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Our exploration of Domain focused on
2021-11-23

Our exploration of Domain 1 focused on the role of the carbonyl linker in (). We found that replacement of this group by a methylene unit as in or direct attachment of the thiophene ring to the central aromatic core as in did not significantly impact potency. The thiophene ring in could be repla
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These differences have led to the recognition that the exten
2021-11-23

These differences have led to the recognition that the extent to which transport contributes to shaping postsynaptic signals likely reflects a balance between the density of transporters and the amount of l-glutamate in the synaptic cleft. Consequently, those synapses exhibiting the characteristics
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Introduction l Glutamate is a
2021-11-23

Introduction l-Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS) that contributes not only to fast synaptic neurotransmission, but also to complex physiological processes like memory, learning, plasticity, and neuronal cell death [30], [81]. Glutamate is
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The SLC A mutations identified in both families appear to
2021-11-23

The SLC45A1 mutations identified in both families appear to be hypomorphic given that they resulted in a reduction but not abolition of intracellular glucose transport by SLC45A1 in our in vitro assay. It is tempting to speculate that recessive mutations causing a more severe dysfunction of the tran
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br Hedgehog HH signaling plays an
2021-11-23

Hedgehog (HH) signaling plays an important role both during embryonic development and adult life. It is involved in the regulation of cell differentiation, cell proliferation and tissue polarity, as well as in the maintenance of stem cells, tissue repair, and regeneration (, ). Three ligands, Indi
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In addition to inactivation of Notch
2021-11-23

In addition to inactivation of Notch, we found that the combination of BTZ and GSI-I downregulated ERK phosphorylation in ALK+ ALCL cells, and we speculate this may occur through the inhibition of upstream regulators of the ERK pathway. These findings emphasize the functional complementation of the
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Another lever to efficiently eradicate tumors including ovar
2021-11-22

Another lever to efficiently eradicate tumors including ovarian cancer might rely on their high addiction to iron [34]. In fact, ultrasmall silica-based nanoparticles, functionalized with melanoma-targeting peptide, efficiently triggered ferroptosis not only in cell culture but also in tumor bearing
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br Discussion As expected RAS prevalence
2021-11-22

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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The relaxant response to carperitide was
2021-11-22

The relaxant response to carperitide was influenced neither by the removal of the endothelium nor by treatment with the nitric oxide synthase inhibitor or nitric oxide scavenger. This result was to be expected as previous studies showing that the vasodilator action of atrial natriuretic peptide is e
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Bioinformatic analysis revealed a putative coiled coil SLD w
2021-11-22

Bioinformatic analysis revealed a putative coiled-coil SLD within CT229 which we show to be essential for intracellular replication and recruitment of Rab GTPases to the inclusion. Mutation of a single amino 2801 residue in the SLD domain (CT229L120D) significantly reduced Rab binding and recruitme
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We found few differential effects on lung function for expos
2021-11-22

We found few differential effects on lung function for exposure to mother’s and father’s smoking in relation to GSTM1 and GSTT1. However, effects related to mother’s or father’s smoking may differ because mothers tend to spend greater amounts of time with young children and mothers may also smoke du
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Most of the GSNOR inhibitors presented
2021-11-22

Most of the GSNOR inhibitors presented here were synthesized according to . The synthesis started from either commercially available ketones or the ketones prepared as described in the . In , condensation of ketone and 2-furanaldehyde provided intermediate in good yield. Furan ring opening of inte
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br Amino acid usage in cancer br Perspective
2021-11-22

Amino vegf tyrosine kinase inhibitor usage in cancer Perspective High glucose consumption is a common feature of several types of tumor cells. Therefore, so far, in vivo positron emission tomography (PET) imaging with the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been used to detect
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br Membrane transporters as a novel
2021-11-22

Membrane transporters as a novel therapeutic target in pediatric TBI The concept of targeting membrane transporters began with identifying a neuroprotective drug and a corresponding transporter inhibitor. Somewhat serendipitously, we discovered that N-acetylcysteine (NAC), a cysteine donor for GS
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br Regulation of GCK by intrinsic conformational dynamics GC
2021-11-22

Regulation of GCK by intrinsic conformational dynamics GCK is a 465-residue, 52-kDa enzyme comprised of two domains, hereafter referred to as the large domain and the small domain, that are separated by a flexible hinge region. As with other proteins that adopt the hexokinase fold, substrates bin
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