VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Towards a Model of Corporate and Social Stakeholder Engagement: Analyzing the Relations Between a French Mutual Bank and Its Members

International audienceThe aim of this article is to develop a new classification of stakeholders based on the concept of corporate and social engagement. Engagement is analyzed as an organizational learning process between the managers of an organization and its stakeholders. It is a necessary condition to improve the organization's impact on its economic, social, and natural environment. Applied to the membership of a French mutual bank in order to identify the members' varying levels of engagement, this new mapping technique may help managers to adapt their practices to the degree of engagement of each identified group of members, and to modify their financial products and communications to foster engagement among as many of these groups as possible

DNA repair modulates the vulnerability of the developing brain to alkylating agents

Neurons of the developing brain are especially vulnerable to environmental agents that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood. The focus of the present study is to demonstrate that DNA damage plays a key role in disrupting neurodevelopment. To examine this hypothesis, we compared the cytotoxic and DNA damaging properties of the methylating agents methylazoxymethanol (MAM) and dimethyl sulfate (DMS) and the mono- and bifunctional alkylating agents chloroethylamine (CEA) and nitrogen mustard (HN2), in granule cell neurons derived from the cerebellum of neonatal wild type mice and three transgenic DNA repair strains. Wild type cerebellar neurons were significantly more sensitive to the alkylating agents DMS and HN2 than neuronal cultures treated with MAM or the half-mustard CEA. Parallel studies with neuronal cultures from mice deficient in alkylguanine DNA glycosylase (Aag[superscript −/−]) or O6-methylguanine methyltransferase (Mgmt[superscript −/−]), revealed significant differences in the sensitivity of neurons to all four genotoxicants. Mgmt−/− neurons were more sensitive to MAM and HN2 than the other genotoxicants and wild type neurons treated with either alkylating agent. In contrast, Aag[superscript −/−] neurons were for the most part significantly less sensitive than wild type or Mgmt[superscript −/−] neurons to MAM and HN2. Aag[superscript −/−] neurons were also significantly less sensitive than wild type neurons treated with either DMS or CEA. Granule cell development and motor function were also more severely disturbed by MAM and HN2 in Mgmt[superscript −/−] mice than in comparably treated wild type mice. In contrast, cerebellar development and motor function were well preserved in MAM-treated Aag[superscript −/−] or MGMT-overexpressing (Mgmt[superscript Tg+]) mice, even as compared with wild type mice suggesting that AAG protein increases MAM toxicity, whereas MGMT protein decreases toxicity. Surprisingly, neuronal development and motor function were severely disturbed in Mgmt[superscript Tg+] mice treated with HN2. Collectively, these in vitro and in vivo studies demonstrate that the type of DNA lesion and the efficiency of DNA repair are two important factors that determine the vulnerability of the developing brain to long-term injury by a genotoxicant.United States. Army Medical Research and Materiel Command (Contract/Grant/Intergovernmental Project Order DAMD 17-98-1-8625)United States. National Institutes of Health (grants CA075576)United States. National Institutes of Health (RO1 C63193)United States. National Institutes of Health (P30 CA043703

Association between mean platelet volume levels and inflammation in SLE patients presented with arthritis

Background: Systemic lupus erythematosus (SLE) may be characterized by periods of remissions and chronic or acute relapses. The complexity of clinical presentation of the SLE patients leads to incorrect evaluation of disease activity. Mean platelet volume (MPV) has been studied as a simple inflammatory marker in several diseases. There is no study in the literature about MPV levels in adult SLE patients with arthritis.Objectives: We aimed to investigate the MPV levels in the SLE population with arthritis during and between activations.Methods: The study consisted of 44 SLE patients with arthritis in activation period (Group 1), the same 44 SLE patients with arthritis in remission period (Group 2) and 44 healthy controls (Group 3). Erythrocyte sedimentation rate (ESR), creactive protein (CRP), white blood cell count, platelet count, and mean platelet volume (MPV) levels were retrospectively recorded from patient files.Results: The mean ages of the SLE subjects were 42 ± 16 years, while the mean ages of controls was 41 ± 17 years. MPV was significantly lower in Group 1(7.66±0.89fL) than in Group 2 (8.61±1.06 fL) and Group 3(8.62±1.11fL) (p<0.0001). The differences between groups reached statistical significance.Conclusions: We suggest that MPV levels decrease in patients with arthritis of SLE activation when compared to the same patients in remission and healthy controls.Key words: Systemic lupus erythematosus, Arthritis, Mean platelet volum

Epigenetic memory in induced pluripotent stem cells

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an ‘epigenetic memory’ of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.National Institutes of Health (U.S.) (NIH grant RO1-DK70055)National Institutes of Health (U.S.) (NIH Grant RO1-DK59279)National Institutes of Health (U.S.) (American Recovery and Reinvestment Act (RC2-HL102815))National Institutes of Health (U.S.) (NIH (K99HL093212-01))Cooley’s Anemia FoundationNational Institutes of Health (U.S.) (NIH LLS (3567-07))National Institutes of Health (U.S.) (NIH grant R37CA054358)National Institutes of Health (U.S.) (NIH grant P50HG003233)National Institutes of Health (U.S.) (NIH grant R01AI047457)National Institutes of Health (U.S.) (NIH Grant R01AI047458)National Institutes of Health (U.S.) (CA86065)National Institutes of Health (U.S.) (HL099999)Thomas and Stacey Siebel FoundationCalifornia Institute for Regenerative Medicine (Fellowship T1-00001

What lies between market and hierarchy? Insights from internalization theory and global value chain theory

In this paper, we suggest that internalization theory might be extended by incorporating complementary insights from GVC theory. More specifically, we argue that internalization theory can explain why lead firms might wish to externalize selected activities, but that it is largely silent on the mechanisms by which those lead firms might exercise control over the resultant externalized relationships with their GVC partners. We advance an explanation linking the choice of control mechanism to two factors: power asymmetries between the lead firms and their GVC partners, and the degree of codifiability of the information to be exchanged in the relationship

The impact of corporate social responsibility disclosure on financial performance : evidence from the GCC Islamic banking sector.

This paper examines the relationship between corporate social responsibility (CSR) and financial performance for Islamic banks in the Gulf Cooperation Council (GCC) region over the period 2000–2014 by generating CSR-related data through disclosure analysis of the annual reports of the sampled banks. The findings of this study indicate that there is a significant positive relationship between CSR disclosure and the financial performance of Islamic banks in the GCC countries. The results also show a positive relationship between CSR disclosure and the future financial performance of GCC Islamic banks, potentially indicating that current CSR activities carried out by Islamic banks in the GCC could have a long-term impact on their financial performance. Furthermore, despite demonstrating a significant positive relationship between the composite measure of the CSR disclosure index and financial performance, the findings show no statistically significant relationship between the individual dimensions of the CSR disclosure index and the current financial performance measure except for ‘mission and vision’ and ‘products and services’. Similarly, the empirical results detect a positive significant association only between ‘mission and vision’ dimension and future financial performance of the examined banks

The Impact of Entrepreneurship Education in Higher Education: A Systematic Review and Research Agenda

Using a teaching model framework, we systematically review empirical evidence on the impact of entrepreneurship education (EE) in higher education on a range of entrepreneurial outcomes, analyzing 159 published articles from 2004 to 2016. The teaching model framework allows us for the first time to start rigorously examining relationships between pedagogical methods and specific outcomes. Reconfirming past reviews and meta-analyses, we find that EE impact research still predominantly focuses on short-term and subjective outcome measures and tends to severely underdescribe the actual pedagogies being tested. Moreover, we use our review to provide an up-to-date and empirically rooted call for less obvious, yet greatly promising, new or underemphasized directions for future research on the impact of university-based entrepreneurship education. This includes, for example, the use of novel impact indicators related to emotion and mind-set, focus on the impact indicators related to the intention-to-behavior transition, and exploring the reasons for some contradictory findings in impact studies including person-, context-, and pedagogical model-specific moderator