• Our previous high throughput screening HTS campaign using

  2020-09-17

  

  Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based PF-8380 assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20], [21], [22], [23],

• EP is the major receptor to mediate PGE

  2020-09-17

  

  EP4 is the major receptor to mediate PGE2-induced inflammatory pain. EP4 is upregulated by RI-1 in DRG neurons [16]. Intrathecal injection of the EP4 agonist produced pain responses [25]. Either systemic or local injection of EP4 antagonists relieves inflammatory pain [3], [16], [26]. However, the

• br Acknowledgements We thank Joseph

  2020-09-16

  

  Acknowledgements We thank Joseph Granger and Bryan Neumann for careful reading of this manuscript. This work is supported by NIH grants AG37609 and HL 60306 to TYC and CCYC. Introduction Eleven million tonnes of waste are produced yearly by the European pulp and paper industry (Monte et al.,

• While agnathans appear to have reduced their Ednr

  2020-09-16

  

  While agnathans appear to have reduced their Ednr repertoire to the Ednra gene (that may have been amplified in the Arctic lamprey), gnathostomes in general have been relatively inert to Ednr gene loss. Strikingly, the only Ednr gene that has been lost repeatedly is EdnrB2 (lost in therian mammals,

• In humans several different small ubiquitin related modifier

  2020-09-16

  

  In humans, several different small ubiquitin-related modifier (SUMO) paralogs can be conjugated to cellular proteins. The human genome codes for five SUMO paralogs (SUMO1–5); of these, SUMO1 and the almost identical SUMO2 and SUMO3 are ubiquitously expressed. Sumoylation is executed by an enzymatic

• brain metabolism br Methods br Results br Discussion Preclin

  2020-09-16

  

  Methods Results Discussion Preclinical data indicate that nepicastat modulates sympathetic drive to the brain metabolism with a mild pressor effect in various animal models of hypertension (Stanney et al., 1998). However in this clinical study, the doses of nepicastat employed did not sign

• Primases are classified into two major groups

  2020-09-16

  

  Primases are classified into two major groups: first, the DnaG primases, found in bacteria and bacteriophages, and second, the archaeoeukaryotic primases. Remarkably, bacterial and archaeoeukaryotic primases have no structural similarity and, presumably, evolved independently (Leipe et al., 1999). T

• br Results br Discussion Repair by

  2020-09-16

  

  Results Discussion Repair by NHEJ implicitly requires the pairing together of broken chromosome ends. A complex of Ku, XRCC4, DNA ligase IV, and XLF (PEC) is necessary and sufficient for this purpose (Reid et al., 2015). Here, we describe dynamic changes in this complex that are triggered by d

• calculating dilution In rats exposed to day of

  2020-09-15

  

  In rats exposed to 1 day of nicotine withdrawal (24 h after the last nicotine administration) we expected a decrease of general locomotor activity and a decrease of global striatal dopamine release, which were assessed in a previous study following 14 days of nicotine exposure and 24 h of nicotine w

• By live imaging of GUL GFP we

  2020-09-15

  

  By live imaging of GUL-1-GFP, we observed the kinetics of aggregate movement within the cell. One of the marked characteristics of GUL-1-GFP cytosolic (but not nuclear-associated) aggregate motion was a “comet-like” movement that was found to be dependent on the presence of properly polymerized micr

• Ten non FH ADH probands fulfilled the

  2020-09-15

  

  Ten non-FH ADH probands fulfilled the diagnostic criteria of hyperabsorbers. Table 2 shows the main lipid characteristics of these subjects and of 10 non-hyperabsorber probands used for comparison. There were differences between groups in body mass index, waist circumference and triglycerides. Other

• Water inorganic salts sugars lipids

  2020-09-15

  

  Water, inorganic salts, sugars, lipids, nucleic acids and proteins are the main basic materials forming the organism. Life activities can be controlled or regulated by a series of complicated and chain-reactive protein–protein interactions. Protein–protein interaction is considered as the bases and

• It is noteworthy that little is known as to the

  2020-09-15

  

  It is noteworthy that little is known as to the role of autophagy in regulation of eNOS phosphorylation and eNOS uncoupling. eNOS monomers, but not eNOS dimers could be degraded by ubiquitination [39], harbingering the existence of protein degradation pathways in modulation of eNOS turnover and acti

• In this study we have explored a functional role

  2020-09-14

  

  In this study we have explored a functional role of the oxysterol/EBI2 system in this process. In 2011 we and others reported the discovery of oxysterols as ligands for EBI2 [6], [7]. Oxysterols are metabolites generated by hydroxylation of cholesterol and have been linked to a variety of fundamenta

• br Results br Discussion Many studies have shown that

  2020-09-14

  

  Results Discussion Many studies have shown that intrinsic properties of the E2 enzyme govern the nature of the Ub modification, including both the multiplicity of the Ub modification and the specific ID-8 type in the case of polyubiquitin chains [3], [4], [9], [14]. Whereas previous studies o

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