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Under increased drug pressure more protease variants with mo
2021-09-30

Under increased drug pressure, more protease variants with more than one substitution will likely become clinically relevant. The accumulation of additional substitutions can allow RAS variants to emerge that alone are not viable, but in combination can rescue the viral fitness. We previously demons
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Our study has strengths and limitations We believe we are
2021-09-30

Our study has strengths and limitations. We believe we are the 1st to report a novel model of secondary hypogonadism. Several animal models for hypogonadotropic hypogonadism (kisspeptin and the kisspeptin receptor knockout) exist but we are unaware of animal models of secondary hypogonadism with dif
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In an attempt to gain increased molecular
2021-09-30

In an attempt to gain increased molecular insights into in vivo transmigration of neutrophils, we applied an aseptic inflammatory skin chamber model. In this model, recruitment of neutrophils is typically associated with phenotypic changes of many plasma membrane localized adhesion receptors in peri
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(+)-Apogossypol Shikonin represents naphtoquinonic compound
2021-09-30

Shikonin represents naphtoquinonic compound isolated from the Chinese plant Lithospermum erythrorhizon[20]. Shikonin treatment inhibits AKT and ERK signaling pathways and induces apoptosis through FOXO transcription factors and mitochondrial pathway [21], [22]. Recent results suggest inhibition of l
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At the second step blind docking simulation of independent
2021-09-30

At the second step, blind docking simulation of 150 independent runs was performed with smaller grid box. Structures of open (1v4t.pdb), semi-closed (4dch.pdb) and two structures of closed configuration of GK (pdb codes are 1v4s and 3vev) were used for simulation (for detailed explanations on can se
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In the present study we set out to discover new
2021-09-30

In the present study we set out to discover new non-steroidal SEGRA and to analyse their mechanism of function. Towards this goal we initiated a virtual screening (VS) approach, utilizing structure-based pharmacophore modeling, in silico docking and molecular dynamics (MD) simulations. Our pharmacop
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br Mechanisms of gap junction internalization disaggregation
2021-09-30

Mechanisms of gap junction internalization: disaggregation, endocytosis and annular gap junctions It has been clearly shown that gap junction internalization can occur by a distinctive mechanism where one cell internalizes an entire gap junction via formation of double membrane structure termed a
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Some clinical reports have suggested
2021-09-30

Some clinical reports have suggested that galanin has a role in the neurobiology of mood disorders [[6], [7], [8], [9], [10]]. In behavioral studies, contradictory results have been reported [11,12]. For example, systemic administration of non-selective galanin receptor agonists, such as galmic [13]
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br Conclusion br Conflict of interest br Acknowledgements
2021-09-29

Conclusion Conflict of interest Acknowledgements Introduction The brain contains abundant fatty acids, which serve as constituents of membranes and as an energy source. In addition, fatty acids and their metabolites contribute to signal transduction between neurons or neurons and glial c
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br Conclusion br Conflict of interest br Acknowledgements
2021-09-29

Conclusion Conflict of interest Acknowledgements Introduction The brain contains abundant fatty acids, which serve as constituents of membranes and as an energy source. In addition, fatty acids and their metabolites contribute to signal transduction between neurons or neurons and glial c
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Thus while there is ample
2021-09-29

Thus, while there is ample evidence to rule out a generalized blockade of TGF-ß signaling by Hippo pathway activation upon establishment of cell–cell contacts, more recent studies have established that, in specific contexts, Hippo and TGF-ß signaling may either interfere or cooperate with each other
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PFI-2 br The value of a model of
2021-09-29

The value of a model of the complex forensic science matrix There have been various models proposed to address the complexity inherent to forensic reconstruction [15], [16], [17]. It is possible to argue that embracing the value of holistic models is important if we are to reclaim the ‘endeavour
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Several layers of regulation for this
2021-09-29

Several layers of regulation for this canonical activation of the HH pathway exist. First, the protein kinase A (PKA), the casein kinase 1α (CK1α) and GSK3β can phosphorylate and mark for proteosomal degradation the GLI transcription factors. [36] Second, Suppressor of Fused (SUFU) binds to GLI and
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It appears that not all GPR agonists require a high
2021-09-29

It appears that not all GPR119 agonists require a high dose to elicit acceptable jasplakinolide sale control. According to preclinical data presented at the GTCbio Diabetes Summit, a 3mg/kg dose of AR-7947 was enough to induce similar blood glucose-lowering effects compared to those achieved by 30m
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We also explored various nitrogen substituents
2021-09-29

We also explored various nitrogen substituents with an aim toward modulating sterics and basicity within the ABH series. No glycine uptake inhibition was detected with non-basic bicycles (data not shown). Isopropyl was the best compromise between desired on-target effect and clearance, however, eff
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