• Clinical trials of all GSIs have ended prematurely raising

  2022-06-05

  

  Clinical trials of all GSIs have ended prematurely, raising the question on our understanding of their target, the γ-secretase/presenilin. Development of compounds to target γ-secretase and reduce Aβ production is complicated by the fact that γ-secretase/presenilin has critical biological function,

• Another small compound targeting IBAT has been

  2022-06-05

  

  Another small compound targeting IBAT has been evaluated in Phase I clinical trial (EudraCT 2013-001175-21) [86]. The oral administration of A4250 to healthy subjects did not give rise to any serious adverse events, was well tolerated and had a similar safety profile as elobixibat; however, it cause

• Liposomes that are less than nm in diameter are

  2022-06-02

  

  Liposomes that are less than 200nm in diameter are necessary to optimize uptake of liposomes by RNase Inhibitor (Oesterling et al., 2014). The liposomes constructed in these experiments were found to be sufficiently small in diameter for use in in vivo and in vitro experiments. Even smaller diamete

• br Memories can last a lifetime long after

  2022-06-02

  

  Memories can last a lifetime, long after the transient events have passed. The fact that information stored in the Cy5 Firefly can outlast the environmental trigger implies that enduring cellular changes in the central nervous system underlie memory. Epigenetic modifications of DNA and chromatin

• Upon LPS stimulation ERK and

  2022-06-02

  

  Upon LPS stimulation, ERK and STAT3 signaling pathways were activated in a time-dependent manner, and the phosphorylation of Y705 occurred later than that of S727 (Supplementary Fig. S5B). STAT3 is known to be phosphorylated on serine 727 (S727) by the mitogen-activated protein (MAP) kinase pathway

• Accompanied with apoptosis other ways of neuronal death also

  2022-06-02

  

  Accompanied with apoptosis, other ways of neuronal death also occur in ischemic 1632 due to the impairment of mitochondrial homeostasis [16]. Oxidative DNA damage activates poly (ADP-ribose) polymerase 1 (PARP-1) to induce regulated necrosis, referred to as parthanatos, in the brain [17]. Over-activ

• Work is presently underway to unveil mechanisms whereby SAHA

  2022-06-02

  

  Work is presently underway to unveil mechanisms whereby SAHA-dependent restoration of cardiomyocyte autophagic flux is protective. Another interesting question pertains to mechanisms whereby class I and class II HDAC inhibitors induce autophagy. It has been demonstrated that TSA reduces transverse a

• Haploid germ cell specific nuclear protein

  2022-06-02

  

  Haploid germ cell-specific nuclear protein kinase (Haspin) proteins are divergent members of the eukaryotic protein kinase family. Haspin (encoded by germ cell-specific gene 2: Gsg2) is found in many eukaryotic lineages (animal, fungi, and plants), and the protein and its mRNA were initially detecte

• In women with stage I II

  2022-06-02

  

  In women with stage I–II endometriosis [17], no difference in the implantation rate per embryo or in the clinical pregnancy rate per transfer was noted between GnRH-agonist and GnRH-antagonist protocol (18.2% vs. 15.4%, P=0.9 and 31.2% vs. 30%, P=1, respectively). It has been suggested that either

• br Introduction The amino acid glycine functions as a

  2022-06-02

  

  Introduction The amino 9292 glycine functions as a neurotransmitter in the vertebrate central nervous system: as an inhibitory neurotransmitter and as a co-agonist of the NMDA-subtype of excitatory glutamatergic receptors (Eulenburg et al., 2005). Under a current hypothesis that schizophrenia re

• An alternative approach to improving pharmacokinetic

  2022-06-02

  

  An alternative approach to improving pharmacokinetic profile while retaining high GlyT1 potency was also pursued. Libraries were prepared in which potency enhancing piperidine C4 substituents were combined with clearance lowering truncated alkyl sulfonamides. The result was the discovery of (). Unl

• The general synthetic routes leading to aspartate and

  2022-06-01

  

  The general synthetic routes, leading to aspartate and 2,3-diaminopropionate analogs, are shown in . As outlined in , aspartic N,N-Dimethylsphingosine mg analogs – were synthesized through standard carbodiimide-mediated coupling between an amine and an appropriately protected aspartic acid. It is wo

• Studies examining cerebral glucose metabolism in MDD using

  2022-06-01

  

  Studies examining cerebral glucose metabolism in MDD using 18 F-fluorodeoxyglucose in positron emission tomography (FDG-PET) showed altered regional glucose metabolism in MDD (Dunn et al., 2002, Kennedy et al., 2001, Kimbrell et al., 2002, Saxena et al., 2001). In a recent meta-analysis by Su and co

• br Experimental br Acknowledgments This project was

  2022-06-01

  

  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

• The ER EK polymorphism is located

  2022-06-01

  

  The ER22/23EK polymorphism is located in the transactivation domain of the GR gene. A single nucleotide polymorphisms (SNPs) has been identified in both of the two adjacent codons (22 and 23). These SNPs are fully linked and are associated with relative GC resistance[32], [44]. Although no associati

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