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We report on four affected children
2021-09-23
We report on four affected children from two unrelated consanguineous actin inhibitor with moderate to severe ID associated with epilepsy and variable neuropsychiatric features. Using whole-exome sequencing, we identified homozygous missense variants in SLC45A1 (OMIM: 605763), which codes for a neu
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The eradication of agonist activity in compound
2021-09-23
The eradication of agonist activity in compound was also confirmed in the ex vivo growth hormone (GH) release experiment conducted in isolated primary rat pituitary Mdivi 1 as shown in . Compound did not produce any noticeable GH secretion at up to 10μM concentration. It could also antagonize the st
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Ghrelin contains an n octanoylation
2021-09-23
Ghrelin contains an n-octanoylation at its Ser3 residue (Kojima et al., 1999). While des-acyl ghrelin is found in high concentrations in the blood, only the lipidated form is active at GHSR (Bednarek et al., 2000). We previously showed that ghrelin interacts with the membrane via its lipid modificat
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br Financial support This work was
2021-09-22
Financial support This work was supported by Fondation pour la Recherche Médicale (Equipe labellisée, DEQ20150331724), Inserm, University of Lille, and Agence Nationale pour la Recherche (ANR-10-LBEX-46 and ANR-10-INBS-08; ProFI project, “Infrastructures Nationales en Biologie et Santé”; “Investi
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In terms of cytotoxicity studies
2021-09-22
In terms of cytotoxicity studies under two-dimensional cell culture conditions, only two of the above-mentioned publications with liposomal formulations of tyrosine kinase inhibitors reported viability data as compared to respective free drugs. On the one hand, liposomal gefitinib exerted strongly r
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Both anxiety like behavior and sucrose preference intake
2021-09-22
Both anxiety-like behavior and sucrose preference/intake were reduced in GPR40/FFAR1 KO male mice, while social behavior was normal in KO mice. These findings indicate that brain GPR40/FFAR1 is involved in the modulation of anxiety- and depression-like behavior in rodents. Previous studies have demo
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In summary although there are still several important questi
2021-09-22
In summary, although there are still several important questions open on the mechanisms that trigger FAK nuclear localization and FAK-dependent gene regulation, Cardoso et al. (2016) provide important new insights on FAK/MEF2-mediated initiation of cardiac hypertrophy. Acknowledgments The author
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RS testing has been extensively validated in patients with e
2021-09-22
RS testing has been extensively validated in patients with early stage, ER+, HER2− patients. TAILORx, a randomized controlled trial to evaluate the role of adjuvant chemotherapy by RS, found no recurrence or survival benefit to the addition of chemotherapy to endocrine therapy in patients with inter
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The therapeutic potential of acetate has been advocated by
2021-09-22
The therapeutic potential of acetate has been advocated by research on neurodegenerative disorders such as Canavan's disease (Arun et al., 2010, Mathew et al., 2005), where oral acetate improved motor function in a genetic model of the disorder, and in studies of behavioural phenotypes associated wi
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In summary P P macrocyclization proved
2021-09-22
In summary, P2-P4 macrocyclization proved to be an effective strategy to drive activity in this series of HCV NS3 protease inhibitors while microsomal stability was enhanced by the introduction of steric bulk along the tether. This modification augmented the previously-described tactic of improving
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These and other observations presented in
2021-09-22
These and other observations presented in the elegant, rigorous study by Thomas et al. (2018) clarify a puzzling enigma regarding the Rab specificities of yeast TRAPP complexes and further highlight an important though under-appreciated role for the C-terminal HVD of Rabs in GEF substrate selection.
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To further investigate the relationship
2021-09-22
To further investigate the relationship between the pro-neurogenic and therapeutic actions, we analyzed the effect of VP2.51 in the presence of the antimitotic agent TMZ. No overt side effects were found at the time of testing as assessed by direct observation of the behavior of the animals in their
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In order to elucidate the
2021-09-22
In order to elucidate the mechanisms behind the observed changes in metabolic activity in the cardiomyoblasts we investigated changes in gene and protein expression subsequent to treatment with PSN632408 with or without concurrent exposure to palmitate. Activating GPR119 in basal and high palmitate
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In addition to their functional
2021-09-22
In addition to their functional activation of GPR109A, compounds of the pyrazolopyrimidine class also enhanced the binding of nicotinic AZD1152-HQPA to the receptor. For instance, increased the binding of H-nicotinic acid to the receptor (black curve) in a concentration-dependent manner, whereas u
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The glycine receptor is an ionotropic neurotransmitter
2021-09-22
The glycine receptor is an ionotropic neurotransmitter receptor coupled to a chloride ion channel. Glycine receptors are typically described as inhibitory and distributed in the spinal cord and brainstem, though mRNA transcription labelling studies in rats show expression in the hippocampus, cingula
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