Integrated Approaches to Drug Discovery for Oxidative Stress-Related Retinal Diseases

Excessive oxidative stress induces dysregulation of functional networks in the retina, resulting in retinal diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy. Although various therapies have been developed to reduce oxidative stress in retinal diseases, most have failed to show efficacy in clinical trials. This may be due to oversimplification of target selection for such a complex network as oxidative stress. Recent advances in high-throughput technologies have facilitated the collection of multilevel omics data, which has driven growth in public databases and in the development of bioinformatics tools. Integration of the knowledge gained from omics databases can be used to generate disease-related biological networks and to identify potential therapeutic targets within the networks. Here, we provide an overview of integrative approaches in the drug discovery process and provide simple examples of how the approaches can be exploited to identify oxidative stress-related targets for retinal diseases

Prevention of Hippocampus Neuronal Damage in lschemic Gerbils by a Novel Lipid Peroxidation Inhibitor (Quinazoline Derivative)

ABSTRACT ABBREVIATIONS: MAP2, microtuble-associated protein 2; PKC, protein kinase C; PDBu, phorbol 12,13-dibutyrate. 90

Raman stimulated neutrino pair emission

A new scheme using macroscopic coherence is proposed to experimentally determine the neutrino mass matrix, in particular the absolute value of neutrino masses, and the mass type, Majorana or Dirac. The proposed process is a collective, coherent Raman scattering followed by neutrino-pair emission from | e of a long lifetime to | g ;.0 + | e .. + i j.i. j + | g with.i. j consisting of six massive neutrino-pairs. Calculated angular distribution has six (i j) thresholds which showup as steps at different angles. Angular locations of thresholds and event rates of the angular distribution make it possible to experimentally determine the smallest neutrino mass to the level of less than several meV, (accordingly all threemasses using neutrino oscillation data), the mass ordering pattern, normal or inverted, and to distinguish whether neutrinos are ofMajorana or Dirac type. Event rates of neutrino-pair emission, when the mechanism of macroscopic coherence amplification works, may become large enough for realistic experiments by carefully selecting certain types of target. The problem to be overcome is macro-coherently amplified quantum electrodynamic background of the process,.0 + | e .. +.2 +.3 + | g , when two extra photons,.2,.3, escape detection. We illustrate our idea using neutral Xe and trivalent Ho ion doped in dielectric crystals

Vaccinium myrtillus (Bilberry) Extracts Reduce Angiogenesis In Vitro and In Vivo

Vaccinium myrtillus (Bilberry) extracts (VME) were tested for effects on angiogenesis in vitro and in vivo. VME (0.3–30 µg ml−1) and GM6001 (0.1–100 µM; a matrix metalloproteinase inhibitor) concentration-dependently inhibited both tube formation and migration of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor-A (VEGF-A). In addition, VME inhibited VEGF-A-induced proliferation of HUVECs. VME inhibited VEGF-A-induced phosphorylations of extracellular signal-regulated kinase 1/2 (ERK 1/2) and serine/threonine protein kinase family protein kinase B (Akt), but not that of phospholipase Cγ (PLCγ). In an in vivo assay, intravitreal administration of VME inhibited the formation of neovascular tufts during oxygen-induced retinopathy in mice. Thus, VME inhibited angiogenesis both in vitro and in vivo, presumably by inhibiting the phosphorylations of ERK 1/2 and Akt. These findings indicate that VME may be effective against retinal diseases involving angiogenesis, providing it can reach the retina after its administration. Further investigations will be needed to clarify the major angiogenesis-modulating constituent(s) of VME

Quantum Degenerate Mixtures of Alkali and Alkaline-earth-like Atoms

We realize simultaneous quantum degeneracy in mixtures consisting of the alkali and alkalineearth-like atoms Li and Yb. This is accomplished within an optical trap by sympathetic cooling of the fermionic isotope $^6$Li with evaporatively cooled bosonic $^{174}$Yb and, separately, fermionic $^{173}$Yb.Using cross-thermalization studies, we also measure the elastic s-wave scattering lengths of both Li-Yb combinations, $|a_{6_{Li}-174_{Yb}}|$ = 1.0$\pm$0.2 nm and $|a_{6_{Li}-173_{Yb}}|$ = 0.9$\pm$0.2 nm. The equality of these lengths is found to be consistent with mass-scaling analysis. The quantum degenerate mixtures of Li and Yb, as realized here, can be the basis for creation of ultracold molecules with electron spin degrees of freedom, studies of novel Efimov trimers, and impurity probes of superfluid systems.Physic