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Does a universal mechanism for TLS exist Our
2021-05-12

Does a universal mechanism for TLS exist? Our previous studies using the bacteriophage T4 DNA polymerase generated the model provided in Fig. 7 that quantifies the molecular forces influencing key steps in the polymerization pathway during the replication of a non-instructional versus miscoding DNA
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Acknowledgments We are grateful to Dr Jean
2021-05-12

Acknowledgments We are grateful to Dr. Jean-Marie Bernassau for his leadership in establishing our virtual screening platform and Dr. Julie Bick for protein purification. X-ray data collection for compound 4 was performed by Shamrock Structures at Southeast Regional Collaborative Access Team (SER-C
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Our finding that activating DDR
2021-05-12

Our finding that activating DDR2 variants are a cause of this disease suggested that the ABL inhibitor dasatinib, a leukemia drug that also inhibits DDR2, could be used for treatment of affected individuals.10, 11 To examine the effect of dasatinib on p.Leu610Pro- and p.Tyr740Cys-induced autophospho
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Pentostatin Collagen alignment can contribute to tissue stif
2021-05-12

Collagen alignment can contribute to tissue stiffening (Malik et al., 2015, Paszek et al., 2005), and ECM stiffness in turn is a powerful activator of integrin function (Levental et al., 2009). These findings highlight the contribution of the mechanical properties of the ECM to signal transduction.
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Some mechanistic experiments performed in the early s
2021-05-12

Some mechanistic experiments performed in the early 2000s by Ongusaha et al. [78], suggest that DDR1 induction protects Peramivir from apoptosis in a p53-dependent manner, and that impairment of DDR1 expression or function leads to a pronounced increase of DNA damage-induced apoptosis. This evidenc
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During the course of our research on mGlu
2021-05-12

During the course of our research on mGlu PAMs,, the hydroxyacetophenone scaffold was found to possess dual mGlu PAM and CysLT1 antagonism activity, presumably as orthosteric antagonist (). There is currently an increasing interest in drug discovery to explore multitarget drugs or polypharmacology
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Artificial permutations have also been exploited by protein
2021-05-11

Artificial permutations have also been exploited by protein engineering to manipulate protein scaffolds, in order to improve catalytic activity, alter substrate or ligand binding affinity, reduce proteolytic susceptibility, increase stability, generate different aggregation states and improve fluore
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Despite the differences in the clustering abilities of DDR b
2021-05-11

Despite the differences in the clustering abilities of DDR1b versus DDR2 upon ligand administration, we also noted striking similarities in the spatial distribution and phosphorylation of DDR1b-YFP and DDR2-GFP. We show for the first time that in MC3T3-E1 cells, after 4 h of collagen administration,
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ELUXA HM EMSI is an ongoing
2021-05-11

ELUXA 1 (HM-EMSI-202) is an ongoing pivotal Phase II global clinical trial, designed to further investigate the efficacy and safety of Olmutinib in patients T790M-positive NSCLC with acquired resistance after first-line EGFR TKIs. Primary endpoint is ORR according to RECIST 1.1, while secondary endp
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Previous in vitro and in vivo studies have
2021-05-11

Previous in vitro and in vivo studies have shown the potent ability of toll-like receptor (TLR) ligands and type I interferon (IFN) signaling to induce CH25H in macrophages and DCs following exposure to innate immune stimuli (Bauman et al., 2009; Diczfalusy et al., 2009; Park and Scott, 2010; Zou et
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Mono and bi ubiquitination of
2021-05-11

Mono- and bi-ubiquitination of two lysines, namely K70 and K76, in a small fraction of p33 replication co-factor has been demonstrated in yeast (Barajas and Nagy, 2010, Li et al., 2008). Because mutations of these lysines reduced TBSV repRNA replication in yeast and affected the ability of p33 to in
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Diabetic retinopathy is a chronic inflammatory disease Local
2021-05-11

Diabetic retinopathy is a chronic inflammatory disease. Local inflammation plays a pivotal role in the pathological development and progression of this disease [24]. In addition to TNF-α, several other cytokines, chemokines, and other factors such as IL-1β, IL-6, and C-reactive protein have been ind
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Phorbol 12,13-dibutyrate Against this backdrop we set out to
2021-05-11

Against this backdrop, we set out to identify synthetic and endogenous ligands that bind directly to and regulate the activity of Nurr1. Owing to the pivotal role Nurr1 plays in producing and processing dopamine, and the need for neurons to tightly regulate dopamine levels, we postulated that the re
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A set of small molecule LigI inhibitors
2021-05-11

A set of small molecule LigI inhibitors were identified through an in silico structure-based screen, using the atomic resolution structure of LigI complexed with nicked DNA [[18], [26]]. This screen yielded inhibitors that were selective for LigI (L82), inhibited both LigI and LigIII (L67) and inhib
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Because of the complexity of
2021-05-11

Because of the complexity of DNA damage and its repair, several pathways are candidates in HN2-induced DPC repair. Considering the 23kDa molecular weight of MGMT, NER may be ineffective for MGMT-adduct removal. This presumption is supported by that the mRNA level of ERCC1, a core gene in NER pathway
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