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Once apoptosis has been initiated the HMGA proteins themselv
2023-09-26
Once apoptosis has been initiated the HMGA proteins themselves undergo marked changes in both the types and extent of their post-translational modifications (PTMs; review in [149,175]), some of which are likely correlated with alterations in chromatin structure. For example, the early stages of apop
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Within the thrombus there is heterogeneity in the activation
2023-09-26
Within the thrombus, there is heterogeneity in the activation of Cinobufagin based on the concentration gradients of soluble agonists emanating from the site of vascular injury, which has been excellently reviewed by Tomaiuolo et al.[1]. As part of the coagulation cascade, active thrombin is generat
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The mechanisms that control Ahr transcription
2023-09-26
The mechanisms that control Ahr transcription are poorly understood, especially when considering cell type-specific regulation. A recent report suggested that the Ahr transcription might be directly promoted by RORγt [retinoic PU-WS13 receptor (RAR)-related orphan receptor γt] based on ChIP-Seq ana
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Ethanol can affect biological systems directly or also throu
2023-09-26
Ethanol can affect biological systems directly, or also through the interactions between these systems, which become important in the actions promoted by alcohol consumption. Its metabolites acetaldehyde and acetate play a key role in the R428 mediating some effects of ethanol (Israel et al., 1994,
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Regarding androgens it is known that they are also
2023-09-25
Regarding androgens, it is known that they are also essential for reproductive success (Walters et al., 2010). At the molecular level, their effects are produced mainly by dihydrotestosterone (DHT), arising from the conversion of testosterone by the enzyme 3-oxo-5-alpha-steroid-4-dehydrogenase (enco
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Protein phosphorylation is an important posttranslational me
2023-09-25
Protein phosphorylation is an important posttranslational mechanism for the regulation of distribution, trafficking, and function of modified proteins (Wang et al., 2014). GluA1 phosphorylation at S845 also has functional consequences (Lu and Roche, 2012). For instance, S845 phosphorylation drove tr
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Hsp also called FK binding protein FKBP is one of
2023-09-25
Hsp56 (also called FK506-binding protein 52, FKBP52) is one of the steroid receptor-associated immunophilins with tetratricopeptide repeat domains, which serve as binding sites for Hsp90 (Peattie et al., 1992). Hsp56 is elevated in breast cancer compared with normal breast tissue (Ward et al., 1999)
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To date attention has been
2023-09-25
To date, attention has been directed towards new molecular targets in luminal phenotype (ER-positive), such as CDK4/6 and, to a lesser extent, androgen receptor (AR) pathways [8]. While the role of CDK4/6 has been elucidated and their inhibitors have shown a benefit in luminal BC, the role of AR in
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np e synthesis Although mature fibrils formed from A aggrega
2023-09-25
Although mature fibrils formed from Aβ np e synthesis have long been thought to be the main neurodegenerative agents in AD, recent evidence suggests that soluble multimers of these pathogenic proteins, referred to here as “oligomers,” may initiate the synaptic and neuronal dysfunction associated wit
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Second the phosphorylation events e
2023-09-25
Second, the phosphorylation events (e.g., α-Thr172 and β-Ser108) needed for AMPK activation by small molecules binding at the ADaM or other sites remains unclear. Within the β-GBD, phosphorylation of β1-Ser108 was shown to be required for the activation by small molecules binding in the ADaM site, s
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br MHCI peptide editing N
2023-09-25
MHCI peptide editing, N-terminal extensions and the peptide loading complex Conventionally, peptide-MHCI binding is thought to require both amino- and carboxyl-termini for stable interaction (Madden, 1995; Bouvier and Wiley, 1994). Peptides with longer than optimal length (10–13 residues) have be
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The proposed formulation is however challenging to solve sin
2023-09-25
The proposed formulation is, however, challenging to solve since the structured sparsity-inducing norms are non-smooth. In order to solve the new objective function, we consider two different approaches: proximal averaging, which takes the average the solutions from the proximal operator for the ind
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To guide our attempts at achieving AKT potency and
2023-09-25
To guide our attempts at achieving AKT potency and selectivity against p70S6K and other kinases from (p70 S6K IC: 0.004 μM) and , we took advantage of exploiting the subtle sequence differences in the active sites of the AGC family kinases, we utilized the information around crystal structure of AK
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The excellent potencies selectivities and improved PK
2023-09-25
The excellent potencies, selectivities and improved PK associated with the piperazine class triggered more extensive off-target screenings of the highlighted compounds. A screen of more than 100 enzymes, receptors, and ion channels resulted in activity at the norepinephrine transporter (NET). This
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TIC10 mg br Acknowledgements br Introduction Autoantibodies
2023-09-23
Acknowledgements Introduction Autoantibodies directed at neurotransmitter receptors and ion channels are pathogenic and/or biomarkers in several autoimmune neurological diseases [1]. For example, autoantibodies directed against voltage-gated potassium channels, the P/Q-type (α1A) voltage-gated
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