RESUMO
Nicotinamide-adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP-ribose) polymerases (PARPs) that add poly(ADP-ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by-product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA-seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Ritmo Circadiano/genética , Regulação da Expressão Gênica de Plantas , Poli(ADP-Ribose) Polimerases/metabolismo , Sirtuínas/metabolismo , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Ritmo Circadiano/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Mutação/genética , NAD+ Nucleosidase/antagonistas & inibidores , NAD+ Nucleosidase/metabolismo , Niacinamida/farmacologia , Fenótipo , Poli(ADP-Ribose) Polimerases/genética , Sementes/efeitos dos fármacos , Sementes/metabolismoRESUMO
Objective: We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age.Method: Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents' concerns about their child's behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 and 24 months of age.Results: Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD.Conclusions: These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Predisposição Genética para Doença , Humanos , Comportamento Impulsivo , Lactente , Pais , TemperamentoRESUMO
BACKGROUND: The 'dysregulation profile' (DP) is a measure of emotional and behavioral dysregulation that may cut across diagnostic boundaries. Siblings of children with autism spectrum disorder (ASD) who do not develop ASD themselves are at risk for atypical outcomes including behavioral challenges and therefore may be a useful population in which to investigate the structure of the DP in preschoolers. METHODS: We sought to examine the factor structure and predictors of the DP in a sample enriched for a wide range of phenotypic variation-36-month-olds with and without family histories of ASD-and to determine whether children with genetic liability for ASD are at risk for a phenotype characterized by elevated dysregulation. Data were collected from 415 children with (n = 253) and without (n = 162) an older sibling with ASD, all without ASD themselves, at 18, 24, and 36 months of age. RESULTS: Our findings replicate prior reports, conducted in predominantly clinically referred and older samples, supporting the superiority of a bifactor model of the DP in the preschool period compared to the second-order and one-factor models. Examiner ratings were longitudinally and concurrently associated with the DP at 36 months of age. Family history of ASD was associated with higher dysregulation in the Anxious/Depressed dimension. CONCLUSIONS: These findings support the relevance of examining the structure of psychopathology in preschoolers and suggest that examiner observations as early as 18 months of age, particularly of overactivity, may help identify risk for later DP-related concerns. Non-ASD preschoolers with family histories of ASD may be at risk for a phenotype characterized by elevated dysregulation particularly in the Anxious/Depressed dimension by age 3.
Assuntos
Ansiedade/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Depressão/fisiopatologia , Predisposição Genética para Doença , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/genética , Pré-Escolar , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Fenótipo , Risco , IrmãosRESUMO
Circadian clocks are 24-h timekeeping mechanisms, which have evolved in plants, animals, fungi and bacteria to anticipate changes in light and temperature associated with the rotation of the Earth. The current paradigm to explain how biological clocks provide timing information is based on multiple interlocking transcription-translation negative feedback loops (TTFL), which drive rhythmic gene expression and circadian behaviour of growth and physiology. Metabolism is an important circadian output, which in plants includes photosynthesis, starch metabolism, nutrient assimilation and redox homeostasis. There is increasing evidence in a range of organisms that these metabolic outputs can also contribute to circadian timing and might also comprise independent circadian oscillators. In this review, we summarise the mechanisms of circadian regulation of metabolism by TTFL and consider increasing evidence that rhythmic metabolism contributes to the circadian network. We highlight how this might be relevant to plant circadian clock function.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Metabolismo Energético , Retroalimentação Fisiológica , Regulação da Expressão Gênica de Plantas , ADP-Ribosil Ciclase/genética , ADP-Ribosil Ciclase/metabolismo , Proteínas de Arabidopsis/genética , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Biossíntese de Proteínas , Transdução de Sinais , Sirtuínas/genética , Sirtuínas/metabolismo , Sacarose/metabolismo , Transcrição GênicaRESUMO
BACKGROUND: An operating room (OR) environment is challenging and complicated. At any given time, several vital tasks are being performed by skilled individuals, including physicians, nurses, and ancillary staff. There is a potential for multifactorial mistakes; many arise because of communication issues. METHODS: To evaluate the current state of perceptions of interdisciplinary communication in an OR setting, a survey was developed and administered to four academic residency training departments of anesthesiology in a single U.S. state. RESULTS: The results of this survey show that perceived poor communication within the OR leads to a lack of emphasis on a multidisciplinary approach to patient care in the OR. CONCLUSIONS: Survey data can be used internally to identify shortcomings in communication at a facility, to stress the importance of communication, and to serve as a powerful education tool to potentially improve patient care. Through this type of survey, which emphasizes communication in the OR, stakeholders can work more effectively to improve patient care and decrease adverse outcomes in the hospital environment.
Assuntos
Comunicação Interdisciplinar , Salas Cirúrgicas , Equipe de Assistência ao Paciente/organização & administração , Centros Médicos Acadêmicos , Adulto , Anestesiologia/educação , Feminino , Grupos Focais , Humanos , Capacitação em Serviço , Masculino , Projetos Piloto , Melhoria de Qualidade , Inquéritos e Questionários , Estados UnidosRESUMO
Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental condition characterized by developmentally extreme and impairing symptoms of inattention and/or hyperactivity/impulsivity. Great interest has emerged in the ways ADHD and its underlying symptom dimensions relate to the development of personality traits. Much extant research on this topic is cross-sectional, relying on self-report measures and male samples. Herein, we present data from a prospective, longitudinal study of a socioeconomically and racially diverse sample of girls, including those with ADHD and a matched neurotypical comparison sample. We examined how parent- and teacher-reported ADHD in middle childhood relate to self-reported Big Five personality traits in adolescence. As expected, childhood ADHD diagnosis prospectively predicted lower self-reported Conscientiousness, lower Agreeableness, and higher Neuroticism in adolescence. With ADHD diagnosis covaried, Inattention (IA) predicted only low Conscientiousness, Hyperactivity/Impulsivity (HI) predicted only low Agreeableness, and neither predicted adolescent Neuroticism. An exploratory moderator analysis showed that family income moderated the effects of IA and HI on the negativity of adolescent self-descriptions of their own personalities, with more pronounced negative effects for girls in families with higher (rather than lower) income. Familial pressures to achieve in higher-income families may be linked to more pronounced negative ramifications of ADHD on personality development.
RESUMO
The Earth's rotation and its orbit around the Sun leads to continual changes in the environment. Many organisms, including plants and animals, have evolved circadian clocks that anticipate these changes in light, temperature, and seasons in order to optimize growth and physiology. Circadian timing is thought to derive from a molecular oscillator that is present in every plant cell. A central aspect of the circadian oscillator is the presence of transcription translation loops (TTLs) that provide negative feedback to generate circadian rhythms. This review examines the evidence that the 24 h circadian clocks of plants regulate the fluxes of solutes and how changes in solute concentrations can also provide feedback to modulate the behaviour of the molecular oscillator. It highlights recent advances that demonstrate interactions between components of TTLs and regulation of solute concentration and transport. How rhythmic control of water fluxes, ions such as K(+), metabolic solutes such as sucrose, micronutrients, and signalling molecules, including Ca(2+), might contribute to optimizing the physiology of the plant is discussed.