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After initial validation of the ability of Ad
2022-07-01
After initial validation of the ability of Ad5-Cre virus to express Cre recombinase protein in glial cells in vitro and in vivo, we employed this virus to induce site-specific deletion of our target GlyT1 in the thalamus, through injection of the cKO GlyT1 mice. This transgenic line was constructed
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The glycine receptor is an ionotropic neurotransmitter recep
2022-07-01
The glycine receptor is an ionotropic neurotransmitter receptor coupled to a chloride ion channel. Glycine receptors are typically described as inhibitory and distributed in the spinal cord and brainstem, though mRNA transcription labelling studies in rats show expression in the hippocampus, cingula
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LIMKi 3 synthesis In respect of clinical development Takeda
2022-07-01
In respect of clinical development Takeda has pioneered the field with the GPR40 agonist TAK-875 or fasiglifam (Figure 2A), which in phase-II studies decreased HbA1c as efficiently as sulfonylurea without signs of hypoglycemia [24]. This was obtained with surprisingly little effect on systemic insul
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br Conclusion In summary a series of novel
2022-07-01
Conclusion In summary, a series of novel GPR40 agonists bearing phenylpropiolic AMG-458 motif with favorable metabolic stability were prepared and evaluated for their activities as GPR40 agonists. Among them, compound 9 was identified as a structurally distinct GPR40 agonist possessing potent ac
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A localization of GK to
2022-07-01
A localization of GK to both a cytoplasmic and perinuclear area of normal rat pancreatic beta-cells was reported in 1996 (Noma et al., 1996), which changed on acute hyperglycemia to a more diffuse staining throughout the cytoplasm. The localization of GK within the nucleus was first reported by Mura
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The experiments indicate that a major
2022-07-01
The experiments indicate that a major component of the vasodilatation is due to antagonism of α 1-adrenoceptors. Evidence for α1-adrenoceptor antagonism is that vasodilatation was observed in AZD8055 preconstricted with α1-adrenoceptor agonists, phenylephrine or methoxamine, but not in vessels prec
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Importantly bioelectric circuits in tissues Fig
2022-07-01
(4) Importantly, bioelectric circuits in tissues (Fig. 2A) have a capacity to store long-term patterning information. An example is planarian anterior-posterior patterning: during regeneration, each fragment cut from a worm needs to build a head and tail at their correct ends. This process is regula
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Although NCT undergoes complex glycosylation processing for
2022-06-30
Although NCT undergoes complex glycosylation processing for maturation through trafficking from endoplasmic reticulum to Golgi or additional compartments, the effect of NCT glycosylation on γ-secretase activity and substrate specificity is still unknown. The present study focused on glycosylation st
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Retinal GAL receptor distribution suggests an intrinsic neur
2022-06-30
Retinal GAL receptor distribution suggests an intrinsic neuronal control since retina lacks an autonomic innervation, and a signal modulation seems most likely here, acting via GALR1 while GALR2 and GALR3 seem to play a rather minor role in this signal transduction. While sources acting on these ret
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Serotonin hydroxytryptamine HT is a monoamine
2022-06-30
Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine with dual functions in the developing and matured brain. 5-HT regulates development of the AS1842856 as a neurotrophic factor and is involved in emotion and cognition as a neurotransmitter in adulthood (Gaspar et al., 2003; Daubert and Condron, 2
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In our study the changes
2022-06-30
In our study, the changes in the α4 and δ subunit expression were accompanied by a significant increase in γ2 subunit expression in almost all analysed hippocampal structures in the fully kindled animals. In contrast, an acute injection of PTZ at a convulsive dose (55mg/kg) evoked a potent decrease
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br Results and discussion br Conclusion In
2022-06-30
Results and discussion Conclusion In summary, we designed and discovered a series of novel GPR40 agonists containing 3,5-dimethylisoxazole with improved tPSA and ideal cLog P. Most of these compounds were confirmed as excellent GPR40 agonists in vitro. Especially, compound 11k exhibited robust
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arginase inhibitor LMWHs are currently recommended for the t
2022-06-30
LMWHs are currently recommended for the treatment of VTE in patients with cancer. Compared to vitamin K antagonists, LMWHs are more effective in reducing the risk of recurrent VTE without increasing the risk of bleeding [13]. However, a post hoc analysis of this arginase inhibitor previous study sh
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The ability of the vasculature to determine the nature and
2022-06-30
The ability of the vasculature to determine the nature and magnitude of a stimulus is essential for the appropriate and proportionate response. The vascular response to injury include rapid changes to blood flow to reduce the loss of blood, followed by increased contact with the sub-endothelial laye
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H O induced astrocyte ATP release through lysosome exocytosi
2022-06-30
H2O2 induced astrocyte ATP release through lysosome exocytosis. The LDH assay and electric microscope results indicated that the increase of extracellular ATP concentration was not due to the cell rupture, but the alternations in cell activities. In addition, when lysosome exocytosis was blocked by
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