A-to-I mRNA editing controls spore death induced by a fungal meiotic drive gene in homologous and heterologous expression systems.

Spore killers are meiotic drive elements that can block the development of sexual spores in fungi. In the maize ear rot and mycotoxin-producing fungus Fusarium verticillioides, a spore killer called SkK has been mapped to a 102-kb interval of chromosome V. Here, we show that a gene within this interval, SKC1, is required for SkK-mediated spore killing and meiotic drive. We also demonstrate that SKC1 is associated with at least 4 transcripts, 2 sense (sense-SKC1a and sense-SKC1b) and 2 antisense (antisense-SKC1a and antisense-SKC1b). Both antisense SKC1 transcripts lack obvious protein-coding sequences and thus appear to be noncoding RNAs. In contrast, sense-SKC1a is a protein-coding transcript that undergoes A-to-I editing to sense-SKC1b in sexual tissue. Translation of sense-SKC1a produces a 70-amino-acid protein (Skc1a), whereas the translation of sense-SKC1b produces an 84-amino-acid protein (Skc1b). Heterologous expression analysis of SKC1 transcripts shows that sense-SKC1a also undergoes A-to-I editing to sense-SKC1b during the Neurospora crassa sexual cycle. Site-directed mutagenesis studies indicate that Skc1b is responsible for spore killing in Fusarium verticillioides and that it induces most meiotic cells to die in Neurospora crassa. Finally, we report that SKC1 homologs are present in over 20 Fusarium species. Overall, our results demonstrate that fungal meiotic drive elements like SKC1 can influence the outcome of meiosis by hijacking a cell's A-to-I editing machinery and that the involvement of A-to-I editing in a fungal meiotic drive system does not preclude its horizontal transfer to a distantly related species.

Examining the responses of the zebrafish (Danio rerio) gastrointestinal system to the suspected obesogen diethylhexyl phthalate.

Epidemiological evidence suggests that phthalate plasticizers may act as "obesogens", which are chemicals that exacerbate obesity. The gastrointestinal (GI) system is the primary exposure route for phthalates, however, the relationship between phthalate-driven perturbations of GI system functions that can influence obesity has yet to be examined. To address this knowledge gap, we exposed Danio rerio (zebrafish) for 60 days to either (1) Control feeding (5 mg/fish/day), (2) Overfeeding (20 mg/fish/day) or (3) Overfeeding with diethyl-hexyl phthalate (DEHP) (20 mg/fish/day with 3 mg/kg DEHP). After 60 days, Overfed and Overfed + DEHP zebrafish had elevated body mass, and hepatosomatic and gonadosomatic indices. RNAseq analysis of the GI revealed enrichment of gene networks related to lipid metabolism in the Overfed + DEHP group. Many of the enriched networks were under transcriptional control of peroxisome proliferator activated receptor alpha (pparα), a known modulator of lipid metabolism, immune function, and GI function. Real-time PCR confirmed that pparα was overexpressed in the Overfed + DEHP zebrafish, further revealing a pathway by which DEHP may influence lipid metabolism via the GI. These data increase our understanding of phthalate-driven effects on GI function and lipid metabolism, identifying gut-specific gene networks that may drive phthalate-exacerbated obesity.

A Rare Case of Penile Metastases as a Harbinger of Primary Pulmonary Adenosquamous Carcinoma.

Although lung cancer has a high propensity for distant metastatic disease, penile metastases from primary lung neoplasms are considered particularly rare. A 71-year-old male presented to our hospital with a rapidly enlarging hard palpable penile mass. MR imaging demonstrated two penile masses centered in the left and right corpus cavernosa. Subsequent CT imaging revealed a spiculated pulmonary mass in the right upper lobe with PET/CT, MRI, and surgical exploration, demonstrating evidence of metastases to the left adrenal gland, right subscapularis muscle, brain, and small bowel. Tissue sampling of lesions in the small bowel, right subscapularis muscle, and penis demonstrated histopathology consistent with an adenosquamous carcinoma which in combination with the appearance of the right upper lobe mass on PET/CT imaging suggested the patient's lung cancer as the primary lesion. Prior to our case, pulmonary adenosquamous carcinoma metastasizing to the penis has only been reported once in the literature. Herein, we report a rare case of penile metastases as the presenting sign of metastatic pulmonary adenosquamous carcinoma characterized with PET/CT and MR imaging.