23 research outputs found
Benchmarking the Self-Assembly of Surfactin Biosurfactant at the LiquidâAir Interface to those of Synthetic Surfactants
The adsorption of surfactin, a lipopeptide biosurfactant, at the liquidâair interface has been investigated in this work. The maximum adsorption density and the nature and the extent of lateral interaction between the adsorbed surfactin molecules at the interface were estimated from surface tension data using the Frumkin model. The quantitative information obtained using the Frumkin model was also compared to those obtained using the Gibbs equation and the LangmuirâSzyszkowski model. Error analysis showed a better agreement between the experimental and the calculated values using the Frumkin model relative to the other two models. The adsorption of surfactin at the liquidâair interface was also compared to those of synthetic anionic, sodium dodecylbenzenesulphonate (SDBS), and nonionic, octaethylene glycol monotetradecyl ether (C14E8), surfactants. It has been estimated that the area occupied by a surfactin molecule at the interface is about 3- and 2.5-fold higher than those occupied by SDBS and C14E8 molecules, respectively. The interaction between the adsorbed molecules of the anionic biosurfactant (surfactin) was estimated to be attractive, unlike the mild repulsive interaction between the adsorbed SDBS molecules
Forebrain Deletion of the Vesicular Acetylcholine Transporter Results in Deficits in Executive Function, Metabolic, and RNA Splicing Abnormalities in the Prefrontal Cortex
One of the key brain regions in cognitive processing and executive function is the prefrontal cortex (PFC), which receives cholinergic input from basal forebrain cholinergic neurons. We evaluated the contribution of synaptically released acetylcholine (ACh) to executive function by genetically targeting the vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive function was assessed using a pairwise visual discrimination paradigm and the 5-choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient mice were able to learn, but were impaired in reversal learning, suggesting that these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice took longer to reach criteria in the 5-CSRT. Although their performance was indistinguishable from that of control mice during low attentional demand, increased attentional demand revealed striking deficits in VAChT-deleted mice. Galantamine, a cholinesterase inhibitor used in Alzheimer\u27s disease, significantly improved the performance of control mice, but not of VAChT-deficient mice on the 5-CSRT. In vivo magnetic resonance spectroscopy showed altered levels of two neurochemical markers of neuronal function, taurine and lactate, suggesting altered PFC metabolism in VAChT-deficient mice. The PFC of these mice displayed a drastic reduction in the splicing factor heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), whose cholinergic-mediated reduction was previously demonstrated in Alzheimer\u27s disease. Consequently, several key hnRNPA2/B1 target transcripts involved in neuronal function present changes in alternative splicing in VAChT-deficient mice, including pyruvate kinase M, a key enzyme involved in lactate metabolism. We propose that VAChT-targeted mice can be used to model and to dissect the neurochemical basis of executive abnormalities
Benchmarking the Self-Assembly of Surfactin Biosurfactant at the LiquidâAir Interface to those of Synthetic Surfactants
Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation
The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF (TNF alpha) levels in murine endotoxemia. This effect was recapitulated by peripheral administration of the compound. BQCA also improved survival in murine endotoxemia and these effects were abolished in M1 mAChR knockout (KO) mice. Selective optogenetic stimulation of basal forebrain cholinergic neurons innervating brain regions with abundant M1 mAChR localization reduced serum TNF in endotoxemic mice. These findings reveal that forebrain cholinergic neurons regulate innate immune responses and inflammation, suggesting the possibility that in diseases associated with cholinergic dysfunction, including Alzheimer\u27s disease this anti-inflammatory regulation can be impaired. These results also suggest novel anti-inflammatory approaches based on targeting forebrain cholinergic signaling in sepsis and other disorders characterized by immune dysregulation
Cholinergic Surveillance over Hippocampal RNA Metabolism and Alzheimer's-Like Pathology
The relationship between long-term cholinergic dysfunction and risk of developing dementia is poorly understood. Here we used mice with deletion of the vesicular acetylcholine transporter (VAChT) in the forebrain to model cholinergic abnormalities observed in dementia. Whole-genome RNA sequencing of hippocampal samples revealed that cholinergic failure causes changes in RNA metabolism. Remarkably, key transcripts related to Alzheimer's disease are affected. BACE1, for instance, shows abnormal splicing caused by decreased expression of the splicing regulator hnRNPA2/B1. Resulting BACE1 overexpression leads to increased APP processing and accumulation of soluble AÎČ1-42. This is accompanied by age-related increases in GSK3 activation, tau hyperphosphorylation, caspase-3 activation, decreased synaptic markers, increased neuronal death, and deteriorating cognition. Pharmacological inhibition of GSK3 hyperactivation reversed deficits in synaptic markers and tau hyperphosphorylation induced by cholinergic dysfunction, indicating a key role for GSK3 in some of these pathological changes. Interestingly, in human brains there was a high correlation between decreased levels of VAChT and hnRNPA2/B1 levels with increased tau hyperphosphorylation. These results suggest that changes in RNA processing caused by cholinergic loss can facilitate Alzheimer's-like pathology in mice, providing a mechanism by which decreased cholinergic tone may increase risk of dementia
Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation
The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF (TNFα) levels in murine endotoxemia. This effect was recapitulated by peripheral administration of the compound. BQCA also improved survival in murine endotoxemia and these effects were abolished in M1 mAChR knockout (KO) mice. Selective optogenetic stimulation of basal forebrain cholinergic neurons innervating brain regions with abundant M1 mAChR localization reduced serum TNF in endotoxemic mice. These findings reveal that forebrain cholinergic neurons regulate innate immune responses and inflammation, suggesting the possibility that in diseases associated with cholinergic dysfunction, including Alzheimer's disease this anti-inflammatory regulation can be impaired. These results also suggest novel anti-inflammatory approaches based on targeting forebrain cholinergic signaling in sepsis and other disorders characterized by immune dysregulation
Remodeling of cholinergic input to the hippocampus after noise exposure and tinnitus induction in Guinea pigs
Here, we investigate remodeling of hippocampal cholinergic inputs after noise exposure and determine the relevance of these changes to tinnitus. To assess the effects of noise exposure on the hippocampus, guinea pigs were exposed to unilateral noise for 2 hr and 2 weeks later, immunohistochemistry was performed on hippocampal sections to examine vesicular acetylcholine transporter (VAChT) expression. To evaluate whether the changes in VAChT were relevant to tinnitus, another group of animals was exposed to the same noise band twice to induce tinnitus, which was assessed using gapâprepulse Inhibition of the acoustic startle (GPIAS) 12âweeks after the first noise exposure, followed by immunohistochemistry. Acoustic Brainstem Response (ABR) thresholds were elevated immediately after noise exposure for all experimental animals but returned to baseline levels several days after noise exposure. ABR wave I amplitudeâintensity functions did not show any changes after 2 or 12âweeks of recovery compared to baseline levels. In animals assessed 2âweeks following noiseâexposure, hippocampal VAChT puncta density decreased on both sides of the brain by 20â60% in exposed animals. By 12âweeks following the initial noise exposure, changes in VAChT puncta density largely recovered to baseline levels in exposed animals that did not develop tinnitus, but remained diminished in animals that developed tinnitus. These tinnitusâspecific changes were particularly prominent in hippocampal synapseârich layers of the dentate gyrus and areas CA3 and CA1, and VAChT density in these regions negatively correlated with tinnitus severity. The robust changes in VAChT labeling in the hippocampus 2 weeks after noise exposure suggest involvement of this circuitry in auditory processing. After chronic tinnitus induction, tinnitusâspecific changes occurred in synapseârich layers of the hippocampus, suggesting that synaptic processing in the hippocampus may play an important role in the pathophysiology of tinnitus.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150542/1/hipo23058.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150542/2/hipo23058_am.pd
Self-assembly of a surfactin nanolayer at solid-liquid and air-liquid interfaces
Surfactin, a sustainable and environmentally friendly surface active agent, is used as a model to study the adsorption of biosurfactants at hydrophobic and hydrophilic solidâliquid interfaces as well as the airâliquid interface. Surfactin adsorption was monitored as a function of time and concentration using surface plasmon resonance (SPR) technique in the case of the solidâliquid interfaces or the drop shape analysis (DSA) technique in the case of the airâliquid interface. The results obtained in this study showed that surfactin adsorption at the âhardâ hydrophobic (functionalized with octadecanethiol) solidâliquid and the âsoftâ airâliquid interface were 1.12 ± 0.01 mg mâ2 (area per molecule of 157 ± 2 Ă
2) and 1.11 ± 0.05 mg mâ2 (area per molecule of 159 ± 7 Ă
2), respectively, demonstrating the negligible effect of the interface âhardnessâ on surfactin adsorption. The adsorption of surfactin at the hydrophilic (functionalized with ÎČ-mercaptoethanol) solidâliquid interface was about threefold lower than its adsorption at the hydrophobicâliquid interfaces, revealing the importance of hydrophobic interaction in surfactin adsorption process. The affinity constant of surfactin for the investigated interfaces follows the following order: air > octadecanethiol > ÎČ-mercaptoethanol. Biosurfactants, such as surfactin, are expected to replace the conventional fossil-based surfactants in several applications, and therefore the current study is a contribution towards the fundamental understanding of biosurfactant behavior, on a molecular level, at hydrophobic and hydrophilic solidâliquid interfaces in addition to the airâliquid interface. Such understanding might aid further optimization of the utilization of surfactin in a number of industrial applications such as enhanced oil recovery, bioremediation, and detergency.Scopu
Demulsification of stable emulsions from produced water using a phase separator with inclined parallel arc coalescing plates
A novel and highly efficient oil-water separator equipped with a series of inclined multiple arc coalescence plates is developed and optimized for the removal of stable oil emulsions from produced water. The synthetic high salinity produced water with stable emulsions was prepared by mixing Catenex oil and the emulsifying surfactant (Armac T) with brine water. A series of experiments were performed to evaluate the effects of the arc coalescence plate geometry, produced water volumetric flow rate, influent oil concentration, and treatment temperature on the oil removal efficiency using the developed separator. Optimal coalescence plate arc geometry for maximum oil removal at different operating conditions was determined. Using the optimal coalescence plate arc geometry. , strong correlations between oil removal efficiency from produced water, volumetric flow rate, and treatment temperature were established. The results demonstrated that the developed oil-water separator is highly effective in the treatment of stable emulsions in produced waters due to the combined effects of chemical demulsification and oil droplet coalescence.Scopu