Metabolites of the new Caledonian sponge Cladocroce incurvata

The deep-water New Caledonian sponge #Cladocroce incurvata$ contains two "polyketide" metabolites. Cladocrocin A (1) appears to be derived from fatty acid with ethyl side chains, thus incorporating butyrate units. Cladocroic acid (2) is a straight chain fatty acid which incorporates a terminal enyne functionality and a cycloproprane ring directly attached to the carboxylic acid function. The structures were elucidated by interpretation of spectral data, and the cis stereochemistry of the cyclopropane ring in cladocroic acid (2) was derived after the synthesis of cis - and trans - 2, 3 - methanohexanoic acid models and nmr spectral comparisons. (Résumé d'auteur

GLP-1 Mediates Regulation of Colonic ACE2 Expression by the Bile Acid Receptor GPBAR1 in Inflammation

Background & Aims: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. Methods: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn’s disease (CD) patients and three mouse models of colitis and Gpbar1−/− mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. Results: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. Conclusions: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α-and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2

Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction

The severe acute respiratory syndrome (SARS)-CoV-2 is the pathogenetic agent of Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE)2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV-2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of Ace2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin activates the Aryl hydrocarbon Receptor (AHR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent TNBS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of Ace2 mRNA expression. Colon levels of Ace2 mRNA were directly correlated with Tnf-α mRNA levels. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV-2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV-2 Spike protein to ACE2 and reduces the SARS-CoV-2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner

Structural and Functional Loss in Restored Wetland Ecosystems

In restored wetland ecosystems with apparently natural hydrology and biological structure, biogeochemical function may remain degraded, even a century after restoration efforts

Financial instrument disclosure in the Italian banking sector. a study on the value relevance of IFRS 7

This paper focuses on the issue of the relevance of financial instruments’ disclosure in the banking sector, considered as a topic of crucial importance especially after the recent financial crisis. Namely, this paper aims to test whether information required by IFRS 7 is value relevant for investors in order to support them in assigning appropriate risk levels in their investment decisions. The regulatory framework of bank’ financial risks is complex since it is formulated by a range of different bodies, including the Basel Committee, the IASB, the National Banking Supervisor and local accounting standards. Literature, however, argues for the incompleteness of such framework. This incompleteness is one of the premises for IFRS 7. The sample consists of the annual reports of all Italian listed banks over a 7-year period, 2007– 2013. To provide some first results, we have used an OLS model. We expect to provide valuable evidence that banks complying with IFRS 7 are rewarded with higher evaluation by the market. Results confirm our expectations, showing a positive association between banks’ value and the financial index disclosure. Our evidence contributes to the value relevance literature and brings useful insights to investors and regulators

Knowledge, innovation, and control towards accountability: a comparative case study

to deepen the countervailing relationship between control and innovation in knowledge-intensive complex organizations. The study adopts a middle range theory perspective (Broadbent and Laughlin, 2013) to explore how control systems and innovation dynamics interact and shape each other in the contexts of high complexity and intensive knowledge creation

Financial instruments disclosure. A study on the value relevance of IFRS 7

This paper focuses on the relevance of financial instruments’ disclosure in the banking sector, considered as a topic of crucial importance especially after the recent financial crisis. Namely, this paper aims to test whether information required by IFRS 7 is value relevant for investors in order to support them in assigning appropriate risk levels in their investment decisions. The regulatory framework of bank’ financial risks is complex since it is formulated by a range of different bodies. Literature, however, argues for the incompleteness of such framework. This incompleteness is one of the premises for IFRS 7. The sample consists of all Italian listed banks over a 7-year period, 2007–2013. Results confirm our expectations, showing a positive association between banks’ value and the financial index disclosure