A Novel Prodrug Approach for Central Nervous System-Selective Estrogen Therapy (open access)

A Novel Prodrug Approach for Central Nervous System-Selective Estrogen Therapy

This article gives an overview of the discovery of small-molecule bioprecursor prodrugs carrying the para-quinol scaffold on the steroidal A-ring that are preferentially metabolized in the CNS to the corresponding estrogens. Selected examples are shown to illustrate that, independently of the route of administrations and duration of treatments, these agents produce high concentration of estrogens only in the CNS without peripheral hormonal liability. 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) has been the best-studied representative of this novel type of prodrugs for brain and retina health. Specific applications in preclinical animal models of centrally-regulated and estrogen-responsive human diseases, including neurodegeneration, menopausal symptoms, cognitive decline and depression, are discussed to demonstrate the translational potential of their prodrug approach for CNS-selective and gender-independent estrogen therapy with inherent therapeutic safety.
Date: November 19, 2019
Creator: Prokai-Tatrai, Katalin & Prókai, László, 1958-
System: The UNT Digital Library
Computational Study of 3d Metals and Their Influence on the Acidity of Methane C–H Bonds (open access)

Computational Study of 3d Metals and Their Influence on the Acidity of Methane C–H Bonds

Article describes experiment where CCSD(T) methods in conjunction with correlation consistent basis sets were used to predict the pKa for the deprotonation of methane in a 3d metal ion adduct, [M···CH4]+ (M = Sc–Cu), in dimethyl sulfoxide solvent, which is modeled by the SMD continuum solvent model.
Date: November 19, 2019
Creator: Zhou, Christopher X. & Cundari, Thomas R., 1964-
System: The UNT Digital Library
We Need Better Understanding About Functional Diversity and Vulnerability of Tropical Freshwater Fishes (open access)

We Need Better Understanding About Functional Diversity and Vulnerability of Tropical Freshwater Fishes

This commentary extends a discussion initiated by Toussaint et al. (Sci Rep 6:22125, 2016) concerning the relationship between global patterns of freshwater fish functional diversity (FD) and its vulnerability to human impacts.
Date: November 19, 2016
Creator: Vitule, Jean R. S.; Agostinho, Angela A.; Azevedo-Santos, Valter M.; Daga, Vanessa S.; Darwall, William R. T.; Fitzgerald, Daniel B. et al.
System: The UNT Digital Library
RNaseH-mediated simultaneous piggyback knockdown of multiple genes in adult zebrafish (open access)

RNaseH-mediated simultaneous piggyback knockdown of multiple genes in adult zebrafish

This article tests if it is possible to piggyback more than one antisense deoxyoligonucleotide (dO) with one vivo morpholino (VMO). The authors previously developed a piggyback knockdown method that was used to knockdown genes in adult zebrafish. In this article, the authors develop a method to knockdown three genes at one time, and by increasing the concentration of VMO by twofold, could knockdown six genes simultaneously. These multiple gene knockdowns will not only increase the efficiency of the method in whole genome-wide knockdowns but will also be useful to study multifactorial disorders.
Date: November 19, 2020
Creator: Raman, Revathi; Ryon, Mia & Jagadeeswaran, Pudur
System: The UNT Digital Library