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A different example of substrate dependent activation is see
2020-06-10

A different example of substrate-dependent activation is seen in CSN5, a JAMM-type DUB found in the eight subunit COP9 signalosome (CSN) [34]. The CSN deconjugates NEDD8 (neural precursor cell expressed developmentally downregulated 8) from Cullin Ring ubiquitin E3 ligases (CRLs). Through this activ
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Indeed the alkyl group is not seen
2020-06-10

Indeed, the -alkyl group is not seen in the original crystallographic electron density omit map prior to positioning either inhibitor in DHODH, nor can it be found in the final maps. Rather, the electron density maps are consistent with hydrolysis of the amide to the acid. Once the scaffold was clea
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Compound was advanced to a chronic
2020-06-10

Compound 52 was advanced to a chronic efficacy study in db/db mice maintained on a high fat diet. Animals were dosed with 0.5% methylcellulose vehicle, CP-690550 Citrate 52 (1, 3 or 15mg/kg, po, Q.D.) or 1 (0.3mg/kg) for 14days. Over the course of the study body weight and food intake were measured
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For the SAR optimization of the right
2020-06-10

For the SAR optimization of the right hand side, it was decided to explore the inclusion of the key carboxylic cell division cycle moiety present in the original DGAT-1 inhibitors from . Analogs were constructed by the synthetic routes outlined in , . In , the methylene-oxy linker was introduced by
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For radiochemotherapy it is well known
2020-06-10

For radiochemotherapy, it is well known that mitotic cell death and apoptosis present the major cell death modes. More recently, autophagy-dependent cell death has been described to occur upon radiochemotherapy (Daido et al., 2005, Song et al., 2017). This form of regulated cell death depends on com
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One specific brain region that may be involved
2020-06-10

One specific Dihydroartemisinin region that may be involved in the reduction of anxiety after anti-SVG-30 treatment is the lateral septum which contains a high density of CRF2 receptors [5], [44]. The lateral septum often exhibits increased immediate early gene expression in response to stress and
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In this study we further investigated
2020-06-10

In this study, we further investigated the involvement of CRF1 and CRF2 receptors of the dPAG in the regulation of panic-related responses. For this, we used two animal models that associate escape behavior with panic attacks: the elevated T maze and the electrical stimulation of the dPAG (for a ful
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br Conflicts of interest br Financial support NZ is
2020-06-09

Conflicts of interest Financial support NZ is an Established Investigator of the Dutch Heart Foundation (2013T111) and is supported by an ERC Consolidator grant (617376) from the European Research Council and by a Vici grant from the Netherlands Organization for Scientific Research (NWO; 91818
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DNA damage represents a persistent threat to genomic
2020-06-09

DNA damage represents a persistent threat to genomic stability. A critical link exists between DNA mutation, chromosomal rearrangement and cancer development. In myeloid malignancies, various chromosomal translocations and/or mutations increased cellular reactive oxygen species (ROS), followed by DS
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Sex has been shown to mediate
2020-06-09

Sex has been shown to mediate the relationship between allelic differences in COMT and behavior (Harrison & Tunbridge, 2008). The COMT promoter region contains 2 estrogen response elements (Xie, Ho, & Ramsden, 1999) that can inhibit the formation of COMT (Jiang, Xie, Ramsden, & Ho, 2003). With regar
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The selective estrogen receptor modulators SERMs are another
2020-06-09

The selective estrogen receptor modulators (SERMs) are another type of estrogen receptor ligands. The main difference between SERMs and xenoestrogens relies on the fact that SERMs present functional duality and are able to act both as agonists and antagonists of the estrogen receptors in different t
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br Material and methods br Results br Discussion Both proges
2020-06-09

Material and methods Results Discussion Both progesterone and estradiol are major ovarian steroids crucial for the development and homeostasis of the female reproductive tract (Patel et al., 2015). In the cervix, estrogen softens the cervical stroma affecting the extracellular matrix (ECM)
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br Materials and methods br Results br Discussion
2020-06-09

Materials and methods Results Discussion Cisplatin, as one member of a class of platinum-containing anti-cancer drugs, which displays a great deal of clinical activity on a wide variety of solid tumors. In addition, cisplatin often used in combination with other chemotherapy drugs to treat
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As the communications interface was developed
2020-06-08

As the communications interface was developed by two separate organisations with differing software processes and tools, a modular approach to the safety case was deemed appropriate. The modular approach related the communications interface safety argument to the safety arguments for both the ACS an
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We found that E and GEN each has mostly similar
2020-06-08

We found that E2 and GEN each has mostly similar effects on recruitment of the epigenetic modulators to the MB-COMT distal promoter (summarized in Table 2). These effects are associated with increased promoter methylation and gene suppression of COMT. It is noted that the array of epigenetic modulat
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