Tracing tetraether lipids from source to sink in the Rhône River system (NW Mediterranean)

In this study, we investigated soils and river suspended particulate matter (SPM) collected in the Rhône and its tributary basins as well as marine surface sediments taken in the Rhône prodelta (Gulf of Lions, NW Mediterranean). Thereby, we traced the signal of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from the source to sink via the Rhône River and its tributaries and identified sources of brGDGTs in rivers and marine sediments. Soil pH rather than the mean annual air temperature (MAAT) explains most of the observed variances of the brGDGT distribution in our soil dataset. The observed changes in the distribution of brGDGTs in the river SPM indicate that brGDGTs brought by the river to the sea are primarily derived from the lower Rhône and its tributary soils, even though in situ production in the river itself cannot be excluded. In marine surface sediments, it appears that the input of riverine brGDGTs is the primary source of brGDGTs in the Rhône prodelta, although the brGDGT composition may be further modified by the in situ production in the marine environment. More work is required to assess fully whether brGDGTs can be used to reconstruct the terrestrial paleoenvironmental changes using marine sediment cores taken in the Rhône prodelta close to the river mouth

Localisation of somatostatin and somatostatin receptors in benign and malignant ovarian tumours

Somatostatin has been identified as having anti-proliferative, anti-angiogenic and pro-apoptotic actions in many tumour systems, and these effects are mediated through a family of five transmembrane G-protein coupled SRIF receptors. Ovarian cancer is the commonest gynaecological malignancy in the UK and maintenance therapy is urgently required. Native somatostatin expression and its receptors sst1,2,3 and 5 were studied with immunohistochemistry in 63 malignant and 35 benign ovarian tumours of various histological types. Fifty-seven out of 63 (90%) of malignant and 26/35 (74%) benign tumours expressed somatostatin. Receptors sst1,2,3 and 5 were expressed variably in epithelial, vascular and stromal compartments for both benign and malignant tumours. Somatostatin was found to correlate significantly with stromal sst1 (P=0.008), epithelial sst1 (P<0.001), stromal sst2 (P=0.019), vascular sst2 (P=0.026), epithelial sst3 (P=0.026), stromal sst5 (P=0.013) and vascular sst5 (P=0.038). Increased expression of native somatostatin correlating with somatostatin receptors in malignant ovarian tumours raises the possibility that either synthetic somatostatin antagonists or receptor agonists may have therapeutic potential

Treatment of advanced pancreatic cancer with the long-acting somatostatin analogue lanreotide: in vitro and in vivo results

Fourteen patients with metastatic pancreatic adenocarcinoma were treated with the long-acting somatostatin (SST) analogue lanreotide. No objective response was obtained, and the median survival was 4 months (range 1.8–7 months). Pancreatic cancer could not be visualized by means of SST-receptor (R) scintigraphy in our patients. In vitro data also demonstrated absence of SSTR2 expression, suggesting pancreatic cancer not to be a potential target for treatment with SST analogues. © 1999 Cancer Research Campaig

Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors

Promoter Hypermethylation-Related Reduced Somatostatin Production Promotes Uncontrolled Cell Proliferation in Colorectal Cancer.

BACKGROUND: Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line. METHODS: Colonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n3 = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n1 = 6; n2 = 6; n3 = 6) and independent samples ((n1 = 6; n2 = 6; n3 = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n1 = 14; n2 = 20; n3 = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n1 = 5; n2 = 5; n3 = 9) was defined using methylation-sensitive restriction enzyme digestion. RESULTS: In case of normal aging SST mRNA expression did not alter, but decreased in cancer (p<0.05). The ratio of SST immunoreactive cells was significantly higher in children (0.70%+/-0.79%) compared to CRC (0%+/-0%) (p<0.05). Octreotide significantly increased the proportion of apoptotic Caco-2 cells. SST showed significantly higher methylation level in tumor samples (30.2%+/-11.6%) compared to healthy young individuals (3.5%+/-1.9%) (p<0.05). CONCLUSIONS: In cancerous colonic mucosa the reduced SST production may contribute to the uncontrolled cell proliferation. Our observation that in colon cancer cells octreotide significantly enhanced cell death and attenuated cell proliferation suggests that SST may act as a regulator of epithelial cell kinetics. The inhibition of SST expression in CRC can be epigenetically regulated by promoter hypermethylation

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features

Sedimentation and Fouling of Optical Surfaces at the ANTARES Site

ANTARES is a project leading towards the construction and deployment of a neutrino telescope in the deep Mediterranean Sea. The telescope will use an array of photomultiplier tubes to detect the Cherenkov light emitted by muons resulting from the interaction with matter of high energy neutrinos. In the vicinity of the deployment site the ANTARES collaboration has performed a series of in-situ measurements to study the change in light transmission through glass surfaces during immersions of several months. The average loss of light transmission is estimated to be only ~2% at the equator of a glass sphere one year after deployment. It decreases with increasing zenith angle, and tends to saturate with time. The transmission loss, therefore, is expected to remain small for the several year lifetime of the ANTARES detector whose optical modules are oriented downwards. The measurements were complemented by the analysis of the ^{210}Pb activity profile in sediment cores and the study of biofouling on glass plates. Despite a significant sedimentation rate at the site, in the 0.02 - 0.05 cm.yr^{-1} range, the sediments adhere loosely to the glass surfaces and can be washed off by water currents. Further, fouling by deposits of light-absorbing particulates is only significant for surfaces facing upwards.Comment: 18 pages, 14 figures (pdf), submitted to Astroparticle Physic