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In repeat dose toxicological studies
2020-08-04
In repeat-dose toxicological studies in rodents (Bijland et al., 2011, Butenhoff et al., 2012, Curran et al., 2008, Qazi et al., 2009, Seacat et al., 2003, Sohlenius et al., 1993) and non-human primates (Seacat et al., 2002), PFOS has been shown to produce responses that are consistent with activati
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Autophagy is an important mechanism for EGFR
2020-08-04
Autophagy is an important mechanism for EGFR degradation and signaling limitation. For example, the protein kinase CK2 inhibitor CX-4945 or the herbal plant derivative celastraol induced autophagic degradation of EGFR and consequently inhibited the survival of cancer 4 aminopyridine mg (So et al.,
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Nepicastat is well tolerated in healthy adults and
2020-08-04
Nepicastat is well tolerated in healthy adults and in patients with congestive heart failure (Hegde and Friday, 1998) (Roche Biosciences, unpublished observations) and may represent a better tolerated, more efficacious treatment for cocaine use disorder than disulfiram. As such, the present study wa
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Structural characterization of A S Given the low specific
2020-08-04
Structural characterization of A1S_0222. Given the low specific activity of our protein preparations and the considerable problems to concentrate the protein to levels above 2.5 mg/mL, we employed SAXS to structurally characterize and generate a low-resolution model of A1S_0222 in solution. Fig. 5 a
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Nitric oxide NO was reported to inhibit HPHs although its
2020-08-03
Nitric oxide (NO) was reported to inhibit HPHs, although its inhibitory mechanism remains controversial [9], [10]. For catalytic hydroxylation of HIF-1α, dioxygen (O2) binds to Fe(II) in the active site of HPHs [11]. NO is a molecular mimic for O2 binding as an Fe(II) ligand. Indeed, high resolution
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The PI K AKT mTOR signaling pathway is involved
2020-08-03
The PI3K/AKT/mTOR signaling pathway is involved in regulating cell proliferation, apoptosis [6], migration and invasion [7]. Dysfunction of PI3K/AKT/mTOR signaling pathway is closely related to cancer development and therapeutic resistance. Downstream effectors of PI3K/AKT/mTOR include members of th
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In the last few years a molecular understanding of
2020-08-03
In the last few years, a molecular understanding of why RING dimerization and the C-terminal residues are critical for ubiquitin transfer by IAPs has become clearer. This appreciation of RING domain function has depended on the availability of stable E2~Ub conjugates that are suitable for in vitro a
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br STAR Methods br Acknowledgments We
2020-08-03
STAR★Methods Acknowledgments We would like to thank the DNA cloning, Protein Production, DNA sequencing facility, and mass spectrometry teams of the MRC Protein Phosphorylation and Ubiquitylation Unit for their support. We would like to thank Prof. Dario Alessi, Prof. Ronald Hay, Prof. Philip
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Opioid analgesics are being increasingly used in neonates as
2020-08-03
Opioid analgesics are being increasingly used in neonates as there are several reported adverse physiologic consequences and probable short and long-term behavioral outcomes due to untreated pain [2], [11], [12], [13], [32]. Long-term use of morphine and other opiates is known to produce tolerance a
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Because decreased levels of DGK in
2020-08-03
Because decreased levels of DGKδ in skeletal muscle are critical for the pathogenesis of type 2 diabetes, as described above, the up-regulation of the DGKδ protein level is crucial for treatment and prevention of the disease. Intriguingly, we recently found that myristic Cinobufagin mg (14:0) signif
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We then evaluated in vivo DHODH mRNA expression using
2020-08-03
We then evaluated in vivo DHODH mRNA Asiatic acid using data from TCGA (Lee, Palm, Grimes, & Ji, 2015). To perform a pan-disease comparison of DHODH expression, log2 TPM expression values were converted to z-scores calculated per patient. Fig. 6 shows that across all 34 diseases (9726 unique patien
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Ehl n et al analyzed cohorts of ovarian carcinoma
2020-07-31
Ehlén et al. analyzed 2 cohorts of ovarian carcinoma patients. CHK1 mRNA expression, analyzed in a series of 267 serous and endometrioid carcinomas, was significantly related to shorter relapse-free survival (RFS) in univariate, but not in multivariate analysis, and was unrelated to OS. In a second
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As an important cell division modulator CDK exerts its funct
2020-07-31
As an important cell division modulator, CDK4 exerts its functional role mainly through phosphorylation of Rb and promotion of the transition from G1 to S phase of the (S)-Methylisothiourea sulfate [43]. In response to mitogenic signals, CDK4/6 combines with cyclin D and transfers into the nucleus.
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Introduction Primitive neuroectodermal tumors PNETs are mali
2020-07-31
Introduction Primitive neuroectodermal tumors (PNETs) are malignant, small round cell tumors of neural crest origin which typically arises from bone or soft tissue in the trunk/axial skeleton/paraspinal regions in adolescents and young adults and comprises of 50% cases with local recurrence and met
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neostigmine mechanism of action br Although we do not know w
2020-07-31
Although we do not know which molecular effectors of ERK pathway are sensitive to mechanical stress, neostigmine mechanism of action experiments suggest that modulation occurs upstream and/or at the level of EGFR (see Figures S6A–S6C; Video S5). Accordingly, a large pool of EGFR is located at adh
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