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Relative to the impact of moderate PAE on markers
2022-02-01

Relative to the impact of moderate PAE on markers of histaminergic neurotransmission, there were four salient observations from the studies reported here. First, it does not appear that moderate PAE affects the number of HDC-positive neurons in the tuberomammillary nucleus of the ventral hypothalamu
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There might be a hedgehog dilemma in a broad class
2022-02-01

There might be a hedgehog dilemma in a broad class of games, but this paper focuses on the case where players only care about : the distance between their attitudes. Here we generalize the main example of a quadratic loss function. So, player ’s payoff is higher when the distance is closer to ’s
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In this study we explore different
2022-02-01

In this study, we explore different mathematical models for describing the IVIVC of a preclinical dataset of 12 different dual GPR109A/GPR81 agonists. The objective is to establish a predictive model of in vivo lipolysis suppression in the rat based on in vitro potency data. First, a nonlinear mixed
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Apart from the different assays used biased agonism could
2022-02-01

Apart from the different assays used, biased agonism could also explain the inconsistent pharmacology of GPR55. Indeed, one study compared the effect of LPIs and Virodhamine in HEK293 androgen receptor stably transfected with human GPR55. They found that the effect of both ligands on intracellular
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br Myelin and metabolism In addition to promoting
2022-02-01

Myelin and metabolism In addition to promoting efficient b catenin inhibitor propagation, myelin is also critical for trophic and metabolic support of axons [56]. To provide metabolites to axons accurately, glia must ‘know’ the metabolic requirements of axons. Could electrical activity by axons
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The mechanism underlying the anorectic effect of OXM
2022-01-31

The mechanism underlying the anorectic effect of OXM is well established. It is centrally mediated via GLP-1 receptor activation, confirmed by both pharmacological blockade of the GLP-1 receptor, and using GLP-1 receptor knock-out mice [2], [11], [12]. However, the mechanism by which it increases en
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Insulin de sensitization has been observed in
2022-01-31

Insulin de-sensitization has been observed in the brains of people with AD [51], [52], [53] and we previously demonstrated that the GLP-1 analogue liraglutide was able to reverse this [54]. Importantly, cdk1 insulin de-sensitization correlates well with cognitive decline [15], [55] and with tau pro
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The Notch cleavage efficiency of Aph aS containing complexes
2022-01-31

The Notch-cleavage efficiency of Aph1aS containing complexes was lower than that of Aph1aL γ-secretases, especially in combination with PS2, suggesting that Aph1aS is a determinant of low Notch-cleavage specificity, considering that the different subcellular localization of PS1 and PS2 didn't affect
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Liver and muscle isozymes have
2022-01-31

Liver and muscle isozymes have been found in vertebrate tissues [2], [5], [6]. The liver FBPase is recognized as a regulatory enzyme of gluconeogenesis. The muscle isozyme participates in the glycogen synthesis from lactate and in the regulation of glycolysis [7], [8], [9]. The basic difference betw
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br Rationale The present study was motivated
2022-01-31

Rationale The present study was motivated to get further insight into the molecular recognition processes of 2-alkyl(amino)ethyl-1,1-bisphosphonates taking compounds 12–14 as reference structures. We have recently demonstrated that TcFPPS inhibitors 12 and 13 bind to the allylic site of the enzym
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Within a live organism cells need to transfer information
2022-01-31

Within a live organism, cells need to transfer information to each other. Exocytosis is one of the critical mechanism which releases variety of ligands into the extracellular space. When cells export material via exocytosis, they first pack into vesicles, then cause the vesicles to tether at the pla
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br Transportation from TGN toward plasma membrane The insuli
2022-01-31

Transportation from TGN toward plasma membrane The insulin molecules are packaged along with other molecules such as C-peptides, amylin, Zn2+, ATP and GABA in synaptic-like macrovesicles (SLMVs, with the diameters of 50–100 nm) and large dense core vesicles (LDCVs, with the diameters of 200–500 n
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Septic shock a condition where endothelium
2022-01-31

Septic shock, a condition where endothelium-derived substances most likely play an important role, is often accompanied by cardiac dysfunction, pulmonary hypertension, systemic hypotension and impaired oxygen utilisation with systemic acidosis (Vincent, 1998). Experimental endotoxaemia shows a simil
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ARRY-380 In conclusion the present study shows
2022-01-31

In conclusion, the present study shows that the endothelin system is of importance in the cardiopulmonary vascular pathophysiology of porcine endotoxin shock. In this model, combination of a selective endothelin ETA and a selective endothelin ETB receptor antagonist markedly improved pulmonary circu
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Numerous strategies of cardiomyocyte protection are
2022-01-30

Numerous strategies of cardiomyocyte protection are effective in preclinical, animal models and in small clinical trials. However, most have disappointed in large clinical trials [4,5]. Failures of cyclosporine and post-conditioning to mitigate reperfusion injury are recent examples [[6], [7], [8]].
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