Reduction of systemic risk by means of Pigouvian taxation

We analyze the possibility of reduction of systemic risk in financial markets through Pigouvian taxation of financial institutions, which is used to support the rescue fund. We introduce the concept of the cascade risk with a clear operational definition as a subclass and a network related measure of the systemic risk. Using financial networks constructed from real Italian money market data and using realistic parameters, we show that the cascade risk can be substantially reduced by a small rate of taxation and by means of a simple strategy of the money transfer from the rescue fund to interbanking market subjects. Furthermore, we show that while negative effects on the return on investment (ROI) are direct and certain, an overall positive effect on risk adjusted return on investments (ROIRA) is visible. Please note that the taxation is introduced as a monetary/regulatory, not as a _scal measure, as the term could suggest. The rescue fund is implemented in a form of a common reserve fund

Lack of Matrilin-2 Favors Liver Tumor Development via Erk1/2 and GSK-3 beta Pathways In Vivo

Matrilin-2 (Matn2) is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/-) mice comparing them with wild-type (WT) mice in a diethylnitrosamine (DEN) model. The liver tissue was analyzed macroscopically, histologically and immunohistochemically, at protein level by Proteome Profiler Arrays and Western blot analysis. Matn2(-/-) mice exhibited higher susceptibility to hepatocarcinogenesis compared to wild-type mice. In the liver of Matn2(-/-) mice, spontaneous microscopic tumor foci were detected without DEN treatment. After 15 mu g/g body weight DEN treatment, the liver of Matn2(-/-) mice contained macroscopic tumors of both larger number and size than the WT liver. In contrast with the WT liver, spontaneous phosphorylation of EGFR, Erk1/2 GSK-3 alpha/beta and retinoblastoma protein (p-Rb), decrease in p21/CIP1 level, and increase in beta-Catenin protein expression were detected in Matn2(-/-) livers. Focal Ki-67 positivity of these samples provided additional support to our presumption that the lack of Matn2 drives the liver into a pro-proliferatory state, making it prone to tumor development. This enhanced proliferative capacity was further increased in the tumor nodules of DEN-treated Matn2(-/-) livers. Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this process activation of EGFR together with that of Erk1/2, as well as inactivation of GSK-3 beta, play strategic roles

Endogenous ownership structure:factors affecting the post-privatisation equity in largest Hungarian firms

Using a data set for the 162 largest Hungarian firms during the period of 1994-1999, this paper explores the determinants of equity shares held by both foreign investors and Hungarian corporations. Evidence is found for a post-privatisation evolution towards more homogeneous equity structures, where dominant categories of Hungarian and foreign owners aim at achieving controlling stakes. In addition, focusing on firm-level characteristics we find that exporting firms attract foreign owners who acquire controlling equity stakes. Similarly, firm-size measurements are positively associated with the presence of foreign investors. However, they are negatively associated with 100% foreign ownership, possibly because the marginal costs of acquiring additional equity are growing with the size of the assets. The results are interpreted within the framework of the existing theory. In particular, following Demsetz and Lehn (1985) and Demsetz and Villalonga (2001) we argue that equity should not be treated as an exogenous variable. As for specific determinants of equity levels, we focus on informational asymmetries and (unobserved) ownership-specific characteristics of foreign investors and Hungarian investors

Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation

A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules

Self perceptions as predictors for return to work 2 years after rehabilitation in orthopedic trauma inpatients.

Purpose This study aimed to identify self-perception variables which may predict return to work (RTW) in orthopedic trauma patients 2 years after rehabilitation. Methods A prospective cohort investigated 1,207 orthopedic trauma inpatients, hospitalised in rehabilitation, clinics at admission, discharge, and 2 years after discharge. Information on potential predictors was obtained from self administered questionnaires. Multiple logistic regression models were applied. Results In the final model, a higher likelihood of RTW was predicted by: better general health and lower pain at admission; health and pain improvements during hospitalisation; lower impact of event (IES-R) avoidance behaviour score; higher IES-R hyperarousal score, higher SF-36 mental score and low perceived severity of the injury. Conclusion RTW is not only predicted by perceived health, pain and severity of the accident at the beginning of a rehabilitation program, but also by the changes in pain and health perceptions observed during hospitalisation

Epigenetic Silencing of MYC By Proteasome Inhibitors

Abstract Proteasome inhibitors were first introduced to the clinic almost 20 years ago and have since become standard of care in multiple myeloma treatment, a cancer of terminally differentiated plasma cells. The proteasome degrades most cellular proteins and identifies targets following ubiquitination by an elaborate enzymatic cascade. Blocking the turnover of proteins with proteasome inhibitors affects many pathways, including signaling, metabolism, and stress responses. Transcriptional and epigenetic regulators are short-lived proteins, and proteasome inhibition is expected to alter gene activity dramatically. However, some of the least understood aspects of proteasome inhibitors involve their effects on epigenetics and transcription. One reason for this knowledge gap is the technical challenge of distinguishing the direct from indirect effects of proteasome inhibition on transcription. To overcome this limitation, we developed an approach to map the nuclear location of protein turnover. We detected MYC target genes as a prevalent site of proteasomal protein degradation in multiple myeloma cells. Multiple myeloma is addicted to the proto-oncogene MYC, and several new approaches are being tested to silence MYC in this cancer. MYC is a short-lived protein, and proteasome inhibitors should stabilize MYC. However, with increased MYC levels, it is unclear why proteasome inhibition would be clinically beneficial. Instead, we found that proteasome inhibition reduces the levels of MYC and the activity of its target genes. The surprising reduction of MYC by proteasome inhibitors makes sense given their clinical effect. To identify the molecular mechanism by which proteasome inhibitors suppress MYC, we performed an integrative genomic analysis on the effects of these drugs and found that MYC is silenced at the transcriptional level by epigenetic suppression of its super-enhancer. We found that acetylated H3K27, a histone modification that increases the accessibility of chromatin and facilitates transcription, is rapidly lost upon proteasome inhibition. We hypothesized that this is caused by the stabilization of a histone deacetylase (HDAC). Based on data from the APEX study, we discovered that HDAC3 antagonizes the activity of MYC, and cancers with high HDAC3 expression correlate with better outcomes. Indeed, we found that proteasome inhibition locally increases HDAC3 levels at target promoters and the MYC super-enhancer and that genetic depletion of HDAC3 reduces the epigenetic effects of proteasome inhibition. In addition to its epigenetic role, HDAC3 has recently been shown to repress genes by disrupting their location. In agreement with these findings, we discovered that target genes relocate into heterochromatin-rich lamina-associated areas of the nucleus upon proteasome inhibition. These results suggest that HDAC3 might also act as a suppressor of MYC in a manner that does not require catalytic deacetylase activity. Such a repressive function would, therefore, not be targeted by HDAC inhibitors. In summary, our study supports a new role of proteasome inhibitors as antagonists of the proto-oncogene MYC. The drugs accomplish this effect by stabilizing HDAC3 at the MYC super-enhancer and MYC target genes. As a consequence, elevated HDAC3 represses chromatin epigenetically and possibly alters the nuclear architecture by relocating chromosomes. These findings are surprising as they point towards a novel mechanism to limit MYC, which is dysregulated in 70% of cancers. Our results may also explain why some highly MYC-addicted cancers have a particular sensitivity towards proteasome inhibitors. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. </jats:sec