• Clinical trials of all GSIs have ended prematurely

  2021-12-13

  

  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,

• Much is known about FPPS structure and

  2021-12-13

  

  Much is known about FPPS structure and function, with over 120 FPPS crystal structures being currently available. This wealth of information is largely the consequence of human FPPS serving as a drug target for the treatment and/or prevention of pathologies such as osteoporosis, hypercalcemia and Pa

• br STAR Methods br Author Contributions

  2021-12-10

  

  STAR★Methods Author Contributions Introduction Hyaluronan, a major constituent of the extracellular matrix (ECM), is produced by hyaluronan synthases (HASs) and degraded by hyaluronidases (HYALs) (Vigetti et al., 2014). Physiologically, hyaluronan exists in a form with a molecular weight of

• To prevent toxicity of free

  2021-12-10

  

  To prevent toxicity of free hemoglobin as well as its degradation metabolites heme and free iron, several scavenger proteins and degradation enzymes protect the body. Haptoglobin (Hp) is the most well described hemoglobin scavenging protein that binds free hemoglobin and transports it to macrophages

• KPT-276 Introduction Heme is an important small molecule and

  2021-12-10

  

  Introduction Heme is an important small molecule and an essential cofactor for a variety of enzymes (George, 1948; Morrison and Stotz, 1954; Maehly, 1952; Igo et al., 1961). During cellular respiration, heme populates cytochromes and serves as an electron acceptor in the electron transport chain (M

• Three additional Type I CDK and CDK

  2021-12-10

  

  Three additional Type I CDK8 and CDK19 kinase inhibitors have also been recently reported. Orally available 3-benzylindazole 12 was discovered by optimization of compounds with HSP90 affinity to yield potent and selective CDK8 inhibitors. Compound 12 showed strong binding activity for CDK8 with an I

• Additionally molecular imaging has great

  2021-12-10

  

  Additionally, molecular imaging has great potential for noninvasive and quantitative imaging of pancreatic β-cells, but each single imaging modality has its own intrinsic strengths and limitations. Functional imaging modalities have high sensitivity (such as SPECT and PET) and anatomical imaging tec

• br Materials and methods br Results br

  2021-12-10

  

  Materials and methods Results Discussion ENU mutagenesis is a powerful approach to identify novel genes or ITD 1 to dissect the molecular basis of mammalian immune system (Siggs, 2014). T cells are critical components in the host defense against pathogens, and their activity has to be prec

• However the GPR R H polymorphism was

  2021-12-10

  

  However, the GPR40 R211H polymorphism was reported to affect the variation of insulin secretory capacity in other ethnic groups. The allele frequency of H211 in Japanese was 78.4%.102, 103 By comparing clinical and metabolic parameters among Japanese men, Ogawa et al. found that histidine homozygote

• Bacterial GluRS comes in two flavors discriminatory

  2021-12-10

  

  Bacterial GluRS comes in two flavors, discriminatory GluRS (D-GluRS) and non-discriminatory GluRS (ND-GluRS). While D-GluRS exclusively catalyses the transfer of Glu to tRNAGlu, the ND-GluRS can also glutamylate tRNAGln forming Glu-tRNAGln. The misacylated product is then transformed to Gln-tRNAGln

• The translation of our rat findings

  2021-12-10

  

  The translation of our rat findings to bovine and human lenses revealed that the expression of glucose transporters was more straightforward in bovine and human than in the rat lens, since only GLUT1 was detected in these lenses. Using the C-terminal GLUT1 antibody, we observed bands for GLUT1 in al

• Swainsonine In the present study compared to diabetic contro

  2021-12-10

  

  In the present study, compared to diabetic control rats, hepatic glucose-6-phosphatase activity was significantly decreased in both SE and METF treated diabetic animals, with the latter producing greater reduction in glucose-6-phosphatase activity. This observation is consistent with the claim of Ta

• In summary two new flexible amine functionalized quinolinium

  2021-12-10

  

  In summary, two new flexible amine-functionalized quinolinium derivatives with far-red region emitting were prepared. The shorter-chain fatty amine side chain in the scaffold of was found to be a more promising G-quadruplex DNA fluorescent probe, suggesting the amine side group plays an important r

• AR-A014418 Prior models suggest that the terminal ends of th

  2021-12-10

  

  Prior models suggest that the terminal ends of the endocrine FGFs individually determine FGFR and KLB recognition, with little or no cross-talk. Our results confirm that short C-terminal sequences are necessary and sufficient to bind KLB and, supportive of a common mechanism, the underlying structur

• GPR which is also known

  2021-12-10

  

  GPR40, which is also known as FFA receptor 1 (FFAR1 or FFA1), was identified as an orphan receptor in the search for novel human galanin receptor (GALR) subtypes in 1997. Using reverse pharmacology approaches measuring calcium transients, GPR40 were deorphanized and characterized as being activated

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