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ldk378 Clinical trials of all GSIs have
2021-12-24
Clinical trials of all GSIs have ended prematurely, raising the question on our understanding of their target, the γ-secretase/presenilin. Development of compounds to target γ-secretase and reduce Aβ production is complicated by the fact that γ-secretase/presenilin has critical biological function,
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br Acknowledgments This study was supported by a Conquer
2021-12-23
Acknowledgments This study was supported by a Conquer Cancer Foundation (American Society for Clinical Oncology) Drug Development Research Professorship Grant (AAA). Introduction Gastric cancer (GC) is one of difficult cancers to treat in terms of its poor prognosis and limited applicability
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Focal adhesion kinase FAK also known as
2021-12-23
Focal adhesion kinase (FAK), also known as protein tyrosine kinase2 (PTK2), is a tyrosine kinase and vital member in integrin-mediated signaling pathways [3]. In response to integrin involvement, FAK would be phosphorylated. It was reported that FAK is involved in cellular adhesion and spreading [4]
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Regulation of gene expression in
2021-12-23
Regulation of gene expression in mammalian cells is governed by the epigenetic machinery, which includes several distinctive yet entangled branches. DNA and histone modifying enzymes, non-coding regulatory RNAs, and ATPase-dependent chromatin remodeling proteins all contribute to the dynamic alterat
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LY2584702 Reactivation of memory engram neurons underlies me
2021-12-23
Reactivation of memory engram neurons underlies memory retrieval. Neurons activated during memory formation are reactivated during the memory test 24, 25, 32. The reactivation is observed in the cerebral cortex as well as in the hippocampus and amygdala 33, 34. The ratio of the reactivation correlat
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However HDACi can also increase the acetylation of
2021-12-23
However, HDACi can also increase the acetylation of other transcription factors that regulate p65 transcriptional activity. The HDACi-induced activation of p65 can be negated by acetylated STAT1, which can specifically bind to p65 and inhibit its transcriptional activity 81, 82, 83. Interestingly,
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br Chemistry The methylsulfanyl dihydro H
2021-12-23
Chemistry The 8-methylsulfanyl-4,5-dihydro-1H-thieno[3,4-g]isothiadizaole scaffold was synthesized from commercially available 1,3-dioxolane-2,1′-cyclohexane-4-one 17 (Scheme 1). The isothiadizaole ring was formed with SOCl2 from N-carboxamide hydrazine imine 19, which was prepared from 17 and hy
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The inhibitory concentration of atrial natriuretic
2021-12-23
The 50% inhibitory concentration of atrial natriuretic factor at midgestation and term are –7.4 ± 0.12 and –7.38 ± 0.11, respectively, demonstrating no gestational age dependency in the effect of atrial natriuretic factor on spontaneous contractile activity. Diethyl amine/nitric oxide starts to inh
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The diseases of ocular surface and the
2021-12-23
The diseases of ocular surface and the cornea are very common in ophthalmological practice and as a result there is a continuous, need for novel therapeutic options. Here, we demonstrated a corneal distribution of GPR35, a potential molecular target for new drugs (; ). The search for the expression
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br Introduction Adipose tissue AT in addition to its functio
2021-12-23
Introduction Adipose tissue (AT), in addition to its function as protein phosphatase inhibitor storage, is an important endocrine organ and it secretes adipokines (Ahima, 2006). Adipose tissue is related to different physiological processes such as energy metabolism, insulin sensitivity, and inf
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To investigate if such an effect is observed in native
2021-12-23
To investigate if such an effect is observed in native GlyT1, we introduced S605D and S605A mutations into GlyT1 and transfected these DNA constructs into N2a cells. For an internal control of calpain cleavage, we also introduced the first 100 amino-acids of the rat GlyT2N terminus upstream of the m
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br Material and methods br Result
2021-12-23
Material and methods Result Discussion The female with well-differentiated endometrial cancer, especially those in the reproductive age have a strong desire to preserve fertility. Therefore, conservative medical treatment with progestin is widely used in the clinic. However, up to 30% of pa
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br Results br Discussion br Materials and Methods br
2021-12-23
Results Discussion Materials and Methods Introduction Deoxyribonucleic kinase inhibitors (DNA) is among the most important biopolymers in living organisms alongside carbohydrates and proteins. DNA is a linear polymer consisting of four types of nucleobases, deoxyribose, and phosphate. Th
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Molecular dynamics studies have proved an
2021-12-23
Molecular dynamics studies have proved an effective means of characterising transition state pathways between the inward- and outward-facing states, and providing the relative propensity for each state. For example, long-timescale simulations of the membrane-embedded LeuT dimer, totalling ∼21 μs, ha
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A number of experimental data declare a tight
2021-12-23
A number of experimental data declare a tight interdependence between the pathological changes of glutamate transport in 235 6 and consequent alterations in glutamate transport and activity/expression of glutamate metabolizing enzymes in platelets (Aliprandi et al., 2005, Behari and Shrivastava, 201
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