• In conclusion we have designed

  2022-02-23

  

  In conclusion, we have designed and characterized a novel series of EAAT-blockers, exemplified by (-[4-(2-bromo-4,5-difluorophenoxy)phenyl]--asparagine)—a potent, selective, competitive non-substrate inhibitor of EAAT-2. As one of the most potent and selective EAAT-2 inhibitors identified to date,

• We report on four affected children from two unrelated

  2022-02-23

  

  We report on four affected children from two unrelated consanguineous CCT245737 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 neuronal g

• br Experimental br Acknowledgments This project was generous

  2022-02-23

  

  Experimental Acknowledgments This project was generously supported by Grünenthal GmbH and IECB. We also thank the staff members of the technical platform of IECB and Grünenthal GmbH for their availability and their skills. Introduction Glucocorticoids (GCs) are essential steroid hormones t

• br Acknowledgments We would like to acknowledge

  2022-02-23

  

  Acknowledgments We would like to acknowledge Jenna Hall, Marita Rivir, Kathleen Smith, Joyce Sorrell, and Emily Yates for assistance with in vivo pharmacology studies. We would like to acknowledge Joe Chabenne and Steph Mowery for assistance with in vitro cell-based assays, and Patrick J. Knerr f

• Next we investigated the transfer of peptides and proteins

  2022-02-23

  

  Next, we investigated the transfer of peptides and proteins between contacting cells by nano-LC-MS/MS analysis using the fractions corresponding to molecules higher than 3 kDa. The MS data analysis revealed the direct transfer of several labelled peptides between receivers and donors. Labelled pepti

• br Acknowledgments The research leading

  2022-02-23

  

  Acknowledgments The research leading to these results was funded by European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 222719 – LIFECYCLE and by the Foundation for Science and Technology of Portugal (FCT), through projects PTDC/MAR-BIO/3890/2012 and PEst-C/

• br FXR FGF in the control of BAs synthesis

  2022-02-23

  

  FXR–FGF15/19 in the control of BAs synthesis The nuclear receptor FXR is the master regulator of BAs homeostasis, modulating their synthesis, Phleomycin and uptake [15]. FXR decreases BA de novo hepatic biosynthesis by reducing the expression of CYP7A1. At the canalicular membrane, newly-synthesi

• Since we were able to reach low

  2022-02-23

  

  Since we were able to reach low micromolar to sub-micromolar potency in both compound series (6 and 7), we were also keen on assessing the preliminary ADME profile (particularly with respect to plasma and liver microsomal stability) of the most active compounds from these series. As it is evident fr

• A large body of literature have

  2022-02-23

  

  A large body of literature have reported that various cellular pathways are dysregulated in NPC [19]. Among these pathways, Akt is frequently hyperactivated in NPC and regulates diverse cellular processes including tumor cell growth, proliferation, metabolism, survival and invasion, as well as angio

• Our observation that glioblastoma tumor cells

  2022-02-23

  

  Our observation that glioblastoma tumor cells express ETA-R in 6/10 cases contrasts with a recent publication reporting ETB-R expression in these tumors [17]. The reason for the discrepancy between that report and the present study might be due to the fact that glioblastomas with oligodendroglial co

• This connection is supported by studies in

  2022-02-23

  

  This connection is supported by studies in the SIV macaque model of HIV, where treatment with methamphetamine, which greatly enhances CNS dopamine levels (Truong, 2005); increased ak7 mg viral load. Methamphetamine also increased expression of the HIV co-receptor CCR5 in CNS macrophages, thereby enh

• p neurotrophin receptor p NTR or

  2022-02-22

  

  p75 neurotrophin receptor (p75NTR or CD271), a member of the tumor necrosis factor receptor superfamily, has been implicated in several steps of glioma tumorgenesis [5]. p75NTR mediates glioma invasion and progression through γ-secretase-dependent and -independent mechanisms [6], [7], and its expres

• In addition to the importance of heme as

  2022-02-22

  

  In addition to the importance of heme as an enzymatic cofactor, heme also acts as an important iron source. In order to access the iron within heme, S. aureus encodes heme degrading enzymes known as heme oxygenases (Skaar et al., 2004b; Wu et al., 2005). The two heme oxygenases encoded by S. aureus,

• In contrast to RhoA Rac and

  2022-02-22

  

  In contrast to RhoA, Rac1 and Rap1 which are stimulated by platelet activators and inhibited by NO/PKG, the GTPase ADP-ribosylation factor 6 (Arf6) is regulated in the reverse way. Platelet agonists like thrombin, collagen, or ADP, reduce Arf6-GTP levels, whereas NO and PGI2 oppose this reduction [1

• As GSH cellular redox status is critical for various

  2022-02-22

  

  As GSH cellular redox status is critical for various biological phenomena including apoptosis and inflammation [34], [35] we hypothesized that inflammation could modulate GSTP1-1 gene expression. Indeed, reactive oxygen species (ROS) are released at inflammation sites and can be eliminated from amyl

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