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PF is orally bioavailable and has appropriate pharmacokineti
2023-03-06

PF-06409577 is orally bioavailable and has appropriate pharmacokinetic properties for use in rodents, allowing us to evaluate its impact on lipid and cholesterol biosynthesis in vivo (Cameron et al., 2016). PF-06409577 lowered the incorporation of 14C-acetate into hepatic lipids in vivo in a dose de
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Introduction AMP activated protein kinase AMPK is mainly kno
2023-03-06

Introduction AMP-activated protein kinase (AMPK) is mainly known as a highly conserved and ubiquitously expressed energy sensor that is highly sensitive to changes in cellular energy levels (by sensing increases in AMP:ATP and ADP:ATP ratios) and makes appropriate adjustment to balance the consumpt
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To elucidate this relationship we developed a spatial model
2023-03-06

To elucidate this relationship, we developed a spatial model of Ca-influx through N-methyl-D-aspartate receptor (NMDAR), CaMKII/PP1 activation, and AMPAR insertion in a realistic spine geometry. Using this model, we show that i) variables in membrane voltage mediated Ca-influx, particularly the numb
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Avasimibe australia br Results We set out
2023-03-06

Results We set out to identify in an unbiased manner a set of candidate “scaling factors” that might participate in transcription-dependent synaptic scaling up. The ex vivo slice and profiling studies were conducted on HsCt5 mice (described later) at postnatal day (P) 14 to P15, an age at which s
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A straightforward synthetic pathway was adopted to synthesiz
2023-03-06

A straightforward synthetic pathway was adopted to synthesize the target compounds as outlined in . The starting chloromethylquinazolinones (–) were synthesized from anthranilic Rose Bengal in two steps following reported procedures., , , The first step involves chloroacetylation of anthranilic ac
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br Current therapies for metabolic diseases Inborn errors of
2023-03-06

Current therapies for metabolic diseases Inborn errors of metabolism caused by deficiency of particular enzymes due to loss of function mutations or deletions have been treated by decreasing the intake of the enzymatic substrate, supplementation with an essential cofactor or vitamin, increasing m
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Perhaps the discovery of this linkage has
2023-03-06

Perhaps the discovery of this linkage has served to catapult much of the work on ABCA1, leaving its family member in need of a relationship with a defined human pathology. In this regard, there is by now a quite mature literature that suggests that ABCA2 may have been overlooked in terms of its impo
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HT receptors are distributed throughout the brain
2023-03-06

5-HT3 receptors are distributed throughout the brain, within the brainstem (e.g., nucleus tractus solitarius, area postrema and spinal trigeminal nucleus) and Malonic acid (e.g., hippocampus, amygdala, nucleus accumbens, putamen and caudate) (Abi-Dargham et al., 1993, Barnes et al., 1989, Bufton et
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While high fat diet models of
2023-03-03

While high-fat diet models of insulin resistance are acceptable approaches for the study of pre-diabetes in humans, they are not suitable for modeling progression towards established type2 diabetes. The pattern of activation of the lipoxygenase pathway in pre-clinical models of type2 diabetes has no
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Why do glutamate and glycine bind
2023-03-03

Why do glutamate and glycine bind to the SNS-314 Mesylate in such different ways? Given the overall structural similarity between the GluN2A and GluN1 LBDs, one might conclude that the LBDs also bind ligands via similar processes. NMDA receptors with engineered disulfide linkages that lock the GluN
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In spite of this unexpectedly after
2023-03-02

In spite of this, unexpectedly, after three-week cherry puree consumption no AC increase was observed, irrespective of the method used (Table 2). A statistically significant decrease of AC was even measured by LOX-FL and ORAC methods (−3.5% and −9%, respectively). Nevertheless, a much more evident d
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It has been proposed that
2023-03-02

It has been proposed that a PrP pathogenic mechanism is a toxic gain of function secondary to the misfolding of mutated PrP. However, such a mechanism might not apply to all mutant PrP species, since some mutations had little effect on the stability and folding kinetics of PrP (Swietnicki et al., 19
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Recently two distinct small molecule inhibitors of PHGDH
2023-03-02

Recently, two distinct small-molecule inhibitors of PHGDH were identified using high-throughput screens, both of which inhibit de novo serine biosynthesis and show selective toxicity to cancer AZ191 mg with high SSP flux [50,51]. The inhibitor NCT-503, which has an IC50 of 2.5μM, reduces the growth
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Last decade has provided a
2023-03-02

Last decade has provided a number of studies indicating that AhR signaling could play a role both in the development and in progression of multiple cancer types, with potential implications for cancer therapy (for review see (Kolluri et al., 2017; Murray et al., 2014)). Activation of AhR is consider
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br Conclusion The HT receptor family
2023-03-02

Conclusion The 5-HT receptor family is complex, and one may ask as does Bryan Roth et al. [205] whether this is useless ck1 inhibitor (i.e. too much redundancy) or an embarrassment of the riches (i.e. many potential targets to choose from to affect normal or pathological function); molecular bio
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