Schaub, J. | Search bioRxiv

bioRxiv2021

Description and analysis of glycosidic residues in the largest open natural products database

Natural products (NP), biomolecules produced by living organisms, inspire the pharmaceutical industry and research due to their structural characteristics and the substituents from which they derive their activities. Glycosidic residues are frequently present in NP structures and have particular pharmacokinetic and pharmacodynamic importance as they improve their solubility and are often involved in molecular transport, target specificity, ligand-target interactions and receptor binding. The COlleCtion of Open Natural prodUcTs (COCONUT) is currently the largest open database of NP and therefore a suitable starting point for the detection and analysis of the diversity of glycosidic residues in NP. In this work, we report and describe the presence of circular, linear, terminal and non-terminal glycosidic units in NP, together with their importance in drug discovery.

bioinformatics↗

bioRxiv2020

The Role of Aquaporin-4 in Optic Nerve Head Astrocytes in Experimental Glaucoma

PurposeTo study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). MethodsC57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression & transport block was also analyzed. ResultsB6 mice presented abundant AQP4 in Muller cells, astrocytes of retina and myelinated ON (MON), but minimal expression in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p[≤]0.05). Bead-injection led to comparable 3D-IOP elevation (p=0.42) and axonal transport blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). ConclusionLack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.

molecular biology↗