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Effect of Oil Sanctions on the Macroeconomic and Household Welfare in Iran: New Evidence from a CGE Model
No full textWe examine the macroeconomic and household welfare consequences of oil sanctions in Iran. We use social accounting matrix (SAM) and develop a computable general equilibrium (CGE) model to simulate selected scenarios in which the exportation of oil from Iran to the rest of the world is banned. Our main results show that higher income households are losing more significantly under oil sanctions. Total imports, exports, private consumption, and GDP fall in response to oil sanctions. Interesting is the increase of net indirect taxes at the time of oil revenues fall. Real exchange rate appreciates in the oil sanction crisis. In addition, labor income increases while the capital income falls in response to oil sanctions in Iran. These simulations are in line with reality of the Iranian economy in post-oil sanction period
Charakterisierung der Einflüsse des Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) und seines Rezeptors PAC1 auf die strukturelle und zelluläre Morphologie des Herzens im murinen ApoE-Knock-Out Modell
No full textFibrose ist ein Kennzeichen des kardialen Remodelings und tritt bei einer Vielzahl kardiovaskulärer Erkrankungen auf. Insbesondere bei der weit verbreiteten heterogenen Gruppe von Herzfunktionsstörungen mit erhaltener linksventrikulärer Ejektionsfraktion (LVEF) wurde die interstitielle Fibrose als ein zentraler pathophysiologischer Faktor identifiziert. Jüngsten Studien zufolge fördern Komorbiditäten, insbesondere aus dem metabolischen Spektrum, eine chronische systemische Entzündung niedrigen Grades mit sekundärer Beteiligung des Herzens, welche zu Fibrose führt und dadurch die kardiale Struktur und infolgedessen Funktion beeinträchtigt.
Der Mangel an wirksamen antifibrotischen Behandlungsmöglichkeiten unterstreicht den dringenden Bedarf an neuen Therapiezielen. Jüngste Hinweise auf die antifibrotische Wirkung des pleiotropen Neuropeptids pituitary adenylate cyclase activating polypeptide (PACAP) bei strahleninduzierter Myokardschädigung geben Anlass für eine gezielte Untersuchung möglicher antifibrotischer Effekte von PACAP im eben skizzierten Zusammenhang.
Ziel der vorliegenden Arbeit ist es daher, die Rolle von PACAP und seines Rezeptors PAC1 bei der Myokardfibrose im metabolischen Stressmodell zu klären.
Hierzu wurden PACAP-/-- und PAC1-/-- C57/Bl6 N-Mäuse mit einem ApoE-/--Stamm gekreuzt und metabolischer Stress wurde durch die Fütterung einer cholesterinangereicherten Diät (CED) über 10 Wochen induziert. Standardfutter (SD) diente als Kontrolldiät. Gewebeproben der Herzkammern wurden für eine histologische FFPE-Analyse mit Hämalaun/Eosin- und Picro-Sirius-Red-Färbungen aufbereitet und einer morphometrischen Quantifizierung der Kardiomyozyten-Querdurchmesser und der myokardialen Fibrose mit Hilfe eines softwarebasierten Bildanalyseverfahrens unterzogen. Zudem wurde die CED-Gruppe mittels immunhistochemischer Markierungen auf das Vorkommen CD90 positiver Zellen, welche eine Fibroblastensubpopulation darstellen, untersucht.
In der CED-Gruppe wurde bei PACAP-/-/ApoE-/-- und PAC1-/-/ApoE-/--Mäusen im Vergleich zu ApoE-/--Mäusen ein statistisch signifikant höheres Ausmaß an Myokardfibrose festgestellt. Das Muster der fibrösen Ablagerungen entsprach dem einer reaktiven interstitiellen Fibrose und betraf beide Ventrikel gleichermaßen.
PAC1-/-/ApoE-/--Mäuse wiesen neben der vermehrten Fibrose im Vergleich zur Kontrollgruppe zudem eine signifikant höhere Anzahl CD90 positiver Zellen pro Herzfläche auf. Die morphometrische Analyse ergab keine makroskopische oder zelluläre Hypertrophie bei PACAP-/-/ApoE-/-- und PAC1-/-/ApoE-/--Mäusen im Vergleich zu ApoE-/--Mäusen nach CED. Signifikante Unterschiede traten ausschließlich nach CED- Fütterung auf und waren bei SD-Fütterung nicht nachweisbar.
Die vorliegende Arbeit liefert neuartige Hinweise für eine signifikante Beteiligung von PACAP und seines Rezeptors PAC1 an der Entwicklung einer metabolisch induzierten interstitiellen Fibrose. Basierend auf den vorliegenden Daten wird die antifibrotische Wirkung von PACAP in erheblichem Umfang über den PAC1-Rezeptor vermittelt und tritt nur unter metabolischen Stressbedingungen auf. Das Fehlen einer makro- und mikroskopischen kardialen Hypertrophie bei PACAP-defizienten oder PAC1-defizienten Mäusen schließt relevante hämodynamische Effekte von PACAP bzw. des PAC1- Rezeptors im untersuchten Modell aus. Die vorliegenden Ergebnisse deuten darauf hin, dass PACAP-Analoga oder PAC1-Rezeptor-Agonisten ein therapeutisches Potenzial zur Verhinderung oder Abschwächung der metabolischen Herzfibrose bieten können.Fibrosis is a hallmark of cardiac remodeling and occurs in a variety of cardiovascular diseases. In particular interstitial fibrosis has been identified as a key pathophysiological factor in the widely heterogeneous group of cardiac dysfunctions with preserved left ventricular ejection fraction (LVEF). According to recent studies comorbidities, particularly from the metabolic spectrum, promote chronic low grade systemic inflammation with secondary involvement of the heart, leading to fibrosis and thereby compromising its structure and subsequently function. The lack of effective antifibrotic treatment options underscores the urgent need for new therapeutic targets. Recent evidence on the antifibrotic effect of the pleiotropic neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) in radiation-induced myocardial injury provides a rationale for a focused investigation of possible antifibrotic effects of PACAP in the aforementioned context.
Therefore, the aim of the present work is to elucidate the role of PACAP and its receptor PAC1 in myocardial fibrosis in a metabolic stress model.
For this purpose, PACAP-/-- and PAC1-/-- C57/Bl6 N mice were crossed with an ApoE-/-- strain, and metabolic stress was induced by feeding a cholesterol-enriched diet (CED) for 10 weeks. Standard diet (SD) served as a control diet. Cardiac ventricle tissue samples were processed for FFPE histological analysis with hemalaun/eosin- and picro- sirius-red-staining and subjected to morphometric quantification of cardiomyocyte cross diameters and myocardial fibrosis using a software-based image analysis technique. In addition, the CED-group was examined for the presence of CD90 positive cells, which represent a fibroblast subpopulation, using immunohistochemical labeling.
In the CED-group a significantly higher extent of myocardial fibrosis was observed in PACAP-/-/ApoE-/-- and PAC1-/-/ApoE-/--mice compared to ApoE-/--mice. The pattern of fibrous deposition resembled typical reactive interstitial fibrosis and affected both ventricles equally. In addition to the higher extent of myocardial fibrosis, PAC1-/-/ApoE-/- -mice also showed a significantly higher number of CD90 positive cells per cardiac area. Measurements of ventricular wall thickness and cardiomyocyte cross diameters revealed no macroscopic or cellular hypertrophy in PACAP-/-/ApoE-/-- and PAC1-/-/ApoE-/--mice compared with ApoE-/--mice after CED. Significant differences occurred exclusively after CED feeding and were not detectable with SD feeding.
The present work provides novel evidence for a significant involvement of PACAP and its receptor PAC1 in the development of interstitial fibrosis induced by metabolic stress. Based on the present data, the antifibrotic effect of PACAP is mediated to a significant extent via the PAC1 receptor and occurs only under metabolic stress conditions. The absence of macro- and microscopic myocardial hypertrophy in PACAP-deficient or PAC1-deficient mice precludes relevant hemodynamic effects of PACAP or the PAC1- receptor in the studied model. Based on the present results, PACAP-analogues or PAC1-receptor-agonists may offer therapeutic potential to prevent or attenuate metabolic cardiac fibrosis
Functional analysis of plexin-B2 in human colon organoids
No full textDer menschliche Gastrointestinaltrakt ist ein System aus Hohlorganen und besitzt essenzielle absorptive, homöostatische, metabolische und schützende Funktionen. Das Epithel erneuert sich alle 5 bis 7 Tage und ist durch spezialisierte Zelltypen an die Bedürfnisse der Organfunktion und des Körpers angepasst. Eine besondere Rolle nehmen intestinale Stammzellen ein, die durch ihre Selbsterneuerung und Multipotenz die Regeneration des Darmepithels steuern. Bei maligner Entartung dieser Zellen entstehen sogenannte Krebsstammzellen, die für einen großen Teil der Therapieresistenz, Metastasierung und Tumorrezidive verantwortlich gemacht werden. Das Plexin- Semaphorin-System nimmt eine zentrale Rolle in physiologischen Vorgängen wie beispielsweise die Organentwicklung, Zellhomöostase und Gewebe- regeneration ein. Es ist aber auch bei pathophysiologischen Prozessen vor allem in Bereich der malignen Neoplasien von Bedeutung. Von besonderem Interesse für diese Dissertation war der Transmembranrezeptor Plexin-B2, da er im menschlichen Darm stark exprimiert ist. Eine Expressionsanalyse von humanen Kolon-Organoiden, die aus Patientenmaterial gewonnen wurden, bestätigte diese Beobachtung. Als Basis weiterführender Experimente wurde eine stabile Langzeitkultur von Kolon- sowie Tumor-Organoiden etabliert. Wnt3a konnte als treibender Faktor zur erfolgreichen Kultur der Kolon-Organoide über mehrere Wochen identifiziert werden. Dagegen zeigten Tumor-Organoide nur unter Wnt3a-freien Bedingungen stabiles Wachstum. Zur funktionellen Analyse von Plexin-B2 wurde die lentivirale Transduktion von humanen Organoiden mit shRNA-Plasmiden zur induzierbaren RNA-Interferenz etabliert und durchgeführt. Die Kultur und weitere Analyse gestaltete sich durch verschiedene Faktoren schwierig. Die Induktion der shRNAs zeigte eine unzureichende Expressions- reduktion von Plexin-B1 und B2 und keine assoziierbare Veränderung der Stammzellmarker LGR5 und EphB2 in den transduzierten Organoiden. Eine Wiederholung der Experimente, Verbesserung des Gentransfers und Gen- Stummschaltung durch Methoden wie Elektroporation und CRISPR/Cas sowie Experimente mit Tumor-Organoiden könnten in Zukunft durchgeführt werden, um eine funktionelle Relevanz von Plexin-B2 weiter zu analysieren.The human gastrointestinal tract has central digestive, absorptive, homeostatic, metabolic, and protective functions. The epithelium renews itself every 5 to 7 days and is adapted to the needs of organ function by specialized cell types. A special role is played by intestinal stem cells, which control the regeneration of the intestinal epithelium through their self-renewal and multipotency. In case of malignancy so-called cancer stem cells develop, which are held responsible for a large part of therapy resistance, metastasis, and tumor recurrence. The plexin- semaphorin system is essential for physiological processes such as organ development, cell morphology, differentiation, homeostasis, and tissue regeneration. However, it also plays a role in pathophysiological processes, especially in the field of malignant neoplasia. Of particular interest for this dissertation was the transmembrane receptor plexin-B2, which is strongly expressed in the human intestine. An expression analysis of human colon organoids obtained from patient material confirmed this observation. As a basis for further experiments, a stable long-term culture of colon as well as tumor organoids was established. Wnt3a was identified as the driving factor for the successful longterm culture of colon organoids over several weeks. In contrast, tumor organoids only showed growth under Wnt3a-free conditions. For the functional analysis of plexin-B2, lentiviral transduction of human organoids with shRNA plasmids for inducible RNA interference was established and performed. The culture and downstream analysis proved difficult due to various factors. The induction of shRNAs showed insufficient expression reduction of plexin-B1 and B2 and no associable alteration of the stem cell markers LGR5 and EphB2 in the transduced organoids. Repetition of the experiments, improvement of gene transfer and gene silencing by methods such as electroporation and CRISPR/Cas as well as experiments with tumor organoids could be performed in the future to further explore the functional relevance of plexin-B2
Financial Markets and Dissent in the ECB’s Governing Council
No full textThe decision-making process in the ECB’s Governing Council remains opaque as the ECB, in contrast to many other central banks, does not publish the votes for or against a policy proposal. In this paper, we construct an index of dissent based on the ECB presidents’ answers to journalists’ questions during the press conference following each meeting. This narrative account of dissent suggests that dissenting votes are cast frequently. We show that the non-forecastable component of dissent weakens the response of long-term interest rates to policy surprises and thus affects the monetary transmission mechanism. The yield response is significantly stronger under unanimity compared to dissent. This finding is robust to several alternative specifications
Partial cross ownership and collusion
No full textThis article finds that non-controlling minority shareholdings among competitors lower the sustainability of collusion. This is the case under an even greater variety of situations than was indicated by earlier literature. The collusion destabilizing effect of minority shareholdings is mainly caused by their unilateral effects, and it is particularly prevalent in the presence of an effective antitrust authority
Central Bank Communication in the Financial Crisis: Evidence from a Survey of Financial Market Participants
No full textIn this paper, we study whether central bank communication has a positive effect on market participants’ perception of central banks’ (i) credibility, (ii) unorthodox measures, and (iii) independence. We utilise a survey of more than 550 financial market participants from around the world who answered questions in reference to the Bank of England (BoE), the Bank of Japan (BoJ), the European Central Bank (ECB), and the Federal Reserve (Fed). We find that market participants believe that the Fed communicates best, followed by the BoE, ECB, and BoJ. Similar rankings are found on the issues of credibility, satisfaction with unconventional monetary policy, and possible deterioration in independence. Using ordered probit models, we show that central bank communication has a positive effect on how central banks are perceived and understood, as it enhances credibility, increases satisfaction with unorthodox measures, and fosters perceived independence of central banks
Multiplexed electrochemical liposomes applied to the detection of nucleic acids for Influenza A, Influenza B and SARS-CoV-2
No full textDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglichThis publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectivelyMultiplexing is a relevant strategy for biosensors to improve accuracy and decision-making due to the increased amount of simultaneously obtained information. Liposomes offer unique benefits for label-based multiplexing since a variety of different marker molecules can be encapsulated, leading to intrinsic signal amplification and enabling a variety of detection formats. We successfully developed an electrochemical (EC) liposome-based platform technology for the simultaneous detection of at least three analytes by studying parameters to ensure specific and sensitive bioassay performance. Influenza A and B and SARS-CoV-2 sequences served as model system in a standard sandwich hybridization assay. Studies included encapsulants, probe distribution on liposomes and capture beads, assay setup and interferences between liposomes to also ensure a generalization of the platform. Ruthenium hexamine(III), potassium hexacyanoferrate(II) and m-carboxy luminol, when encapsulated separately into a liposome, provided desirable long-term stability of at least 12 months and no cross-signals between liposomes. Through the optimization process, low limits of detections of 1.6 nmol L−1, 125 pmol L−1 and 130 pmol L−1, respectively, were achieved in a multiplexed assay setup, which were similar to singleplex assays. Non-specific interactions were limited to 25.1%, 7.6% and 7.5%, respectively, through sequential liposome incubations and singleplex capture bead designs. Here, ruthenium hexamine liposomes had only mediocre performance so that low overall signal strength translated into higher LODs and worse specificity. A different marker such as ferroin may be an option in the future. The identification of further electrochemical markers will provide new opportunities for liposomes to function as multiplex, orthogonal or internal standard labels in electrochemical bioassays
Preferences for Dynamic Electricity Tariffs: A Comparison of Households in Germany and Japan
No full textWe evaluate a stated choice experiment on dynamic electricity tariffs based on two representative household surveys from Germany and Japan. Our results indicate significant differences between German and Japanese respondents’ preferences towards dynamic tariffs, with the latter generally being more open to dynamic pricing. Furthermore, our unique experimental design allows to disentangle preferences for inter- and intraday price changes, which are two essential tariff characteristics. In this respect, our results suggest that households need significant compensation in order to accept frequently changing price patters. In contrast, they are mostly indifferent with respect to the number of price changes per day. Besides the implementation of an environmental treatment message, we additionally investigate tariff characteristics, which aim at overcoming household acceptance barriers. To this end, a restrictive use of households’ consumption data, price caps, as well as highlighting the environmental benefits associated to dynamic tariffs present themselves as suitable tools to reduce households’ aversion to dynamic electricity tariffs
Shopping hours and entry – An empirical anlysis of Aldi’s opening hours
No full textAldi, the biggest discounter in Germany, started to systematically extend shopping hours of its stores in 2016. We interpret the decision to extend opening hours of a specific Aldi store as entry into a new market. By using a novel data set containing the opening hours of nearly all German grocery retailers, we find that consumer and firm learning influence that decision. The presence of a nearby Aldi already opened longer increases the probability that a given Aldi extends its opening hours. However, if a nearby competitors store is short opened, the probability that Aldi extends opening hours decreases
The human factor H protein family – an update
No full textDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglichThis publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectivelyComplement is an ancient and complex network of the immune system and, as
such, it plays vital physiological roles, but it is also involved in numerous pathological processes. The proper regulation of the complement system is important to allow its sufficient and targeted activity without deleterious side-effects. Factor H is a major complement regulator, and togetherwith its splice variant factor H-like protein 1 and the five human factor H-related (FHR) proteins, they have been linked to various diseases. The role of factor H in inhibiting complement activation is well studied, but the function of the FHRs is less characterized. Current evidence supports the main role of the FHRs as enhancers of complement activation and opsonization, i.e., counter-balancing the inhibitory effect of factor H. FHRs emerge as soluble pattern recognition molecules and positive regulators of the complement system. In addition, factor H and some of the FHR proteins were shown to modulate the activity of immune cells, a non-canonical function outside the complement cascade. Recent efforts have intensified to study factor H and the FHRs and develop new tools for the distinction, quantification and functional characterization of members of this protein family. Here, we provide an update and overview on the versatile roles of factor H family proteins, what we know about their biological functions in healthy conditions and in diseases