• A high throughput screening campaign

  2023-11-21

  

  A high-throughput screening campaign led to the discovery of the first series of both potent and selective ATR kinase inhibitors by Vertex Pharmaceuticals (Charrier et al., 2011). One of these compounds, VE-821, was shown to be a potent ATP-competitive inhibitor of ATR with minimal cross-reactivity

• Cerebral ischemia occurs following the occlusion of a

  2023-11-21

  

  Cerebral ischemia occurs following the occlusion of a cerebral artery by a thrombus and causes cell swelling due to cytotoxic edema and BBB disruption with vasogenic edema (Loreto and Reggio, 2010, Nakaji et al., 2006, Shibata et al., 2004). Vasogenic edema is directly linked to alteration of the BB

• Arginase deficiency is a rare urea cycle

  2023-11-21

  

  Arginase deficiency is a rare urea cycle disorder with hyperargininemia and profound neurological impairment as hallmark features. Arginase-1-deficient mouse models have been created, and they exhibit a profound lethal phenotype approximately 2 weeks after birth in the global knockout (KO) mice or a

• ARG I is one of the

  2023-11-21

  

  ARG I is one of the most important mammalian enzymes responsible for nitrogen metabolism since it comprises the main route for the elimination of excess nitrogen resulting from amino pathways cu and nucleotide metabolism [18]. ARG I deficiency leads to hyperargininemia, characterized by progressive

• br Epidemiology br Genetics The dominantly inherited

  2023-11-21

  

  Epidemiology Genetics The dominantly inherited PrP cerebral amyloidoses are genetically transmitted with a penetrance of almost 100%. Early linkage analysis studies helped to established the relationship between GSS and mutations in the PRNP gene. PRNP is located on the short arm of chromosome

• br AR expression in breast tissue Although

  2023-11-21

  

  AR expression in breast tissue Although androgenic signalling is chiefly associated with the development and maintenance of primary and secondary male characteristics, especially during puberty when the testes are by far the major source of testosterone, the AR also plays important functions in f

• Intriguingly androgens may also have an indirect effect on A

  2023-11-21

  

  Intriguingly androgens may also have an indirect effect on AR gene expression through inhibition of the GATA2 transcription factor gene (He et al., 2014) (Table 1). Using ChIP-seq, GATA2 was found to bind to a regulatory element 5.5 kb upstream of the TSS of the AR gene and enhanced transcription, w

• br Experimental Procedures br Acknowledgments br Introductio

  2023-11-21

  

  Experimental Procedures Acknowledgments Introduction Cellular and molecular mechanisms underlying synaptic plasticity in the Wnt agonist 1 are thought to be involved in memory acquisition. Synaptic plasticity is categorised into two main types, long-term depression (LTD) and long-term poten

• When arachidonic acid is used as a substrate the

  2023-11-20

  

  When arachidonic Angiotensin 1/2 (1-5) is used as a substrate, the platelet-type 12S-lipoxygenase produces predominantly the 12S-hydroperoxy derivative. In contrast, the leukocyte-type 12S-lipoxygenases generate substantial amounts of the 15-lipoxygenase product in addition to the 12S-hydroperoxy d

• br Materials and methods br Results br Discussion Intracellu

  2023-11-20

  

  Materials and methods Results Discussion Intracellular metabolic pathways of sugar, such as glycolysis and TCA cycle, provide material and energy for the synthesis of other substances, including amino acids. Thus, the content of sugars and their metabolic pathways are important for amino N6

• Imatinib was first approved for the treatment of

  2023-11-20

  

  Imatinib was first approved for the treatment of Philadelphia chromosome positive chronic myelogenous leukemia in 2001 [25]. This first approved small molecule antagonist is quite unusual in that it provides a durable response that lasts for more than a decade in the majority of patients. Imatinib h

• br Conflict s of interest br

  2023-11-20

  

  Conflict(s) of interest Retinopathy of prematurity (ROP) is a leading cause of childhood blindness Retinopathy of prematurity (ROP) is a disease of premature infants which disrupts normal retinal vascularization (Fleck and McIntosh, 2008). With increased survival of extremely premature infants

• At the last follow up nine patients

  2023-11-20

  

  At the last follow-up, nine patients had discontinued pyridostigmine within the first year postoperatively. Only one patient required pyridostigmine at a higher dose, but this was accompanied by successful weaning of prednisolone. None of the 5 patients who were on pyridostigmine treatment alone pri

• Our study like that of Zill et al included

  2023-11-20

  

  Our study, like that of Zill et al. (2012) included European Caucasians, although their population was much smaller (n=162) and more heterogeneous (19–72years). Further, potential confounding or effect modification by other health, lifestyle or genetic factors was not considered. These differences m

• Having established the structural requirements for potency i

  2023-11-20

  

  Having established the structural requirements for potency in both the biochemical and biomarker (CRA) assays, we evaluated key compounds in the metabolic stability assay. Disappointingly, we found that all compounds had high intrinsic clearances in mouse microsomes. To ascertain whether the in vitr

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