Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. Given these commonalities, we hypothesized that a related protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also exhibit similar properties and therefore could contribute to disease. Here, we report an analysis of EWSR1 in multiple functional assays, including mutational screening in ALS patients and controls. We identified three missense variants in EWSR1 in ALS patients, which were absent in a large number of healthy control individuals. We show that disease-specific variants affect EWSR1 localization in motor neurons. We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. Postmortem analysis of sporadic ALS cases also revealed cytoplasmic mislocalization of EWSR1. Together, our studies highlight a potential role for EWSR1 in ALS, provide a collection of functional assays to be used to assess roles of additional RNA-binding proteins in disease and support an emerging concept that a class of aggregation-prone RNA-binding proteins might contribute broadly to ALS and related neurodegenerative diseases.     

Otologic considerations in a full face transplant recipient

Facial transplantation provides a functional and aesthetic solution to severe facial disfigurement previously unresolved by conventional reconstruction. Few facial allografts have been ear containing; hence, there is limited knowledge of the postoperative otologic considerations. We describe the case of a 44‐year‐old man who underwent transplantation of the total face, eyelids, ears, scalp, and skeletal subunits in 2015 after an extensive thermal injury. We detail the patient's transition from osseointegrated prosthetic ears to an ear‐containing facial allograft, and describe the unique surgical approach and challenges encountered. Subsequent bilateral revision meatoplasties were performed, which provided relief from stenosis of the external auditory meatus. Laryngoscope, 129:2008–2011, 2019     

Oral benign neoplasms: A retrospective study of 790 patients over a 14-year period

Introduction and objectiveOral benign neoplasms (OBNs) exhibit some features that can guide the professionals to the correct diagnosis and best treatment. Through retrospective studies, medical records can be reviewed to better describe a given population and, furthermore, help clinicians in routine practice. In this context, the objective of this paper was to analyze the cases of OBNs of an oral pathology referral department, from 2003 to 2017, in order to better understand their epidemiological and clinicopathological characteristics.MethodsA total of 8355 histopathological reports were analyzed. Lesions diagnosed as OBNs were selected and the following variables were recorded: gender, age, histological type of the lesion, anatomical location, rate and pattern of growth, type of base, color, symptomatology and diagnostic hypotheses on clinical examination.ResultsOBNs represented 9.4% of all lesions diagnosed. The most frequent histopathological types were fibroma (39.9%), papilloma (22%), fibroblastoma (13.1%), lipoma (10.2%) and hemangioma (6.1%). Overall, most cases affected females (n = 518; 65.6%) and in the fifth decade of life (n = 148; 18.7%). The oral mucosa was the most common site (n = 265; 33.5%). The most common features of each OBN were also highlighted.ConclusionThe most common OBNs were fibroma, papilloma, fibroblastoma, lipoma and hemangioma. Overall, the OBN presented common clinical features; however, in particular cases, there are some characteristics that can lead the professionals to the correct diagnosis. Nevertheless, in general, histopathological analysis must be performed to confirm diagnosis. Intraosseous tumors and large lesions may require imaging tests to help diagnosis.     

Mononuclear cell-fibroblast interactions in scleroderma

We studied cell proliferation and collagen biosynthesis in cocultures of dermal fibroblasts with peripheral blood mononuclear cells (MNC) from scleroderma patients and from age-matched normal controls. Autologous one-way mixed MNC-fibroblast cultures revealed that fibroblasts do not stimulate MNC proliferation. Conversely, MNC stimulate autologous fibroblasts from scleroderma patients as well as from normal controls. This effect is increased in cells from scleroderma patients in which it seems to be mediated both by cell-to-cell interaction and through the production of soluble factors by MNC. In normal control cell systems we found no proliferative effect of supernatants of unstimulated cells or from those stimulated in autologous mixed-lymphocyte reactions. Coculture of fibroblasts with autologous MNC resulted in increased [14C]proline incorporation into both collagenic and noncollagenic proteins. This effect was mediated mostly by soluble factors that are released into the culture medium. Protein synthesis by MNC-fibroblast cocultures from scleroderma patients was significantly greater than protein synthesis by those from normal controls. Culture supernatants from unstimulated MNC or from autologous mixed-lymphocyte cultures caused a slight decrease in collagenic protein synthesis by cultured fibroblasts from scleroderma patients but not by those from normal controls. This effect of culture supernatants could be reproduced, and magnified, with purified IL-1 on cells from either patients or controls. Our findings indicate abnormal MNC-fibroblast interactions in scleroderma that could play an important role in the pathogenesis of fibrosis, the hallmark of this condition.     

Papillomaviruses in human skin warts and their incidence in an Argentine population

Human papillomavirus genomic types present in human warts of an Argentine population were studied. HPV DNA from single warts was obtained using an alkaline extraction procedure that resulted in a clean DNA preparation, which could be analyzed with several endonucleases. This method was used to isolate and insert the HPV DNAs of two genomic types into the Bam HI site of the pBR322 plasmid. Restriction maps of both HPV DNAs were constructed. According to these maps, one of the genomic variations was identical to HPV1a and the other to HPV2a. The incidence of HPV2 and of HPV1 in different types of skin warts was studied by a dot blot hybridization assay. Twenty-two out of 28 common warts were positive for HPV2 and negative for HPV1; four were positive for HPV1 and negative for HPV2 and two were negative for both. Five out of six plantar warts were positive for HPV1, and one was negative for both. Three out of seven filiform warts were positive for HPV2, three were positive for both probes, and one was negative for both. Southern blot analysis of HPV2 positive samples indicated that 80% were HPV2a and 20% another subtype not yet characterized. All plantar warts contained HPV1a. Msp I/Hpa II restriction analysis confirms previous results indicating that HPV1a DNA is partially methylated, while no evidence of methylation was found for HPV2a DNA.