These mutations promote the misfolding of the proteins into a prion-like conformation. The misfolded form of TDP-43 forms cytoplasmic inclusions in affected neurons, and is found depleted in the nucleus. In addition to ALS/MND and FTLD-U, TDP-43 pathology is a feature of many cases of Alzheimers disease, Parkinsons disease and Huntingtons disease. The misfolding of TDP-43 is largely directed by its prion-like domain. This domain is inherently prone to misfolding, while pathological mutations in TDP-43 have been found to increase this propensity to misfold, explaining the presence of these mutations in familial cases of ALS/MND. As in yeast, the prion-like domain of TDP-43 has been shown to be both necessary and sufficient for protein misfolding and aggregation.Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration. The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation. Weaponization
Prions could theoretically be employed as a weaponized agent. With potential fatality rates of 100%, prions could be an effective bio-weapon. An unfavorable aspect is prions very long incubation periods. Persistent heavy exposure of prions to the intestine might shorten the overall onset. Another aspect of using prions in warfare is the difficulty of detection and decontamination. History
In the 18th and 19th centuries, exportation of sheep from Spain was observed to coincide with a disease called scrapie.
Parasomnias  are a category of sleep disorders that involve abnormal movements, behaviors, emotions, perceptions, and dreams that occur while falling asleep, sleeping, between sleep stages, or during arousal from sleep. Parasomnias are dissociated sleep states which are partial arousals during the transitions between wakefulness, NREM sleep, and REM sleep, and their combinations. Classification
The newest version of the International Classification of Sleep Disorders (ICSD, 3rd. Ed.) uses State Dissociation as the paradigm for parasomnias. Unlike before, where wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were considered exclusive states, research has shown that combinations of these states are possible and thus, may result in unusual unstable states that could eventually manifest as parasomnias or as altered levels of awareness.Although the previous definition is technically correct, it contains flaws. The consideration of the State Dissociation paradigm facilitates the understanding of the sleep disorder and provides a classification of 10 core categories. Non-rapid eye movement (NREM)-related parasomnias
NREM parasomnias are arousal disorders that occur during stage 3 (or 4 by the R&K standardization) of NREM sleep—also known as slow wave sleep (SWS). They are caused by a physiological activation in which the patients brain exits from SWS and is caught in between a sleeping and waking state. In particular, these disorders involve activation of the autonomic nervous system, motor system, or cognitive processes during sleep or sleep-wake transitions.Some NREM parasomnias (sleep-walking, night-terrors, and confusional arousal) are common during childhood but decrease in frequency with increasing age.