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1.
Elife ; 82019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950791

RESUMO

The circadian clock relies on regulated degradation of clock proteins to maintain rhythmicity. Despite this, we know few components that mediate protein degradation. This is due to high levels of functional redundancy within plant E3 ubiquitin ligase families. In order to overcome this issue and discover E3 ubiquitin ligases that control circadian function, we generated a library of transgenic Arabidopsis plants expressing dominant-negative 'decoy' E3 ubiquitin ligases. We determined their effects on the circadian clock and identified dozens of new potential regulators of circadian function. To demonstrate the potency of the decoy screening methodology to overcome redundancy and identify bona fide clock regulators, we performed follow-up studies on MAC3A (PUB59) and MAC3B (PUB60). We show that they redundantly control circadian period by regulating splicing. This work demonstrates the viability of ubiquitin ligase decoys as a screening platform to overcome genetic challenges and discover E3 ubiquitin ligases that regulate plant development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Relógios Circadianos , Regulação da Expressão Gênica de Plantas , Testes Genéticos/métodos , Ubiquitina-Proteína Ligases/metabolismo , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Plantas Geneticamente Modificadas , Proteólise , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ubiquitina-Proteína Ligases/genética
2.
Psychiatry Res ; 257: 51-55, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28727991

RESUMO

AIMS: (1) Determine the accuracy of self-reported height, weight, and body mass index (BMI) calculated from those values in a population suffering from both serious mental illness (SMI) and overweight/obesity; (2) identify any associations that may predict error in self-reported measurements. Data were collected from screening appointments for two clinical trials for adult patients with SMI and overweight/obesity (BMI > 28) who gained weight while on antipsychotic medications. Both studies were conducted at the same urban community mental health center. Differences in self-reported and measured height, weight, and BMI were calculated. Analysis included age, sex, race, psychiatric diagnosis, and level of education. BMI calculated from self-reported height and weight were significantly lower (-0.47kg/m2) than measured values. Height was significantly overestimated (1.04cm), while weight was underestimated (0.055kg). Men underestimated BMI more than women (0.55 vs. 0.41kg/m2). Increasing age correlated with lower accuracy of self-reported height and BMI. No differences due to psychiatric diagnosis, race, or education were found. BMI calculated from self-reported height and weight from patients with SMI and overweight/obesity is as accurate as the self-reported measurements collected from the general population and, while measurement is best, self-reports can be used as a tool for screening for obesity.


Assuntos
Estatura , Peso Corporal , Confiabilidade dos Dados , Pessoas Mentalmente Doentes/psicologia , Obesidade/psicologia , Autorrelato , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
3.
Neurosci Lett ; 600: 137-42, 2015 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-26054939

RESUMO

Spontaneous retinal waves play a critical role in the establishment of precise neuronal connections in the developing visual system. Retinal waves in mammals progress through three distinct developmental stages prior to eye opening. Using multielectrode array (MEA) recording from the rabbit retina, this study found characteristic changes in the spontaneous spike pattern in the ganglion cell layer during the transition from stage II to stage III retinal waves. These changes led to an increased diversity in the spatiotemporal pattern of the spontaneous activity, consistent with a potential role of stage III retinal waves in the establishment of diverse, cell type-specific neuronal connectivity during visual system development. The study also showed that GABAergic inhibition, predominantly mediated by GABAA receptors, was critical in breaking down large waves of ganglion cell spiking into spatially restricted and temporally diverse spike patterns at stage III, suggesting an important role of amacrine cells in shaping the diverse spontaneous activity patterns of developing ganglion cells.


Assuntos
Potenciais de Ação , Receptores de GABA-A/fisiologia , Receptores de GABA-B/fisiologia , Células Ganglionares da Retina/fisiologia , Células Amácrinas/fisiologia , Animais , Antagonistas GABAérgicos/farmacologia , Ácidos Fosfínicos/farmacologia , Piridazinas/farmacologia , Piridinas/farmacologia , Coelhos , Retina/crescimento & desenvolvimento , Retina/fisiologia
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