Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer

Long noncoding RNAs (lncRNAs) are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression

Long Non-Coding RNAs: New Players in Hematopoiesis and Leukemia

Long non-coding RNAs (lncRNAs) are important regulators of gene expression that influence almost every step in the life cycle of genes, from transcription to mRNA splicing, RNA decay, and translation. Besides their participation to normal physiology, lncRNA expression and function have been already associated to cancer development and progression. Here, we review the functional role and mechanisms of action of lncRNAs in normal hematopoiesis and how their misregulation may be implicated in the development of blood cell cancer, such as leukemia

Business capital accumulation and the user cost: is there a heterogeneity bias? JRC Working Papers in Economics and Finance, 2017/11

Empirical models of capital accumulation estimated on aggregate data series are based on the assumption that capital asset types respond in the same way to cost variables. Likewise, aggregate models do not consider potential heterogeneity in investment behavior originating on the demand side for capital, e.g. at the sector level. We show that the underlying assumption of homogeneity may indeed lead to misspecification of standard aggregate investment models. Using data from 23 sectors in 10 OECD countries over the period 1984-2007, we adopt a fully disaggregated approach – by asset types and sectors – to estimate the responsiveness of investment to the tax-adjusted user cost of capital. While accounting for the different sources of heterogeneity, we find that fixed capital accumulation is significantly affected by changes in the user cost. However, the estimated substitution elasticities are smaller than one - the benchmark value under a Cobb-Douglas production function. We do not find robust evidence that the long run substitution elasticities are statistically different across asset types.JRC.B.1-Finance and Econom

The effects of dietary antioxidants on oxidative stress levels in European Starlings, Sturnus vulgaris

Migratory birds rely heavily on the condition of their muscles and the quality of their fat stores to make it safely to their destinations. But unfortunately, they cope with severe muscle damage due to their extremely long endurance flights, which can greatly affect their performance in a negative way. Antioxidants (AOs) are components that combat this muscle damage. Uric acid is considered to be an endogenous antioxidant and reliable biomarker for oxidative damage and is released during muscle catabolism. In this study, female European Starlings underwent a strict training regime leading up to a 6-hour migration simulation. Groups of starlings, both trained and untrained, were fed diets with either no dietary antioxidants added or diets supplemented with antioxidants in the form of anthocyanin. Blood was drawn at three time points- a background sample as a base statistic, a post-flight sample immediately after migratory flight, and a final sample two days after flight recovery. Uric acid levels were measured in blood plasma using TECO Diagnostics Uric Acid Reagent Set. I predict that the uric acid levels will be significantly higher in the absence of the dietary antioxidant, especially in trained birds, as the body will only have access to their endogenous AOs. I also predict that levels of uric acid will be significantly lower in the presence of the dietary AOs due to the decreased amount of oxidative damage and the break down lean tissue. Preliminary results suggest a possible correlation between levels of uric acid and dietary antioxidants

PENGEMBANGAN MEDIA MODUL TEMATIK MATERI POKOK GAYA UNTUK SISWA KELAS IV DI MADRASAH IBTIDAIYAH AL-FALAH GRESIK

Abstrak Berdasarkan hasil studi pendahuluan yakni hasil kegiatan wawancara dan observasi dengan guru mata pelajaran Tematik. Peneliti mendapati bahwa pada materi pokok gaya mata pelajaran Tematik, siswa mengalami kesulitan dalam memahami materi tersebut. Hal ini karena materi perlu pengulangan dan tidak tersedianya sumber belajar. Akibatnya mempengaruhi pada tidak tercapainya tujuan pembelajaran yang telah dirumuskan, yaitu dengan rendahnya nilai ketuntasan yang diperoleh siswa dibawah rata- rata sebanyak 50% dari total keseluruhan siswa yang harus mencapai nilai KKM sebesar 75. Tujuan pengembangan media modul ini dibuat sebagai upaya pemecahan masalah belajar melalui analisis kebutuhaan, sehingga melalui media ini diharapkan dapat meningkatkan ketercapaian suatu tujuan pembelajaran serta meningkatkan hasil belajar siswa. Pengembangan media ini menggunakan model pengembangan R&D. Pelaksanaan uji coba dilakukan beberapa tahap yaitu validasi ahli materi, ahli media, dan uji coba pada siswa. Metode pengumpulan data menggunakan wawancara terstruktur, angket, dan tes. Teknik analisis data menggunakan rumus P yang digunakan untuk mengukur persentase, kemudian untuk instrument tes menggunakan rumus Rpbis dan Uji T-tes. Hasil uji validasi kelayakan media permainan berdasarkan hasil perhitungan angket ahli materi adalah 100%, kemudian hasil perhitungan angket ahli media adalah 72,5%. Data hasil uji coba perorangan memperoleh skor 96%, data hasil uji coba kelompok kecil memperoleh skor 96%, dan data hasil uji coba kelompok besar memperoleh skor 97,5%. Berdasarkan kriteria pada bab III dari uji coba pada siswa media yang dikembangkan dinyatakan layak. Data perolehan uji-t dari pre-test dan post-test diperoleh besar = 19,38 > = 2.03, dapat disimpulkan bahwa peneliti telah berhasil mengembangkan media modul yang efektif untuk materi pokok gaya pada siswa kelas IV di MI Al-Falah Gresik. Kata Kunci: Pengembangan Media, Media Modul, Tematik IPA Abstract Based on preliminary study result that is result of interview and observation activity with thematic subject teacher. Researchers found that on the subject matter of thematic Thematic style, students have difficulty in understanding the material. This is because the material needs repetition and unavailability of learning resources. As a result, it can affect the achievement of the learning objectives that have been formulated, that is, by the low value of mastery obtained by the students below the average of 50% of the total students who must reach the KKM value of 75. The purpose of media development of this module is made as an effort to solve learning problems through the analysis of needs, so that through this media is expected to increase the achievement of a learning objective and improve student learning outcomes. The development of this medium uses the R & D development model. Implementation of trials carried out several stages of validation of material experts, media experts, and testing on students. Methods of data collection using structured interviews, questionnaires, and tests. The data analysis technique uses the formula P used to measure the percentage, then for the test instrument using the formula of Rpbis and T-test. The result of media validation feasibility test based on the result of questionnaire of material expert is 100%, then the result of questionnaire of media expert is 72,5%. Individual trial results scored 96%, small group trial data scored 96%, and large group trial data scored 97,5%. Based on the criteria in chapter III of trials on students developed media declared eligible. The data of t-test obtained from pre-test and post-test obtained t_hitung = 19,38> t_tabel = 2.03, it can be concluded that the researcher has succeeded in developing an effective module media for the subject matter of style in fourth grade students at MI Al-Falah Gresik. Keywords: Development Media, Module Media, Thematic Scienc

Taxation and the Quality of Institutions: Asymmetric Effects on FDI

Economic integration has intensified international competition to attract productive capital. This paper analyzes, both theoretically and empirically, the effect of tax policies and institutional quality on the allocation of FDI - two aspects that the economic literature has extensively investigated, though only in isolation. I build a simple two-country partial equilibrium model to study competition among governments vying for potential investors whose location choices are driven by both the quality of institutions and the corporate tax rate. Modeling good governance as a public good, it is shown that the jurisdiction providing better institutions is able to levy a higher tax on capital. Moreover, provided firms are sensitive enough to institutional quality, it attracts a larger share of investment than the low-quality/low-tax location. The main predictions of the model are tested on FDI stocks to 63 economies using a simple difference gravity equation derived from discrete choice theory of firms' location. Using a pair of destination countries as the unit of analysis eliminates the need to control for multilateral interdependence among receiving countries, a source of possible bias in the traditional gravity specification in the levels. The empirical evidence corroborates the claim that the sensitivity of foreign investment to the tax rate varies significantly between host countries characterized by different levels of institutional quality. The findings are robust to a number of sensitivity checks and to the use of instrumental variables to tackle endogeneity of the institutional quality variable.foreign direct investment, fiscal competition, institutions, public goods

Profit shifting by EU banks: evidence from country-by-country reporting JRC Working Papers in Economics and Finance, 2018/4

We investigate profit shifting by the largest and systemically relevant European multinational banks using new data made available through country-by-country reporting for the financial years 2014-2016. We capture tax incentives for income shifting using a multilateral tax differential between the local tax rate and the tax rates in the other countries where the bank has operations. We find that profits - particularly those recorded in tax havens - are negatively affected by corporate taxation. Moreover, the bulk of income shifting seems to take place among subsidiaries, as foreign-to-foreign tax differences matter significantly more that home-to-foreign differentials. Simulation results suggest that the amount of shifted profits in tax havens is about 38% of true profits. The ratio between shifted and true profits drops to about 7% when selected non havens are considered.JRC.B.1-Finance and Econom

Regulation of ribosome function by RNA modifications in hematopoietic development and leukemia: it is not only a matter of m6A

Growth and maturation of hematopoietic stem cells (HSCs) are largely controlled at both transcriptional and post-transcriptional levels. In particular, hematopoietic development requires a tight control of protein synthesis. Furthermore, translational deregulation strongly contributes to hematopoietic malignancies. Researchers have recently identified a new layer of gene expression regulation that consists of chemical modification of RNA species, which led to the birth of the epitranscriptomics field. RNA modifications provide an additional level of control in hematopoietic development by acting as post-transcriptional regulators of lineage-specific genetic programs. Other reviews have already described the important role of the N6-methylation of adenosine (m6A) within mRNA species in regulating hematopoietic differentiation and diseases. The aim of this review is to summarize the current status of the role of RNA modifications in the regulation of ribosome function, beyond m6A. In particular, we discuss the importance of RNA modifications in tRNA and rRNA molecules. By balancing translational rate and fidelity, they play an important role in regulating normal and malignant hematopoietic development

PIN domain of Nob1p is required for D-site cleavage in 20S pre-rRNA

Nob1p (Yor056c) is essential for processing of the 20S pre-rRNA to the mature 18S rRNA. It is part of a pre-40S ribosomal particle that is transported to the cytoplasm and subsequently cleaved at the 3' end of mature 18S rRNA (D-site). Nob1p is also reported to participate in proteasome biogenesis, and it was therefore unclear whether its primary activity is in ribosome synthesis. In this work, we describe a homology model of the PIN domain of Nob1p, which structurally mimics Mg(2+)-dependent exonucleases despite negligible similarity in primary sequence. Insights gained from this model were used to design a point mutation that was predicted to abolish the postulated enzymatic activity. Cells expressing Nob1p with this mutation failed to cleave the 20S pre-rRNA. This supports both the significance of the structural model and the idea that Nob1p is the long-sought D-site endonuclease