Circadian rhythm profiles in porcine ICU subjects

Purpose: To explore the natural trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM), and gas exchange (GE) in mechanically ventilated swine, as these variables affect the duration of mechanical ventilation. ^ Design: A secondary analysis to describe and compare circadian rhythms of study variables in swine mechanically ventilated for ≤ 7 days. ^ Setting: Porcine Intensive Care Unit (ICU).^ Sample: Six male swine. ^ Methods: Sedation requirements were recorded hourly and the CBT, PM and GE variables were sampled every 1 s – 1 min for ≤ 7 days. The data sets for each pig with > 5 days ICU length of stay were divided into one section representing the first 3 days and one section representing subsequent days. The Lomb periodogram was used to estimate the circadian time period for each variable, and cosinor analysis with the estimated time period to obtain amplitude and mesor. Circadian to ultradian bandpower ratio to assess rhythm quality and stability over time and goodness-of-fit index to describe biological significance of a rhythm were used. Together, these two parameters were used to define rhythm robustness over time. The masking effect of sedation as a potential confounder of the circadian rhythms of CBT, PM, and GE was explored, and circadian rhythm profiles of CBT of pigs in the ICU setting were compared with those of the same pigs in the ambulatory setting. ^ Results: All pigs had significant rhythms in CBT, respiratory rate, and peripheral oxygen saturation across ICU data sets. Healthier pigs had more robust rhythms of study variables over time. Sedation did not appear to mask the circadian rhythms of CBT, PM, and GE. The circadian rhythm of CBT was less robust in the ICU setting than in the ambulatory setting. ^ Conclusions: Individual subject observations provided preliminary evidence that robustness of rhythms varies with subject acuity. Comparison of profiles of circadian rhythms among ICU subjects with similar acuity and disease processes is warranted to determine if the profiles in the present study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from mechanical ventilation. ^

AtGRP7, a nuclear RNA-binding protein as a component of a circadian-regulated negative feedback loop in Arabidopsis thaliana

The endogenous clock that drives circadian rhythms is thought to communicate temporal information within the cell via cycling downstream transcripts. A transcript encoding a glycine-rich RNA-binding protein, Atgrp7, in Arabidopsis thaliana undergoes circadian oscillations with peak levels in the evening. The AtGRP7 protein also cycles with a time delay so that Atgrp7 transcript levels decline when the AtGRP7 protein accumulates to high levels. After AtGRP7 protein concentration has fallen to trough levels, Atgrp7 transcript starts to reaccumulate. Overexpression of AtGRP7 in transgenic Arabidopsis plants severely depresses cycling of the endogenous Atgrp7 transcript. These data establish both transcript and protein as components of a negative feedback circuit capable of generating a stable oscillation. AtGRP7 overexpression also depresses the oscillation of the circadian-regulated transcript encoding the related RNA-binding protein AtGRP8 but does not affect the oscillation of transcripts such as cab or catalase mRNAs. We propose that the AtGRP7 autoregulatory loop represents a “slave” oscillator in Arabidopsis that receives temporal information from a central “master” oscillator, conserves the rhythmicity by negative feedback, and transduces it to the output pathway by regulating a subset of clock-controlled transcripts.

The circadian clock controls the expression pattern of the circadian input photoreceptor, phytochrome B

Developmental and physiological responses are regulated by light throughout the entire life cycle of higher plants. To sense changes in the light environment, plants have developed various photoreceptors, including the red/far-red light-absorbing phytochromes and blue light-absorbing cryptochromes. A wide variety of physiological responses, including most light responses, also are modulated by circadian rhythms that are generated by an endogenous oscillator, the circadian clock. To provide information on local time, circadian clocks are synchronized and entrained by environmental time cues, of which light is among the most important. Light-driven entrainment of the Arabidopsis circadian clock has been shown to be mediated by phytochrome A (phyA), phytochrome B (phyB), and cryptochromes 1 and 2, thus affirming the roles of these photoreceptors as input regulators to the plant circadian clock. Here we show that the expression of PHYB∷LUC reporter genes containing the promoter and 5′ untranslated region of the tobacco NtPHYB1 or Arabidopsis AtPHYB genes fused to the luciferase (LUC) gene exhibit robust circadian oscillations in transgenic plants. We demonstrate that the abundance of PHYB RNA retains this circadian regulation and use a PHYB∷Luc fusion protein to show that the rate of PHYB synthesis is also rhythmic. The abundance of bulk PHYB protein, however, exhibits only weak circadian rhythmicity, if any. These data suggest that photoreceptor gene expression patterns may be significant in the daily regulation of plant physiology and indicate an unexpectedly intimate relationship between the components of the input pathway and the putative circadian clock mechanism in higher plants.

Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock

Interlocked feedback loops may represent a common feature among the regulatory systems controlling circadian rhythms. The Neurospora circadian feedback loops involve white collar-1 (wc-1), wc-2, and frequency (frq) genes. We show that WC-1 and WC-2 proteins activate the transcription of frq gene, whereas FRQ protein plays dual roles: repressing its own transcription, probably by interacting with the WC-1/WC-2 complex, and activating the expression of both WC proteins. Thus, they form two interlocked feedback loops: one negative and one positive. We establish the physiological significance of the interlocked positive feedback loops by showing that the levels of WC-1 and WC-2 determine the robustness and stability of the clock. Our data demonstrate that with WC-1 being the limiting factor in the WC-1/WC-2 complex, the greater the levels of WC-1 and WC-2, the higher the level of the FRQ oscillation and the more robust the overt rhythms. Our data also show that, despite considerable changes in the levels of WC-1, WC-2, and FRQ, the period of the clock has been limited to a small range, suggesting that the interlocked circadian feedback loops are also important for determining the circadian period length of the clock.

Circadian gating of cell division in cyanobacteria growing with average doubling times of less than 24 hours.

To ascertain whether the circadian oscillator in the prokaryotic cyanobacterium Synechococcus PCC 7942 regulates the timing of cell division in rapidly growing cultures, we measured the rate of cell division, DNA content, cell size, and gene expression (monitored by luminescence of the PpsbAI::luxAB reporter) in cultures that were continuously diluted to maintain an approximately equal cell density. We found that populations dividing at rates as rapid as once per 10 h manifest circadian gating of cell division, since phases in which cell division slows or stops recur with a circadian periodicity. The data clearly show that Synechococcus cells growing with doubling times that are considerably faster than once per 24 h nonetheless express robust circadian rhythms of cell division and gene expression. Apparently Synechococcus cells are able to simultaneously sustain two timing circuits that express significantly different periods.

Ethobehavioral Studies of Fear, Sex, and Biological Rhythms

Thesis (Ph.D.)--University of Washington, 2016-06

The molecular basis of temperature compensation in the Arabidopsis circadian clock

Circadian clocks maintain robust and accurate timing over a broad range of physiological temperatures, a characteristic termed temperature compensation. In Arabidopsis thaliana, ambient temperature affects the rhythmic accumulation of transcripts encoding the clock components TIMING OF CAB EXPRESSION1 (TOC1), GIGANTEA (GI), and the partially redundant genes CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). The amplitude and peak levels increase for TOC1 and GI RNA rhythms as the temperature increases (from 17 to 27 degrees C), whereas they decrease for LHY. However, as temperatures decrease ( from 17 to 12 degrees C), CCA1 and LHY RNA rhythms increase in amplitude and peak expression level. At 27 degrees C, a dynamic balance between GI and LHY allows temperature compensation in wild-type plants, but circadian function is impaired in Ihy and gi mutant plants. However, at 12 degrees C, CCA1 has more effect on the buffering mechanism than LHY, as the cca1 and gi mutations impair circadian rhythms more than Ihy at the lower temperature. At 17 degrees C, GI is apparently dispensable for free-running circadian rhythms, although partial GI function can affect circadian period. Numerical simulations using the interlocking-loop model show that balancing LHY/CCA1 function against GI and other evening-expressed genes can largely account for temperature compensation in wild-type plants and the temperature-specific phenotypes of gi mutants.

Circadian gene variants and susceptibility to type 2 diabetes:a pilot study

Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants.

Circadian rhythm disruption and post-surgical recovery

Circadian rhythms, patterns of each twenty-four hour period, are found in most bodily functions. The biological cycles of between 20 and 28 hours have a profound effect on an individual's mood, level of performance, and physical well being. Loss of synchrony of these biological rhythms occurs with hospitalization, surgery and anesthesia. The purpose of this comparative, correlational study was to determine the effects of circadian rhythm disruption in post-surgical recovery. Data were collected during the pre-operative and post-operative periods in the following indices: body temperature, blood pressure, heart rate, urine cortisol level and locomotor activity. The data were analyzed by cosinor analysis for evidence of circadian rhythmicity and disruptions throughout the six day study period which encompassed two days pre-operatively, two days post-operatively, and two days after hospital discharge. The sample consisted of five men and five women who served as their own pre-surgical control. The surgical procedures were varied. Findings showed evidence of circadian disruptions in all subjects post-operatively, lending support for the hypotheses.

Cross-talk and regulatory interactions between the essential response regulator RpaB and cyanobacterial circadian clock output

The response regulator RpaB (regulator of phycobilisome associated B), part of an essential two-component system conserved in cyanobacteria that responds to multiple environmental signals, has recently been implicated in the control of cell dimensions and of circadian rhythms of gene expression in the model cyanobacterium Synechococcus elongatus PCC 7942. However, little is known of the molecular mechanisms that underlie RpaB functions. In this study we show that the regulation of phenotypes by RpaB is intimately connected with the activity of RpaA (regulator of phycobilisome associated A), the master regulator of circadian transcription patterns. RpaB affects RpaA activity both through control of gene expression, a function requiring an intact effector domain, and via altering RpaA phosphorylation, a function mediated through the N-terminal receiver domain of RpaB. Thus, both phosphorylation cross-talk and coregulation of target genes play a role in the genetic interactions between the RpaA and RpaB pathways. In addition, RpaB∼P levels appear critical for survival under light:dark cycles, conditions in which RpaB phosphorylation is environmentally driven independent of the circadian clock. We propose that the complex regulatory interactions between the essential and environmentally sensitive NblS-RpaB system and the SasA-RpaA clock output system integrate relevant extra- and intracellular signals to the circadian clock.

Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk

Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiological regulators of host circadian gene expression. We utilised a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equivalent tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addition oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and associated genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression. Disruptions to circadian rhythm in mice and humans have been associated with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiological regulators of host circadian gene expression. We utilised a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equivalent tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addition oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and associated genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression.

Circadian Phase Control - Genetic Algorithm and Non-linear Control Approach

This paper deals with the phase control for Neurospora circadian rhythm. The nonlinear control, given by tuning the parameters (considered as controlled variables) in Neurospora dynamical model, allows the circadian rhythms tracking a reference one. When there are many parameters (e.g. 3 parameters in this paper) and their values are unknown, the adaptive control law reveals its weakness since the parameters converging and control objective must be guaranteed at the same time. We show that this problem can be solved using the genetic algorithm for parameters estimation. Once the unknown parameters are known, the phase control is performed by chaos synchronization technique.

Variabilidade da frequencia cardiaca em trabalhadores em turnos

Universidade Estadual de Campinas . Faculdade de Educação Física

Caracterização e distribuição de cronotipos no sul do Brasil: diferenças de gênero e estação de nascimento

OBJETIVO: Investigar a tipologia circadiana e as diferenças de gênero em universitários do sul do Brasil. MÉTODOS: Voluntários (736) de 17 a 49 anos preencheram a versão brasileira do Questionário de Cronotipo (QC), tradução do Morningness-eveningness Questionnaire (MEQ) de Horne e Östberg. Medidas de tendência central e dispersão e curva de distribuição dos escores do QC (Kolmogorov-Smirnov) foram calculadas de acordo com gênero (teste t de Student), idade, estação de nascimento e desconforto com o horário de verão (qui-quadrado). RESULTADOS: Foram incluídos 648 indivíduos (36% homens, 64% mulheres), com perdas de 12% por questionários incorretos. A distribuição dos escores do QC evidenciou uma curva normal (amplitude = 18-77; média = 46,6; desvio-padrão = 10,8). Nesta amostra, 32% foram vespertinos, 54% intermediários e 14% matutinos. As médias do QC foram significativamente diferentes (p = 0,003): homens (44,9 ± 10,8) comparados com mulheres (47,5 ± 10,7) e 70% dos que nasceram na primavera e no verão foram vespertinos (p = 0,015), sem associação gênero-estação do ano. CONCLUSÃO: Homens e nascidos na primavera-verão evidenciaram preferência pela vespertinidade, não havendo diferença de gênero com relação à estação de nascimento. Nossos resultados estão de acordo com estudos realizados no hemisfério norte que mostraram, também, uma associação entre a estação de nascimento e o cronotipo.

Internal and external time conflicts in adolescents: sleep characteristics and interventions

Daytime fatigue and lack of sleep seem to increase throughout adolescent years. Several environmental, psychological, and biological factors have been associated with the development of sleep across adolescence. The aim of the present article is to summarize these factors and to give examples of various outcomes in sleep patterns among adolescents studied in different cultural settings. It is obvious from earlier work that many adolescents have displaced circadian rhythms and lack of adaptation to school hours due to an early school start or additional burdens for work. Several interventions have aimed to help the adaptation process by supporting sleep processes and changing scheduling, in this way promoting classroom alertness. In summary, adolescents worldwide shorten their sleep due to schoolwork hours and additional work, especially by disturbing their sleep due to circadian misalignment