Disruption of nucleocytoplasmic trafficking as a cellular senescence driver

Senescent cells exhibit a reduced response to intrinsic and extrinsic stimuli. This diminished reaction may be explained by the disrupted transmission of nuclear signals. However, this hypothesis requires more evidence before it can be accepted as a mechanism of cellular senescence. A proteomic analysis of the cytoplasmic and nuclear fractions obtained from young and senescent cells revealed disruption of nucleocytoplasmic trafficking (NCT) as an essential feature of replicative senescence (RS) at the global level. Blocking NCT either chemically or genetically induced the acquisition of an RS-like senescence phenotype, named nuclear barrier-induced senescence (NBIS). A transcriptome analysis revealed that, among various types of cellular senescence, NBIS exhibited a gene expression pattern most similar to that of RS. Core proteomic and transcriptomic patterns common to both RS and NBIS included upregulation of the endocytosis-lysosome network and downregulation of NCT in senescent cells, patterns also observed in an aging yeast model. These results imply coordinated aging-dependent reduction in the transmission of extrinsic signals to the nucleus and in the nucleus-to-cytoplasm supply of proteins/RNAs. We further showed that the aging-associated decrease in Sp1 transcription factor expression was critical for the downregulation of NCT. Our results suggest that NBIS is a modality of cellular senescence that may represent the nature of physiological aging in eukaryotes. © 2021, The Author(s).1

Adenovirus pneumonia treated with Cidofovir in an immunocompetent high school senior

Most adenovirus infections are self-limiting in immunocompetent individuals. Here, we report a case of adenovirus pneumonia in a 17-year-old immunocompetent male. He was admitted to our emergency room complaining of a febrile sense, cough, and diarrhea for four days. Crackles in the left lung and a high fever (40.7 °C) were revealed. Initial chest X-ray and computed tomography images showed consolidation in the left lung. We immediately started empirical antibiotic treatment, but his clinical symptoms and pneumonic consolidation in radiography had not improved by hospital day three. Because adenovirus was detected in his sputum using RT-PCR, he was administered Cidofovir. After 24 h of Cidofovir treatment, the symptoms and fever subsided, and the consolidation in his X-ray was significantly reduced by hospital day nine. The early administration of Cidofovir could be beneficial for the treatment of adenovirus infection in immunocompetent patients. Keywords: Adenovirus, Cidofovir, Healthy, Young adult, Pneumonia, Immunocompeten

A novel FLCN gene mutation causing Birt–Hogg–Dubé syndrome in a Korean family

Spontaneous pneumothorax is a common manifestation of Birt–Hogg–Dubé (BHD) syndrome, an inherited disorder caused by mutation of the folliculin (FLCN) gene. A 44-year-old female with a history of breast cancer was diagnosed with recurrent pneumothorax. Chest CT showed multiple cysts with left lung pneumothorax, and she received surgery for the diagnosis. Because the patient also had a family history of spontaneous pneumothorax, a FLCN genetic examination was conducted. A novel heterozygous, likely pathogenic variant (NM_144997.5:c.779+2T > C) was detected in the proband, her mother, and aunt. This is the first report of a new mutation of FLCN gene in a BHD syndrome patient