Collapsin response mediator proteins (CRMPs) are important molecules in neurite outgrowth and axonal guidance. Within the CRMP family, CRMP-2 has been implicated in several neurological diseases (Alzheimer's, epilepsy, and ischemia). Here, we investigated the integrity of CRMPs (CRMP-1, -2, -4, -5) after in vitro neurotoxin treatment and in vivo traumatic brain injury (TBI). After maitotoxin (MTX) and NMDA treatment of primary cortical neurons, a dramatic decrease of intact CRMP-1, -2 and -4 proteins were observed, accompanied by the appearance of distinct 55-kDa and 58-kDa breakdown products (BDP) for CRMP-2 and -4, respectively. Inhibition of calpain activation prevented NMDA-induced CRMP-2 proteolysis and redistribution of CRMP-2 from the neurites to the cell body, while attenuating neurite damage and neuronal cell injury. Similarly, CRMP-1, -2, and -4 were also found degraded in rat cortex and hippocampus following controlled cortical impact (CCI), an in vivo model of TBI. The appearance of the 55-kDa CRMP-2 BDP was observed to increase, in a time-dependent manner, between 24 and 48 h in the ipsilateral cortex, and by 48 hours in the hippocampus. The observed 55-kDa CRMP-2 BDP following TBI was reproduced by in vitro incubation of naive brain lysate with activated calpain-2, but not activated caspase-3. Sequence analysis revealed several possible cleavage sites near the C-terminus of CRMP-2. Collectively, this study demonstrated that CRMP-1, -2, and -4 are degraded following both acute traumatic and neurotoxic injury. Furthermore, calpain-2 was identified as the possible proteolytic mediator of CRMP-2 following excitotoxic injury and TBI, which appears to correlate well with neuronal cell injury and neurite damage. It is possible that the calpain-mediated truncation of CRMPs following TBI may be an inhibiting factor for post-injury neurite regeneration.
Throughout history, various civilizations developed methodologies for the collection and disposal of human waste. The methodologies throughout the centuries have been characterized by technological peaks on the one hand, and by the disappearance of the technologies and their reappearance on the other. The purpose of this article is to trace the development of sewage collection and transport with an emphasis on toilets in ancient civilizations. Evolution of the major achievements in the scientific fields of sanitation with emphasis on the lavatory (or toilets) technologies through the centuries up to the present are presented. Valuable insights into ancient wastewater technologies and management with their apparent characteristics of durability, adaptability to the environment, and sustainability are provided. Gradual steps improved the engineering results until the establishment of the contemporary toilet system, which provides a combined solution for flushing, odor control, and the sanitation of sewerage. Even though the lack of proper toilet facilities for a great percentage of the present day global population is an embarrassing fact, the worldwide efforts through millennia for the acquisition of a well-engineered toilet were connected to the cultural level of each period.
Positron emission tomography (PET) scan with tracer [ 18 F]-fluorodeoxy-glucose ( 18 F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson’s disease (IPD). Previous studies using 18 F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18 F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individuals were included as normal controls. Following 18 F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hypermetabolism was observed in the cerebellum and vermis. There was a negative correlation ( p =0.007, r =-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y ( P =0.033, r =-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.
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