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The biological function of NPRA is demonstrated primarily th
2022-03-15
The biological function of NPRA is demonstrated primarily through the ANP/BNP-dependent GC catalytic activity of the receptor and the production of cGMP, which is regulated by several factors, including hormones, growth factors, physiological milieu, and the ligand itself [26,34,[36], [37], [38], [3
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Whilst it has long been appreciated
2022-03-15
Whilst it has long been appreciated that Rho-family GTPases are able to signal directly to focal adhesions, it is also becoming increasingly clear that they can achieve this indirectly, through their influence on the extracellular matrix to which the integrins bind. Cdc42 and RhoA have long been kno
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br Animal models of NASH The
2022-03-15
Animal models of NASH The human NAS system (see above) is largely reproducible in NAFLD mouse models [37] and, therefore, has been increasingly applied in the preclinical assessment of liver histological responses to test compounds. In general, the NAS system is well suited for this purpose, alth
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br Introduction Atherothrombosis is associated with the pres
2022-03-14
Introduction Atherothrombosis is associated with the presence of a low-grade, subclinical smoldering inflammatory response [1]. Several inflammatory markers, among them high-sensitive C-reactive protein (hs-CRP) [2], the erythrocyte sedimentation rate (ESR) [3], fibrinogen concentrations [4], int
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Studies of human and mouse GPR
2022-03-14
Studies of human and mouse GPR84, as ascertained by mRNA levels in various tissues, have determined that GPR84 is highly expressed on bone marrow cells, splenic T and B cells, and circulating granulocytes/monocytes/macrophages. In the latter cells, mRNA expression of is up-regulated only under infla
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Previous studies have suggested that GPR protects from bone
2022-03-14
Previous studies have suggested that GPR40 protects from bone loss via inhibition of osteoclasts. Wittrant et al. used GPR40 knock-out mice and primary osteoclasts to investigate the role of GPR40 on bone remodelling. Their results in primary osteoclast cultures and the RAW264.7 cell line showed tha
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This GluR A independent mechanism by which the associative s
2022-03-14
This GluR-A-independent mechanism, by which the associative strength of spatial locations can be increased (and/or decreased) gradually over many trials, and which presumably underlies spatial reference memory acquisition during tasks such as the Morris watermaze or the radial maze (Zamanillo et al.
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UO 126 As we showed earlier a to min incubation with mM
2022-03-14
As we showed earlier [19], a 20- to 30-min incubation with 2mM t-BHP resulted in erythrocyte swelling, which was less in a Ca2+-containing medium. Given that this effect was abolished in the presence of the Gardos channel inhibitor CLT, as well as in media high in K+, we suggested the contribution f
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Moreover after the initial bleaching of
2022-03-14
Moreover, after the initial bleaching of the fluorescent molecules in the targeted cell exposed to laser illumination, the neighboring reservoir trifluoperazine hydrochloride are expected to give in return new fluorescent ones if the cells are coupled together by gap junction channels. This suppose
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br Presenilins and apoptosis Apoptosis
2022-03-14
Presenilins and apoptosis Apoptosis, also known as programmed cell death, has a critically important role in tissue homeostasis, development, normal ageing and the pathogenesis of several diseases, including cancer and neurological disorders. The presenilins were first linked to apoptosis when ce
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Recently they reported an enyne chemotype
2022-03-14
Recently, they reported an enyne chemotype agonist (21, Fig. 13) with low lipophilicity, small polar surface area (PSA) and high potency (Clog P=3.8, tPSA=37 A2, EC50=20nM), further derived from TUG-424. The compound endowed fast oral SC-514 synthesis (tmax=15min) and a decent pharmacokinetic profi
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In order to understand the determinants of high affinity of
2022-03-14
In order to understand the determinants of high affinity of with amide side chain, an X-ray crystal structure of human liver FBPase in complex with was determined (). The position of phosphonate group and tricyclic scaffold of is similar to those of with no side chain, which suggests the formati
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The suboptimal trypsin selectivity profile of DPC
2022-03-14
The suboptimal trypsin selectivity profile of DPC423 prompted us to investigate additional P moieties for potency and selectivity. Glycinamide P () showed low nanomolar binding affinity against fXa which suggested that this P moiety sits deeper into the S pocket of fXa. To further elaborate on this
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WDR5 0103 This study appears to provide an
2022-03-14
This study appears to provide an additional example, albeit an unanticipated one, of the importance of renal ETB receptor function in the normal control of blood pressure and salt and water homeostasis. ETB receptor-deficient rats, collecting duct-specific ETB receptor knockout mice, and rats chroni
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Dysregulation of catecholaminergic neurotransmission particu
2022-03-14
Dysregulation of catecholaminergic neurotransmission, particularly the dopaminergic system, has long been correlated with the development of neuroinflammation and HAND. Studies specifically examining role of catecholamines in HIV pathogenesis, particularly focused on NeuroHIV, are relatively few. Ho
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