Let’s talk about risk! : Stock market effects of risk disclosure for European energy utilities

We analyze how risk reporting by European energy utilities is related to uncertainty about firms’ future prospects. Using an unsupervised machine learning topic model, we classify the content of the risk reports presented in the notes to the financial statements into different risk topics over the period from 2007 to 2017. We find that more risk reporting is related to lower idiosyncratic volatility and that this relation is especially evident for reporting about credit risk, risk management processes, economic risk, and accounting-related risk. We also find that the uncertainty-decreasing effect of risk disclosure extends to a positive relation between risk disclosure and firm value. Our study contributes to the call for more transparency in risk reporting and disclosure. Interestingly, we are unable to identify a climate-related risk topic, and further tests show only a rudimentary disclosure of climate-related risks. Combining the usefulness of the current risk disclosure regulation with the current lack of climate-related risk disclosures, we see good reasons for increased mandatory climate-related risk disclosures

Die membranproximale Domäne von ADAM17 - Ein Schlüssel zur Regulation der Proteaseaktivität

Ektodomänen-Shedding stellt eine irreversible, posttranslationale Modifikation dar, die unter anderem zur Freisetzung von biologisch aktiven Ektodomänen führt. A Disintegrin And Metalloprotease 17 (ADAM17) ist mit über 80 Substraten eine, für physiologische Prozesse wie Entzündungsreaktionen oder Regenerationsprozesse, wichtige Sheddase. Trotz der bedeutenden Rolle von ADAM17 ist bis heute nur wenig über die Regulation ihrer Shedding-Aktivität bekannt. In früheren Studien wurde gezeigt, dass extrazelluäre Proteindisulfidisomerasen (PDIs) mit ADAM17 interagieren und eine strukturelle Änderung innerhalb der Ektodomäne von ADAM17 herbeiführen. Dies hat eine Inaktivierung von ADAM17 zur Folge. In dieser Arbeit wurde gezeigt, dass die PDIs mit der membranproximalen Domäne von ADAM17 (MPD17) interagieren und diese durch die Isomerisierung zweier Disulfidbrücken von einer offenen in eine geschlossene Form überführen. Dabei liegt im aktiven ADAM17 die offene, flexible MPD17 vor, während im inaktiven Zustand die MPD17 die geschlossene Form einnimmt. Der Wechsel von der offenen zu der geschlossenen Form reguliert CANDIS (Conserved ADAM-SeventeeN Dynamic Interaction Sequence), ein hochkonservierter Bereich innerhalb der Stalk-Region von ADAM17, der in der Lage ist die beiden Substrate IL-6R und IL-1RII zu binden. Nur wenn die MPD17 in der offenen Form vorliegt, werden diese Substrate von CANDIS gebunden. Die geschlossene MPD17 verhindert hingegen den Zugang der Substrate zu CANDIS. Neue Daten zeigen, dass das ADAM17-vermittelte Shedding-Ereignis durch eine transiente Phosphatidylserin-Translokation ausgelöst wird. In dieser Arbeit wurde in diesem Zusammenhang geklärt, dass nur die offene MPD17, und nicht die geschlossene Form, spezifisch Ortho-Phospho-L-Serin (OPLS) bindet. Daraus lässt sich schließen, dass das Shedding-Ereignis in Zusammenhang mit einer Bindung der offenen MPD17 an die Phosphatidylserinpräsentierende Zellmembran steht. Diese Bindung ist in der geschlossenen, inaktiven Form nicht möglich. Die Ergebnisse dieser Arbeit zeigen die fundamentale Bedeutung der MPD17 und CANDIS für die Shedding-Aktivität von ADAM17 und ermöglichen so ein tieferes Verständnis der ADAM17-Regulation.Ectodomain shedding is an irreversible posttranslational modification which leads to the release of biologically active ectodomains of transmembrane proteins. A disintegrin and metalloprotease 17 (ADAM17) is an important sheddase which can cleave more than 80 different substrates and is therefore involved in various physiological and pathophysiological processes, including inflammation and regeneration. Despite the importance of ADAM17, the regulation of the shedding activity is scarcely understood. It is known from previous studies that extracellular protein disulphide isomerases (PDIs) interact with ADAM17 which results in a structural change in the ectodomain of the protease. This interaction leads to the inactivation of ADAM17. In this study, it was shown that the PDIs interact with the membrane-proximal domain of ADAM17 (MPD17) and that this domain can be converted from an open conformation into a closed one through isomerisation of disulphide-bonds. Thereby, the open and more flexible form relates to the active ADAM17 while the MPD17 shows the closed and rather rigid conformation in the inactive protease. The shift from the open to the closed conformation regulates CANDIS (Conserved ADAM Seventeen Dynamic Interaction Sequence), a highly conserved sequence within the stalk region of ADAM17 which is able to bind the two substrates IL-6R and IL-1RII. This interaction can only occur when the MPD17 is in the open conformation while the closed form prevents the interaction between CANDIS and the substrates. Recent results show that ADAM17 mediated shedding can be triggered by transient exposure of phosphatidylserine (PS). Along that line, it was shown in this study that solely the active form of MPD17, but not the closed one, can bind to OPLS (ortho-phospho-l-serine). This leads to the conclusion that an ADAM17 mediated shedding event includes the binding of the open conformation of the MPD17 to the PS-presenting plasma membrane. This binding does not occur when MPD17 is in the closed conformation. In conclusion, this study shows the fundamental relevance of the MPD17 and CANDIS for the shedding activity and allows a deeper understanding of the regulation of ADAM17

Assessment of simplified momentum equations for free surface flows through rigid porous media

In many applications, free surface flow through rigid porous media has to be modeled. Examples refer to coastal engineering applications as well as geotechnical or biomedical applications. Albeit the frequent applications, slight inconsistencies in the formulation of the governing equations can be found in the literature. The main goal of this paper is to identify these differences and provide a quantitative assessment of different approaches. Following a review of the different formulations, simulation results obtained from three alternative formulations are compared with experimental and numerical data. Results obtained by 2D and 3D test cases indicate that the predictive differences returned by the different formulations remain small for most applications, in particular for small porous Reynolds number ReP < 5000. Thus it seems justified to select a simplified formulation that supports an efficient algorithm and coding structure in a computational fluid dynamics environment. An estimated accuracy depending on the porous Reynolds number or the mean grain diameter is given for the simplified formulation.Open Access funding enabled and organized by Projekt DEAL.Peer ReviewedPostprint (published version

Let's Talk About Risk! Stock Market Effects of Risk Disclosure for European Energy Utilities

We analyze how risk reporting by European energy utilities is related to uncertainty about firms’ future prospects. Using an unsupervised machine learning topic model, we classify the content of the risk reports presented in the notes to the financial statements into different risk topics over the period from 2007 to 2017. We find that more risk reporting is related to lower idiosyncratic volatility and that this relation is especially evident for reporting about credit risk, risk management processes, economic risk, and accounting-related risk. We also find that the uncertainty-decreasing effect of risk disclosure extends to a positive relation between risk disclosure and firm value. Our study contributes to the call for more transparency in risk reporting and disclosure. Interestingly, we are unable to identify a climate-related risk topic, and further tests show only a rudimentary disclosure of climate-related risks. Combining the usefulness of the current risk disclosure regulation with the current lack of climate-related risk disclosures, we see good reasons for increased mandatory climate-related risk disclosures

Interleukin-11 (IL-11) receptor cleavage by the rhomboid protease RHBDL2 induces IL-11 trans-signaling

Interleukin-11 (IL-11) is a pleiotropic cytokine with both pro- and anti-inflammatory properties. It activates its target cells via binding to the membrane-bound IL-11 receptor (IL-11R), which then recruits a homodimer of the ubiquitously expressed, signal-transducing receptor gp130. Besides this classic signaling pathway, IL-11 can also bind to soluble forms of the IL-11R (sIL-11R), and IL-11/sIL-11R complexes activate cells via the induction of gp130 homodimerization (trans-signaling). We have previously reported that the metalloprotease ADAM10 cleaves the membrane-bound IL-11R and thereby generates sIL-11R. In this study, we identify the rhomboid intramembrane protease RHBDL2 as a so far unrecognized alternative sheddase that can efficiently trigger IL-11R secretion. We determine the cleavage site used by RHBDL2, which is located in the extracellular part of the receptor in close proximity to the plasma membrane, between Ala-370 and Ser-371. Furthermore, we identify critical amino acid residues within the transmembrane helix that are required for IL-11R proteolysis. We also show that ectopically expressed RHBDL2 is able to cleave the IL-11R within the early secretory pathway and not only at the plasma membrane, indicating that its subcellular localization plays a central role in controlling its activity. Moreover, RHBDL2-derived sIL-11R is biologically active and able to perform IL-11 trans-signaling. Finally, we show that the human mutation IL-11R-A370V does not impede IL-11 classic signaling, but prevents RHBDL2-mediated IL-11R cleavage

Molecular characterization of the craniosynostosis‐associated interleukin‐11 receptor variants p.T306_S308dup and p.E364_V368del

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and is an important factor for bone homeostasis. IL-11 binds to and signals via the membrane-bound IL-11 receptor (IL-11R, classic signaling) or soluble forms of the IL-11R (sIL-11R, trans-signaling). Mutations in the IL11RA gene, which encodes the IL-11R, are associated with craniosynostosis, a human condition in which one or several of the sutures close prematurely, resulting in malformation of the skull. The biological mechanisms of how mutations within the IL-11R are linked to craniosynostosis are mostly unexplored. In this study, we analyze two variants of the IL-11R described in craniosynostosis patients: p.T306_S308dup, which results in a duplication of three amino-acid residues within the membrane-proximal fibronectin type III domain, and p.E364_V368del, which results in a deletion of five amino-acid residues in the so-called stalk region adjacent to the plasma membrane. The stalk region connects the three extracellular domains to the transmembrane and intracellular region of the IL-11R and contains cleavage sites for different proteases that generate sIL-11R variants. Using a combination of bioinformatics and different biochemical, molecular, and cell biology methods, we show that the IL-11R-T306_S308dup variant does not mature correctly, is intracellularly retained, and does not reach the cell surface. In contrast, the IL-11R-E364_V368del variant is fully biologically active and processed normally by proteases, thus allowing classic and trans-signaling of IL-11. Our results provide evidence that mutations within the IL11RA gene may not be causative for craniosynostosis and suggest that other regulatory mechanism(s) are involved but remain to be identified