic activity, and eight of them were shown to be cytotoxic. A mass spectrometry (MS)-based metabolomics approach was used to determine the chemical composition of the extracts. This analysis highlighted clear differences in the metabolomes of three sponge specimens, and all of them were identified as Haliclona (Rhizoniera) rosea (Bowerbank, 1866). Therefore, these specimens were selected for further investigation. Haliclona rosea metabolomes contained a class of potential key compounds, the 3-alkyl pyridine alkaloids (3-APA) responsible for the cytotoxic activity of the fractions. Several 3-APA compounds were tentatively identified including haliclamines, cyclostellettamines, viscosalines and viscosamines. Among these compounds, cyclostellettamine P was tentatively identified for the first time by using ion mobility MS in time-aligned parallel (TAP) fragmentation mode. In this work, we show the potential of applying metabolomics strategies and in particular the utility of coupling ion mobility with MS for the molecular characterization of sponge specimens