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1.
Cell ; 139(6): 1130-42, 2009 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-20005806

RESUMO

In mammals, the transcription factor SRY, encoded by the Y chromosome, is normally responsible for triggering the indifferent gonads to develop as testes rather than ovaries. However, testis differentiation can occur in its absence. Here we demonstrate in the mouse that a single factor, the forkhead transcriptional regulator FOXL2, is required to prevent transdifferentiation of an adult ovary to a testis. Inducible deletion of Foxl2 in adult ovarian follicles leads to immediate upregulation of testis-specific genes including the critical SRY target gene Sox9. Concordantly, reprogramming of granulosa and theca cell lineages into Sertoli-like and Leydig-like cell lineages occurs with testosterone levels comparable to those of normal XY male littermates. Our results show that maintenance of the ovarian phenotype is an active process throughout life. They might also have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.


Assuntos
Transdiferenciação Celular , Fatores de Transcrição Forkhead/metabolismo , Ovário/metabolismo , Testículo/metabolismo , Animais , Feminino , Proteína Forkhead Box L2 , Fatores de Transcrição Forkhead/genética , Deleção de Genes , Células da Granulosa/citologia , Masculino , Camundongos , Oócitos/metabolismo , Ovário/citologia , Células de Sertoli/citologia , Testículo/citologia
2.
Psychiatry Res ; 330: 115574, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37924772

RESUMO

Mental illness research routinely includes unfamiliar or potentially frightening procedures like lumbar puncture (LP), contributing to low enrollment and retention. Previous studies related to LP acceptance have focused on older individuals, and little information on participant preferences for educational materials is available. We developed an online survey assessing existing knowledge, comfort and concerns, and preferences for educational materials in the context of our clinical study on schizophrenia spectrum conditions (SSCs). We found that participants were generally knowledgeable and interested in engaging with clinical SSC research. Frequency of engagement with research publications differed significantly by participant groups and age. Comfort levels were consistently highest for study procedures other than LP, though surprisingly the average number of informational needs per procedure was not significantly different for LP compared to other procedures. Preferences for format and source of educational materials varied across participant groups and age. Our results suggest that younger individuals with an SSC diagnosis are likely to have limited exposure to information, and proactively providing accessible and accurate educational materials may improve positive perceptions of LP. Providing content in a range of formats and sources will ensure that participants and their support networks have access to their preferred resources.


Assuntos
Transtornos Mentais , Esquizofrenia , Humanos , Retroalimentação , Transtornos Mentais/terapia , Esquizofrenia/terapia , Pacientes
3.
Sci Data ; 5: 180260, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30512012

RESUMO

Olfactory experience can alter the molecular and cellular composition of chemosensory neurons within the olfactory sensory epithelia of mice. We sought to investigate the scope of cellular and molecular changes within a mouse's olfactory system as a function of its exposure to complex and salient sets of odors: those emitted from members of the opposite sex. We housed mice either separated from members of the opposite sex (sex-separated) or together with members of the opposite sex (sex-combined) until six months of age, resulting in the generation of four cohorts of mice. From each mouse, the main olfactory epithelium (MOE), vomeronasal organ (VNO), and olfactory bulb (OB) were removed and RNA-extracted. A total of 36 RNA samples, representing three biological replicates per sex/condition/tissue combination, were analyzed for integrity and used to prepare RNA-seq libraries, which were subsequently analyzed via qPCR for the presence of tissue- or sex-specific markers. Libraries were paired-end sequenced to a depth of ~20 million fragments per replicate and the data were analyzed using the Tuxedo suite.


Assuntos
Perfilação da Expressão Gênica , Bulbo Olfatório , Mucosa Olfatória , Receptores Odorantes/genética , Caracteres Sexuais , Órgão Vomeronasal , Animais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , Odorantes , Bulbo Olfatório/fisiologia , Mucosa Olfatória/fisiologia , Órgão Vomeronasal/fisiologia
4.
Nat Commun ; 9(1): 5081, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514924

RESUMO

Within the mammalian olfactory sensory epithelium, experience-dependent changes in the rate of neuronal turnover can alter the relative abundance of neurons expressing specific chemoreceptors. Here we investigate how the mouse olfactory sensory receptor repertoire changes as a function of exposure to odors emitted from members of the opposite sex, which are highly complex and sexually dimorphic. Upon housing mice either sex-separated or sex-combined until six months of age, we find that sex-separated mice exhibit significantly more numerous differentially expressed genes within their olfactory epithelia. A subset of these chemoreceptors exhibit altered expression frequencies following both sex-separation and olfactory deprivation. We show that several of these receptors detect either male- or female-specific odors. We conclude that the distinct odor experiences of sex-separated male and female mice induce sex-specific differences in the abundance of neurons that detect sexually dimorphic odors.


Assuntos
Neurônios Receptores Olfatórios/metabolismo , Caracteres Sexuais , Comportamento Sexual Animal/fisiologia , Olfato/fisiologia , Animais , Comportamento Animal , Feminino , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Odorantes , Mucosa Olfatória/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo
5.
Biochem Mol Biol Educ ; 46(4): 318-326, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29528558

RESUMO

In the past ten years, increasing evidence has demonstrated that scientific teaching and active learning improve student retention and learning gains in the sciences. Graduate teaching assistants (GTAs), who play an important role in undergraduate education at many universities, require training in these methods to encourage implementation, long-term adoption, and advocacy. Here, we describe the design and evaluation of a two-day training workshop for first-year GTAs in the life sciences. This workshop combines instruction in current research and theory supporting teaching science through active learning as well as opportunities for participants to practice teaching and receive feedback from peers and mentors. Postworkshop assessments indicated that GTA participants' knowledge of key topics increased during the workshop. In follow-up evaluations, participants reported that the workshop helped them prepare for teaching. This workshop design can easily be adapted to a wide range of science disciplines. Overall, the workshop prepares graduate students to engage, include, and support undergraduates from a variety of backgrounds when teaching in the sciences. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:318-326, 2018.


Assuntos
Educação de Pós-Graduação , Aprendizagem Baseada em Problemas , Ciência/educação , Estudantes , Ensino , Humanos
6.
FEBS J ; 278(7): 1002-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21281448

RESUMO

In mouse sex determination, the presence or absence of Sertoli cells in the developing gonad is essential for the decision to form either a testis or an ovary. The transcription factor SOX9 has emerged as the master regulator of Sertoli cell differentiation during testis development and thus the crucial gene to determine sex. It is the target of two sets of regulatory controls, one positive and one negative, where one set tries to gain dominance over the other in the early gonad and then to establish and maintain the activity or silence of Sox9 throughout life. The data reveal the importance of the positive regulatory loops to reinforce initial decisions, whereas the maintenance of the gonadal phenotype appears to rely on the active repression of the opposite pathway.


Assuntos
Mamíferos/fisiologia , Fatores de Transcrição SOX9/metabolismo , Processos de Determinação Sexual/fisiologia , Animais , Diferenciação Celular/fisiologia , Linhagem da Célula , Feminino , Fator 9 de Crescimento de Fibroblastos/genética , Fator 9 de Crescimento de Fibroblastos/metabolismo , Gônadas/fisiologia , Humanos , Masculino , Camundongos , Prostaglandina D2/genética , Prostaglandina D2/metabolismo , Fatores de Transcrição SOX9/genética , Células de Sertoli/fisiologia
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