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Knowing that our strongest phenotypic differences between
2021-10-21
Knowing that our strongest phenotypic differences between the genotypes involved feeding behavior in various contexts, we decided to examine the case of restricted feeding and food anticipatory activity. Animals faced with a restricted schedule of food availability develop a series of anticipatory b
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Nicastrin is heavily glycosylated contributing KDa to
2021-10-21
Nicastrin is heavily glycosylated, contributing 40–70KDa to the molecular weight of human γ-secretase. Among the 16 predicted N-linked glycosylation sites in the ECD, 11 have been unambiguously identified. The glycans appear to mostly stabilize the local structure, thus contributing to the folding a
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The cytotoxicity of these compounds against Hep B cells was
2021-10-21
The cytotoxicity of these compounds against Hep3B cells was assessed using the MTT assay. As shown in , compounds in series and (except ), which retained the carboxyl at C-17, showed no appreciable cytotoxic activity (IC > 100 μM), whereas compounds in series (except ,) were modestly cytotoxic, i
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Substitutions V L F V and Q
2021-10-21
Substitutions V36L, F43V and Q80H were identified in the present study. RAS V36L is associated with resistance to boceprevir [18]. In 2015, Brazilian clinical practice guidelines on the management of hepatitis C no longer included combined therapies with boceprevir or telaprevir as a treatment optio
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br Methods br Results and discussion br Conclusions In
2021-10-21
Methods Results and discussion Conclusions In this work, 100-ns MDSs were applied on the WT and on the R155K and D168A single point mutations of the NS3/4A protease in the apo form and in complex with ASV, a current drug in phase III clinical trials. According to the PCA, these two mutation
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Although it has been observed in
2021-10-20
Although it has been observed in numerous studies and by many investigators that intraplatelet cGMP elevation results in platelet inhibition, there are a few papers which proposed a platelet stimulatory role for cGMP when elevated in response to NO donors or PDE5 inhibitors in mouse and human platel
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GPR has been implicated in
2021-10-20
GPR55 has been implicated in neuropathic and inflammatory pain (Staton et al., 2008) and bone remodeling (Whyte et al., 2009). Thus delineating the pharmacology of this receptor and the discovery of selective agonists and antagonists merits further study and could lead to new therapeutics. Acknow
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Because of its excellent GPR
2021-10-20
Because of its excellent GPR119 potency, good hERG selectivity and favorable rat t, Milnacipran HCl was scaled-up and further profiled. The synthetic protocols described in , were both suitable for a multi-gram scale synthesis of compound . An off-target screen was performed against an extensive
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Ghsr may have therapeutic value in disorders associated with
2021-10-20
Ghsr may have therapeutic value in disorders associated with impairments in AHN. As anxiety disorders and enhanced fear responses observed in PTSD are linked with overgeneralization of similar but distinct memories (i.e poor discrimination), we suggest that acyl-ghrelin’s anti-anxiety effect (Lutter
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Emerging evidence has shown that pharmacological FXR
2021-10-20
Emerging evidence has shown that pharmacological FXR agonism attenuates chronic alcohol treatment-induced liver injury and steatosis [18], [19], while whole-body FXR knockout worsens alcohol-induced liver injury [19]. This suggests that FXR plays an important role in ALD development. However, defici
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br Clinical assessment of iron
2021-10-20
Clinical assessment of iron chelation Towards the new concept of conservative iron chelation: iron scavenging and redeployment For any chelator to be of clinical value in disorders of regional siderosis they ought to be endowed with a requisite accessibility to the relevant sites and different
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Additionally to their peripheral effects evidence indicate a
2021-10-20
Additionally to their peripheral effects, evidence indicate a role for ETs in the central nervous system (Mosqueda-Garcı́a et al., 1993). Indeed, using Northern blot analysis and in situ hybridization it has been shown the presence of immunoreactive ET of non-vascular origin and of neuronal location
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In conclusion we have demonstrated that the ejection of stru
2021-10-20
In conclusion, we have demonstrated that the ejection of structural zinc ions from G9a and GLP in the presence of selenium-, and sulfur-containing electrophilic small 5-ht leads to inhibition of these two biomedically important epigenetic enzymes. Our work demonstrates that clinically used ebselen,
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Based on the in vitro findings summarized here we posited
2021-10-20
Based on the in vitro findings summarized here, we posited that, in the intact brain, release of ROS from iron-laden astrocytes to the local neuropil elicits oxidative damage and degeneration of indigent dopaminergic projections and other vulnerable neuronal elements (Schipper, 2001). Of particular
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Edrophonium chloride Acknowledgements We appreciated the con
2021-10-20
Acknowledgements We appreciated the contributions of Ana Carolina Galha, Selma XSL Pinheiro and Islene Azevedo for technical assistances. In addition, we wish to thank Adilson José de Almeida (in memoriam), Moyra M Portilho, Vanessa A Marques and Letícia P Scalioni, for data analysis during the set
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