Traumatic brain injury (TBI) has been predicted to be a predisposing factor for amyotrophic lateral sclerosis (ALS) and other neurological disorders. Despite the importance of TBI in ALS progression, the underlying cellular and molecular mechanisms are still an enigma. Here, we examined the contribution of TBI as an extrinsic factor and investigated whether TBI influences the susceptibility of developing neurodegenerative symptoms. To evaluate the effects of TBI in vivo, we applied mild to severe trauma to Drosophila and found that TBI leads to the induction of stress granules (SGs) in the brain. The degree of SGs induction directly correlates with the level of trauma. Furthermore, we observed that the level of mortality is directly proportional to the number of traumatic hits. Interestingly, trauma-induced SGs are ubiquitin, p62 and TDP-43 positive, and persistently remain over time suggesting that SGs might be aggregates and exert toxicity in our fly models. Intriguingly, TBI on animals expressing ALS-linked genes increased mortality and locomotion dysfunction suggesting that mild trauma might aggravate neurodegenerative symptoms associated with ALS. Furthermore, we found elevated levels of high molecular weight ubiquitinated proteins and p62 in animals expressing ALS-causing genes with TBI, suggesting that TBI may lead to the defects in protein degradation pathways. Finally, we observed that genetic and pharmacological induction of autophagy enhanced the clearance of SGs and promoted survival of flies in vivo. Together, our study demonstrates that trauma can induce SG formation in vivo and might enhance neurodegenerative phenotypes in the fly models of ALS.

Mutations in fused in sarcoma (FUS) lead to amyotrophic lateral sclerosis (ALS) with varying ages of onset, progression and severity. This suggests that unknown genetic factors contribute to disease pathogenesis. Here we show the identification of muscleblind as a novel modifier of FUS-mediated neurodegeneration in vivo. Muscleblind regulates cytoplasmic mislocalization of mutant FUS and subsequent accumulation in stress granules, dendritic morphology and toxicity in mammalian neuronal and human iPSC-derived neurons. Interestingly, genetic modulation of endogenous muscleblind was sufficient to restore survival motor neuron (SMN) protein localization in neurons expressing pathogenic mutations in FUS, suggesting a potential mode of suppression of FUS toxicity. Upregulation of SMN suppressed FUS toxicity in Drosophila and primary cortical neurons, indicating a link between FUS and SMN. Our data provide in vivo evidence that muscleblind is a dominant modifier of FUS-mediated neurodegeneration by regulating FUS-mediated ALS pathogenesis.

This is a case of a proximal corpus cavernosa fracture presenting with scrotal edema and butterfly perineal ecchymosis sparing the penile shaft. Preoperative MRI obviated the need for circumferential incision and degloving of the penis and guided immediate incision over the area of corporal injury. The presentation, diagnostic work-up, and surgical treatment are discussed.

shrunken", filled with stone debris, with thickened mucosa and erythematous patches upon post-mortem evaluation. Two causes exist as explanation for these findings: a urethral stricture and schistosomiasis. It is possible that Napoleon developed a urethral stricture from gonococcal urethritis from his first wife, Josephine. It is thought that she likely contracted gonorrhea prior to their marriage in 1796 and tubal scarring from the infection was the reason she could not give Napoleon an heir (Figure 1). Furthermore, Napoleon may have contracted schistosomiasis while in Egypt. Referred to as the "land of menstruating men" by physicians within Napoleon's company given the wide prevalence of hematuria, Egypt was endemic with the flatworm Schistosoma haematobium during the time of his Egypt campaign. While known to cause hematuria, chronic cystitis, and dysuria, Schistosoma infections have also been shown to increase risk of bladder stones and therefore could explain Napoleon's urologic troubles later in life. On the eve of the Battle of Borodino, Napoleon was described to have had a severe episode of dysuria. While he won the Battle, it was the single bloodiest day in the Napoleonic Wars. He was further affected by bouts of dysuria before the Battle of Waterloo where his loss lead to his eventual exile. It is possible that Napoleon's acute dysuria affected his military decision making, costing him tremendous manpower at Borodino and his empire at Waterloo. CONCLUSIONS: Napoleon was afflicted with dysuria throughout his adult life, likely from a urethral stricture, schistosomiasis, or both. This debilitated him throughout his life into his exile and death and may have played a role in his military miscalculations and subsequent fall from power.