Methods for Analyzing the Role of DNA Methylation and Chromatin Structure in Regulating T Lymphocyte Gene Expression

Chromatin structure, determined in part by DNA methylation, is established during differentiation and prevents expression of genes unnecessary for the function of a given cell type. We reported that DNA methylation and chromatin structure contributes to lymphoid-specific ITGAL (CD11a) and PRF1 (perforin) expression. We used bisulfite sequencing to compare methylation patterns in the ITGAL promoter and 5' flanking region of T cells and fibroblasts, and in the PRF1 promoter and upstream enhancer of CD4+ and CD8+ T cells with fibroblasts. The effects of methylation on promoter function were tested using regional methylation of reporter constructs, and confirmed by DNA methyltransferase inhibition. The relationship between DNA methylation and chromatin structure was analyzed by DNaseI hypersensitivity. Herein we described the methods and results in greater detail

Regulating Systemic Risk

The failure to spot emerging systemic risk and prevent the current global financial crisis warrants a reexamination of the approach taken so far to crisis prevention. The paper argues that financial crises can be prevented, as they build up over time due to policy mistakes and eventually erupt in slow motion. While one cannot predict the precise timing of crises, one can avert them by identifying and dealing with sources of instability. For this purpose, policymakers need to strengthen top-down macroprudential supervision, complemented by bottom-up microprudential supervision. The paper explores such a strategy and the institutional setting required to implement it at the national level. Given that the recent regulatory reforms that have been undertaken to address systemic risks are inadequate to prevent and combat future crises, the paper argues that national measures to promote financial stability are crucial and that the Westphalian principles governing international financial oversight should be rejected. The paper proposes that while an effective national systemic regulator should be established, strong international cooperation is indispensable for financial stability

Chicken CRTAM Binds Nectin-Like 2 Ligand and Is Upregulated on CD8⁺ αβ and γδ T Lymphocytes with Different Kinetics

During a search for immunomodulatory receptors in the chicken genome, we identified a previously cloned chicken sequence as CRTAM homologue by its overall identity and several conserved sequence features. For further characterization, we generated a CRTAM specific mab. No staining was detectable in freshly isolated cell preparations from thymus, bursa, caecal tonsils, spleen, blood and intestine. Activation of splenocytes with recombinant IL-2 increased rapid CRTAM expression within a 2 h period on about 30% of the cells. These CRTAM+ cells were identified as CD8+ γδ T lymphocytes. In contrast, CRTAM expression could not be stimulated on PBL with IL-2, even within a 48 h stimulation period. As a second means of activation, T cell receptor (TCR) crosslinking using an anti-αβ-TCR induced CRTAM on both PBL and splenocytes. While CRTAM expression was again rapidly upregulated on splenocytes within 2 h, it took 48 h to reach maximum levels of CRTAM expression in PBL. Strikingly, albeit the stimulation of splenocytes was performed with anti-αβ-TCR, CRTAM expression after 2 h was mainly restricted to CD8+ γδ T lymphocytes, however, the longer anti-TCR stimulation of peripheral blood lymphocytes (PBL) resulted in CRTAM expression on αβ T lymphocytes. In order to characterize the potential ligand we cloned and expressed chicken Necl-2, a member of the nectin and nectin-like family which is highly homologous to its mammalian counterpart. Three independent assays including a reporter assay, staining with a CRTAM-Ig fusion protein and a cell conjugate assay confirmed the interaction of CRTAM with Necl-2 which could also be blocked by a soluble CRTAM-Ig fusion protein or a CRTAM specific mab. These results suggest that chicken CRTAM represents an early activation antigen on CD8+ T cells which binds to Necl-2 and is upregulated with distinct kinetics on αβ versus γδ T lymphocytes

Characterization of a nonvirulent variant of lymphocytic choriomeningitis virus

A cold-adapted, nonvirulent variant of the Armstrong strain of lymphocytic choriomeningitis virus was isolated from infected L929 cells maintained at 25° C. This variant, designated P17, was capable of replicating in the central nervous system of mice without causing disease and conferring immunity to back challenge with the parental strain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41689/1/705_2005_Article_BF01320786.pd

Basel Compliance and Financial Stability: Evidence from Islamic Banks

We find that compliance with the Basel Core Principles (BCPs) has a strong positive effect on the stability of conventional banks, and a positive but less pronounced effect on the stability of Islamic banks. We also find that the main impact of compliance is an increase in capital ratios, whereas other components of the Z-score are negatively affected. This reflects the desire of banks to be more closely integrated into the global financial system by holding higher capital ratios. The findings also justify the 2015 decision of the Islamic Financial Services Board to publish similar principles for Islamic banks

Epigenetic regulation of prostate cancer

Prostate cancer is a commonly diagnosed cancer in men and a leading cause of cancer deaths. Whilst the underlying mechanisms leading to prostate cancer are still to be determined, it is evident that both genetic and epigenetic changes contribute to the development and progression of this disease. Epigenetic changes involving DNA hypo- and hypermethylation, altered histone modifications and more recently changes in microRNA expression have been detected at a range of genes associated with prostate cancer. Furthermore, there is evidence that particular epigenetic changes are associated with different stages of the disease. Whilst early detection can lead to effective treatment, and androgen deprivation therapy has a high response rate, many tumours develop towards hormone-refractory prostate cancer, for which there is no successful treatment. Reliable markers for early detection and more effective treatment strategies are, therefore, needed. Consequently, there is a considerable interest in the potential of epigenetic changes as markers or targets for therapy in prostate cancer. Epigenetic modifiers that demethylate DNA and inhibit histone deacetylases have recently been explored to reactivate silenced gene expression in cancer. However, further understanding of the mechanisms and the effects of chromatin modulation in prostate cancer are required. In this review, we examine the current literature on epigenetic changes associated with prostate cancer and discuss the potential use of epigenetic modifiers for treatment of this disease

Price Convergence in the Enlarged Internal Market

In this paper we investigate the effects of EU enlargement on price convergence. The internal market is expected to boost integration and increase efficiency and welfare through a convergence of prices in product markets. Two principal drivers are crucial to explain price developments. On the one hand, higher competition exerts a downward pressure on prices because of lower mark ups. On the other hand, the catching up process of low income countries leads to a rise in the price levels and higher inflation over a transition period. Using comparative price levels for 41 product categories price convergence can be established. However, the speed of convergence is rather slow, with half lives around 10 years. The enlargement has slightly stimulated convergence towards the mean price, and this impact is robust across different groups of countries. Moreover, the driving forces of convergence are explored. In line with theoretical predictions, the rise in competition exerts a downward pressure on prices, while catching up of low income countries leads to a rise in price levels and higher inflation. The findings have important implications, as price convergence facilitates the working of common economic policies