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In this study we generated mice in which the
2020-06-11

In this study we generated mice in which the native Bcl6 locus was engineered to produce a form of Bcl6 containing a mutant RD2 domain that disrupts its repressor function. We found that RD2 domain is essential for pre-GC B cell differentiation and clustering into nascent GC within follicles, in par
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TRAF and TRAF were initially identified as
2020-06-11

TRAF1 and TRAF2 were initially identified as tumor necrosis factor receptor 2 (TNRF2)-associated components, TRAF4 was overexpressed in breast carcinoma cells, whereas TRAF3, TRAF5 and TRAF6 were discovered by their interaction with specific domains in the cytoplasmic tails of trans-membrane recepto
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br Ubiquitination and deubiquitination pathways Ubiquitinati
2020-06-11

Ubiquitination and deubiquitination pathways Ubiquitination is a part of the post-translational modification (PTM) process. Ubiquitination affects proteins in various ways, but its main functions are to signal protein degradation via the 26S proteasome, modify cellular location of proteins, affec
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Twin studies have shown that P has moderate heritability Zuc
2020-06-11

Twin studies have shown that P has moderate heritability. Zuckerman (1989) reviewed the earlier studies of P or related traits and found a median heritability of 0.51. However, twin studies using an Eysenckian P scale have tended to estimate somewhat lower heritabilities than this, in the range 0.36
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Except for S adenosylmethionine SAM Fig
2020-06-11

Except for S-adenosylmethionine (SAM, Fig. 1), sources of endogenous DNA alkylation are not well defined. Other possible sources include nitroso compounds related to the well known mutagen methylnitrosourea which are generated in vitro by nitrosation of cellular amines including amino acids, protein
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br Acknowledgments We thank Jon Clardy Juan Manuel
2020-06-11

Acknowledgments We thank Jon Clardy, Juan Manuel Domínguez, José Francisco García Bustos, and the GlaxoSmithKline (GSK) Plasmodium falciparum dihydroorotate dehydrogenase project team for their contributions, helpful advice, and discussions. Introduction Dihydroorotate dehydrogenase (DHODH) i
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br Materials and methods br Results br Discussion We
2020-06-10

Materials and methods Results Discussion We have evaluated the breast cancer prevention potential of PR blockade under conditions that included exposure to progestogens that are relevant to women (progesterone and MPA) and are known to differ in their receptor-binding and down-stream effect
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In vitro studies suggest that
2020-06-10

In vitro studies suggest that cPLA2α does not show clear preference for the headgroup present at the sn-3 position, although a slight preference for zwitterionic phospholipids such as PC and PE has recently been pointed out [24]. In this regard, mass spectrometry analyses of glycerophospholipid hydr
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Our data demonstrate that MPO increased ETRB mRNA expression
2020-06-10

Our data demonstrate that MPO increased ETRB mRNA expression, which translated into an increase in ETRB protein expression, which proved to be dependent on the enzyme\'s catalytic activity. Of importance, addition of MPO was sufficient to increase ETRB expression, revealing that endogenous (endothel
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Through an unknown mechanism RING
2020-06-10

Through an unknown mechanism, RING/Ubox-type E3 dimers and the N-terminal tail have been shown to function as a modulator of full E3 ubiquitin ligase activity [27]. LRSAM1 promotes a significant enhancement in the formation of the high-molecular-weight products or E3 activity when the RING domain is
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Introduction Ubiquitylation is a post translational modifica
2020-06-10

Introduction Ubiquitylation is a post-translational modification which impacts almost every biological process in the cell. Dysregulation of the ubiquitylation pathway is associated with several diseases, including cancer, neurodegenerative disorders, and immunological dysfunctions. Single ubiquit
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Due to the high attractiveness of
2020-06-10

Due to the high attractiveness of E2 and E3 ligases as drug targets, a number of drug discovery assays have been published, based on detection by fluorescence (Dudgeon et al., 2010, Krist et al., 2016, Zhang et al., 2004), ccr2 antagonist (Davydov et al., 2004, Huang et al., 2005, Kenten et al., 20
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alk5 receptor In the present work we ask whether
2020-06-10

In the present work, we ask whether rNMP incorporation is an evolutionarily conserved property of DNA synthesis in Archaea. For this purpose, we used the best characterized hyperthermophilic anaerobe, Pyrococcus abyssi GE5 [47]. This strain duplicates its genome as fast as Bacteria, supported by euk
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The identification of a gatekeeper mutation also suggests
2020-06-10

The identification of a gatekeeper Phosphatase Inhibitor Cocktail 3 (100X in DMSO) receptor also suggests that alternative DDR2 inhibitors may be required to overcome acquired resistance. Additional DDR2 inhibitors that have been isolated include the recently identified alkaloid natural products di
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The homologous DDRs are composed
2020-06-10

The homologous DDRs are composed of an N-terminal discoidin homology domain, followed by a sequence of ∼220 amino acids unique to the DDRs, a transmembrane domain, a large juxtamembrane domain, and a conserved cytoplasmic tyrosine kinase domain. In a previous study, we demonstrated that DDR activati
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