Regulation of Imprinted Genes in the brain by the ATRX Chromatin Remodeling Protein

Alpha-thalassemia mental retardation, X-linked (ATRX) is a SWI/SNF-like chromatin remodeling protein, enriched at heterochromatic regions of the genome. Disruption of ATRX in humans causes a neurodevelopmental disorder known as ATR‐X Syndrome, and has been linked to paediatric neuronal cancers, suggesting an important role for ATRX in the regulation of chromatin structure in the developing brain. At the outset of this study direct ATRX target genes had not yet been identified. This thesis identifies imprinted genes as targets of ATRX in the developing brain, and explores the mechanism of ATRX regulation at these sites, using the H19/Igf2 imprinted domain as a model. The findings indicate that in the forebrain ATRX localizes to the maternal allele of the H19 imprinting control region (H19 ICR) with methyl CpG binding protein 2 (MeCP2), CCCTC‐binding factor (CTCF) and Cohesin, three important regulators of chromatin structure. ATRX is recruited by MeCP2 to the H19 ICR, where it then governs the profile of post‐translational histone modifications and nucleosome occupancy to maintain CTCF and Cohesin binding. CTCF and Cohesin are essential constituents of the cis and trans chromatin interactions that regulate the expression of imprinted genes. Loss of either ATRX or MeCP2 disrupts cis chromosomal interactions across H19/Igf2. A role for ATRX in cis at several imprinted genes is supported by its ability to bind directly to many imprinted domains. Taken together, these findings indicate that ATRX can regulate the expression of target genes in the brain by altering nucleosome positioning to control local chromatin interactions

Investor confidence and mutual fund performance in emerging markets: insights from India and Pakistan

Purpose: This paper investigates the impact of investor confidence on mutual fund performance in two relatively vulnerable but leading emerging markets, India and Pakistan. Design/methodology/approach: A pooled OLS model is used to look at two alternative measures of investor confidence and test for the relationship between investor confidence and mutual fund returns. To check the robustness of the findings, the authors also implement Two Stage Least Squares and Generalized Method of Moments techniques to control for unobserved heterogeneity, simultaneity, and dynamic endogeneity problems in the regressors. Findings: The paper finds that the returns of mutual funds are positively associated with investor confidence and an interaction effect exists between investor confidence and persistence in performance. The paper also confirms that returns from mutual funds are associated with different fund characteristics such as fund size, turnover, expense, liquidity, performance persistence and the fund’s age. These findings remain robust to alternative model specifications and measures of investor confidence. Originality/value While the previous literature mainly focuses on mutual fund characteristics and the macroeconomic determinants of mutual fund returns, this paper demonstrates that investor confidence plays an important role in determining mutual fund performance. The authors attribute this finding to two relatively unique features of the emerging markets in our study. A lack of awareness of mutual funds as being a low-cost investment vehicle and the interplay of cultural and behavioural changes have prevented investor’s savings from being channelled into investment products, away from gold or property

Minority versus majority: the choice of acquisition in Asia-Pacific countries

This paper examines the relationship between the financial constraints of the acquiring firms and their choice of a minority over a majority acquisition. Our findings show that the likelihood of bidders undertaking a minority acquisition increases with financial constraints, including the deviation from target capital structure, and overleverage deficit. We also find that the impacts of leverage deviation on the likelihood of bidders engaging in a minority or majority acquisition is asymmetric for underleveraged and overleveraged firms. In addition, international bidders are less likely to take a minority acquisition if the target is operating in i) countries with a higher degree of Political Stability and Absence of Violence/Terrorism, ii) countries with higher degree to which individuals are able to participate in selecting their government, as well as having more freedom of expression, freedom of association, and a free media. Lastly, minority acquisitions are more common in a country with a more developed market. As such, in a fluid social order it looks like acquirers really need majority control

Growth, human development, and trade: the Asian experience

This study looks at the three-way relationship between economic growth, human development, and openness to trade in a large panel of developing Asian economies. Using a theoretically motivated simultaneous equations system, we find that although human development contributes positively to economic growth, in the case of our Asian sample growth does not appear to have had a positive influence on human development. Uneven growth accompanied by lagging institutional development, preventing human capital formation, might have inhibited human development in the short to medium run. Complementary to the literature showing that growth is sustainable only when accompanied by human development, we confirm a role for trade liberalisation policies in achieving higher growth as well as human development

Relativising human rights

Standards-based measures of country human rights performance yields a performance ranking for countries that is “absolute” or reflects the current state of human rights performance without taking into account the relative social, political, or economic conditions within countries. While absolute ranking is useful, it can lead to perverse outcomes in other areas of work. This article provides an alternative method for ranking country human rights performance that takes into account an array of additional variables that are related to the protection of civil and political rights. The method involves creating a relative score to compare different measures of human rights performance over time and across different regions. This approach leads to a view of relative human rights performance that should be of interest to human rights scholars and practitioners

Questions of quality in repositories of open educational resources: a literature review

Open educational resources (OER) are teaching and learning materials which are freely available and openly licensed. Repositories of OER (ROER) are platforms that host and facilitate access to these resources. ROER should not just be designed to store this content – in keeping with the aims of the OER movement, they should support educators in embracing open educational practices (OEP) such as searching for and retrieving content that they will reuse, adapt or modify as needed, without economic barriers or copyright restrictions. This paper reviews key literature on OER and ROER, in order to understand the roles ROER are said or supposed to fulfil in relation to furthering the aims of the OER movement. Four themes which should shape repository design are identified, and the following 10 quality indicators (QI) for ROER effectiveness are discussed: featured resources; user evaluation tools; peer review; authorship of the resources; keywords of the resources; use of standardised metadata; multilingualism of the repositories; inclusion of social media tools; specification of the creative commons license; availability of the source code or original files. These QI form the basis of a method for the evaluation of ROER initiatives which, in concert with considerations of achievability and long-term sustainability, should assist in enhancement and development. Keywords: open educational resources; open access; open educational practice; repositories; quality assuranc

Measuring firm-level productivity convergence in the UK: the role of taxation and R&D investment

This paper examines the direct effects of corporate tax on firm productivity along with the interaction effects of tax policy and R&D activity on productivity at firm level for over 13,062 firms during 2004-2011. Our main findings are first, that there is evidence for productivity convergence and we find that there is a positive robust relationship between R&D and firm productivity, whereas tax policy has a negative distortionary effect on TFP. Second, firms with greater export orientation do not seem to achieve much improvement in productivity, whereas the favourable productivity effect in the case of R&D-based firms suggests that if there are tax incentives in place for R&D type activity, it can promote innovation and drive productivity convergence (lagging firms closing the technology gap with those at the frontier), particularly so when there is a continued decline in overall economic activity. The results also show a significant non-linear effect of tax rate on firm-level productivity, identifying an inverse U-shaped relationship

Cooperation and optimism in a social dilemma

We examine the influence of optimism about local and foreign people on social cooperation using a public goods game. Firstly, we find that optimism fuels social cooperation, and secondly, that this positive effect holds when optimism is focused either jointly or individually

Three Dimensional Dual Labelled DNA Fluorescent In Situ Hybridization Analysis in Fixed Tissue Sections

Emerging studies demonstrate that three-dimensional organization of chromatin in the nucleus plays a vital role in regulating the genome. DNA fluorescent in situ hybridization (FISH) is a common molecular technique used to visualize the location of DNA sequences. The vast majority of DNA FISH studies are conducted on cultured cells due to the technical difficulties encountered using fixed tissue sections. However, the use of cultured cells poses important limitations that could yield misleading results, making in vivo analysis a far superior approach. Here we present a protocol for multiplexed three dimensional DNA FISH in mouse brain sections, which is also applicable to other tissues. Paraffin-embedded tissues could be used but the embedding and preparation of the samples is time-consuming and often associated with poor antigenicity. To overcome this problem we:•developed a FISH technique using fixed, frozen cryosections;•provide specific instructions for tissue processing for proper fixation and freezing, including equilibration in sucrose gradients to maintain proper cellular structure;•include optimized permeabilization and washing steps to achieve specific signal and to limit background fluorescence in tissue sections