Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1

© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An alternative pathway for ATR activation has been proposed to occur via stalled RNA polymerase II (RNAPII). However, how RNAPII might signal to activate ATR remains unknown. Here, we show that ATR signaling is increased after depletion of the RNAPII phosphatase PNUTS-PP1, which dephosphorylates RNAPII in its carboxy-terminal domain (CTD). High ATR signaling was observed in the absence and presence of ionizing radiation, replication stress and even in G1, but did not correlate with DNA damage or RPA chromatin loading. R-loops were enhanced, but overexpression of EGFP-RNaseH1 only slightly reduced ATR signaling after PNUTS depletion. However, CDC73, which interacted with RNAPII in a phospho-CTD dependent manner, was required for the high ATR signaling, R-loop formation and for activation of the endogenous G2 checkpoint after depletion of PNUTS. In addition, ATR, RNAPII and CDC73 co-immunoprecipitated. Our results suggest a novel pathway involving RNAPII, CDC73 and PNUTS-PP1 in ATR signaling and give new insight into the diverse functions of ATR.Norwegian Cancer Society [3367910]; South-Eastern Norway Health Authorities [2014035, 2013017]; Norwegian Research Council [275918]; EEA Czech-Norwegian Research Programme (Norwegian Financial Mechanism 2009–2014 and the Ministry of Education, Youth and Sports [Project Contract no. MSMT-22477/2014 (7F14061)]. Funding for open access charge: Norwegian Research Council.info:eu-repo/semantics/publishedVersio

Introducing the party-interest group relationships in contemporary democracies datasets

Few existing datasets on parties and interest groups include data from both sides and a wide variety of interest groups and parties. We contribute to filling this gap by making several interconnected new datasets publicly available. The PartyInterest Group Relationships in Contemporary Democracies (PAIRDEM) datasets include cross-national data from three different surveys of (1) central party organizations, (2) legislative party groups, and (3) interest groups. A fourth dataset based on coding of party statutes and party finance data was established together with the Political Party Database The datasets contain novel indicators on party-group relationships in up to 21 mature democracies. In this research note, we first present the main content of the datasets and the research design. Second, we present descriptive statistics documenting the extent of organizational ties between parties and groups in contemporary democracies. Third, we illustrate more advanced usage through a simple application

Penggunaan Media Gambar Dalam Meningkatkan Kemampuan Membaca Permulaan Siswa Kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai

Pokok permasalahan dalam penelitian ini adalah rendahnya tingkat kemampuan membaca permulaan siswa kelas I SDN Uwedaka dalam pembelajaran Bahasa Indonesia. Tujuan Penelitian adalah untuk meningkatkan kemampuan membaca permulaan siswa kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai. Berdasarkan hasil observasi yang didapatkan masih terdapat beberapa siswa yang sama sekali belum bisa membaca. Pembelajaran membaca permulaan di SDN Uwedaka selama ini hanya menggunakan media pembelajaran yang konvensional yaitu dengan menggunakan papan tulis, pembelajaran yang hanya berpusat pada guru, penggunaan media dalam pembelajaran sebagai alat bantu masih sangat terbatas, hal ini menyebabkan kemampuan membaca permulaan yang masih rendah dan terlihat hampir 65% siswa masih mengalami kesulitan membaca dalam proses belajar mengajar. Metode yang digunakan adalah metode deskriptif kualitatif dan kuantitatif. Data kualitatif didapatkan dari hasil tes dan observasi siswa dan guru. data kuantitatif didapatkan dari hasil tes belajar. Desain penelitian ini mengacu pada desain oleh Kemmis dan Mc Taggart yang terdiri dari empat tahapan, yaitu perencanaan, pelaksanaan tindakan, observasi dan refleksi. Data dikumpulkan melalui penilaian proses dan penilaian hasil setiap akhir tindakan. Penelitian ini dilakukan dalam dua siklus. Pada siklus I diperoleh nilai rata-rata siswa yaitu sebesar 67 dengan ketuntasan belajar klasikal sebesar 40% serta daya serap 66,6%. Pada siklus II, nilai rata-rata meningkat menjadi 83 dengan ketuntasan klasikal sebesar 100% serta daya serap klasikal sebesar 83,3%. Bersarkan hasil penelitian maka dapat disimpulkan bahwa penggunaan media gambar dapat meningkatkan kemampuan membaca permulaan terhadap siswa kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai

Policy today or office tomorrow?

Interest groups play an important role in contemporary democracies. They aggregate interests, spread information and attempt to influence policies. But how can we explain that some groups have an easier time than others finding a willing ear amongst legislative party groups? Parties have up until recently been overlooked in the literature about bias in interest group influence, despite them being important actors in contemporary democracies. This thesis examines one piece of the larger puzzle; bias in interest group influence on the party’s legislative branches. Hypotheses are deducted from a rational choice framework that sees bias in interest group influence on legislative party groups as a resource exchange where parties give interest groups policy influence today in exchange for interest group resources that can help the party obtain office and policy in the future. Explanatory factors related to issue, party and interest group characteristics are explored. Both media issue salience, party issue salience, interest group resources and party size are found to have an effect on bias in interest group influence. While there are several variables with a significant effect, I do not find support for any of my hypotheses. Nevertheless, there seems to be an interesting covariation between several of the variables I include in the analysis and bias in interest group influence. These are relationships that deserve more attention in the future

CSR in International Business - Creating Shared Value

The world is experiencing several global issues of economic, social, cultural, and humanitarian characters, and they are continuously increasing in scale. Multinational corporations (MNCs) are considered as both contributors to the problems, but also as a big part of the solutions. Consequently, the pressure put on firms to take responsibility for their actions is increasing, and corporate social responsibility (CSR) has emerged as an inescapable priority for managers. However, MNCs investments in CSR are moderate, namely because the firms consider such investments as a cost factor only. A literature review on the subject of CSR within international business revealed that research investigating what MNCs may receive in return of their CSR investments, is absent. This study responds to the lack of research by addressing how MNCs may use CSR to create shared value, benefiting both the firm itself, as well as the society. The focus centres on the issue of whether and how shared value can be achieved through creating either a competitive advantage or a blue ocean, by engaging in responsible actions. In order to investigate the subject, a case study is performed on two Norwegian MNCs that have incorporated responsible actions in their business strategies, as the only actors in their respective industries. The findings of this study reveal that MNCs can create shared value by pursuing the two different methods investigated. It is found that MNCs can create a competitive advantage by differentiating themselves from their competitors by acting responsibly. Additionally, a blue ocean can be created by initiating a value innovation based on CSR. However, in order for both methods to be viable, certain guidelines must be followed, and preconditions must be fulfilled. Based on the findings in this thesis, a strategy framework and tool is developed in order to provide clear guidance for other MNCs, on how to best achieve shared value creation. We call it the Green Planet Strategy. In order to create shared value, the firm must develop a sustainable value innovation, that is, a value innovation based on responsible actions. Such an innovation is created by reducing firm risks and costs, while increasing the value offering to the customers. Additionally, the responsible strategy must have relevance, which is achieved by addressing the most pressing issues in the specific industry. Helpful guidance, preconditions, as well as tools are presented to help the firm create the best possible sustainable value innovation. The findings of this study provide evidence for managers that business opportunities exist within CSR, and that CSR is not solely an expense. Thus, managers must discard this wrongful perception of CSR and acknowledge the opportunities that exist within this field. However, without true commitment from the top management, these opportunities can never be fully exploited. Furthermore, policy-makers need to intensify their work to impose additional and stricter regulations on MNCs. Additionally, indirect policy-makers must acknowledge their responsibility regarding this work

Systematic assessment of prognostic gene signatures for breast cancer shows distinct influence of time and ER status

BACKGROUND: The aim was to assess and compare prognostic power of nine breast cancer gene signatures (Intrinsic, PAM50, 70-gene, 76-gene, Genomic-Grade-Index, 21-gene-Recurrence-Score, EndoPredict, Wound-Response and Hypoxia) in relation to ER status and follow-up time. METHODS: A gene expression dataset from 947 breast tumors was used to evaluate the signatures for prediction of Distant Metastasis Free Survival (DMFS). A total of 912 patients had available DMFS status. The recently published METABRIC cohort was used as an additional validation set. RESULTS: Survival predictions were fairly concordant across most signatures. Prognostic power declined with follow-up time. During the first 5 years of followup, all signatures except for Hypoxia were predictive for DMFS in ER-positive disease, and 76-gene, Hypoxia and Wound-Response were prognostic in ER-negative disease. After 5 years, the signatures had little prognostic power. Gene signatures provide significant prognostic information beyond tumor size, node status and histological grade. CONCLUSIONS: Generally, these signatures performed better for ER-positive disease, indicating that risk within each ER stratum is driven by distinct underlying biology. Most of the signatures were strong risk predictors for DMFS during the first 5 years of follow-up. Combining gene signatures with histological grade or tumor size, could improve the prognostic power, perhaps also of long-term survival