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In order to investigate whether this off target
2022-06-13
In order to investigate whether this off-target activity was related to a particular structural feature of this inno-206 or was characteristic of the series, compounds , and were selected as being matched pairs with compound but with structural variation in terms of the R, R and R groups, respec
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One clue to how evolution has solved
2022-06-13
One clue to how evolution has solved such spatiotemporal challenges comes from studies revealing that lymph node (LN) organization is more complex than originally presumed, suggesting that steady-state microanatomical features are crucial for effective immune responses (reviewed by Qi et al., 2014).
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Sepsis was defined as a systemic inflammatory response
2022-06-13
Sepsis was defined as a systemic inflammatory response syndrome (SIRS) associated with severe infection in 1992 [9]. However, in the Third International Consensus Definitions for Sepsis and Septic Shock [10], it was redefined as life-threatening organ dysfunction provoked by a dysregulated host res
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GKRP binds to the inactive super open conformation
2022-06-13
GKRP binds to the inactive, super-open conformation of GCK, acting as a competitive inhibitor of glucose association with the enzyme (Fig. 3) [45]. Upon formation of the inhibitory complex with GKRP, GCK is sequestered into the hepatocyte nucleus [48]. The detailed mechanism by which GKRP mediates t
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UM171 Analogous to all GPCRs the GLP
2022-06-13
Analogous to all GPCRs, the GLP-1R transduces signals from the outside of the cell to the inside by allosterically converting a ligand-binding event to activation of intracellular effectors. The GLP-1R couples to several intracellular effectors and this pleiotropic coupling is physiologically releva
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These various observations indicate that GIP plays an import
2022-06-13
These various observations indicate that GIP plays an important role in the normal compensatory islet response to high fat feeding. This likely reflects the loss of the combined actions of intra-islet GIP together with intestinally-derived GIP entering the islet vasculature following secretion from
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br Acknowledgments The authors would like to thank
2022-06-13
Acknowledgments The authors would like to thank principal investigator Edward John Pratt, MD (Lilly-NUS Centre for Clinical Pharmacology, Singapore) and study investigator Martha Hernandez-Illas MD (QPS-MRA) along with site staff, and trial participants and their families. We thank Zvonko Milicev
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The caseins are a family of milk phosphoproteins
2022-06-13
The caseins are a family of milk phosphoproteins whose biological function is to provide supersaturating concentrations of calcium, phosphates, and essential SAG to the neonate (Vonderhaar and Ziska, 1989). α- and β-caseins, the most abundant of the milk caseins, are described as calcium sensitive
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The present data suggest that the decrease of
2022-06-10
The present data suggest that the decrease of liver BAs was mainly due to the decrease of hepatic BAs synthesis because the BA synthetic enzymes Cyp7a1, Cyp7b1 and Cyp8b1 were markedly reduced. The increase may also be due to the increase of hepatic BAs efflux, because the liver BA efflux transporte
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The extensive worldwide research efforts in the decade follo
2022-06-10
The extensive worldwide research efforts in the decade following FFA1 de-orphaning aimed at developing clinically useful FFA1 agonists were nearly halted after Takeda’s first-in-class agent fasiglifam (TAK-875) was discontinued in phase III of human trials. On the date of submission of this manuscr
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b-Casomorphin (1-3) Receptor activator of NF B ligand RANKL
2022-06-10
Receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) stimulate the generation of osteoclast b-Casomorphin (1-3) [10], [11], [12], [13]. In response to sphingosine 1-phosphate (S1P) signaling, osteoclasts then attach to regions of bone undergoing resorption [14]
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br Acknowledgments This research was supported by the Nation
2022-06-10
Acknowledgments This research was supported by the National Institutes of Health Grants GM58442 and GM084152, as well as the National Institutes of Health Predoctoral Training Grant 5T32GM008700-13. We thank Eric Oldfield (University of Illinois, Urbana-Champaign) for providing the FDPS inhibitor
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Remarkably most of these molecules are also quite effective
2022-06-10
Remarkably, most of these molecules are also quite effective in interfering with the proliferation of the drug-resistant cancer cell lines, with IC50 values ranging from 0.59 to 2.93 μM against MCF-7/ADR cells, and from 0.160 to 1.17 μM against NSCLC-resistant H1975 cells. Among these molecules, com
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Here we show in contrast to previous work that
2022-06-10
Here we show, in contrast to previous work, that several phenotypes associated with Orb6 inactivation, including increased cell width, are independent of Gef1. We further find that Orb6 positively regulates exocytosis, also independently of Gef1. To identify novel targets of Orb6, we performed quant
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Introduction The Antiretroviral Therapy ART in the last deca
2022-06-10
Introduction The Antiretroviral Therapy (ART), in the last decade, has been providing a better treatment for the Human Immunodeficiency Virus 1 (HIV) infection, by reducing its viral load to undetectable levels and recovering the immune system. In fact, according to the last data from UNAIDS the mo
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