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Modulating protein stability specifically inhibiting ubiquit
2021-07-14

Modulating protein stability, specifically inhibiting ubiquitin E3 ligases, provides potential advantages over other druggable targets given the presence of biochemically multiple, unique pharmacophores within complexes that can bind a variety of small molecules [12]. The FBXO3 inhibitors used here
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NAD+ synthesis Midazolam oral clearance is used for characte
2021-07-13

Midazolam oral clearance is used for characterization of both intestinal and hepatic CYP3A activity. However, the identification and subsequent use of metabolic markers of CYP3A activity can eliminate the need for unnecessary administration of probe drugs such as midazolam. Such metabolic markers wo
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Deregulated Wnt signaling either due to pathway
2021-07-13

Deregulated Wnt signaling, either due to pathway mutations or otherwise aberrant pathway activity, is common in CLL [81], [82]. In addition to targets described above, alvocidib also inhibits glycogen synthase kinase 3 (GSK3)-β at higher nanomolar concentrations [37]. Despite intuition and experimen
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As the principal receptors for regulating the inflammatory
2021-07-13

As the principal receptors for regulating the inflammatory process in mammals, CXCR1 and CXCR2 have an important role in regulating the trafficking of phagocytes such as neutrophils, monocytes and macrophages (Viola and Luster, 2008). The evidence gathered to date from fish studies are in agreement
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br Materials and methods br Results To
2021-07-13

Materials and methods Results To investigate the effect of 17βE on cell proliferation in the human renal tubular epithelia, BrdU uptake was measured in HRTEC primary and 3D-HRTEC cultures, allowing determination of the DNA replication rate. Representative microphotographs show BrdU uptake in H
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Several questions remain to be addressed
2021-07-13

Several questions remain to be addressed. The hormones and metabolites that modulate expression of EERγ in the steps leading to maturation need to be identified to learn more about physiological and pathophysiological regulation of EERγ in β cells. Considering that ERRγ repressed cell cycle genes in
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Which other approaches can complement signaling optogenetics
2021-07-13

Which other approaches can complement signaling optogenetics to paint a more complete picture of developmental Erk signaling? For now, the authors have dynamically manipulated Erk signaling but measured the Erk output at steady-state using classic immunofluorescence techniques (Johnson and Toettcher
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It has previously been established that
2021-07-12

It has previously been established that DDRs play an important role in collagen regulation in at least two distinct ways: (1) activation of DDRs by collagen results in up-regulation of the matrix metalloproteinases, which results in cleavage and degradation of the ECM20., 21., [22] and (2) Saikosapo
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Studies have focused on a hydrophobic cage at
2021-07-12

Studies have focused on a hydrophobic cage at the CULT domain, conserved from bacteria to mammals, as it binds to substrates and IMiDs (Chamberlain et al., 2014, Lupas et al., 2015). In addition, CRBN ligand-mediated protein degradation was highly conserved, which was confirmed in vertebrates by foc
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br Author contribution br Acknowledgements
2021-07-12

Author contribution Acknowledgements We want to thank Dr. Manuel Rodriguez, Dr. Ch. Blattner, Dr. Jorge Moscat, Dr. Erwin Knecht and Dr. Peter Tontonoz for materials. This work has been supported by grants from the Spanish Ministry of Education and ScienceSAF2011-27442 and a grant from General
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An important question is to what extent any
2021-07-12

An important question is to what extent any differences in radioligand characteristics may have contributed to discrepancies between studies. Two studies on schizophrenia addressed this question directly by using [11C]SCH 23390 and [11C]NCC 112 in the same individuals, not finding any differences be
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br Materials and methods br
2021-07-12

Materials and methods Results Discussion Cysteine proteases are upregulated under oxidative stress and play an important role in the preservation of cellular metabolism (Usui et al., 2007). Cysteine proteases are also important under abiotic stresses for plants to degrade proteins denatured
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br Acknowledgements br Introduction In Arabidopsis thaliana
2021-07-12

Acknowledgements Introduction In Arabidopsis thaliana (L.) Heynh, there are at least four copies of the caseine kinase-like gene Ck1, which is involved in peptide phosphorylation in mammals [1]. These genes are distributed on Nicotinic Acid 1, 2, 4, and 5. A similar number of copies for Ck1 h
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br Conclusions br Introduction Today just as
2021-07-12

Conclusions Introduction Today – just as for the past 50 years – the most commonly used repellent in the world is DEET (Fradin, 1998; Pickett et al., 2008). The active ingredient, N,N-Diethyl-m-toluamide, is an oily synthetic substance applied topically to the skin in order to alter the host f
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The four other mutations S T V I T
2021-07-12

The four other mutations (S281T, V317I, T328A and A329S) were not detected in the absence of the A286S. This could suggest that when all of them are present, there would be a tri-dimensional structural modification that would interfere with the binding of the insecticide and produce different levels
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