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br Discussion As expected RAS prevalence for treatment exper
2022-01-24

Discussion As expected, RAS prevalence for treatment-experienced patients who failed therapy with first-wave, first-generation drugs telaprevir/boceprevir was higher compared to non-experienced patients likely due to drug-selective pressure. For non-responders to previous therapy, resistance subs
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NPxY was recognized as the first short signal sequence
2022-01-24

NPxY was recognized as the first short signal sequence motif in the cytoplasmic domain of membrane receptors and proteins with critical roles in internalization and trafficking of receptor molecules [130]. Including LDL receptor, beta-1 integrin, megalin, beta-amyloid precursor protein, EGF receptor
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As comparators compounds and were
2022-01-24

As comparators, compounds and were made using the pyrazolopyridine core with the CF triazole attached. The 2-fluorophenyl group was replaced with the methylpyrimidine in compound . The potency of these compounds were very good and compound looks attractive from a physicochemical perspective as it
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br Acknowledgements br Introduction The glutathione S transf
2022-01-24

Acknowledgements Introduction The glutathione S-transferase (GST, EC 2.5.1.18) family of multifunctional enzymes plays a particularly important role in cellular detoxification [1]. Over-expression of the GSTP1 isoform characterizes many human tumor cell lines derived from stomach, brain and co
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Immunology Inflammation Compound Library synthesis We hypoth
2022-01-24

We hypothesized that modulating redox stress by altering endogenous antioxidant content (overexpression of catalase) and/or via dietary intervention will improve energy metabolism, adipose tissue function, and overall glucose and lipid homeostasis. To better understand the interplay between redox re
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Following activation it is necessary for a subset
2022-01-24

Following activation, it is necessary for a subset of activated effector T cells to survive as long-lived memory T cells. Metabolically, this transition is dependent upon the ability of the cell to downregulate aerobic glycolysis and transition back to a more oxidative phenotype. In fact, enhancemen
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As preclinical toxicity and efficacy both appear to
2022-01-24

As preclinical toxicity and efficacy both appear to be associated with GlyT1 inhibition, it remains to be determined whether on-target toxicity can be separated from efficacy. The present study evaluated a series of GlyT1 inhibitors for target potency, mode of inhibition, residence time, activity in
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Mapping and separation of the anti
2022-01-24

Mapping and separation of the anti-GlyT1C epitopes allowed us to verify the existence of calpain cleavage sites in isolated mouse synaptosomes. In order to allow calcium to enter the intrasynaptosomal compartment and activate endogenous calpain, we incubated synaptosomes in hypoosmotic high (200μM)
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The life cycle of T cruzi requires both vertebrate
2022-01-21

The life cycle of T. cruzi requires both vertebrate and invertebrate hosts. In the insect (invertebrate) vector, the protozoan undergoes extracellular replication, whereas in the mammalian (vertebrate) host it replicates by obligate intracellular multiplication (Rodrigues et al., 2014). Hence, the p
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br Discussion Our results indicate that marked
2022-01-21

Discussion Our results indicate that marked changes in the relative distribution of AMPA receptors in microsomal and synaptic fractions occur during the postnatal period, and that these changes are correlated with changes in different populations of AMPA binding sites. At early postnatal ages (PN
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br Discussion In the present
2022-01-21

Discussion In the present study, we have demonstrated the effect of a high-fat diet upon wild-type and glut3 pregestational female phenotype and shown that it leads to obesity due to an increase in white adipose tissue contributing to the overall fat mass. Despite this observed obesity along with
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br The GLI code The GLI code model considers
2022-01-21

The GLI code The GLI code model [21], [22] considers the total GLI function as a balance of positive activator (GLIA) and negative repressive (GLIR) activities with GLI1 being mostly a positive transcription factor and GLI3 mostly a transcriptional repressor. The GLIA:GLIR ratio is thus critical,
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br Acknowledgements This work was supported by a fellowship
2022-01-21

Acknowledgements This work was supported by a fellowship to C.H. under the ‘100 Foreign Expert’ scheme of the Shanxi province government(R100456). Conflict of interest: Dr. Holscher is a named inventor on a patent submitted by Lancaster University on the use of dual GLP-1/GIP analogues in neurod
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br Introduction Calorie restriction CR in the absence
2022-01-21

Introduction Calorie restriction (CR), in the absence of malnutrition, has beneficial effects on conotoxin function, including reducing the incidence of age-related neurodegenerative disease (Gräff et al., 2013), eliciting anti-depressant behavior (Lutter et al., 2008) and improving memory functi
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Retinal GAL receptor distribution suggests an intrinsic neur
2022-01-21

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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