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1.
Ann N Y Acad Sci ; 1522(1): 5-14, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36851882

RESUMO

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.


Assuntos
Bioética , Cognição , Genética Humana , Música , Humanos
2.
Head Neck Pathol ; 13(3): 286-297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30120721

RESUMO

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.


Assuntos
Adenoma Pleomorfo/patologia , Biomarcadores Tumorais/análise , Calicreínas/análise , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
J Can Dent Assoc ; 80: e14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25055228

RESUMO

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.


Assuntos
Ameloblastoma/patologia , Ameloblastoma/cirurgia , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/cirurgia , Procedimentos Cirúrgicos Bucais , Procedimentos de Cirurgia Plástica , Articulação Temporomandibular/patologia , Articulação Temporomandibular/cirurgia , Ameloblastoma/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Radiografia Panorâmica , Articulação Temporomandibular/diagnóstico por imagem , Tomografia Computadorizada por Raios X
4.
Org Lett ; 11(5): 1051-4, 2009 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-19196161

RESUMO

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.


Assuntos
Antifúngicos/síntese química , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/síntese química , Pirróis/síntese química , Pirrolnitrina/síntese química , Compostos de Anilina/química , Antifúngicos/química , Técnicas de Química Combinatória , Estrutura Molecular , Nitrobenzenos/química , Pirróis/química , Pirrolnitrina/química
5.
J Biol Chem ; 280(11): 10018-24, 2005 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-15644327

RESUMO

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.


Assuntos
Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Receptores do Fator de Necrose Tumoral/química , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/química , Fator de Necrose Tumoral alfa/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Fator Ativador de Células B , Receptor do Fator Ativador de Células B , Sítios de Ligação , Antígenos CD40/biossíntese , Ligante de CD40/química , Linhagem Celular , Separação Celular , DNA Complementar/metabolismo , Ativação Enzimática , Citometria de Fluxo , Humanos , Immunoblotting , Imunoprecipitação , Camundongos , Dados de Sequência Molecular , Mutação , Plasmídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Receptores do Fator de Necrose Tumoral/metabolismo , Retroviridae/genética , Ribonucleases/metabolismo , Transdução de Sinais , Espectrometria de Fluorescência , Fator 2 Associado a Receptor de TNF/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Transfecção , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo
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