All Publications

  • Adult residual rectourethral fistula and diverticulum presenting decades after imperforate anus repair: acase report. Journal of medical case reports McShane, E. K., Gurland, B., Sheth, V. R., Bruzoni, M., Enemchukwu, E. 2021; 15 (1): 370


    BACKGROUND: This report describes a rare surgical case of an intraabdominal mass in a middle-aged patient 40years after imperforate anus repair.CASE PRESENTATION: A 44-year-old Latino male with history of repaired anorectal malformation presented with recurrent urinary tract infections and rectal prolapse with bothersome bleeding and fecal incontinence. During his preoperative evaluation, he was initially diagnosed with a prostatic utricle cyst on the basis of magnetic resonance imaging findings, which demonstrated a cystic, thick-walled mass with low signal contents that extended inferiorly to insert into the distal prostatic urethra. However, at the time of surgical resection, the thick-walled structure contained an old, firm fecaloma. The final pathology report described findings consistent with colonic tissue, suggesting a retained remnant of the original fistula and diverticulum.CONCLUSIONS: Although rare, persistent rectourethral fistula tracts and rectal diverticula after imperforate anus repair can cause symptoms decades later, requiring surgical intervention. This is an important diagnostic consideration for any adult patient with history of imperforate anus.

    View details for DOI 10.1186/s13256-021-02921-3

    View details for PubMedID 34261520

  • Structural mimicry drives HIV-1 Rev-mediated HERV-K expression. Journal of molecular biology O'Carroll, I. P., Fan, L., Kroupa, T., McShane, E. K., Theodore, C., Yates, E. A., Kondrup, B., Ding, J., Martin, T. S., Rein, A., Wang, Y. 2020


    Expression of the Human Endogenous Retrovirus Type K (HERV-K), the youngest and most active HERV, has been associated with various cancers and neurodegenerative diseases. As in all retroviruses, a fraction of HERV-K transcripts is exported from the nucleus in unspliced or incompletely spliced forms to serve as templates for translation of viral proteins. In a fraction of HERV-K loci (Type 2 proviruses), nuclear export of the unspliced HERV-K mRNA appears to be mediated by a cis-acting signal on the mRNA, the RcRE, and the protein Rec-these are analogous to the RRE-Rev system in HIV-1. Interestingly, the HIV-1 Rev protein is able to mediate the nuclear export of the HERV-K RcRE, contributing to elevated HERV-K expression in HIV-infected patients. We aimed to understand the structural basis for HIV Rev-HERV-K RcRE recognition. We examined the conformation of the RcRE RNA in solution using small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM). We found that the 433-nt long RcRE can assume folded or extended conformations as observed by AFM. SAXS analysis of a truncated RcRE variant revealed an "A"-shaped topological structure similar to the one previously reported for the HIV-1 RRE. The effect of the overall topology was examined using several deletion variants. SAXS and biochemical analyses demonstrated that the "A" shape is necessary for efficient Rev-RcRE complex formation in vitro and nuclear export activity in cell culture. The findings provide insight into the mechanism of HERV-K expression and a structural explanation for HIV-1 Rev-mediated expression of HERV-K in HIV-infected patients. Importance Expression of the human endogenous retrovirus type K (HERV-K) has been associated with various cancers and autoimmune diseases. Nuclear export of both HIV-1 and HERV-K mRNAs is dependent on the interaction between a small viral protein (Rev in HIV-1 and Rec in HERV-K) and a region on the mRNA (RRE in HIV-1 and RcRE in HERV-K). HIV-1 Rev is able to mediate the nuclear export of RcRE-containing HERV-K mRNAs, which contributes to elevated production of HERV-K proteins in HIV-infected patients. We report the solution conformation of the RcRE RNA-the first three-dimensional topological structure for a HERV molecule-and find that the RcRE resembles the HIV-1 nuclear export signal, RRE. The finding reveals the structural basis for the increased HERV-K expression observed in HIV-infected patients. Elevated HERV expression, mediated by HIV infection or other stressors, can have various HERV-related biological consequences. The findings provide structural insight for regulation of HERV-K expression.

    View details for DOI 10.1016/j.jmb.2020.11.010

    View details for PubMedID 33197463