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Biological evaluations of the compounds were done both using
2022-01-28
Biological evaluations of the compounds were done both using HCV protease and replicon assays. Results are shown in . The protease inhibitory IC’s were determined using a FRET assay with HCV NS3/4A 1a protease domain. The replicon EC’s were determined using a replicon luciferase cell-based assay. Th
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In order to study the role of haspin
2022-01-28
In order to study the role of haspin’s kinase activity in mitosis (and other cellular processes) and its potential role in cancer, we sought to identify and optimize inhibitors. Utilizing a recently developed time-resolved fluorescence resonance energy transfer (TR-FRET) high throughput screening (H
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Here we report the genomic structure and the phylogenetic an
2022-01-28
Here we report the genomic structure and the phylogenetic analysis of testis-specific Ser/Thr kinase haspin gene. Materials and methods Results Discussion The isolation and analysis of haspin genomic DNA showed that haspin was an intron-less gene and localized in an intron of integrin αM29
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After initial validation of the ability
2022-01-28
After initial validation of the ability of Ad5-Cre virus to express Cre recombinase protein in glial cells in vitro and in vivo, we employed this virus to induce site-specific deletion of our target GlyT1 in the thalamus, through injection of the cKO GlyT1 mice. This transgenic line was constructed
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FG-4592 Recent research reveals that human alkyladenine DNA
2022-01-28
Recent research reveals that human alkyladenine DNA glycosylase (hAAG) is an important protein enzyme which can specifically recognize and excise a variety of alkylated purines and deoxyinosine from DNA [12]. hAAG plays pivotal roles in maintaining genomic integrity, and it is involved in FG-4592 r
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br Ligand binding free energies In order to
2022-01-28
Ligand-binding free energies In order to compute the absolute free Cy3 NHS ester associated with binding a ligand to a flexible iGluR LBD, a theory that accounts for all the principal thermodynamic contributions from ligand docking and LBD closure had to be developed. This was accomplished using
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Although encoded by a single
2022-01-28
Although encoded by a single gene, GR displays considerable heterogeneity through the combined effects of alternative mRNA splicing, alternative translation initiation, and complex post-translational modification. Differential expression of the various GR isoforms may contribute to tissue-specific f
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Both preclinical and clinical studies
2022-01-27
Both preclinical and clinical studies have identified a distributed set of CNS nuclei that participate in cognitive control of feeding behavior. Preclinical studies that utilize restricted access feeding schedules (RFS) indicate that rodents learn to anticipate delivery of scheduled meals as indicat
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Two excellent GSMs with clear pharmacological effect across
2022-01-27
Two excellent GSMs with clear pharmacological effect across rats, dogs, monkeys, and human subjects are BMS-932481 and BMS-986133 with IC50 at 6.6 and 3.5 nM to reduce Aβ42, respectively. Both GSMs exhibit dose- and time-dependent activity in vivo by decreasing Aβ1-42 and Aβ1-40 levels while increas
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Interestingly GAL has also been shown
2022-01-27
Interestingly, GAL has also been shown to be co-expressed and/or secreted in luteinizing hormone releasing hormone (LHRH) (Merchenthaler et al., 1991, Marks et al., 1994) and kisspeptin (KISS) neurons (Porteous et al., 2011). Furthermore, GAL was shown to stimulate luteinizing hormone (LH) secretion
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Accumulating evidence suggests that the NGF family
2022-01-27
Accumulating evidence suggests that the NGF family of neurotrophins have important modulatory roles in opioid analgesia and addiction [36]. The NGF family of neurotrophins include NGF, GSK J4 free base derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) [37]. BDNF kno
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br Introduction Regulation of transcription is a critical ev
2022-01-27
Introduction Regulation of transcription is a critical event of the embryonic development and epigenetic mechanisms such as histone modifications and DNA methylation appear important in mediating temporal changes, and differences among cells/tissues, of temporary stabilized transcriptomes (Mas et
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Author contribution br Funding This work
2022-01-27
Author contribution Funding This work was supported by funding from St Vincent’s AMR. Hologic provided Panther equipment and Aptima HCV Quant Dx Viral Load assays. The sponsors had no rule in the analysis and interpretation of the study results, the manufacturer of reagents used in this study d
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Moreover we have demonstrated that internalization and subce
2022-01-27
Moreover, we have demonstrated that internalization and subcellular trafficking of NPRA, using IF staining (IFS) and co-IP of plasma membrane, endosomal, lysosomal, and recycling endosome markers to follow intracellular trafficking and signaling by confocal IF microscopy (CIF) and immunoblotting (IB
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All experiments in this study were performed at
2022-01-27
All experiments in this study were performed at pD 6.1 for reasons described above. This leaves a question about the implications of stereochemistry in vivo. At physiological pH the GSTP1-1 catalyzed rate of EASG formation is only 1.1-fold higher than the non-enzymatic rate [26]. However, when human
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