Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance.

Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase is required to terminate Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short-lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body α/β neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

Ethanol-water separation by pervaporation

The separation of ethanol-water mixtures is of great importance for the production of ethanol from biomass. Both ultrafiltration and pervaporation processes can be used for the continuous processing of fermentation and separation, The removal of ethanol from the ultrafiltration permeate can be accomplished by pervaporation. Separation of ethanol-water mixtures by the pervaporation process has been investigated. Results are presented for membranes which are preferentially permeable for ethanol and for others which are preferentially water permeable. Details on the preparation of several membrane types (homogeneous, asymmetric and composite) are given. A schematic process diagram is given in which the fermentation of sugars to ethanol is membrane-controlled

PRODUCTION OF ETHANOL BY FED-BATCH FERMENTATION

The production of ethanol, from glucose in batch and fed batch culture, was investigated. In the fed batch culture, the glucose feeding was added into the culture at 16th hour of fermentation. The effects of different glucose concentration feeding rates on ethanol fermentation were investigated for fed batch culture. The 2gL-1hr-1 glucose concentration feeding rate was found to give higher ethanol yield (2.47 g ethanol g glucose-1), with respect to substrate consumed as compared to 8 gL-1hr-1 (0.23 g ethanol g glucose-1) and 4 gL-1hr-1 (0.20 g ethanol g glucose-1). The ethanol yield with respect to substrate consumed obtained in batch culture was 0.81 g ethanol g glucose-1. The fed batch culture at 2 gL-1hr-1 glucose concentration feeding rate was proven to be a better fermentation system than the batch culture. The specific growth rate, specific glucose consumption rate and specific ethanol production rate for the fed batch fermentation, at 2 gL-1hr-1 glucose concentration feeding rate, were 0.065 hr-1, 1.20 hr-1 and 0.0009 hr-1, respectively

Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor GluN2A (NR2A) Subunit

Background and purpose:  Alcohol produces its behavioural effects in part due to inhibition of N-methyl-d-aspartate (NMDA) receptors in the CNS. Previous studies have identified amino acid residues in membrane-associated domains 3 (M3) and 4 (M4) of the NMDA receptor that influence ethanol sensitivity. In addition, in other alcohol-sensitive ion channels, sedative-hypnotic agents have in some cases been shown to act at sites distinct from the sites of ethanol action. In this study, we compared the influence of mutations at these sites on sensitivity to ethanol and trichloroethanol, a sedative-hypnotic agent that is a structural analogue of ethanol. Experimental approach:  We constructed panels of mutants at ethanol-sensitive positions in the GluN2A (NR2A) NMDA receptor subunit and transiently expressed these mutants in human embryonic kidney 293 cells. We used whole-cell patch-clamp recording to assess the actions of ethanol and trichloroethanol in these mutant NMDA receptors. Key results:  Ethanol sensitivity of mutants at GluN2A(Ala825) was not correlated with any physicochemical measures tested. Trichloroethanol sensitivity was altered in two of three ethanol-insensitive mutant GluN2A subunits: GluN2A(Phe637Trp) in M3 and GluN2A(Ala825Trp) in M4, but not GluN2A(Met823Trp). Trichloroethanol sensitivity decreased with increasing molecular volume at Phe637 or increasing hydrophobicity at Ala825 and was correlated with ethanol sensitivity at both sites. Conclusions and implications:  Evidence obtained to date is consistent with a role of GluN2A(Ala825) as a modulatory site for ethanol and trichloroethanol sensitivity, but not as a binding site. Trichloroethanol appears to inhibit the NMDA receptor in a manner similar, but not identical to, that of ethanol

Business Sphere, Vol. 19, no.1

Ethanol, the clean-burning, high octane fuel distilled from Iowa’s corn fields, has the potential to free the U.S. from its foreign oil dependence. Transforming corn into ethanol, however, takes energy, usually in the form of natural gas or coal. Ames-based Frontline BioEnergy is developing biomass-to-energy conversion methods that reduce an ethanol plant’s consumption of fossil fuels, making ethanol an even greener product. As Iowa’s ethanol industry continues to grow, developing energy from biomass could result in huge savings for the state’s production facilities

Ethanol internal reforming in solid oxide fuel cells: A path toward high performance metal-supported cells for vehicular applications

Internal reforming of ethanol fuel was investigated on high-performance metal-supported solid oxide fuel cells (MS-SOFCs) with infiltrated catalysts. The hydrogen concentration and internal reforming effects were evaluated systematically with different fuels including: hydrogen, simulated reformate, anhydrous ethanol, ethanol water blend, and hydrogen-nitrogen mixtures. A simple infiltration of Ni reforming catalyst into 40 vol% Ni-Sm0.20Ce0.80O2-δ (Ni-SDCN40) and fuel-side metal support leads to complete internal reforming, as confirmed by comparison to simulated reformate. The performance difference between hydrogen and fully-reformed ethanol is attributed entirely to decrease in hydrogen concentration. High peak power density was achieved for a range of conditions, for example 1.0 W cm−2 at 650 °C in ethanol-water blend, and 1.4 W cm−2 at 700 °C in anhydrous ethanol fuel. Initial durability tests with ethanol-water blend show promising stability for 100 h at 700 °C and 0.7 V. Carbon is not deposited in the Ni-SDCN40 anode during operation

The adsorption and desorption of ethanol ices from a model grain surface

Reflection absorption infrared spectroscopy (RAIRS) and temperature programed desorption (TPD) have been used to probe the adsorption and desorption of ethanol on highly ordered pyrolytic graphite (HOPG) at 98 K. RAIR spectra for ethanol show that it forms physisorbed multilayers on the surface at 98 K. Annealing multilayer ethanol ices (exposures > 50 L) beyond 120 K gives rise to a change in morphology before crystallization within the ice occurs. TPD shows that ethanol adsorbs and desorbs molecularly on the HOPG surface and shows four different species in desorption. At low coverage, desorption of monolayer ethanol is observed and is described by first-order kinetics. With increasing coverage, a second TPD peak is observed at a lower temperature, which is assigned to an ethanol bilayer. When the coverage is further increased, a second multilayer, less strongly bound to the underlying ethanol ice film, is observed. This peak dominates the TPD spectra with increasing coverage and is characterized by fractional-order kinetics and a desorption energy of 56.3 +/- 1.7 kJ mol(-1). At exposures exceeding 50 L, formation of crystalline ethanol is also observed as a high temperature shoulder on the TPD spectrum at 160 K. (c) 2008 American Institute of Physics

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol