Post traumatic stress disorder (PTSD) is a chronic anxiety disorder initiated by an intensely threatening, traumatic event. There is a great need for more efficacious pharmacotherapy and preventive treatments for PTSD. In animals, corticotropin-releasing factor (CRF) and the CRF1 receptor play a critical role in behavioural and neuroendocrine responses to stress. We tested the hypothesis that CRF1 activation is required for initiation and consolidation of long-term effects of trauma on anxiety-like behaviour in the predator exposure (predator stress) model of PTSD. Male C57BL6 mice were treated with the selective CRF1 antagonist CRA0450 (2, 20 mg/kg) 30 min before or just after predator stress. Long-term effects of stress on rodent anxiety were measured 7 d later using acoustic startle, elevated plus maze (EPM), light/dark box, and hole-board tests. Predator stress increased startle amplitude and delayed startle habituation, increased time in and decreased exits from the dark chamber in the light/dark box test, and decreased risk assessment in the EPM. CRF1 antagonism had limited effects on these behaviours in non-stressed controls, with the high dose decreasing risk assessment in the EPM. However, in stressed animals CRF1 antagonism blocked initiation and consolidation of stressor effects on startle, and returned risk assessment to baseline levels in predator-stressed mice. These findings implicate CRF1 activation in initiation and post-trauma consolidation of predator stress effects on anxiety-like behaviour, specifically on increased arousal as measured by exaggerated startle behaviours. These data support further research of CRF1 antagonists as potential prophylactic treatments for PTSD.
The effects of pretreatment by dilute acid and sulfite pretreatment to overcome recalcitrance of lignocellulose (SPORL) on substrate morphology, cell wall physical and chemical structures, along with the subsequent enzymatic hydrolysis of lodgepole pine substrate were investigated. FE-SEM and TEM images of substrate structural morphological changes showed that SPORL pretreatment resulted in fiber separation, where SPORL high pH (4.2) pretreatment exhibited better fiber separation than SPORL low pH (1.9) pretreatment. Dilute acid pretreatment produced very poor fiber separation, consisting mostly of fiber bundles. The removal of almost all hemicelluloses in the dilute acid pretreated substrate did not overcome recalcitrance to achieve a high cellulose conversion when lignin removal was limited. SPORL high pH pretreatment removed more lignin but less hemicellulose, while SPORL low pH pretreatment removed about the same amount of lignin and hemicelluloses in lodgepole pine substrates when compared with dilute acid pretreatment. Substrates pretreated with either SPORL process had a much higher cellulose conversion than those produced with dilute acid pretreatment. Lignin removal in addition to removal of hemicellulose in SPORL pretreatment plays an important role in improving the cellulose hydrolysis of the substrate.
When pretreating woody biomass for the production of cellulosic ethanol, a mechanical downsizing step is commonly included to ensure an appropriate particle size for enzyme hydrolysis. Different methods of mechanical downsizing will result in wood particles with markedly different physical structures. Dry grinding methods, such as knife-milling, will produce a powder-like substrate, which consists of cut or truncated fiber bundles. The substrate will also have a reduced pore volume because of the required drying. Using a disc-refiner, wet wood chips are separated into single wood fibers and loosened fiber bundles, increasing available surface area and avoiding pore collapse because of drying. The following study compared knifemilled and disc-refined substrates produced from native and dilute-acid-pretreated wood chips to determine the impact of the mechanical-downsizing method on the enzyme digestibility and physical characteristics of a hardwood substrate. For dilute-acidpretreated aspen, disc-refining produced a substrate that was 58−80% digestible, while knife-milling produced a substrate that was 24−36% digestible. The difference in substrate digestibility was partially attributed to hornification during the drying step and also attributed to differences in physical structure because of the downsizing method. Analysis via microscopy indicated that disc-refined substrates had a greater length, smaller width, and greater fibrillation then the knife-milled substrates. The discrefined substrates also had a more exposed cellulose surface and a greater volume of accessible pores.
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