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GK allosteric activators validate the importance
2021-09-22
GK allosteric activators validate the importance of GK from a therapeutic perspective, but the nature of allosteric activation of GK remains unclear. The GK allosteric activator site, the pocket where GKAs bind, is ~20 Å remote from the active site (Fig. 1A). The allosteric site is the locus of many
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br Conclusion Our experiments have confirmed the effects
2021-09-22
Conclusion Our experiments have confirmed the effects of fasting, DIO, and E2 on the expression of Ghsr, Npy, and Agrp in the ARC (Briggs et al., 2013, Briggs et al., 2010, Brown and Clegg, 2010, Coppola et al., 2007, Palou et al., 2009, Roepke et al., 2008, Verhulst et al., 2012). However, gene
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While earlier reports on ferroptosis did not clarify mitocho
2021-09-18
While earlier reports on ferroptosis did not clarify mitochondrial damage and consequent death signaling in this paradigm of oxidative death, evidence from recent studies in neuronal systems strongly suggested a mechanistic link between enhanced lipid peroxide formation and loss of mitochondrial int
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Hyperactivation of Notch pathway can
2021-09-18
Hyperactivation of Notch1 pathway can give rise to transformation into T-ALL in murine models. In more than 50% of acute T-cell lymphoblastic leukemias oncogenic activating mutations of Notch1 have been detected and inactivation of Notch1 signaling impairs leukemia cell proliferation and promotes ap
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Here we showed that microinjection of siRNA at
2021-09-18
Here we showed that microinjection of siRNA at the MII stage efficiently reduced endogenous EZH2 mRNA and protein. Although the percentage of cleaving embryos was not affected, zingerone synthesis formation and blastocyst cell number were both reduced in EZH2 knockdown groups (Table 1). Similar res
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In the next set of experiments we sought to determine
2021-09-18
In the next set of experiments, we sought to determine the source of lysosomal Cap Firefly Luciferase mRNA inhibition by oxidative stress. Lysosomal exocytosis probably involves multiple steps including vesicle positioning, delivery, docking and fusion. The previous evidence and data in Fig. 1C,D s
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br Introduction Local anesthetics LAs are a set of common
2021-09-18
Introduction Local anesthetics (LAs) are a set of common medicines used for pain management in clinical settings. Up to now, LAs have been extensively used for peripheral nerve blocks, interventional spinal procedures, and epidural anesthesia [1]. In addition to their anesthetic and analgesic eff
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br An approach for the key challenges
2021-09-18
An approach for the key challenges facing forensic science One of the key challenges for forensic science is to avoid being side-tracked by one of the louder narratives in the media that the big problem forensic science faces is ‘junk science’ and ‘rogue scientists’. These are clearly important i
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HPgV coinfection has been associated with reduced liver
2021-09-18
HPgV coinfection has been associated with reduced liver disease in HPgV/HCV/HIV triply infected patients (Barbosa Ade et al., 2009, Berzsenyi et al., 2007, Berzsenyi et al., 2009, Berzsenyi et al., 2011). It is possible that HCV NS3 protease inhibitors could inhibit HPgV replication diminishing its
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Here we dissect X chromosome dosage compensation DC in C
2021-09-18
Here, we dissect X chromosome dosage compensation (DC) in C. elegans to determine the effect of chromatin modifications on higher-order chromosome structure during long-range gene regulation. DC is exemplary because it controls hundreds of genes simultaneously, it distinguishes X chromosomes from a
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To date several studies have suggested that serum HER could
2021-09-18
To date, several studies have suggested that serum HER2 could be used as a biomarker for monitoring the disease course and the patient's response to therapy [110], [111]. However, the clinical usefulness of serum HER2 has not been fully validated because of conflicting data [31]. The enzyme-linked i
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It is important to note
2021-09-18
It is important to note that the GC-C expression is retained in colon tumours, and therefore GC-C expression can be used as a marker to diagnose metastatic colon cancer [42]. However, expression of uroguanylin and guanylin is often lost in colorectal cancer progression [43]. Therefore, the anti-prol
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The expression of COX has been
2021-09-17
The expression of COX-2 has been correlated with the density of amyloid plaque [65]. A study reported that IMX was effective in suppressing the expression of iNOS and IL-6, but not COX-2, in LPS-stimulated BV2 microglial cells [52]. In this study, IMX did not alter upregulation of COX-2 induced by
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The Bcl and Bcl xL
2021-09-17
The Bcl-2 and Bcl-xL genes contain the CRE binding site in their promoter regions for CREB and CBP to bind to, so CREB phosphorylation was shown to up-regulate these anti-apoptotic genes, Bcl-2 and Bcl-xL [[29], [30], [31]]. Bcl-2 and Bcl-xL prevent the activation of caspases and the release of mito
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In summary through medicinal chemistry
2021-09-17
In summary, through medicinal chemistry design and computer-assisted conformational modeling, the initial lead was evolved into a series of dihydrobenzofuran derivatives, , as potent GPR119 agonists. Optimization of general structure at various regions of the molecule, including the substituent on
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