RV POSEIDON Cruise Report POS473 LORELEI II: LOphelia REef Lander Expedition and Investigation II, Tromsø – Bergen – Esbjerg, 15.08. – 31.08. – 04.09.2014

As a result of the raising CO2-emissions and the resultant ocean acidification (decreasing pH and carbonate ion concentration), the impact on marine organism that build their skeletons and protective shells with calcium carbonate (e.g., mollusks, sea urchins, coccolithophorids, and stony corals) becomes more and more detrimental. In the last few years, many experiments with tropical reef building corals have shown, that a lowering of the carbonate ion concentration significantly reduces calcification rates and therefore growth (e.g., Gattuso et al. 1999; Langdon et al. 2000, 2003; Marubini et al. 2001, 2002). In the middle of this century, many tropical coral reefs may well erode faster than they can rebuild. Cold-water corals are living in an environment (high geographical latitude, cold and deep waters) already close to a critical carbonate ion concentration below calcium carbonate dissolves. Actual projections indicate that about 70% of the currently known Lophelia reef structures will be in serious danger until the end of the century (Guinotte et al. 2006). Therefore L. pertusa was cultured at GEOMAR to determine its long-term response to ocean acidification. Our work has revealed that – unexpectedly and controversially to the majority of warm-water corals – this species is potentially able to cope with elevated concentrations of CO2. Whereas short-term (1 week) high CO2 exposure resulted in a decline of calcification by 26-29 % for a pH decrease of 0.1 units and net dissolution of calcium carbonate, L. pertusa was capable to acclimate to acidified conditions in long-term (6 months) incubations, leading to slightly enhanced rates of calcification (Form & Riebesell, 2012). But all these studies were carried out in the laboratory under controlled conditions without considering natural variability and ecosystem interactions with the associated fauna. Moreover, only very little is known about the nutrition (food sources and quantity) of cold-water corals in their natural habitat. In a multifactorial laboratory study during BIOACID phase II we could show that food availability is one of the key drivers that promote the capability of these organisms to withstand environmental pressures such as alterations in the carbonate chemistry and temperature (Büscher, Form & Riebesell, in prep.). To take into account the influences of natural fluctuations and interactions (e.g. bioerosion), we aim to merge in-situ results from the two research cruises POS455 and POS473 with laboratory experimental studies for a comprehensive understanding of likely ecosystem responses under past, present and future environmental conditions

Epithelial Tissues Have Varying Degrees of Susceptibility to KrasG12D-Initiated Tumorigenesis in a Mouse Model

Activating mutations in the Kras gene are commonly found in some but not all epithelial cancers. In order to understand the susceptibility of different epithelial tissues to Kras-induced tumorigenesis, we introduced one of the most common Kras mutations, KrasG12D, broadly in epithelial tissues. We used a mouse model in which the G12D mutation is placed in the endogenous Kras locus controlled by inducible, Cre-mediated recombination in tissues expressing cytokeratin 19 including the oral cavity, GI tract, lungs, and ducts of the liver, kidney, and the pancreas. Introduction of the KrasG12D mutation in adult mouse tissues led to neoplastic changes in some but not all of these tissues. Notably, many hyperplasias, metaplasias and adenomas were observed in the oral cavity, stomach, colon and lungs, suggesting that exposure to products of the outside environment promotes KrasG12D-initiated tumorigenesis. However, environmental exposure did not consistently correlate with tumor formation, such as in the small intestine, suggesting that there are also intrinsic differences in susceptibility to Kras activation. The pancreas developed small numbers of mucinous metaplasias with characteristics of early stage pancreatic intraepithelial neoplasms (PanINs), supporting the hypothesis that pancreatic ducts have the potential to give rise pancreatic cancer

A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention.

We show that BRAF(V600E) initiates an alternative pathway to colorectal cancer (CRC), which progresses through a hyperplasia/adenoma/carcinoma sequence. This pathway underlies significant subsets of CRCs with distinctive pathomorphologic/genetic/epidemiologic/clinical characteristics. Genetic and functional analyses in mice revealed a series of stage-specific molecular alterations driving different phases of tumor evolution and uncovered mechanisms underlying this stage specificity. We further demonstrate dose-dependent effects of oncogenic signaling, with physiologic Braf(V600E) expression being sufficient for hyperplasia induction, but later stage intensified Mapk-signaling driving both tumor progression and activation of intrinsic tumor suppression. Such phenomena explain, for example, the inability of p53 to restrain tumor initiation as well as its importance in invasiveness control, and the late stage specificity of its somatic mutation. Finally, systematic drug screening revealed sensitivity of this CRC subtype to targeted therapeutics, including Mek or combinatorial PI3K/Braf inhibition

gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis

Although gastrointestinal cancers are frequently associated with chronic inflammation, the underlying molecular links have not been comprehensively deciphered. Using loss- and gain-of-function mice in a colitis-associated cancer model, we establish here a link comprising the gp130/Stat3 transcription factor signaling axis. Mutagen-induced tumor growth and multiplicity are reduced following intestinal epithelial cell (IEC)-specific Stat3 ablation, while its hyperactivation promotes tumor incidence and growth. Conversely, IEC-specific Stat3 deficiency enhances susceptibility to chemically induced epithelial damage and subsequent mucosal inflammation, while excessive Stat3 activation confers resistance to colitis. Stat3 has the capacity to mediate IL-6- and IL-11-dependent IEC survival and to promote proliferation through G1 and G2/M cell-cycle progression as the common tumor cell-autonomous mechanism that bridges chronic inflammation to tumor promotion

A complex secretory program orchestrated by the inflammasome controls paracrine senescence

Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15INK4b and p21CIP1. Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo

Basalt Features Observed in Outcrops, Cores, Borehole Video Imagery and Geophysical Logs, and Basalt Hydrogeologic Study at the Idaho National Engineering Laboratory, Eastern Idaho

A study was undertaken to examine permeable zones identified in boreholes open to the underlying basalt and to describe the vertical cross flows present in the boreholes. To understand the permeable zones in the boreholes detailed descriptions and measurements of three outcrops in the Snake River Plain, three cores at the Idaho Chemical Processing Plant (ICPP) at the INEL, and over fifty borehole TV logs from the INEL were carried out. Based on the observations made on the three outcrops an idealized basalt lava flow model was generated that used a set of nomenclature that would be standard for the basalt lava flows studied. An upper vesicular zone, a sometimes absent columnar zone, central zone, and lower vesicular zone make up the basalt lava flow model. The overall distinction between the different zones are based on the vesicle shape size, vesicularity, and fractures present. The results of the studies also indicated that the basalt lava flows at the INEL are distal to medial facies pahoehoe lava flows with close fitting contacts. The most permeable zones identified in these basalts are fractured vesiculated portions of the top of the lava flow, the columnar areas, and basalt-flow contacts in order of importance. This was determined from impeller flowmeter logging at the INEL. Having this information a detailed stratigraphy of individual basalt lava flows and the corresponding permeable units were generated. From this it was concluded that groundwater flow at the ICPP prefers to travel along thin basalt lava flows or flow-units. Flow direction and velocity of intrawell flows detected by flowmeter is controlled by a nearby pumping well

Sexuality in Males With Congenital Adrenal Hyperplasia Resulting From 21-Hydroxylase Deficiency

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