Lithostratigraphy of the Cretaceous–Paleocene Nuussuaq Group, Nuussuaq Basin, West Greenland

The Nuussuaq Basin is the only exposed Cretaceous–Paleocene sedimentary basin in West Greenland and is one of a complex of linked rift basins stretching from the Labrador Sea to northern Baffin Bay. These basins developed along West Greenland as a result of the opening of the Labrador Sea in Late Mesozoic to Early Cenozoic times. The Nuussuaq Basin is exposed in West Greenland between 69°N and 72°N on Disko, Nuussuaq, Upernivik Ø, Qeqertarsuaq, Itsaku and Svartenhuk Halvø and has also been recorded in a number of shallow and deep wells in the region. The sediments are assigned to the more than 6 km thick Nuussuaq Group (new) which underlies the Palaeogene plateau basalts of the West Greenland Basalt Group. The sediment thickness is best estimated from seismic data; in the western part of the area, seismic and magnetic data suggest that the succession is at least 6 km and possibly as much as 10 km thick. The exposed Albian–Paleocene part of the succession testifies to two main episodes of regional rifting and basin development: an Early Cretaceous and a Late Cretaceous – Early Paleocene episode prior to the start of sea-floor spreading in mid-Paleocene time. This exposed section includes fan delta, fluviodeltaic, shelfal and deep marine deposits. The Nuussuaq Group is divided into ten formations, most of which have previously been only briefly described, with the exception of their macrofossil content. In ascending stratigraphic order, the formations are: the Kome Formation, the Slibestensfjeldet Formation (new), the Upernivik Næs Formation, the Atane Formation (including four new members – the Skansen, Ravn Kløft, Kingittoq and Qilakitsoq Members – and one new bed, the Itivnera Bed), the Itilli Formation (new, including four new members, the Anariartorfik, Umiivik, Kussinerujuk and Aaffarsuaq Members), the Kangilia Formation (including the redefined Annertuneq Conglomerate Member and the new Oyster–Ammonite Conglomerate Bed), the Quikavsak Formation (including three new members: the Tupaasat, Nuuk Qiterleq and Paatuutkløften Members), the Agatdal Formation, the Eqalulik Formation (new, including the Abraham Member), and the Atanikerluk Formation (including five members: the Naujât, Akunneq (new), Pingu (new), Umiussat and Assoq (new) Members)

SILAC-MS Based Characterization of LPS and Resveratrol Induced Changes in Adipocyte Proteomics:Resveratrol as Ameliorating Factor on LPS Induced Changes

Adipose tissue inflammation is believed to play a pivotal role in the development obesity-related morbidities such as insulin resistance. However, it is not known how this (low-grade) inflammatory state develops. It has been proposed that the leakage of lipopolysaccharides (LPS), originating from the gut microbiota, through the gut epithelium could drive initiation of inflammation. To get a better understanding of which proteins and intracellular pathways are affected by LPS in adipocytes, we performed SILAC proteomic analysis and identified proteins that were altered in expression. Furthermore, we tested the anti-inflammatory compound resveratrol. A total of 927 proteins were quantified by the SILAC method and of these 57- and 64 were significantly up- and downregulated by LPS, respectively. Bioinformatic analysis (GO analysis) revealed that the upregulated proteins were especially involved in the pathways of respiratory electron transport chain and inflammation. The downregulated proteins were especially involved in protein glycosylation. One of the latter proteins, GALNT2, has previously been described to regulate the expression of liver lipases such as ANGPTL3 and apoC-III affecting lipid metabolism. Furthermore, LPS treatment reduced the protein levels of the insulin sensitizing adipokine, adiponectin, and proteins participating in the final steps of triglyceride- and cholesterol synthesis. Generally, resveratrol opposed the effect induced by LPS and, as such, functioning as an ameliorating factor in disease state. Using an unbiased proteomic approach, we present novel insight of how the proteome is altered in adipocytes in response to LPS as seen in obesity. We suggest that LPS partly exerts its detrimental effects by altering glycosylation processes of the cell, which is starting to emerge as important posttranscriptional regulators of protein expression. Furthermore, resveratrol could be a prime candidate in ameliorating dysfunctioning adipose tissue induced by inflammatory stimulation

The orphan G protein-coupled receptor GPR139 is activated by the peptides:Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW

GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC(50) values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle “similar targets bind similar ligands”, we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca(2+)-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low micromolar range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH(1-9) was found to correspond to the product of a predicted cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH(1-9). Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides

The orphan G protein-coupled receptor GPR139 is activated by the peptides: adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW

GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids L-tryptophan and L-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle "similar targets bind similar ligands”, we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca2+-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low μM range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH1-9 was found to correspond to the product of a predicted cleavage site in the prepro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH1-9. Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides.This work was supported by the Lundbeck Foundation (separate grants to H.B.-O., D.S.P and D.E.G. [R169-2013-16327]), the A. P. Møller Foundation for the Advancement of Science (H.B.-O.), the European Research Council (DE-ORPHAN 639125; DEG), the Carlsberg Foundation (D.S.P.) and The Danish Council for Independent Research (DFF – 1331-00180) and the Wellcome Trust (098497/Z/12/Z), NIHR Biomedical Research Centre, MRC, Bernard Wolfe Endowment and ERC (282374) (I.S.F.

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained