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br STAR Methods br Introduction Secretase is
2021-12-22
STAR★Methods Introduction γ-Secretase is a membrane-embedded proteolytic complex belonging to a diverse family of intramembrane-cleaving proteases and is composed of four integral membrane proteins: presenilin (PS), nicastrin (NCT), anterior pharynx-defective 1 (Aph-1), and presenilin enhancer
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To improve the performance of the immunoassay
2021-12-22
To improve the performance of the immunoassay, various nanomaterials including carbon nanospheres [9], gold nanoparticles [10] and transition metal compounds [11] were used to immobilize natural enzymes as the label. Natural enzymes, such as horseradish peroxidase (HRP) [12] and glucose oxidase (GOD
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Subsequently BAs are secreted in the portal
2021-12-22
Subsequently, BAs are secreted in the portal vein by the heterodimeric organic solute transporter OSTα/β [15]. At this level, BAs are transported back to the liver, where the great majority is reabsorbed by the sodium (Na)-Taurocholate Cotransporter Protein (NTCP) and organic anion transporting poly
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Some malignant human tumors cells also express FPRs and
2021-12-22
Some malignant human tumors Cy5.5 hydrazide also express FPRs and respond to bacterial or endogenous agonists by increased motility and growth. For instance, FPRs expressed by human gastric cancer cells, mediate epithelial–mesenchymal transition, cell proliferation, migration, and resistance to apop
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To efficiently develop bioactive ligands
2021-12-21
To efficiently develop bioactive ligands even if the structural information of the target protein is unknown, we have presented a three-dimensional structural diversity-oriented strategy based on structural properties of a chiral cyclopropane. Our strategy has allowed us to design and synthesize a s
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A recent novel and important finding is that YAP connects
2021-12-21
A recent novel and important finding is that YAP connects cellular growth with anabolism; YAP suppresses the transcriptional induction of genes which importantly regulate gluconeogenesis in the liver; namely glucose-6-phosphatase catalytic subunit (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1
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The central region of Azalanstat can be substituted with con
2021-12-21
The central region of Azalanstat can be substituted with connecting alkyl chains of different nature and length. Interesting results were given by compounds with a four or five Alda 1 chain, incorporating heteroatoms, such as oxygen (Fig. 2, compound 4) or sulfur, and different functional groups su
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Continuing studies of endocannabinoid ligands at GPR
2021-12-21
Continuing studies of endocannabinoid ligands at GPR55 reveal that virodhamine (O-arachidonylethanolamine) and AEA can act as a partial agonists at GPR55; at high micromolar concentrations can inhibit β-arrestin recruitment (Sharir et al., 2012). It is likely that there are allosteric as well as ort
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Disrupting the dialog between microbiota and
2021-12-21
Disrupting the dialog between microbiota and the host, especially at the level of mucosal immunology, is expected to have profound effects on disease development. By using the AOM+DSS model of colitis-associated CRC, Singh et al. (2014) showed that development of inflammation and CRC are exacerbated
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As preclinical toxicity and efficacy both
2021-12-21
As preclinical toxicity and efficacy both appear to be associated with GlyT1 inhibition, it remains to be determined whether on-target toxicity can be separated from efficacy. The present study evaluated a series of GlyT1 inhibitors for target potency, mode of inhibition, residence time, activity in
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The amyloid precursor protein APP
2021-12-21
The amyloid precursor protein (APP) is a membrane protein thought to be involved in plasticity, synapse formation and repair, and export of metal ions [68]. The APP present in the brain can be cleaved by three different secretases [73], [74]. Cleavage of APP first by alpha secretase and then gamma-s
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Crystal structure of CD LEL have
2021-12-21
Crystal structure of CD81-LEL have revealed the head sub-domain to be implicated in binding to HCV (Kitadokoro et al., 2001). In a study using African green monkey CD81, T163A, F186 L, E188K and D196E mutations disrupted HCV E2 binding (Higginbottom et al., 2000). In our docking studies, T163 and D1
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Insulin de sensitization has been observed in the brains
2021-12-21
Insulin de-sensitization has been observed in the brains of people with AD [51], [52], [53] and we previously demonstrated that the GLP-1 analogue liraglutide was able to reverse this [54]. Importantly, px12 mg insulin de-sensitization correlates well with cognitive decline [15], [55] and with tau p
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Experiments show that CSD propagation can be slowed or
2021-12-21
Experiments show that CSD propagation can be slowed or interrupted by pre-existing lesions or areas of high astrocytic density (Chen et al., 2006), and reduced expression of astrocytic gap junctions significantly increases the size of ischemic infarcts (Nakase et al., 2003). By decreasing the gap ju
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The highest metabolic stability observed for compound k
2021-12-21
The highest metabolic stability observed for compound 4k (EC50=0.41μM corresponding to 218ng/mL) among the four selected frontrunner candidates was the principal decisive point in nominating this compounds for pharmacokinetic characterization in mice at the dosage of 10mg/kg (administered intravenou
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