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Heavy alcohol consumption reported by three of
2021-10-16

Heavy alcohol consumption, reported by three of five referred patients with chronic HCV infection and cirrhosis, is a risk factor for cirrhosis in p.C282Y homozygotes [19], [47] and adults with chronic HCV infection [48]. Although none of the present referred patients were diagnosed to have porphyri
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NPxY was recognized as the first
2021-10-16

NPxY was recognized as the first short signal sequence motif in the cytoplasmic domain of membrane receptors and proteins with critical roles in internalization and trafficking of receptor molecules [130]. Including LDL receptor, beta-1 integrin, megalin, beta-amyloid precursor protein, EGF receptor
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Increasing number of experimental data reveal that
2021-10-16

Increasing number of experimental data reveal that both ROS and RNS are multifunctional molecules playing a substantial role in plant physiology and particularly in seed biology (Bailly et al., 2008; Šírová et al., 2011; Yu et al., 2014). Dual function of RNS can be described by the model of “nitros
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Screening of the compounds allowed for a number of interesti
2021-10-16

Screening of the compounds allowed for a number of interesting SAR observations. First of all, pyridyl analogue demonstrated that a pyridine ring would be beneficial for both log as well as increasing the potency (entry 2 versus entry 1). Electron-poor aryl groups next to the oxadiazolone were detr
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br GSMs Secretase cleavage of APP generates a
2021-10-15

GSMs γ-Secretase cleavage of APP generates a number of Aβ peptides [32], [137]. In most cells Aβ1–37, 38, 39, and 42 are produced at low levels (typically each represents 5–20% of total Aβ detected) and the major species generated is Aβ1–40 (typically over 50% of total Aβ). Other Aβ peptides can
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To obviate the mitogenic FGF activity
2021-10-15

To obviate the mitogenic FGF19 activity, several engineered FGF19 variants have been generated aiming to maintain the metabolic activity excluding the protumorigenic ones. One variant, M70, that differs from wild-type FGF19 by 5-amino acids deletion at the N-terminus and the substitution of 3-amino
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To obviate the mitogenic FGF activity
2021-10-15

To obviate the mitogenic FGF19 activity, several engineered FGF19 variants have been generated aiming to maintain the metabolic activity excluding the protumorigenic ones. One variant, M70, that differs from wild-type FGF19 by 5-amino acids deletion at the N-terminus and the substitution of 3-amino
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Recently they reported an enyne chemotype agonist Fig with l
2021-10-15

Recently, they reported an enyne chemotype agonist (21, Fig. 13) with low lipophilicity, small polar surface area (PSA) and high potency (Clog P=3.8, tPSA=37 A2, EC50=20nM), further derived from TUG-424. The compound endowed fast oral JIB-04 (tmax=15min) and a decent pharmacokinetic profile, a sati
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In addition to FAK P MAPK kDa
2021-10-15

In addition to FAK, P-38 MAPK (38 kDa polypeptide) serves as cross-talk effector for signal transduction, enabling this factor to play a vital role in numerous biological processes (Cuenda and Rousseau, 2007). Pharmacologically modulation of P-38 has shown to be an effective approach in the orientat
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Previous studies have shown that inhibition of
2021-10-15

Previous studies have shown that inhibition of voltage-gated Na+ MHC class II antigen (45-57) [Homo sapiens] has a reduced effect on GABAergic boutons compared with other neurotransmitter phenotypes,46, 47 and voltage-gated Na+ channel subtypes are differentially expressed in hippocampus. In additi
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br Materials and methods br Results br Discussion Although
2021-10-15

Materials and methods Results Discussion Although there is general agreement that GPR109A has anti-lipolytic activity and that the NEFA reduction in response to nicotinic PF-3758309 is mediated by GPR109A, whether GPR109A activation has any impact on plasma TG levels is unclear. Since the
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Interestingly zaprinast administration not only prevents the
2021-10-15

Interestingly, zaprinast administration not only prevents the development of hypersensitivity but also enhances opioid effectiveness. Opioids have long been considered among the most effective drugs used to treat pain (Watkins et al., 2005; Mika et al., 2013; Szczudlik et al., 2014a, Szczudlik et al
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FSH and LH are glycoprotein dimers
2021-10-15

FSH and LH, are glycoprotein dimers that are comprised of two subunits, a common α-subunit (αGSU) and a distinct β-subunit (FSHβ or LHβ, respectively), which determines the biological specificity of the gonadotropins (Ciccone and Kaiser, 2009, Gharib et al., 1990). The AG014699 of the gonadotropin
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Spatial working memory improved in the Balb
2021-10-15

Spatial working memory improved in the Balb/c strain at a dose of VU0410120 (i.e., 30mg/kg) that disrupted spatial working memory in the Swiss Webster comparator strain. Consistent with a recent PET study in rhesus macaques suggesting a relationship between the extent of the dose-dependent occupancy
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br Discussion Our results indicate that marked changes in
2021-10-15

Discussion Our results indicate that marked changes in the relative distribution of AMPA receptors in microsomal and synaptic fractions occur during the postnatal period, and that these changes are correlated with changes in different populations of AMPA binding sites. At early postnatal ages (PN
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