• br Acknowledgements Professor Olli A J nne

  2019-07-03

  

  Acknowledgements Professor Olli A. Jänne is warmly thanked for support and for providing excellent research facilities. Professor Patrik Finne is acknowledged for his help with statistical analyses. Drs Ronald Evans, Vincent Giguère, Jorma Palvimo, Malcolm Parker, and Anastasia Kralli are acknowl

• br Concluding remarks br Transparency

  2019-07-03

  

  Concluding remarks Transparency document Acknowledgements Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572 (RS). The content is solely the responsibility of the authors and does not neces

• How does an increase in E affinity for the RING

  2019-07-03

  

  How does an increase in E2 affinity for the RING domain favor higher activity and polyubiquitination by the E2? Binding of the RING domain to the E2 positions the donor Ub in the E2~Ub conjugate in a closed complex [16], [17], [18] that increases the reactivity of the thioester [60]. A higher affin

• br Sphingosine kinase One of the enzymes

  2019-07-03

  

  Sphingosine kinase One of the enzymes closely related to DGKs are the sphingosine kinases (SKs). These enzymes catalyze the conversion of sphingosine (Sph) to sphingosine-1-phosphate (S1P). SKs and DGKs are closely related lipid kinase in term of basic enzymology and the mechanism of regulation a

• Due to cell cell interactions high

  2019-07-03

  

  Due to cell-cell interactions, high concentrations of LTs can be locally generated in a short period of time during an inflammatory response, thus potentiating LT function. The cellular communication can be mediated between immune cells as well as between immune cells other cell types. Several studi

• Dexamethasone DEX a potent synthetic glucocorticoid drug is

  2019-07-03

  

  Dexamethasone (DEX), a potent synthetic glucocorticoid drug, is effective for treatment of a range of inflammatory and autoimmune conditions as well as the reduction of side effects associated with chemotherapy. On the Czech Republic pharmaceutical market, DEX is incorporated into eighteen drugs use

• br Use of CDK inhibitors in CLL today

  2019-07-03

  

  Use of CDK inhibitors in CLL today There has been explosive development of novel therapeutics for CLL in the last decade and a massive transformation of practice is underway [75]. Most of this development and excitement revolves around B-cell receptor (BCR) signaling inhibitors: the Bruton tyrosi

• br Additional CDKs with a role

  2019-07-03

  

  Additional CDKs with a role in cancer Small molecule CDK inhibitors The majority of protein kinase inhibitors developed to date are type I inhibitors: they bind at the ATP–binding site, are ATP-competitive and target the kinase in its active state; with the activation loop DFG motif in the ‘in

• The assessment process is even more difficult

  2019-07-03

  

  The assessment process is even more difficult when Commercial-Off-The-Shelf (COTS) components – whose internals are partially or totally unknown – come into play. COTS are being increasingly used by the industry to reduce costs and to shorten development (and possibly deployment) time. However, sinc

• br Discussion Several DPP inhibitors are currently

  2019-07-02

  

  Discussion Several DPP-4 inhibitors are currently available for use in the treatment of type 2 diabetes mellitus. Due to the different chemical structures there are marked differences both in the binding kinetics on the target enzyme [10] and also different pathways of elimination [13] exist. In

• Interest in DGKs increased as it became clear

  2019-07-02

  

  Interest in DGKs increased as it became clear that not only are they important for lipid homeostasis, they serve to modulate the relative levels of diacylglycerol (DAG) and phosphatidic ci-1033 what (PtdOH) that play critical roles in a variety of signaling pathways (Eichmann and Lass, 2015; Liu et

• Studies carried out with LTRAs before

  2019-07-02

  

  Studies carried out with LTRAs before the identification of the CysLT2R, showed a controversial picture, as results that suggest a role for cysteinyl-LTs in the expansion of ischemic damage and in cardiac dysfunction during reperfusion [5], [68], [69] were evenly balanced by others suggesting that t

• br Introduction Alzheimer s disease AD is

  2019-07-02

  

  Introduction Alzheimer’s disease (AD) is the progressive version of mild cognitive impairment and usually met by the elderly population. It falls into the class of neurodegenerative disorders that attacks the nociceptin receptor nerves cells, or neurons, resulting in loss of memory, impairment o

• Introduction Progesterone also known as

  2019-07-02

  

  Introduction Progesterone, also known as P4, is a steroid hormone acting as a key component in the complex regulation of female reproductive function. P4 plays major physiological roles in the uterus and ovary by releasing mature oocytes helping in implantation and maintenance of pregnancy, as well

• The serotonin transporter gene encodes

  2019-07-02

  

  The serotonin transporter gene () encodes an integral membrane protein that transports serotonin from the synaptic spaces into the presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent way. This protein is a target of psychomotor stimulants

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