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In summary we hypothesize that
2021-07-19
In summary, we hypothesize that targeting the A1R–D1R heterotetramer with heteromer-selective drugs might improve safety and efficacy of the pharmacological therapy for RLS and other motor diseases, resulting in fewer side effects than classical drugs developed for targeting monomeric A1R or D1R.
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br Roles of TLS polymerases outside
2021-07-19
Roles of TLS polymerases outside DNA damage tolerance Preparing the ground for more DNA damage: adaptive responses through gene induction Conclusions and perspectives Although known for many decades, the relevance of TLS in genome stability is normally considered secondary to mechanisms tha
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br Biological roles of DGK br
2021-07-19
Biological roles of DGKϵ Summary and future perspectives The most 5-hme-CTP segment of DGKϵ, comprised of residues 20–42, appears to have no role in binding the lipid substrate DAG or in the acyl chain specificity of substrate phosphorylation. Nevertheless, the sequence in this segment of DGK
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Global inhibition of integrin signaling
2021-07-19
Global inhibition of integrin signaling with EDTA here suggests that integrin signaling potentially cooperates with DDR2 in collagen induction of lysyl oxidase. This notion is supported by a recent study that shows DDR2 cooperation with specific integrins in cell adhesion to collagen [47]. It is of
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Three dimensional conformational changes in the cargo protei
2021-07-19
Three-dimensional conformational changes in the cargo protein’s NES, caused by protein phosphorylation, dephosphorylation, or mutation, can regulate CRM1 binding (Craig et al., 2002, Vogt et al., 2005). Additional protein modifications such as sumoylation, ubiquitination, acetylation, and/or the bin
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In the intestine absorbed cholesterol
2021-07-19
In the intestine, absorbed cholesterol can either be esterified by ACAT2 (Soat2) and packed into chylomicrons, transported back to the intestinal lumen by ABCG5/ABCG8, or it can be transported into HDL by ABCA1. ACAT2 is confined to enterocytes and hepatocytes and esterifies cholesterol for intracel
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br Funding This work was supported by intramural
2021-07-19
Funding This work was supported by intramural funding of the Department of Internal Medicine I-Cardiology, University Hospital Aachen, RWTH Aachen. Acknowledgments Introduction Cyclic adenosine monophosphate (cAMP) is a central second messenger that controls a plethora of vital functions.
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In contrast crystal structures of
2021-07-17
In contrast, crystal structures of the oxyester-linked Ubc13 and UbcH5b conjugates (Eddins et al., 2006, Sakata et al., 2010), and the NMR structure of the disulfide-linked UbcH8 conjugate (Serniwka & Shaw, 2009), revealed distinct open conformations (Fig. 10.3). In part, differences in the position
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br Common features of TdT pol and
2021-07-17
Common features of TdT, pol μ and pol λ TdT, pol μ and pol λ remain in a closed conformation throughout their catalytic cycle, contrary to pol β [24•, 53, 54•]. One possible explanation for this observation is that they have traded fidelity (which requires open-to-closed transition) for a very ti
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Importantly piPolB holds a great promise for developing
2021-07-17
Importantly, piPolB holds a great promise for developing novel biotechnological applications. For instance, in vitro activities of piPolB, namely, strand displacement and faithful, processive DNA polymerization, can be harnessed for efficient primer-independent whole-genome amplification, whereas th
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Quercetin competitively inhibited BFC activity in human reco
2021-07-17
Quercetin competitively inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 with Ki=15.4±1.52μM, and myricetin noncompetitively with Ki=74.6±7.99μM (Fig. 4). The degree of inhibition by quercetin was not affected by a pre-incubation step and was similar in the microsomes from both gend
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The use of inhibitors clearly has its caveats and
2021-07-17
The use of inhibitors clearly has its caveats and the field should come to a consensus on etomoxir concentration to maximally block LC-FAO while minimalizing off-target effects. The current papers convincingly show that 200 μM is too high, but it should be noted that 3 μM does not fully suppress LC-
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Several highly selective COX inhibitors coxibs have been rep
2021-07-17
Several highly selective COX-2 inhibitors (coxibs) have been reported and marketed [6], including celecoxib [7] and etoricoxib [8] (Fig. 1). Even though these drugs produce less ulceration than conventional NSAIDs, coxibs still produce significant gastric and cardiovascular side effects due to the d
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Rambabu et al reported A series of
2021-07-17
Rambabu et al. reported A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives synthesized from readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and further reacted with different substituted am
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This study demonstrates that GUL affects multiple
2021-07-17
This study demonstrates that GUL-1 affects multiple pathways/processes. As GUL-1 is likely to function as an RNA-binding protein, it is conceivable that the mRNAs involved are bound to GUL-1 as part of the regulatory function of the protein. In fact, in S. cerevisiae Ssd1 was shown to bind multiple
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