Ketamine exerts powerful anesthetic, psychotic and anti-depressant effects in both healthy volunteers and clinically-depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this NMDA receptor antagonist drug. Here, we provide behavioral and molecular evidence for the actions of ketamine using a new vertebrate model for psychiatric disorders: the zebrafish. Sub-anesthetic doses of ketamine produced a variety of abnormal behaviors in zebrafish that were qualitatively analogous to those previously measured in humans and rodents treated with drugs that produce transient psychosis. In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress. Finally, we also show that SIRT1, a histone deacetylase widely recognized for its link to cell survival is also affected by hypoxia crises. These results establish a relevant assay system in which the effects of psychotomimetic drugs can rapidly be assessed, and provide a plausible and novel neuronal mechanism through which ketamine affects critical sensory circuits that monitor breathing behavior.
A novel series of oxy-diester-functionalized gemini surfactants (Cm-E2O-Cm) were synthesized and a comprehensive analysis of their biophysicochemical properties was carried out.
Waxy
crude oil has become a crucial unconventional oil alternative
owing to the depleting conventional oil resources. However, ascertaining
flow assurance in a waxy crude oil pipeline at low temperatures is
challenging due to the high viscosity and gelation properties of waxy
crude oil and wax deposition on the pipeline wall. Researchers and
industries use different classes of chemical additives to resolve
the flow assurance issues. The current review aims to build a relationship
between the structural properties of chemical additives and their
flow improvement efficacy. A wide array of compounds reported in the
past decade has been critically examined to understand the progress
in the field. Polymers form a bulk of these compounds. However, there
is a shift toward polymer nanocomposites owing to their better effect
compared to pure polymers. Surfactants, organic solvents, and other
molecules have also been utilized as additives to ensure flow during
waxy crude oil transportation. The presence of different structural
properties such as alkyl chain length, aromatic rings, size of aromatic
rings, polar groups, and others have been related to their effect
on the flowability of waxy crude oil. Moreover, the factors related
to scaling of lab-scale results to industry level have been enumerated.
The future directions and perspectives related to utilizing structure–efficacy
relationships of chemical additives have been discussed. In contrast
to the existing literature, special importance has been given to the
chemical structures of additives and their molecular interactions
with waxy oils. The perspective of the structure–efficacy relationship
will help in designing novel additives with greater efficacy and suitability
for waxy crude oil.
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