• An even more striking difference is observed when

  2019-07-02

  

  An even more striking difference is observed when comparing active site residues, which are evolutionarily very well conserved in other soluble PPases 18, 19. In 31 known PPase sequences, 13 functionally important active site residues are conserved in all sequences, but only two of them (D70 and D97

• br Introduction Sphingolipids are ubiquitous membrane compon

  2019-07-02

  

  Introduction Sphingolipids are ubiquitous membrane components of all eukaryotic cells belonging to a group of complex lipids. The basic structure of sphingolipids is composed of a sphingoid long chain base (LCB) linked to a fatty calpain inhibitor 1 via an amide bond to form a ceramide [1]. In an

• Six substrate recognition sites SRS

  2019-07-02

  

  Six substrate recognition sites (SRS1-SRS6) have been identified at positions 102-123, 204-209, 238-244, 301-319, 374-382 and 483-492 (Table 2, underlined residues) based on Gotoh\'s proposal [30]. CYP3A163 displays the similar characteristic long sequences between helices F and G presenting two add

• br Transparency document br Acknowledgments This work

  2019-07-02

  

  Transparency document Acknowledgments This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (the National Program of Sustainability I, Grants LO1204 and LO1304), by the Czech Science Foundation (15-17282Y) and by Palacký University Olomouc (IGA_PrF_2017_0

• In this context our observation

  2019-07-02

  

  In this context, our observation that the 2b3a inhibitors predictor of positive QFN-CMV responses is background CMV seropositivity was not unexpected. Older age, despite well-known effects of CMV memory inflation did not appear to independently impact QFN-CMV responses in our study. The inter-play

• The expression of EBI has been found

  2019-07-02

  

  The expression of EBI2 has been found to be dysregulated in several types of B cell malignancies and is thus reduced in e.g. diffuse large B-cell lymphomas [12] and chronic lymphocytic leukemia [13] and increased in post-transplantation lymphoproliferative disorders (PTLDs) [14]. EBI2 is also highl

• Previous study showed that CXCR plays an important

  2019-07-02

  

  Previous study showed that CXCR plays an important role in viral infection and that CXCR1, as an important molecule in CXCR, also plays important roles in viral pathogenesis [[39], [40], [41], [42]]. In mammals, CXCR1 plays an important role in resisting viral infection [43,44], and CXCR1 plays an i

• Redundancy of tumor promoting signaling pathways is

  2019-07-02

  

  Redundancy of tumor promoting signaling pathways is one of the mechanisms that prevent a lasting effect of targeted therapies, as has been demonstrated by the growing number of alternative pathways that confer resistance to EGFR-targeted therapies [3]. We show here that CSF-1R can, at least partiall

• Khan et al studied the effects of two

  2019-07-02

  

  Khan et al. studied the effects of two structurally divergent coumarins viz calipteryxin 3 and (3′S,4′S)-3′,4′-disenecioyloxy-3′,4′-dihydroseselin 4 from Seseli recinosum, in lipopolysaccharide (LPS)-stimulated murine macrophages. The study revealed that calipteryxin and (3′S,4′S)-3′,4′-disenecioylo

• During the past decade it became increasingly clear

  2019-07-02

  

  During the past decade, it became increasingly clear that the affinity and efficacy of small agonists acting on the orthosteric binding site of a GPCR can be modulated by ligands that bind to a topographically distinct (allosteric) binding site on the same GPCR molecule 33, 39, 40, 41, 42. This allo

• Constitutive activity of Ras Raf MEK

  2019-07-02

  

  Constitutive activity of Ras/Raf/MEK/ERK pathway plays a critical role on melanoma growth, thus inhibition of activity of Ras, Raf and MEK can reduce ERK activity, leading to a decrease in melanoma cell proliferation, survival and invasion (Burotto et al., 2014; Paluncic et al., 2016). Our results a

• As for the molecular mechanism Ferguson BD suggested that Ep

  2019-07-02

  

  As for the molecular mechanism, Ferguson BD suggested that EphB4/EphrinB2 stimulation induced topoisomerase I activity in small cell lung cancer cell lines. Treatment of BAY 87-2243 with EphrinB2/Fc induced topoisomerase activity as assessed by DNA relaxation in cells with high EphB4 expression lev

• Introduction Neuropathic pain occurs in approximately one th

  2019-07-02

  

  Introduction Neuropathic pain occurs in approximately one-third of patients with diabetes and is refractory to currently available analgesic drugs (Abbott et al., 2011). This painful diabetic neuropathy (PDN) is associated with elevated levels of methylglyoxal (MG; a reactive glucose metabolite) an

• br Results br Discussion In this paper we present

  2019-07-02

  

  Results Discussion In this paper we present insights into the observed specificities of inhibitors targeting the ubiquitin-activating and related E1 mitomycin via crystal structures of the specific NEDD8-E1 inhibitor MLN4924, the dual NEDD8/Ub E1 inhibitor ABPA3, and the selective Ub-E1 inhib

• br Third trimester crossing the threshold

  2019-07-01

  

  Third trimester – crossing the threshold to immunocompetence Summary Regrettably, studies on the fetal immune system have yet to yield practical results. While it is becoming apparent that the fetal immune response plays a role in determining the outcome of congenital CMV infection, we still l

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