The enantiomers of glucuronolactone are excellent chirons for the synthesis of the 10 stereoisomeric 2,5-dideoxy-2,5-iminohexitols by formation of the pyrrolidine ring by nitrogen substitution at C2 and C5, with either retention or inversion of configuration; the stereochemistry at C3 may be adjusted during the synthesis to give seven stereoisomers from each enantiomer. A definitive side-by-side comparison of the glycosidase inhibition of a panel of 13 glycosidases showed that 8 of the 10 stereoisomers showed significant inhibition of at least one glycosidase.
Perceptual organisation must select one interpretation from several alternatives to guide behaviour. Computational models suggest that this could be achieved through an interplay between inhibition and excitation across competing types of neural population coding for each interpretation. Here, to test for such models, we used magnetic resonance spectroscopy to measure non-invasively the concentrations of inhibitory γ-aminobutyric acid (GABA) and excitatory glutamate-glutamine (Glx) in several brain regions. Human participants first performed auditory and visual multistability tasks that produced spontaneous switching between percepts. Then, we observed that longer percept durations during behaviour were associated with higher GABA/Glx ratios in the sensory area coding for each modality. When participants were asked to voluntarily modulate their perception, a common factor across modalities emerged: the GABA/Glx ratio in the posterior parietal cortex tended to be positively correlated with the amount of effective volitional control. Our results provide direct evidence implicating that the balance between neural inhibition and excitation within sensory regions resolves perceptual competition. This powerful computational principle appears to be leveraged by both audition and vision, implemented independently across modalities, but modulated by an integrated control process.
A series of neoglycoconjugates derived from deoxynojirimycin has been prepared by click connection with functionalised adamantanes. They have been assayed as glycosidase inhibitors, as inhibitors of the glycoenzymes relevant to the treatment of Gaucher disease, as well as correctors of the defective ion-transport protein involved in cystic fibrosis. We have demonstrated that it is possible to selectively either strongly inhibit ER-α-glucosidases and ceramide glucosyltransferase or restore the activity of CFTR in CF-KM4 cells by varying the length of the alkyl chain linking DNJ and adamantane.
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