Pulmonary Langerhans Cell Histiocytosis in a young Non-Smoking Female --Too many Rituals spoil the Lung.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare idiopathic cystic interstitial granulomatous lung disease seen almost exclusively in cigarette smokers. It typically occurs between 20-40 years of age and equally distributed among both sexes. Management includes smoking cessation, avoidance of second-hand smoke, and close follow-up. Corticosteroids may be required in those with symptomatic disease with worsening lung function despite smoking cessation and progressive nodular stage of the disease. Here, we report an interesting case of biopsy-proven PLCH in a young never smoker female. Detailed questioning revealed significant exposure to incense smoke, highlighting a rare presentation of non-cigarette smoke-related PLCH. Avoidance of incense smoke combined with oral prednisolone (0.5mg/kg) tapered over 6 months led to complete resolution of symptoms, disappearance of nodules in high resolution computed tomography (HRCT) of the thorax and improvement in lung function.

Nanoscopic investigation of C9orf72 poly-GA oligomers on nuclear membrane disruption by a photoinducible platform.

Glycine-alanine dipeptide repeats (GA DPRs) translated from the mutated C9orf72 gene have recently been correlated with amyotrophic lateral sclerosis (ALS). While GA DPRs aggregates have been suggested as amyloid, the biophysical features and cytotoxicity of GA DPRs oligomers has not been explored due to its unstable nature. In this study, we develop a photoinducible platform based on methoxynitrobenzene chemistry to enrich GA DPRs that allows monitoring the oligomerization process of GA DPRs in cells. By applying advanced microscopies, we examined the GA DPRs oligomerization process nanoscopically in a time-dependent manner. We provided direct evidences to demonstrate GA DPRs oligomers rather than nanofibrils disrupt nuclear membrane. Moreover, we found GA DPRs hamper nucleocytoplasmic transport in cells and cause cytosolic retention of TAR DNA-binding protein 43 in cortical neurons. Our results highlight the toxicity of GA DPRs oligomers, which is a key step toward elucidating the pathological roles of C9orf72 DPRs.