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The H N mutation in
2024-01-24
The H373N mutation in exon 6 has not previously been reported [3], [4], [5], [6]; thus, this mutation appears to be a novel mutation. The functional expression study demonstrated that the H373N mutation results in almost complete loss of enzymatic activity. Thus, it is highly likely that the H373N m
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br Discussion In our current study
2024-01-24
Discussion In our current study, we demonstrated that both the metastatic and recurrent ovarian cancer tissues expressed lower levels of p62 when compared with the patient-matched primary tumor samples. High estrogen antagonist levels of p62 were associated with long progression-free survival of
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Endoplasmic reticulum ER stress resulting from accumulation
2024-01-24
Endoplasmic reticulum (ER) stress resulting from accumulation of misfolded proteins in ER lumen stimulates a chain of adaptive responses termed as the unfolded protein response (UPR). Glucose related protein (GRP78/BiP), key ER chaperone essential for the activation of the ER-transmembrane signaling
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We initially established using fMRI that auditory
2024-01-24
We initially established using fMRI that auditory processing by the caudomedial nidopallium (NCM) of male European starlings (Sturnus vulgaris) of species-specific aspects of songs (whistles and warblings i.e. high-pitched trills coming from the end of the warbling that are found in the repertoire o
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Under some pathological conditions AT R internalization is d
2024-01-24
Under some pathological conditions, AT1R internalization is decreased when agonist exposure is prolonged. This weakens or removes the AT1R desensitization effect and leads to AT1R and downstream signal overactivation. AT1R overactivation can result in continued biological effects such as sustained v
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The specific mechanism and neurotoxic
2024-01-24
The specific mechanism and neurotoxic Aβ MK-2206 are yet to be elucidated, however recent studies have provided significant evidence for the amyloid channel hypothesis. These reports have established that relatively small oligomers ( Conflict of interest Acknowledgements This work was financed
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Consistent with the in vitro results
2024-01-24
Consistent with the in vitro results, memantine ameliorated Aβ-induced cytotoxicity in rat primary cortical cultures. Studies reported that memantine protected neurons against the damage caused by aggregated Aβ40 or Aβ42 oligomers in vivo[26], [27]. These results suggest that, in addition to its neu
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The lactam emerged as lead candidate due
2024-01-24
The lactam (6) emerged as lead candidate due to its high selectivity, outstanding potency (against ALK or in clinically known ALK mutants), low in vitro clearance, and low efflux potential. The lactam (6) was selected for further profiling against the resistant ALK mutants. Preclinical rat pharmacok
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These results validate the docked pose of the ALR e
2024-01-24
These results validate the docked pose of the ALR2-3e complex in comparison to the docked complex of the ALR2-4c complex of which the compound docked completely out of the binding pocket of ALR2 (). This concludes to that the removal of the acetic climbazole moiety leads to inactive or weakly acti
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Activation of AhR is also
2024-01-24
Activation of AhR is also known to upregulate the expression of AhRR (AhR repressor), an inhibitor protein of AhR [29]. However, the exact mechanism by which AhRR represses AhR signaling is not well understood. The initial study by Mimura and colleagues suggested that AhRR is capable of directly com
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The activation of the A BR
2024-01-23
The activation of the A2BR subtype triggers different intracellular metabolic pathways, often linked to the activation of adenylyl cyclase and increased levels of intracellular cAMP (Lynge et al., 2003, Bernareggi et al., 2015). The nAChR-channel TOK-001 synthesis mediated by the cAMP/PKA pathway wa
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G actin has a molecular weight of kD
2024-01-23
G-actin has a molecular weight of 42 kD and dimensions about 55 × 55 × 35 Å3. It consists of 375 amino acids arranged into two individual domains (Alberts et al., 2014). A central cleft bisects the protein into two aforementioned domains which surround a deep cleft containing ATP or ADP and a tightl
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hsp90 inhibitor To reconstruct the amino acid sequence of an
2024-01-23
To reconstruct the amino hsp90 inhibitor sequence of an ancestral β subunit a molecular phylogeny is required, which is inferred from a β subunit sequence alignment. To build this alignment we searched the NCBI database for proteins similar in sequence to the human muscle-type β subunit precursor pr
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Defining the multiple roles of autophagy in
2024-01-23
Defining the multiple roles of autophagy in stroke has been a rapidly evolving and exciting venue for translational research, with innovative products being applied from bench to bedside. Spanning pharmacological pathway manipulation and functional experimental validation, altered autophagy activati
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To test the compounds metabolic stability we measured
2024-01-23
To test the compounds metabolic stability, we measured the half-life of compounds and in mouse hepatic microsomes (1mg/mL) and found them to have modest stability, with half-lives of 7.5 and 2.9min respectively, indicating these compounds may be unsuitable for studies. In order to gain structural i
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