RESUMEN
New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together diverse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.
Asunto(s)
Bioética , Cognición , Genética Humana , Música , HumanosRESUMEN
Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1-15 messenger ribonucleic acid and proteins in PA specimens to determine a KLK expression profile for this tumor. Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to quantitative real-time reverse transcription polymerase chain reaction to detect KLK1-15 mRNA. Expression of KLK1, KLK12, KLK13, and KLK8 proteins were then evaluated via immunostaining techniques. Statistical analyses were performed with the level of significance set at P < .05. We observed downregulation of KLK1, KLK12, and KLK13 mRNA expression, and immunostaining studies revealed downregulation of the corresponding proteins. Histologic evidence of capsular perforation was associated with increased KLK1 protein expression. Tumor size was not associated with capsular invasion and/or perforation. This study is the first to detail a KLK expression profile for PA at both the transcriptional level and the protein level. Future work is required to develop clinical applications of these findings.
Asunto(s)
Adenoma Pleomórfico/patología , Biomarcadores de Tumor/análisis , Calicreínas/análisis , Neoplasias de las Glándulas Salivales/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Reconstruction of large mandibular defects, whether involving the temporomandibular joint (TMJ) or not, has historically been achieved with autogenous grafts, such as free costochondral grafts and vascularized bone grafts. Ensuring intact, functioning microcirculation is critical for graft survival in the face of postoperative radiation therapy secondary to malignant tumour ablation. However, in the case of benign tumours, such as ameloblastomas, postoperative radiation therapy is not required, thus increasing the options for reconstruction. Alloplastic components coupled with nonvascularized bone grafts have been used successfully to restore mandibular form, function and esthetics after extensive mandibular resection. In this article, we describe a case of a multiply recurrent ameloblastoma treated by left hemimandibulectomy and immediate reconstruction with a custom-fabricated alloplastic system in combination with an anterior iliac crest bone graft. The result was a high degree of mandibular function and facial cosmesis, minimal donor-site morbidity, and nearly immediate return to function.
Asunto(s)
Ameloblastoma/patología , Ameloblastoma/cirugía , Neoplasias Mandibulares/patología , Neoplasias Mandibulares/cirugía , Procedimientos Quirúrgicos Orales , Procedimientos de Cirugía Plástica , Articulación Temporomandibular/patología , Articulación Temporomandibular/cirugía , Ameloblastoma/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Masculino , Neoplasias Mandibulares/diagnóstico por imagen , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Radiografía Panorámica , Articulación Temporomandibular/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
A general approach to halogenated arylpyrroles, including the antifungal natural product pyrrolnitrin, is described using newly synthesized halogenated pyrroles and 2,6-disubstituted nitrobenzenes or 2,6-disubstituted anilines.
Asunto(s)
Antifúngicos/síntesis química , Hidrocarburos Halogenados/química , Hidrocarburos Halogenados/síntesis química , Pirroles/síntesis química , Pirrolnitrina/síntesis química , Compuestos de Anilina/química , Antifúngicos/química , Técnicas Químicas Combinatorias , Estructura Molecular , Nitrobencenos/química , Pirroles/química , Pirrolnitrina/químicaRESUMEN
BAFF receptor (BAFFR) is a member of the TNF receptor (TNFR) superfamily that regulates the survival and maturation of B cells. BAFFR exerts its signaling function by inducing activation of NF-kappaB, although the underlying mechanism has not been well defined. By using a chimeric BAFFR, we show that BAFFR preferentially induces the noncanonical NF-kappaB signaling pathway. This specific function of BAFFR is mediated by a sequence motif, PVPAT, which is homologous to the TRAF-binding site (PVQET) present in CD40, a TNFR known to induce both the canonical and noncanonical NF-kappaB pathways. Mutation of this putative TRAF-binding motif within BAFFR abolishes its interaction with TRAF3 as well as its ability to induce noncanonical NF-kappaB. Interestingly, modification of the PVPAT sequence to the typical TRAF-binding sequence, PVQET, is sufficient to render the BAFFR capable of inducing strong canonical NF-kappaB signaling. Further, this functional acquisition of the modified BAFFR is associated with its stronger and more rapid association with TRAF3. These findings suggest that the PVPAT sequence of BAFFR not only functions as a key signaling motif of BAFFR but also determines its signaling specificity in the induction of the noncanonical NF-kappaB pathway.