• br STAR Methods br Acknowledgments We thank Prof Y

  2022-04-16

  

  STAR★Methods Acknowledgments We thank Prof. Y. Tomari at the University of Tokyo for experimental advice and K. Hanada for technical assistance. This research was supported by Grants-in-Aid for Scientific Research on Innovative Areas “Nascent Chain Biology” (JP15H01548 and JP17H05677 to T.I. a

• A second feature of the Ras type

  2022-04-16

  

  A second feature of the Ras-type GTPases is that their ‘on’ and ‘off’ states are temporally and often spatially separated from one another. This feature is essential for GTPases mediating signaling and other processes that need to be kept ‘off’ until the arrival of signaling cues. The need to recrui

• br Acknowledgments This research was supported by

  2022-04-16

  

  Acknowledgments This research was supported by the Czech Ministry of Education, Youth and Sports by grants MSM LH11013 and Czech Grant Agency (501/12/0590). David Kopečný and Martina Kopečná were supported by the grant LO1204 from the National Program of Sustainability I by the Ministry of Educat

• Bupivacaine is one of the local anesthetics

  2022-04-16

  

  Bupivacaine is one of the local anesthetics commonly used in spinal anesthesia. Previous studies had shown that bupivacaine induced neuronal apoptosis and axon degeneration among various neuronal populations in spinal cord, such as sciatic nerves and dorsal root pemetrexed disodium (DRG) neurons [5]

• Some biguanides can cross the mitochondrial membrane

  2022-04-16

  

  Some biguanides can cross the mitochondrial membrane and increase L-lactate formation by inhibiting oxidative LY2409881 [34]. On the other hand, it has also been reported that levels of fasting plasma lactate in T2DM patients are similar regardless of whether or not metformin is administered [35] an

• The physiological role of lactate induced antilipolytic effe

  2022-04-16

  

  The physiological role of lactate-induced antilipolytic effects is less clear. It has been speculated that GPR81 mediates the inhibition of lipolysis during intensive exercise, a condition which results in high systemic lactate plasma concentrations 9, 10. Owing to oxygen shortage resulting from int

• The pharmacokinetics of was obtained

  2022-04-16

  

  The pharmacokinetics of was obtained in mouse, rat and dog to determine if it had a suitable profile to investigate the effects of the GPR120 mechanism (). had an adequate half-life, low clearance in all 3 species, and high blood levels and bioavailability. The low volume of distribution (V) indi

• As part of our discovery efforts searching for

  2022-04-16

  

  As part of our discovery efforts searching for small molecule GPR119 agonists, we analyzed active pharmacophores of known agonists from the literature, and found that -methylsulfonylphenyl and substituted 4-hydroxyl piperidine are common fragments. In our initial efforts, we linked these two fragme

• br Results and discussion br Conclusion In

  2022-04-16

  

  Results and discussion Conclusion In summary, starting from our previous lead 77 4 australia 1, we replaced the 5-nitropyrimidine core with pyrimidopyrimidine to obtain a series of novel compounds as drug candidates of GPR119 agonist for treatment of type 2 diabetes. Some derivatives showed go

• Thermal analysis of the NQ peptide was

  2022-04-16

  

  Thermal analysis of the NQ21 peptide was performed with the Solar CM2203 spectrofluorometer. We prepared three 1 μg/mL peptide solutions with different Dacinostat levels (5.0, 7.4, 8.5) in 0.01 M phosphate buffers. Each solution was slowly heated up from 28 °C to 54 °C with a step of 1 °C. Spectra

• To further investigate the molecular

  2022-04-16

  

  To further investigate the molecular mechanisms that underlie glycine's β-cell protective effects through its antioxidative activity in diabetes, we used a H2O2/high glucose-induced apoptosis cell model. Similar effects on ROS generation of high glucose and H2O2 support the in vivo results, suggesti

• Previous studies have suggested that GPR protects from bone

  2022-04-15

  

  Previous studies have suggested that GPR40 protects from bone loss via inhibition of osteoclasts. Wittrant et al. used GPR40 knock-out mice and primary osteoclasts to investigate the role of GPR40 on bone remodelling. Their results in primary osteoclast cultures and the RAW264.7 cell line showed tha

• Cytokines and hormones influence both gap junctions and endo

  2022-04-15

  

  Cytokines and hormones influence both gap junctions [106] and endocrine activity in the pituitary [3]. Long-term treatment (2 h) with the proinflammatory cytokines interleukin-1β (Il-1β) and tumor necrosis factor-α (TNF-α) transiently increases Cx43 expression and cell coupling in TtT/GF Ezatiostat

• Of the cases identified herein three known

  2022-04-15

  

  Of the 52 cases identified herein, three known and 11 novel FGFR fusion partners were identified. Notably, an oligomerization domain, including coiled-coil dimerization domains similar to that seen in echinoderm microtubule associated protein like 4 gene (EML4), which is the most common ALK partner

• Much is known about FPPS structure and function with over

  2022-04-15

  

  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

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