B-type natriuretic peptide is a determinant of the nocturnal increase in blood pressure independently of arterial hypertrophy and hypoxia.

PubMed

Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro; Ohyagi, Yasumasa; Matsuda, Fumihiko; Kohara, Katsuhiko

2016-12-01

Loss of the nocturnal blood pressure (BP) drop is a risk factor for cardiovascular outcomes. However, clinical parameters that predispose to changes in nocturnal BP are currently uncertain. Given the possible involvement of salt sensitivity in nocturnal BP levels, we investigated a hypothesized association between plasma B-type natriuretic peptide (BNP) levels - a marker of body fluid retention - and nocturnal BP in a general population. Study participants were 1020 general individuals. Participants were divided into four groups (riser, nondipper, dipper, and extreme dipper) by their percentage changes in nocturnal SBP measured using an ambulatory BP monitor. Plasma BNP levels were positively associated with circadian BP change (β = 0.162, P < 0.001) independently of carotid hypertrophy (β = 0.133, P < 0.001), and awake heart rate (β = -0.102, P = 0.001) and SBP (β = -0.246, P < 0.001). Risers showed 1.6 times higher BNP levels than dippers, whereas oxygen desaturation during sleep was frequently observed in nondippers. Results of multinomial logistic regression analysis indicated that BNP level was a significant determinant for the riser pattern [odds ratio (OR) 1.27 (BNP 10 pg/ml), P < 0.001], whereas oxygen desaturation was specifically associated with the nondipping pattern (OR 1.04, P = 0.001). When participants were subdivided by BNP level, risers were more frequent in the high BNP subgroup (19.5%) than in the low BNP subgroup (6.7%) (OR 3.39, P < 0.001). A slight increase in plasma BNP level was independently associated with rising nocturnal BP. Our results may help to understand the pathophysiology of circadian BP variation, and be a clue to identify individuals who require careful BP monitoring.

Circadian rhythm of urinary potassium excretion during treatment with an angiotensin receptor blocker.

PubMed

Ogiyama, Yoshiaki; Miura, Toshiyuki; Watanabe, Shuichi; Fuwa, Daisuke; Tomonari, Tatsuya; Ota, Keisuke; Kato, Yoko; Ichikawa, Tadashi; Shirasawa, Yuichi; Ito, Akinori; Yoshida, Atsuhiro; Fukuda, Michio; Kimura, Genjiro

2014-12-01

We have reported that the circadian rhythm of urinary potassium excretion (U(K)V) is determined by the rhythm of urinary sodium excretion (U(Na)V) in patients with chronic kidney disease (CKD). We also reported that treatment with an angiotensin receptor blocker (ARB) increased the U(Na)V during the daytime, and restored the non-dipper blood pressure (BP) rhythm into a dipper pattern. However, the circadian rhythm of U(K)V during ARB treatment has not been reported. Circadian rhythms of U(Na)V and U(K)V were examined in 44 patients with CKD undergoing treatment with ARB. Whole-day U(Na)V was not altered by ARB whereas whole-day U(K)V decreased. Even during the ARB treatment, the significant relationship persisted between the night/day ratios of U(Na)V and U(K)V (r=0.56, p<0.0001). Whole-day U(K)V/U(Na)V ratio (p=0.0007) and trans-tubular potassium concentration gradient (p=0.002) were attenuated but their night/day ratios remained unchanged. The change in the night/day U(K)V ratio correlated directly with the change in night/day U(Na)V ratio (F=20.4) rather than with the changes in aldosterone, BP or creatinine clearance. The circadian rhythm of U(K)V was determined by the rhythm of UNaV even during ARB treatment. Changes in the circadian U(K)V rhythm were not determined by aldosterone but by U(Na)V. © The Author(s) 2013.

Cardioprotective effects of SGLT2 inhibitors are possibly associated with normalization of the circadian rhythm of blood pressure.

PubMed

Rahman, Asadur; Hitomi, Hirofumi; Nishiyama, Akira

2017-06-01

Improvement in cardiovascular (CV) morbidity and mortality in the EMPA-REG OUTCOME study provides new insight into the therapeutic use of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Although SGLT2 inhibitors have several pleiotropic effects, the underlying mechanism responsible for their cardioprotective effects remains undetermined. In this regard, the absence of a nocturnal fall in blood pressure (BP), that is, non-dipping BP, is a common phenomenon in type 2 diabetes and has a crucial role in the pathogenesis of CV morbidity and mortality. In most clinical trials, SGLT2 inhibitors reduce both systolic BP (~3-5 mm Hg) and diastolic BP (~2 mm Hg) in patients with type 2 diabetes. In addition, recent clinical and animal studies have revealed that SGLT2 inhibitors enable the change in BP circadian rhythm from a non-dipper to a dipper type, which is possibly associated with the improvement in CV outcomes in patients with type 2 diabetes. In this review, recent data on the effect of SGLT2 inhibitors on the circadian rhythm of BP will be summarized. The possible underlying mechanisms responsible for the SGLT2 inhibitor-induced improvement in the circadian rhythm of BP will also be discussed.

Cugini's syndrome in statu nascendi. Oratio contra morem prevalentem et pro chronobiologica ratione ad pressione sanguinis curandam. A plea against the prevailing custom and in favor of a chronobiological approach to treating blood pressure.

PubMed

Cornélissen, G; Halberg, F; Beaty, L; Kumagai, Y; Halberg, E; Halberg, J; Lee, J; Schwartzkopff, O; Otsuka, K

2009-01-01

An increase in the circadian amplitude (A) of blood pressure (BP) had been reported to precede a rise in the circadian BP average (MESOR, M), as pre-hypertension in the stroke-prone Okamoto rat. In humans, children with a positive family history of high BP and/or related cardiovascular disease had, on average, a larger BP-A than children with a negative family history, and an elevated BP-A was associated with intermediate values of the left ventricular mass index (LVMI), whereas an elevation in BP-M was only observed for larger LVMI values. Against this background, with 24-hour ambulatory monitoring (ABPM) interpreted chronobiologically, Pietro Cugini (University La Sapienza of Rome, Italy) has reported an elevation of both the circadian BP-M and BP-A as occurring with a minimal change (hypertensive) retinopathy. He determined by cosinor the extent of predictable BP change within a day as BP-2A, estimated by the least squares fit of a 24-hour cosine curve to the data. As compared to controls without retinopathy, he found a retinal end-organ involvement associated with average systolic (S) / diastolic (D) BP-Ms of 124/76 vs. 112/72 mmHg, with corresponding SBP/DBP-As of 12/10 vs. 8/7 mmHg. We refer to "Cugini's syndrome", suggesting the need for clarification, preferably in longitudinal studies, of any generalizable sequence in end-organ involvement, that may occur in the course of the development of some human Vascular Variability Disorders (VVDs) of unknown etiology, that include an elevation of the circadian BP-A and/or BP-M, concomitantly or separately in a sequence with the BP-A increase preceding that in BP-M, as in models of high BP in the rat or vice versa. Seven-day half-hourly or hourly around-the-clock monitoring of BP and HR variability interpreted chronobiologically, C-ABPM, as a minimum, is recommended for routine medical care to detect VVDs consisting of 1. MESOR-hypertension, MH; 2. Circadian Hyper-Amplitude-Tension, CHAT (BP overswing); 3. odd timing of the circadian rhythm of BP but not that of HR; 4. above-threshold pulse pressure; and/or 5. below-threshold HR variability. All conditions are best determined by 24-hour/7-day or, when abnormality is detected, longer C-ABPM. Eventually, all conditions will need to be assessed in the light of reference values from gender- and age-matched peers, as is now the case for the fi rst three VVDs listed above. When C-ABPM is not practicable, a 7-day series of 3-hourly manual self-measurements during waking (and one measurement about mid-sleep) (C-MBPM) is recommended. When continuous monitoring becomes possible, as it is within the state of the science, detecting Cugini's syndrome will also become possible with the clarification as to whether any change in BP-M and/or BP-A occurs concomitantly or sequentially, with changes in BP-A anticipated to precede changes in BP-M.

Circadian rhythm of blood pressure and the renin-angiotensin system in the kidney.

PubMed

Ohashi, Naro; Isobe, Shinsuke; Ishigaki, Sayaka; Yasuda, Hideo

2017-05-01

Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD. Moreover, urinary AGT levels of the night-to-day (N/D) ratio of urinary AGT were positively correlated with the levels of N/D of urinary protein, albumin excretion and BP. In addition, animal studies have demonstrated that the expression of intrarenal RAS components, such as AGT, angiotensin II (AngII) and AngII type 1 receptor proteins, increased and peaked at the same time as BP and urinary protein excretion during the resting phase, and the amplitude of the oscillations of these proteins was augmented in a chronic progressive nephritis animal compared with a control. Thus, the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which both are associated with diurnal variations in BP. It is possible that augmented glomerular permeability increases AGT excretion levels into the tubular lumen and that circadian fluctuation of glomerular permeability influences the circadian rhythm of the intrarenal RAS.

Rotigotine Improves Abnormal Circadian Rhythm of Blood Pressure in Parkinson's Disease.

PubMed

Oka, Hisayoshi; Nakahara, Atuso; Umehara, Tadashi

2018-05-15

Cardiovascular autonomic failure is commonly associated with Parkinson's disease (PD), affecting the daily lives of patients. Rotigotine was recently reported not to influence cardiovascular autonomic responses in contrast to other dopaminergic drugs. The effect of rotigotine on daily blood pressure (BP) fluctuations might reflect autonomic failure in patients with PD. Twenty-five PD patients who were receiving rotigotine and 12 patients not receiving rotigotine were recruited. Systolic BP during the daytime and nighttime was measured by 24-h BP monitoring at an interval of 2 years. The patients were divided into 3 groups according to the BP fluctuation type: dippers (nocturnal fall in BP ≥10%), non-dippers (0-10%), and risers (< 0%). The time course of BP was compared between the patients given rotigotine and those not given rotigotine. Among the 25 patients who received rotigotine, the BP type worsened in 2 patients, was unchanged in 16 patients, and improved in 7 patients. Among the 12 patients who were not receiving rotigotine, the BP type worsened in 5 patients, was unchanged in 4 patients, and improved only in 3 patients (p = 0.042). Rotigotine improves the abnormal circadian rhythm of BP in patients with PD. Rotigotine was suggested to have favorable effects on cardiovascular autonomic responses and circadian rhythm in patients with PD. © 2018 S. Karger AG, Basel.

Prevalence of hypertension and circadian blood pressure variations in patients with obstructive sleep apnoea-hypopnoea syndrome.

PubMed

Wang, Yan; Li, Caili; Feng, Liting; Feng, Jing; Cao, Jie; Chen, Baoyuan

2014-06-01

To investigate the prevalence of hypertension and circadian blood pressure (BP) variations in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Patients referred to a sleep clinic underwent polysomnography with measurement of BP at four time points. They were classified into four groups (control, and mild, moderate or severe sleep apnoea) using the apnoea-hypopnoea index (AHI). Circadian variation was assessed using night-time to daytime mean BP (R(N/D)) and morning to evening mean BP (R(M/E)) ratios. Hypertension was significantly more common in patients with OSAHS (50.5%) than in controls (30.4%). AHI was positively correlated with hypertension after controlling for related confounders. Mean BP values at all four time points rose with increasing AHI. The increase in night-time and morning values was more pronounced than the increase in daytime and evening values in patients with OSAHS, resulting in loss of the normal BP diurnal rhythm. The R(N/D) and R(M/E) ratios increased with increasing AHI. Daytime BP was significantly correlated with AHI and the lowest oxygen saturation value. OSAHS was shown to be an independent risk factor for hypertension. It was also associated with loss of the normal BP diurnal rhythm. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Riser Blood Pressure Pattern Is Associated With Mild Cognitive Impairment in Heart Failure Patients.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Nishimura, Yoshioki; Hoshide, Satoshi; Kario, Kazuomi

2016-02-01

The riser pattern, an abnormal blood pressure (BP) rhythm in which sleep BP exceeds awake BP, is a predictor of future stroke events. Although the riser pattern is caused by autonomic dysfunction, its significance in heart failure (HF) patients is not established. HF patients often suffered from cognitive impairment (CI), but the relationship between riser pattern and CI is not clearly understood. We tested the hypothesis that the riser pattern is associated with mild CI, a form of brain damage that could develop to dementia. We performed Mini-Mental State Examination (MMSE), ambulatory BP monitoring (ABPM), echocardiography, and blood tests in 444 HF patients just before leaving hospitals. Mild CI, a measure of cognitive function, was defined as the score <26. The mean age of the patients was 68±13 years; 61.5% were male; 22.5% were riser pattern. The MMSE score was significantly lower in the Riser group than in the Non-dipper and Dipper group (23±4 vs. 25±5, 26±4, respectively, P < 0.01). In multivariable logistic regression analysis, a riser pattern was significantly associated with mild CI (odds ratio 2.38, 95% confidence intervals 1.29-4.42, P < 0.01) after adjusting for significant covariates. The riser pattern was associated with mild CI in HF patients. An abnormal circadian BP rhythm in HF patients is clinically significant as a potential indicator of subclinical brain damage. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Renal Denervation vs. Spironolactone in Resistant Hypertension: Effects on Circadian Patterns and Blood Pressure Variability.

PubMed

de la Sierra, Alejandro; Pareja, Julia; Armario, Pedro; Barrera, Ángela; Yun, Sergi; Vázquez, Susana; Sans, Laia; Pascual, Julio; Oliveras, Anna

2017-01-01

Sympathetic renal denervation (SRD) has been proposed as a therapeutic alternative for patients with resistant hypertension not controlled on pharmacological therapy. Two studies have suggested an effect of SRD in reducing short-term blood pressure variability (BPV). However, this has not been addressed in a randomized comparative trial. We aimed to compare the effects of spironolactone and SRD on circadian BP and BPV. This is a post-hoc analysis of a randomized trial in 24 true resistant hypertensive patients (15 men, 9 women; mean age 64 years) comparing 50mg of spironolactone (n = 13) vs. SRD (n = 11) on 24-hour BP. We report here the comparative effects on daytime (8 am-10 pm) and nighttime (0 am-6 am) BP, night-to-day ratios and BP and heart rate variabilities (SD and coefficient of variation of 24-hour, day and night, as well as weighted SD and average real variability (ARV)). Spironolactone was more effective than SRD in reducing daytime systolic (P = 0.006), daytime diastolic (P = 0.006), and nighttime systolic (P = 0.050) BP. No differences were observed in the night-to-day ratios. In contrast, SRD-reduced diastolic BPV (24 hours, daytime, nighttime, weighted, and ARV; all P < 0.05) with respect to spironolactone, without significant differences in systolic BPV. Spironolactone is more effective than SRD in reducing ambulatory BP. However, BPV is significantly more reduced with SRD. This effect could be important in terms of potential prevention beyond BP reduction and deserves further investigation. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

NASA Astrophysics Data System (ADS)

Qin, Chuanjie; Shao, Ting

2015-05-01

The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene ( Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%-88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.

Rationale, study design, and implementation of the ACS1 study: effect of azilsartan on circadian and sleep blood pressure as compared with amlodipine.

PubMed

Kario, Kazuomi; Hoshide, Satoshi

2014-06-01

The ACS1 (Azilsartan Circadian and Sleep Pressure - the first study) is a multicenter, randomized, open-label, two parallel-group study carried out to investigate the efficacy of an 8-week oral treatment with azilsartan 20 mg in comparison with amlodipine 5 mg. The patients with stage I or II primary hypertension will be randomly assigned to either an azilsartan group (n=350) or an amlodipine group (n=350). The primary endpoint is a change in nocturnal systolic blood pressure (BP) as measured by ambulatory BP monitoring at the end of follow-up relative to the baseline level during the run-in period. In addition, we will carry out the same analysis after dividing four different nocturnal BP dipping statuses (extreme-dippers, dippers, nondipper, and risers). The findings of this study will help in establishing an appropriate antihypertensive treatment for hypertensive patients with a disrupted circadian BP rhythm.

Rationale, study design, and implementation of the ACS1 study: effect of azilsartan on circadian and sleep blood pressure as compared with amlodipine

PubMed Central

Hoshide, Satoshi

2014-01-01

Objective The ACS1 (Azilsartan Circadian and Sleep Pressure – the first study) is a multicenter, randomized, open-label, two parallel-group study carried out to investigate the efficacy of an 8-week oral treatment with azilsartan 20 mg in comparison with amlodipine 5 mg. Materials and methods The patients with stage I or II primary hypertension will be randomly assigned to either an azilsartan group (n=350) or an amlodipine group (n=350). The primary endpoint is a change in nocturnal systolic blood pressure (BP) as measured by ambulatory BP monitoring at the end of follow-up relative to the baseline level during the run-in period. In addition, we will carry out the same analysis after dividing four different nocturnal BP dipping statuses (extreme-dippers, dippers, nondipper, and risers). Conclusion The findings of this study will help in establishing an appropriate antihypertensive treatment for hypertensive patients with a disrupted circadian BP rhythm. PMID:24637789

Abnormal Circadian Blood Pressure Profile as a Prognostic Marker in Patients with Nonischemic Dilated Cardiomyopathy.

PubMed

Sawamura, Akinori; Okumura, Takahiro; Takeshita, Kyosuke; Watanabe, Naoki; Kano, Naoaki; Mori, Hiroaki; Fukaya, Kenji; Morimoto, Ryota; Hirashiki, Akihiro; Bando, Yasuko Kureishi; Murohara, Toyoaki

An abnormal circadian blood pressure (BP) profile is considered a risk factor for cardiovascular disease. However, its significance in heart failure patients with nonischemic etiology is unknown. Herein, we investigated the prognostic value of a circadian BP profile in patients with nonischemic dilated cardiomyopathy (NIDCM). We enrolled 114 NIDCM patients (76 males, mean age 53.1 years). The percent nighttime BP fall (%NBPF) was defined using ambulatory BP monitoring as a percent decrease in mean systolic BP in nighttime from daytime. All patients were divided into three groups: dipper (%NBPF ≥10), non-dipper (0 ≤ %NBPF < 10), and riser (%NBPF <0). Riser patients had the highest serum creatinine levels (dipper, 0.78 ± 0.20 mg/dl; non-dipper, 0.85 ± 0.21 mg/dl; riser, 0.99 ± 0.23 mg/dl; p = 0.006). In survival analysis, riser patients had the highest cumulative cardiac-related deaths (log-rank, p = 0.001), which was an independent predictor of cardiac-related deaths (hazard ratio, 12.6; 95% confidence interval, 1.76-253; p = 0.01). Multivariate analysis revealed that the norepinephrine level at 24-hour collected urine (24 h U-NE) and the serum creatinine level were independent determinants of %NBPF (adjusted R2 = 0.20; 24 h U-NE, p = 0.0001; serum creatinine, p = 0.04). The riser profile was associated with poor prognosis of NIDCM, which may reflect impaired sympathetic nervous system activity. Evaluating the circadian BP profile may be useful for risk stratification in NIDCM patients. © 2016 S. Karger AG, Basel.

Separate aftereffects of morning and evening exercise on ambulatory blood pressure in prehypertensive men.

PubMed

Brito, Leandro C; Rezende, Rafael A; Mendes, Caroline; Silva-Junior, Natan D; Tinucci, Taís; Cipolla-Neto, José; de Moraes Forjaz, Cláudia L

2018-01-01

Clinic postexercise hypotension (PEH) is different after aerobic exercise performed in the morning and in the evening. Thus, ambulatory PEH should also differ after exercises conducted at different times of day. However, because of the circadian pattern of blood pressure (BP), ambulatory PEH should be assessed considering a control condition. Thus, this study was designed to verify the effects of morning and evening exercises on postexercise ambulatory BP averages and circadian parameters by comparing responses obtained at each time of day after an exercise and a control session. Thirteen prehypertensive men underwent four sessions (randomized order): two in the morning (9 am) and two in the evening (6:30 pm). At each time of day, a control (C) and an exercise (E: cycle ergometer 45 min, 50% VO2peak) sessions were performed. After the sessions, an ambulatory BP and heart rate (HR) monitoring was started for 24 h. Paired t-test or Wilcoxon Signed Rank Test were used to compare the E and the C sessions at each time of day. In the morning, 24 h, daytime and nighttime HR were higher after the E than the C session. In the evening, nighttime systolic BP (116±11 vs. 120±10 mmHg, P=0.04) and rate pressure product (7981±1294 vs. 8583±1523 mmHg.bpm, P=0.04), as well as MESOR (128±11 vs. 130±10 mmHg, P=0.03) were lower in the E than the C session. In prehypertensive men, morning exercise increased ambulatory HR, while evening exercise decreased nighttime BP and cardiac work, reducing the MESOR of systolic BP.

[Metabolic syndrome and bipolar disorder: Is sleep the missing link?

PubMed

Brochard, H; Boudebesse, C; Henry, C; Godin, O; Leboyer, M; Étain, B

2016-12-01

To examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP). A systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords "metabolic syndrome", "obesity", "leptin" and "circadian disorders", "sleeping disorders" and cross-referencing them with "bipolar disorder". The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome. Forty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients' relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation. Circadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

mRNA levels of circadian clock components Bmal1 and Per2 alter independently from dosing time-dependent efficacy of combination treatment with valsartan and amlodipine in spontaneously hypertensive rats.

PubMed

Potucek, Peter; Radik, Michal; Doka, Gabriel; Kralova, Eva; Krenek, Peter; Klimas, Jan

2017-01-01

Chronopharmacological effects of antihypertensives play a role in the outcome of hypertension therapy. However, studies produce contradictory findings when combination of valsartan plus amlodipine (VA) is applied. Here, we hypothesized different efficacy of morning versus evening dosing of VA in spontaneously hypertensive rats (SHR) and the involvement of circadian clock genes Bmal1 and Per2. We tested the therapy outcome in short-term and also long-term settings. SHRs aged between 8 and 10 weeks were treated with 10 mg/kg of valsartan and 4 mg/kg of amlodipine, either in the morning or in the evening with treatment duration 1 or 6 weeks and compared with parallel placebo groups. After short-term treatment, only morning dosing resulted in significant blood pressure (BP) control (measured by tail-cuff method) when compared to placebo, while after long-term treatment, both dosing groups gained similar superior results in BP control against placebo. However, mRNA levels of Bmal1 and Per2 (measured by RT-PCR) exhibited an independent pattern, with similar alterations in left and right ventricle, kidney as well as in aorta predominantly in groups with evening dosing in both, short-term and also long-term settings. This was accompanied by increased cardiac mRNA expression of plasminogen activator inhibitor-1. In summary, morning dosing proved to be advantageous due to earlier onset of antihypertensive action; however, long-term treatment was demonstrated to be effective regardless of administration time. Our findings also suggest that combination of VA may serve as an independent modulator of circadian clock and might influence disease progression beyond the primary BP lowering effect.

The relationship between red blood cell distribution width and blood pressure abnormal dipping in patients with essential hypertension: a cross-sectional study.

PubMed

Su, Dan; Guo, Qi; Gao, Ya; Han, Jin; Yan, Bin; Peng, Liyuan; Song, Anqi; Zhou, Fuling; Wang, Gang

2016-02-23

To investigate whether red blood cell distribution width (RDW) is associated with the blood pressure (BP) reverse-dipper pattern in patients with hypertension. Cross-sectional study. Single centre. Patients with essential hypertension were included in our study (n=708). The exclusion criteria included age <18 or >90 years, incomplete clinical data, night workers, diagnosis of secondary hypertension, under antihypertensive treatment, intolerance for the 24 h ambulatory BP monitoring (ABPM) and BP reading success rate <70%. Physical examination and ABPM were performed for all patients in our study. The value of RDW was measured using an automated haematology analyser. The distribution of RDW in patients with hypertension among different circadian BP pattern groups was analyzed using analysis of variance (ANOVA). Multinomial logistic regression was applied to explore the associations of RDW and other relevant variables with ABPM results. There was significantly increased RDW in reverse dippers (13.52 ± 1.05) than dippers (13.25 ± 0.85) of hypertension (p=0.012). Moreover, multinomial logistic regression analysis showed that RDW (OR 1.325, 95% CI 1.037 to 1.692, p=0.024) and diabetes mellitus (OR 2.286, 95% CI 1.380 to 3.788, p=0.001) were significantly different when comparing the reverse-dipper BP pattern with the dipper pattern. However, there was no difference of RDW between the non-dipper pattern and the reverse-dipper pattern (OR 1.036, 95% CI 0.867 to 1.238, p=0.693). In addition to this, RDW was negatively correlated with the decline rate of nocturnal systolic BP (r=-0.113; p=0.003) and diastolic BP (r=-0.101; p=0.007). Our results suggested that RDW might associate with the abnormal dipper BP patterns of either reverse dipping or non-dipping homogeneously examined with 24 h ABPM. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome.

PubMed

Rahman, Asadur; Kittikulsuth, Wararat; Fujisawa, Yoshihide; Sufiun, Abu; Rafiq, Kazi; Hitomi, Hirofumi; Nakano, Daisuke; Sohara, Eisei; Uchida, Shinichi; Nishiyama, Akira

2016-05-01

Experiments were carried out to investigate whether diuretics (hydrochlorothiazide + furosemide) impact on the effects of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor on glucose metabolism and blood pressure (BP) in metabolic syndrome SHR/NDmcr-cp(+/+) rats (SHRcp). Male 13-week-old SHRcp were treated with: vehicle; the SGLT2-inhibitor luseogliflozin (10 mg/kg per day); diuretics (hydrochlorothiazide; 10 mg/kg/day + furosemide; 5 mg/kg per day); or luseogliflozin + diuretics (n = 5-8 for each group) daily by oral gavage for 5 weeks. BP and glucose metabolism were evaluated by a telemetry system and oral glucose tolerance test, respectively. Vehicle-treated SHRcp developed nondipper type hypertension (dark vs. light-period mean arterial pressure: 148.6 ± 0.7 and 148.0 ± 0.7 mmHg, respectively, P = 0.2) and insulin resistance. Compared with vehicle-treated animals, luseogliflozin-treated rats showed an approximately 4000-fold increase in urinary excretion of glucose and improved glucose metabolism. Luseogliflozin also significantly decreased BP and turned the circadian rhythm of BP from a nondipper to dipper pattern (dark vs. light-period mean arterial pressure: 138.0 ± 1.6 and 132.0 ± 1.3 mmHg, respectively, P < 0.01), which were associated with a significant increase in urinary excretion of sodium. Addition of diuretics did not influence luseogliflozin-induced improvement of glucose metabolism and circadian rhythm of BP in SHRcp. These data suggest that a SGLT2 inhibitor elicits its beneficial effects on glucose metabolism and hypertension in study participants with metabolic syndrome undergoing treatment with diuretics.

Abnormalities in ambulatory blood pressure monitoring in hypertensive patients with diabetes.

PubMed

Gorostidi, Manuel; de la Sierra, Alejandro; González-Albarrán, Olga; Segura, Julián; de la Cruz, Juan J; Vinyoles, Ernest; Llisterri, José L; Aranda, Pedro; Ruilope, Luis M; Banegas, José R

2011-11-01

Our aim was to assess the ambulatory blood pressure monitoring (ABPM) characteristics or patterns in hypertensive patients with diabetes compared with non-diabetic hypertensives. We performed a cross-sectional analysis of a 68,045 patient database from the Spanish Society of Hypertension ABPM Registry, a nation-wide network of >1200 primary-care physicians performing ABPM under standardized conditions in daily practice. We identified 12,600 (18.5%) hypertensive patients with diabetes. When compared with patients without diabetes, diabetic hypertensives exhibited higher systolic blood pressure (BP) levels in every ABPM period (daytime 135.4 vs. 131.8, and nighttime 126.0 vs. 121.0 mm Hg, P<0.001 for both) despite they were receiving more antihypertensive drugs (mean number 1.71 vs. 1.23, P<0.001). Consequently, diabetic patients suffered from lack of control of BP more frequently than non-diabetic subjects particularly during the night (65.5% vs. 57.4%, P<0.001). Prevalence of a non-dipping BP profile (64.2% vs. 51.6%, P<0.001) was higher in diabetic patients. In the other hand, prevalence of 'white-coat' hypertension in diabetic patients was 33.0%. We conclude that there was a remarkably high prevalence of alterations in ABPM in patients with diabetes. Abnormalities in systolic BP, particularly during the night, and in circadian BP pattern could be linked with the excess of BP-related cardiovascular risk of diabetes. A wider use of ABPM in diabetic patients should be considered.

Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology.

PubMed

Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Desevaux, Cyril; Deurinck, Mark; Giraudel, Jérôme M; Danhof, Meindert

2013-11-01

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age. Although observations of time-variant changes in the renin cascade are available in dogs, no detailed chronobiological investigation has been conducted so far. The present studies were designed to explore the circadian variations of plasma renin activity (RA) and urinary aldosterone-to-creatinine ratio (UA:C) in relation to blood pressure (BP), sodium (UNa, UNa,fe), and potassium (UK, UK,fe) renal handling. Data derived from intensive blood and urine sampling, as well as continuous BP monitoring, were collected throughout a 24-h time period, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of day and night observations were compared by parametric statistics. Our results show that variables of the renin cascade, BP, and urinary electrolytes oscillate with significant day-night differences in dogs. An approximately 2-fold (1.6-3.2-fold) change between the average day and night measurements was found for RA (p < 0.001), UA:C (p = 0.01), UK,fe (p = 0.01), and UNa (p = 0.007). Circadian variations in BP, albeit small (less than 10 mm Hg), were statistically significant (p < 0.01) and supported by the model-based analysis. For all variables but UNa and UNa,fe, the levels were higher at night than during the day. The data also indicate that blood pressure oscillates in parallel to the RAAS, such that, as opposed to healthy humans, BP does not drop at night in dogs. The postprandial decrease in RA is assumed to be related to body fluid volume expansion secondary to water and sodium intake, whereas the reduction of UA:C reflects aldosterone-stimulated secretion by the renin-angiotensin II pathway. UNa and UNa,fe peaked in the afternoon, about 7-8 h after food intake, which is consistent with the "impulse-response pattern" of sodium excretion described in previous publications. Finally, UK and UK,fe mirrored aldosterone-mediated potassium secretion in the kidney tubules. To describe the circadian variations of the various variables, two different mathematical representations were applied. A cosine model with a fixed 24-h period was found to fit the periodic variations of RA, UA:C, UK, UK,fe, and BP well, whereas changes in UNa and UNa,fe were best characterized by a surge model. The use of nonlinear mixed effects allowed estimation of population characteristics that can influence the periodicity of the RAAS. Specifically, sodium intake was found to interact with the tonic and the phasic secretion of renin, suggesting that varying feeding time could also impact the chronobiology of the renin cascade.

Perfect 24-h management of hypertension: clinical relevance and perspectives.

PubMed

Kario, K

2017-04-01

Out-of-office blood pressure (BP) measured by home BP monitoring, or ambulatory BP monitoring, was demonstrated to be superior to office BP for the prediction of cardiovascular events. The J-HOP study of a nationwide Japanese cohort demonstrated that morning home BP is the best stroke predictor. In the prospective HONEST study of >21 000 hypertensives, on-treatment morning home BP was shown to be a strong predictor both of future coronary artery disease and stroke events. In subjects whose office BP was maintained at ⩾150 mm Hg, there was no increase in cardiovascular events when their morning systolic BP was well-controlled at <125 mm Hg. Since Asians show greater morning BP surges, it is particularly important for Asians to achieve 'perfect 24-hr BP control,' that is, the 24-h BP level, nocturnal BP dipping and BP variability including morning surge. The morning BP surge and the extremes of disrupted circadian rhythm (riser and extreme dipper patterns) are independent risks for stroke in hypertensives. A morning BP-guided approach is thus the first step toward perfect 24-h BP control, followed by the control of nocturnal hypertension. In the resonance hypothesis, the synergistic resonance of BP variability phenotypes would produce an extraordinary large 'dynamic BP surge' that can trigger a cardiovascular event, especially in high-risk patients with systemic hemodynamic atherothrombotic syndrome, a vicious cycle of exaggerated BP variability and vascular disease. In the future, information and communications technology and artificial intelligence technology with the innovation of wearable continuous surge BP monitoring will contribute to 'anticipation medicine' with the goal of zero cardiovascular events.

Bedtime Blood Pressure Chronotherapy Significantly Improves Hypertension Management.

PubMed

Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Mojón, Artemio; Crespo, Juan J; Ríos, María T; Smolensky, Michael H

2017-10-01

Consistent evidence of numerous studies substantiates the asleep blood pressure (BP) mean derived from ambulatory BP monitoring (ABPM) is both an independent and a stronger predictor of cardiovascular disease (CVD) risk than are daytime clinic BP measurements or the ABPM-determined awake or 24-hour BP means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of 6 different classes and their combinations significantly improves BP control, particularly sleep-time BP, and reduces adverse effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Decadal Cycles in the Human Cardiovascular System

PubMed Central

Halberg, Franz; Cornelissen, Germaine; Sothern, Robert B.; Hillman, Dewayne; Watanabe, Yoshihiko; Haus, Erhard; Schwartzkopff, Othild; Best, William R.

2013-01-01

Seven of the eight authors of this report each performed physiologic self-surveillance, some around the clock for decades. We here document the presence of long cycles (decadals, including circaundecennians) in the time structure of systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR). Because of the non-stationary nature in time and space of these and other physiologic and environmental periodic components that, like the wind, can appear and disappear in a given or other geographic location at one or another time, they have been called “Aeolian”. The nonlinear estimation of the uncertainties of the periods (τs) of two or more variables being compared has been used to determine whether these components are congruent or not, depending on whether their CIs (95% confidence intervals) overlap or not. Among others, congruence has been found for components with τs clustering around 10 years in us and around us. There is a selective assortment among individuals, variables and cycle characteristics (mean and circadian amplitude and acrophase). Apart from basic interest, like other nonphotic solar signatures such as transyears with periods slightly longer than one year or about 33-year Brückner-Egeson-Lockyer (BEL) cycles, about 10-year and longer cycles present in 7 of 7 self-monitoring individuals are of interest in the diagnosis of Vascular Variability Anomalies (VVAs), including MESOR-hypertension, and others. Some of the other VVAs, such as a circadian overswing, i.e., CHAT (Circadian Hyper-Aplitude-Tension), or an excessive pulse pressure, based on repeated 7-day around-the-clock records, can represent a risk of severe cardiovascular events, greater than that of a high BP. The differential diagnosis of physiologic cycles, infradians (components with a τ longer than 28 hours) as well as circadians awaits the collection of reference values for the infradian parameters of the cycles described herein. Just as in stroke-prone spontaneously hypertensive rats during the weeks after weaning CHAT precedes an elevation of the BP MESOR, a decadal overswing seems to precede the occurrence of high BP in two of the subjects here examined. Only around-the-clock monitoring in health for the collection of reference values will allow on their basis the differential diagnosis of the onsets of a circadian versus a circadecadal overswing in BP and the specification whether, and if so, when to initiate hypotensive non-drug or drug treatment. PMID:24860279

Identification, Characterization, and Diel Pattern of Expression of Canonical Clock Genes in Nephrops norvegicus (Crustacea: Decapoda) Eyestalk

PubMed Central

Sbragaglia, Valerio; Lamanna, Francesco; M. Mat, Audrey; Rotllant, Guiomar; Joly, Silvia; Ketmaier, Valerio; de la Iglesia, Horacio O.; Aguzzi, Jacopo

2015-01-01

The Norway lobster, Nephrops norvegicus, is a burrowing decapod with a rhythmic burrow emergence (24 h) governed by the circadian system. It is an important resource for European fisheries and its behavior deeply affects its availability. The current knowledge of Nephrops circadian biology is phenomenological as it is currently the case for almost all crustaceans. In attempt to elucidate the putative molecular mechanisms underlying circadian gene regulation in Nephrops, we used a transcriptomics approach on cDNA extracted from the eyestalk, a structure playing a crucial role in controlling behavior of decapods. We studied 14 male lobsters under 12–12 light-darkness blue light cycle. We used the Hiseq 2000 Illumina platform to sequence two eyestalk libraries (under light and darkness conditions) obtaining about 90 millions 100-bp paired-end reads. Trinity was used for the de novo reconstruction of transcriptomes; the size at which half of all assembled bases reside in contigs (N50) was equal to 1796 (light) and 2055 (darkness). We found a list of candidate clock genes and focused our attention on canonical ones: timeless, period, clock and bmal1. The cloning of assembled fragments validated Trinity outputs. The putative Nephrops clock genes showed high levels of identity (blastx on NCBI) with known crustacean clock gene homologs such as Eurydice pulchra (period: 47%, timeless: 59%, bmal1: 79%) and Macrobrachium rosenbergii (clock: 100%). We also found a vertebrate-like cryptochrome 2. RT-qPCR showed that only timeless had a robust diel pattern of expression. Our data are in accordance with the current knowledge of the crustacean circadian clock, reinforcing the idea that the molecular clockwork of this group shows some differences with the established model in Drosophila melanogaster. PMID:26524198

Blood pressure response to CPAP treatment in subjects with obstructive sleep apnoea: the predictive value of 24-h ambulatory blood pressure monitoring.

PubMed

Castro-Grattoni, Anabel L; Torres, Gerard; Martínez-Alonso, Montserrat; Barbé, Ferran; Turino, Cecilia; Sánchez-de-la-Torre, Alicia; Cortijo, Anunciacion; Duran-Cantolla, Joaquin; Egea, Carlos; Cao, Gonzalo; Sánchez-de-la-Torre, Manuel

2017-10-01

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h -1 ) were included; 28.4% had hypertension. 62 patients finished the study, and 60 were analysed. The daytime diastolic BP (-2 mmHg) and norepinephrine (-109.5 nmol·day -1 ) were reduced after CPAP, but no changes in the 24-h BP, night-time BP, dopamine, epinephrine, CRP, leptin or adiponectin were detected. The nocturnal normotension was associated with an increased night-time-BP (+4 mmHg) after CPAP, whereas nocturnal hypertension was associated with a reduction of 24-h BP (-3 mmHg). A multivariate linear regression model showed differential night-time BP changes after CPAP. Specifically, low night-time heart rate (<68 bpm) and BP dipper profile were associated with increased night-time BP and new diagnosis of nocturnal hypertension.Our results suggest that nocturnal hypertension, circadian BP pattern and night-time heart rate could be clinical predictors of BP response to CPAP and support the usefulness of 24-h ABPM for OSA patients before treatment initiation. These results need to be confirmed in further studies. Copyright ©ERS 2017.

Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Hewitt, L Arthur; Rowse, Gerald J; White, William B

2016-10-01

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour "off-drug" data were collected. "On-drug" assessment was conducted after 4-5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 ± 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP ≥10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of a bacterial probiotic on ruminal pH and volatile fatty acids during subacute ruminal acidosis (SARA) in cattle.

PubMed

Goto, Hiroko; Qadis, Abdul Qadir; Kim, Yo-Han; Ikuta, Kentaro; Ichijo, Toshihiro; Sato, Shigeru

2016-11-01

Effects of a bacterial probiotic (BP) on ruminal fermentation and plasma metabolites were evaluated in four Holstein cattle (body weight, 645 ± 62 kg; mean ± SD) with induced subacute ruminal acidosis (SARA). SARA was induced by feeding a SARA-inducing diet, and thereafter, 20, 50 or 100 g per head of a commercial BP was administered for 7 consecutive days during the morning feeding. Cattle without BP served as the control. The 24-hr mean ruminal pH in the control was lower, whereas those in the BP groups administered 20 or 50 g were significantly higher compared to the control from days 2 to 7. Circadian patterns of the 1-hr mean ruminal pH were identical (6.4-6.8) among all cattle receiving BP. Although the mean minimum pH in the control on day -7 and day 0 was <5.8, the pH in the treatment groups on day 7 was >5.8 and significantly higher than that of the control group ( >5.2). Ruminal volatile fatty acid (VFA) concentrations were not affected by BP treatment; however, the BP groups had lower lactic acid levels compared with the control group at 20:00 on day 7. Additionally, non-esterified fatty acid levels decreased from 8:00 to 20:00 in all BP groups on day 7. These results suggest that administration of 20 to 50 g of a multi-strain BP for 7 days might improve the low pH and high lactic acid level of the ruminal fluid in SARA cattle.

Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1β gene expression in pancreatic islet β-cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakabayashi, Hiroko; Ohta, Yasuharu, E-mail: yohta@yamaguchi-u.ac.jp; Yamamoto, Masayoshi

2013-05-03

Highlights: •Arnt mRNA expressed in a circadian manner in mouse pancreatic islets. •Expressions of Dbp and Arnt damped in the islets of a diabetic model mouse. •DBP and E4BP4 regulate Arnt promoter activity by direct binding. •Arnt may have a role in connecting circadian rhythm and metabolism. -- Abstract: Aryl hydrocarbon receptor nuclear translocator (ARNT)/hypoxia inducible factor-1β (HIF-1β) has emerged as a potential determinant of pancreatic β-cell dysfunction and type 2 diabetes in humans. An 82% reduction in Arnt expression was observed in islets from type 2 diabetic donors as compared to non-diabetic donors. However, few regulators of Arnt expressionmore » have been identified. Meanwhile, disruption of the clock components CLOCK and BMAL1 is known to result in hypoinsulinemia and diabetes, but the molecular details remain unclear. In this study, we identified a novel molecular connection between Arnt and two clock-controlled output genes, albumin D-element binding protein (Dbp) and E4 binding protein 4 (E4bp4). By conducting gene expression studies using the islets of Wfs1{sup −/−} A{sup y}/a mice that develop severe diabetes due to β-cell apoptosis, we demonstrated clock-related gene expressions to be altered in the diabetic mice. Dbp mRNA decreased by 50%, E4bp4 mRNA increased by 50%, and Arnt mRNA decreased by 30% at Zeitgever Time (ZT) 12. Mouse pancreatic islets exhibited oscillations of clock gene expressions. E4BP4, a D-box negative regulator, oscillated anti-phase to DBP, a D-box positive regulator. We also found low-amplitude circadian expression of Arnt mRNA, which peaked at ZT4. Over-expression of DBP raised both mRNA and protein levels of ARNT in HEK293 and MIN6 cell lines. Arnt promoter-driven luciferase reporter assay in MIN6 cells revealed that DBP increased Arnt promoter activity by 2.5-fold and that E4BP4 competitively inhibited its activation. In addition, on ChIP assay, DBP and E4BP4 directly bound to D-box elements within the Arnt promoter in MIN6 cells. These results suggest that in mouse pancreatic islets mRNA expression of Arnt fluctuates significantly in a circadian manner and that the down-regulation of Dbp and up-regulation E4bp4 contribute to direct suppression of Arnt expression in diabetes.« less

Offshore fleet workers and the circadian adaptation of core body temperature, blood pressure and heart rate to 12-h shifts: a field study.

PubMed

Hansen, Jakob Hønborg; Geving, Ingunn Holmen; Reinertsen, Randi Eidsmo

2010-01-01

The aim of this study was to investigate the circadian adaptation of tcr (core body temperature), BP (blood pressure), HR (heart rate) and subjective sleep quality after 7 days of working 12-h night shifts in offshore fleet workers. Night workers (N = 7) (18:00-6:00) and day workers (N = 7) (6:00-18:00) were recruited from a Norwegian offshore company operating in the North Sea. We measured t(cr), BP and HR on days 1 and 7. An increase of 0.6 °C (p = .03) was observed within the group of night workers from day 1 to day 7. Between the night and day workers there was a significant difference of 0.6 °C from day 1 to day 7 (p = .01). Sleep latency and sleep length also showed significant differences between the groups (p = .01 and p = .04). There was an interaction effect in tiredness during the shift (p = .02). The significant increase in tcr indicates an adaptation in the night workers to the new working schedule, and the extended working hours and sleep deprivation are hypothesized to be the main cause of the increased t(cr). Light exposure, altered pattern of food availability and physical activity are likely to have contributed as well. Subjective sleep quality showed inconclusive results.

Clock genes explain large proportion of phenotypic variance in systolic blood pressure and this control is not modified by environmental temperature

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. METHODS: We examin...

Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment

PubMed Central

Tarumi, Takashi; Harris, Thomas S.; Hill, Candace; German, Zohre; Riley, Jonathan; Turner, Marcel; Womack, Kyle B.; Kerwin, Diana R.; Monson, Nancy L.; Stowe, Ann M.; Mathews, Dana; Cullum, C. Munro

2015-01-01

Objective: To determine whether cortical β-amyloid (Aβ) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI). Methods: Forty participants with aMCI were included in this study. Cortical Aβ depositions were measured by 18F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum. Circadian BP profiles were measured by 24-hour ambulatory monitoring during awake and sleep periods. The dipping status of sleep BP (i.e., the percent changes from the awake BP) was calculated and dichotomized into the dipper (≥10%) and nondipper (<10%) groups. Dynamic CBF regulation was assessed by a transfer function analysis between beat-to-beat changes in BP and CBF velocity measured from the middle cerebral artery during a repeated sit-stand maneuver. Results: Age was positively correlated with a greater Aβ deposition in the posterior cingulate, precuneus, and mean cortex. Accounting for the age effect, attenuated reductions in sleep systolic BP were associated with higher levels of posterior cingulate SUVR. Consistently, the nondippers exhibited a higher SUVR in the posterior cingulate than the dippers. Transfer function gain between changes in BP and CBF velocity was diminished in the nondippers, and moreover those individuals with a lower gain exhibited a higher SUVR in the posterior cingulate. Conclusions: Attenuated reductions in sleep BP are associated with a greater Aβ burden in the posterior cingulate and altered dynamic CBF regulation in patients with aMCI. PMID:26537049

Effects of a bacterial probiotic on ruminal pH and volatile fatty acids during subacute ruminal acidosis (SARA) in cattle

PubMed Central

GOTO, Hiroko; QADIS, Abdul Qadir; KIM, Yo-Han; IKUTA, Kentaro; ICHIJO, Toshihiro; SATO, Shigeru

2016-01-01

Effects of a bacterial probiotic (BP) on ruminal fermentation and plasma metabolites were evaluated in four Holstein cattle (body weight, 645 ± 62 kg; mean ± SD) with induced subacute ruminal acidosis (SARA). SARA was induced by feeding a SARA-inducing diet, and thereafter, 20, 50 or 100 g per head of a commercial BP was administered for 7 consecutive days during the morning feeding. Cattle without BP served as the control. The 24-hr mean ruminal pH in the control was lower, whereas those in the BP groups administered 20 or 50 g were significantly higher compared to the control from days 2 to 7. Circadian patterns of the 1-hr mean ruminal pH were identical (6.4–6.8) among all cattle receiving BP. Although the mean minimum pH in the control on day –7 and day 0 was <5.8, the pH in the treatment groups on day 7 was >5.8 and significantly higher than that of the control group ( >5.2). Ruminal volatile fatty acid (VFA) concentrations were not affected by BP treatment; however, the BP groups had lower lactic acid levels compared with the control group at 20:00 on day 7. Additionally, non-esterified fatty acid levels decreased from 8:00 to 20:00 in all BP groups on day 7. These results suggest that administration of 20 to 50 g of a multi-strain BP for 7 days might improve the low pH and high lactic acid level of the ruminal fluid in SARA cattle. PMID:27430197

The Circadian Variation of Psychophysiological Reactivity to Stress : A Study of Individual Differences

DTIC Science & Technology

1994-08-25

and/ or peak during the morning hours (Millar- Craig , Bishop, and Raftery, 1978; Turton and Deegan , 1974; and Weitzman et al., 1971). Furthermore, a...hematological factors showing distinct c i rcadian variations (e.g. Millar- Craig , Bishop, and Raftery, 1978; Weitzman, Fukushima, Nogeire, Roffwarg...examined the circadian variation o f blood pressure (BP), and have observed a morning peak in blood pressure (e.g., Millar- Craig , Bishop, & Raftery

Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome.

PubMed

Depner, Christopher M; Melanson, Edward L; McHill, Andrew W; Wright, Kenneth P

2018-06-05

Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.

Circadian blood pressure rhythm in normotensive offspring of hypertensive parents.

PubMed

Toker, Rabia Tutuncu; Yildirim, Ali; Demir, Tevfik; Ucar, Birsen; Kilic, Zubeyir

2015-01-01

The aim of this study was to explore the circadian blood pressure (BP) rhythm using ambulatory BP monitoring (ABPM) in normotensive children with a family history of essential hypertension. Group 1 consisted of children with hypertensive mothers and/or fathers (n = 20), Group 2 consisted of children with hypertensive grandparents (n = 20), and Group 3 consisted of children with normotensive parents (n = 20). All participating children underwent a 24-h ABPM and echocardiography. Significantly higher systolic burden was found in children with hypertensive parents (p < 0.05) and grandparents (p < 0.05) compared to controls. Ambulatory BP measurements had a higher daytime systolic BP in Group 1 compared to controls (p < 0.05). While left ventricular (LV) posterior wall thickness was similar in Group 1 and Group 2, it was significantly higher in both of these groups compared to the controls. The LV mass index (LVMI) was significantly higher in Group 1 than in controls (p < 0.05). However, diastolic BP was significantly higher in dippers compared to non-dippers (p < 0.05). LV posterior wall thickness, interventricular septum thickness and LVMI were significantly higher among non-dippers compared to dippers (p < 0.05). In children with a family history of hypertension, a positive correlation between nocturnal systolic BP and LVMI was found, and increasing nocturnal BP values were associated with increasing LVMI (p < 0.01). In children with a family history of hypertension, target-organ damage may precede the clinical detection of hypertension, and in those with a nocturnal non-dipper status, a more marked effect on LVMI may occur.

Association between light exposure at night and nighttime blood pressure in the elderly independent of nocturnal urinary melatonin excretion.

PubMed

Obayashi, Kenji; Saeki, Keigo; Iwamoto, Junko; Ikada, Yoshito; Kurumatani, Norio

2014-07-01

Circadian misalignment between internal and environmental rhythms dysregulates blood pressure (BP) variability because of disruption of the biological clock, resulting in increased nighttime BP. Although exposure to light-at-night is associated with the circadian misalignment, it remains unclear whether exposure to light-at-night in home settings is associated with nighttime BP. In this cross-sectional analysis of 528 elderly individuals (mean age: 72.8 years), we measured bedroom light intensity at 1-min intervals on two consecutive nights along with ambulatory BP, overnight urinary melatonin excretion and actigraphy. With regard to adjusted mean comparisons using analysis of covariance, the light-at-night group (average: ≥5 lux; n = 109) showed significantly higher nighttime systolic BP (SBP; adjusted mean: 120.8 vs. 116.5 mmHg, p = 0.01) and diastolic BP (70.1 vs. 67.1 mmHg, p < 0.01) compared with the Darker group (average: <5 lux; n = 419) independently of potential confounding factors including overnight urinary melatonin excretion and actigraphic sleep quality. We observed consistent associations between light-at-night and nighttime BP in different cutoff values for light-at-night intensity (i.e. 3 and 10 lux). In conclusion, exposure to light-at-night in home settings is significantly associated with increased nighttime BP in elderly individuals independently of overnight urinary melatonin excretion. A 4.3 mmHg increase in nighttime SBP is associated with a 6.1% increase in total mortality, which corresponds to approximately 10 000 annual excess deaths in Japanese elderly population.

Central blood pressure variability is increased in hypertensive patients with target organ damage.

PubMed

de la Sierra, Alejandro; Pareja, Julia; Yun, Sergi; Acosta, Eva; Aiello, Francesco; Oliveras, Anna; Vázquez, Susana; Armario, Pedro; Blanch, Pedro; Sierra, Cristina; Calero, Francesca; Fernández-Llama, Patricia

2018-02-01

We aimed to evaluate the association of aortic and brachial short-term blood pressure variability (BPV) with the presence of target organ damage (TOD) in hypertensive patients. One-hundred seventy-eight patients, aged 57 ± 12 years, 33% women were studied. TOD was defined by the presence of left ventricular hypertrophy on echocardiogram, microalbuminuria, reduced glomerular filtration rate, or increased aortic pulse wave velocity. Aortic and brachial BPV was assessed by 24-hour ambulatory BP monitoring (Mobil-O-Graph). TOD was present in 92 patients (51.7%). Compared to those without evidence of TOD, they had increased night-to-day ratios of systolic and diastolic BP (both aortic and brachial) and heart rate. They also had significant increased systolic BPV, as measured by both aortic and brachial daytime and 24-hours standard deviations and coefficients of variation, as well as for average real variability. Circadian patterns and short-term variability measures were very similar for aortic and brachial BP. We conclude that BPV is increased in hypertensive-related TOD. Aortic BPV does not add relevant information in comparison to brachial BPV. ©2018 Wiley Periodicals, Inc.

[24-Hour blood pressure profile in patients with mild and moderate arterial hypertension and sleep apnea/hypopnea].

PubMed

Zelveian, P A; Oshchepkova, E V; Buniatian, M S; Badikov, D N; Rogoza, A N

2001-01-01

To evaluate 24-hour blood pressure (BP) profile in arterial hypertension (AH) patients (pts) with desaturation signs of sleep apnea/hypopnea syndrome (SAHS). We investigated 61 pts (44 males and 17 females) aged between 23-70 (52 +/- 2) years with mild to moderate AH. BP monitoring was performed with multisensor system TM-2425 (A&D, Japan). We assessed the following parameters: mean 24-h, awake, sleep systolic (S), diastolic (D) and pulse (P) BPs, systolic and diastolic BP loads ("normalized area under the curve"--NAUC). A normal circadian rhythm of BP was defined when nocturnal fall of SBP was > 10% and < 20%. The morning rise of BP we assessed by speed of increase of mean BP from 4 a.m. to 12 a.m. The nocturnal monitoring of arterial oxygen saturation(SaO2) was performed with pulseoximeter "NONIN 8500M" (USA). The analysis of the results was performed with the original program ARM-SaO2". The presence of SAHS was confirmed when the number of 4% desaturations were greater than 15 per hour or in the presence of group episodes of 4% desaturation below 90%. In 19 pts we revealed desaturation signs of SAHS. The comparison group included pts without SAHS (n = 42). We compared the groups regarding 24-h BP profile parameters. SAHS group had the following parameters significantly higher: mean 24-h (151.7 +/- 4.5 vs 142.9 +/- 2.4 mm Hg, p < 0.07) and sleep SBPs (142.8 +/- 5.1 vs 132.7 +/- 2.6 mm Hg, p < 0.05); mean 24-h (65.2 +/- 2.6 vs 55.9 +/- 1.9 mm Hg, p < 0.008), daytime (65.6 +/- 2.7 vs 56.6 +/- 2.0 mm Hg, p < 0.01) and sleep PBPs (64.1 +/- 2.7 vs 53.1 +/- 1.9 mm Hg, p < 0.002); 24-h (20.1 +/- 3.8 vs 12.6 +/- 1.8 mm Hg, p < 0.05) and sleep NAUC of SBP (24.6 +/- 4.4 vs 15.3 +/- 2.2 mm Hg, p < 0.03). In the group with SAHS were significantly higher the frequency of abnormal circadian rhythm of SBP (84 vs 57%, p < 0.05) and the speed of morning rise of mean BP (23.3 +/- 5.9 vs 8.5 +/- 2.8 mm Hg/h, p < 0.01). Our results suggest that pts with desaturation signs of SAHS are characterized by unfavourable changes in 24-h BP profile parameters, first of all owning to sleep systolic and pulse blood pressures with alteration of circadian rhythm and high speed of morning rise of BP.

Peripheral Circadian Clock Rhythmicity Is Retained in the Absence of Adrenergic Signaling

PubMed Central

Reilly, Dermot F.; Curtis, Anne M.; Cheng, Yan; Westgate, Elizabeth J.; Rudic, Radu D.; Paschos, Georgios; Morris, Jacqueline; Ouyang, Ming; Thomas, Steven A.; FitzGerald, Garret A.

2009-01-01

Objective The incidence of heart attack and stroke undergo diurnal variation. Molecular clocks have been described in the heart and the vasculature; however it is largely unknown how the suprachiasmatic nucleus (SCN) entrains these peripheral oscillators. Methods and Results Norepinephrine and epinephrine, added to aortic smooth muscle cells (ASMCs) in vitro, altered Per1, E4bp4, and dbp expression and altered the observed oscillations in clock gene expression. However, oscillations of Per1, E4bp4, dbp, and Per2 were preserved ex vivo in the aorta, heart, and liver harvested from dopamine β-hydroxylase knockout mice (Dbh−/−) that cannot synthesize either norepinephrine or epinephrine. Furthermore, clock gene oscillations in heart, liver, and white adipose tissue phase shifted identically in Dbh−/− mice and in Dbh+/− controls in response to daytime restriction of feeding. Oscillation of clock genes was similarly preserved ex vivo in tissues from Dbh+/− and Dbh−/− chronically treated with both propranolol and terazosin, thus excluding compensation by dopamine in Dbh−/− mice. Conclusions Although adrenergic signaling can influence circadian timing in vitro, peripheral circadian rhythmicity is retained despite its ablation in vivo. PMID:17975121

Expression pattern of circadian genes and steroidogenesis-related genes after testosterone stimulation in the human ovary.

PubMed

Chen, Minghui; Xu, Yanwen; Miao, Benyu; Zhao, Hui; Luo, Lu; Shi, Huijuan; Zhou, Canquan

2016-09-10

Previous studies have shown that circadian genes might be involved in the development of polycystic ovarian syndrome (PCOS). Hyperandrogenism is a hallmark feature of PCOS. However, the effect of hyperandrogenism on circadian gene expression in human granulosa cells is unknown, and the general expression pattern of circadian genes in the human ovary is unclear. Expression of the circadian proteins CLOCK and PER2 in human ovaries was observed by immunohistochemistry. The mRNA expression patterns of the circadian genes CLOCK, PER2, and BMAL1, and the steroidogenesis-related genes STAR, CYP11A1, HSD3B2, and CYP19A1 in cultured human luteinized granulosa cells were analyzed over the course of 48 h after testosterone treatment by quantitative polymerase chain reaction. Immunostaining of CLOCK and PER2 protein was detected in the granulosa cells of dominant antral follicles but was absent in the primordial, primary, or preantral follicles of human ovaries. After testosterone stimulation, expression of PER2 showed an oscillating pattern, with two peaks occurring at the 24th and 44th hours; expression of CLOCK increased significantly to the peak at the 24th hour, whereas expression of BMAL1 did not change significantly over time in human luteinized granulosa cells. Among the four steroidogenesis-related genes evaluated, only STAR displayed an oscillating expression pattern with two peaks occurring at the 24th and 40th hours after testosterone stimulation. Circadian genes are expressed in the dominant antral follicles of the human ovary. Oscillating expression of the circadian gene PER2 can be induced by testosterone in human granulosa cells in vitro. Expression of STAR also displayed an oscillating pattern after testosterone stimulation. Our results indicate a potential relationship between the circadian clock and steroidogenesis in the human ovary, and demonstrate the effect of testosterone on circadian gene expression in granulosa cells.

Circadian rhythm, sleep pattern, and metabolic consequences: an overview on cardiovascular risk factors.

PubMed

Machado, Roberta Marcondes; Koike, Marcia Kiyomi

2014-04-01

Sleep duration is a risk factor for cardiovascular disease. Alteration in sleep pattern can induce the loss of circadian rhythmicity. Chronically, this desynchronization between endogenous rhythm and behavioral cycles can lead to an adverse metabolic profile, a proinflammatory condition and can increase the risk of cardiovascular disease. The circadian cycle can vary due to environmental cues. The circadian pacemaker is located in the suprachiasmatic nuclei; this central clock coordinates the circadian rhythm in the central nervous system and peripheral tissues. The mechanisms involved in sleep disturbance, circadian misalignment and adverse metabolic effects have yet to be fully elucidated. This review looks over the association among sleep alteration, circadian rhythm and the development of risk factors implicated in cardiovascular disease.

Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac dynamics

PubMed Central

Ivanov, Plamen Ch.; Hu, Kun; Hilton, Michael F.; Shea, Steven A.; Stanley, H. Eugene

2007-01-01

The endogenous circadian pacemaker influences key physiologic functions, such as body temperature and heart rate, and is normally synchronized with the sleep/wake cycle. Epidemiological studies demonstrate a 24-h pattern in adverse cardiovascular events with a peak at ≈10 a.m. It is unknown whether this pattern in cardiac risk is caused by a day/night pattern of behaviors, including activity level and/or influences from the internal circadian pacemaker. We recently found that a scaling index of cardiac vulnerability has an endogenous circadian peak at the circadian phase corresponding to ≈10 a.m., which conceivably could contribute to the morning peak in cardiac risk. Here, we test whether this endogenous circadian influence on cardiac dynamics is caused by circadian-mediated changes in motor activity or whether activity and heart rate dynamics are decoupled across the circadian cycle. We analyze high-frequency recordings of motion from young healthy subjects during two complementary protocols that decouple the sleep/wake cycle from the circadian cycle while controlling scheduled behaviors. We find that static activity properties (mean and standard deviation) exhibit significant circadian rhythms with a peak at the circadian phase corresponding to 5–9 p.m. (≈9 h later than the peak in the scale-invariant index of heartbeat fluctuations). In contrast, dynamic characteristics of the temporal scale-invariant organization of activity fluctuations (long-range correlations) do not exhibit a circadian rhythm. These findings suggest that endogenous circadian-mediated activity variations are not responsible for the endogenous circadian rhythm in the scale-invariant structure of heartbeat fluctuations and likely do not contribute to the increase in cardiac risk at ≈10 a.m. PMID:18093917

Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac dynamics.

PubMed

Ivanov, Plamen Ch; Hu, Kun; Hilton, Michael F; Shea, Steven A; Stanley, H Eugene

2007-12-26

The endogenous circadian pacemaker influences key physiologic functions, such as body temperature and heart rate, and is normally synchronized with the sleep/wake cycle. Epidemiological studies demonstrate a 24-h pattern in adverse cardiovascular events with a peak at approximately 10 a.m. It is unknown whether this pattern in cardiac risk is caused by a day/night pattern of behaviors, including activity level and/or influences from the internal circadian pacemaker. We recently found that a scaling index of cardiac vulnerability has an endogenous circadian peak at the circadian phase corresponding to approximately 10 a.m., which conceivably could contribute to the morning peak in cardiac risk. Here, we test whether this endogenous circadian influence on cardiac dynamics is caused by circadian-mediated changes in motor activity or whether activity and heart rate dynamics are decoupled across the circadian cycle. We analyze high-frequency recordings of motion from young healthy subjects during two complementary protocols that decouple the sleep/wake cycle from the circadian cycle while controlling scheduled behaviors. We find that static activity properties (mean and standard deviation) exhibit significant circadian rhythms with a peak at the circadian phase corresponding to 5-9 p.m. ( approximately 9 h later than the peak in the scale-invariant index of heartbeat fluctuations). In contrast, dynamic characteristics of the temporal scale-invariant organization of activity fluctuations (long-range correlations) do not exhibit a circadian rhythm. These findings suggest that endogenous circadian-mediated activity variations are not responsible for the endogenous circadian rhythm in the scale-invariant structure of heartbeat fluctuations and likely do not contribute to the increase in cardiac risk at approximately 10 a.m.

Nursing frequency alters circadian patterns of mammary gene expression in lactating mice

USDA-ARS?s Scientific Manuscript database

Milking frequency impacts lactation in dairy cattle and in rodent models of lactation. The role of circadian gene expression in this process is unknown. The hypothesis tested was that changing nursing frequency alters the circadian patterns of mammary gene expression. Mid-lactation CD1 mice were stu...

Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells.

PubMed

Baburski, Aleksandar Z; Sokanovic, Srdjan J; Andric, Silvana A; Kostic, Tatjana S

2017-05-01

The Leydig cell physiology displays a circadian rhythm driven by a complex interaction of the reproductive axis hormones and circadian system. The final output of this regulatory process is circadian pattern of steroidogenic genes expression and testosterone production. Aging gradually decreases robustness of rhythmic testosterone secretion without change in pattern of LH secretion. Here, we analyzed effect of aging on circadian variation of cAMP and cGMP signaling in Leydig cells. Results showed opposite effect of aging on cAMP and cGMP daily variation. Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of genes involved in cAMP production (increased circadian pattern of Adcy7, Adcy9, Adcy10 and decreased Adcy3); cAMP degradation (increased Pde4a, decreased Pde8b, canceled rhythm of Pde4d, completely reversed circadian pattern of Pde7b and Pde8a); and circadian expression of protein kinase A subunits (Prkac/PRKAC and Prkar2a). Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP circadian oscillations in Leydig cells. In addition, the expression of cGMP-dependent kinase, Prkg1/PRKG1 is up-regulated. It seems that aging potentiate cGMP- and reduce cAMP-signaling in Leydig cells. Since both signaling pathways affect testosterone production and clockwork in the cells, further insights into these signaling pathways will help to unravel disorders linked to the circadian timing system, aging and reproduction.

Night-time heart rate nondipping: clinical and prognostic significance in the general population.

PubMed

Cuspidi, Cesare; Facchetti, Rita; Bombelli, Michele; Sala, Carla; Tadic, Marijana; Grassi, Guido; Mancia, Giuseppe

2018-06-01

Studies addressing the association between a reduced drop of heart rate (HR) at night with subclinical organ damage and cardiovascular events in the general population are scanty. We evaluated this issue in individuals enrolled in the Pressioni Monitorate E Loro Associazioni study. At entry, 2021 individuals underwent diagnostic tests including laboratory investigations, 24-h ambulatory blood pressure (BP) monitoring and echocardiography. Participants were followed from the initial medical visit for a time interval of 148 ± 27 months. To explore the association of circadian HR rhythm and outcomes, participants were classified in the primary analysis according to quartiles of nocturnal HR decrease. In secondary analyses, the population was also classified according nondipping nocturnal HR (defined as a drop in average HR at night lower than 10% compared with day-time values) and next in four categories: first, BP/HR dipper, second, BP/HR nondipper, third, HR dipper/BP nondipper, fourth, HR nondipper/BP dipper). A flattened circadian HR rhythm (i.e. lowest quartile of night-time HR dip) was independently associated with left atrial enlargement, but not to left ventricular hypertrophy; moreover, it was predictive of fatal and nonfatal cardiovascular events, independently of several confounders (hazard ratio 1.8, confidence interval: 1.13-2.86, P < 0.01 vs. highest quartile). A blunted dipping of nocturnal HR is associated with preclinical cardiac damage in terms of left atrial enlargement and is predictive cardiovascular morbidity and mortality in the general population.

Factors Associated With Preterm Infants' Circadian Sleep/Wake Patterns at the Hospital.

PubMed

Lan, Hsiang-Yun; Yin, Ti; Chen, Jyu-Lin; Chang, Yue-Cune; Liaw, Jen-Jiuan

2017-08-01

This prospective repeated-measures study explored potential factors (postmenstrual age, body weight, gender, chronological age, illness severity, and circadian rhythm) related to preterm infants' circadian sleep/wake patterns. Circadian sleep/wake patterns were measured using an Actiwatch for 3 continuous days in preterm infants (gestational age of 28-36.4 weeks) in a neonatal intensive care unit and hospital nursery. Potential factors associated with circadian sleep/wake patterns were analyzed using the generalized estimating equation. For our sample of 30 preterm infants, better sleep/wake patterns were associated with male gender, younger postmenstrual and chronological age, lower body weight, and less illness severity. Preterm infants' total sleep time ( B = 41.828, p < .01) and percentage of sleep time ( B = 3.711, p < .01) were significantly longer at night than during the day. These findings can help clinicians recognize preterm infants' sleep problems, signaling the need to provide individualized support to maintain these infants' sleep quality during their early life.

Circadian variation in the circulatory responses to exercise: relevance to the morning peaks in strokes and cardiac events

PubMed Central

2009-01-01

Sudden cardiac and cerebral events are most common in the morning. A fundamental question is whether these events are triggered by the increase in physical activity after waking, and/or a result of circadian variation in the responses of circulatory function to exercise. Although signaling pathways from the master circadian clock in the suprachiasmatic nuclei to sites of circulatory control are not yet understood, it is known that cerebral blood flow, autoregulation and cerebrovascular reactivity to changes in CO2 are impaired in the morning and, therefore, could explain the increased risk of cerebrovascular events. Blood pressure (BP) and the rate pressure product (RPP) show marked ‘morning surges’ when people are studied in free-living conditions, making the rupture of a fragile atherosclerotic plaque and sudden cardiac event more likely. Since cerebral autoregulation is reduced in the morning, this surge in BP may also exacerbate the risk of hemorrhagic and ischemic strokes in the presence of other acute and chronic risk factors. Increased sympathetic activity, decreased endothelial function, and increased platelet aggregability could also be important in explaining the morning peak in cardiac and cerebral events but how these factors respond to exercise at different times of day is unclear. Evidence is emerging that the exercise-related responses of BP and RPP are increased in the morning when prior sleep is controlled. We recommend that such ‘semi-constant routine’ protocols are employed to examine the relative influence of the body clock and exogenous factors on the 24-h variation in other circulatory factors. PMID:19826832

The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light

PubMed Central

Ben-Moshe, Zohar; Alon, Shahar; Mracek, Philipp; Faigenbloom, Lior; Tovin, Adi; Vatine, Gad D.; Eisenberg, Eli; Foulkes, Nicholas S.; Gothilf, Yoav

2014-01-01

Light constitutes a primary signal whereby endogenous circadian clocks are synchronized (‘entrained’) with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3′UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light. PMID:24423866

Purinergic Signaling in Neuron-Astrocyte Interactions, Circadian Rhythms, and Alcohol Use Disorder

PubMed Central

Lindberg, Daniel; Andres-Beck, Lindsey; Jia, Yun-Fang; Kang, Seungwoo; Choi, Doo-Sup

2018-01-01

Alcohol use disorder (AUD) is a debilitating condition marked by cyclic patterns of craving, use, and withdrawal. These pathological behaviors are mediated by multiple neurotransmitter systems utilizing glutamate, GABA, dopamine, ATP, and adenosine. In particular, purines such as ATP and adenosine have been demonstrated to alter the phase and function of the circadian clock and are reciprocally regulated by the clock itself. Importantly, chronic ethanol intake has been demonstrated to disrupt the molecular circadian clock and is associated with altered circadian patterns of activity and sleep. Moreover, ethanol has been demonstrated to disrupt purinergic signaling, while dysfunction of the purinergic system has been implicated in conditions of drug abuse such as AUD. In this review, we summarize our current knowledge regarding circadian disruption by ethanol, focusing on the reciprocal relationship that exists between oscillatory neurotransmission and the molecular circadian clock. In particular, we offer detailed explanations and hypotheses regarding the concerted regulation of purinergic signaling and circadian oscillations by neurons and astrocytes, and review the diverse mechanisms by which purinergic dysfuction may contribute to circadian disruption or alcohol abuse. Finally, we describe the mechanisms by which ethanol may disrupt or hijack endogenous circadian rhythms to induce the maladaptive behavioral patterns associated with AUD. PMID:29467662

D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of blood pressure in hypertensive patients.

PubMed

Agorasti, Athanasia; Trivellas, Theodoros; Mourvati, Efthimia; Papadopoulos, Vasilios; Tsatalas, Konstantinos; Vargemezis, Vasilios; Passadakis, Ploumis

2013-06-01

The aim of this study is to assess whether the haemostatic markers D-dimer, factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping status in treated hypertensive patients; so, as easy available laboratory data can predict non-dipping pattern and help with the selection of the patients whom circadian blood pressure should be re-examined. Forty treated hypertensive patients with essential hypertension were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Daytime and nocturnal average systolic, diastolic and mean blood pressures were calculated. Patients were characterised as "non-dippers" on the basis of a less than 10 % decline in nocturnal blood pressure (BP); either systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function, FVIII activity and VWF antigen as marker of endothelial dysfunction were measured on plasma. The predictive efficiency was analysed by receiver operating characteristic (ROC) curves. Youden index was used for the estimation of the cut-off points and the associated values for sensitivity and 1-specificity. Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers as compared with dippers, irrespective of the classification used (BP index); all P < 0.05. The ROC curves indicated a good diagnostic efficiency for D-dimer (AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755) and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern (systolic, diastolic or mean) in the study population; all P < 0.05. Among the three haemostatic markers, D-dimer presents the most satisfactory sensitivity/1-specificity for the differentiation of non-dippers, with a cut-off point >168 ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375). In conclusion, D-dimer has a good predictive value for non-dipping pattern and the decision for the 24-h ambulatory blood pressure re-monitoring among dippers could rely on its values.

Circadian Role in Daily Pattern of Cardiovascular Risk

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch.; Hu, Kun; Chen, Zhi; Hilton, Michael F.; Stanley, H. Eugene; Shea, Steven A.

2004-03-01

Numerous epidemiological studies demonstrate that sudden cardiac death, pulmonary embolism, myocardial infarction, and stroke have a 24-hour daily pattern with a broad peak between 9-11am. Such a daily pattern in cardiovascular risk could be attributable to external factors, such as the daily behavior patterns, including sleep-wake cycles and activity levels, or internal factors, such as the endogenous circadian pacemaker. Findings of significant alternations in the temporal organization and nonlinear properties of heartbeat fluctuations with disease and with sleep-wake transitions raise the intriguing possibility that changes in the mechanism of control associated with behavioral sleep-wake transition may be responsible for the increased cardiac instability observed in particular circadian phases. Alternatively, we hypothesize that there is a circadian clock, independent of the sleep-wake cycle, which affects the cardiac dynamics leading to increased cardiovascular risk. We analyzed continuous recordings from healthy subjects during 7 cycles of forced desynchrony routine wherein subjects' sleep-wake cycles are adjusted to 28 hours so that their behaviors occur across all circadian phases. Heartbeat data were divided into one-hour segments. For each segment, we estimated the correlations and the nonlinear properties of the heartbeat fluctuations at the corresponding circadian phase. Since the sleep and wake contributions are equally weighted in our experiment, a change of the properties of the heartbeat dynamics with circadian phase suggest a circadian rhythm. We show significant circadian-mediated alterations in the correlation and nonlinear properties of the heartbeat resembling those observed in patients with heart failure. Remarkably, these dynamical alterations are centered at 60 degrees circadian phase, coinciding with the 9-11am window of cardiac risk.

Comparison of ambulatory blood pressure parameters of hypertensive patients with and without chronic kidney disease.

PubMed

Mojón, Artemio; Ayala, Diana E; Piñeiro, Luis; Otero, Alfonso; Crespo, Juan J; Moyá, Ana; Bóveda, Julia; de Lis, Jesús Pérez; Fernández, José R; Hermida, Ramón C

2013-03-01

There is strong association between chronic kidney disease (CKD) and increased prevalence of hypertension, risk of end-organ damage, and cardiovascular disease (CVD). Non-dipping, as determined by ambulatory blood pressure (BP) monitoring (ABPM), is frequent in CKD and has also been consistently associated with increased CVD risk. The reported prevalence of non-dipping in CKD is highly variable, probably due to relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary fixed clock-hour spans. Accordingly, we assessed the circadian BP pattern of patients with and without CKD by 48-h ABPM to increase reproducibility of the results. This cross-sectional study involved 10 271 hypertensive patients (5506 men/4765 women), 58.0 ± 14.2 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 3227 (1925 men/1302 women) had CKD. At the time of recruitment, 568/2234 patients with/without CKD were untreated for hypertension. Patients with than without CKD were more likely to be men and of older age, have diagnoses of obstructive sleep apnea, metabolic syndrome, diabetes, and/or obesity, plus have higher glucose, creatinine, uric acid, and triglyceride, but lower cholesterol, concentrations. In patients with CKD, ambulatory systolic BP (SBP) was significantly elevated (p < .001), mainly during the hours of nighttime sleep, independent of presence/absence of BP-lowering treatment. In patients without CKD, ambulatory diastolic BP (DBP), however, was significantly higher (p < .001), mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p < .001) for the entire 24 h in patients with CKD. Prevalence of non-dipping was significantly higher in patients with than without CKD (60.6% vs. 43.2%; p < .001). The largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean > awake SBP mean (17.6% vs. 7.1% in patients with and without CKD, respectively; p < .001). The riser BP pattern significantly and progressively increased from 8.1% among those with stage 1 CKD to a very high 34.9% of those with stage 5 CKD. Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with CKD; thus, among the uncontrolled hypertensive patients with CKD, 90.7% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with CKD. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was 2.5-fold more prevalent in CKD, and up to 5-fold more prevalent in end-stage renal disease. Patients with CKD also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. Collectively, these findings indicate that CKD should be included among the clinical conditions for which ABPM is mandatory for proper diagnosis and CVD risk assessment, as well as a means to establish the best therapeutic scheme to increase CVD event-free survival.

The importance of hormonal circadian rhythms in daily feeding patterns: An illustration with simulated pigs.

PubMed

Boumans, Iris J M M; de Boer, Imke J M; Hofstede, Gert Jan; la Fleur, Susanne E; Bokkers, Eddie A M

2017-07-01

The interaction between hormonal circadian rhythms and feeding behaviour is not well understood. This study aimed to deepen our understanding of mechanisms underlying circadian feeding behaviour in animals, using pigs, Sus scrofa, as a case study. Pigs show an alternans feeding pattern, that is, a small peak of feed intake at the beginning of the day and a larger peak at the end of the day. We simulated the feeding behaviour of pigs over a 24h period. The simulation model contained mechanisms that regulate feeding behaviour of animals, including: processing of feed in the gastrointestinal tract, fluctuation in energy balance, circadian rhythms of melatonin and cortisol and motivational decision-making. From the interactions between these various processes, feeding patterns (e.g. feed intake, meal frequency, feeding rate) emerge. These feeding patterns, as well as patterns for the underlying mechanisms (e.g. energy expenditure), fitted empirical data well, indicating that our model contains relevant mechanisms. The circadian rhythms of cortisol and melatonin explained the alternans pattern of feeding in pigs. Additionally, the timing and amplitude of cortisol peaks affected the diurnal and nocturnal peaks in feed intake. Furthermore, our results suggest that circadian rhythms of other hormones, such as leptin and ghrelin, are less important in circadian regulation of feeding behaviour than previously thought. These results are relevant to animal species with a metabolic and endocrine system similar to that of pigs, such as humans. Moreover, the modelling approach to understand feeding behaviour can be applied to other animal species. Copyright © 2017 Elsevier Inc. All rights reserved.

Deriving the reference value from the circadian motor active patterns in the "non-dementia" population, compared to the "dementia" population: What is the amount of physical activity conducive to the good circadian rhythm.

PubMed

Kodama, Ayuto; Kume, Yu; Tsugaruya, Megumi; Ishikawa, Takashi

2016-01-01

The circadian rhythm in older adults is commonly known to change with a decrease in physical activity. However, the association between circadian rhythm metrics and physical activity remains unclear. The objective of this study was to examine circadian activity patterns in older people with and without dementia and to determine the amount of physical activity conducive to a good circadian measurement. Circadian parameters were collected from 117 older community-dwelling people (66 subjects without dementia and 52 subjects with dementia); the parameters were measured continuously using actigraphy for 7 days. A receiver operating characteristic (ROC) curve was applied to determine reference values for the circadian rhythm parameters, consisting of interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA), in older subjects. The ROC curve revealed reference values of 0.55 for IS, 1.10 for IV, and 0.82 for RA. In addition, as a result of the ROC curve in the moderate-to-vigorous physical Activity (MVPA) conducive to the reference value of the Non-parametric Circadian Rhythm Analysis per day, the optimal reference values were 51 minutes for IV and 55 minutes for RA. However, the IS had no classification accuracy. Our results demonstrated the reference values derived from the circadian parameters of older Japanese population with or without dementia. Also, we determined the MVPA conducive to a good circadian rest-active pattern. This reference value for physical activity conducive to a good circadian rhythm might be useful for developing a new index for health promotion in the older community-dwelling population.

Activity, sleep and ambient light have a different impact on circadian blood pressure, heart rate and body temperature rhythms.

PubMed

Gubin, D G; Weinert, D; Rybina, S V; Danilova, L A; Solovieva, S V; Durov, A M; Prokopiev, N Y; Ushakov, P A

2017-01-01

The aim of the present study was to investigate the impact of endogenous and exogenous factors for the expression of the daily rhythms of body temperature (BT), blood pressure (BP) and heart rate (HR). One hundred and seventy-three young adults (YA), 17-24 years old (y.o.), of both genders were studied under a modified constant-routine (CR) protocol for 26 h. Participants were assigned randomly to groups with different lighting regimens: CR-LD, n = 77, lights (>400 l×) on from 09:00 to 17:00 h and off (<10 l×) from 17:00 to 09:00 next morning; CR-LL, n = 81, lights on (>400 l×) during the whole experimental session; CR-DD, n = 15, constant dim light (<10 l×) during the whole experiment. Systolic (SBP) and diastolic (DBP) BP, HR and BT were measured every 2 h. For comparison, the results of the former studies performed under conditions of regular life with an activity period from 07:00 to 23:00 h and sleep from 23:00 till 07:00 h (Control) were reanalyzed. Seven-day Ambulatory Blood Pressure Monitoring (ABPM) records from 27 YA (16-38 y.o.) and BT self-measurement data from 70 YA (17-30 y.o.) taken on ≥ 3 successive days at 08:00, 11:00, 14:00, 17:00, 20:00, 23:00 and 03:00 were available. The obtained daily patterns were different between Control and CR-DD groups, due to effects of activity, sleep and light. The comparison of Control and CR-LD groups allowed the effects of sleep and activity to be estimated since the lighting conditions were similar. The activity level substantially elevated SBP, but not DBP. Sleep, on the other hand, lowered the nighttime DBP, but has no effect on SBP. HR was affected both by activity and sleep. In accordance with previous studies, these results confirm that the steep BP increase in the morning is not driven by the circadian clock, but rather by sympathoadrenal factors related to awakening and corresponding anticipatory mechanisms. The effect on BT was not significant. To investigate the impact of light during the former dark time and darkness during the former light time, the CR-LL and CR-DD groups were each compared with the CR-LD group. Light delayed the evening decrease of BT, most likely via a suppression of the melatonin rise. Besides, it had a prominent arousal effect on SBP both in the former light and dark phases, a moderate effect on DBP and no effect on HR. Darkness induced decline in BT. BP values were decreased during the former light time. No effects on HR were found. Altogether, the results of the present paper show that BT, BP and HR are affected by exogenous factors differently. Moreover, the effect was gender-specific. Especially, the response of BT and BP to ambient light was evident only in females. We suppose that the distinct, gender-specific responses of SBP, DBP and HR to activity, sleep and ambient light do reflect fundamental differences in the circadian control of various cardiovascular functions. Furthermore, the presented data are important for the elaboration of updated reference standards, the interpretation of rhythm disorders and for personalized chronotherapeutic approaches to prevent adverse cardiovascular events more effectively.

Novel Mechanism for Disrupted Circadian Blood Pressure Rhythm in a Rat Model of Metabolic Syndrome—The Critical Role of Angiotensin II

PubMed Central

Sueta, Daisuke; Kataoka, Keiichiro; Koibuchi, Nobutaka; Toyama, Kensuke; Uekawa, Ken; Katayama, Tetsuji; MingJie, Ma; Nakagawa, Takashi; Waki, Hidefumi; Maeda, Masanobu; Yasuda, Osamu; Matsui, Kunihiko; Ogawa, Hisao; Kim‐Mitsuyama, Shokei

2013-01-01

Background This study was performed to determine the characteristics and mechanism of hypertension in SHR/NDmcr‐cp(+/+) rats (SHRcp), a new model of metabolic syndrome, with a focus on the autonomic nervous system, aldosterone, and angiotensin II. Methods and Results We measured arterial blood pressure (BP) in SHRcp by radiotelemetry combined with spectral analysis using a fast Fourier transformation algorithm and examined the effect of azilsartan, an AT1 receptor blocker. Compared with control Wistar‐Kyoto rats (WKY) and SHR, SHRcp exhibited a nondipper‐type hypertension and displayed increased urinary norepinephrine excretion and increased urinary and plasma aldosterone levels. Compared with WKY and SHR, SHRcp were characterized by an increase in the low‐frequency power (LF) of systolic BP and a decrease in spontaneous baroreflex gain (sBRG), indicating autonomic dysfunction. Thus, SHRcp are regarded as a useful model of human hypertension with metabolic syndrome. Oral administration of azilsartan once daily persistently lowered BP during the light period (inactive phase) and the dark period (active phase) in SHRcp more than in WKY and SHR. Thus, angiotensin II seems to be involved in the mechanism of disrupted diurnal BP rhythm in SHRcp. Azilsartan significantly reduced urinary norepinephrine and aldosterone excretion and significantly increased urinary sodium excretion in SHRcp. Furthermore, azilsartan significantly reduced LF of systolic BP and significantly increased sBRG in SHRcp. Conclusions These results strongly suggest that impairment of autonomic function and increased aldosterone in SHRcp mediate the effect of angiotensin II on circadian blood pressure rhythms. PMID:23629805

Role of Circadian Rhythms in Potassium Homeostasis

PubMed Central

Gumz, Michelle L.; Rabinowitz, Lawrence

2013-01-01

It has been known for decades that urinary potassium excretion varies with a circadian pattern. In this review, we consider the historical evidence for this phenomenon and present an overview of recent developments in the field. Extensive evidence from the latter part of the last century clearly demonstrates that circadian potassium excretion does not depend on endogenous aldosterone. Of note is the recent discovery that the expression of several renal potassium transporters varies with a circadian pattern that appears to be consistent with substantial clinical data regarding daily fluctuations in urinary potassium levels. We propose the circadian clock mechanism as a key regulator of renal potassium transporters, and consequently renal potassium excretion. Further investigation into the mechanism of regulation of renal potassium transport by the circadian clock is warranted in order to increase our understanding of the clinical relevance of circadian rhythms to potassium homeostasis. PMID:23953800

Preliminary characterization of persisting circadian rhythms during space flight: Neurospora as a model system

NASA Technical Reports Server (NTRS)

Sulzman, F. W.

1981-01-01

The effects of the Spacelab environment on the circadian rhythms in microorganisms are investigated. Neurospora is chosen because of its well characterized circadian rhythm of growth. Growth rate, banding patterns, and circadian period and phase information are studied.

A New Perspective for Parkinson's Disease: Circadian Rhythm.

PubMed

Li, Siyue; Wang, Yali; Wang, Fen; Hu, Li-Fang; Liu, Chun-Feng

2017-02-01

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

Characteristics of white coat hypertension in Chinese Han patients with type 2 diabetes mellitus.

PubMed

Zhou, Jianguang; Liu, Changyun; Shan, Peijia; Zhou, Yingqi; Xu, Erli; Ji, Yufeng

2014-01-01

This study documented the prevalence and clinical features of white coat hypertension (WCH) among Chinese Han patients with type 2 diabetes mellitus (T2DM). Clinic and ambulatory blood pressure (BP) measurements were compared in 856 patients with T2DM to determine the frequency of WCH (WCH was defined as clinical blood pressure ≥140/90 mmHg and daytime blood pressure <135/85 mmHg and/or 24-h ambulatory BP (ABP) mean value of <130/80 mmHg on ambulatory BP monitoring (ABPM). Weight, waist circumference (WC), body mass index (BMI), waist to height ratio (WHtR), fasting blood glucose, glycosylated hemoglobin level and circadian BP patterns were also measured to find clinical features predictive of WCH in T2DM. The prevalence of WCH was 7.36% (63/856) in the overall population, 6.13% (29/473) in male and 8.88% (34/383) in female (p < 0.05). WCH accounted for 14.03% (63/449) of diagnosed hypertension. Age, course of T2DM, male WC were independent protective factors, whereas female sex, smoking and alcohol consumption were independent risk factors for WCH in T2DM. Non-dippers and reverse dippers made up larger proportion of the WCH group (p < 0.01). WCH is relatively common among T2DM patients, it is a unique condition distinct from essential hypertension (EH), and WCH patients also exhibit significant differences in clinical parameters.

Circadian and circaseptan (about-weekly) aspects of immigrant Indians’ blood pressure and heart rate in California, USA

PubMed Central

Sundaram, B.; Holley, D.C.; Cornélissen, G.; Naik, D.; Hanumansetty, R.; Singh, R.B.; Otsuka, K.; Halberg, F.

2008-01-01

Time structurally (chronomically) interpreted half-hourly monitoring of blood pressure (BP) and heart rate (HR) for at least 7 days and preferably for 17 days is recommended, separately for a diagnosis of BP disorders and when necessary again for the same or longer spans for treatment, whenever a positive diagnosis of a disorder is made. In this study, 30 clinically healthy subjects underwent 7-day monitoring and provided a series of findings, including the detection of Circadian Hyper-Amplitude-Tension (CHAT), that is blood pressure overswinging, which carries a high risk of hard cardiovascular events. The results specifically bear upon south-east Asian-Indian immigrants. They show that cardiovascular disease risk increases with age, with a positive family history of hypertension and/or other cardiovascular diseases and even with the duration of stay in the USA. A relation to body mass index is also shown. Such monitoring for prehabilitation may eventually reduce the need for rehabilitation. PMID:16275512

Comparison of freely-moving telemetry Chinese Miniature Experiment Pigs (CMEPs) to beagle dogs in cardiovascular safety pharmacology studies.

PubMed

Yuan, Haitao; Zhao, Jing; Guo, Jiabin; Wu, Ruiqin; He, Li; Cui, Yaxiong; Feng, Min; Zhang, Tingfen; Hou, Mingyue; Guo, Qian; Zhang, Lijun; Jia, Li; Huang, Chang; Ye, Lin; Peng, Shuangqing

2014-01-01

Telemetry beagle dogs are the most frequently used species in cardiovascular telemetry assessments. However, beagle dogs may not be always suitable for all of the tests. Recently minipigs have received increased attention for these studies. Differences between the two species regarding the response of their cardiovascular systems to environmental stimuli are unclear. This study investigates how the telemetry minipig compares to beagle dog as a test subject and also refines the experimental protocols necessary to obtain accurate data. Beagle dogs and Chinese Miniature Experiment Pigs (CMEPs) were implanted with telemetry transmitters and the influences of gavage, feeding and the circadian cycle on various cardiovascular parameters were investigated. ECG signal quality from CMEPs was superior to that of the beagle dogs. Poor ECG signal quality, elevated HR, BP and locomotor activity associated with gavage and feeding were observed in both species. ECG signal quality, BP and locomotor activity recovered more quickly in the CMEPs than in the beagle dogs. Residual elevation of HR found in CMEPs lasted approximately 4h post-feeding, which has a profound influence on the circadian cycle. A diurnal rhythm in CMEP with a significant increase of body temperature during the dark period and a clear circadian rhythm of locomotor activity in both species were observed. The present data demonstrated that gavage, feeding and circadian cycle were having an enormous influence on BP, HR and locomotor activity in both species. If drug-induced effects are expected rapidly after oral administration and feeding, CMEP seems to be a favorable choice. Also, due to the effects of feeding on HR, CMEPs should fast at least 5h before the start of recording or should not be fed during the study where the Tmax of a given compound might occur very late. It also should be taken into consideration when the test article has a potential effect on body temperature by using CMEPs. In summary, the telemetry CMEP is a valuable alternative to the beagle dog for cardiovascular telemetry studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Circadian clock and cardiac vulnerability: A time stamp on multi-scale neuroautonomic regulation

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch.

2005-03-01

Cardiovascular vulnerability displays a 24-hour pattern with a peak between 9AM and 11AM. This daily pattern in cardiac risk is traditionally attributed to external factors including activity levels and sleep-wake cycles. However,influences from the endogenous circadian pacemaker independent from behaviors may also affect cardiac control. We investigate heartbeat dynamics in healthy subjects recorded throughout a 10-day protocol wherein the sleep/wake and behavior cycles are desynchronized from the endogenous circadian cycle,enabling assessment of circadian factors while controlling for behavior-related factors. We demonstrate that the scaling exponent characterizing temporal correlations in heartbeat dynamics over multiple time scales does exhibit a significant circadian rhythm with a sharp peak at the circadian phase corresponding to the period 9-11AM, and that this rhythm is independent from scheduled behaviors and mean heart rate. Our findings of strong circadian rhythms in the multi-scale heartbeat dynamics of healthy young subjects indicate that the underlying mechanism of cardiac regulation is strongly influenced by the endogenous circadian pacemaker. A similar circadian effect in vulnerable individuals with underlying cardiovascular disease would contribute to the morning peak of adverse cardiac events observed in epidemiological studies.

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

PubMed

Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

2016-12-01

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

PubMed

Truong, Kimberly K; Lam, Michael T; Grandner, Michael A; Sassoon, Catherine S; Malhotra, Atul

2016-07-01

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature.

PubMed

Dashti, Hassan S; Aslibekyan, Stella; Scheer, Frank A J L; Smith, Caren E; Lamon-Fava, Stefania; Jacques, Paul; Lai, Chao-Qiang; Tucker, Katherine L; Arnett, Donna K; Ordovás, José M

2016-01-01

Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature. In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18 mm Hg lower systolic BP [SBP; β ± SE = -0.18 ± 0.05 mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; -0.10 ± 0.03 mm Hg; P = 0.001]. Similar results were seen in the BPRHS for SBP only. Clock genes explained a statistically significant proportion of the variance in SBP [V G/V P ± SE = 0.071 ± 0.03; P = 0.001] in GOLDN, but not in the BPRHS, and we did not observe associations between individual SNPs and BP. Environmental temperature did not influence the identified genetic associations. We identified clock genes that explained a statistically significant proportion of the phenotypic variance in SBP, supporting the importance of the circadian pathway underlying cardiac physiology. Although temperature was associated with BP, it did not affect results with genetic markers in either study. Therefore, it does not appear that temperature measures are necessary for interpreting associations between clock genes and BP. Trials related to this study were registered at clinicaltrials.gov as NCT00083369 (Genetic and Environmental Determinants of Triglycerides) and NCT01231958 (Boston Puerto Rican Health Study). © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2015. This work is written by (a) US Government employees(s) and is in the public domain in the US.

Time-Dependent Trapping of Pollinators Driven by the Alignment of Floral Phenology with Insect Circadian Rhythms

PubMed Central

Lau, Jenny Y. Y.; Guo, Xing; Pang, Chun-Chiu; Tang, Chin Cheung; Thomas, Daniel C.; Saunders, Richard M. K.

2017-01-01

Several evolutionary lineages in the early divergent angiosperm family Annonaceae possess flowers with a distinctive pollinator trapping mechanism, in which floral phenological events are very precisely timed in relation with pollinator activity patterns. This contrasts with previously described angiosperm pollinator traps, which predominantly function as pitfall traps. We assess the circadian rhythms of pollinators independently of their interactions with flowers, and correlate these data with detailed assessments of floral phenology. We reveal a close temporal alignment between patterns of pollinator activity and the floral phenology driving the trapping mechanism (termed ‘circadian trapping’ here). Non-trapping species with anthesis of standard duration (c. 48 h) cannot be pollinated effectively by pollinators with a morning-unimodal activity pattern; non-trapping species with abbreviated anthesis (23–27 h) face limitations in utilizing pollinators with a bimodal circadian activity; whereas species that trap pollinators (all with short anthesis) can utilize a broader range of potential pollinators, including those with both unimodal and bimodal circadian rhythms. In addition to broadening the range of potential pollinators based on their activity patterns, circadian trapping endows other selective advantages, including the possibility of an extended staminate phase to promote pollen deposition, and enhanced interfloral movement of pollinators. The relevance of the alignment of floral phenological changes with peaks in pollinator activity is furthermore evaluated for pitfall trap pollination systems. PMID:28713403

Sleep, circadian rhythm and body weight: parallel developments.

PubMed

Westerterp-Plantenga, Margriet S

2016-11-01

Circadian alignment is crucial for body-weight management, and for metabolic health. In this context, circadian alignment consists of alignment of sleep, meal patterns and physical activity. During puberty a significant reduction in sleep duration occurs, and pubertal status is inversely associated with sleep duration. A consistent inverse association between habitual sleep duration and body-weight development occurs, independent of possible confounders. Research on misalignment reveals that circadian misalignment affects sleep-architecture and subsequently disturbs glucose-insulin metabolism, substrate oxidation, leptin- and ghrelin concentrations, appetite, food reward, hypothalamic-pituitary-adrenal-axis activity and gut-peptide concentrations enhancing positive energy balance and metabolic disturbance. Not only aligning meals and sleep in a circadian way is crucial, also regular physical activity during the day strongly promotes the stability and amplitude of circadian rhythm, and thus may serve as an instrument to restore poor circadian rhythms. Endogenicity may play a role in interaction of these environmental variables with a genetic predisposition. In conclusion, notwithstanding the separate favourable effects of sufficient daily physical activity, regular meal patterns, sufficient sleep duration and quality sleep on energy balance, the overall effect of the amplitude and stability of the circadian rhythm, perhaps including genetic predisposition, may integrate the separate effects in an additive way.

A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

PubMed

El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

2018-06-20

Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Sleep and circadian rhythm disruption in schizophrenia†

PubMed Central

Wulff, Katharina; Dijk, Derk-Jan; Middleton, Benita; Foster, Russell G.; Joyce, Eileen M.

2012-01-01

Background Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions. Aims A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption. Method We examined the relationship between sleep-wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadian clock timing, by collecting weekly 48 h profiles of a urinary metabolite of melatonin in 20 out-patients with schizophrenia and 21 healthy control individuals matched for age, gender and being unemployed. Results Significant sleep/circadian disruption occurred in all the participants with schizophrenia. Half these individuals showed severe circadian misalignment ranging from phase-advance/delay to non-24 h periods in sleep-wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production. Conclusions Severe circadian sleep/wake disruptions exist despite stability in mood, mental state and newer antipsychotic treatment. They cannot be explained by the individuals' level of everyday function. PMID:22194182

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer

PubMed Central

Truong, Kimberly K.; Lam, Michael T.; Grandner, Michael A.; Sassoon, Catherine S.

2016-01-01

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption. PMID:27104378

Circadian rhythm of the Leydig cells endocrine function is attenuated during aging.

PubMed

Baburski, Aleksandar Z; Sokanovic, Srdjan J; Bjelic, Maja M; Radovic, Sava M; Andric, Silvana A; Kostic, Tatjana S

2016-01-01

Although age-related hypofunction of Leydig cells is well illustrated across species, its circadian nature has not been analyzed. Here we describe changes in circadian behavior in Leydig cells isolated from adult (3-month) and aged (18- and 24-month) rats. The results showed reduced circadian pattern of testosterone secretion in both groups of aged rats despite unchanged LH circadian secretion. Although arrhythmic, the expression of Insl3, another secretory product of Leydig cells, was decreased in both groups. Intracellular cAMP and most important steroidogenic genes (Star, Cyp11a1 and Cyp17a1), together with positive steroidogenic regulator (Nur77), showed preserved circadian rhythm in aging although rhythm robustness and expression level were attenuated in both aged groups. Aging compromised cholesterol mobilization and uptake by Leydig cells: the oscillatory transcription pattern of genes encoding HDL-receptor (Scarb1), hormone sensitive lipase (Lipe, enzyme that converts cholesterol esters from lipid droplets into free cholesterol) and protein responsible for forming the cholesterol esters (Soat2) were flattened in 24-month group. The majority of examined clock genes displayed circadian behavior in expression but only a few of them (Bmal1, Per1, Per2, Per3 and Rev-Erba) were reduced in 24-month-old group. Furthermore, aging reduced oscillatory expression pattern of Sirt1 and Nampt, genes encoding key enzymes that connect cellular metabolism and circadian network. Altogether circadian amplitude of Leydig cell's endocrine function decreased during aging. The results suggest that clock genes are more resistant to aging than genes involved in steroidogenesis supporting the hypothesis about peripheral clock involvement in rhythm maintenance during aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Prognostic significance of inverse spatial QRS-T angle circadian pattern in myocardial infarction survivors.

PubMed

Giannopoulos, Georgios; Dilaveris, Polychronis; Batchvarov, Velislav; Synetos, Andreas; Hnatkova, Katerina; Gatzoulis, Konstantinos; Malik, Marek; Stefanadis, Christodoulos

2009-01-01

We investigated the predictive value of the spatial QRS-T angle (QRSTA) circadian variation in myocardial infarction (MI) patients. Analyzing 24-hour recordings (SEER MC, GE Marquette) from 151 MI patients (age 63 +/- 12.7), the QRSTA was computed in derived XYZ leads. QRS-T angle values were compared between daytime and night time. The end point was cardiac death or life-threatening ventricular arrhythmia in 1 year. Overall, QRSTA was slightly higher during the day vs. the night (91 degrees vs. 87 degrees, P = .005). However, 33.8% of the patients showed an inverse diurnal QRSTA variation (higher values at night), which was correlated to the outcome (P = .001, odds ratio 6.7). In multivariate analysis, after entering all factors exhibiting univariate trend towards significance, inverse QRSTA circadian pattern remained significant (P = .036). Inverse QRSTA circadian pattern was found to be associated with adverse outcome (22.4%) in MI patients, whereas a normal pattern was associated (96%) with a favorable outcome.

Identification of human circadian genes based on time course gene expression profiles by using a deep learning method.

PubMed

Cui, Peng; Zhong, Tingyan; Wang, Zhuo; Wang, Tao; Zhao, Hongyu; Liu, Chenglin; Lu, Hui

2018-06-01

Circadian genes express periodically in an approximate 24-h period and the identification and study of these genes can provide deep understanding of the circadian control which plays significant roles in human health. Although many circadian gene identification algorithms have been developed, large numbers of false positives and low coverage are still major problems in this field. In this study we constructed a novel computational framework for circadian gene identification using deep neural networks (DNN) - a deep learning algorithm which can represent the raw form of data patterns without imposing assumptions on the expression distribution. Firstly, we transformed time-course gene expression data into categorical-state data to denote the changing trend of gene expression. Two distinct expression patterns emerged after clustering of the state data for circadian genes from our manually created learning dataset. DNN was then applied to discriminate the aperiodic genes and the two subtypes of periodic genes. In order to assess the performance of DNN, four commonly used machine learning methods including k-nearest neighbors, logistic regression, naïve Bayes, and support vector machines were used for comparison. The results show that the DNN model achieves the best balanced precision and recall. Next, we conducted large scale circadian gene detection using the trained DNN model for the remaining transcription profiles. Comparing with JTK_CYCLE and a study performed by Möller-Levet et al. (doi: https://doi.org/10.1073/pnas.1217154110), we identified 1132 novel periodic genes. Through the functional analysis of these novel circadian genes, we found that the GTPase superfamily exhibits distinct circadian expression patterns and may provide a molecular switch of circadian control of the functioning of the immune system in human blood. Our study provides novel insights into both the circadian gene identification field and the study of complex circadian-driven biological control. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. Copyright © 2017. Published by Elsevier B.V.

The Heart´s rhythm 'n' blues: Sex differences in circadian variation patterns of vagal activity vary by depressive symptoms in predominantly healthy employees.

PubMed

Jarczok, Marc N; Aguilar-Raab, Corina; Koenig, Julian; Kaess, Michael; Borniger, Jeremy C; Nelson, Randy J; Hall, Martica; Ditzen, Beate; Thayer, Julian F; Fischer, Joachim E

2018-03-15

Successful regulation of emotional states is positively associated to mental health, while difficulties in regulating emotions are negatively associated to overall mental health and in particular associated with anxiety or depression symptoms. A key structure associated to socio-emotional regulatory processes is the central autonomic network. Activity in this structure is associated to vagal activity can be indexed noninvasively and simply by measures of peripheral cardiac autonomic modulations such as heart rate variability. Vagal activity exhibits a circadian variation pattern, with a maximum during nighttime. Depression is known to affect chronobiology. Also, depressive symptoms are known to be associated with decreased resting state vagal activity, but studies investigating the association between circadian variation pattern of vagal activity and depressive symptoms are scarce. We aim to examine these patterns in association to symptom severity of depression using chronobiologic methods. Data from the Manheim Industrial Cohort Studies (MICS) were used. A total of 3,030 predominantly healthy working adults underwent, among others, ambulatory 24-h hear rate-recordings, detailed health examination and online questionnaires and were available for this analysis. The root mean sum of successive differences (RMSSD) was used as an indicator of vagally mediated heart rate variability. Three individual-level cosine function parameters (MESOR, amplitude, acrophase) were estimated to quantify circadian variation pattern. Multivariate linear regression models including important covariates such as age, sex, and lifestyle factors as well as an interaction effect of sex with depressive symptoms were used to estimate the association of circadian variation pattern of vagal activity with depressive symptoms simultaneously. The analysis sample consisted of 20.2% females and an average age 41 with standard deviation of 11 years. Nonparametric bivariate analysis revealed significant MESOR and amplitude differences between the 90 th percentile split, but not on acrophase. Multivariate linear regression models estimated depressive symptoms to be negatively associated with the 24h mean (MESOR) and oscillation amplitude in men but positively associated in women. This pattern of findings indicates a blunted day-night rhythm of vagal activity in men with greater depressive symptoms as well as a moderation effect of sex in the association of CVP and depressive symptoms. This is the first study investigating circadian variation pattern by mild depressive symptoms in a large, rather healthy occupational sample. Depressive symptoms were associated with decreased circadian variation pattern of vagal activity in men but with increased circadian variation pattern in women. The possible underlying mechanism(s) are discussed using the neurovisceral integration model. These findings may have implications for the knowledge on etiology, diagnosis, course, and treatment of depressive symptoms and thus may be of significant public health relevance.

Influence of feeding schedules on the chronobiology of renin activity, urinary electrolytes and blood pressure in dogs.

PubMed

Mochel, Jonathan P; Fink, Martin; Bon, Charlotte; Peyrou, Mathieu; Bieth, Bruno; Desevaux, Cyril; Deurinck, Mark; Giraudel, Jérôme M; Danhof, Meindert

2014-06-01

The contribution of the renin-angiotensin-aldosterone system (RAAS) to the development of congestive heart failure (CHF) and hypertension (HT) has long been recognized. Medications that are commonly used in the course of CHF and HT are most often given with morning food for the sake of convenience and therapeutic compliance. However, biological rhythms and their responsiveness to environmental clues such as food intake may noticeably impact the effectiveness of drugs used in the management of cardiovascular disorders. Only sparse information about the effect of feeding schedules on the biology of the RAAS and blood pressure (BP) is presently available. Two studies were designed to explore the chronobiology of renin activity (RA), BP, renal sodium (UNa,fe) and potassium (UK,fe) handling in relation to meal timing in dogs. In a first experiment (Study a), blood and urinary samples for measurement of RA, UNa,fe and UK,fe were drawn from 18 healthy beagle dogs fed a normal-sodium diet at either 07:00, 13:00 or 19:00 h. In a second experiment (Study b), BP was recorded continuously from six healthy, telemetered beagle dogs fed a similar diet at 07:00, or 19:00 h. Data were collected throughout 24-h time periods, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of early versus late time after feeding observations were further compared using parametric statistics. In agreement with our previous investigations, the results indicate that RA, UNa,fe, UK,fe, systolic, and diastolic BP oscillate with a circadian periodicity in dogs fed a regular diet at 07:00 h. A cosine model with a fixed 24-h period was found to fit the variations of RA, UK,fe and BP well, whereas cyclic changes in UNa,fe were best characterized by means of a combined cosine and surge model, reflecting a postprandial sodium excretion followed by a monotonous decay. Our data show that feeding time has a marked influence on the chronobiology of the renin cascade, urinary electrolytes, and BP. Introducing a 6- or 12-h delay in the dogs' feeding schedule caused a shift of similar magnitude (05:06 and 12:32 h for Studies a and b, respectively) in the rhythm of these biomarkers. In all study groups, RA and BP exhibited a marked fall just after food intake. The drop in RA is consistent with sodium and water-induced body fluid expansion, while the reduction of BP could be related to the decreased activity of renin and the secretion of vasodilatory gut peptides. An approximately 1.5-fold (1.2-1.6-fold) change between the average early and late time after feeding observations was found for RA (p < 0.0001), UNa,fe (p < 0.01) and UK,fe (p < 0.05). Postprandial variations in BP, albeit small (ca. 10 mmHg), were statistically significant (p < 0.01) and supported by the model-based analysis. In conclusion, the timing of food intake appears to be pivotal to the circadian organization of the renin cascade and BP. This synchronizing effect could be mediated by feeding-related signals, such as dietary sodium, capable of entraining circadian oscillators downstream of the master, light-dark-adjusted pacemaker in the suprachiasmatic nucleus.

Circadian rhythm of body temperature in an ectotherm (Iguana iguana).

PubMed

Tosini, G; Menaker, M

1995-09-01

Ectothermic animals regulate their body temperatures primarily by behavioral adjustment in relation to the thermal characteristics of the environment. Several studies have shown that some vertebrate ectotherms may show a daily pattern of body temperature selection when given a choice of environmental temperature. The pattern of body temperature selection free-runs when the animals are kept in constant darkness, demonstrating the existence of circadian regulation. To test whether there might also be a low amplitude circadian rhythm of body temperature itself, we examined the pattern of body temperature and locomotor activity of the lizard Iguana iguana held in a constant environmental temperature. Both variables were recorded for 3 days in a light:dark cycle and then for 10 days in constant dim light (0.1 lux). Under these conditions the body temperature of the lizard oscillates with a circadian period as does the locomotor behavior. These results demonstrate for the first time that ectothermic animals may display physiologically generated circadian rhythms of body temperature similar to those recorded in endotherms. In some animals the circadian rhythms of body temperature and locomotor activity showed different free-running periods, demonstrating that the body temperature rhythm was not caused by locomotor activity and suggesting internal desyncronization of the two rhythms.

Circadian processes in the RNA life cycle.

PubMed

Torres, Manon; Becquet, Denis; Franc, Jean-Louis; François-Bellan, Anne-Marie

2018-05-01

The circadian clock drives daily rhythms of multiple physiological processes, allowing organisms to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of at least 30% of expressed genes. While the ability for the endogenous timekeeping system to generate a 24-hr cycle is a cell-autonomous mechanism based on negative autoregulatory feedback loops of transcription and translation involving core-clock genes and their protein products, it is now increasingly evident that additional mechanisms also govern the circadian oscillations of clock-controlled genes. Such mechanisms can take place post-transcriptionally during the course of the RNA life cycle. It has been shown that many steps during RNA processing are regulated in a circadian manner, thus contributing to circadian gene expression. These steps include mRNA capping, alternative splicing, changes in splicing efficiency, and changes in RNA stability controlled by the tail length of polyadenylation or the use of alternative polyadenylation sites. RNA transport can also follow a circadian pattern, with a circadian nuclear retention driven by rhythmic expression within the nucleus of particular bodies (the paraspeckles) and circadian export to the cytoplasm driven by rhythmic proteins acting like cargo. Finally, RNA degradation may also follow a circadian pattern through the rhythmic involvement of miRNAs. In this review, we summarize the current knowledge of the post-transcriptional circadian mechanisms known to play a prominent role in shaping circadian gene expression in mammals. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Processing > RNA Editing and Modification RNA Export and Localization > Nuclear Export/Import. © 2018 Wiley Periodicals, Inc.

Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?

PubMed

Vogel, Suzan W N; Bijlenga, Denise; Tanke, Marjolein; Bron, Tannetje I; van der Heijden, Kristiaan B; Swaab, Hanna; Beekman, Aartjan T F; Kooij, J J Sandra

2015-11-01

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) have a high prevalence of obesity. This is the first study to investigate whether circadian rhythm disruption is a mechanism linking ADHD symptoms to obesity. ADHD symptoms and two manifestations of circadian rhythm disruption: sleep problems and an unstable eating pattern (skipping breakfast and binge eating later in the day) were assessed in participants with obesity (n= 114), controls (n= 154), and adult ADHD patients (n= 202). Participants with obesity had a higher prevalence of ADHD symptoms and short sleep on free days as compared to controls, but a lower prevalence of ADHD symptoms, short sleep on free days, and an unstable eating pattern as compared to ADHD patients.We found that participants with obesity had a similar prevalence rate of an unstable eating pattern when compared to controls. Moreover, mediation analyses showed that both sleep duration and an unstable eating pattern mediated the association between ADHD symptoms and body mass index (BMI). Our study supports the hypothesis that circadian rhythm disruption is a mechanism linking ADHD symptoms to obesity. Further research is needed to determine if treatment of ADHD and circadian rhythm disruption is effective in the prevention and treatment of obesity in patients with obesity and/or ADHD. Copyright © 2015 Elsevier Inc. All rights reserved.

Circadian Activity Rhythms, Time Urgency, and Achievement Concerns.

ERIC Educational Resources Information Center

Watts, Barbara L.

Many physiological and psychological processes fluctuate throughout the day in fairly stable, rhythmic patterns. The relationship between individual differences in circadian activity rhythms and a sense of time urgency were explored as well as a number of achievement-related variables. Undergraduates (N=308), whose circadian activity rhythms were…

Mother-infant circadian rhythm: development of individual patterns and dyadic synchrony.

PubMed

Thomas, Karen A; Burr, Robert L; Spieker, Susan; Lee, Jungeun; Chen, Jessica

2014-12-01

Mutual circadian rhythm is an early and essential component in the development of maternal-infant physiological synchrony. The aim of this to examine the longitudinal pattern of maternal-infant circadian rhythm and rhythm synchrony as measured by rhythm parameters. In-home dyadic actigraphy monitoring at infant age 4, 8, and 12 weeks. Forty-three healthy mother-infant pairs. Circadian parameters derived from cosinor and non-parametric analysis including mesor, magnitude, acrophase, L5 and M10 midpoints (midpoint of lowest 5 and highest 10h of activity), amplitude, interdaily stability (IS), and intradaily variability (IV). Mothers experienced early disruption of circadian rhythm, with re-establishment of rhythm over time. Significant time effects were noted in increasing maternal magnitude, amplitude, and IS and decreasing IV (p<.001). Infants demonstrated a developmental trajectory of circadian pattern with significant time effects for increasing mesor, magnitude, amplitude, L5, IS, and IV (p<.001). By 12 weeks, infant phase advancement was evidenced by mean acrophase and M10 midpoint occurring 60 and 43 min (respectively) earlier than at 4 weeks. While maternal acrophase remained consistent over time, infants became increasingly phase advanced relative to mother and mean infant acrophase at 12 weeks occurred 60 min before mother. Mother-infant synchrony was evidenced in increasing correspondence of acrophase at 12 weeks (r=0.704), L5 (r=0.453) and M10 (r=0.479) midpoints. Development of mother-infant synchrony reflects shared elements of circadian rhythm. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mother-Infant Circadian Rhythm: Development of Individual Patterns and Dyadic Synchrony

PubMed Central

Thomas, Karen A.; Burr, Robert L.; Spieker, Susan; Lee, Jungeun; Chen, Jessica

2014-01-01

Background Mutual circadian rhythm is an early and essential component in the development of maternal-infant physiological synchrony. Aims To examine the longitudinal pattern of maternal-infant circadian rhythm and rhythm synchrony as measured by rhythm parameters. Study Design In-home dyadic actigraphy monitoring at infant age 4, 8, and 12 weeks. Subjects Forty-three healthy mother-infant pairs. Outcome Measures Circadian parameters derived from cosinor and non-parametric analysis including mesor, magnitude, acrophase, L5 and M10 midpoints (midpoint of lowest 5 and highest 10 hours of activity), amplitude, interdaily stability (IS), and intradaily variability (IV). Results Mothers experienced early disruption of circadian rhythm, with re-establishment of rhythm over time. Significant time effects were noted in increasing maternal magnitude, amplitude, and IS and decreasing IV (p < .001). Infants demonstrated a developmental trajectory of circadian pattern with significant time effects for increasing mesor, magnitude, amplitude, L5, IS, and IV (p < .001). By 12 weeks, infant phase advancement was evidenced by mean acrophase and M10 midpoint occurring 60 and 43 minutes (respectively) earlier than at 4 weeks. While maternal acrophase remained consistent over time, infants became increasingly phase advanced relative to mother and mean infant acrophase at 12 weeks occurred 60 minutes before mother. Mother-infant synchrony was evidenced in increasing correspondence of acrophase at 12 weeks (r = 0.704), L5 (r = 0.453) and M10 (r = 0.479) midpoints. Conclusions Development of mother-infant synchrony reflects shared elements of circadian rhythm. PMID:25463836

Comparison of hormone and electrolyte circadian rhythms in male and female humans

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Winget, C. M.; Goodwin, A. E.; Reilly, T.

1977-01-01

Circadian rhythm characteristics in healthy male and female humans were studied at 4-hour intervals for urine volume, cortisol, 5-hydroxyindoleacetic acid (5-HIAA), Na, K, Na/K ratios in the urine, as well as plasma cortisol. While plasma and urinary cortisol rhythms were very similar in both sexes, the described rhythms in urine volume, electrolyte, and 5-HIAA excretion differ for the two sexes. The results suggest that sex differences exist in the circadian patterns of important hormone and metabolic functions and that the internal synchrony of circadian rhythms differs for the two sexes. The results seem to indicate that the rhythmical secretion of cortisol does not account for the pattern of Na and K excretion.

Chronobiology of alcohol: studies in C57BL/6J and DBA/2J inbred mice.

PubMed

Rosenwasser, Alan M; Fixaris, Michael C

2013-02-17

Human alcoholics display dramatic disruptions of circadian rhythms that may contribute to the maintenance of excessive drinking, thus creating a vicious cycle. While clinical studies cannot establish direct causal mechanisms, recent animal experiments have revealed bidirectional interactions between circadian rhythms and ethanol intake, suggesting that the chronobiological disruptions seen in human alcoholics are mediated in part by alterations in circadian pacemaker function. The present study was designed to further explore these interactions using C57BL/6J (B6) and DBA/2J (D2) inbred mice, two widely employed strains differing in both circadian and alcohol-related phenotypes. Mice were maintained in running-wheel cages with or without free-choice access to ethanol and exposed to a variety of lighting regimens, including standard light-dark cycles, constant darkness, constant light, and a "shift-lag" schedule consisting of repeated light-dark phase shifts. Relative to the standard light-dark cycle, B6 mice showed reduced ethanol intake in both constant darkness and constant light, while D2 mice showed reduced ethanol intake only in constant darkness. In contrast, shift-lag lighting failed to affect ethanol intake in either strain. Access to ethanol altered daily activity patterns in both B6 and D2 mice, and increased activity levels in D2 mice, but had no effects on other circadian parameters. Thus, the overall pattern of results was broadly similar in both strains, and consistent with previous observations that chronic ethanol intake alters circadian activity patterns while environmental perturbation of circadian rhythms modulates voluntary ethanol intake. These results suggest that circadian-based interventions may prove useful in the management of alcohol use disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Alteration of circadian rhythm during epileptogenesis: implications for the suprachiasmatic nucleus circuits.

PubMed

Xiang, Yan; Li, Zhi-Xiao; Zhang, Ding-Yu; He, Zhi-Gang; Hu, Ji; Xiang, Hong-Bing

2017-01-01

It is important to realize that characterization of the circadian rhythm patterns of seizure occurrence can implicate in diagnosis and treatment of selected types of epilepsy. Evidence suggests a role for the suprachiasmatic nucleus (SCN) circuits in overall circadian rhythm and seizure susceptibility both in animals and humans. Thus, we conclude that SCN circuits may exert modifying effects on circadian rhythmicity and neuronal excitability during epileptogenesis. SCN circuits will be studied in our brain centre and collaborating centres to explore further the interaction between the circadian rhythm and epileptic seizures. More and thorough research is warranted to provide insight into epileptic seizures with circadian disruption comorbidities such as disorders of cardiovascular parameters and core body temperature circadian rhythms.

Clocks for the city: circadian differences between forest and city songbirds.

PubMed

Dominoni, D M; Helm, B; Lehmann, M; Dowse, H B; Partecke, J

2013-07-22

To keep pace with progressing urbanization organisms must cope with extensive habitat change. Anthropogenic light and noise have modified differences between day and night, and may thereby interfere with circadian clocks. Urbanized species, such as birds, are known to advance their activity to early morning and night hours. We hypothesized that such modified activity patterns are reflected by properties of the endogenous circadian clock. Using automatic radio-telemetry, we tested this idea by comparing activity patterns of free-living forest and city European blackbirds (Turdus merula). We then recaptured the same individuals and recorded their activity under constant conditions. City birds started their activity earlier and had faster but less robust circadian oscillation of locomotor activity than forest conspecifics. Circadian period length predicted start of activity in the field, and this relationship was mainly explained by fast-paced and early-rising city birds. Although based on only two populations, our findings point to links between city life, chronotype and circadian phenotype in songbirds, and potentially in other organisms that colonize urban habitats, and highlight that urban environments can significantly modify biologically important rhythms in wild organisms.

Endogenous circadian rhythm in vasovagal response to head-up tilt

PubMed Central

Hu, Kun; Scheer, Frank AJL; Laker, Michael; Smales, Carolina; Shea, Steven A

2011-01-01

Background The incidence of syncope exhibits a daily pattern with more occurrences in the morning, possibly due to influences from the endogenous circadian system and/or the daily pattern of behavioral/emotional stimuli. This study tested the hypothesis that the circadian system modulates cardiovascular responses to postural stress, leading to increased susceptibility to syncope at specific times of day. Methods and Results Twelve subjects underwent a 13-day in-laboratory protocol, in which subjects’ sleep-wake cycles were adjusted to 20 hours for 12 cycles. A 15-minute title-table test (60° head-up) was performed ~4.5 hours after scheduled awakening in each cycle so that twelve tests in each subject were distributed evenly across the circadian cycle. Out of 144 tests, signs/symptoms of presyncope were observed in 21 tests in 6 subjects. These presyncope events displayed a clear circadian rhythm (P=0.028) with 17 cases (81%) in the circadian phase range corresponding to ~22:30-10:30 (4.25 times of the probability from the other half of the circadian cycle). Significant circadian rhythms were also observed in hemodynamic and autonomic function markers (blood pressure, heart rate, epinephrine, norepinephrine, and indices of cardiac vagal tone) that may underlie the circadian rhythm of presyncope susceptibility. Conclusion The circadian system affects cardiovascular responses to postural stressors resulting in greater susceptibility to presyncope during the biological night. This finding suggests that night-shift workers and people with disrupted sleep at night may have great risk of syncope due to their exposure to postural stressors during the biological night. PMID:21339480

Cold and hunger induce diurnality in a nocturnal mammal.

PubMed

van der Vinne, Vincent; Riede, Sjaak J; Gorter, Jenke A; Eijer, Willem G; Sellix, Michael T; Menaker, Michael; Daan, Serge; Pilorz, Violetta; Hut, Roelof A

2014-10-21

The mammalian circadian system synchronizes daily timing of activity and rest with the environmental light-dark cycle. Although the underlying molecular oscillatory mechanism is well studied, factors that influence phenotypic plasticity in daily activity patterns (temporal niche switching, chronotype) are presently unknown. Molecular evidence suggests that metabolism may influence the circadian molecular clock, but evidence at the level of the organism is lacking. Here we show that a metabolic challenge by cold and hunger induces diurnality in otherwise nocturnal mice. Lowering ambient temperature changes the phase of circadian light-dark entrainment in mice by increasing daytime and decreasing nighttime activity. This effect is further enhanced by simulated food shortage, which identifies metabolic balance as the underlying common factor influencing circadian organization. Clock gene expression analysis shows that the underlying neuronal mechanism is downstream from or parallel to the main circadian pacemaker (the hypothalamic suprachiasmatic nucleus) and that the behavioral phenotype is accompanied by phase adjustment of peripheral tissues. These findings indicate that nocturnal mammals can display considerable plasticity in circadian organization and may adopt a diurnal phenotype when energetically challenged. Our previously defined circadian thermoenergetics hypothesis proposes that such circadian plasticity, which naturally occurs in nocturnal mammals, reflects adaptive maintenance of energy balance. Quantification of energy expenditure shows that diurnality under natural conditions reduces thermoregulatory costs in small burrowing mammals like mice. Metabolic feedback on circadian organization thus provides functional benefits by reducing energy expenditure. Our findings may help to clarify relationships between sleep-wake patterns and metabolic phenotypes in humans.

Simulated shift work in rats perturbs multiscale regulation of locomotor activity

PubMed Central

Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A. J. L.; Shea, Steven A.; Buijs, Ruud M.; Hu, Kun

2014-01-01

Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation. PMID:24829282

Brown Norway and Zucker Lean Rats Demonstrate Circadian Variation in Ventilation and Sleep Apnea

PubMed Central

Fink, Anne M.; Topchiy, Irina; Ragozzino, Michael; Amodeo, Dionisio A.; Waxman, Jonathan A.; Radulovacki, Miodrag G.; Carley, David W.

2014-01-01

Study Objectives: Circadian rhythms influence many biological systems, but there is limited information about circadian and diurnal variation in sleep related breathing disorder. We examined circadian and diurnal patterns in sleep apnea and ventilatory patterns in two rat strains, one with high sleep apnea propensity (Brown Norway [BN]) and the other with low sleep apnea propensity (Zucker Lean [ZL]). Design/Setting: Chronically instrumented rats were randomized to breathe room air (control) or 100% oxygen (hyperoxia), and we performed 20-h polysomnography beginning at Zeitgeber time 4 (ZT 4; ZT 0 = lights on, ZT12 = lights off). We examined the effect of strain and inspired gas (twoway analysis of variance) and analyzed circadian and diurnal variability. Measurements and Results: Strain and inspired gas-dependent differences in apnea index (AI; apneas/h) were particularly prominent during the light phase. AI in BN rats (control, 16.9 ± 0.9; hyperoxia, 34.0 ± 5.8) was greater than in ZL rats (control, 8.5 ± 1.0; hyperoxia, 15.4 ± 1.1, [strain effect, P < 0.001; gas effect, P = 0.001]). Hyperoxia reduced respiratory frequency in both strains, and all respiratory pattern variables demonstrated circadian variability. BN rats exposed to hyperoxia demonstrated the largest circadian fluctuation in AI (amplitude = 17.9 ± 3.7 apneas/h [strain effect, P = 0.01; gas effect, P < 0.001; interaction, P = 0.02]; acrophase = 13.9 ± 0.7 h; r2 = 0.8 ± 1.4). Conclusions: Inherited, environmental, and circadian factors all are important elements of underlying sleep related breathing disorder. Our method to examine sleep related breathing disorder phenotypes in rats may have implications for understanding vulnerability for sleep related breathing disorder in humans. Citation: Fink AM; Topchiy I; Ragozzino M; Amodeo DA; Waxman JA; Radulovacki MG; Carley DW. Brown Norway and Zucker Lean rats demonstrate circadian variation in ventilation and sleep apnea. SLEEP 2014;37(4):715-721. PMID:24899760

Circadian aspects of adipokine regulation in rodents.

PubMed

Challet, Etienne

2017-12-01

Most hormones display daily fluctuations of secretion during the 24-h cycle. This is also the case for adipokines, in particular the anorexigenic hormone, leptin. The temporal organization of the endocrine system is principally controlled by a network of circadian clocks. The circadian network comprises a master circadian clock, located in the suprachiasmatic nucleus of the hypothalamus, synchronized to the ambient light, and secondary circadian clocks found in various peripheral organs, such as the adipose tissues. Besides circadian clocks, other factors such as meals and metabolic status impact daily profiles of hormonal levels. In turn, the precise daily pattern of hormonal release provides temporal signaling information. This review will describe the reciprocal links between the circadian clocks and rhythmic secretion of leptin, and discuss the metabolic impact of circadian desynchronization and altered rhythmic leptin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of outdoor temperature on prewaking morning surge and nocturnal decline in blood pressure in a Japanese population.

PubMed

Murakami, Shougo; Otsuka, Kuniaki; Kono, Tatsuji; Soyama, Akiko; Umeda, Tatsuya; Yamamoto, Naomune; Morita, Hideaki; Yamanaka, Gaku; Kitaura, Yasushi

2011-01-01

Seasonal variations in blood pressure (BP) have often been attributed to meteorological factors, especially changes in outdoor temperature. We evaluated the direct association between meteorological factors and circadian BP variability. Twenty-four-hour ambulatory BP was monitored continuously for 7 days in 158 subjects. Mean awake, asleep, morning (first 2 h after waking) BP, prewaking morning BP surge (morning systolic BP (SBP)-mean SBP during the 2-h period before waking) and nocturnal BP decline were measured each day. We compared BP values for the lowest and highest days with regard to the daily mean outdoor temperature and mean atmospheric pressure. Morning BP and prewaking morning BP surge on the coldest day were significantly higher than those on the warmest day (morning SBP, 136.6 ± 1.6 vs. 133.1 ± 1.5 mm Hg, P = 0.002; morning diastolic BP, 84.4 ± 0.9 vs. 82.6 ± 0.9 mm Hg, P = 0.02; and prewaking morning BP surge, 20.8 ± 1.3 vs. 15.3 ± 1.3 mm Hg, P = 0.0004). The magnitude of nocturnal BP decline on the coldest day was significantly greater than that on the warmest day (15.8 ± 0.7 vs. 13.9 ± 0.7%, P = 0.01). Outdoor temperature is an important determinant of morning BP, prewaking morning BP surge and the magnitude of nocturnal BP decline. These findings may have important implications in management of hypertension and prevention of cardiovascular events.

Circadian expression of clock and putative clock-controlled genes in skeletal muscle of the zebrafish.

PubMed

Amaral, Ian P G; Johnston, Ian A

2012-01-01

To identify circadian patterns of gene expression in skeletal muscle, adult male zebrafish were acclimated for 2 wk to a 12:12-h light-dark photoperiod and then exposed to continuous darkness for 86 h with ad libitum feeding. The increase in gut food content associated with the subjective light period was much diminished by the third cycle, enabling feeding and circadian rhythms to be distinguished. Expression of zebrafish paralogs of mammalian transcriptional activators of the circadian mechanism (bmal1, clock1, and rora) followed a rhythmic pattern with a ∼24-h periodicity. Peak expression of rora paralogs occurred at the beginning of the subjective light period [Zeitgeber time (ZT)07 and ZT02 for roraa and rorab], whereas the highest expression of bmal1 and clock paralogs occurred 12 h later (ZT13-15 and ZT16 for bmal and clock paralogs). Expression of the transcriptional repressors cry1a, per1a/1b, per2, per3, nr1d2a/2b, and nr1d1 also followed a circadian pattern with peak expression at ZT0-02. Expression of the two paralogs of cry2 occurred in phase with clock1a/1b. Duplicated genes had a high correlation of expression except for paralogs of clock1, nr1d2, and per1, with cry1b showing no circadian pattern. The highest expression difference was 9.2-fold for the activator bmal1b and 51.7-fold for the repressor per1a. Out of 32 candidate clock-controlled genes, only myf6, igfbp3, igfbp5b, and hsf2 showed circadian expression patterns. Igfbp3, igfbp5b, and myf6 were expressed in phase with clock1a/1b and had an average of twofold change in expression from peak to trough, whereas hsf2 transcripts were expressed in phase with cry1a and had a 7.2-fold-change in expression. The changes in expression of clock and clock-controlled genes observed during continuous darkness were also observed at similar ZTs in fish exposed to a normal photoperiod in a separate control experiment. The role of circadian clocks in regulating muscle maintenance and growth are discussed.

Ambulatory Blood Pressure Monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults.

PubMed

Hermida, Ramón C; Smolensky, Michael H; Ayala, Diana E; Portaluppi, Francesco

2015-01-01

New information has become available since the ISC, AAMCC, and SECAC released their first extensive guidedelines to improve the diagnosis and treatment of adult arterial hypertension. A critical assessment of evidence and a comparison of what international guidelines now propose are the basis for the following statements, which update the recommendations first issued in 2013. Office blood pressure (BP) measurements should no longer be considered to be the "gold standard" for the diagnosis of hypertension and assessment of cardiovascular risk. Relying on office BP, even when supplemented with at-home wake-time self-measurements, to identify high-risk individuals, disregarding circadian BP patterning and asleep BP level, leads to potential misclassification of 50% of all evaluated persons. Accordingly, ambulatory BP monitoring is the recommended reference standard for the diagnosis of true hypertension and accurate assessment of cardiovascular risk in all adults ≥18 yrs of age, regardless of whether office BP is normal or elevated. Asleep systolic BP mean is the most significant independent predictor of cardiovascular events. The sleep-time relative SBP decline adds prognostic value to the statistical model that already includes the asleep systolic BP mean and corrected for relevant confounding variables. Accordingly, the asleep systolic BP mean is the recommended protocol to diagnose hypertension, assess cardiovascular risk, and predict cardiovascular event-free interval. In men, and in the absence of compelling clinical conditions, reference thresholds for diagnosing hypertension are 120/70 mmHg for the asleep systolic/diastolic BP means derived from ambulatory BP monitoring. However, in women, in the absence of complicating co-morbidities, the same thresholds are lower by 10/5 mmHg, i.e., 110/65 mmHg for the asleep means. In high-risk patients, including those diagnosed with diabetes or chronic kidney disease, and/or those having experienced past cardiovascular events, the thresholds are even lower by 15/10 mmHg, i.e., 105/60 mmHg. Bedtime treatment with the full daily dose of ≥1 hypertension medications is recommended as a cost-effective means to improve the management of hypertension and reduce hypertension-associated risk. Bedtime treatment entailing the full daily dose of ≥1 conventional hypertension medications must be the therapeutic regimen of choice for the elderly and those with diabetes, resistant and secondary hypertension, chronic kidney disease, obstructive sleep apnea, and medical history of past cardiovascular events, among others, given their documented high prevalence of sleep-time hypertension.

Association of intrinsic circadian period with morningness-eveningness, usual wake time, and circadian phase

NASA Technical Reports Server (NTRS)

Duffy, J. F.; Rimmer, D. W.; Czeisler, C. A.

2001-01-01

The biological basis of preferences for morning or evening activity patterns ("early birds" and "night owls") has been hypothesized but has remained elusive. The authors reported that, compared with evening types, the circadian pacemaker of morning types was entrained to an earlier hour with respect to both clock time and wake time. The present study explores a chronobiological mechanism by which the biological clock of morning types may be set to an earlier hour. Intrinsic period, a fundamental property of the circadian system, was measured in a month-long inpatient study. A subset of participants also had their circadian phase assessed. Participants completed a morningness-eveningness questionnaire before study. Circadian period was correlated with morningness-eveningness, circadian phase, and wake time, demonstrating that a fundamental property of the circadian pacemaker is correlated with the behavioral trait of morningness-eveningness.

Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.

PubMed

Lu, Yuan; Reyes, Jose; Walter, Sean; Gonzalez, Trevor; Medrano, Geraldo; Boswell, Mikki; Boswell, William; Savage, Markita; Walter, Ronald

2018-06-01

Evolutionarily conserved diurnal circadian mechanisms maintain oscillating patterns of gene expression based on the day-night cycle. Xiphophorus fish have been used to evaluate transcriptional responses after exposure to various light sources and it was determined that each source incites distinct genetic responses in skin tissue. However, basal expression levels of genes that show oscillating expression patterns in day-night cycle, may affect the outcomes of such experiments, since basal gene expression levels at each point in the circadian path may influence the profile of identified light responsive genes. Lack of knowledge regarding diurnal fluctuations in basal gene expression patterns may confound the understanding of genetic responses to external stimuli (e.g., light) since the dynamic nature of gene expression implies animals subjected to stimuli at different times may be at very different stages within the continuum of genetic homeostasis. We assessed basal gene expression changes over a 24-hour period in 200 select Xiphophorus gene targets known to transcriptionally respond to various types of light exposure. We identified 22 genes in skin, 36 genes in brain and 28 genes in liver that exhibit basal oscillation of expression patterns. These genes, including known circadian regulators, produced the expected expression patterns over a 24-hour cycle when compared to circadian regulatory genes identified in other species, especially human and other vertebrate animal models. Our results suggest the regulatory network governing diurnal oscillating gene expression is similar between Xiphophorus and other vertebrates for the three Xiphophorus organs tested. In addition, we were able to categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit circadian based oscillating expression patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian rhythms, time-restricted feeding, and healthy aging.

PubMed

Manoogian, Emily N C; Panda, Satchidananda

2017-10-01

Circadian rhythms optimize physiology and health by temporally coordinating cellular function, tissue function, and behavior. These endogenous rhythms dampen with age and thus compromise temporal coordination. Feeding-fasting patterns are an external cue that profoundly influence the robustness of daily biological rhythms. Erratic eating patterns can disrupt the temporal coordination of metabolism and physiology leading to chronic diseases that are also characteristic of aging. However, sustaining a robust feeding-fasting cycle, even without altering nutrition quality or quantity, can prevent or reverse these chronic diseases in experimental models. In humans, epidemiological studies have shown erratic eating patterns increase the risk of disease, whereas sustained feeding-fasting cycles, or prolonged overnight fasting, is correlated with protection from breast cancer. Therefore, optimizing the timing of external cues with defined eating patterns can sustain a robust circadian clock, which may prevent disease and improve prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans with dementia

PubMed Central

Hu, Kun; Harper, David G.; Shea, Steven A.; Stopa, Edward G.; Scheer, Frank A. J. L.

2013-01-01

Human motor activity has a robust, intrinsic fractal structure with similar patterns from minutes to hours. The fractal activity patterns appear to be physiologically important because the patterns persist under different environmental conditions but are significantly altered/reduced with aging and Alzheimer's disease (AD). Here, we report that dementia patients, known to have disrupted circadian rhythmicity, also have disrupted fractal activity patterns and that the disruption is more pronounced in patients with more amyloid plaques (a marker of AD severity). Moreover, the degree of fractal activity disruption is strongly associated with vasopressinergic and neurotensinergic neurons (two major circadian neurotransmitters) in postmortem suprachiasmatic nucleus (SCN), and can better predict changes of the two neurotransmitters than traditional circadian measures. These findings suggest that the SCN impacts human activity regulation at multiple time scales and that disrupted fractal activity may serve as a non-invasive biomarker of SCN neurodegeneration in dementia. PMID:23863985

Simulated shift work in rats perturbs multiscale regulation of locomotor activity.

PubMed

Hsieh, Wan-Hsin; Escobar, Carolina; Yugay, Tatiana; Lo, Men-Tzung; Pittman-Polletta, Benjamin; Salgado-Delgado, Roberto; Scheer, Frank A J L; Shea, Steven A; Buijs, Ruud M; Hu, Kun

2014-07-06

Motor activity possesses a multiscale regulation that is characterized by fractal activity fluctuations with similar structure across a wide range of timescales spanning minutes to hours. Fractal activity patterns are disturbed in animals after ablating the master circadian pacemaker (suprachiasmatic nucleus, SCN) and in humans with SCN dysfunction as occurs with aging and in dementia, suggesting the crucial role of the circadian system in the multiscale activity regulation. We hypothesized that the normal synchronization between behavioural cycles and the SCN-generated circadian rhythms is required for multiscale activity regulation. To test the hypothesis, we studied activity fluctuations of rats in a simulated shift work protocol that was designed to force animals to be active during the habitual resting phase of the circadian/daily cycle. We found that these animals had gradually decreased mean activity level and reduced 24-h activity rhythm amplitude, indicating disturbed circadian and behavioural cycles. Moreover, these animals had disrupted fractal activity patterns as characterized by more random activity fluctuations at multiple timescales from 4 to 12 h. Intriguingly, these activity disturbances exacerbated when the shift work schedule lasted longer and persisted even in the normal days (without forced activity) following the shift work. The disrupted circadian and fractal patterns resemble those of SCN-lesioned animals and of human patients with dementia, suggesting a detrimental impact of shift work on multiscale activity regulation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

PubMed

Ajabnoor, Ghada M; Bahijri, Suhad; Borai, Anwar; Abdulkhaliq, Altaf A; Al-Aama, Jumana Y; Chrousos, George P

2014-01-01

Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (p<0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk.

Circadian Rhythms Regulate Amelogenesis

PubMed Central

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A.; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-01-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24h) intervals both at RNA and protein levels. This study also reveals that two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stage of amelogenesis might be under circadian control. Changes in clock genes expression patterns might result in significant alterations of enamel apposition and mineralization. PMID:23486183

The role of the circadian system in fractal neurophysiological control

PubMed Central

Pittman-Polletta, Benjamin R.; Scheer, Frank A.J.L.; Butler, Matthew P.; Shea, Steven A.; Hu, Kun

2013-01-01

Many neurophysiological variables such as heart rate, motor activity, and neural activity are known to exhibit intrinsic fractal fluctuations - similar temporal fluctuation patterns at different time scales. These fractal patterns contain information about health, as many pathological conditions are accompanied by their alteration or absence. In physical systems, such fluctuations are characteristic of critical states on the border between randomness and order, frequently arising from nonlinear feedback interactions between mechanisms operating on multiple scales. Thus, the existence of fractal fluctuations in physiology challenges traditional conceptions of health and disease, suggesting that high levels of integrity and adaptability are marked by complex variability, not constancy, and are properties of a neurophysiological network, not individual components. Despite the subject's theoretical and clinical interest, the neurophysiological mechanisms underlying fractal regulation remain largely unknown. The recent discovery that the circadian pacemaker (suprachiasmatic nucleus) plays a crucial role in generating fractal patterns in motor activity and heart rate sheds an entirely new light on both fractal control networks and the function of this master circadian clock, and builds a bridge between the fields of circadian biology and fractal physiology. In this review, we sketch the emerging picture of the developing interdisciplinary field of fractal neurophysiology by examining the circadian system’s role in fractal regulation. PMID:23573942

Circadian desynchronization

PubMed Central

Granada, Adrián E.; Cambras, Trinitat; Díez-Noguera, Antoni; Herzel, Hanspeter

2011-01-01

The suprachiasmatic nucleus (SCN) coordinates via multiple outputs physiological and behavioural circadian rhythms. The SCN is composed of a heterogeneous network of coupled oscillators that entrain to the daily light–dark cycles. Outside the physiological entrainment range, rich locomotor patterns of desynchronized rhythms are observed. Previous studies interpreted these results as the output of different SCN neural subpopulations. We find, however, that even a single periodically driven oscillator can induce such complex desynchronized locomotor patterns. Using signal analysis, we show how the observed patterns can be consistently clustered into two generic oscillatory interaction groups: modulation and superposition. In seven of 17 rats undergoing forced desynchronization, we find a theoretically predicted third spectral component. Combining signal analysis with the theory of coupled oscillators, we provide a framework for the study of circadian desynchronization. PMID:22419981

Individual variation in circadian rhythms of sleep, EEG, temperature, and activity among monkeys - Implications for regulatory mechanisms.

NASA Technical Reports Server (NTRS)

Crowley, T. J.; Halberg, F.; Kripke, D. F.; Pegram, G. V.

1971-01-01

Investigation of circadian rhythms in a number of variables related to sleep, EEG, temperature, and motor activity in rhesus monkeys on an LD 12:12 schedule. Circadian rhythms were found to appear in each of 15 variables investigated. Statistical procedures assessed the variables for evidence of common regulation in these aspects of their circadian rhythms: acrophase (timing), amplitude (extent of change), and level (24-hr mean value). Patterns appearing in the data suggested that the circadian rhythms of certain variables are regulated in common. The circadian modulation of activity in the beta and sigma frequency bands of the EEG was correlated with statistical significance in acrophase, level, and amplitude. The delta frequency band appeared to be under circadian rhythm regulation distinct from that of the other bands. The circadian rhythm of REM stage sleep was like that of beta activity in level and amplitude. The data indicate that REM stage may share some common regulation of circadian timing with both stage 3-4 sleep and with temperature. Generally, however, the circadian rhythm of temperature appeared to bear little relation to the circadian rhythms of motor activity, EEG, or sleep.

Disruption of Circadian Rhythms by Light During Day and Night.

PubMed

Figueiro, Mariana G

2017-06-01

This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: A preliminary report.

PubMed

Almeneessier, Aljohara S; Bahammam, Ahmed S; Sharif, Munir M; Bahammam, Salman A; Nashwan, Samar Z; Pandi Perumal, Seithikurippu R; Cardinali, Daniel P; Alzoghaibi, Mohammad

2017-01-01

We hypothesized that if we control for food composition, caloric intake, light exposure, sleep schedule, and exercise, intermittent fasting would not influence the circadian pattern of melatonin. Therefore, we designed this study to assess the effect of intermittent fasting on the circadian pattern of melatonin. Eight healthy volunteers with a mean age of 26.6 ± 4.9 years and body mass index of 23.7 ± 3.5 kg/m 2 reported to the Sleep Disorders Center (the laboratory) on four occasions: (1) adaptation, (2) 4 weeks before Ramadan while performing Islamic intermittent fasting for 1 week (fasting outside Ramadan [FOR]), (3) 1 week before Ramadan (nonfasting baseline [BL]), and (4) during the 2 nd week of Ramadan while fasting ( Ramadan ). The plasma levels of melatonin were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00 h. The light exposure, meal composition, energy expenditure, and sleep schedules remained the same while the participants stayed at the laboratory. The melatonin levels followed the same circadian pattern during the three monitoring periods (BL, FOR, and Ramadan ). The peak melatonin level was at 02:00 h and the trough level was at 11:00 h in all studied periods. Lower melatonin levels at 22:00 h were found during fasting compared to BL. Cosinor analysis revealed no significant changes in the acrophase of melatonin levels. In this preliminary report, under controlled conditions of light exposure, meal composition, energy expenditure, and sleep-wake schedules, intermittent fasting has no significant influence on the circadian pattern of melatonin.

The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: A preliminary report

PubMed Central

Almeneessier, Aljohara S.; Bahammam, Ahmed S.; Sharif, Munir M.; Bahammam, Salman A.; Nashwan, Samar Z.; Pandi Perumal, Seithikurippu R.; Cardinali, Daniel P.; Alzoghaibi, Mohammad

2017-01-01

AIMS: We hypothesized that if we control for food composition, caloric intake, light exposure, sleep schedule, and exercise, intermittent fasting would not influence the circadian pattern of melatonin. Therefore, we designed this study to assess the effect of intermittent fasting on the circadian pattern of melatonin. METHODS: Eight healthy volunteers with a mean age of 26.6 ± 4.9 years and body mass index of 23.7 ± 3.5 kg/m2 reported to the Sleep Disorders Center (the laboratory) on four occasions: (1) adaptation, (2) 4 weeks before Ramadan while performing Islamic intermittent fasting for 1 week (fasting outside Ramadan [FOR]), (3) 1 week before Ramadan (nonfasting baseline [BL]), and (4) during the 2nd week of Ramadan while fasting (Ramadan). The plasma levels of melatonin were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00 h. The light exposure, meal composition, energy expenditure, and sleep schedules remained the same while the participants stayed at the laboratory. RESULTS: The melatonin levels followed the same circadian pattern during the three monitoring periods (BL, FOR, and Ramadan). The peak melatonin level was at 02:00 h and the trough level was at 11:00 h in all studied periods. Lower melatonin levels at 22:00 h were found during fasting compared to BL. Cosinor analysis revealed no significant changes in the acrophase of melatonin levels. CONCLUSIONS: In this preliminary report, under controlled conditions of light exposure, meal composition, energy expenditure, and sleep-wake schedules, intermittent fasting has no significant influence on the circadian pattern of melatonin. PMID:28808490

PDF Signaling Is an Integral Part of the Drosophila Circadian Molecular Oscillator.

PubMed

Mezan, Shaul; Feuz, Jean Daniel; Deplancke, Bart; Kadener, Sebastian

2016-10-11

Circadian clocks generate 24-hr rhythms in physiology and behavior. Despite numerous studies, it is still uncertain how circadian rhythms emerge from their molecular and neural constituents. Here, we demonstrate a tight connection between the molecular and neuronal circadian networks. Using fluorescent transcriptional reporters in a Drosophila ex vivo brain culture system, we identified a reciprocal negative regulation between the master circadian regulator CLK and expression of pdf, the main circadian neuropeptide. We show that PDF feedback is required for maintaining normal oscillation pattern in CLK-driven transcription. Interestingly, we found that CLK and neuronal firing suppresses pdf transcription, likely through a common pathway involving the transcription factors DHR38 and SR, establishing a direct link between electric activity and the circadian system. In sum, our work provides evidence for the existence of an uncharacterized CLK-PDF feedback loop that tightly wraps together the molecular oscillator with the circadian neuronal network in Drosophila. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

How does healthy aging impact on the circadian clock?

PubMed

Popa-Wagner, Aurel; Buga, Ana-Maria; Dumitrascu, Dinu Iuliu; Uzoni, Adriana; Thome, Johannes; Coogan, Andrew N

2017-02-01

Circadian rhythms are recurring patterns in a host of physiological and other parameters that recur with periods of near 24 h. These rhythms reflect the temporal organization of an organism's homeostatic control systems and as such are key processes in ensuring optimal physiological performance. Dysfunction of circadian processes is linked with adverse health conditions. In this review we highlight the evidence that normal, healthy aging is associated with changes in the circadian system; we examine the molecular mechanisms through which such changes may arise, discuss whether more robust circadian function is a predictor of longevity and highlight the role of circadian rhythms in age-related diseases. Overall, the literature shows that aging is associated with marked changes in circadian processes, both at the behavioral and molecular levels, and the molecular mechanisms through which such changes arise remain to be elucidated, but may involve inflammatory process, redox homeostasis and epigenetic modifications. Understanding the nature of age-related circadian dysfunction will allow for the design of chronotherapeutic intervention strategies to attenuate circadian dysfunction and thus improve health and quality of life.

Circadian rhythms regulate amelogenesis.

PubMed

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-07-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

Two pedigrees of familial advanced sleep phase syndrome in Japan.

PubMed

Satoh, Kohtoku; Mishima, Kazuo; Inoue, Yuichi; Ebisawa, Takashi; Shimizu, Tetsuo

2003-06-15

To determine whether a known missense mutation (bp2106 A/G) in hPer2 (a human homolog of the Drosophila period gene) for familial advanced sleep phase syndrome in a Caucasian family is involved in Japanese familial advanced sleep phase syndrome pedigrees. We identified 2 new Japanese families with advanced sleep phase syndrome, and a systematic survey was carried out in 28 relatives of theses 2 families. A total of 9 affected subjects were identified. The affected members showed significantly strong morningness tendencies compared with the unaffected members in various circadian parameters including the Horne-Ostberg Morningness-Eveningness Questionnaire score (77.3 +/- 4.8 vs 57.5 +/- 7.6, p < 0.001), average sleep-onset time (20:45 +/- 75 min vs 23:16 +/- 64 min, p < 0.02), and average wake time (4:55 +/- 38 min vs 6:13 +/- 25 min, p < 0.01), as well as saliva dim-light melatonin-onset time (20:15 +/- 21 min vs 22:25 +/- 65 min, p < 0.02). DNA samples were obtained from 7 affected and 7 unaffected subjects. None of the tested subjects possessed the missense mutation (bp2106 A/G) in hPer2. Furthermore, there is no significant linkage between affected subjects with hPer2 region by 2-point mapping and by direct sequencing of 23 exons of hPer2. These findings support the notion of genetic heterogeneity of familial advanced sleep phase syndrome cases in humans. The search for more familial advanced sleep phase syndrome cases and for loci other than hPer2 are necessary to further examine the roles of circadian-related genes in genetically determined human circadian rhythm disorders.

How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains.

PubMed

Combe, Roy; Mudgett, John; El Fertak, Lahcen; Champy, Marie-France; Ayme-Dietrich, Estelle; Petit-Demoulière, Benoit; Sorg, Tania; Herault, Yann; Madwed, Jeffrey B; Monassier, Laurent

2016-01-01

Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies. The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry). In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges. Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry and studies in the active phase are essential prerequisites.

Influence of age, strain and season on circadian periodicity of pituitary, gonadal and adrenal hormones in the serum of male laboratory rats.

PubMed

Wong, C C; Döhler, K D; Geerlings, H; von zur Mühlen, A

1983-01-01

The influence of age, strain and season on the circadian pattern of serum levels of LH, FSH, prolactin androgens and corticosterone was studied in five groups of male laboratory rats. Significant 24-hour periodicity was observed for serum levels of corticosterone in all five groups, for androgen levels in four, for prolactin levels in three, for LH levels in two and for FSH levels in one group of rats. There were significant influences of age, strain and season on the temporal patterns and/or on 24-hour mean serum hormone levels. The results indicate that some of the disagreements on existence or nonexistence of circadian rhythms and on rhythm patterns in serum hormone levels may be explained by the fact that animals of different ages or strains had been used or that experiments were performed at different times of the year.

Chronobiology of chronic pain: focus on diurnal rhythmicity of neuropathic pain.

PubMed

Gilron, Ian; Ghasemlou, Nader

2014-12-01

Although circadian rhythmicity has long been recognized in various nociceptive pain conditions such as arthritis, diurnal pain patterns in neuropathic conditions have only recently been described. The purpose of this article is to review emerging evidence and discuss future research to further understand this phenomenon. Secondary analyses of neuropathic pain clinical trials demonstrate that pain intensity fluctuations exhibit a distinct diurnal pattern that contrasts that of nociceptive pain conditions. Ongoing preclinical investigations support the phenomenon of circadian pain fluctuations and provide the opportunity to better describe pain chronobiology and to elucidate underlying mechanisms of circadian pain rhythmicity. The observation of clinically relevant diurnal pain variability in neuropathic conditions has important implications for future research and treatment of pain. This is an immature research field, and further investigation is needed to better characterize these patterns in more detail, investigate contributory mechanisms, and to develop therapeutic strategies that exploit this phenomenon.

Daily Rhythms in Mobile Telephone Communication

PubMed Central

Aledavood, Talayeh; López, Eduardo; Roberts, Sam G. B.; Reed-Tsochas, Felix; Moro, Esteban; Dunbar, Robin I. M.; Saramäki, Jari

2015-01-01

Circadian rhythms are known to be important drivers of human activity and the recent availability of electronic records of human behaviour has provided fine-grained data of temporal patterns of activity on a large scale. Further, questionnaire studies have identified important individual differences in circadian rhythms, with people broadly categorised into morning-like or evening-like individuals. However, little is known about the social aspects of these circadian rhythms, or how they vary across individuals. In this study we use a unique 18-month dataset that combines mobile phone calls and questionnaire data to examine individual differences in the daily rhythms of mobile phone activity. We demonstrate clear individual differences in daily patterns of phone calls, and show that these individual differences are persistent despite a high degree of turnover in the individuals’ social networks. Further, women’s calls were longer than men’s calls, especially during the evening and at night, and these calls were typically focused on a small number of emotionally intense relationships. These results demonstrate that individual differences in circadian rhythms are not just related to broad patterns of morningness and eveningness, but have a strong social component, in directing phone calls to specific individuals at specific times of day. PMID:26390215

Daily Rhythms in Mobile Telephone Communication.

PubMed

Aledavood, Talayeh; López, Eduardo; Roberts, Sam G B; Reed-Tsochas, Felix; Moro, Esteban; Dunbar, Robin I M; Saramäki, Jari

2015-01-01

Circadian rhythms are known to be important drivers of human activity and the recent availability of electronic records of human behaviour has provided fine-grained data of temporal patterns of activity on a large scale. Further, questionnaire studies have identified important individual differences in circadian rhythms, with people broadly categorised into morning-like or evening-like individuals. However, little is known about the social aspects of these circadian rhythms, or how they vary across individuals. In this study we use a unique 18-month dataset that combines mobile phone calls and questionnaire data to examine individual differences in the daily rhythms of mobile phone activity. We demonstrate clear individual differences in daily patterns of phone calls, and show that these individual differences are persistent despite a high degree of turnover in the individuals' social networks. Further, women's calls were longer than men's calls, especially during the evening and at night, and these calls were typically focused on a small number of emotionally intense relationships. These results demonstrate that individual differences in circadian rhythms are not just related to broad patterns of morningness and eveningness, but have a strong social component, in directing phone calls to specific individuals at specific times of day.

Metabolic effects of bariatric surgery in mouse models of circadian disruption.

PubMed

Arble, D M; Sandoval, D A; Turek, F W; Woods, S C; Seeley, R J

2015-08-01

Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption. VSG led to a reduction in body weight and fat mass in both Clock(Δ19) mutant and constant-light mouse models (P<0.05), resulting in an overall metabolic improvement independent of circadian disruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (P<0.05). Together these data demonstrate that VSG is an effective treatment for the obesity associated with circadian disruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption.

Controlled patterns of daytime light exposure improve circadian adjustment in simulated night work.

PubMed

Dumont, Marie; Blais, Hélène; Roy, Joanie; Paquet, Jean

2009-10-01

Circadian misalignment between the endogenous circadian signal and the imposed rest-activity cycle is one of the main sources of sleep and health troubles in night shift workers. Timed bright light exposure during night work can reduce circadian misalignment in night workers, but this approach is limited by difficulties in incorporating bright light treatment into most workplaces. Controlled light and dark exposure during the daytime also has a significant impact on circadian phase and could be easier to implement in real-life situations. The authors previously described distinctive light exposure patterns in night nurses with and without circadian adaptation. In the present study, the main features of these patterns were used to design daytime light exposure profiles. Profiles were then tested in a laboratory simulation of night work to evaluate their efficacy in reducing circadian misalignment in night workers. The simulation included 2 day shifts followed by 4 consecutive night shifts (2400-0800 h). Healthy subjects (15 men and 23 women; 20-35 years old) were divided into 3 groups to test 3 daytime light exposure profiles designed to produce respectively a phase delay (delay group, n=12), a phase advance (advance group, n=13), or an unchanged circadian phase (stable group, n=13). In all 3 groups, light intensity was set at 50 lux during the nights of simulated night work. Salivary dim light melatonin onset (DLMO) showed a significant phase advance of 2.3 h (+/-1.3 h) in the advance group and a significant phase delay of 4.1 h (+/-1.3 h) in the delay group. The stable group showed a smaller but significant phase delay of 1.7 h (+/-1.6 h). Urinary 6-sulfatoxymelatonin (aMT6s) acrophases were highly correlated to salivary DLMOs. Urinary aMT6s acrophases were used to track daily phase shifts. They showed that phase shifts occurred rapidly and differed between the 3 groups by the 3rd night of simulated night work. These results show that significant phase shifts can be achieved in night workers by controlling daytime light exposure, with no nighttime intervention.

TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.

PubMed

Kijak, Ewelina; Pyza, Elżbieta

2017-01-01

Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly's brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.

TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster

PubMed Central

Kijak, Ewelina; Pyza, Elżbieta

2017-01-01

Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly’s visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly’s brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies. PMID:28196106

Circadian genes, the stress axis, and alcoholism.

PubMed

Sarkar, Dipak K

2012-01-01

The body's internal system to control the daily rhythm of the body's functions (i.e., the circadian system), the body's stress response, and the body's neurobiology are highly interconnected. Thus, the rhythm of the circadian system impacts alcohol use patterns; at the same time, alcohol drinking also can alter circadian functions. The sensitivity of the circadian system to alcohol may result from alcohol's effects on the expression of several of the clock genes that regulate circadian function. The stress response system involves the hypothalamus and pituitary gland in the brain and the adrenal glands, as well as the hormones they secrete, including corticotrophin-releasing hormone, adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain-signaling molecules, including endogenous opioids such as β-endorphin. Alcohol consumption influences the activity of this system and vice versa. Finally, interactions exist between the circadian system, the hypothalamic-pituitary-adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes may control functions of the stress response system and that these interactions are affected by alcohol.

Akt1 Controls the Timing and Amplitude of Vascular Circadian Gene Expression

PubMed Central

Luciano, Amelia K.; Santana, Jeans M.; Velazquez, Heino; Sessa, William C.

2017-01-01

The AKT signaling pathway is important for circadian rhythms in mammals and flies (Drosophila). However, AKT signaling in mammals is more complicated since there are 3 isoforms of AKT, each performing slightly different functions. Here we study the most ubiquitous AKT isoform, Akt1, and its role at the organismal level in the central and vascular peripheral clocks. Akt1−/− mice exhibit relatively normal behavioral rhythms with only minor differences in circadian gene expression in the liver and heart. However, circadian gene expression in the Akt1−/− aorta, compared with control aorta, follows a distinct pattern. In the Akt1−/− aorta, positive regulators of circadian transcription have lower amplitude rhythms and peak earlier in the day, and negative circadian regulators are expressed at higher amplitudes and peak later in the day. In endothelial cells, negative circadian regulators exhibit an increased amplitude of expression, while the positive circadian regulators are arrhythmic with a decreased amplitude of expression. This indicates that Akt1 conditions the normal circadian rhythm in the vasculature more so than in other peripheral tissues where other AKT isoforms or kinases might be important for daily rhythms. PMID:28452287

Akt1 Controls the Timing and Amplitude of Vascular Circadian Gene Expression.

PubMed

Luciano, Amelia K; Santana, Jeans M; Velazquez, Heino; Sessa, William C

2017-06-01

The AKT signaling pathway is important for circadian rhythms in mammals and flies ( Drosophila). However, AKT signaling in mammals is more complicated since there are 3 isoforms of AKT, each performing slightly different functions. Here we study the most ubiquitous AKT isoform, Akt1, and its role at the organismal level in the central and vascular peripheral clocks. Akt1 -/- mice exhibit relatively normal behavioral rhythms with only minor differences in circadian gene expression in the liver and heart. However, circadian gene expression in the Akt1 -/- aorta, compared with control aorta, follows a distinct pattern. In the Akt1 -/- aorta, positive regulators of circadian transcription have lower amplitude rhythms and peak earlier in the day, and negative circadian regulators are expressed at higher amplitudes and peak later in the day. In endothelial cells, negative circadian regulators exhibit an increased amplitude of expression, while the positive circadian regulators are arrhythmic with a decreased amplitude of expression. This indicates that Akt1 conditions the normal circadian rhythm in the vasculature more so than in other peripheral tissues where other AKT isoforms or kinases might be important for daily rhythms.

Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value

PubMed Central

Bloch, Guy; Barnes, Brian M.; Gerkema, Menno P.; Helm, Barbara

2013-01-01

Circadian rhythms are ubiquitous in many organisms. Animals that are forced to be active around the clock typically show reduced performance, health and survival. Nevertheless, we review evidence of animals showing prolonged intervals of activity with attenuated or nil overt circadian rhythms and no apparent ill effects. We show that around-the-clock and ultradian activity patterns are more common than is generally appreciated, particularly in herbivores, in animals inhabiting polar regions and habitats with constant physical environments, in animals during specific life-history stages (such as migration or reproduction), and in highly social animals. The underlying mechanisms are diverse, but studies suggest that some circadian pacemakers continue to measure time in animals active around the clock. The prevalence of around-the-clock activity in diverse animals and habitats, and an apparent diversity of underlying mechanisms, are consistent with convergent evolution. We suggest that the basic organizational principles of the circadian system and its complexity encompass the potential for chronobiological plasticity. There may be trade-offs between benefits of persistent daily rhythms versus plasticity, which for reasons still poorly understood make overt daily arrhythmicity functionally adaptive only in selected habitats and for selected lifestyles. PMID:23825202

Metabolic consequences of sleep and circadian disorders

PubMed Central

Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

2014-01-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

Metabolic consequences of sleep and circadian disorders.

PubMed

Depner, Christopher M; Stothard, Ellen R; Wright, Kenneth P

2014-07-01

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed.

Differences in cortisol profiles and circadian adjustment time between nurses working night shifts and regular day shifts: A prospective longitudinal study.

PubMed

Niu, Shu-Fen; Chung, Min-Huey; Chu, Hsin; Tsai, Jui-Chen; Lin, Chun-Chieh; Liao, Yuan-Mei; Ou, Keng-Liang; O'Brien, Anthony Paul; Chou, Kuei-Ru

2015-07-01

This study explored the differences in the circadian salivary cortisol profiles between nurses working night shifts and regular day shifts following a slow rotating shift schedule to assess the number of days required for adjusting the circadian rhythm of salivary cortisol levels in nurses working consecutive night shifts and the number of days off required to restore the diurnal circadian rhythm of salivary cortisol levels. This was a prospective, longitudinal, parallel-group comparative study. The participants were randomly assigned to night and day-shift groups, and saliva samples were collected to measure their cortisol levels and circadian secretion patterns. Significant differences were observed in the overall salivary cortisol pattern parameters (cortisol awakening response, changes in cortisol profiles between 6 and 12h after awakening, and changes in cortisol profiles between 30 min and 12 h after awakening) from Days 2 to 4 of the workdays between both groups. However, on Day 2 of the days off, both groups exhibited similar cortisol profiles and the cortisol profiles in the night-shift group were restored. Nurses working night shifts require at least 4 days to adjust their circadian rhythms of cortisol secretions. Moreover, on changing from night shift to other shifts, nurses must be allowed more than 2 days off work. Copyright © 2015 Elsevier Ltd. All rights reserved.

Altered circadian patterns of salivary cortisol in individuals with schizophrenia: A critical literature review.

PubMed

Coulon, Nathalie; Brailly-Tabard, Sylvie; Walter, Michel; Tordjman, Sylvie

2016-11-01

This article focuses on stress vulnerability in schizophrenia through an integrated clinical and biological approach. The objective of this article is to better understand the relationships between vulnerability, stress and schizophrenia. First, the concept of vulnerability is defined and several models of vulnerability in schizophrenia are reviewed. Second, a section is developed on the biology of stress, and more specifically on the stress responses of the hypothalamo-pitutary adrenal (HPA) axis. Then, studies of cortisol circadian rhythms are summarized, suggesting hyper-reactivity of the HPA axis in patients with schizophrenia and high risk individuals for schizophrenia. The results support the models of stress vulnerability in schizophrenia and the hypothesis of high cortisol levels as an endophenotype in this disorder. In conclusion, this article highlights the interest of studying the cortisol circadian rhythms in schizophrenia and opens the perspective to identify high risk individuals for schizophrenia by measuring circadian patterns of salivary cortisol. Copyright © 2017 Elsevier Ltd. All rights reserved.

The usefulness of GPS telemetry to study wolf circadian and social activity

USGS Publications Warehouse

Merrill, Samuel B.; Mech, L. David

2003-01-01

This study describes circadian and social movement patterns of 9 wolves and illustrates capabilities and limitations of Global Positioning System (GPS) telemetry for analysis of animal activity patterns. Global Positioning System telemetry was useful in determining when pack members were traveling together or apart and how long a breeding female wolf spent near her pups (e.g., 10-month-old pups were left unattended by their mother for as long as 17 days).

[Descriptive study of ambulatory blood pressure monitoring in the Primary Care Nursing clinic].

PubMed

Garzón-Quiñones, Marina; Gallardo-Gonzalo, Cristina; Padín-Minaya, Cristina; López-Pisa, Rosa M; Rodríguez-Latre, Luisa M

2013-01-01

To analyze the clinical characteristics and the circadian patterns of patients who received ambulatory blood pressure monitoring (ABPM) by a Primary Care Team. A descriptive, observational, cross-sectional study at community level. People older than 18 years on ABPM (2007-2011). demographic, cardiovascular disease, diabetes mellitus, cardiovascular risk factors, any type of arterial hypertension and circadian pattern. Intruments of measurement: 2 validated instruments with comparable results were used. The instruments for ABPM were placed during the nursing visit. The instruments were then removed after 24h, and the data was retrieved and recorded in the computerized clinical history. A total of 326 people were studied, with a mean age of 60.53±12.96 years, of whom 56.7% were male. According to ABPM the patient results showed that: 38.5% had «white coat» arterial hypertension, 36.2% were classified as poorly controlled arterial hypertension, 17.2% had masked hypertension, and 8% with isolated hypertension. Dipper circadian patterns were present in 39.6% of patients and non- dipper in 60.4%. ABPM allows to Primary Health Care professionals to check the actual situation of the blood pressure over 24h and analyze the circadian pattern. In clinical practice this involves having a comprehensive care strategy on life style, as well as adherence to treatment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans

PubMed Central

Shea, Steven A.; Hilton, Michael F.; Orlova, Christine; Ayers, R. Timothy; Mantzoros, Christos S.

2010-01-01

Leptin and adiponectin play important physiological roles in regulating appetite, food intake, and energy balance and have pathophysiological roles in obesity and anorexia nervosa. To assess the relative contributions of day/night patterns in behaviors (sleep/wake cycle and food intake) and of the endogenous circadian pacemaker on observed day/night patterns of adipokines, in six healthy subjects we measured circulating leptin, soluble leptin receptor, adiponectin, glucose, and insulin levels throughout a constant routine protocol (38 h of wakefulness with constant posture, temperature, and dim light, as well as identical snacks every 2 h) and throughout sleep and fasting periods before and after the constant routine. There were significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening. Sleep/fasting resulted in additional systematic decreases in leptin, glucose, and insulin, whereas wakefulness/food intake resulted in a systematic increase in leptin. Thus, the day/night pattern in leptin is likely caused by combined effects from the endogenous circadian pacemaker and day/night patterns in behaviors. Our data imply that alterations in the sleep/wake schedule would lead to an increased daily range in circulating leptin, with lowest leptin upon awakening, which, by influencing food intake and energy balance, could be implicated in the increased prevalence of obesity in the shift work population. PMID:15687326

Circadian and circannual rhythms in the metabolism and ventilation of red-eared sliders (Trachemys scripta elegans).

PubMed

Reyes, Catalina; Milsom, William K

2010-01-01

Endogenous circadian and circannual rhythms may exist in the metabolism, ventilation, and breathing pattern of turtles that could further prolong dive times during daily and seasonal periods of reduced activity. To test this hypothesis, turtles were held under seasonal or constant environmental conditions over a 1-yr period, and in each season, V(O)(2) and respiratory variables were measured in all animals under both the prevailing seasonal conditions and the constant conditions for 24 h. Endogenous circadian and circannual rhythms in metabolism and ventilation occurred independent of ambient temperature, photoperiod, and activity, although long-term entrainment to daily and seasonal changes in temperature and photoperiod were required for them to be expressed. Metabolism and ventilation were always higher during the photophase, and the day-night difference was greater at any given temperature when the photoperiod was provided. When corrected for temperature, turtles had elevated metabolic and ventilation rates in the fall and spring (corresponding to the reproductive seasons) and suppressed metabolism and ventilation during winter. The strength of the circadian rhythm varied seasonally, with proportionately larger day-night differences in colder seasons. Daily and seasonal cycles in ventilation largely followed metabolism, although daily and seasonal changes did occur in the breathing pattern independent of levels of total ventilation. These endogenous circadian and circannual changes in metabolism, ventilation, and breathing pattern prolonged dive times at night and in winter and may serve to reduce the costs of breathing and transport and risk of predation.

Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

PubMed Central

Reed, James W

2016-01-01

SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose control. PMID:27822054

An Approximation to the Temporal Order in Endogenous Circadian Rhythms of Genes Implicated in Human Adipose Tissue Metabolism

PubMed Central

GARAULET, MARTA; ORDOVÁS, JOSÉ M.; GÓMEZ-ABELLÁN, PURIFICACIÓN; MARTÍNEZ, JOSE A.; MADRID, JUAN A.

2015-01-01

Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI ≥ 40 kg/m2). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P <0.05). Amplitude of most genes rhythms was high (>30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. PMID:21520059

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keith, Dove; Finlay, Liam; Butler, Judy

Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve thesemore » results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.« less

Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

PubMed Central

Mora-Rodríguez, Ricardo; Pallarés, Jesús García; López-Samanes, Álvaro; Ortega, Juan Fernando; Fernández-Elías, Valentín E.

2012-01-01

Purpose To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg−1; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, double-blind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75% 1RM load) and muscle power adaptations (1 m s−1 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOKLEG) were measured to identify caffeine's action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85% 1RM) 6 repetitions bout of SQ (POST). Results In the PMPLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AMPLAC treatment (3.0%–7.5%; p≤0.05). During AMCAFF trial, muscle strength and power output increased above AMPLAC levels (4.6%–5.7%; p≤0.05) except for BP velocity with 1 m s−1 load (p = 0.06). During AMCAFF, EVOKLEG and NE (a surrogate of maximal muscle sympathetic nerve activation) were increased above AMPLAC trial (14.6% and 96.8% respectively; p≤0.05). Conclusions These results indicate that caffeine ingestion reverses the morning neuromuscular declines in highly resistance-trained men, raising performance to the levels of the afternoon trial. Our electrical stimulation data, along with the NE values, suggest that caffeine increases neuromuscular performance having a direct effect in the muscle. PMID:22496767

Reversal of the sleep-wake cycle by heroin self-administration in rats.

PubMed

Coffey, Alissa A; Guan, Zhiwei; Grigson, Patricia S; Fang, Jidong

2016-05-01

The goal of this study was to examine how heroin self-administration, abstinence, and extinction/reinstatement affect circadian sleep-wake cycles and the associated sleep architecture. We used electroencephalography (EEG) and electromyography (EMG) to measure sleep patterns in male Sprague-Dawley rats over 16 trials of heroin self-administration (acquisition), 14 days of abstinence, and a single day of extinction and drug-induced reinstatement. Rats self-administering heroin showed evidence of reversed (diurnal) patterns of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep throughout acquisition. During abstinence, their wake and NREM sleep patterns were immediately restored to the normal nocturnal distribution. REM patterns remained inverted for the first 3-6 days of abstinence in heroin self-administering rats. The single extinction/reinstatement test was without effect. These data suggest that heroin may have the ability to affect circadian distribution of sleep and wakefulness, either indirectly, where animals shift their sleep-wake cycle to allow for drug taking, or directly, through wake-promoting actions or actions at circadian oscillators in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Circadian rhythm of salivary cortisol in Asian elephants (Elephas maximus): a factor to consider during welfare assessment.

PubMed

Menargues, Asunción; Urios, Vicente; Limiñana, Ruben; Mauri, Montserrat

2012-01-01

Elevated glucocorticoid levels during an extended time period might be a stress indicator in nonhuman animals. Therefore, knowledge of the circadian pattern of cortisol secretion is very important to correctly interpret data obtained for welfare assessment of animals in captivity through salivary cortisol. In order to define the circadian rhythm of salivary cortisol secretion in the Asian elephant (Elephas maximus), morning and evening saliva samples of 3 Asian elephants were collected and analyzed by radioimmunoassay. Significantly higher salivary cortisol concentrations were found in the morning than in the evening in all individuals. These results show that salivary cortisol of Asian elephants follows a diurnal pattern of secretion, which could be taken into account when using this methodology to assess welfare in captive Asian elephants.

Administration-time-dependent effects of hypertension treatment on ambulatory blood pressure in patients with chronic kidney disease.

PubMed

Crespo, Juan J; Piñeiro, Luis; Otero, Alfonso; Castiñeira, Carmen; Ríos, María T; Regueiro, Antonio; Mojón, Artemio; Lorenzo, Sonia; Ayala, Diana E; Hermida, Ramón C

2013-03-01

Many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in the blood pressure (BP)-lowering efficacy, duration of action, and safety of most classes of hypertension medications. Most important, it was recently documented that routine ingestion of the full daily dose of ≥1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Nocturnal hypertension and non-dipping (<10% decline in the asleep relative to the awake BP mean), as determined by ambulatory BP monitoring (ABPM), are frequent in chronic kidney disease (CKD) and both are associated with increased CVD risk. Here, we investigated the influence of hypertension treatment time on the circadian BP pattern and degree of BP control of hypertensive patients with CKD evaluated by 48-h ABPM. This cross-sectional study evaluated 2659 such patients (1585 men/1074 women), 64.9 ± 13.2 (mean ± SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM; 1446 were ingesting all BP-lowering medications upon awakening, whereas 1213 patients were ingesting ≥1 medications at bedtime. Among the latter, 359 patients were ingesting all medications at bedtime, whereas 854 were ingesting the full daily dose of some medications upon awakening and the others at bedtime. Those ingesting all medications upon awakening had significantly higher total cholesterol and low-density lipoprotein (LDL) cholesterol than those ingesting ≥1 medications at bedtime. Moreover, patients ingesting all medications at bedtime had the lowest fasting glucose, serum creatinine, and uric acid. Ingestion of ≥1 medications at bedtime was significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than treatment with all medications upon awakening. The sleep-time relative SBP decline was significantly attenuated in patients ingesting all medications upon awakening (p < .001). Thus, the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening (68.3%) than when ≥1 of them was ingested at bedtime (54.2%; p < .001 between groups), and even further attenuated (47.9%) when all of them were ingested at bedtime (p < .001). Additionally, the prevalence of a riser BP pattern, associated with highest CVD risk, was much greater (21.5%) among patients ingesting all medications upon awakening, compared with those ingesting some (15.7%) or all medications at bedtime (10.6%; p < .001 between groups), independent of CKD severity (disease stage). The latter group also showed a significantly higher prevalence of properly controlled ambulatory BP (p < .001) that was achieved by a significantly lower number of hypertension medications (p < .001) compared with patients treated upon awakening. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of a blunted nighttime BP decline, i.e., lower prevalence of markers of CVD risk, in patients with CKD ingesting hypertension medications at bedtime than in those ingesting all of them upon awakening. These collective findings indicate that bedtime hypertension treatment, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of hypertension and avoid treatment-induced nocturnal hypotension, should be the preferred therapeutic scheme for CKD.

Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension.

PubMed

Hermida, Ramón C; Ríos, María T; Crespo, Juan J; Moyá, Ana; Domínguez-Sardiña, Manuel; Otero, Alfonso; Sánchez, Juan J; Mojón, Artemio; Fernández, José R; Ayala, Diana E

2013-03-01

Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p < .001 between groups). Additionally, the prevalence of the riser BP pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID-treatment regimens, compared with the bedtime regimen (17.6%; p < .001 between groups). Patients of the bedtime regimen also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) as a result of a greater proportion of them showing complete control of asleep SBP and DBP means. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of blunted nighttime BP decline, i.e., lower prevalence of CVD risk markers, in RH patients ingesting the full daily dose of ≥1 hypertension medications at bedtime than in those ingesting all of them upon awakening or ≥1 of them as split doses BID. In RH, ingesting the same medications BID neither improves ambulatory BP control nor reduces the prevalence of non-dipping, and cannot be considered chronotherapy. Collectively, findings of this study indicate that a bedtime hypertension medication regimen, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true RH and avoid treatment-induced nocturnal hypotension, should be the therapeutic scheme of choice for patients who, by conventional cuff methods (and in the absence of ABPM) and the morning-treatment regimen, have been mistakenly judged to be resistant to therapy.

Daily Light Exposure Patterns Reveal Phase and Period of the Human Circadian Clock.

PubMed

Woelders, Tom; Beersma, Domien G M; Gordijn, Marijke C M; Hut, Roelof A; Wams, Emma J

2017-06-01

Light is the most potent time cue that synchronizes (entrains) the circadian pacemaker to the 24-h solar cycle. This entrainment process is an interplay between an individual's daily light perception and intrinsic pacemaker period under free-running conditions. Establishing individual estimates of circadian phase and period can be time-consuming. We show that circadian phase can be accurately predicted (SD = 1.1 h for dim light melatonin onset, DLMO) using 9 days of ambulatory light and activity data as an input to Kronauer's limit-cycle model for the human circadian system. This approach also yields an estimated circadian period of 24.2 h (SD = 0.2 h), with longer periods resulting in later DLMOs. A larger amount of daylight exposure resulted in an earlier DLMO. Individuals with a long circadian period also showed shorter intervals between DLMO and sleep timing. When a field-based estimation of tau can be validated under laboratory studies in a wide variety of individuals, the proposed methods may prove to be essential tools for individualized chronotherapy and light treatment for shift work and jetlag applications. These methods may improve our understanding of fundamental properties of human circadian rhythms under daily living conditions.

Daily Light Exposure Patterns Reveal Phase and Period of the Human Circadian Clock

PubMed Central

Woelders, Tom; Beersma, Domien G. M.; Gordijn, Marijke C. M.; Hut, Roelof A.; Wams, Emma J.

2017-01-01

Light is the most potent time cue that synchronizes (entrains) the circadian pacemaker to the 24-h solar cycle. This entrainment process is an interplay between an individual’s daily light perception and intrinsic pacemaker period under free-running conditions. Establishing individual estimates of circadian phase and period can be time-consuming. We show that circadian phase can be accurately predicted (SD = 1.1 h for dim light melatonin onset, DLMO) using 9 days of ambulatory light and activity data as an input to Kronauer’s limit-cycle model for the human circadian system. This approach also yields an estimated circadian period of 24.2 h (SD = 0.2 h), with longer periods resulting in later DLMOs. A larger amount of daylight exposure resulted in an earlier DLMO. Individuals with a long circadian period also showed shorter intervals between DLMO and sleep timing. When a field-based estimation of tau can be validated under laboratory studies in a wide variety of individuals, the proposed methods may prove to be essential tools for individualized chronotherapy and light treatment for shift work and jetlag applications. These methods may improve our understanding of fundamental properties of human circadian rhythms under daily living conditions. PMID:28452285

Circadian pattern of fibrillatory events in non-Brugada-type idiopathic ventricular fibrillation with a focus on J waves.

PubMed

Aizawa, Yoshiyasu; Sato, Masahito; Ohno, Seiko; Horie, Minoru; Takatsuki, Seiji; Fukuda, Keiichi; Chinushi, Masaomi; Usui, Tatsuya; Aonuma, Kazutaka; Hosaka, Yukio; Haissaguerre, Michel; Aizawa, Yoshifusa

2014-12-01

The circadian pattern of ventricular fibrillation (VF) episodes in patients with idiopathic ventricular fibrillation (IVF) is poorly understood. The purpose of this study was to assess the circadian pattern of VF occurrence in patients with IVF. Excluding Brugada syndrome and other primary electrical diseases, the circadian pattern of VF occurrence was determined in 64 patients with IVF. The clinical and electrocardiographic characteristics were compared among patients with nocturnal (midnight to 6:00 AM) VF and nonnocturnal VF in relation to J waves. A J wave was defined as either notching or a slur at the QRS terminal >0.1 mV above the isoelectric line in contiguous leads. The overall distribution pattern of VF occurrence showed 2 peaks at approximately 6:00 AM and around 8:00 PM. Nocturnal VF was observed in 20 patients (31.3%), and J waves were present in 14 of these 20 individuals (70.0%), whereas J waves were less frequent in the 44 nonnocturnal patients with VF: 16 (36.4%) (P = .0117). Among patients with J waves, nocturnal VF was observed in 46.7% with a peak at approximately 4:00 AM. Nocturnal VF was less common in patients without J waves, occurring in only 17.6% (P = .0124). Both the type and location of J waves and the pattern of the ST segment were similar between the nocturnal and nonnocturnal VF groups. J waves were associated with a VF storm and long-term arrhythmia recurrence. In IVF, the presence of J waves may characterize a higher nocturnal incidence of VF and a higher acute and chronic risk of recurrence. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Quantifying light-dependent circadian disruption in humans and animal models.

PubMed

Rea, Mark S; Figueiro, Mariana G

2014-12-01

Although circadian disruption is an accepted term, little has been done to develop methods to quantify the degree of disruption or entrainment individual organisms actually exhibit in the field. A variety of behavioral, physiological and hormonal responses vary in amplitude over a 24-h period and the degree to which these circadian rhythms are synchronized to the daily light-dark cycle can be quantified with a technique known as phasor analysis. Several studies have been carried out using phasor analysis in an attempt to measure circadian disruption exhibited by animals and by humans. To perform these studies, species-specific light measurement and light delivery technologies had to be developed based upon a fundamental understanding of circadian phototransduction mechanisms in the different species. When both nocturnal rodents and diurnal humans, experienced different species-specific light-dark shift schedules, they showed, based upon phasor analysis of the light-dark and activity-rest patterns, similar levels of light-dependent circadian disruption. Indeed, both rodents and humans show monotonically increasing and quantitatively similar levels of light-dependent circadian disruption with increasing shift-nights per week. Thus, phasor analysis provides a method for quantifying circadian disruption in the field and in the laboratory as well as a bridge between ecological measurements of circadian entrainment in humans and parametric studies of circadian disruption in animal models, including nocturnal rodents.

Patterns of activity expressed by juvenile horseshoe crabs.

PubMed

Dubofsky, E A; Simpson, S D; Chabot, Christopher C; Watson, Winsor H

2013-09-01

Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian and circatidal clocks controlling visual sensitivity and locomotion, respectively. The goal of this study was to determine the types of activity rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10 light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD). Horseshoe crab activity was recorded with a digital time-lapse video system that used an infrared-sensitive camera so animals could be monitored at night. In LD, 15 animals expressed daily patterns of activity, 6 displayed a circatidal pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily patterns of locomotion, 7 had a significant preference (P < 0.05) for diurnal activity and 3 for nocturnal activity; the remainder did not express a significant preference for day or night activity. In DD, 13 horseshoe crabs expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although these results suggest the presence of a circadian clock influencing circatidal patterns of locomotion, these apparent circadian rhythms may actually represent the expression of just one of the two bouts of activity driven by the putative circalunidian clocks that control their tidal rhythms. Overall, these results indicate that, like adults, juvenile horseshoe crabs express both daily and tidal patterns of activity and that at least one, and maybe both, of these patterns is driven by endogenous clocks.

Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice.

PubMed

Bedrosian, Tracy A; Herring, Kamillya L; Weil, Zachary M; Nelson, Randy J

2011-07-12

Both normal aging and dementia are associated with dysregulation of the biological clock, which contributes to disrupted circadian organization of physiology and behavior. Diminished circadian organization in conjunction with the loss of cholinergic input to the cortex likely contributes to impaired cognition and behavior. One especially notable and relatively common circadian disturbance among the aged is "sundowning syndrome," which is characterized by exacerbated anxiety, agitation, locomotor activity, and delirium during the hours before bedtime. Sundowning has been reported in both dementia patients and cognitively intact elderly individuals living in institutions; however, little is known about temporal patterns in anxiety and agitation, and the neurobiological basis of these rhythms remains unspecified. In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice. We then attempted to treat the observed behavioral disturbances in the aged mice using chronic nightly melatonin treatment. Finally, we tested the hypothesis that time-of-day differences in acetylcholinesterase and choline acetyltransferase expression and general neuronal activation (i.e., c-Fos expression) coincide with the behavioral symptoms. Our results show a temporal pattern of anxiety-like behavior that emerges in elderly mice. This behavioral pattern coincides with elevated locomotor activity relative to adult mice near the end of the dark phase, and with time-dependent changes in basal forebrain acetylcholinesterase expression. Transgenic APP mice show a similar behavioral phenomenon that is not observed among age-matched wild-type mice. These results may have useful applications to the study and treatment of age- and dementia-related circadian behavioral disturbances, namely, sundowning syndrome.

Remote reprogramming of hepatic circadian transcriptome by breast cancer.

PubMed

Hojo, Hiroaki; Enya, Sora; Arai, Miki; Suzuki, Yutaka; Nojiri, Takashi; Kangawa, Kenji; Koyama, Shinsuke; Kawaoka, Shinpei

2017-05-23

Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcription factors, represented by Rev-erba and Rorg, exhibited abnormal daily expression rhythm in the liver of 4T1-bearing mice. Accordingly, expression patterns of specific set of downstream circadian genes were compromised. Osgin1, a marker for oxidative stress, was an example. Specific downstream genes, including E2f8, a transcriptional repressor that controls cellular polyploidy, displayed a striking pattern of disruption, "day-night reversal." Meanwhile, we found that the liver of 4T1-bearing mice suffered from increased oxidative stress. The tetraploid hepatocytes population was concomitantly increased in 4T1-bearing mice, which has not been previously appreciated as a cancer-induced phenotype. In summary, the current study provides a comprehensive characterization of the 4T1-affected hepatic circadian transcriptome that possibly underlies cancer-induced physiological alteration in the liver.

Dynamic Patterns in Mood Among Newly Diagnosed Patients With Major Depressive Episode or Panic Disorder and Normal Controls

PubMed Central

Katerndahl, David; Ferrer, Robert; Best, Rick; Wang, Chen-Pin

2007-01-01

Objective: The purpose of this pilot study was to compare the dynamic patterns of hourly mood variation among newly diagnosed primary care patients with major depressive disorder or panic disorder with patterns in patients with neither disorder. Method: Five adult patients with major depressive episode, 5 with panic disorder, and 5 with neither disorder were asked to complete hourly self-assessments of anxiety and depression (using 100-mm visual analog scales) for each hour they were awake during a 30-day period. Time series were analyzed using ARIMA (autoregression, integration, moving average) modeling (to assess periodicity), Lyapunov exponents (to assess sensitivity to initial conditions indicative of chaotic patterns), and correlation dimension saturation (to assess whether an attractor is limiting change). The study was conducted from March to June 2003. Results: Controls displayed circadian rhythms with underlying chaotic variability. Depressed patients did not display circadian rhythm, but did show chaotic dynamics. Panic disorder patients showed circadian rhythms, but 2 of the 4 patients completing the self-assessments displayed nonchaotic underlying patterns. Conclusions: Patients with major depressive disorder or panic disorder may differ from controls and from each other in their patterns of mood variability. There is a need for more research on the dynamics of mood among patients with mental disorders. PMID:17632650

Making the clock tick: the transcriptional landscape of the plant circadian clock.

PubMed

Ronald, James; Davis, Seth J

2017-01-01

Circadian clocks are molecular timekeepers that synchronise internal physiological processes with the external environment by integrating light and temperature stimuli. As in other eukaryotic organisms, circadian rhythms in plants are largely generated by an array of nuclear transcriptional regulators and associated co-regulators that are arranged into a series of interconnected molecular loops. These transcriptional regulators recruit chromatin-modifying enzymes that adjust the structure of the nucleosome to promote or inhibit DNA accessibility and thus guide transcription rates. In this review, we discuss the recent advances made in understanding the architecture of the Arabidopsis oscillator and the chromatin dynamics that regulate the generation of rhythmic patterns of gene expression within the circadian clock.

The melatonin-sensitive circadian clock of the enteric bacterium Enterobacter aerogenes.

PubMed

Paulose, Jiffin K; Cassone, Vincent M

2016-09-02

Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26°C to 40°C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves.

Daily pattern of energy distribution and weight loss.

PubMed

Raynor, Hollie A; Li, Fan; Cardoso, Chelsi

2018-08-01

Timing of energy intake, a temporal dietary pattern, may enhance health. Eating a greater amount of energy earlier and a smaller amount of energy later in the day, a behavioral circadian rhythm, may assist with chronoenhancement. Chronoenhancement seeks to enhance entrainment (synchronization) of biological and behavioral circadian rhythms. In humans, research reports that eating a greater amount of energy early and a smaller amount of energy later in the day increases dietary induced thermogenesis, improves cardiometabolic outcomes, and enhances weight loss. However, little human research has examined if this eating pattern enhances regularity of biological circadian rhythm. In a randomized controlled 8-week pilot study, the influence of energy distribution timing on weight loss and regularity of sleep onset and wake times (marker for biological circadian rhythm) was examined. Within an hypocaloric, three-meal prescription, participants (n = 8) were assigned to either: 1) Morning: 50%, 30%, and 20% of kcal at breakfast, lunch, and dinner, respectively; or 2) Evening: 20%, 30%, and 50% of kcal at breakfast, lunch, and dinner, respectively. Percent weight loss and regularity of sleep onset and wake times were significantly (p < 0.05) greater for Morning than Evening. To enhance understanding of the influence of energy distribution timing on health, longer studies conducted in free-living participants, with dietary intake assessed using time-stamped methods, that include measures of the circadian timing system are needed. This small review is based upon a symposium presentation at the Society of the Study of Ingestive Behavior in 2017. Copyright © 2018 Elsevier Inc. All rights reserved.

Does the circadian clock drift when pilots fly multiple transpacific flights with 1- to 2-day layovers?

PubMed

Gander, Philippa; Mulrine, Hannah M; van den Berg, Margo J; Wu, Lora; Smith, Alexander; Signal, Leigh; Mangie, Jim

2016-01-01

On trips with multiple transmeridian flights, pilots experience successive non-24 h day/night cycles with circadian and sleep disruption. One study across a 9-day sequence of transpacific flights (no in-flight sleep, 1-day layovers between flights) reported an average period in the core body temperature rhythm of 24.6 h (circadian drift). Consequently, pilots were sometimes flying through the circadian performance nadir and had to readapt to home base time at the end of the trip. The present study examined circadian drift in trip patterns with longer flights and in-flight sleep. Thirty-nine B747-400 pilots (19 captains, 20 first officers, mean age = 55.5 years) were monitored on 9- to 13-day trips with multiple return flights between East Coast USA and Japan (in 4-pilot crews) and between Japan and Hawaii (in 3-pilot crews), with 1-day layovers between each flight. Measures included total in-flight sleep (actigraphy, log books) and top of descent (TOD) measures of sleepiness (Karolinska Sleepiness Scale), fatigue (Samn-Perelli Crew Status Check) and psychomotor vigilance task (PVT) performance. Circadian rhythms of individual pilots were not monitored. To detect circadian drift, mixed-model analysis of variance examined whether for a given flight, total in-flight sleep and TOD measures varied according to when the flight occurred in the trip sequence. In addition, sleep propensity curves for pre-trip and post-trip days were examined (Chi-square periodogram analyses). Limited data suggest that total in-flight sleep of relief crew at landing may have decreased across successive East Coast USA-Japan (flights 1, 3, 5 or 7; median arrival 03:45 Eastern Daylight Time (EDT)). However, PVT response speed at TOD was faster on East Coast USA-Japan flights later in the trip. On these flights, circadian drift would result in flights later in the trip landing closer to the evening wake maintenance zone, when sleep is difficult and PVT response speeds are fastest. On Japan-East Coast USA flights (flights 2, 4, 6 or 8; median arrival time 14:52 EDT), PVT response speeds were slower on flight 8 than on flight 2. Circadian drift would move these arrivals progressively earlier in the SCN pacemaker cycle, where PVT response speeds are slower. Across the five post-trip days, 12 pilots (Group A) immediately resumed their pre-trip sleep pattern of a single nocturnal sleep episode; 9 pilots (Group B) had a daytime nap on most days that moved progressively earlier until it merged with nocturnal sleep and 17 pilots (Group C) had nocturnal sleep and intermittent naps. Chi-square periodogram analyses of the sleep propensity curves for each group across baseline and post-trip days suggest full adaptation to EDT from post-trip day 1 (dominant period = 24 h). However, in Groups B and C, the patterns of split sleep post-trip compared to pre-trip suggest that this may be misleading. We conclude that the trends in total in-flight sleep and significant changes in PVT performance speed at TOD provide preliminary evidence for circadian drift, as do persistent patterns of split sleep post-trip. However, new measures to track circadian rhythms in individual pilots are needed to confirm these findings.

Chronic Maternal Low-Protein Diet in Mice Affects Anxiety, Night-Time Energy Expenditure and Sleep Patterns, but Not Circadian Rhythm in Male Offspring

PubMed Central

Mahadevan, Sangeetha K.; Fiorotto, Marta L.; Van den Veyver, Ignatia B.

2017-01-01

Offspring of murine dams chronically fed a protein-restricted diet have an increased risk for metabolic and neurobehavioral disorders. Previously we showed that adult offspring, developmentally exposed to a chronic maternal low-protein (MLP) diet, had lower body and hind-leg muscle weights and decreased liver enzyme serum levels. We conducted energy expenditure, neurobehavioral and circadian rhythm assays in male offspring to examine mechanisms for the body-weight phenotype and assess neurodevelopmental implications of MLP exposure. C57BL/6J dams were fed a protein restricted (8%protein, MLP) or a control protein (20% protein, C) diet from four weeks before mating until weaning of offspring. Male offspring were weaned to standard rodent diet (20% protein) and single-housed until 8–12 weeks of age. We examined body composition, food intake, energy expenditure, spontaneous rearing activity and sleep patterns and performed behavioral assays for anxiety (open field activity, elevated plus maze [EPM], light/dark exploration), depression (tail suspension and forced swim test), sociability (three-chamber), repetitive (marble burying), learning and memory (fear conditioning), and circadian behavior (wheel-running activity during light-dark and constant dark cycles). We also measured circadian gene expression in hypothalamus and liver at different Zeitgeber times (ZT). Male offspring from separate MLP exposed dams had significantly greater body fat (P = 0.03), less energy expenditure (P = 0.004), less rearing activity (P = 0.04) and a greater number of night-time rest/sleep bouts (P = 0.03) compared to control. MLP offspring displayed greater anxiety-like behavior in the EPM (P<0.01) but had no learning and memory deficit in fear-conditioning assay (P = 0.02). There was an effect of time on Per1, Per 2 and Clock circadian gene expression in the hypothalamus but not on circadian behavior. Thus, transplacental and early developmental exposure of dams to chronic MLP reduces food intake and energy expenditure, increases anxiety like behavior and disturbs sleep patterns but not circadian rhythm in adult male offspring. PMID:28099477

A Comparative Study of Circadian Rhythm Functioning and Sleep in People with Asperger Syndrome

ERIC Educational Resources Information Center

Hare, Dougal Julian; Jones, Steven; Evershed, Kate

2006-01-01

The circadian rhythm functioning and sleep patterns of 10 adults with Asperger syndrome were investigated using actigraphy. When compared with data from neurotypical adults, both statistical and clinically significant differences were found between the two groups, with the adults with Asperger syndrome showing marked abnormalities in both the…

The association of circadian clock candidate genes to increased adiposity in the TIGER study

USDA-ARS?s Scientific Manuscript database

Obesity is a highly prevalent disease that has become a major health crisis in the United States. A number of studies have suggested a link between the altered sleep/wake patterns associated with our "24 hour" lifestyle and obesity. We hypothesize that disruption of the circadian clock intrinsic t...

Effects of short-term feed deprivation and melatonin implants on circadian patterns of leptin in the horse.

PubMed

Buff, P R; Morrison, C D; Ganjam, V K; Keisler, D H

2005-05-01

Leptin is a protein hormone produced by adipose tissue that influences hypothalamic mechanisms regulating appetite and energy balance. In species tested thus far, including horses, concentrations of leptin increase as animal fat mass increases. The variables and mechanisms that influence the secretion of leptin are not well known, nor is it known in equine species how the secretion of leptin is influenced by acute alterations in energy balance, circadian patterns, and/or reproductive competence. Our objectives were to determine in horses: 1) whether plasma concentrations of leptin are secreted in a circadian and/or a pulsatile pattern; 2) whether a 48-h period of feed restriction would alter plasma concentrations of leptin, growth hormone, or insulin; and 3) whether ovariectomy and/or a melatonin implant would affect leptin. In Exp. 1, mares exposed to ambient photoperiod of visible light (11 h, 33 min to 11 h, 38 min), received treatments consisting of a 48-h feed restriction (RES) or 48 h of alfalfa hay fed ad libitum (FED). Mares were maintained in a dry lot before sampling and were tethered to a rail during sampling. Analyses revealed that leptin was not secreted in a pulsatile manner, and that mean leptin concentrations were greater (P < 0.001) in FED vs. RES mares (17.20 +/- 0.41 vs. 7.29 +/- 0.41 ng/mL). Plasma growth hormone was pulsatile, and mean concentrations were greater in RES than FED mares (2.15 +/- 0.31 vs. 1.08 +/- 0.31 ng/mL; P = 0.05). Circadian patterns of leptin secretion were observed, but only in FED mares (15.39 +/- 0.58 ng/mL for morning vs. 19.00 +/- 0.58 ng/mL for evening; P < 0.001). In Exp. 2, mares that were ovariectomized or intact received either a s.c. melatonin implant or a sham implant. Thereafter, blood was sampled at weekly intervals at 1000 and 1700. Concentrations of leptin in samples collected at 1700 were greater (P < 0.001) than in those collected at 1000 (28.24 +/- 1.7 vs. 22.07 +/- 1.7 ng/mL). Neither ovariectomy nor chronic treatment with melatonin affected plasma concentrations of leptin or the circadian pattern of secretion. These data provide evidence that plasma leptin concentrations in the equine are sensitive to acute changes in nutritional status and vary in a circadian pattern that is sensitive to fasting but not to melatonin treatment or ovariectomy.

Circadian gene methylation profiles are associated with obesity, metabolic disturbances and carbohydrate intake.

PubMed

Ramos-Lopez, Omar; Samblas, Mirian; Milagro, Fermin I; Riezu-Boj, Jose I; Crujeiras, A B; Martinez, J Alfredo; Project, Mena

2018-03-26

The circadian clock regulates the daily rhythms of several physiological and behavioral processes. Disruptions in clock genes have been associated with obesity and related comorbidities. This study aimed to analyze the association of DNA methylation signatures at circadian rhythm pathway genes with body mass index (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was determined by microarray in white blood cells from 474 adults from the Methyl Epigenome Network Association (MENA) project. Kyoto Encyclopedia of Genes and Genomes database was used to identify the genes integrating the circadian rhythm pathway. Network enrichment analyses were performed with the PathDIP platform. Associations between circadian methylation patterns with anthropometric measurements, the metabolic profile, clinical data and dietary intakes were analyzed. DNA methylation patterns of nine CpG sites at six circadian rhythm pathway genes were strongly correlated with BMI (false discovery rates <0.0001). These CpGs encompassed cg09578018 (RORA), cg20406576 (PRKAG2), cg10059324 (PER3), cg01180628 (BHLHE40), cg23871860 (FBXL3), cg16964728 (RORA), cg14129040 (CREB1), cg07012178 (PRKAG2) and cg24061580 (PRKAG2). Interestingly, network enrichment analyses revealed that the six BMI-associated genes statistically contributed to the regulation of the circadian rhythm pathway (p = 1.9E-10). In addition, methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628 (BHLHE40) and cg10059324 (PER3) also correlated with insulin resistance (p < 0.0001) and mean arterial blood pressure (p < 0.0001). Furthermore, relevant correlations (p < 0.05) between methylation at cg09578018 (RORA) and cg01180628 (BHLHE40) with total energy and carbohydrate intakes were found. This investigation revealed potential associations of DNA methylation profiles at circadian genes with obesity, metabolic disturbances and carbohydrate intake, with potential impact on weight homeostasis.

CHRONOBIOLOGY OF HIGH BLOOD PRESSURE

PubMed Central

Cornélissen, G.; Halberg, F.; Bakken, E. E.; Wang, Z.; Tarquini, R.; Perfetto, F.; Laffi, G.; Maggioni, C.; Kumagai, Y.; Homolka, P.; Havelková, A.; Dušek, J.; Svačinová, H.; Siegelová, J.; Fišer, B.

2008-01-01

BIOCOS, the project aimed at studying BIOlogical systems in their COSmos, has obtained a great deal of expertise in the fields of blood pressure (BP) and heart rate (HR) monitoring and of marker rhythmometry for the purposes of screening, diagnosis, treatment, and prognosis. Prolonging the monitoring reduces the uncertainty in the estimation of circadian parameters; the current recommendation of BIOCOS requires monitoring for at least 7 days. The BIOCOS approach consists of a parametric and a non-parametric analysis of the data, in which the results from the individual subject are being compared with gender- and age-specified reference values in health. Chronobiological designs can offer important new information regarding the optimization of treatment by timing its administration as a function of circadian and other rhythms. New technological developments are needed to close the loop between the monitoring of blood pressure and the administration of antihypertensive drugs. PMID:19122770

Circadian manifestations of barbiturate habituation, addiction and withdrawal in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ehret, C. F.; Peraino, C.; Meinert, J. C.

1979-01-01

The present study uses circadian rhythm observations on rats to include diverse habituation and drug ingestion (phenobarbital) circumstances, including a comparison of the effect of pre-entrainment cycles of programmed feeding and illumination and subsequent conditions of exposure of duration sufficient to permit a steady-state in the appearance of circadian patterns derived from core-temperature telemetry and from automated food-consumption measurements. Finally, measurements were permitted to continue long enough after the drug was withdrawn from the diet to allow characterization of an abstinence syndrome, indicative of addiction.

Transmedulla Neurons in the Sky Compass Network of the Honeybee (Apis mellifera) Are a Possible Site of Circadian Input

PubMed Central

Zeller, Maximilian; Held, Martina; Bender, Julia; Berz, Annuska; Heinloth, Tanja; Hellfritz, Timm; Pfeiffer, Keram

2015-01-01

Honeybees are known for their ability to use the sun’s azimuth and the sky’s polarization pattern for spatial orientation. Sky compass orientation in bees has been extensively studied at the behavioral level but our knowledge about the underlying neuronal systems and mechanisms is very limited. Electrophysiological studies in other insect species suggest that neurons of the sky compass system integrate information about the polarization pattern of the sky, its chromatic gradient, and the azimuth of the sun. In order to obtain a stable directional signal throughout the day, circadian changes between the sky polarization pattern and the solar azimuth must be compensated. Likewise, the system must be modulated in a context specific way to compensate for changes in intensity, polarization and chromatic properties of light caused by clouds, vegetation and landscape. The goal of this study was to identify neurons of the sky compass pathway in the honeybee brain and to find potential sites of circadian and neuromodulatory input into this pathway. To this end we first traced the sky compass pathway from the polarization-sensitive dorsal rim area of the compound eye via the medulla and the anterior optic tubercle to the lateral complex using dye injections. Neurons forming this pathway strongly resembled neurons of the sky compass pathway in other insect species. Next we combined tracer injections with immunocytochemistry against the circadian neuropeptide pigment dispersing factor and the neuromodulators serotonin, and γ-aminobutyric acid. We identified neurons, connecting the dorsal rim area of the medulla to the anterior optic tubercle, as a possible site of neuromodulation and interaction with the circadian system. These neurons have conspicuous spines in close proximity to pigment dispersing factor-, serotonin-, and GABA-immunoreactive neurons. Our data therefore show for the first time a potential interaction site between the sky compass pathway and the circadian clock. PMID:26630286

Transmedulla Neurons in the Sky Compass Network of the Honeybee (Apis mellifera) Are a Possible Site of Circadian Input.

PubMed

Zeller, Maximilian; Held, Martina; Bender, Julia; Berz, Annuska; Heinloth, Tanja; Hellfritz, Timm; Pfeiffer, Keram

2015-01-01

Honeybees are known for their ability to use the sun's azimuth and the sky's polarization pattern for spatial orientation. Sky compass orientation in bees has been extensively studied at the behavioral level but our knowledge about the underlying neuronal systems and mechanisms is very limited. Electrophysiological studies in other insect species suggest that neurons of the sky compass system integrate information about the polarization pattern of the sky, its chromatic gradient, and the azimuth of the sun. In order to obtain a stable directional signal throughout the day, circadian changes between the sky polarization pattern and the solar azimuth must be compensated. Likewise, the system must be modulated in a context specific way to compensate for changes in intensity, polarization and chromatic properties of light caused by clouds, vegetation and landscape. The goal of this study was to identify neurons of the sky compass pathway in the honeybee brain and to find potential sites of circadian and neuromodulatory input into this pathway. To this end we first traced the sky compass pathway from the polarization-sensitive dorsal rim area of the compound eye via the medulla and the anterior optic tubercle to the lateral complex using dye injections. Neurons forming this pathway strongly resembled neurons of the sky compass pathway in other insect species. Next we combined tracer injections with immunocytochemistry against the circadian neuropeptide pigment dispersing factor and the neuromodulators serotonin, and γ-aminobutyric acid. We identified neurons, connecting the dorsal rim area of the medulla to the anterior optic tubercle, as a possible site of neuromodulation and interaction with the circadian system. These neurons have conspicuous spines in close proximity to pigment dispersing factor-, serotonin-, and GABA-immunoreactive neurons. Our data therefore show for the first time a potential interaction site between the sky compass pathway and the circadian clock.

Lithium lengthens circadian period of cultured brain slices in area specific manner.

PubMed

Yoshikawa, Tomoko; Honma, Sato

2016-11-01

Lithium has been used for the treatment of bipolar disorder (BD). However, the mechanisms how lithium exerts its mood stabilizing effects remain to be studied. The disorder in circadian pacemaking has been suggested as an underlying mechanism of the characteristic mood instability of the BD. Lithium is also known to lengthen the circadian periods. We recently proposed that chronic methamphetamine treatment induced circadian oscillation as a complex oscillator including multiple dopaminergic brain areas, and the complex oscillator regulates behavior rhythm independent from the central circadian oscillator in the suprachiasmatic nucleus (SCN). Sleep-wake pattern of rapid cycling BD exhibits similar rhythm disorganization to methamphetamine treated animals. Therefore, we hypothesized that the dysregulated circadian rhythm in BD patients is caused by desynchronization of sleep-wake rhythms from the central clock in the SCN, and that mood stabilizing effect of lithium is achieved through their resynchronization. In the present experiment, we examined how lithium affects the circadian rhythms of brain areas involved in the complex oscillator as well as the SCN. Here we report that lithium lengthens the circadian periods in the SCN, olfactory bulb, median eminence and substantia nigra with dose and area specific manner. The effective lithium dose was much higher than the plasma levels that are required for lengthening the circadian behavior rhythms as well for therapeutic use. Low dose of lithium did not lengthen the period but enhanced the amplitude of circadian rhythms, which may exert therapeutic effects on BD. Copyright © 2016 Elsevier B.V. All rights reserved.

Absence of Circadian Rhythms of Preterm Premature Rupture of Membranes and Preterm Placental Abruption

PubMed Central

Luque-Fernandez, Miguel Angel; Ananth, Cande V.; Sanchez, Sixto E.; Qiu, Chun-fang; Hernandez-Diaz, Sonia; Valdimarsdottir, Unnur; Gelaye, Bizu; Williams, Michelle A.

2014-01-01

Purpose Data regarding circadian rhythm in the onset of spontaneous preterm premature rupture of membranes (PROM) and placental abruption (PA) cases are conflicting. We modeled the time of onset of preterm PROM and PA cases and examined if the circadian profiles varied based on the gestational age at delivery. Methods We used parametric and nonparametric methods, including trigonometric regression in the framework of generalized linear models, to test the presence of circadian rhythms in the time of onset of preterm PROM and PA cases, among 395 women who delivered a singleton between 2009 and 2010 in Lima, Peru. Results We found a diurnal circadian pattern, with a morning peak at 07h:32’ (95%CI:05h:46’ – 09h:18’) among moderate preterm PROM cases (P-value<0.001), and some evidence of a diurnal circadian periodicity among PA cases in term infants (P-value=0.067). However, we did not find evidence of circadian rhythms in the time of onset of extremely or very preterm PROM (P-value=0.259) and preterm PA (P-value=0.224). Conclusions The circadian rhythms of the time of onset of preterm PROM and PA cases varied based on gestational weeks at delivery. While circadian rhythms were presented among moderate preterm PROM and term PA cases, there was no evidence of circadian rhythms among preterm PA and very or extremely preterm PROM cases, underlying other mechanisms associated with the time of onset. PMID:25453346

Introduction: circadian rhythm and its disruption: impact on reproductive function.

PubMed

Casper, Robert F; Gladanac, Bojana

2014-08-01

Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Circadian rhythm and menopause.

PubMed

Pines, A

2016-12-01

Circadian rhythm is an internal biological clock which initiates and monitors various physiological processes with a fixed time-related schedule. The master circadian pacemaker is located in the suprachiasmatic nucleus in the hypothalamus. The circadian clock undergoes significant changes throughout the life span, at both the physiological and molecular levels. This cyclical physiological process, which is very complex and multifactorial, may be associated with metabolic alterations, atherosclerosis, impaired cognition, mood disturbances and even development of cancer. Sex differences do exist, and the well-known sleep disturbances associated with menopause are a good example. Circadian rhythm was detected in the daily pattern of hot flushes, with a peak in the afternoons. Endogenous secretion of melatonin decreases with aging across genders, and, among women, menopause is associated with a significant reduction of melatonin levels, affecting sleep. Although it might seem that hot flushes and melatonin secretion are likely related, there are not enough data to support such a hypothesis.

Working under daylight intensity lamp: an occupational risk for developing circadian rhythm sleep disorder?

PubMed

Doljansky, J T; Kannety, H; Dagan, Y

2005-01-01

A 47-yr-old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep-wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part-time position 7 yrs ago, because he was unable to maintain a regular full-time job schedule. A 10-day actigraphic record revealed an irregular sleep-wake pattern with extensive day-to-day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep-wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond-grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep-wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10-day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep-wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep-wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep-wake cycle and melancholy.

Physiological effects of light on the human circadian pacemaker

NASA Technical Reports Server (NTRS)

Shanahan, T. L.; Czeisler, C. A.

2000-01-01

The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

Diurnal oscillations of soybean circadian clock and drought responsive genes.

PubMed

Marcolino-Gomes, Juliana; Rodrigues, Fabiana Aparecida; Fuganti-Pagliarini, Renata; Bendix, Claire; Nakayama, Thiago Jonas; Celaya, Brandon; Molinari, Hugo Bruno Correa; de Oliveira, Maria Cristina Neves; Harmon, Frank G; Nepomuceno, Alexandre

2014-01-01

Rhythms produced by the endogenous circadian clock play a critical role in allowing plants to respond and adapt to the environment. While there is a well-established regulatory link between the circadian clock and responses to abiotic stress in model plants, little is known of the circadian system in crop species like soybean. This study examines how drought impacts diurnal oscillation of both drought responsive and circadian clock genes in soybean. Drought stress induced marked changes in gene expression of several circadian clock-like components, such as LCL1-, GmELF4- and PRR-like genes, which had reduced expression in stressed plants. The same conditions produced a phase advance of expression for the GmTOC1-like, GmLUX-like and GmPRR7-like genes. Similarly, the rhythmic expression pattern of the soybean drought-responsive genes DREB-, bZIP-, GOLS-, RAB18- and Remorin-like changed significantly after plant exposure to drought. In silico analysis of promoter regions of these genes revealed the presence of cis-elements associated both with stress and circadian clock regulation. Furthermore, some soybean genes with upstream ABRE elements were responsive to abscisic acid treatment. Our results indicate that some connection between the drought response and the circadian clock may exist in soybean since (i) drought stress affects gene expression of circadian clock components and (ii) several stress responsive genes display diurnal oscillation in soybeans.

Diurnal Oscillations of Soybean Circadian Clock and Drought Responsive Genes

PubMed Central

Marcolino-Gomes, Juliana; Rodrigues, Fabiana Aparecida; Fuganti-Pagliarini, Renata; Bendix, Claire; Nakayama, Thiago Jonas; Celaya, Brandon; Molinari, Hugo Bruno Correa; de Oliveira, Maria Cristina Neves; Harmon, Frank G.; Nepomuceno, Alexandre

2014-01-01

Rhythms produced by the endogenous circadian clock play a critical role in allowing plants to respond and adapt to the environment. While there is a well-established regulatory link between the circadian clock and responses to abiotic stress in model plants, little is known of the circadian system in crop species like soybean. This study examines how drought impacts diurnal oscillation of both drought responsive and circadian clock genes in soybean. Drought stress induced marked changes in gene expression of several circadian clock-like components, such as LCL1-, GmELF4- and PRR-like genes, which had reduced expression in stressed plants. The same conditions produced a phase advance of expression for the GmTOC1-like, GmLUX-like and GmPRR7-like genes. Similarly, the rhythmic expression pattern of the soybean drought-responsive genes DREB-, bZIP-, GOLS-, RAB18- and Remorin-like changed significantly after plant exposure to drought. In silico analysis of promoter regions of these genes revealed the presence of cis-elements associated both with stress and circadian clock regulation. Furthermore, some soybean genes with upstream ABRE elements were responsive to abscisic acid treatment. Our results indicate that some connection between the drought response and the circadian clock may exist in soybean since (i) drought stress affects gene expression of circadian clock components and (ii) several stress responsive genes display diurnal oscillation in soybeans. PMID:24475115

Environmental disruption of the circadian clock leads to altered sleep and immune responses in mouse.

PubMed

Phillips, Derrick J; Savenkova, Marina I; Karatsoreos, Ilia N

2015-07-01

In mammals, one of the most salient outputs of the circadian (daily) clock is the timing of the sleep-wake cycle. Modern industrialized society has led to a fundamental breakdown in the relationship between our endogenous timekeeping systems and the solar day, disrupting normal circadian rhythms. We have argued that disrupted circadian rhythms could lead to changes in allostatic load, and the capacity of organisms to respond to other environmental challenges. In this set of studies, we apply a model of circadian disruption characterized in our lab in which mice are housed in a 20h long day, with 10h of light and 10h of darkness. We explored the effects of this environmental disruption on sleep patterns, to establish if this model results in marked sleep deprivation. Given the interaction between circadian, sleep, and immune systems, we further probed if our model of circadian disruption also alters the innate immune response to peripheral bacterial endotoxin challenge. Our results demonstrate that this model of circadian disruption does not lead to marked sleep deprivation, but instead affects the timing and quality of sleep. We also show that while circadian disruption does not lead to basal changes in the immune markers we explored, the immune response is affected, both in the brain and the periphery. Together, our findings further strengthen the important role of the circadian timing system in sleep regulation and immune responses, and provide evidence that disrupting the circadian clock increases vulnerability to further environmental stressors, including immunological challenges. Copyright © 2014 Elsevier Inc. All rights reserved.

Daily methylphenidate and atomoxetine treatment impacts on clock gene protein expression in the mouse brain.

PubMed

Baird, Alison L; Coogan, Andrew N; Kaufling, Jennifer; Barrot, Michel; Thome, Johannes

2013-06-04

Circadian rhythms are repeating patterns of physiological and other parameters that recur with periods of approximately 24h, and are generated by an endogenous circadian timekeeping mechanism. Such circadian rhythms, and their underlying molecular mechanisms, are known to be altered by a number of central nervous system acting pharmacological compounds, as well as becoming perturbed in a number of common psychiatric and neurological conditions. The psychostimulant methylphenidate and the non-stimulant atomoxetine are used in the pharmacotherapy of attention deficit hyperactivity disorder, a common condition in which circadian rhythms have been reported to be altered. In the present study we have examined the effects of daily methylphenidate or atomoxetine treatment across 7 days on circadian clock gene product expression across numerous brain regions in the male mouse to test the potential impact of such compounds on circadian timing. We report drug, brain region and molecular specific effects of such treatments, including alterations in expression profiles in the suprachiasmatic nucleus, the master circadian pacemaker. These results indicate that drugs used in the clinical management of attention deficit hyperactivity disorder can alter molecular factors that are believed to underpin circadian timekeeping, and such effects may be of importance in both the therapeutic and side effect profiles of such drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

PubMed

Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

2018-01-15

Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

The effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach.

PubMed

Skeldon, Anne C; Phillips, Andrew J K; Dijk, Derk-Jan

2017-03-27

Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity ('social jet-lag'). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag.

Influence of the Circadian System on Disease Severity

PubMed Central

Litinski, Mikhail; Scheer, Frank AJL; Shea, Steven A

2009-01-01

Synopsis The severity of many diseases varies across the day and night. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, and/or endogenous circadian rhythms in physiology. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease and certain cancers in shift workers. Here we describe the magnitude, relevance and potential biological basis of such daily changes in disease severity and of circadian/behavioral misalignment, and present how these insights may help in the development of appropriate chronotherapy. PMID:20161149

Specific Transcriptome Changes Associated with Blood Pressure Reduction in Hypertensive Patients After Relaxation Response Training.

PubMed

Bhasin, Manoj K; Denninger, John W; Huffman, Jeff C; Joseph, Marie G; Niles, Halsey; Chad-Friedman, Emma; Goldman, Roberta; Buczynski-Kelley, Beverly; Mahoney, Barbara A; Fricchione, Gregory L; Dusek, Jeffery A; Benson, Herbert; Zusman, Randall M; Libermann, Towia A

2018-05-01

Mind-body practices that elicit the relaxation response (RR) have been demonstrated to reduce blood pressure (BP) in essential hypertension (HTN) and may be an adjunct to antihypertensive drug therapy. However, the molecular mechanisms by which the RR reduces BP remain undefined. Genomic determinants associated with responsiveness to an 8-week RR-based mind-body intervention for lowering HTN in 13 stage 1 hypertensive patients classified as BP responders and 11 as nonresponders were identified. Transcriptome analysis in peripheral blood mononuclear cells identified 1771 genes regulated by the RR in responders. Biological process- and pathway-based analysis of transcriptome data demonstrated enrichment in the following gene categories: immune regulatory pathways and metabolism (among downregulated genes); glucose metabolism, cardiovascular system development, and circadian rhythm (among upregulated genes). Further in silico estimation of cell abundance from the microarray data showed enrichment of the anti-inflammatory M2 subtype of macrophages in BP responders. Nuclear factor-κB, vascular endothelial growth factor, and insulin were critical molecules emerging from interactive network analysis. These findings provide the first insights into the molecular mechanisms that are associated with the beneficial effects of the RR on HTN.

Specific Transcriptome Changes Associated with Blood Pressure Reduction in Hypertensive Patients After Relaxation Response Training

PubMed Central

Bhasin, Manoj K.; Denninger, John W.; Huffman, Jeff C.; Joseph, Marie G.; Niles, Halsey; Chad-Friedman, Emma; Goldman, Roberta; Buczynski-Kelley, Beverly; Mahoney, Barbara A.; Fricchione, Gregory L.; Dusek, Jeffery A.; Benson, Herbert; Zusman, Randall M.

2018-01-01

Abstract Objective: Mind–body practices that elicit the relaxation response (RR) have been demonstrated to reduce blood pressure (BP) in essential hypertension (HTN) and may be an adjunct to antihypertensive drug therapy. However, the molecular mechanisms by which the RR reduces BP remain undefined. Design: Genomic determinants associated with responsiveness to an 8-week RR-based mind–body intervention for lowering HTN in 13 stage 1 hypertensive patients classified as BP responders and 11 as nonresponders were identified. Results: Transcriptome analysis in peripheral blood mononuclear cells identified 1771 genes regulated by the RR in responders. Biological process- and pathway-based analysis of transcriptome data demonstrated enrichment in the following gene categories: immune regulatory pathways and metabolism (among downregulated genes); glucose metabolism, cardiovascular system development, and circadian rhythm (among upregulated genes). Further in silico estimation of cell abundance from the microarray data showed enrichment of the anti-inflammatory M2 subtype of macrophages in BP responders. Nuclear factor-κB, vascular endothelial growth factor, and insulin were critical molecules emerging from interactive network analysis. Conclusions: These findings provide the first insights into the molecular mechanisms that are associated with the beneficial effects of the RR on HTN. PMID:29616846

Association of salivary cortisol with chronomics of 24 hours ambulatory blood pressure/heart rate among night shift workers.

PubMed

Anjum, B; Verma, N S; Tiwari, S; Singh, R; Mahdi, A A; Singh, R B; Singh, R K

2011-08-01

Recent studies indicate a circadian rhythm in blood pressure and heart rate and its association with various neurotransmitters. In the present study, we examine the circadian nature of blood pressure/heart rate and salivary cortisol in night shift workers and whether these circadian changes produced by night shifts are reversible. Sixteen healthy nurses of both genders, aged 20-40 years, performing day and night shift duties, were randomly selected out of 22 who volunteered for this study. Ambulatory blood pressure monitoring was done in all the subjects and salivary cortisol levels were analyzed during both day and night shift duties. There were clinically significant changes in the Acrophase of blood pressure and cortisol levels, indicating ecphasia (odd timing of systolic blood pressure) individually during night as well as day shifts. However, this pattern was statistically not significant. A reverse pattern of Acrophase was observed in 8 out of 16 subjects when they were posted on day shift. No significant change was found in midline estimating statistics of rhythm (MESOR) of blood pressure values. Changes in Double amplitude (Predictable change) were observed in 8 subjects during night shifts as well as in 7 subjects during day shifts. However, the pattern was not similar and night workers had an altered circadian pattern in the night as well as during day shifts. Changes in Double amplitude, Acrophase and Salivary cortisol were found during night as well as day shifts but these changes were not statistically significant (p > 0.05) due to incomplete recovery during day shifts (changes again seen when they came back to day shifts). Salivary cortisol levels were lowest in early morning, increased at midnight and further increased in the afternoon during night shifts along with ecphasia. It is possible that nurses working the night shift felt more tired due to the altered circadian cycle.

Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster.

PubMed

Ma, Lingling; Ma, Jun; Xu, Kanyan

2015-01-01

Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China's Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight.

Effect of Spaceflight on the Circadian Rhythm, Lifespan and Gene Expression of Drosophila melanogaster

PubMed Central

Xu, Kanyan

2015-01-01

Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China’s Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight. PMID:25798821

Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice.

PubMed

Zhao, Yue; Liu, Min; Chan, Xue Ying; Tan, Sue Yee; Subramaniam, Sharrada; Fan, Yong; Loh, Eva; Chang, Kenneth Tou En; Tan, Thiam Chye; Chen, Qingfeng

2017-11-02

Many immune parameters show circadian rhythms during the 24-hour day in mammals. The most striking circadian oscillation is the number of circulating immune cells that display an opposite rhythm between humans and mice. The physiological roles and mechanisms of circadian variations in mouse leukocytes are well studied, whereas for humans they remain unclear because of the lack of a proper model. In this study, we found that consistent with their natural host species, mouse and human circulating leukocytes exhibited opposite circadian oscillations in humanized mice. This cyclic pattern of trafficking correlated well with the diurnal expression levels of C-X-C chemokine receptor 4, which were controlled by the intracellular hypoxia-inducible factor 1α/aryl hydrocarbon receptor nuclear translocator-like heterodimer. Furthermore, we also discovered that p38 mitogen-activated protein kinases/mitogen-activated 2 had opposite effects between mice and humans in generating intracellular reactive oxygen species, which subsequently regulated HIF-1α expression. In conclusion, we propose humanized mice as a robust model for human circadian studies and reveal insights on a novel molecular clock network in the human circadian rhythm. © 2017 by The American Society of Hematology.

Temporal dynamics of circadian phase shifting response to consecutive night shifts in healthcare workers: role of light-dark exposure.

PubMed

Stone, Julia E; Sletten, Tracey L; Magee, Michelle; Ganesan, Saranea; Mulhall, Megan D; Collins, Allison; Howard, Mark; Lockley, Steven W; Rajaratnam, Shantha M W

2018-06-01

Shift work is highly prevalent and is associated with significant adverse health impacts. There is substantial inter-individual variability in the way the circadian clock responds to changing shift cycles. The mechanisms underlying this variability are not well understood. We tested the hypothesis that light-dark exposure is a significant contributor to this variability; when combined with diurnal preference, the relative timing of light exposure accounted for 71% of individual variability in circadian phase response to night shift work. These results will drive development of personalised approaches to manage circadian disruption among shift workers and other vulnerable populations to potentially reduce the increased risk of disease in these populations. Night shift workers show highly variable rates of circadian adaptation. This study examined the relationship between light exposure patterns and the magnitude of circadian phase resetting in response to night shift work. In 21 participants (nursing and medical staff in an intensive care unit) circadian phase was measured using 6-sulphatoxymelatonin at baseline (day/evening shifts or days off) and after 3-4 consecutive night shifts. Daily light exposure was examined relative to individual circadian phase to quantify light intensity in the phase delay and phase advance portions of the light phase response curve (PRC). There was substantial inter-individual variability in the direction and magnitude of phase shift after three or four consecutive night shifts (mean phase delay -1:08 ± 1:31 h; range -3:43 h delay to +3:07 h phase advance). The relative difference in the distribution of light relative to the PRC combined with diurnal preference accounted for 71% of the variability in phase shift. Regression analysis incorporating these factors estimated phase shift to within ±60 min in 85% of participants. No participants met criteria for partial adaptation to night work after three or four consecutive night shifts. Our findings provide evidence that the phase resetting that does occur is based on individual light exposure patterns relative to an individual's baseline circadian phase. Thus, a 'one size fits all' approach to promoting adaptation to shift work using light therapy, implemented without knowledge of circadian phase, may not be efficacious for all individuals. © 2018 Monash University. The Journal of Physiology © 2018 The Physiological Society.

Circadian Sleep-Wake Rhythm of Older Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Maaskant, Marijke; van de Wouw, Ellen; van Wijck, Ruud; Evenhuis, Heleen M.; Echteld, Michael A.

2013-01-01

The circadian sleep-wake rhythm changes with aging, resulting in a more fragmented sleep-wake pattern. In individuals with intellectual disabilities (ID), brain structures regulating the sleep-wake rhythm might be affected. The aims of this study were to compare the sleep-wake rhythm of older adults with ID to that of older adults in the general…

Effects of time-of-day of hypertension treatment on ambulatory blood pressure and clinical characteristics of patients with type 2 diabetes.

PubMed

Moyá, Ana; Crespo, Juan J; Ayala, Diana E; Ríos, María T; Pousa, Lorenzo; Callejas, Pedro A; Salgado, José L; Mojón, Artemio; Fernández, José R; Hermida, Ramón C

2013-03-01

Generally, hypertensive patients ingest all their blood pressure (BP)-lowering agents in the morning. However, many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in BP-lowering efficacy, duration of action, and safety of most classes of hypertension medications, and it was recently documented that routine ingestion of ≥1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Non-dipping (<10% decline in asleep relative to awake BP mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and is associated with increased CVD risk. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and analytical parameters of hypertensive patients with type 2 diabetes evaluated by 48-h ABPM. This cross-sectional study involved 2429 such patients (1465 men/964 women), 65.9 ± 10.6 (mean ± SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM. Among the participants, 1176 were ingesting all BP-lowering medications upon awakening, whereas 1253 patients were ingesting ≥1 medications at bedtime. Among the latter, 336 patients were ingesting all BP-lowering medications at bedtime, whereas 917 were ingesting the full daily dose of some hypertension medications upon awakening and the full dose of others at bedtime. Those ingesting ≥1 medications at bedtime versus those ingesting all medications upon awakening had lower likelihood of metabolic syndrome and chronic kidney disease (CKD); had significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; and had higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. Moreover, patients ingesting all medications at bedtime had lowest fasting glucose, serum creatinine, uric acid, and prevalence of proteinuria and CKD. Ingestion of ≥1 medications at bedtime was also significantly associated with lower asleep systolic (SBP) and diastolic BP (DBP) means than treatment with all medications upon awakening. Sleep-time relative SBP and DBP decline was significantly attenuated in patients ingesting all medications upon awakening (p < .001). Thus, the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening (68.6%) than when ≥1 of them was ingested at bedtime (55.8%; p < .001 between groups), and even further attenuated (49.7%) when all of them were ingested at bedtime (p < .001). Additionally, prevalence of the riser BP pattern, associated with highest CVD risk, was much greater (23.6%) among patients ingesting all medications upon awakening, compared with those ingesting some (20.0%) or all medications at bedtime (12.2%; p < .001 between groups). The latter group also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) that was achieved by a significantly lower number of hypertension medications (p < .001) compared with patients treated upon awakening. Our findings demonstrate significantly lower asleep SBP mean and attenuated prevalence of a blunted nighttime BP decline, i.e., lower prevalence of markers of CVD risk, and improved metabolic profile in patients with type 2 diabetes ingesting hypertension medications at bedtime than in those ingesting all of them upon awakening. These collective findings indicate that bedtime hypertension treatment, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of hypertension and avoid treatment-induced nocturnal hypotension, should be the preferred therapeutic scheme for type 2 diabetes.

Dim nighttime light impairs cognition and provokes depressive-like responses in a diurnal rodent.

PubMed

Fonken, Laura K; Kitsmiller, Emily; Smale, Laura; Nelson, Randy J

2012-08-01

Circadian disruption is a common by-product of modern life. Although jet lag and shift work are well-documented challenges to circadian organization, many more subtle environmental changes cause circadian disruption. For example, frequent fluctuations in the timing of the sleep/wake schedule, as well as exposure to nighttime lighting, likely affect the circadian system. Most studies of these effects have focused on nocturnal rodents, which are very different from diurnal species with respect to their patterns of light exposure and the effects that light can have on their activity. Thus, the authors investigated the effect of nighttime light on behavior and the brain of a diurnal rodent, the Nile grass rat. Following 3 weeks of exposure to standard light/dark (LD; 14:10 light [~150 lux] /dark [0 lux]) or dim light at night (dLAN; 14:10 light [~150 lux] /dim [5 lux]), rats underwent behavioral testing, and hippocampal neurons within CA1, CA3, and the dentate gyrus (DG) were examined. Three behavioral effects of dLAN were observed: (1) decreased preference for a sucrose solution, (2) increased latency to float in a forced swim test, and (3) impaired learning and memory in the Barnes maze. Light at night also reduced dendritic length in DG and basilar CA1 dendrites. Dendritic length in the DG positively correlated with sucrose consumption in the sucrose anhedonia task. Nighttime light exposure did not disrupt the pattern of circadian locomotor activity, and all grass rats maintained a diurnal activity pattern. Together, these data suggest that exposure to dLAN can alter affective responses and impair cognition in a diurnal animal.

The relevance of restrained eating behavior for circadian eating patterns in adolescents

PubMed Central

Alexy, Ute; Diederichs, Tanja; Buyken, Anette E.; Roßbach, Sarah

2018-01-01

Background Restrained Eating, i.e. the tendency to restrict dietary intake to control body-weight, often emerges during adolescence and may result in changes in circadian eating patterns. Objective The objective of the present investigation was to determine the cross-sectional relevance of restrained eating for characteristics of circadian eating pattern in adolescents and whether changes in restrained eating are accompanied by concurrent changes in circadian eating pattern over the course of adolescence. Methods Two questionnaires assessing restrained eating (Score 0–30) with parallel 3-day weighed dietary records from two different time points were available from 209 (♂:101, ♀:108) 11–18 year old adolescents of the DONALD study. Mixed linear regression models were used to analyze whether restrained eating was associated with eating occasion frequency, snack frequency and morning and evening energy intake [in % of daily energy intake, %E]. Linear regression models were used to examine whether changes in restrained eating were associated with changes in the mentioned variables. Results Among girls, greater restrained eating was cross-sectionally associated with higher morning energy intake (p = 0.03). Further, there was a tendency towards lower evening energy intake with higher levels of restrained eating for the whole sample (p = 0.06). No cross-sectional associations were found with eating occasion or snack frequency. Each one-point increase in restrained eating during adolescence was related to a concurrent decrease in eating occasion frequency by 0.04 (95% CI -0.08; -0.01, p = 0.02) and in evening energy intake by 0.36%E (95% CI -0.70; -0.03, p = 0.04). A tendency towards decreasing snack frequency with increasing restrained eating was observed (β = -0.03, 95% CI -0.07; 0.00, p = 0.07). No association was found between changes in restrained eating and concurrent changes in morning energy intake. Conclusion We found indications for cross-sectional and prospective associations between restrained eating and chronobiological aspects of food intake in adolescents. Our results suggest that restrained eating should be considered a relevant determinant of circadian eating patterns. PMID:29791516

A Western dietary pattern is associated with higher blood pressure in Iranian adolescents.

PubMed

Hojhabrimanesh, Abdollah; Akhlaghi, Masoumeh; Rahmani, Elham; Amanat, Sasan; Atefi, Masoumeh; Najafi, Maryam; Hashemzadeh, Maral; Salehi, Saedeh; Faghih, Shiva

2017-02-01

The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents. This cross-sectional study was conducted among a representative sample (n = 557) of Shirazi adolescents aged 12-19 years. Participants' systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12 months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups. Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9 mmHg, P = 0.001; and for mean BP: mean difference 4.2 mmHg, P = 0.003). A similar but statistically insignificant difference was observed in terms of diastolic BP. The findings suggest that a Western dietary pattern is associated with higher BP in Iranian adolescents. However, additional large-scale prospective studies with adequate methodological quality are required to confirm these findings.

The relationship between a blunted morning surge and a reversed nocturnal blood pressure dipping or "riser" pattern.

PubMed

Fujiwara, Takeshi; Tomitani, Naoko; Sato, Keiko; Okura, Ayako; Suzuki, Noriyuki; Kario, Kazuomi

2017-11-01

The authors sought to determine the association between the blunted morning blood pressure (BP) surge and nocturnal BP dipping of the "riser" pattern in 501 patients with hypertension enrolled in the ACHIEVE-ONE (Ambulatory Blood Pressure Control and Home Blood Pressure [Morning and Evening] Lowering by the N-Channel Blocker Cilnidipine) trial. The patients' sleep-trough morning BP surge and prewaking surge were calculated and then classified according to their nocturnal systolic BP reduction pattern as extreme dippers, dippers, nondippers, and risers. The prevalence of the riser pattern was significantly higher in both the lowest sleep-trough morning BP surge decile and the prewaking surge decile (blunted surge group) compared with the remaining deciles (56.0% vs 10.4% [P<.0001] and 59.2% vs 10.2% [P<.0001], respectively). The riser pattern was a significant determinant of both blunted sleep-trough morning BP surge (odds ratio, 73.3; P<.0001) and blunted prewaking surge (odds ratio, 14.8; P<.0001). The high prevalence of the riser pattern in patients with blunted morning BP surges may account for the cardiovascular risk previously reported in such patients. ©2017 Wiley Periodicals, Inc.

Metabolic molecular markers of the tidal clock in the marine crustacean Eurydice pulchra

PubMed Central

O’Neill, John Stuart; Lee, Kate D.; Zhang, Lin; Feeney, Kevin; Webster, Simon George; Blades, Matthew James; Kyriacou, Charalambos Panayiotis; Hastings, Michael Harvey; Wilcockson, David Charles

2015-01-01

Summary In contrast to the well mapped molecular orchestration of circadian timekeeping in terrestrial organisms, the mechanisms that direct tidal and lunar rhythms in marine species are entirely unknown. Using a combination of biochemical and molecular approaches we have identified a series of metabolic markers of the tidal clock of the intertidal isopod Eurydice pulchra. Specifically, we show that the overoxidation of peroxiredoxin (PRX), a conserved marker of circadian timekeeping in terrestrial eukaryotes [1], follows a circatidal (approximately 12.4 hours) pattern in E. pulchra, in register with the tidal pattern of swimming. In parallel, we show that mitochondrially encoded genes are expressed with a circatidal rhythm. Together, these findings demonstrate that PRX overoxidation rhythms are not intrinsically circadian; rather they appear to resonate with the dominant metabolic cycle of an organism, regardless of its frequency. Moreover, they provide the first molecular leads for dissecting the tidal clockwork. PMID:25898100

Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight. Part 1; Circadian Rhythms and Temperature Regulation

NASA Technical Reports Server (NTRS)

Fuller, C. A.; Alpatov, A. M.; Hoban-Higgins, T. M.; Klimovitsky, V. Y.

1994-01-01

Mammals have developed the ability to adapt to most variations encountered in their everyday environment. For example, homeotherms have developed the ability to maintain the internal cellular environment at a relatively constant temperature. Also, in order to compensate for temporal variations in the terrestrial environment, the circadian timing system has evolved. However, throughout the evolution of life on earth, living organisms have been exposed to the influence of an unvarying level of earth's gravity. As a result changes in gravity produce adaptive responses which are not completely understood. In particular, spaceflight has pronounced effects on various physiological and behavioral systems. Such systems include body temperature regulation and circadian rhythms. This program has examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite, COSMOS 2044, were exposed to 14 days of microgravity while constantly monitoring the circadian patterns temperature regulation, heart rate and activity. This experiment has extended our previous observations from COSMOS 1514, as well as providing insights into the physiological mechanisms that produce these changes.

Light Therapy and Alzheimer’s Disease and Related Dementia: Past, Present, and Future

PubMed Central

Hanford, Nicholas; Figueiro, Mariana

2012-01-01

Sleep disturbances are common in persons with Alzheimer’s disease or related dementia (ADRD), resulting in a negative impact on the daytime function of the affected person and on the wellbeing of caregivers. The sleep/wake pattern is directly driven by the timing signals generated by a circadian pacemaker, which may or may not be perfectly functioning in those with ADRD. A 24-hour light/dark pattern incident on the retina is the most efficacious stimulus for entraining the circadian system to the solar day. In fact, a carefully orchestrated light/dark pattern has been shown in several controlled studies of older populations, with and without ADRD, to be a powerful non-pharmacological tool to improve sleep efficiency and consolidation. Discussed here are research results from studies looking at the effectiveness of light therapy in improving sleep, depression, and agitation in older adults with ADRD. A 24-hour lighting scheme to increase circadian entrainment, improve visibility, and reduce the risk of falls in those with ADRD is proposed, and future research needs are discussed. PMID:23099814

Light therapy and Alzheimer's disease and related dementia: past, present, and future.

PubMed

Hanford, Nicholas; Figueiro, Mariana

2013-01-01

Sleep disturbances are common in persons with Alzheimer's disease or related dementia (ADRD), resulting in a negative impact on the daytime function of the affected person and on the wellbeing of caregivers. The sleep/wake pattern is directly driven by the timing signals generated by a circadian pacemaker, which may or may not be perfectly functioning in those with ADRD. A 24-hour light/dark pattern incident on the retina is the most efficacious stimulus for entraining the circadian system to the solar day. In fact, a carefully orchestrated light/dark pattern has been shown in several controlled studies of older populations, with and without ADRD, to be a powerful non-pharmacological tool to improve sleep efficiency and consolidation. Discussed here are research results from studies looking at the effectiveness of light therapy in improving sleep, depression, and agitation in older adults with ADRD. A 24-hour lighting scheme to increase circadian entrainment, improve visibility, and reduce the risk of falls in those with ADRD is proposed, and future research needs are discussed.

Sleep and circadian rhythms in long duration space flight - Antarctica as an analogue environment

NASA Technical Reports Server (NTRS)

Gander, Philippa H.

1992-01-01

The feasibility of using Antarctica as an environment for studying the impact of unusual 24 h environmental cycles (zeitgebers) on the circadian system is discussed. Adaptation of circadian rhythms and sleep of three scientists travelling from New Zealand to Antarctica during summer (which is analogous to arrival at a lunar base during the lunar day) has been studied. Data obtained indicate that sleep occurred at the same clock time, but sleep quality was poorer in Antarctica, which can be explained by the fact that the circadian system delayed by about 2 h in Antarctica, as would be expected in a weaker zeitgeber environment. It is suggested that sleep could be improved by altering patterns of exposure to the available zeitgebers to increase their effective strength.

Nanohole and dot patterning processes on quartz substrate by R-θ electron beam lithography and nanoimprinting

NASA Astrophysics Data System (ADS)

Watanabe, Tsuyoshi; Taniguchi, Kazutake; Suzuki, Kouta; Iyama, Hiromasa; Kishimoto, Shuji; Sato, Takashi; Kobayashi, Hideo

2016-06-01

Fine hole and dot patterns with bit pitches (bp’s) of less than 40 nm were fabricated in the circular band area of a quartz substrate by R-θ electron beam lithography (EBL), reactive ion etching (RIE), and nanoimprinting. These patterning processes were studied to obtain minimum pitch sizes of hole and dot patterns without pattern collapse. The patterning on the circular band was aimed to apply these patterning processes to future high-density bit-patterned media (BPM) for hard disk drive (HDD) and permanent memory for the long life archiving of digital data. In hole patterning, a minimum-22-nm-bp and 8.2-nm-diameter pattern (1.3 Tbit/in.2) was obtained on a quartz substrate by optimizing the R-θ EBL and RIE processes. Dot patterns were replicated on another quartz substrate by nanoimprinting using a hole-patterned quartz substrate as a master mold followed by RIE. In dot patterning, a minimum-30-nm-bp and 18.5-nm-diameter pattern (0.7 Tbit/in.2) was obtained by introducing new descum conditions. It was observed that the minimum bp of successful patterning increased as the fabrication process proceeded, i.e., from 20 nm bp in the first EBL process to 30 nm bp in the last quartz dot patterning process. From the measured diameters of the patterns, it was revealed that pattern collapse was apt to occur when the value of average diameter plus 3 sigma of diameter was close to the bp. It was suggested that multiple fabrication processes caused the degradation of pattern quality; therefore, hole patterning is more suitable than dot patterning for future applications owing to the lower quality degradation by its simple fabrication process.

Circadian Rhythms Differ between Sexes and Closely Related Species of Nasonia Wasps

PubMed Central

Bertossa, Rinaldo C.; van Dijk, Jeroen; Diao, Wenwen; Saunders, David; Beukeboom, Leo W.; Beersma, Domien G. M.

2013-01-01

Activity rhythms in 24 h light-dark cycles, constant darkness, and constant light conditions were analyzed in four different Nasonia species for each sex separately. Besides similarities, clear differences are evident among and within Nasonia species as well as between sexes. In all species, activity in a light-dark cycle is concentrated in the photophase, typical for diurnal organisms. Contrary to most diurnal insect species so far studied, Nasonia follows Aschoff's rule by displaying long (>24 h) internal rhythms in constant darkness but short (<24 h) in constant light. In constant light, N. vitripennis males display robust circadian activity rhythms, whereas females are usually arrhythmic. In contrast to other Nasonia species, N. longicornis males display anticipatory activity, i.e. activity shortly before light-on in a light-dark cycle. As expected, N. oneida shows activity patterns similar to those of N. giraulti but with important differences in key circadian parameters. Differences in circadian activity patterns and parameters between species may reflect synchronization of specific life-history traits to environmental conditions. Scheduling mating or dispersion to a specific time of the day could be a strategy to avoid interspecific hybridization in Nasonia species that live in sympatry. PMID:23555911

Correlations between the circadian patterns of body temperature, metabolism and breathing in rats.

PubMed

Mortola, Jacopo P

2007-02-15

It had been demonstrated previously that the circadian patterns of activity and state of arousal are not essential for the manifestation of the daily patterns of pulmonary ventilation (V(E)), tidal volume (V(T)) and breathing frequency (f). In this study we investigated the extent of the linkage between the circadian pattern of breathing and those of body temperature (T(b)) and metabolic rate (oxygen consumption, V(O2), and carbon dioxide production, V(CO2)). Rats were instrumented for measurements of T(b) (by telemetry), and placed in a chamber for continuous 13-day period of measurement of breathing (by a modification of the barometric methodology), and of V(O2) and V(CO2) (by an open flow method). After the first 4 days in control conditions under a 12 h light:12 h dark (L:D) cycle, a perturbation was introduced on day 4, with an L-phase prolongation of 12 h, and on day 9, with an D-phase prolongation of 12 h. During the control days 1-4, all variables had daily oscillations (higher values in D), in phase with each other. During the perturbations (days 4-13), changes in T(b), V(O2) and V(CO2), averaged over the whole period, correlated significantly better with f than with V(T). Day-by-day X-Y loops indicated that V (E), V(T) and f could lead significantly the changes of T(b), V(O2) and V(CO2), and that these relations changed throughout the perturbation period. In addition, f and V(T) did not change necessarily in phase with each other. It is concluded that neither the oscillation in T(b) nor that in metabolism can be considered the direct cause of the daily oscillation of breathing. Presumably, the circadian pattern of breathing reflects the interplay of the daily patterns of many variables, none acting as the primary guide of the breathing daily rhythm.

Associations between circadian and stress response cortisol in children.

PubMed

Simons, Sterre S H; Cillessen, Antonius H N; de Weerth, Carolina

2017-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the cortisol circadian rhythm is associated with cortisol stress responses in 6-year-old children. To this end, 149 normally developing children (M age  = 6.09 years; 70 girls) participated in an innovative social evaluative stress test that effectively provoked increases in cortisol. To determine the cortisol stress response, six cortisol saliva samples were collected and two cortisol stress response indices were calculated: total stress cortisol and cortisol stress reactivity. To determine children's cortisol circadian rhythm eight cortisol circadian samples were collected during two days. Total diurnal cortisol and diurnal cortisol decline scores were calculated as indices of the cortisol circadian rhythm. Hierarchical regression analyses indicated that higher total diurnal cortisol as well as a smaller diurnal cortisol decline, were both uniquely associated with higher total stress cortisol. No associations were found between the cortisol circadian rhythm indices and cortisol stress reactivity. Possible explanations for the patterns found are links with children's self-regulatory capacities and parenting quality.

The effects of self-selected light-dark cycles and social constraints on human sleep and circadian timing: a modeling approach

PubMed Central

Skeldon, Anne C.; Phillips, Andrew J. K.; Dijk, Derk-Jan

2017-01-01

Why do we go to sleep late and struggle to wake up on time? Historically, light-dark cycles were dictated by the solar day, but now humans can extend light exposure by switching on artificial lights. We use a mathematical model incorporating effects of light, circadian rhythmicity and sleep homeostasis to provide a quantitative theoretical framework to understand effects of modern patterns of light consumption on the human circadian system. The model shows that without artificial light humans wakeup at dawn. Artificial light delays circadian rhythmicity and preferred sleep timing and compromises synchronisation to the solar day when wake-times are not enforced. When wake-times are enforced by social constraints, such as work or school, artificial light induces a mismatch between sleep timing and circadian rhythmicity (‘social jet-lag’). The model implies that developmental changes in sleep homeostasis and circadian amplitude make adolescents particularly sensitive to effects of light consumption. The model predicts that ameliorating social jet-lag is more effectively achieved by reducing evening light consumption than by delaying social constraints, particularly in individuals with slow circadian clocks or when imposed wake-times occur after sunrise. These theory-informed predictions may aid design of interventions to prevent and treat circadian rhythm-sleep disorders and social jet-lag. PMID:28345624

Time stamp in conditioned place avoidance can be set to different circadian phases.

PubMed

Cain, Sean W; McDonald, Robert J; Ralph, Martin R

2008-05-01

We have reported that the expression of conditioned place avoidance (CPA) in the golden hamster is regulated in a circadian pattern such that the preference is exhibited strongly at the circadian time of prior training but not at other circadian times [Cain, S. W., Chou, T., & Ralph, M. R. (2004a). Circadian modulation of performance on an aversion-based place learning task in hamsters. Behavioural Brain Research, 150(1-2), 201-205]. In that study, animals that were trained at a specific circadian time to discriminate between a "safe" context and one paired with foot shock, showed strong avoidance of the paired context at 24 and 48h following the last training session, and showed no avoidance at 32 and 40h following training. In the present study, we hypothesized that this "time stamp" effect is settable to any circadian phase. This was tested by training animals at one of two times of day (ZT13 or ZT4) and testing whether a time stamp would be observed, with avoidance occurring only when training and testing times match. Results confirmed our hypothesis, suggesting that the time stamp in the performance of learned tasks can be set to any circadian phase. Such an ability may allow animals in nature to predict the recurrence of 24h events, regardless of the time of day the event was encountered.

Circadian rhythms have significant effects on leaf-to-canopy scale gas exchange under field conditions.

PubMed

Resco de Dios, Víctor; Gessler, Arthur; Ferrio, Juan Pedro; Alday, Josu G; Bahn, Michael; Del Castillo, Jorge; Devidal, Sébastien; García-Muñoz, Sonia; Kayler, Zachary; Landais, Damien; Martín-Gómez, Paula; Milcu, Alexandru; Piel, Clément; Pirhofer-Walzl, Karin; Ravel, Olivier; Salekin, Serajis; Tissue, David T; Tjoelker, Mark G; Voltas, Jordi; Roy, Jacques

2016-10-20

Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO 2 and H 2 O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron. Canopy and leaf-level fluxes were constantly monitored under field-like environmental conditions, and under constant environmental conditions (no variation in temperature, radiation, or other environmental cues). We show direct experimental evidence at canopy scales of the circadian regulation of daytime gas exchange: 20-79 % of the daily variation range in CO 2 and H 2 O fluxes occurred under circadian entrainment in canopies of an annual herb (bean) and of a perennial shrub (cotton). We also observed that considering circadian regulation improved performance by 8-17 % in commonly used stomatal conductance models. Our results show that circadian controls affect diurnal CO 2 and H 2 O flux patterns in entire canopies in field-like conditions, and its consideration significantly improves model performance. Circadian controls act as a 'memory' of the past conditions experienced by the plant, which synchronizes metabolism across entire plant canopies.

Circadian consequences of social organization in the ant species Camponotus compressus

NASA Astrophysics Data System (ADS)

Sharma, Vijay Kumar; Lone, Shahnaz Rahman; Goel, Anubhuthi; Chandrashekaran, M. K.

The locomotor activity rhythm of different castes of the ant species Camponotus compressus was monitored individually under laboratory light/dark (LD) cycles, and under continuous darkness (DD). The colony of this ant species comprises two sexual castes, the queens and the males, and three worker castes, namely the major, media, and minor workers. The virgin males and virgin queens display rhythmic activity patterns, but the mated queens were arrhythmic while laying eggs, with the rhythmicity resuming soon after egg-laying. Under the LD regime, major workers showed nocturnal patterns, while about 75% of the media workers displayed nocturnal patterns and about 25% showed diurnal patterns. Under the DD regime, most major workers exhibited circadian rhythm of activity with a single steady state, whereas media workers displayed two types of activity patterns, with activity patterns changing after 6-9 days in DD (turn-arounds). The pre-turn-around τ of the ants that showed nocturnal activity patterns during LD entrainment was <24 h after release into DD, which then became >24 h, after 6-9 days. On the other hand, the pre-turn-around τ of those ants that exhibited diurnal patterns during LD entrainment was first >24 h after release into DD, and then became <24 h, after 6-9 days. The activity of the minor workers neither entrained to LD cycles nor showed any sign of free-run in DD. It appears that the circadian clocks of the ant species C. compressus are flexible, and may perhaps depend upon the tasks assigned to them in the colony.

Changes in neuropeptide Y immunoreactivity and transcript levels in circadian system structures of the diurnal rodent, the thirteen-lined ground squirrel

PubMed Central

Vidal, Luis; Lugo, Nidza

2007-01-01

The intergeniculate leaflet (IGL) and its neuropeptide Y (NPY) projection to the main circadian clock, the suprachiasmatic nucleus (SCN), have been the focus of extensive research conducted, for the most part, on nocturnal rodent species. However, a variety of anatomical and physiological differences between the circadian system of diurnal and nocturnal species have been reported. These differences led us to question whether the role of NPY in the circadian system of the diurnal ground squirrel differs from that in nocturnal rodents. We used semi-quantitative immunohistochemistry to analyze NPY content in SCN terminals of squirrels sacrificed at specific times of the day and compared the data to previous published results from the rat. Additionally, NPY mRNA was quantified using real-time PCR to determine if varying NPY-immunoreactivity (-ir) levels could be the result of changes in peptide transcription. Our results demonstrate that NPY-ir levels in the ground squirrel SCN peak during the middle of the night unlike what is observed in the rat. Cell counts of NPY-ir neurons in the IGL revealed a pattern of variation 6 hr out of phase compared to what was observed in the SCN. NPY mRNA levels showed only one sharp increase in the middle of the night, coinciding with increases in NPY-ir levels observed in the SCN. Differences in the pattern of fluctuation of NPY in the SCN between the rat and squirrel suggest that this peptide may serve distinct roles in the circadian system of diurnal and nocturnal species. Our data provide the first evidence of the relationship between transcript and peptide levels in the circadian system of a diurnal species. PMID:17109825

Circadian rhythms in insect disease vectors

PubMed Central

Meireles-Filho, Antonio Carlos Alves; Kyriacou, Charalambos Panayiotis

2013-01-01

Organisms from bacteria to humans have evolved under predictable daily environmental cycles owing to the Earth’s rotation. This strong selection pressure has generated endogenous circadian clocks that regulate many aspects of behaviour, physiology and metabolism, anticipating and synchronising internal time-keeping to changes in the cyclical environment. In haematophagous insect vectors the circadian clock coordinates feeding activity, which is important for the dynamics of pathogen transmission. We have recently witnessed a substantial advance in molecular studies of circadian clocks in insect vector species that has consolidated behavioural data collected over many years, which provided insights into the regulation of the clock in the wild. Next generation sequencing technologies will facilitate the study of vector genomes/transcriptomes both among and within species and illuminate some of the species-specific patterns of adaptive circadian phenotypes that are observed in the field and in the laboratory. In this review we will explore these recent findings and attempt to identify potential areas for further investigation. PMID:24473802

Various Regulatory Modes for Circadian Rhythmicity and Sexual Dimorphism in the Non-Neuronal Cardiac Cholinergic System.

PubMed

Oikawa, Shino; Kai, Yuko; Mano, Asuka; Ohata, Hisayuki; Nemoto, Takahiro; Kakinuma, Yoshihiko

2017-08-01

Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS) regulated by a positive feedback system; however, its other regulatory mechanisms remain to be elucidated, which include the epigenetic control or regulation by the female sex steroid, estrogen. Here, the NNCCS was shown to possess a circadian rhythm; its activity was upregulated in the light-off phase via histone acetyltransferase (HAT) activity and downregulated in the light-on phase. Disrupting the circadian rhythm altered the physiological choline acetyltransferase (ChAT) expression pattern. The NNCCS circadian rhythm may be regulated by miR-345, independently of HAT, causing decreased cardiac ChAT expression. Murine cardiac ChAT expression and ACh contents were increased more in female hearts than in male hearts. This upregulation was downregulated by treatment with the estrogen receptor antagonist tamoxifen, and in contrast, estrogen reciprocally regulated cardiac miR-345 expression. These results suggest that the NNCCS is regulated by the circadian rhythm and is affected by sexual dimorphism.

RNA-seq analysis of Drosophila clock and non-clock neurons reveals neuron-specific cycling and novel candidate neuropeptides.

PubMed

Abruzzi, Katharine C; Zadina, Abigail; Luo, Weifei; Wiyanto, Evelyn; Rahman, Reazur; Guo, Fang; Shafer, Orie; Rosbash, Michael

2017-02-01

Locomotor activity rhythms are controlled by a network of ~150 circadian neurons within the adult Drosophila brain. They are subdivided based on their anatomical locations and properties. We profiled transcripts "around the clock" from three key groups of circadian neurons with different functions. We also profiled a non-circadian outgroup, dopaminergic (TH) neurons. They have cycling transcripts but fewer than clock neurons as well as low expression and poor cycling of clock gene transcripts. This suggests that TH neurons do not have a canonical circadian clock and that their gene expression cycling is driven by brain systemic cues. The three circadian groups are surprisingly diverse in their cycling transcripts and overall gene expression patterns, which include known and putative novel neuropeptides. Even the overall phase distributions of cycling transcripts are distinct, indicating that different regulatory principles govern transcript oscillations. This surprising cell-type diversity parallels the functional heterogeneity of the different neurons.

Are circadian rhythms new pathways to understand Autism Spectrum Disorder?

PubMed

Geoffray, M-M; Nicolas, A; Speranza, M; Georgieff, N

2016-11-01

Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep-wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin. This first point raises the hypothesis that circadian rhythms could have an implication in ASD etiology. Moreover, circadian rhythms are generated by auto-regulatory genetic feedback loops, driven by transcription factors CLOCK and BMAL1, who drive transcription daily patterns of a wide number of clock-controlled genes (CCGs) in different cellular contexts across tissues. Among these, are some CCGs coding for synapses molecules associated to ASD susceptibility. Furthermore, evidence emerges about circadian rhythms control of time brain development processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice.

PubMed

Smarr, Benjamin L; Grant, Azure D; Perez, Luz; Zucker, Irving; Kriegsfeld, Lance J

2017-06-12

Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.

Ovariectomy influences the circadian rhythm of locomotor activity and the photic phase shifts in the volcano mouse.

PubMed

Juárez-Tapia, Cinthia; Miranda-Anaya, Manuel

2017-12-01

Recently, the relationship between the circadian system and female reproduction has been of great interest; ovarian hormones can modify the amount and distribution of daily activity differently in rodent species. The volcano mouse Neotomodon alstoni is a species in which it is possible to study the circadian rhythm of locomotion, and it offers comparative information about the influence of ovaries on the circadian system. In this study, we used infrared crossings to compare free movement in intact and sham-operated or ovariectomized mice. We analyzed behavioral and endocrine changes related to the estrous cycle and locomotor circadian rhythm in free-running mice and photic phase shifting. Evidence shows that intact mice present a scalloped pattern of daily activity during the estrous cycle. In constant darkness, the ovariectomy reduces the total amount of activity, shortens the free-running circadian period of locomotion and increases photic phase shifts during the early subjective night. During entrainment, the ovariectomized mice increased the amplitude of total activity during the scotophase, and delay the time of activity onset. These results suggest that ovarian hormones in N. alstoni modulate the circadian rhythm of locomotor activity in a species-specific manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian clocks in the cnidaria: environmental entrainment, molecular regulation, and organismal outputs.

PubMed

Reitzel, Adam M; Tarrant, Ann M; Levy, Oren

2013-07-01

The circadian clock is a molecular network that translates predictable environmental signals, such as light levels, into organismal responses, including behavior and physiology. Regular oscillations of the molecular components of the clock enable individuals to anticipate regularly fluctuating environmental conditions. Cnidarians play important roles in benthic and pelagic marine environments and also occupy a key evolutionary position as the likely sister group to the bilaterians. Together, these attributes make members of this phylum attractive as models for testing hypotheses on roles for circadian clocks in regulating behavior, physiology, and reproduction as well as those regarding the deep evolutionary conservation of circadian regulatory pathways in animal evolution. Here, we review and synthesize the field of cnidarian circadian biology by discussing the diverse effects of daily light cycles on cnidarians, summarizing the molecular evidence for the conservation of a bilaterian-like circadian clock in anthozoan cnidarians, and presenting new empirical data supporting the presence of a conserved feed-forward loop in the starlet sea anemone, Nematostella vectensis. Furthermore, we discuss critical gaps in our current knowledge about the cnidarian clock, including the functions directly regulated by the clock and the precise molecular interactions that drive the oscillating gene-expression patterns. We conclude that the field of cnidarian circadian biology is moving rapidly toward linking molecular mechanisms with physiology and behavior.

Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats

PubMed Central

Sufiun, Abu; Rafiq, Kazi; Fujisawa, Yoshihide; Rahman, Asadur; Mori, Hirohito; Nakano, Daisuke; Kobori, Hiroyuki; Ohmori, Koji; Masaki, Tsutomu; Kohno, Masakazu; Nishiyama, Akira

2015-01-01

A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors have antihypertensive effects. Here, we aim to examine the effect of vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian-dipping pattern during the development of salt-dependent hypertension in Dahl salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl) plus vehicle or vildagliptin (3 or 10 mg kg−1 twice daily by oral gavage) for 7 days. Blood pressure was measured by the telemetry system. High-salt diet for 7 days significantly increased the mean arterial pressure (MAP), systolic blood pressure (SBP) and were also associated with an extreme dipping pattern of blood pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels and attenuated the development of salt-induced hypertension. Furthermore, vildagliptin significantly increased urine sodium excretion and normalized the dipping pattern of blood pressure. In contrast, intracerebroventricular infusion of vildagliptin (50, 500 or 2500 μg) did not alter MAP and heart rate in DSS rats. These data suggest that salt-dependent hypertension initially develops with an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may elicit beneficial antihypertensive effects, including the improvement of abnormal circadian blood pressure pattern, by enhancing urinary sodium excretion. PMID:25588850

Sleepiness and Cognitive Performance among Younger and Older Adolescents across a 28-Hour Forced Desynchrony Protocol.

PubMed

Wu, Lora J; Acebo, Christine; Seifer, Ronald; Carskadon, Mary A

2015-12-01

Quantify the homeostatic and circadian effects on sleepiness and performance of adolescents. Examine age-related changes in homeostatic and circadian regulation of sleepiness and performance by comparing younger and older adolescent groups. Three-week laboratory study including 12 cycles of a 28-h forced desynchrony protocol. Controlled laboratory environment with individual sleep and performance testing rooms and shared common areas. Twenty-seven healthy adolescents including 16 females. Ages ranged from 9.6-15.2 years and participants were split into younger (n = 14 ages 9-12) and older (n = 13 ages 13-15) groups based on median age split of 13.0 years. N/A. Testing occurred every 2 h during scheduled wake periods. Measures included sleep latency during repeated nap opportunities and scores from a computerized neurobehavioral assessment battery including a 10-min psychomotor vigilance task, a digit symbol substitution task, and the Karolinska Sleepiness Scale. Significant main effects of circadian and homeostatic factors were observed, as well as several circadian and homeostatic interaction effects. Age group did not have a significant main effect on sleep and performance data. A significant interaction of circadian phase and age group was found for sleep latency, with younger adolescents showing greater circadian modulation than older teens during the circadian night. Adolescents demonstrated a similar pattern of response to forced desynchrony as reported for adults. Sleepiness and performance were affected by homeostatic and circadian factors, and age group did not interact with homoeostatic and circadian factors for subjective sleepiness and most performance metrics. Younger adolescents had a shorter latency to sleep onset than older during the circadian bin spanning 4 to 8 h after the onset of melatonin secretion. © 2015 Associated Professional Sleep Societies, LLC.

Constant light disrupts the circadian rhythm of steroidogenic proteins in the rat adrenal gland.

PubMed

Park, Shin Y; Walker, Jamie J; Johnson, Nicholas W; Zhao, Zidong; Lightman, Stafford L; Spiga, Francesca

2013-05-22

The circadian rhythm of corticosterone (CORT) secretion from the adrenal cortex is regulated by the suprachiasmatic nucleus (SCN), which is entrained to the light-dark cycle. Since the circadian CORT rhythm is associated with circadian expression of the steroidogenic acute regulatory (StAR) protein, we investigated the 24h pattern of hormonal secretion (ACTH and CORT), steroidogenic gene expression (StAR, SF-1, DAX1 and Nurr77) and the expression of genes involved in ACTH signalling (MC2R and MRAP) in rats entrained to a normal light-dark cycle. We found that circadian changes in ACTH and CORT were associated with the circadian expression of all gene targets; with SF-1, Nurr77 and MRAP peaking in the evening, and DAX1 and MC2R peaking in the morning. Since disruption of normal SCN activity by exposure to constant light abolishes the circadian rhythm of CORT in the rat, we also investigated whether the AM-PM variation of our target genes was also disrupted in rats exposed to constant light conditions for 5weeks. We found that the disruption of the AM-PM variation of ACTH and CORT secretion in rats exposed to constant light was accompanied by a loss of AM-PM variation in StAR, SF-1 and DAX1, and a reversed AM-PM variation in Nurr77, MC2R and MRAP. Our data suggest that circadian expression of StAR is regulated by the circadian expression of nuclear receptors and proteins involved in both ACTH signalling and StAR transcription. We propose that ACTH regulates the secretion of CORT via the circadian control of steroidogenic gene pathways that become dysregulated under the influence of constant light. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Circadian melatonin concentration rhythm is lost in pregnant women with altered blood pressure rhythm.

PubMed

Tranquilli, A L; Turi, A; Giannubilo, S R; Garbati, E

2004-03-01

We assessed the correlation between the rhythm of melatonin concentration and circadian blood pressure patterns in normal and hypertensive pregnancy. Ambulatory 24-h blood pressure and blood samples every 4 h were monitored in 16 primigravidae who had shown an abnormal circadian blood pressure pattern (eight pre-eclamptic and eight normotensive) in pregnancy and 6-12 months after pregnancy. The circadian rhythm was analyzed by chronobiological measures. Eight normotensive women with maintained blood pressure rhythm served as controls. During pregnancy, melatonin concentration was significantly higher in pre-eclamptic than in normotensive women (pre-eclampsia, 29.4 +/- 1.9 pg/ml, normotensin, altered rhythm, 15.6 +/- 2.1; controls, 22.7 +/- 1.8; p < 0.001). This difference faded after pregnancy, owing to the fall observed in pre-eclampsia (11.8 +/- 3.2 pg/ml, 9.8 +/- 2.1, and 11.1 +/- 2.0, respectively; NS). The rhythm of melatonin concentration was lost in all pregnant women with loss of blood pressure rhythm. After pregnancy, normotensive women showed a reappearance of both melatonin and blood pressure rhythm, whereas pre-eclamptic women showed a reappearance of blood pressure but not melatonin rhythm. The loss of blood pressure rhythm in pregnancy is consistent with the loss of melatonin concentration rhythm. In pre-eclamptic women, the normalization of blood pressure rhythm, while melatonin rhythm remained altered, suggests a temporal or causal priority of circadian concentration of melatonin in the determination of blood pressure trend.

Chronobiology, endocrinology, and energy- and food-reward homeostasis.

PubMed

Gonnissen, H K J; Hulshof, T; Westerterp-Plantenga, M S

2013-05-01

Energy- and food-reward homeostasis is the essential component for maintaining energy balance and its disruption may lead to metabolic disorders, including obesity and diabetes. Circadian alignment, quality sleep and sleep architecture in relation to energy- and food-reward homeostasis are crucial. A reduced sleep duration, quality sleep and rapid-eye movement sleep affect substrate oxidation, leptin and ghrelin concentrations, sleeping metabolic rate, appetite, food reward, hypothalamic-pituitary-adrenal (HPA)-axis activity, and gut-peptide concentrations, enhancing a positive energy balance. Circadian misalignment affects sleep architecture and the glucose-insulin metabolism, substrate oxidation, homeostasis model assessment of insulin resistance (HOMA-IR) index, leptin concentrations and HPA-axis activity. Mood disorders such as depression occur; reduced dopaminergic neuronal signaling shows decreased food reward. A good sleep hygiene, together with circadian alignment of food intake, a regular meal frequency, and attention for protein intake or diets, contributes in curing sleep abnormalities and overweight/obesity features by preventing overeating; normalizing substrate oxidation, stress, insulin and glucose metabolism including HOMA-IR index, and leptin, GLP-1 concentrations, lipid metabolism, appetite, energy expenditure and substrate oxidation; and normalizing food reward. Synchrony between circadian and metabolic processes including meal patterns plays an important role in the regulation of energy balance and body-weight control. Additive effects of circadian alignment including meal patterns, sleep restoration, and protein diets in the treatment of overweight and obesity are suggested. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

No effect of pinealectomy on the parallel shift in circadain rhythms of adrenocortical activity and food intake in blinded rats.

PubMed

Takahashi, K; Inoue, K; Takahashi, Y

1976-10-01

Twenty-four-hr patterns of plasma corticosterone levels were determined at 4-hr intervals every 3-4 weeks in sighted and blinded pinealectomized rats of adult age. Through the whole period of the experiment, 24-hr patterns of food intake were also measured weekly. The sighted rats manifested the same 24-hr patterns of plasma corticosterone levels and food intake for 15 weeks after pinealectomy as those observed in the intact control rats. The magnitude of peak levels of plasma corticosterone and the amount of food intake did not differ between the two groups. A phase shift in circadian rhythms of plasma corticosterone levels and food intake was observed in both groups of blinded rats, with and without pinealectomy. Between the two groups, the patterns of phase shift were essentially similar for 10 weeks examined after optic enucleation. The peak elevation of plasma levels took place at 11 p.m. at the end of the 4th week after optic enucleation. Thereafter, 4- to 8-hr delay of peak appearance was observed every 3 weeks. No significant differences were found in peak values between the two groups of blinded rats. Furthermore, the circadian rhythm of food intake shifted in parallel with that of plasma corticosterone levels. A phase reversal of these two activities was observed between the 8th and 10th week after the operation. These results indicate that the pineal gland does not play any important role either in the maintenance of normal circadian periodicities of adrenocortical activity and food intake or in the shift in circadian rhythms of the two activities in the blinded rats.

Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder.

PubMed

Malkani, Roneil G; Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C

2018-04-15

To report the diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder (N24SWD). We report a series of seven sighted patients with N24SWD clinically evaluated by history and sleep diaries, and when available wrist actigraphy and salivary melatonin levels, and treated with timed melatonin and bright light therapy. Most patients had a history of a delayed sleep-wake pattern prior to developing N24SWD. The typical sleep-wake pattern of N24SWD was seen in the sleep diaries (and in actigraphy when available) in all patients with a daily delay in midpoint of sleep ranging 0.8 to 1.8 hours. Salivary dim light melatonin onset (DLMO) was evaluated in four patients but was missed in one. The estimated phase angle from DLMO to sleep onset ranged from 5.25 to 9 hours. All six patients who attempted timed melatonin and bright light therapy were able to entrain their sleep-wake schedules. Entrainment occurred at a late circadian phase, possibly related to the late timing of melatonin administration, though the patients often preferred late sleep times. Most did not continue treatment and continued to have a non-24-hour sleep-wake pattern. N24SWD is a chronic debilitating disorder that is often overlooked in sighted people and can be challenging to diagnose and treat. Tools to assess circadian pattern and timing can be effectively applied to aid the diagnosis. The progressive delay of the circadian rhythm poses a challenge for determining the most effective timing for melatonin and bright light therapies. Furthermore, once the circadian sleep-wake rhythm is entrained, long-term effectiveness is limited because of the behavioral and environmental structure that is required to maintain stable entrainment. © 2018 American Academy of Sleep Medicine.

The expression of the clock gene cycle has rhythmic pattern and is affected by photoperiod in the moth Sesamia nonagrioides.

PubMed

Kontogiannatos, Dimitrios; Gkouvitsas, Theodoros; Kourti, Anna

2017-06-01

To obtain clues to the link between the molecular mechanism of circadian and photoperiod clocks, we have cloned the circadian clock gene cycle (Sncyc) in the corn stalk borer, Sesamia nonagrioides, which undergoes facultative diapause controlled by photoperiod. Sequence analysis revealed a high degree of conservation among insects for this gene. SnCYC consists of 667 amino acids and structural analysis showed that it contains a BCTR domain in its C-terminal in addition to the common domains found in Drosophila CYC, i.e. bHLH, PAS-A, PAS-B domains. The results revealed that the sequence of Sncyc showed a similarity to that of its mammalian orthologue, Bmal1. We also investigated the expression patterns of Sncyc in the brain of larvae growing under long-day 16L: 8D (LD), constant darkness (DD) and short-day 10L: 14D (SD) conditions using qRT-PCR assays. The mRNAs of Sncyc expression was rhythmic in LD, DD and SD cycles. Also, it is remarkable that the photoperiodic conditions affect the expression patterns and/or amplitudes of circadian clock gene Sncyc. This gene is associated with diapause in S. nonagrioides, because under SD (diapause conditions) the photoperiodic signal altered mRNA accumulation. Sequence and expression analysis of cyc in S. nonagrioides shows interesting differences compared to Drosophila where this gene does not oscillate or change in expression patterns in response to photoperiod, suggesting that this species is an interesting new model to study the molecular control of insect circadian and photoperiodic clocks. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.

PubMed

Chappell, Patrick E; White, Rachel S; Mellon, Pamela L

2003-12-03

Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.

Scaling the amplitudes of the circadian pattern of resting oxygen consumption, body temperature and heart rate in mammals.

PubMed

Mortola, Jacopo P; Lanthier, Clement

2004-09-01

We questioned whether the amplitudes of the circadian pattern of body temperature (T(b)), oxygen consumption (V (O(2))) and heart rate (HR) changed systematically among species of different body weight (W). Because bodies of large mass have a greater heat capacitance than those of smaller mass, if the relative amplitude (i.e., amplitude/mean value) of metabolic rate was constant, one would expect the T(b) oscillation to decrease with the increase in the species W. We compiled data of T(b), V (O(2)) and HR from a literature survey of over 200 studies that investigated the circadian pattern of these parameters. Monotremata, Marsupials and Chiroptera, were excluded because of their characteristically low metabolic rate and T(b). The peak-trough ratios of V (O(2)) (42 species) and HR (35 species) averaged, respectively, 1.57+/-0.08, and 1.35+/-0.07, and were independent of W. The daily high values of T(b) did not change, while the daily low T(b) values slightly increased, with the species W; hence, the high-low T(b) difference (57 species) decreased with W (3.3 degrees C.W(-0.13)). However, the decrease in T(b) amplitude with W was much less than expected from physical principles, and the high-low T(b) ratio remained significantly above unity even in the largest mammals. Thus, it appears that in mammals, despite the huge differences in physical characteristics, the amplitude of the circadian pattern is a fixed (for V (O(2)) and HR), or almost fixed (for T(b)), fraction of the 24-h mean value. Presumably, the amplitudes of the oscillations are controlled parameters of physiological significance.

Solving the mystery of human sleep schedules one mutation at a time.

PubMed

Hallows, William C; Ptáček, Louis J; Fu, Ying-Hui

2013-01-01

Sleep behavior remains one of the most enigmatic areas of life. The unanswered questions range from "why do we sleep?" to "how we can improve sleep in today's society?" Identification of mutations responsible for altered circadian regulation of human sleep lead to unique opportunities for probing these territories. In this review, we summarize causative circadian mutations found from familial genetic studies to date. We also describe how these mutations mechanistically affect circadian function and lead to altered sleep behaviors, including shifted or shortening of sleep patterns. In addition, we discuss how the investigation of mutations can not only expand our understanding of the molecular mechanisms regulating the circadian clock and sleep duration, but also bridge the pathways between clock/sleep and other human physiological conditions and ailments such as metabolic regulation and migraine headaches.

Chronobiology and obesity: Interactions between circadian rhythms and energy regulation.

PubMed

Summa, Keith C; Turek, Fred W

2014-05-01

Recent advances in the understanding of the molecular, genetic, neural, and physiologic basis for the generation and organization of circadian clocks in mammals have revealed profound bidirectional interactions between the circadian clock system and pathways critical for the regulation of metabolism and energy balance. The discovery that mice harboring a mutation in the core circadian gene circadian locomotor output cycles kaput (Clock) develop obesity and evidence of the metabolic syndrome represented a seminal moment for the field, clearly establishing a link between circadian rhythms, energy balance, and metabolism at the genetic level. Subsequent studies have characterized in great detail the depth and magnitude of the circadian clock's crucial role in regulating body weight and other metabolic processes. Dietary nutrients have been shown to influence circadian rhythms at both molecular and behavioral levels; and many nuclear hormone receptors, which bind nutrients as well as other circulating ligands, have been observed to exhibit robust circadian rhythms of expression in peripheral metabolic tissues. Furthermore, the daily timing of food intake has itself been shown to affect body weight regulation in mammals, likely through, at least in part, regulation of the temporal expression patterns of metabolic genes. Taken together, these and other related findings have transformed our understanding of the important role of time, on a 24-h scale, in the complex physiologic processes of energy balance and coordinated regulation of metabolism. This research has implications for human metabolic disease and may provide unique and novel insights into the development of new therapeutic strategies to control and combat the epidemic of obesity. © 2014 American Society for Nutrition.

Chronotype and circadian rhythm in bipolar disorder: A systematic review.

PubMed

Melo, Matias C A; Abreu, Rafael L C; Linhares Neto, Vicente B; de Bruin, Pedro F C; de Bruin, Veralice M S

2017-08-01

Despite a complex relationship between mood, sleep and rhythm, the impact of circadian disruptions on bipolar disorder (BD) has not been clarified. The purpose of this systematic review was to define current evidence regarding chronotype and circadian rhythm patterns in BD patients. 42 studies were included, involving 3432 BD patients. Disruption of the biological rhythm was identified, even in drug-naïve BD patients and independently of mood status. Daily profiles of melatonin levels and cortisol indicated a delayed phase. Depression was more frequently associated with circadian alterations than euthymia. Few studies evaluated mania, demonstrating irregular rhythms. Evening type was more common in BD adults. Studies about the influence of chronotype on depressive symptoms showed conflicting results. Only one investigation observed the influences of chronotype in mania, revealing no significant association. Effects of psychoeducation and lithium on rhythm in BD patients were poorly studied, demonstrating no improvement of rhythm parameters. Studies about genetics are incipient. In conclusion, disruption in circadian rhythm and eveningness are common in BD. Prospective research evaluating the impact of circadian disruption on mood symptoms, metabolism, seasonality, the influence of age and the effects of mood stabilizers are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression

PubMed Central

2013-01-01

Background Clinical psychiatry has always been limited by the lack of objective tests to substantiate diagnoses and a lack of specific treatments that target underlying pathophysiology. One area in which these twin failures has been most frustrating is major depression. Due to very considerable progress in the basic and clinical neurosciences of sleep-wake cycles and underlying circadian systems this situation is now rapidly changing. Discussion The development of specific behavioral or pharmacological strategies that target these basic regulatory systems is driving renewed clinical interest. Here, we explore the extent to which objective tests of sleep-wake cycles and circadian function - namely, those that measure timing or synchrony of circadian-dependent physiology as well as daytime activity and nighttime sleep patterns - can be used to identify a sub-class of patients with major depression who have disturbed circadian profiles. Summary Once this unique pathophysiology is characterized, a highly personalized treatment plan can be proposed and monitored. New treatments will now be designed and old treatments re-evaluated on the basis of their effects on objective measures of sleep-wake cycles, circadian rhythms and related metabolic systems. PMID:23521808

[Ambulatory blood pressure monitoring for hypertension diagnosis?

PubMed

Gijón Conde, T; Banegas, J R

2017-01-01

The early and accurate diagnosis of hypertension is essential given its importance in the development of cardiovascular disease. The boundaries between normal blood pressure (BP) and hypertension are arbitrary and based on the benefits of treating exceeding those of not treating. Conventional BP measurement at the clinic only offers information of a particular time and presents multiple biases dependent on inherent variability of BP and measurement technique itself. Multiple studies have demonstrated the prognosis superiority in the development of cardiovascular disease of ambulatory blood pressure monitoring (ABPM), allows detection of white coat hypertension, avoiding overdiagnosis and overtreatment, and the detection of patients with masked hypertension who are at risk of underdetection and undertreatment. ABPM also assess nightime BP and circadian variability, providing additional prognostic value. ABPM is recognized in the diagnosis of hypertension in 2011 British NICE Guidelines, very argued at the 2013 European Society of Hypertension guidelines, and recommended in the US Preventive Services Task Force in 2015, 2016 Canadian Guidelines and the 2016 Spanish Program of Preventive Activities and Health Promotion (PAPPS). Its generalization is likely to be only a matter of time. Copyright © 2017 Sociedad Española de Hipertension-Liga Española para la Lucha de la Hipertensión Arterial (SEH-LELHA). Publicado por Elsevier España, S.L.U. All rights reserved.

Circadian timed episodic-like memory - a bee knows what to do when, and also where.

PubMed

Pahl, Mario; Zhu, Hong; Pix, Waltraud; Tautz, Juergen; Zhang, Shaowu

2007-10-01

This study investigates how the colour, shape and location of patterns could be memorized within a time frame. Bees were trained to visit two Y-mazes, one of which presented yellow vertical (rewarded) versus horizontal (non-rewarded) gratings at one site in the morning, while another presented blue horizontal (rewarded) versus vertical (non-rewarded) gratings at another site in the afternoon. The bees could perform well in the learning tests and various transfer tests, in which (i) all contextual cues from the learning test were present; (ii) the colour cues of the visual patterns were removed, but the location cue, the orientation of the visual patterns and the temporal cue still existed; (iii) the location cue was removed, but other contextual cues, i.e. the colour and orientation of the visual patterns and the temporal cue still existed; (iv) the location cue and the orientation cue of the visual patterns were removed, but the colour cue and temporal cue still existed; (v) the location cue, and the colour cue of the visual patterns were removed, but the orientation cue and the temporal cue still existed. The results reveal that the honeybee can recall the memory of the correct visual patterns by using spatial and/or temporal information. The relative importance of different contextual cues is compared and discussed. The bees' ability to integrate elements of circadian time, place and visual stimuli is akin to episodic-like memory; we have therefore named this kind of memory circadian timed episodic-like memory.

Using dynamic Brownian bridge movement modelling to measure temporal patterns of habitat selection.

PubMed

Byrne, Michael E; Clint McCoy, J; Hinton, Joseph W; Chamberlain, Michael J; Collier, Bret A

2014-09-01

Accurately describing animal space use is vital to understanding how wildlife use habitat. Improvements in GPS technology continue to facilitate collection of telemetry data at high spatial and temporal resolutions. Application of the recently introduced dynamic Brownian bridge movement model (dBBMM) to such data is promising as the method explicitly incorporates the behavioural heterogeneity of a movement path into the estimated utilization distribution (UD). Utilization distributions defining space use are normally estimated for time-scales ranging from weeks to months, obscuring much of the fine-scale information available from high-volume GPS data sets. By accounting for movement heterogeneity, the dBBMM provides a rigorous, behaviourally based estimate of space use between each set of relocations. Focusing on UDs generated between individual sets of locations allows us to quantify fine-scale circadian variation in habitat use. We used the dBBMM to estimate UDs bounding individual time steps for three terrestrial species with different life histories to illustrate how the method can be used to identify fine-scale variations in habitat use. We also demonstrate how dBBMMs can be used to characterize circadian patterns of habitat selection and link fine-scale patterns of habitat use to behaviour. We observed circadian patterns of habitat use that varied seasonally for a white-tailed deer (Odocoileus virginianus) and coyote (Canis latrans). We found seasonal patterns in selection by the white-tailed deer and were able to link use of conifer forests and agricultural fields to behavioural state of the coyote. Additionally, we were able to quantify the date in which a Rio Grande wild turkey (Meleagris gallopavo intermedia) initiated laying as well as when during the day, she was most likely to visit the nest site to deposit eggs. The ability to quantify circadian patterns of habitat use may have important implications for research and management of wildlife. Additionally, the ability to link such patterns to behaviour may aid in the development of mechanistic models of habitat selection. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

Circadian rhythms have significant effects on leaf-to-canopy scale gas exchange under field conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Resco de Dios, Víctor; Gessler, Arthur; Ferrio, Juan Pedro

Background Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO 2 and H 2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron. Canopy and leaf-level fluxes were constantly monitored under field-like environmental conditions, and under constant environmental conditions (nomore » variation in temperature, radiation, or other environmental cues). Results We show direct experimental evidence at canopy scales of the circadian regulation of daytime gas exchange: 20–79 % of the daily variation range in CO 2 and H 2O fluxes occurred under circadian entrainment in canopies of an annual herb (bean) and of a perennial shrub (cotton). We also observed that considering circadian regulation improved performance by 8–17 % in commonly used stomatal conductance models. Conclusions Our results show that circadian controls affect diurnal CO 2 and H 2O flux patterns in entire canopies in field-like conditions, and its consideration significantly improves model performance. Lastly, circadian controls act as a ‘memory’ of the past conditions experienced by the plant, which synchronizes metabolism across entire plant canopies.« less

Circadian rhythms have significant effects on leaf-to-canopy scale gas exchange under field conditions

DOE PAGES

Resco de Dios, Víctor; Gessler, Arthur; Ferrio, Juan Pedro; ...

2016-10-20

Background Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO 2 and H 2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron. Canopy and leaf-level fluxes were constantly monitored under field-like environmental conditions, and under constant environmental conditions (nomore » variation in temperature, radiation, or other environmental cues). Results We show direct experimental evidence at canopy scales of the circadian regulation of daytime gas exchange: 20–79 % of the daily variation range in CO 2 and H 2O fluxes occurred under circadian entrainment in canopies of an annual herb (bean) and of a perennial shrub (cotton). We also observed that considering circadian regulation improved performance by 8–17 % in commonly used stomatal conductance models. Conclusions Our results show that circadian controls affect diurnal CO 2 and H 2O flux patterns in entire canopies in field-like conditions, and its consideration significantly improves model performance. Lastly, circadian controls act as a ‘memory’ of the past conditions experienced by the plant, which synchronizes metabolism across entire plant canopies.« less

Ring-shaped pulse oximeter and its application: measurement of SpO2 and blood pressure during sleep and during flight.

PubMed

Kishimoto, Aya; Tochikubo, Osamu; Ohshige, Kenji; Yanaga, Akihiko

2005-01-01

Respiratory and cardiovascular functions show circadian and day-to-day changes. We have developed a wireless ring-shaped pulse oximeter in collaboration with MC Medical Inc. and Advanced Medical Inc. We investigated the accuracy of this pulse oximeter and its application in daily life. Percutaneous arterial oxygen saturation (SpO2) of 47 volunteers was measured simultaneously with the ring-shaped pulse oximeter and a standard pulse oximeter. A total of 103 volunteers underwent measurement of SpO2 for 24 hr, and 11 healthy volunteers underwent measurement of SpO2 and blood pressure (BP) during flight. SpO2 and heart rate (HR) were measured and recorded every 20 sec, cabin barometric pressure and cabin oxygen concentration equivalent to sea level were measured minute-to-minute, and BP was measured every 3 min with a portable BP recorder during each flight. The SpO2 values measured with the ring-shaped pulse oximeter were similar to those measured with the standard method. The mean SpO2 during sleep was significantly lower in the group with high-normal BP or mild hypertension than in the group with normal BP. During flight, the mean change in SpO2 was -2.4 +/- 1.7% during nose-up flight, and 2.1 +/- 2.6% during nose-down flight. There was a significant correlation between change in SpO2 and change in systolic BP during nose-up flight. The wireless ring-shaped pulse oximeter was useful for investigating changes in SpO2 and its effect on BP in daily life during sleep and during air travel.

Major contribution of the medial amygdala to hypertension in BPH/2J genetically hypertensive mice.

PubMed

Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-04-01

BPH/2J mice are recognized as a neurogenic model of hypertension primarily based on overactivity of the sympathetic nervous system and greater neuronal activity in key autonomic cardiovascular regulatory brain regions. The medial amygdala (MeAm) is a forebrain region that integrates the autonomic response to stress and is the only region found to have greater Fos during the night and daytime in BPH/2J compared with BPN/3J mice. To determine the contribution of the MeAm to hypertension, the effect of neuronal ablation on blood pressure (BP) was assessed in BPH/2J (n=7) and normotensive BPN/3J mice (n=7). Mice were preimplanted with radiotelemetry devices to measure 24-hour BP and cardiovascular responses to stress, before and 1 to 3 weeks after bilateral lesions of the MeAm. Baseline BP was 121±4 mm Hg in BPH/2J and 101±2 mm Hg in BPN/3J mice (Pstrain<0.001). MeAm lesions reduced BP by 11±2 mm Hg in BPH/2J mice (Plesion<0.001) but had no effect in BPN/3J mice. The hypotensive effect of lesions in BPH/2J mice was similar during both day and night, suggesting that the MeAm has tonic effects on BP, but the pressor response to stress was maintained in both strains. Midfrequency BP power was attenuated in both strains (Plesion<0.05) and the depressor responses to pentolinium after enalaprilat pretreatment was attenuated after lesions in BPH/2J mice (Plesion<0.001; n=3). These findings indicate that the MeAm provides a tonic contribution to hypertension in BPH/2J mice, which is independent of its role in stress reactivity or circadian BP influences.

A stochastic differential equation model of diurnal cortisol patterns

NASA Technical Reports Server (NTRS)

Brown, E. N.; Meehan, P. M.; Dempster, A. P.

2001-01-01

Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems.

Diel pattern of circadian clock and storage protein gene expression in leaves and during seed filling in cowpea (Vigna unguiculata).

PubMed

Weiss, Julia; Terry, Marta I; Martos-Fuentes, Marina; Letourneux, Lisa; Ruiz-Hernández, Victoria; Fernández, Juan A; Egea-Cortines, Marcos

2018-02-14

Cowpea (Vigna unguiculata) is an important source of protein supply for animal and human nutrition. The major storage globulins VICILIN and LEGUMIN (LEG) are synthesized from several genes including LEGA, LEGB, LEGJ and CVC (CONVICILIN). The current hypothesis is that the plant circadian core clock genes are conserved in a wide array of species and that primary metabolism is to a large extent controlled by the plant circadian clock. Our aim was to investigate a possible link between gene expression of storage proteins and the circadian clock. We identified cowpea orthologues of the core clock genes VunLHY, VunTOC1, VunGI and VunELF3, the protein storage genes VunLEG, VunLEGJ, and VunCVC as well as nine candidate reference genes used in RT-PCR. ELONGATION FACTOR 1-A (ELF1A) resulted the most suitable reference gene. The clock genes VunELF3, VunGI, VunTOC1 and VunLHY showed a rhythmic expression profile in leaves with a typical evening/night and morning/midday phased expression. The diel patterns were not completely robust and only VungGI and VungELF3 retained a rhythmic pattern under free running conditions of darkness. Under field conditions, rhythmicity and phasing apparently faded during early pod and seed development and was regained in ripening pods for VunTOC1 and VunLHY. Mature seeds showed a rhythmic expression of VunGI resembling leaf tissue under controlled growth chamber conditions. Comparing time windows during developmental stages we found that VunCVC and VunLEG were significantly down regulated during the night in mature pods as compared to intermediate ripe pods, while changes in seeds were non-significant due to high variance. The rhythmic expression under field conditions was lost under growth chamber conditions. The core clock gene network is conserved in cowpea leaves showing a robust diel expression pattern except VunELF3 under growth chamber conditions. There appears to be a clock transcriptional reprogramming in pods and seeds compared to leaves. Storage protein deposition may be circadian regulated under field conditions but the strong environmental signals are not met under artificial growth conditions. Diel expression pattern in field conditions may result in better usage of energy for protein storage.

Biochemical basis for the biological clock

NASA Technical Reports Server (NTRS)

Morre, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morre, Dorothy M.

2002-01-01

NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

Circadian Rhythms in Diet-Induced Obesity.

PubMed

Engin, Atilla

2017-01-01

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN). Its circadian rhythm is arranged with the predictable daily mealtimes. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. However, the hypothalamus has a crucial role in the regulation of energy balance rather than food intake. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. The timing of three-meal schedules indicates close association with the plasma levels of insulin and preceding food availability. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the development of metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. While CLOCK expression levels are increased with high fat diet-induced obesity, peroxisome proliferator-activated receptor (PPAR) alpha increases the transcriptional level of brain and muscle ARNT-like 1 (BMAL1) in obese subjects. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity. Modifying the time of feeding alone can greatly affect body weight. Changes in the circadian clock are associated with temporal alterations in feeding behavior and increased weight gain. Thus, shift work is associated with increased risk for obesity, diabetes and cardio-vascular diseases as a result of unusual eating time and disruption of circadian rhythm.

Circadian Differences in the Contribution of the Brain Renin-Angiotensin System in Genetically Hypertensive Mice

PubMed Central

Jackson, Kristy L.; Marques, Francine Z.; Lim, Kyungjoon; Davern, Pamela J.; Head, Geoffrey A.

2018-01-01

Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS) and reactive oxygen species (ROS) reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle. The aim of the present study was to determine whether central AT1 receptor stimulation and the associated ROS signaling contribute to hypertension in BPH/2J mice in a circadian dependent manner. Methods: Blood pressure (BP) was measured in BPH/2J and normotensive BPN/3J mice (n = 7–8) via pre-implanted telemetry devices. Acute intracerebroventricular (ICV) microinjections of AT1 receptor antagonist, candesartan, and the superoxide dismutase (SOD) mimetic, tempol, were administered during the dark and light period of the 24 h light cycle via a pre-implanted ICV guide cannula. In separate mice, the BP effect of ICV infusion of the AT1 receptor antagonist losartan for 7 days was compared with subcutaneous infusion to determine the contribution of the central RAS to hypertension in BPH/2J mice. Results: Candesartan administered ICV during the dark period induced depressor responses which were 40% smaller in BPH/2J than BPN/3J mice (Pstrain < 0.05), suggesting AT1 receptor stimulation may contribute less to BP maintenance in BPH/2J mice. During the light period candesartan had minimal effect on BP in either strain. ICV tempol had comparable effects on BP between strains during the light and dark period (Pstrain > 0.08), suggesting ROS signaling is also not contributing to the hypertension in BPH/2J mice. Chronic ICV administration of losartan (22 nmol/h) had minimal effect on BPN/3J mice. By contrast in BPH/2J mice, both ICV and subcutaneously administered losartan induced similar hypotensive responses (−12.1 ± 1.8 vs. −14.7 ± 1.8 mmHg, Proute = 0.31). Conclusion: While central effects of peripheral losartan cannot be excluded, we suggest the hypotensive effect of chronic ICV losartan was likely peripherally mediated. Thus, based on both acute and chronic AT1 receptor inhibition and acute ROS inhibition, our findings suggest that greater activation of central AT1 receptors or ROS are unlikely to be mediating the hypertension in BPH/2J mice. PMID:29615926

Circadian Clock-Regulated Expression of Phytochrome and Cryptochrome Genes in Arabidopsis1

PubMed Central

Tóth, Réka; Kevei, Éva; Hall, Anthony; Millar, Andrew J.; Nagy, Ferenc; Kozma-Bognár, László

2001-01-01

Many physiological and biochemical processes in plants exhibit endogenous rhythms with a period of about 24 h. Endogenous oscillators called circadian clocks regulate these rhythms. The circadian clocks are synchronized to the periodic environmental changes (e.g. day/night cycles) by specific stimuli; among these, the most important is the light. Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator. In this work, we analyzed the spatial, temporal, and long-term light-regulated expression patterns of the Arabidopsis phytochrome (PHYA to PHYE) and cryptochrome (CRY1 and CRY2) promoters fused to the luciferase (LUC+) reporter gene. The results revealed new details of the tissue-specific expression and light regulation of the PHYC and CRY1 and 2 promoters. More importantly, the data obtained demonstrate that the activities of the promoter::LUC+ constructs, with the exception of PHYC::LUC+, display circadian oscillations under constant conditions. In addition, it is shown by measuring the mRNA abundance of PHY and CRY genes under constant light conditions that the circadian control is also maintained at the level of mRNA accumulation. These observations indicate that the plant circadian clock controls the expression of these photoreceptors, revealing the formation of a new regulatory loop that could modulate gating and resetting of the circadian clock. PMID:11743105

IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.

PubMed

Baumann, Anja; Feilhauer, Katharina; Bischoff, Stephan C; Froy, Oren; Lorentz, Axel

2015-03-01

Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa. Copyright © 2014 Elsevier Ltd. All rights reserved.

Circadian Clocks in the Cnidaria: Environmental Entrainment, Molecular Regulation, and Organismal Outputs

PubMed Central

Reitzel, Adam M.; Tarrant, Ann M.; Levy, Oren

2013-01-01

The circadian clock is a molecular network that translates predictable environmental signals, such as light levels, into organismal responses, including behavior and physiology. Regular oscillations of the molecular components of the clock enable individuals to anticipate regularly fluctuating environmental conditions. Cnidarians play important roles in benthic and pelagic marine environments and also occupy a key evolutionary position as the likely sister group to the bilaterians. Together, these attributes make members of this phylum attractive as models for testing hypotheses on roles for circadian clocks in regulating behavior, physiology, and reproduction as well as those regarding the deep evolutionary conservation of circadian regulatory pathways in animal evolution. Here, we review and synthesize the field of cnidarian circadian biology by discussing the diverse effects of daily light cycles on cnidarians, summarizing the molecular evidence for the conservation of a bilaterian-like circadian clock in anthozoan cnidarians, and presenting new empirical data supporting the presence of a conserved feed-forward loop in the starlet sea anemone, Nematostella vectensis. Furthermore, we discuss critical gaps in our current knowledge about the cnidarian clock, including the functions directly regulated by the clock and the precise molecular interactions that drive the oscillating gene-expression patterns. We conclude that the field of cnidarian circadian biology is moving rapidly toward linking molecular mechanisms with physiology and behavior. PMID:23620252

Conserved Daily Transcriptional Programs in Carica papaya

PubMed Central

Zdepski, Anna; Wang, Wenqin; Priest, Henry D.; Ali, Faraz; Alam, Maqsudul; Mockler, Todd C.

2008-01-01

Most organisms have internal circadian clocks that mediate responses to daily environmental changes in order to synchronize biological functions to the correct times of the day. Previous studies have focused on plants found in temperate and sub-tropical climates, and little is known about the circadian transcriptional networks of plants that typically grow under conditions with relatively constant day lengths and temperatures over the year. In this study we conducted a genomic and computational analysis of the circadian biology of Carica papaya, a tropical tree. We found that predicted papaya circadian clock genes cycle with the same phase as Arabidopsis genes. The patterns of time-of-day overrepresentation of circadian-associated promoter elements were nearly identical across papaya, Arabidopsis, rice, and poplar. Evolution of promoter structure predicts the observed morning- and evening-specific expression profiles of the papaya PRR5 paralogs. The strong conservation of previously identified circadian transcriptional networks in papaya, despite its tropical habitat and distinct life-style, suggest that circadian timing has played a major role in the evolution of plant genomes, consistent with the selective pressure of anticipating daily environmental changes. Further studies could exploit this conservation to elucidate general design principles that will facilitate engineering plant growth pathways for specific environments. Electronic supplementary material The online version of this article (doi:10.1007/s12042-008-9020-3) contains supplementary material, which is available to authorized users. PMID:20671772

Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogaster.

PubMed Central

Hardin, P E; Hall, J C; Rosbash, M

1992-01-01

Mutations in the disconnected (disco) gene act to disrupt neural cell patterning in the Drosophila visual system. These mutations also affect adult locomotor activity rhythms, as disco flies are arrhythmic under conditions of constant darkness (DD). To determine the state of the circadian pacemaker in disco mutants, we constructed with pers double mutants (a short period allele of the period gene) and assayed their behavioral rhythms in light-dark cycles (LD), and their biochemical rhythms of period gene expression under both LD and DD conditions. The results demonstrate that disco flies are rhythmic, indicating that they have an active circadian pacemaker that can be entrained by light. They also suggest that disco mutants block or interfere with elements of the circadian system located between the central pacemaker and its outputs that mediate overt rhythms. Images PMID:1740100

Molecular bases of circadian rhythmicity in renal physiology and pathology

PubMed Central

Bonny, Olivier; Vinciguerra, Manlio; Gumz, Michelle L.; Mazzoccoli, Gianluigi

2013-01-01

The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental–social cues and physiological–behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time–dependent changes in renal pathology. PMID:23901050

Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.

PubMed

Honma, Kazue; Hikosaka, Maki; Mochizuki, Kazuki; Goda, Toshinao

2016-04-01

Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day. We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice. Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD. These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Phase shift in the 24-hour rhythm of hippocampal EEG spiking activity in a rat model of temporal lobe epilepsy

PubMed Central

Stanley, David A.; Talathi, Sachin S.; Parekh, Mansi B.; Cordiner, Daniel J.; Zhou, Junli; Mareci, Thomas H.; Ditto, William L.

2013-01-01

For over a century epileptic seizures have been known to cluster at specific times of the day. Recent studies have suggested that the circadian regulatory system may become permanently altered in epilepsy, but little is known about how this affects neural activity and the daily pattern of seizures. To investigate, we tracked long-term changes in the rate of spontaneous hippocampal EEG spikes (SPKs) in a rat model of temporal lobe epilepsy. In healthy animals, SPKs oscillated with near 24-h period; however, after injury by status epilepticus, a persistent phase shift of ∼12 h emerged in animals that later went on to develop chronic spontaneous seizures. Additional measurements showed that global 24-h rhythms, including core body temperature and theta state transitions, did not phase shift. Instead, we hypothesized that locally impaired circadian input to the hippocampus might be responsible for the SPK phase shift. This was investigated with a biophysical computer model in which we showed that subtle changes in the relative strengths of circadian input could produce a phase shift in hippocampal neural activity. MRI provided evidence that the medial septum, a putative circadian relay center for the hippocampus, exhibits signs of damage and therefore could contribute to local circadian impairment. Our results suggest that balanced circadian input is critical to maintaining natural circadian phase in the hippocampus and that damage to circadian relay centers, such as the medial septum, may disrupt this balance. We conclude by discussing how abnormal circadian regulation may contribute to the daily rhythms of epileptic seizures and related cognitive dysfunction. PMID:23678009

Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice.

PubMed

Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D; Barandas, Rita; Malinow, Roberto; Welsh, David K

2016-12-01

Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice

PubMed Central

Landgraf, Dominic; Long, Jaimie E.; Proulx, Christophe D.; Barandas, Rita; Malinow, Roberto; Welsh, David K.

2016-01-01

Background Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. Methods We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). Results In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Conclusions Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. PMID:27113500

The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing

PubMed Central

Bartok, Osnat; Teesalu, Mari; Ashwall-Fluss, Reut; Pandey, Varun; Hanan, Mor; Rovenko, Bohdana M; Poukkula, Minna; Havula, Essi; Moussaieff, Arieh; Vodala, Sadanand; Nahmias, Yaakov; Kadener, Sebastian; Hietakangas, Ville

2015-01-01

Nutrient sensing pathways adjust metabolism and physiological functions in response to food intake. For example, sugar feeding promotes lipogenesis by activating glycolytic and lipogenic genes through the Mondo/ChREBP-Mlx transcription factor complex. Concomitantly, other metabolic routes are inhibited, but the mechanisms of transcriptional repression upon sugar sensing have remained elusive. Here, we characterize cabut (cbt), a transcription factor responsible for the repressive branch of the sugar sensing transcriptional network in Drosophila. We demonstrate that cbt is rapidly induced upon sugar feeding through direct regulation by Mondo-Mlx. We found that CBT represses several metabolic targets in response to sugar feeding, including both isoforms of phosphoenolpyruvate carboxykinase (pepck). Deregulation of pepck1 (CG17725) in mlx mutants underlies imbalance of glycerol and glucose metabolism as well as developmental lethality. Furthermore, we demonstrate that cbt provides a regulatory link between nutrient sensing and the circadian clock. Specifically, we show that a subset of genes regulated by the circadian clock are also targets of CBT. Moreover, perturbation of CBT levels leads to deregulation of the circadian transcriptome and circadian behavioral patterns. PMID:25916830

Environmental factors influencing biological rhythms in newborns: From neonatal intensive care units to home.

PubMed

Bueno, Clarissa; Menna-Barreto, Luiz

2016-01-01

Photic and non-photic environmental factors are suggested to modulate the development of circadian rhythms in infants. Our aim is to evaluate the development of biological rhythms (circadian or ultradian) in newborns in transition from Neonatal Intensive Care Units (NICU) to home and along the first 6 months of life, to identify masking and entraining environment factors along development. Ten newborns were evaluated in their last week inside the NICU and in the first week after being delivered home; 6 babies were also followed until 6 months of corrected age. Activity, recorded with actimeters, wrist temperature and observed sleep and feeding behavior were recorded continuously along their last week inside the NICU and in the first week at home and also until 6 months of corrected age for the subjects who remained in the study. Sleep/wake and activity/rest cycle showed ultradian patterns and the sleep/wake was strongly influenced by the 3 h feeding schedule inside the NICU, while wrist temperature showed a circadian pattern that seemed no to be affected by environmental cycles. A circadian rhythm emerges for sleep/wake behavior in the first week at home, whereas the 3 h period vanishes. Both activity/rest and wrist temperature presented a sudden increase in the contribution of the circadian component immediately after babies were delivered home, also suggesting a masking effect of the NICU environment. We found a positive correlation of postconceptional age and the increase in the daily component of activity and temperature along the following 6 months, while feeding behavior became arrhythmic.

Circadian rhythmometry of mammalian radiosensitivity

NASA Technical Reports Server (NTRS)

Haus, E.; Halberg, F.; Loken, M. K.; Kim, Y. S.

1974-01-01

In the case of human bone marrow, the largest number of mitoses is seen in the evening in diurnally active men, mitotic activity being at a minimum in the morning. The opposite pattern is observed for nocturnal animals such as rats and mice on a regimen of light during the daytime alternating with darkness during the night hours. The entirety of these rhythms plays an important role in the organism's responses to environmental stimuli, including its resistance to potentially harmful agents. Conditions under which circadian rhythms can be observed and validated by inferential statistical means are discussed while emphasizing how artifacts of the laboratory environment can be shown to obscure circadian periodic variations in radiosensitivity.

The expression patterns of the clock genes period and timeless are affected by photoperiod in the Mediterranean corn stalk borer, Sesamia nonagrioides.

PubMed

Kontogiannatos, Dimitrios; Gkouvitsas, Theodoros; Kourti, Anna

2017-01-01

To obtain clues to the link between the molecular mechanism of circadian and photoperiod clocks, we cloned two circadian clock genes, period (per) and timeless (tim) from the moth Sesamia nonagrioides, which undergoes facultative diapause controlled by photoperiod. Sequence analysis revealed a high degree of conservation among the compared insects fοr both genes. We also investigated the expression patterns of per and tim in brains of larvae growing under 16L:8D (long days), constant darkness (DD) and 10L:14D (short days) conditions by qPCR assays. The results showed that mRNA accumulations encoding both genes exhibited diel oscillations under different photoperiods. The oscillation of per and tim mRNA, under short-day photoperiod differed from long-day. The difference between long-day and short-day conditions in the pattern of mRNA levels of per and tim appears to distinguish photoperiodic conditions clearly and both genes were influenced by photoperiod in different ways. We infer that not all photoperiodic clocks of insects interact with circadian clocks in the same fashion. Our results suggest that transcriptional regulations of the both clock genes act in the diapause programing in S. nonagrioides. The expression patterns of these genes are affected by photoperiod but runs with 24 h by entrainment to daily environmental cues. © 2016 Wiley Periodicals, Inc.

The usefulness of GPS telemetry to study wolf circadian and social activity

USGS Publications Warehouse

Merrill, S.B.; David, Mech L.

2003-01-01

This study describes circadian and social movement patterns of 9 wolves and illustrates capabilities and limitations of Global Positioning System (GPS) telemetry for analysis of animal activity patterns. Wolves were studied at the Camp Ripley National Guard Training Site in Little Falls, Minnesota, and were captured via helicopter net-gunning. All study wolves showed nocturnal movement patterns regardless of time of year. One wolf's movement pattern switched to diurnal when he conducted an extraterritorial foray from his natal territory. All data sets with GPS intervals ???1 hour (n = 4) showed crepuscular movement peaks. We identified patterns of den visitation and attendance, estimated minimum distances traveled and minimum rates of movement, and observed that GPS location intervals may affect perceived rates of wolf travel. Global Positioning System telemetry was useful in determining when pack members were traveling together or apart and how long a breeding female wolf spent near her pups (e.g., 10-month-old pups were left unattended by their mother for as long as 17 days).

The orphan receptor Rev-erbα gene is a target of the circadian clock pacemaker

PubMed Central

Triqueneaux, Gérard; Thenot, Sandrine; Kakizawa, Tomoko; Antoch, Marina P; Safi, Rachid; Takahashi, Joseph S; Delaunay, Franck; Laudet, Vincent

2013-01-01

Rev-erbα is a ubiquitously expressed orphan nuclear receptor which functions as a constitutive transcriptional repressor and is expressed in vertebrates according to a robust circadian rhythm. We report here that two Rev-erbα mRNA isoforms, namely Rev-erbα1 and Rev-erbα2, are generated through alternative promoter usage and that both show a circadian expression pattern in an in vitro system using serum-shocked fibroblasts. Both promoter regions P1 (Rev-erbα1) and P2 (Rev-erbα2) contain several E-box DNA sequences, which function as response elements for the core circadian-clock components: CLOCK and BMAL1. The CLOCK–BMAL1 heterodimer stimulates the activity of both P1 and P2 promoters in transient transfection assay by 3–6-fold. This activation was inhibited by the overexpression of CRY1, a component of the negative limb of the circadian transcriptional loop. Critical E-box elements were mapped within both promoters. This regulation is conserved in vertebrates since we found that the CLOCK–BMAL1 heterodimer also regulates the zebrafish Rev-erbα gene. In line with these data Rev-erbα circadian expression was strongly impaired in the livers of Clock mutant mice and in the pineal glands of zebrafish embryos treated with Clock and Bmal1 antisense oligonucleotides. Together these data demonstrate that CLOCK is a critical regulator of Rev-erbα circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erbα in the circadian clock output. PMID:15591021

Long-term imaging of circadian locomotor rhythms of a freely crawling C. elegans population

PubMed Central

Winbush, Ari; Gruner, Matthew; Hennig, Grant W.; van der Linden, Alexander M.

2016-01-01

Background Locomotor activity is used extensively as a behavioral output to study the underpinnings of circadian rhythms. Recent studies have required a populational approach for the study of circadian rhythmicity in Caenorhabditis elegans locomotion. New method We describe an imaging system for long-term automated recording and analysis of locomotion data of multiple free-crawling C. elegans animals on the surface of an agar plate. We devised image analysis tools for measuring specific features related to movement and shape to identify circadian patterns. Results We demonstrate the utility of our system by quantifying circadian locomotor rhythms in wild-type and mutant animals induced by temperature cycles. We show that 13 °C:18 °C (12:12 h) cycles are sufficient to entrain locomotor activity of wild-type animals, which persist but are rapidly damped during 13 °C free-running conditions. Animals with mutations in tax-2, a cyclic nucleotide-gated (CNG) ion channel, significantly reduce locomotor activity during entrainment and free-running. Comparison with existing method(s) Current methods for measuring circadian locomotor activity is generally restricted to recording individual swimming animals of C. elegans, which is a distinct form of locomotion from crawling behavior generally observed in the laboratory. Our system works well with up to 20 crawling adult animals, and allows for a detailed analysis of locomotor activity over long periods of time. Conclusions Our population-based approach provides a powerful tool for quantification of circadian rhythmicity of C. elegans locomotion, and could allow for a screening system of candidate circadian genes in this model organism. PMID:25911068

Biological Rhythms and Temperature Regulation in Rhesus Monkeys During Spaceflight

NASA Technical Reports Server (NTRS)

Fuller, Charles A. (Principal Investigator)

1996-01-01

This program examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite COSMOS 2229 were exposed to 11 2/3 days of microgravity. The circadian patterns temperature regulation, heart rate and activity were monitored constantly. This experiment has extended previous observations from COSMOS 1514 and 2044, as well as provided insights into the physiological mechanisms that produce these changes.

Regulation of Mammalian Physiology by Interconnected Circadian and Feeding Rhythms

PubMed Central

Atger, Florian; Mauvoisin, Daniel; Weger, Benjamin; Gobet, Cédric; Gachon, Frédéric

2017-01-01

Circadian clocks are endogenous timekeeping systems that adapt in an anticipatory fashion the physiology and behavior of most living organisms. In mammals, the master pacemaker resides in the suprachiasmatic nucleus and entrains peripheral clocks using a wide range of signals that differentially schedule physiology and gene expression in a tissue-specific manner. The peripheral clocks, such as those found in the liver, are particularly sensitive to rhythmic external cues like feeding behavior, which modulate the phase and amplitude of rhythmic gene expression. Consequently, the liver clock temporally tunes the expression of many genes involved in metabolism and physiology. However, the circadian modulation of cellular functions also relies on multiple layers of posttranscriptional and posttranslational regulation. Strikingly, these additional regulatory events may happen independently of any transcriptional oscillations, showing that complex regulatory networks ultimately drive circadian output functions. These rhythmic events also integrate feeding-related cues and adapt various metabolic processes to food availability schedules. The importance of such temporal regulation of metabolism is illustrated by metabolic dysfunctions and diseases resulting from circadian clock disruption or inappropriate feeding patterns. Therefore, the study of circadian clocks and rhythmic feeding behavior should be of interest to further advance our understanding of the prevention and therapy of metabolic diseases. PMID:28337174

Circadian regulation of reproduction: from gamete to offspring.

PubMed

Boden, M J; Varcoe, T J; Kennaway, D J

2013-12-01

Few challenges are more critical to the survival of a species than reproduction. To ensure reproductive success, myriad aspects of physiology and behaviour need to be tightly orchestrated within the animal, as well as timed appropriately with the external environment. This is accomplished through an endogenous circadian timing system generated at the cellular level through a series of interlocked transcription/translation feedback loops, leading to the overt expression of circadian rhythms. These expression patterns are found throughout the body, and are intimately interwoven with both the timing and function of the reproductive process. In this review we highlight the many aspects of reproductive physiology in which circadian rhythms are known to play a role, including regulation of the estrus cycle, the LH surge and ovulation, the production and maturation of sperm and the timing of insemination and fertilisation. We will also describe roles for circadian rhythms in support of the preimplantation embryo in the oviduct, implantation/placentation, as well as the control of parturition and early postnatal life. There are several key differences in physiology between humans and the model systems used for the study of circadian disruption, and these challenges to interpretation will be discussed as part of this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.

PubMed

Ben-Moshe Livne, Zohar; Alon, Shahar; Vallone, Daniela; Bayleyen, Yared; Tovin, Adi; Shainer, Inbal; Nisembaum, Laura G; Aviram, Idit; Smadja-Storz, Sima; Fuentes, Michael; Falcón, Jack; Eisenberg, Eli; Klein, David C; Burgess, Harold A; Foulkes, Nicholas S; Gothilf, Yoav

2016-11-01

The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior.

Lighting the darkness of addiction: can phototherapy enhance contingency-management-based treatment of substance-related and addictive disorders?

PubMed

Siporin, Sheldon

2014-01-01

Maladaptive patterns of substance use are serious social problems. Both pharmacological and nonpharmacological treatments are available, but nondrug options may be preferable because they avoid the expense and adverse side effects of psychotropic medication. Contingency management (CM) and nondrug social and recreational activities (NDSRAs) are based on operant conditioning principles and seek to decrease substance use by means of nondrug rewards. However, their efficacy may be hindered where brain reward circuitry is dysfunctional. Research shows that substance abuse biases neural reward systems in favor of drug-induced highs, while disrupting circadian-based rhythms. Circadian systems also have been found to influence human reward pathways. Possibly, a bidirectional relationship exists between circadian disturbance and substance abuse effects. If so, repair of abnormal circadian rhythms might help normalize reward response in substance abusers, with positive effects on CM or NDSRA treatment outcomes. Phototherapy has been effective in repairing circadian rhythms in persons with seasonal affective disorder and other chronobiological conditions. This article proposes that it similarly may repair circadian response in substance abusers, thereby normalizing brain reward systems. By doing so, it would enhance the efficacy of CM and NDSRA therapies and may also help prevent relapse. Given its low cost and ease of administration, phototherapy seems a promising avenue to pursue.

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waters, Katrina M.; Sontag, Ryan L.; Weber, Thomas J., E-mail: Thomas.Weber@pnl.gov

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional programmore » encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response.« less

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior

PubMed Central

Alon, Shahar; Vallone, Daniela; Tovin, Adi; Shainer, Inbal; Nisembaum, Laura G.; Aviram, Idit; Smadja-Storz, Sima; Fuentes, Michael; Falcón, Jack; Eisenberg, Eli; Klein, David C.; Burgess, Harold A.; Foulkes, Nicholas S.; Gothilf, Yoav

2016-01-01

The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior. PMID:27870848

Development of salivary cortisol circadian rhythm in preterm infants.

PubMed

Ivars, Katrin; Nelson, Nina; Theodorsson, Annette; Theodorsson, Elvar; Ström, Jakob O; Mörelius, Evalotte

2017-01-01

To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life. This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire. A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02). Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

Characterization of locomotor activity circadian rhythms in athymic nude mice

PubMed Central

2013-01-01

Background The relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice. Methods General activity circadian rhythms in 2–4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light–dark schedule) was analyzed. Results Free-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light–dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups. Conclusions Since athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics. PMID:23369611

Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

PubMed

Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

2011-04-01

Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels.

Circadian exosomal expression of renal thiazide-sensitive NaCl cotransporter (NCC) and prostasin in healthy individuals.

PubMed

Castagna, Annalisa; Pizzolo, Francesca; Chiecchi, Laura; Morandini, Francesca; Channavajjhala, Sarath Kiran; Guarini, Patrizia; Salvagno, Gianluca; Olivieri, Oliviero

2015-06-01

A circadian timing system is involved in the maintenance of fluid and electrolyte balance and blood pressure control. Aldosterone and vasopressin modulate ion transporters and channels crucial in sodium (Na) and water reabsorption such as the epithelium Na channel and the renal thiazide-sensitive NaCl cotransporter (NCC). We analyzed in urinary exosomes the intraday variations of NCC and prostasin expression and the association with electrolytes and water balance parameters. Blood and urine samples were collected at five time points during the day from five healthy subjects. Blood renin, aldosterone, cortisol, ACTH, and plasmatic and urinary Na, potassium, creatinine, adiuretin (ADH), NCC, and prostasin were evaluated. ACTH and cortisol showed a circadian pattern, similarly to aldosterone, while exosomal NCC and prostasin pattern were similar to urinary ADH, decreased in the morning and subsequently increased in the afternoon and evening. In urinary exosomes, NCC and prostasin had a diurnal pattern parallel to ADH and aquaporin 2, confirming that, in healthy subjects, both prostasin and NCC relate to water balance. These results provide suggestions for a possible chronotherapeutic approach in patients treated with thiazides, diuretic drugs acting as specific inhibitors of NCC-mediated Na reabsorption. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Circadian egg production by Echinostoma caproni (Digenea: Echinostomatidae) in ICR mice.

PubMed

Platt, Thomas R; Hussey, Gabrielle L; Zelmer, Derek A

2013-04-01

Circadian egg production by Echinostoma caproni was investigated in ICR mice. Four female mice were infected with 25 E. caproni metacercariae, maintained in individual cages on a 12:12 light:dark cycle, and provided food and water ad libitum. Twenty-eight, 51, and 58 days post-infection, mice were transferred to individual, wire-bottomed cages and feces were collected every 2 hr for 24 hr. The feces were weighed and processed immediately to estimate the number of eggs present. Fecal output and egg production were standardized to unit maxima for analysis. Standardized egg count and standardized fecal output followed distinctly circadian patterns and covaried. Egg production was highest from 2200 to 0200 hr and lowest from 1000 to 1800 hr. These correspond to the highest and lowest fecal production, and highest and lowest periods of host activity, respectively. Egg density (eggs/g of feces) covaried weakly with fecal output with an additional peak at 0800-1000 hr, suggesting E. caproni is responding to changes in host physiology in timing of the production and release of eggs into the intestine. The continuous production and release of eggs during the patent period, coupled with the circadian pattern of daily egg release by E. caproni , would result in the widest dispersal of eggs in the host environment and enhance transmission to the first intermediate host.

Aspartate Decarboxylase is Required for a Normal Pupa Pigmentation Pattern in the Silkworm, Bombyx mori.

PubMed

Dai, Fangyin; Qiao, Liang; Cao, Cun; Liu, Xiaofan; Tong, Xiaoling; He, Songzhen; Hu, Hai; Zhang, Li; Wu, Songyuan; Tan, Duan; Xiang, Zhonghuai; Lu, Cheng

2015-06-16

The pigmentation pattern of Lepidoptera varies greatly in different development stages. To date, the effects of key genes in the melanin metabolism pathway on larval and adult body color are distinct, yet the effects on pupal pigmentation remains unclear. In the silkworm, Bombyx mori, the black pupa (bp) mutant is only specifically melanized at the pupal stage. Using positional cloning, we found that a mutation in the Aspartate decarboxylase gene (BmADC) is causative in the bp mutant. In the bp mutant, a SINE-like transposon with a length of 493 bp was detected ~2.2 kb upstream of the transcriptional start site of BmADC. This insertion causes a sharp reduction in BmADC transcript levels in bp mutants, leading to deficiency of β-alanine and N-β-alanyl dopamine (NBAD), but accumulation of dopamine. Following injection of β-alanine into bp mutants, the color pattern was reverted that of the wild-type silkworms. Additionally, melanic pupae resulting from knock-down of BmADC in the wild-type strain were obtained. These findings show that BmADC plays a crucial role in melanin metabolism and in the pigmentation pattern of the silkworm pupal stage. Finally, this study contributes to a better understanding of pupa pigmentation patterns in Lepidoptera.

Aspartate Decarboxylase is Required for a Normal Pupa Pigmentation Pattern in the Silkworm, Bombyx mori

PubMed Central

Dai, Fangyin; Qiao, Liang; Cao, Cun; Liu, Xiaofan; Tong, Xiaoling; He, Songzhen; Hu, Hai; Zhang, Li; Wu, Songyuan; Tan, Duan; Xiang, Zhonghuai; Lu, Cheng

2015-01-01

The pigmentation pattern of Lepidoptera varies greatly in different development stages. To date, the effects of key genes in the melanin metabolism pathway on larval and adult body color are distinct, yet the effects on pupal pigmentation remains unclear. In the silkworm, Bombyx mori, the black pupa (bp) mutant is only specifically melanized at the pupal stage. Using positional cloning, we found that a mutation in the Aspartate decarboxylase gene (BmADC) is causative in the bp mutant. In the bp mutant, a SINE-like transposon with a length of 493 bp was detected ~2.2 kb upstream of the transcriptional start site of BmADC. This insertion causes a sharp reduction in BmADC transcript levels in bp mutants, leading to deficiency of β-alanine and N-β-alanyl dopamine (NBAD), but accumulation of dopamine. Following injection of β-alanine into bp mutants, the color pattern was reverted that of the wild-type silkworms. Additionally, melanic pupae resulting from knock-down of BmADC in the wild-type strain were obtained. These findings show that BmADC plays a crucial role in melanin metabolism and in the pigmentation pattern of the silkworm pupal stage. Finally, this study contributes to a better understanding of pupa pigmentation patterns in Lepidoptera. PMID:26077025

Expression conservation within the circadian clock of a monocot: natural variation at barley Ppd-H1 affects circadian expression of flowering time genes, but not clock orthologs.

PubMed

Campoli, Chiara; Shtaya, Munqez; Davis, Seth J; von Korff, Maria

2012-06-21

The circadian clock is an endogenous mechanism that coordinates biological processes with daily changes in the environment. In plants, circadian rhythms contribute to both agricultural productivity and evolutionary fitness. In barley, the photoperiod response regulator and flowering-time gene Ppd-H1 is orthologous to the Arabidopsis core-clock gene PRR7. However, relatively little is known about the role of Ppd-H1 and other components of the circadian clock in temperate crop species. In this study, we identified barley clock orthologs and tested the effects of natural genetic variation at Ppd-H1 on diurnal and circadian expression of clock and output genes from the photoperiod-response pathway. Barley clock orthologs HvCCA1, HvGI, HvPRR1, HvPRR37 (Ppd-H1), HvPRR73, HvPRR59 and HvPRR95 showed a high level of sequence similarity and conservation of diurnal and circadian expression patterns, when compared to Arabidopsis. The natural mutation at Ppd-H1 did not affect diurnal or circadian cycling of barley clock genes. However, the Ppd-H1 mutant was found to be arrhythmic under free-running conditions for the photoperiod-response genes HvCO1, HvCO2, and the MADS-box transcription factor and vernalization responsive gene Vrn-H1. We suggest that the described eudicot clock is largely conserved in the monocot barley. However, genetic differentiation within gene families and differences in the function of Ppd-H1 suggest evolutionary modification in the angiosperm clock. Our data indicates that natural variation at Ppd-H1 does not affect the expression level of clock genes, but controls photoperiodic output genes. Circadian control of Vrn-H1 in barley suggests that this vernalization responsive gene is also controlled by the photoperiod-response pathway. Structural and functional characterization of the barley circadian clock will set the basis for future studies of the adaptive significance of the circadian clock in Triticeae species.

Plasticity of circadian activity and body temperature rhythms in golden spiny mice.

PubMed

Cohen, Rotem; Smale, Laura; Kronfeld-Schor, Noga

2009-04-01

Most animals can be categorized as nocturnal, diurnal, or crepuscular. However, rhythms can be quite plastic in some species and vary from one individual to another within a species. In the golden spiny mouse (Acomys russatus), a variety of rhythm patterns have been seen, and these patterns can change considerably as animals are transferred from the field into the laboratory. We previously suggested that these animals may have a circadian time-keeping system that is fundamentally nocturnal and that diurnal patterns seen in their natural habitat reflect mechanisms operating outside of the basic circadian time-keeping system (i.e., masking). In the current study, we further characterized plasticity evident in the daily rhythms of golden spiny mice by measuring effects of lighting conditions and access to a running wheel on rhythms in general activity (GA) and body temperature (Tb). Before the wheel was introduced, most animals were active mainly during the night, though there was considerable inter-individual variability and patterns were quite plastic. The introduction of the wheel caused an increase in the level of nighttime activity and Tb in most individuals. The periods of the rhythms in constant darkness (DD) were very similar, and even slightly longer in this study (24.1+/-0.2 h) than in an earlier one in which animals had not been provided with running wheels. We found no correlation between the distance animals ran in their wheels and the period of their rhythms in DD. Re-entrainment after phase delays of the LD cycle occurred more rapidly in the presence than absence of the running wheel. The characteristics of the rhythms of golden spiny mice seen in this study may be the product of natural selection favoring plasticity of the circadian system, perhaps reflecting what can happen during an evolutionary transition as animals move from a nocturnal to a diurnal niche.

[Chrono-nutrition and chrono-exercise].

PubMed

Shibata, Shigenobu; Sasaki, Hiroyuki; Ikeda, Yuko

2013-12-01

The circadian rhythm controls many physiological functions, such as feeding, motor activity, endocrine secretion and autonomic nerve. Regular feeding pattern can entrain the peripheral circadian clock, whereas peripheral clock systems can control the absorption distribution, metabolism and excretion of nutrients, suggesting mutual interactions between circadian clocks and nutrition/food. The interactions were so-called by "chrono-nutrition", and bigger meals for breakfast were good for entrainment of peripheral clock and protection of obesity. Similar to chrono-nutrition the timing of exercise ("chrono-exercise") is important for both entrainment signals and energy expenditure. Evening exercise and/or feeding then exercise was good timing exercise for protection of obesity. Taken all, it is suggested that timing of feeding and exercise is now one of key factors for metabolic syndrome.

Calcitonin control of calcium metabolism during weightlessness

NASA Technical Reports Server (NTRS)

Soliman, Karam F. A.

1993-01-01

The main objective of this proposal is to elucidate calcitonin role in calcium homeostasis during weightlessness. In this investigation our objectives are to study: the effect of weightlessness on thyroid and serum calcitonin, the effect of weightlessness on the circadian variation of calcitonin in serum and the thyroid gland, the role of light as zeitgeber for calcitonin circadian rhythm, the circadian pattern of thyroid sensitivity to release calcitonin in response to calcium load, and the role of serotonin and norepinephrine in the control of calcitonin release. The main objective of this research/proposal is to establish the role of calcitonin in calcium metabolism during weightlessness condition. Understanding the mechanism of these abnormalities will help in developing therapeutic means to counter calcium imbalance in spaceflights.

Chronobiology of epilepsy: diagnostic and therapeutic implications of chrono-epileptology.

PubMed

Loddenkemper, Tobias; Lockley, Steven W; Kaleyias, Joseph; Kothare, Sanjeev V

2011-04-01

The combination of chronobiology and epilepsy offers novel diagnostic and therapeutic management options. Knowledge of the interactions between circadian periodicity, entrainment, sleep patterns, and epilepsy may provide additional diagnostic options beyond sleep deprivation and extended release medication formulations. It may also provide novel insights into the physiologic, biochemical, and genetic regulation processes of epilepsy and the circadian clock, rendering new treatment options. Temporal fluctuations of seizure susceptibility based on sleep homeostasis and circadian phase in selected epilepsies may provide predictability based on mathematical models. Chrono-epileptology offers opportunities for individualized patient-oriented treatment paradigms based on chrono-pharmacology, differential medication dosing, chrono-drug delivery systems, and utilization of "zeitgebers" such as chronobiotics or light-therapy and desynchronization strategies among others.

Role of light and the circadian clock in the rhythmic oscillation of intraocular pressure: Studies in VPAC2 receptor and PACAP deficient mice.

PubMed

Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens; Jørgensen, Henrik Løvendahl

2018-04-01

The intraocular pressure of mice displays a daily rhythmicity being highest during the dark period. The present study was performed to elucidate the role of the circadian clock and light in the diurnal and the circadian variations in intraocular pressure in mice, by using animals with disrupted clock function (VPAC2 receptor knockout mice) or impaired light information to the clock (PACAP knockout mice). In wildtype mice, intraocular pressure measured under light/dark conditions showed a statistically significant 24 h sinusoidal rhythm with nadir during the light phase and peak during the dark phase. After transfer of the wildtype mice into constant darkness, the intraocular pressure increased, but the rhythmic changes in intraocular pressure continued with a pattern identical to that obtained during the light/dark cycle. The intraocular pressure in VPAC2 receptor deficient mice during light/dark conditions also showed a sinusoidal pattern with significant changes as a function of a 24 h cycle. However, transfer of the VPAC2 receptor knockout mice into constant darkness completely abolished the rhythmic changes in intraocular pressure. The intraocular pressure in PACAP deficient mice oscillated significantly during both 24 h light and darkness and during constant darkness. During LD conditions, the amplitude of PACAP deficient was significantly lower compared to wildtype mice, resulting in higher daytime and lower nighttime values. In conclusion, by studying the VPAC2 receptor knockout mouse which lacks circadian control and the PACAP knockout mouse which displays impaired light signaling, we provided evidence that the daily intraocular pressure rhythms are primarily generated by the circadian master clock and to a lesser extent by environmental light and darkness. Copyright © 2018 Elsevier Ltd. All rights reserved.

Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet.

PubMed

Navigatore-Fonzo, Lorena S; Delgado, Silvia M; Gimenez, Maria Sofia; Anzulovich, Ana C

2014-01-01

Alterations in enzymatic antioxidant defense systems lead to a deficit of cognitive functions and altered hippocampal synaptic plasticity. The objectives of this study were to investigate endogenous rhythms of catalase (CAT) and glutathione peroxidase (GPx) expression and activity, as well as CREB1 mRNA, in the rat hippocampus, and to evaluate to which extent the vitamin A deficiency could affect those temporal patterns. Rats from control and vitamin A-deficient (VAD) groups received a diet containing 4000 IU of vitamin A/kg diet, or the same diet devoid of vitamin A, respectively, during 3 months. Rats were maintained under 12-hour-dark conditions, during 10 days before the sacrifice. Circadian rhythms of CAT, GPx, RXRγ, and CREB1 mRNA levels were determined by reverse transcriptrase polymerase chain reaction in hippocampus samples isolated every 4 hours during a 24-hour period. CAT and GPx enzymatic activities were also determined by kinetic assays. Regulatory regions of clock and antioxidant enzymes genes were scanned for E-box, RXRE, and CRE sites. E-box, RXRE, and CRE sites were found on regulatory regions of GPx and CAT genes, which display a circadian expression in the rat hippocampus. VAD phase shifted CAT, GPx, and RXRγ endogenous rhythms without affecting circadian expression of CREB1. CAT and GPx expression and enzymatic activity are circadian in the rat hippocampus. The VAD affected the temporal patterns antioxidant genes expression, probably by altering circadian rhythms of its RXR receptors and clock factors; thus, it would impair the temporal orchestration of hippocampal daily cognitive performance.

"Summer Shift": A Potential Effect of Sunshine on the Time Onset of ST-Elevation Acute Myocardial Infarction.

PubMed

Cannistraci, Carlo Vittorio; Nieminen, Tuomo; Nishi, Masahiro; Khachigian, Levon M; Viikilä, Juho; Laine, Mika; Cianflone, Domenico; Maseri, Attilio; Yeo, Khung Keong; Bhindi, Ravinay; Ammirati, Enrico

2018-04-06

ST-elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. Here, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. The "summer shift" of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season-dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

PubMed

Riestra, Pia; Gebreab, Samson Y; Xu, Ruihua; Khan, Rumana J; Gaye, Amadou; Correa, Adolfo; Min, Nancy; Sims, Mario; Davis, Sharon K

2017-06-23

Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (SNPs) and body mass index (BMI). We also evaluated the association of SNPs with BMI related factors such as sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) from the Jackson Heart Study. Genotype data for the selected 23 CLOCK gene SNPS was obtained by imputation with IMPUTE2 software and reference phase data from the 1000 genome project. Genetic analyses were conducted with PLINK RESULTS: We found a significant association between the CLOCK SNP rs2070062 and sleep duration, participants carriers of the T allele showed significantly shorter sleep duration compared to non-carriers after the adjustment for individual proportions of European ancestry (PEA), socio economic status (SES), body mass index (BMI), alcohol consumption and smoking status that reach the significance threshold after multiple testing correction. In addition, we found nominal associations of the CLOCK SNP rs6853192 with longer sleep duration and the rs6820823, rs3792603 and rs11726609 with BMI. However, these associations did not reach the significance threshold after correction for multiple testing. In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans.

Sleep-like behavior and 24-h rhythm disruption in the Tc1 mouse model of Down syndrome.

PubMed

Heise, I; Fisher, S P; Banks, G T; Wells, S; Peirson, S N; Foster, R G; Nolan, P M

2015-02-01

Down syndrome is a common disorder associated with intellectual disability in humans. Among a variety of severe health problems, patients with Down syndrome exhibit disrupted sleep and abnormal 24-h rest/activity patterns. The transchromosomic mouse model of Down syndrome, Tc1, is a trans-species mouse model for Down syndrome, carrying most of human chromosome 21 in addition to the normal complement of mouse chromosomes and expresses many of the phenotypes characteristic of Down syndrome. To date, however, sleep and circadian rhythms have not been characterized in Tc1 mice. Using both circadian wheel-running analysis and video-based sleep scoring, we showed that these mice exhibited fragmented patterns of sleep-like behaviour during the light phase of a 12:12-h light/dark (LD) cycle with an extended period of continuous wakefulness at the beginning of the dark phase. Moreover, an acute light pulse during night-time was less effective in inducing sleep-like behaviour in Tc1 animals than in wild-type controls. In wheel-running analysis, free running in constant light (LL) or constant darkness (DD) showed no changes in the circadian period of Tc1 animals although they did express subtle behavioural differences including a reduction in total distance travelled on the wheel and differences in the acrophase of activity in LD and in DD. Our data confirm that Tc1 mice express sleep-related phenotypes that are comparable with those seen in Down syndrome patients with moderate disruptions in rest/activity patterns and hyperactive episodes, while circadian period under constant lighting conditions is essentially unaffected. © 2015 Medical Research Council. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright light duration?

PubMed Central

Crowley, Stephanie J.; Eastman, Charmane I.

2015-01-01

OBJECTIVE Efficient treatments to phase advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. METHODS Fifty adults (27 males) aged 25.9±5.1 years participated. Sleep/dark was advanced 1 hour/day for 3 treatment days. Participants took 0.5 mg melatonin 5 hours before baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright light (~5000 lux) patterns upon waking each morning: four 30-minute exposures separated by 30 minutes of room light (2 h group); four 15-minute exposures separated by 45 minutes of room light (1 h group), and one 30-minute exposure (0.5 h group). Dim light melatonin onsets (DLMOs) before and after treatment determined the phase advance. RESULTS Compared to the 2 h group (phase shift=2.4±0.8 h), smaller phase advance shifts were seen in the 1 h (1.7±0.7 h) and 0.5 h (1.8±0.8 h) groups. The 2-hour pattern produced the largest phase advance; however, the single 30-minute bright light exposure was as effective as 1 hour of bright light spread over 3.25 h, and produced 75% of the phase shift observed with 2 hours of bright light. CONCLUSIONS A 30-minute morning bright light exposure with afternoon melatonin is an efficient treatment to phase advance human circadian rhythms. PMID:25620199

Phase advancing human circadian rhythms with morning bright light, afternoon melatonin, and gradually shifted sleep: can we reduce morning bright-light duration?

PubMed

Crowley, Stephanie J; Eastman, Charmane I

2015-02-01

Efficient treatments to phase-advance human circadian rhythms are needed to attenuate circadian misalignment and the associated negative health outcomes that accompany early-morning shift work, early school start times, jet lag, and delayed sleep phase disorder. This study compared three morning bright-light exposure patterns from a single light box (to mimic home treatment) in combination with afternoon melatonin. Fifty adults (27 males) aged 25.9 ± 5.1 years participated. Sleep/dark was advanced 1 h/day for three treatment days. Participants took 0.5 mg of melatonin 5 h before the baseline bedtime on treatment day 1, and an hour earlier each treatment day. They were exposed to one of three bright-light (~5000 lux) patterns upon waking each morning: four 30-min exposures separated by 30 min of room light (2-h group), four 15-min exposures separated by 45 min of room light (1-h group), and one 30-min exposure (0.5-h group). Dim-light melatonin onsets (DLMOs) before and after treatment determined the phase advance. Compared to the 2-h group (phase shift = 2.4 ± 0.8 h), smaller phase-advance shifts were seen in the 1-h (1.7 ± 0.7 h) and 0.5-h (1.8 ± 0.8 h) groups. The 2-h pattern produced the largest phase advance; however, the single 30-min bright-light exposure was as effective as 1 h of bright light spread over 3.25 h, and it produced 75% of the phase shift observed with 2 h of bright light. A 30-min morning bright-light exposure with afternoon melatonin is an efficient treatment to phase-advance human circadian rhythms. Copyright © 2014 Elsevier B.V. All rights reserved.

Sleep/awake status throughout the night and circadian motor activity patterns in older nursing-home residents with or without dementia, and older community-dwelling people without dementia.

PubMed

Kume, Yu; Kodama, Ayuto; Sato, Kotaro; Kurosawa, Satoko; Ishikawa, Takashi; Ishikawa, Sachiko

2016-12-01

Sleep disturbances are commonly observed in older nursing home residents, mainly in combination with dementia. However, sleep-associated circadian motor activity patterns have not been thoroughly investigated in Japanese nursing homes. The present study aimed to respectively clarify the effect of community living and the presence of dementia on sleep disturbances and interrupted activity rhythm of older nursing-home residents with or without dementia and older community-dwelling people without dementia. Actigraph devices worn on the participants' non-dominant wrists for seven days were used to collect objective measurements of the sleep/awake status throughout the night and the circadian motor activity patterns. The presence of dementia was assessed by a trained medical doctor using the residents' records and the Clinical Dementia Rating (CDR). The functional capacity of the participants was determined using the Barthel Index (BI). Fifty-one older people in Akita prefecture were included in the current study, consisting of 17 residents with dementia (mean age: 82.2 years), 17 residents without dementia (84.5 years), and 17 community-dwelling people (83.6 years). The results showed that older nursing-home residents with dementia had significantly a lower rate of sleep efficiency and a longer awake time throughout the night than the other groups. Older nursing-home residents with and without dementia had more fragmented rhythm than community-dwelling people without dementia. These results provide evidence of poor sleep/awake status throughout the night and interrupted circadian activity rhythms in nursing-home residents with and without dementia. However, further studies performed according to dementia classifications are needed.

24-hour pattern of falls in hospitalized and long-term care institutionalized elderly persons: A systematic review of the published literature.

PubMed

López-Soto, Pablo Jesús; Manfredini, Roberto; Smolensky, Michael H; Rodríguez-Borrego, María Aurora

2015-05-01

Falls are common among the elderly > 65 years of age and can result in both serious trauma and costly medical care. The epidemiology of falls in the elderly typically focuses on identifying contributory exogenous environmental and endogenous age-related physical, cognitive and other health status factors; however, one potentially important variable seldom considered is time of fall. We sought to determine if falls in hospitalized/institutionalized elderly persons exhibit 24 h and other temporal patterns, since knowledge of such could be useful in their prevention. We conducted a systematic review of the published literature to critically appraise and synthesize the methods and findings of previous reports addressing clock-time, day-of-week and month-of-year fall patterns of institutionalized elderly cohorts. Medline, SCOPUS, Ovid SP and Web of Knowledge were systematic assessed, entering search terms of "accidental fall", "circadian rhythm", "biological clocks", "circadian clocks", "activity cycles", "periodicity", and with databases accepting an age limiter, "age of 65(+) years". Methodological quality was assessed by STROBE and CONSORT checklists, respectively, in observational and clinical studies. Publications were reviewed if meeting inclusion criteria of: (i) being an empirical study, (ii) adopting circadian and/or other period rhythmicity as a fall risk, and (iii) focusing on hospitalized/institutionalized falls in those ≥ 65 years of age; plus exclusion criteria of: (i) cohort < 65 years of age and (ii) reports as dissertations or editorials. The search retrieved 170 publications; however, only nine met all inclusion/exclusion criteria. Typically, past studies disregarded the temporal aspects of fall incidents; the few that did varied in quality, institutional setting, and patient type, i.e. medical diagnoses. Overall, findings suggest a single or double-peak 24 h pattern of fall incidence, with time of greatest incidence seemingly associated with circadian rhythm-dependent differences in the symptom intensity of dominating medical diagnoses (e.g. heart failure versus Alzheimer syndrome) among sample cohorts plus location (e.g. bathroom versus hallway) of occurrence. Future research is urgently required to define temporal patterns in falls and their etiology, e.g. relative to circadian and other rhythms in both the manifestation and intensity of medical conditions and adverse effects of medications according to scheduling, plus staff personnel number and work schedules as it affects patient oversight, and cyclic environmental conditions (e.g. light intensity exposure) to best design preventive measures.

The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes.

PubMed

Leonardo-Mendonça, Roberto C; Martinez-Nicolas, Antonio; de Teresa Galván, Carlos; Ocaña-Wilhelmi, Javier; Rusanova, Iryna; Guerra-Hernández, Eduardo; Escames, Germaine; Acuña-Castroviejo, Darío

2015-01-01

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency.

Mouse genotypes drive the liver and adrenal gland clocks

NASA Astrophysics Data System (ADS)

Košir, Rok; Prosenc Zmrzljak, Uršula; Korenčič, Anja; Juvan, Peter; Ačimovič, Jure; Rozman, Damjana

2016-08-01

Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. We show that the genotype of mouse lines defines the circadian gene expression patterns. Expression of majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in the adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in dark - dark (DD) and light - dark conditions (LD), exome sequencing and data mining proposed that mouse lines differ in single nucleotide variants in the binding regions of clock related transcription factors in open chromatin regions. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs. This is supported by the genotype effect in adrenal glands that is largest under LD, and by the high number of single nucleotide variants in the Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. Different phenotypes of the two mouse lines and changed amino acid sequence of the Period 2 protein possibly contribute further to the observed differences in circadian gene expression.

Localization and expression of putative circadian clock transcripts in the brain of the nudibranch Melibe leonina.

PubMed

Duback, Victoria E; Sabrina Pankey, M; Thomas, Rachel I; Huyck, Taylor L; Mbarani, Izhar M; Bernier, Kyle R; Cook, Geoffrey M; O'Dowd, Colleen A; Newcomb, James M; Watson, Winsor H

2018-09-01

The nudibranch, Melibe leonina, expresses a circadian rhythm of locomotion, and we recently determined the sequences of multiple circadian clock transcripts that may play a role in controlling these daily patterns of behavior. In this study, we used these genomic data to help us: 1) identify putative clock neurons using fluorescent in situ hybridization (FISH); and 2) determine if there is a daily rhythm of expression of clock transcripts in the M. leonina brain, using quantitative PCR. FISH indicated the presence of the clock-related transcripts clock, period, and photoreceptive and non-photoreceptive cryptochrome (pcry and npcry, respectively) in two bilateral neurons in each cerebropleural ganglion and a group of <10 neurons in the anterolateral region of each pedal ganglion. Double-label experiments confirmed colocalization of all four clock transcripts with each other. Quantitative PCR demonstrated that the genes clock, period, pcry and npcry exhibited significant differences in expression levels over 24 h. These data suggest that the putative circadian clock network in M. leonina consists of a small number of identifiable neurons that express circadian genes with a daily rhythm. Copyright © 2018 Elsevier Inc. All rights reserved.

Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

PubMed Central

Barclay, Johanna L.; Husse, Jana; Bode, Brid; Naujokat, Nadine; Meyer-Kovac, Judit; Schmid, Sebastian M.; Lehnert, Hendrik; Oster, Henrik

2012-01-01

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers. PMID:22629359

Mutations in EID1 and LNK2 caused light-conditional clock deceleration during tomato domestication.

PubMed

Müller, Niels A; Zhang, Lei; Koornneef, Maarten; Jiménez-Gómez, José M

2018-05-22

Circadian period and phase of cultivated tomato ( Solanum lycopersicum ) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1 , the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps. We reveal signatures of selection across the genomic region of LNK2 and different patterns of fixation of the mutant alleles. Strikingly, LNK2 and EID1 are both involved in light input to the circadian clock, indicating that domestication specifically targeted this input pathway. In line with this, we show that the clock deceleration in the cultivated tomato is light-dependent and requires the phytochrome B1 photoreceptor. Such conditional variation in circadian rhythms may be key for latitudinal adaptation in a variety of species, including crop plants and livestock.

Transcriptome analysis of molecular mechanisms responsible for light-stress response in Mythimna separata (Walker)

PubMed Central

Duan, Yun; Gong, ZhongJun; Wu, RenHai; Miao, Jin; Jiang, YueLi; Li, Tong; Wu, XiaoBo; Wu, YuQing

2017-01-01

Light is an important environmental signal for most insects. The Oriental Armyworm, Mythimna separata, is a serious pest of cereal crops worldwide, and is highly sensitive to light signals during its developmental and reproductive stages. However, molecular biological studies of its response to light stress are scarce, and related genomic information is not available. In this study, we sequenced and de novo assembled the transcriptomes of M. separata exposed to four different light conditions: dark, white light (WL), UV light (UVL) and yellow light (YL). A total of 46,327 unigenes with an average size of 571 base pairs (bp) were obtained, among which 24,344 (52.55%) matched to public databases. The numbers of genes differentially expressed between dark vs WL, dark vs UVL, dark vs YL, and UVL vs YL were 12,012, 12,950, 14,855, and 13,504, respectively. These results suggest that light exposure altered gene expression patterns in M. separata. Putative genes involved in phototransduction-fly, phototransduction, circadian rhythm-fly, olfactory transduction, and taste transduction were identified. This study thus identified a series of candidate genes and pathways potentially related to light stress in M. separata. PMID:28345615

Hepatic Leukemia Factor Promotes Resistance To Cell Death: Implications For Therapeutics and Chronotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waters, Katrina M.; Sontag, Ryan L.; Weber, Thomas J.

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional programmore » encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation.« less

Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

PubMed

Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

2016-02-01

This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. Copyright © 2015 Elsevier Inc. All rights reserved.

Digital Daily Cycles of Individuals

NASA Astrophysics Data System (ADS)

Aledavood, Talayeh; Lehmann, Sune; Saramäki, Jari

2015-10-01

Humans, like almost all animals, are phase-locked to the diurnal cycle. Most of us sleep at night and are active through the day. Because we have evolved to function with this cycle, the circadian rhythm is deeply ingrained and even detectable at the biochemical level. However, within the broader day-night pattern, there are individual differences: e.g., some of us are intrinsically morning-active, while others prefer evenings. In this article, we look at digital daily cycles: circadian patterns of activity viewed through the lens of auto-recorded data of communication and online activity. We begin at the aggregate level, discuss earlier results, and illustrate differences between population-level daily rhythms in different media. Then we move on to the individual level, and show that there is a strong individual-level variation beyond averages: individuals typically have their distinctive daily pattern that persists in time. We conclude by discussing the driving forces behind these signature daily patterns, from personal traits (morningness/eveningness) to variation in activity level and external constraints, and outline possibilities for future research.

Circadian oscillations of microbial and functional composition in the human salivary microbiome

PubMed Central

Takayasu, Lena; Suda, Wataru; Takanashi, Kageyasu; Iioka, Erica; Kurokawa, Rina; Shindo, Chie; Hattori, Yasue; Yamashita, Naoko; Nishijima, Suguru; Oshima, Kenshiro

2017-01-01

Abstract The human microbiomes across the body evidently interact with various signals in response to biogeographical physiological conditions. To understand such interactions in detail, we investigated how the salivary microbiome in the oral cavity would be regulated by host-related signals. Here, we show that the microbial abundance and gene participating in keeping the human salivary microbiome exhibit global circadian rhythm. Analysis of the 16S rRNA sequences of salivary microbial samples of six healthy adults collected at 4-h intervals for three days revealed that the microbial genera accounting for 68.4–89.6% of the total abundance were observed to significantly oscillate with the periodicity of ∼24 h. These oscillation patterns showed high variations amongst individuals, and the extent of circadian variations in individuals was generally lower than that of interindividual variations. Of the microbial categories oscillated, those classified by aerobic/anaerobic growth and Gram staining, Firmicutes including Streptococcus and Gemella, and Bacteroidetes including Prevotella showed high association with the circadian oscillation. The circadian oscillation was completely abolished by incubating the saliva in vitro, suggesting that host’s physiological changes mostly contributed to the microbial oscillation. Further metagenomic analysis showed that circadian oscillation enriched the functions of environmental responses such as various transporters and two-component regulatory systems in the evening, and those of metabolisms such as the biosynthesis of vitamins and fatty acids in the morning. PMID:28338745

Circadian Clearance of a Fungal Pathogen from the Lung Is Not Based on Cell-intrinsic Macrophage Rhythms.

PubMed

Chen, Shan; Fuller, Kevin K; Dunlap, Jay C; Loros, Jennifer J

2018-02-01

Circadian rhythms govern immune cell function, giving rise to time-of-day variation in the recognition and clearance of bacterial or viral pathogens; to date, however, no such regulation of the host-fungal interaction has been described. In this report, we use murine models to explore circadian control of either fungal-macrophage interactions in vitro or pathogen clearance from the lung in vivo. First, we show that expression of the important fungal pattern recognition receptor Dectin-1 ( clec7a), from either bone marrow-derived or peritoneum-derived macrophages, is not under circadian regulation at either the level of transcript or cell surface protein expression. Consistent with this finding, the phagocytic activity of macrophages in culture against spores of the pathogen Aspergillus fumigatus also did not vary over time. To account for the multiple cell types and processes that may be coordinated in a circadian fashion in vivo, we examined the clearance of A. fumigatus from the lungs of immunocompetent mice. Interestingly, animals inoculated at night demonstrated a 2-fold enhancement in clearance compared with animals inoculated in the morning. Taken together, our data suggest that while molecular recognition of fungi by immune cells may not be circadian, other processes in vivo may still allow for time-of-day differences in fungal clearance from the lung.

Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism.

PubMed

Nir, I; Meir, D; Zilber, N; Knobler, H; Hadjez, J; Lerner, Y

1995-12-01

An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.

Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation.

PubMed

Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Escobar, Carolina; Buijs, Ruud M; Hu, Kun

2016-01-01

One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations-similar fluctuation structure at different time scales-that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)-a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)-the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The differential impacts of food restriction on fractal activity control in intact and DMH-lesioned animals suggest that the DMH plays a crucial role in integrating these different time cues to the circadian network for multiscale regulation of motor activity.

Circadian Disruptions of Heart Rate Variability among Weekly Consecutive-12-hour 2 Shift Workers in the Automobile Factory in Korea.

PubMed

Son, Mia; Sung, Juhon; Yum, Myunggul; Kong, Jung Ok; Lee, Hye Un; Kim, In A; Kim, Jung Yeon

2004-05-01

The objective of this study is to compare the circadian patterns of heart rate variability assessed by 24-hour ambulatory electrocardiographic (ECG) recordings during day shift and night shift among the workers in the 5 days-concecutive- 12-hour shift in an automobile factory in Korea. The study population consisted 300 workers, who were randomly selected among the 8700 total workers in one car factory. To analyse circadian variation, the 24-hour ECG recordings (Marquette) were measured during day shift (08: 00-20: 00 h) and night shift (20: 00-08: 00 h). Analysis was performed for all time and frequency domain measures of HRV. 233 workers completed taking 24-hour ECG recordings. This study shows that the 24 hourcircadian variation mainly follows work/sleep cycle rather than day/night cycle among shift workers. This study also shows that among the night shift, the circadian variation between work and sleep cycle decreased compared to the work/sleep cycle among day shift workers. All time and frequency domain parameters (except LF/HF ratio) show significantly different between work and sleep in the day shift and night shift. These changes in heart rate variability circadian rhythms reflect significant reductions in cardiac parasympathetic activity with the most marked reduction in normal vagal activity among the shift workers. Especially, it suggests the circadian rhytm has blunted among the night workers. The quantification of the circadian variation in HRV can be a surrogates of workers' potential health risk, as well as suggests possible mechanisms through which the shift works compromise workers' health.

Usual normalization strategies for gene expression studies impair the detection and analysis of circadian patterns.

PubMed

Figueredo, Diego de Siqueira; Barbosa, Mayara Rodrigues; Coimbra, Daniel Gomes; Dos Santos, José Luiz Araújo; Costa, Ellyda Fernanda Lopes; Koike, Bruna Del Vechio; Alexandre Moreira, Magna Suzana; de Andrade, Tiago Gomes

2018-03-01

Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered. In this study, we controlled experimental conditions from the amount of initial brain tissue samples through extraction steps, cDNA synthesis, and quantitative real time PCR (qPCR) to demonstrate a circadian oscillation of total RNA concentration. We also identified that the normalization of the RNA's yield affected the rhythmic profiles of different genes, including Per1-2 and Bmal1. Five widely used HKGs (Actb, Eif2a, Gapdh, Hprt1, and B2m) also presented rhythmic variations not detected by geNorm algorithm. In addition, the analysis of exogenous microRNAs (Cel-miR-54 and Cel-miR-39) spiked during RNA extraction suggests that the yield was affected by total RNA concentration, which may impact circadian studies of small RNAs. The results indicate that the approach of tissue normalization without total RNA equalization prior to cDNA synthesis can avoid bias from endogenous broad variations in transcript levels. Also, the circadian analysis of 2 -Cycle threshold (Ct) data, without HKGs, may be an alternative for chronobiological studies under controlled experimental conditions.

Human responses to bright light of different durations.

PubMed

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Relationship between Human Pupillary Light Reflex and Circadian System Status

PubMed Central

Bonmati-Carrion, Maria Angeles; Hild, Konstanze; Isherwood, Cheryl; Sweeney, Stephen J.; Revell, Victoria L.; Skene, Debra J.; Rol, Maria Angeles; Madrid, Juan Antonio

2016-01-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs), whose photopigment melanopsin has a peak of sensitivity in the short wavelength range of the spectrum, constitute a common light input pathway to the olivary pretectal nucleus (OPN), the pupillary light reflex (PLR) regulatory centre, and to the suprachiasmatic nuclei (SCN), the major pacemaker of the circadian system. Thus, evaluating PLR under short wavelength light (λmax ≤ 500 nm) and creating an integrated PLR parameter, as a possible tool to indirectly assess the status of the circadian system, becomes of interest. Nine monochromatic, photon-matched light stimuli (300 s), in 10 nm increments from λmax 420 to 500 nm were administered to 15 healthy young participants (8 females), analyzing: i) the PLR; ii) wrist temperature (WT) and motor activity rhythms (WA), iii) light exposure (L) pattern and iv) diurnal preference (Horne-Östberg), sleep quality (Pittsburgh) and daytime sleepiness (Epworth). Linear correlations between the different PLR parameters and circadian status index obtained from WT, WA and L recordings and scores from questionnaires were calculated. In summary, we found markers of robust circadian rhythms, namely high stability, reduced fragmentation, high amplitude, phase advance and low internal desynchronization, were correlated with a reduced PLR to 460–490 nm wavelengths. Integrated circadian (CSI) and PLR (cp-PLR) parameters are proposed, that also showed an inverse correlation. These results demonstrate, for the first time, the existence of a close relationship between the circadian system robustness and the pupillary reflex response, two non-visual functions primarily under melanopsin-ipRGC input. PMID:27636197

Influence of gestational diabetes on circadian rhythms of children and their association with fetal adiposity.

PubMed

Zornoza-Moreno, Matilde; Fuentes-Hernández, Silvia; Prieto-Sánchez, María T; Blanco, José E; Pagán, Ana; Rol, María-Ángeles; Parrilla, Juan J; Madrid, Juan A; Sánchez-Solis, Manuel; Larqué, Elvira

2013-09-01

To analyse the circadian rhythm maturation of temperature, activity and sleep during the first year of life in offspring of diabetic mothers (ODM) and its relationship with obesity markers. A prospective analysis of the children of 63 pregnant women (23 controls, 21 gestational diabetes mellitus (GDM) controlled with diet and 19 GDM with insulin). Fetal abdominal circumference was evaluated ecographically during gestation. Skin temperature and rest-activity rhythms were monitored for 3 consecutive days in children at 15 days and 1, 3 and 6 months. Anthropometrical parameters of the children were evaluated during the first year of life. Children from the GDM groups tended to higher fetal abdominal circumference z-score than controls at the beginning of the last trimester (p = 0.077) and at delivery (p = 0.078). Mean skin temperature or activity was not different among the groups. The I < O sleep index pointed to increasing concordance with parental sleeping at 3 and 6 months but no significant GDM-dependent differences. However, some of the parameters that define temperature maturation and also the circadian function index from the temperature-activity variable were significantly lower at 6 months in the GDM + insulin group. Fetal abdominal circumference z-score, as a predictor of fetal adiposity, correlated negatively with parameters related to circadian rhythm maturation as the circadian/ultradian rhythm (P1 /Pult ratio). Fetal adiposity correlated with a worse circadian rhythm regulation in ODM. In addition, ODM insulin-treated showed a disturbed pattern of the circadian function index of temperature activity at 6 months of age. Copyright © 2013 John Wiley & Sons, Ltd.

Mitochondrial DNA pattern of the fine shrimp Metapenaeus elegans (De Man, 1907) in the lagoon of Segara Anakan, Central Java, using Hind III

NASA Astrophysics Data System (ADS)

Nugraha, Fitra Arya Dwi; Holil, Kholifah; Kurniawan, Nia

2017-05-01

Ecological damages to the Lagoon of Segara Anakan, Central Java, as well as large-scale and continuous exploitation are threatening the sustainability of fine shrimp, Metapenaeus elegans, and resources. Information in regards to genetic resources is crucial to establish long-term conservation programs and to preserve germplasm quality. This study aims to evaluate the number and size of the fragment which is digested with restriction enzyme Hind III. Seven individuals of Metapenaeus elegans from the Lagoon of Segara Anakan were examined using Hind III. Amplification of mitochondrial DNA resulted in 950 bp, and the digestion using Hind III generated four fragments consisting of 114 bp, 200 bp, 250 bp, and 386 bp, which formed a monomorphic pattern. The restriction pattern showed the probability of homozygosity of alleles that restricted using Hind III. Homozygosity indicates no variation of DNA sequence.

Differential Patterns of Abnormal Activity and Connectivity in the Amygdala-Prefrontal Circuitry in Bipolar-I and Bipolar-NOS Youth

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Farchione, Tiffany; Diwadkar, Vaibhav; Pruitt, Patrick; Radwan, Jacqueline; Axelson, David A.; Birmaher, Boris; Phillips, Mary L.

2011-01-01

Objective: The functioning of neural systems supporting emotion processing and regulation in youth with bipolar disorder not otherwise specified (BP-NOS) remains poorly understood. We sought to examine patterns of activity and connectivity in youth with BP-NOS relative to youth with bipolar disorder type I (BP-I) and healthy controls (HC). Method:…

The Relationship between Autism Spectrum Disorder and Melatonin during Fetal Development.

PubMed

Jin, Yunho; Choi, Jeonghyun; Won, Jinyoung; Hong, Yonggeun

2018-01-18

The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD) during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is secreted by the pineal gland, has well-established neuroprotective and circadian entraining effects. During pregnancy, the hormone crosses the placenta into the fetal circulation and transmits photoperiodic information to the fetus allowing the establishment of normal sleep patterns and circadian rhythms that are essential for normal neurodevelopment. Melatonin synthesis is frequently impaired in patients with ASD. The hormone reduces oxidative stress, which is harmful to the central nervous system. Therefore, the neuroprotective and circadian entraining roles of melatonin may reduce the risk of neurodevelopmental disorders such as ASD.

Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer.

PubMed

Matteucci, Elena; Consani, Cristina; Masoni, Maria Chiara; Giampietro, Ottavio

2010-10-05

Normotensive non-diabetic relatives of type 1 diabetes (T1D) patients have an abnormal blood pressure response to exercise testing that is associated with indices of metabolic syndrome and increased oxidative stress. The primary aim of this study was to investigate the circadian variability of blood pressure and the ambulatory arterial stiffness index (AASI) in healthy siblings of T1D patients vs healthy control subjects who had no first-degree relative with T1D. Secondary aims of the study were to explore the influence of both cardiovascular autonomic function and erythrocyte electron transfer activity as oxidative marker on the ambulatory blood pressure profile. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was undertaken in 25 controls, 20 T1D patients and 20 siblings. In addition to laboratory examination (including homeostasis model assessment of insulin sensitivity) and clinical testing of autonomic function, we measured the rate of oxidant-induced erythrocyte electron transfer to extracellular ferricyanide (RBC vfcy). Systolic blood pressure (SBP) midline-estimating statistic of rhythm and pulse pressure were higher in T1D patients and correlated positively with diabetes duration and RBC vfcy; autonomic dysfunction was associated with diastolic BP ecphasia and increased AASI. Siblings had higher BMI, lower insulin sensitivity, larger SBP amplitude, and higher AASI than controls. Daytime SBP was positively, independently associated with BMI and RBC vfcy. Among non-diabetic people, there was a significant correlation between AASI and fasting plasma glucose. Siblings of T1D patients exhibited a cluster of sub-clinical metabolic abnormalities associated with consensual perturbations in BP variability. Moreover, our findings support, in a clinical setting, the proposed role of transplasma membrane electron transport systems in vascular pathobiology.

Holiday and School-Term Sleep Patterns of Australian Adolescents

ERIC Educational Resources Information Center

Warner, Suzanne; Murray, Greg; Meyer, Denny

2008-01-01

The holiday and school-term sleep patterns of 310 Australian senior school students were surveyed in a longitudinal study, along with self-reported sleep quality, mood, daytime functioning, grades and circadian preference. Evidence was found that with the impact of school schedule, students accrued a significant sleep debt, obtaining insufficient…

Light at night alters daily patterns of cortisol and clock proteins in female Siberian hamsters.

PubMed

Bedrosian, T A; Galan, A; Vaughn, C A; Weil, Z M; Nelson, R J

2013-06-01

Humans and other organisms have adapted to a 24-h solar cycle in response to life on Earth. The rotation of the planet on its axis and its revolution around the sun cause predictable daily and seasonal patterns in day length. To successfully anticipate and adapt to these patterns in the environment, a variety of biological processes oscillate with a daily rhythm of approximately 24 h in length. These rhythms arise from hierarchally-coupled cellular clocks generated by positive and negative transcription factors of core circadian clock gene expression. From these endogenous cellular clocks, overt rhythms in activity and patterns in hormone secretion and other homeostatic processes emerge. These circadian rhythms in physiology and behaviour can be organised by a variety of cues, although they are most potently entrained by light. In recent history, there has been a major change from naturally-occurring light cycles set by the sun, to artificial and sometimes erratic light cycles determined by the use of electric lighting. Virtually every individual living in an industrialised country experiences light at night (LAN) but, despite its prevalence, the biological effects of such unnatural lighting have not been fully considered. Using female Siberian hamsters (Phodopus sungorus), we investigated the effects of chronic nightly exposure to dim light on daily rhythms in locomotor activity, serum cortisol concentrations and brain expression of circadian clock proteins (i.e. PER1, PER2, BMAL1). Although locomotor activity remained entrained to the light cycle, the diurnal fluctuation of cortisol concentrations was blunted and the expression patterns of clock proteins in the suprachiasmatic nucleus and hippocampus were altered. These results demonstrate that chronic exposure to dim LAN can dramatically affect fundamental cellular function and emergent physiology. © 2013 British Society for Neuroendocrinology.

Noninvasive beat-to-beat finger arterial pressure monitoring during orthostasis: a comprehensive review of normal and abnormal responses at different ages.

PubMed

van Wijnen, V K; Finucane, C; Harms, M P M; Nolan, H; Freeman, R L; Westerhof, B E; Kenny, R A; Ter Maaten, J C; Wieling, W

2017-12-01

Over the past 30 years, noninvasive beat-to-beat blood pressure (BP) monitoring has provided great insight into cardiovascular autonomic regulation during standing. Although traditional sphygmomanometric measurement of BP may be sufficient for detection of sustained orthostatic hypotension, it fails to capture the complexity of the underlying dynamic BP and heart rate responses. With the emerging use of noninvasive beat-to-beat BP monitoring for the assessment of orthostatic BP control in clinical and population studies, various definitions for abnormal orthostatic BP patterns have been used. Here, age-related changes in cardiovascular control in healthy subjects will be reviewed to define the spectrum of the most important abnormal orthostatic BP patterns within the first 180 s of standing. Abnormal orthostatic BP responses can be defined as initial orthostatic hypotension (a transient systolic BP fall of >40 mmHg within 15 s of standing), delayed BP recovery (an inability of systolic BP to recover to a value of >20 mmHg below baseline at 30 s after standing) and sustained orthostatic hypotension (a sustained decline in systolic BP of ≥20 mmHg occurring 60-180 s after standing). In the evaluation of patients with light-headedness, pre(syncope), (unexplained) falls or suspected autonomic dysfunction, it is essential to distinguish between normal cardiovascular autonomic regulation and these abnormal orthostatic BP responses. The prevalence, clinical relevance and underlying pathophysiological mechanisms of these patterns differ significantly across the lifespan. Initial orthostatic hypotension is important for identifying causes of syncope in younger adults, whereas delayed BP recovery and sustained orthostatic hypotension are essential for evaluating the risk of falls in older adults. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Tales around the clock: Poly(A) tails in circadian gene expression.

PubMed

Beta, Rafailia A A; Balatsos, Nikolaos A A

2018-06-17

Circadian rhythms are ubiquitous time-keeping processes in eukaryotes with a period of ~24 hr. Light is perhaps the main environmental cue (zeitgeber) that affects several aspects of physiology and behaviour, such as sleep/wake cycles, orientation of birds and bees, and leaf movements in plants. Temperature can serve as the main zeitgeber in the absence of light cycles, even though it does not lead to rhythmicity through the same mechanism as light. Additional cues include feeding patterns, humidity, and social rhythms. At the molecular level, a master oscillator orchestrates circadian rhythms and organizes molecular clocks located in most cells. The generation of the 24 hr molecular clock is based on transcriptional regulation, as it drives intrinsic rhythmic changes based on interlocked transcription/translation feedback loops that synchronize expression of genes. Thus, processes and factors that determine rhythmic gene expression are important to understand circadian rhythms. Among these, the poly(A) tails of RNAs play key roles in their stability, translational efficiency and degradation. In this article, we summarize current knowledge and discuss perspectives on the role and significance of poly(A) tails and associating factors in the context of the circadian clock. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNA Processing > 3' End Processing. © 2018 Wiley Periodicals, Inc.

The effect of intermittent fasting during Ramadan on sleep, sleepiness, cognitive function, and circadian rhythm.

PubMed

Qasrawi, Shaden O; Pandi-Perumal, Seithikurippu R; BaHammam, Ahmed S

2017-09-01

Studies have shown that experimental fasting can affect cognitive function, sleep, and wakefulness patterns. However, the effects of experimental fasting cannot be generalized to fasting during Ramadan due to its unique characteristics. Therefore, there has been increased interest in studying the effects of fasting during Ramadan on sleep patterns, daytime sleepiness, cognitive function, sleep architecture, and circadian rhythm. In this review, we critically discuss the current research findings in those areas during the month of Ramadan. Available data that controlled for sleep/wake schedule, sleep duration, light exposure, and energy expenditure do not support the notion that Ramadan intermittent fasting increases daytime sleepiness and alters cognitive function. Additionally, recent well-designed studies showed no effect of fasting on circadian rhythms. However, in non-constrained environments that do not control for lifestyle changes, studies have demonstrated sudden and significant delays in bedtime and wake time. Studies that controlled for environmental factors and sleep/wake schedule reported no significant disturbances in sleep architecture. Nevertheless, several studies have consistently reported that the main change in sleep architecture during fasting is a reduction in the proportion of REM sleep.

Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

PubMed

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

2017-01-01

Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian circuit to generate robust 24-h rhythms.

Naturally occurring circadian rhythm and sleep duration are related to executive functions in early adulthood.

PubMed

Kuula, Liisa; Pesonen, Anu-Katriina; Heinonen, Kati; Kajantie, Eero; Eriksson, Johan Gunnar; Andersson, Sture; Lano, Aulikki; Lahti, Jari; Wolke, Dieter; Räikkönen, Katri

2018-02-01

Experimental sleep deprivation studies suggest that insufficient sleep and circadian misalignment associates with poorer executive function. It is not known whether this association translates to naturally occurring sleep patterns. A total of 512 of full-term-born members of the Arvo Ylppö Longitudinal Study [mean age = 25.3, standard deviation (SD) = 0.65] (44.3% men) wore actigraphs to define sleep duration, its irregularity and circadian rhythm (sleep mid-point) during a 1-week period (mean 6.9 nights, SD = 1.7). Performance-based executive function was assessed with the Trail-Making Test, Conners' Continuous Performance Test and Stroop. The self-rated adult version of Behavior Rating Inventory of Executive Function was used to assess trait-like executive function. We found that performance-based and self-reported trait-like executive function correlated only modestly (all correlations ≤0.17). Shorter sleep duration associated with more commission errors. Later circadian rhythm associated with poorer trait-like executive function, as indicated by the Brief Metacognitive Index and the Behavior Regulation Index. Those belonging to the group with the most irregular sleep duration performed slower than others in the Trail-Making Test Part A. All associations were adjusted for sex, age, socioeconomic status and body mass index. In conclusion, naturally occurring insufficient sleep and later circadian rhythm showed modest associations with poorer executive function. Shorter habitual sleep duration was associated with lower scores of performance-based tests of executive function, and later circadian rhythm was associated mainly with poorer trait-like executive function characteristics. Our findings suggest additionally that sleep duration and circadian rhythm associate with different domains of executive function, and there are no additive effects between the two. © 2017 European Sleep Research Society.

Enhancement of NAD+-dependent SIRT1 deacetylase activity by methylselenocysteine resets the circadian clock in carcinogen-treated mammary epithelial cells

PubMed Central

Fang, Mingzhu; Guo, Wei-Ren; Park, Youngil; Kang, Hwan-Goo; Zarbl, Helmut

2015-01-01

We previously reported that dietary methylselenocysteine (MSC) inhibits N-methyl-N-nitrosourea (NMU)-induced mammary tumorigenesis by resetting circadian gene expression disrupted by the carcinogen at the early stage of tumorigenesis. To investigate the underlying mechanism, we developed a circadian reporter system comprised of human mammary epithelial cells with a luciferase reporter driven by the promoter of human PERIOD 2 (PER2), a core circadian gene. In this in vitro model, NMU disrupted cellular circadian rhythm in a pattern similar to that observed with SIRT1-specific inhibitors; in contrast, MSC restored the circadian rhythms disrupted by NMU and protected against SIRT1 inhibitors. Moreover, NMU inhibited intracellular NAD+/NADH ratio and reduced NAD+-dependent SIRT1 activity in a dose-dependent manner, while MSC restored NAD+/NADH and SIRT1 activity in the NMU-treated cells, indicating that the NAD+-SIRT1 pathway was targeted by NMU and MSC. In rat mammary tissue, a carcinogenic dose of NMU also disrupted NAD+/NADH oscillations and decreased SIRT1 activity; dietary MSC restored NAD+/NADH oscillations and increased SIRT1 activity in the mammary glands of NMU-treated rats. MSC-induced SIRT1 activity was correlated with decreased acetylation of BMAL1 and increased acetylation of histone 3 lysine 9 at the Per2 promoter E-Box in mammary tissue. Changes in SIRT1 activity were temporally correlated with loss or restoration of rhythmic Per2 mRNA expression in NMU-treated or MSC-rescued rat mammary glands, respectively. Together with our previous findings, these results suggest that enhancement of NAD+-dependent SIRT1 activity contributes to the chemopreventive efficacy of MSC by restoring epigenetic regulation of circadian gene expression at early stages of mammary tumorigenesis. PMID:26544624

Exercise-induced albuminuria vs circadian variations in blood pressure in type 1 diabetes.

PubMed

Tadida Meli, Isabelle Hota; Tankeu, Aurel T; Dehayem, Mesmin Y; Chelo, David; Noubiap, Jean Jacques N; Sobngwi, Eugene

2017-02-15

To investigated the relationship between exercise-induced ambulatory blood pressure measurement (ABPM) abnormalities in type 1 diabetes mellitus (T1DM) adolescents. We conducted a case-control at the National Obesity Center of the Yaoundé Central Hospital, Cameroon. We compared 24 h ABPM and urinary albumin-to-creatinine ratio (ACR) at rest and after a standardized treadmill exercise between 20 Cameroonian T1DM patients and 20 matched controls. T1DM adolescents were aged 12-18 years, with diabetes for at least one year, without proteinuria, with normal office blood pressure (BP) and renal function according to the general reference population. Non-diabetic controls were adolescents of general population matched for sex, age and BMI. Mean duration of diabetes was 4.2 ± 2.8 years. The mean 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively 116 ± 9 mmHg in the diabetic group vs 111 ± 8 mmHg in the non-diabetic ( P = 0.06), and 69 ± 7 mm Hg vs 66 ± 5 mm Hg ( P = 0.19). There was no difference in the diurnal pattern of BP in diabetes patients and non-diabetic controls (SBP: 118 ± 10 mmHg vs 114 ± 10 mmHg, P = 0.11; DBP: 71 ± 7 mmHg vs 68 ± 6 mmHg, P = 0.22). Nighttime BP was higher in the diabetic group with respect to SBP (112 ± 11 mmHg vs 106 ± 7 mmHg, P = 0.06) and to the mean arterial pressure (MAP) (89 ± 9 mmHg vs 81 ± 6 mmHg, P = 0.06). ACR at rest was similar in both groups (5.5 mg/g vs 5.5 mg/g, P = 0.74), but significantly higher in diabetes patients after exercise (10.5 mg/g vs 5.5 mg/g, P = 0.03). SBP was higher in patients having exercise-induced albuminuria (116 ± 10 mmHg vs 108 ± 10 mmHg, P = 0.09). Exercise-induced albuminuria could be useful for early diagnosis of kidney damage in adolescents with T1DM.

Measurements of monopolar and bipolar current spreads using forward-masking with a fixed probe.

PubMed

Bingabr, Mohamed G; Espinoza-Varas, Blas; Sigdel, Saroj

2014-05-01

This research employed a forward-masking paradigm to estimate the current spread of monopolar (MP) and bipolar (BP) maskers, with current amplitudes adjusted to elicit the same loudness. Since the spatial separation between active and return electrodes is smaller in BP than in MP configurations, the BP current spread is more localized and presumably superior in terms of speech intelligibility. Because matching the loudness requires higher current in BP than in MP stimulation, previous forward-masking studies show that BP current spread is not consistently narrower across subjects or electrodes within a subject. The present forward-masking measures of current spread differ from those of previous studies by using the same BP probe electrode configuration for both MP and BP masker configurations, and adjusting the current levels of the MP and BP maskers so as to match them in loudness. With this method, the estimate of masker current spread would not be contaminated by differences in probe current spread. Forward masking was studied in four cochlear implant patients, two females and two males, with speech recognition scores higher than 50%; that is, their auditory-nerve survival status was more than adequate to carry out the experiments. The data showed that MP and BP masker configurations produce equivalent masking patterns (and current spreads) in three participants. A fourth participant displayed asymmetrical patterns with enhancement rather than masking in some cases, especially when the probe and masker were at the same location. This study showed equivalent masking patterns for MP and BP maskers when the BP masker current amplitude was increased to match the loudness of the MP masker, and the same BP probe configuration is used with both maskers. This finding could help to explain why cochlear implant users often fail to accrue higher speech intelligibility benefit from BP stimulation.

Relationship Between 24-Hour Ambulatory Blood Pressure and Cognitive Function in Community-Living Older Adults: The UCSD Ambulatory Blood Pressure Study.

PubMed

Conway, Kyle S; Forbang, Nketi; Beben, Tomasz; Criqui, Michael H; Ix, Joachim H; Rifkin, Dena E

2015-12-01

Twenty-four-hour ambulatory blood pressure (BP) patterns have been associated with diminished cognitive function in hypertensive and very elderly populations. The relationship between ambulatory BP patterns and cognitive function in community-living older adults is unknown. We conducted a cross-sectional study in which 24-hour ambulatory BP, in-clinic BP, and cognitive function measures were obtained from 319 community-living older adults. The mean age was 72 years, 66% were female, and 13% were African-American. We performed linear regression with performance on the Montreal Cognitive Assessment (MoCA) as the primary outcome and 24-hour BP patterns as the independent variable, adjusting for age, sex, race/ethnicity, education, and comorbidities. Greater nighttime systolic dipping (P = 0.046) and higher 24-hour diastolic BP (DBP; P = 0.015) were both significantly associated with better cognitive function, whereas 24-hour systolic BP (SBP), average real variability, and ambulatory arterial stiffness were not. Higher 24-hour DBP and greater nighttime systolic dipping were significantly associated with improved cognitive function. Future studies should examine whether low 24-hour DBP and lack of nighttime systolic dipping predict future cognitive impairment. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Circadian Rhythm Sleep-Wake Disorders.

PubMed

Pavlova, Milena

2017-08-01

The endogenous circadian rhythms are one of the cardinal processes that control sleep. They are self-sustaining biological rhythms with a periodicity of approximately 24 hours that may be entrained by external zeitgebers (German for time givers), such as light, exercise, and meal times. This article discusses the physiology of the circadian rhythms, their relationship to neurologic disease, and the presentation and treatment of circadian rhythm sleep-wake disorders. Classic examples of circadian rhythms include cortisol and melatonin secretion, body temperature, and urine volume. More recently, the impact of circadian rhythm on several neurologic disorders has been investigated, such as the timing of occurrence of epileptic seizures as well as neurobehavioral functioning in dementia. Further updates include a more in-depth understanding of the symptoms, consequences, and treatment of circadian sleep-wake disorders, which may occur because of extrinsic misalignment with clock time or because of intrinsic dysfunction of the brain. An example of extrinsic misalignment occurs with jet lag during transmeridian travel or with intrinsic circadian rhythm sleep-wake disorders such as advanced or delayed sleep-wake phase disorders. In advanced sleep-wake phase disorder, which is most common in elderly individuals, sleep onset and morning arousal are undesirably early, leading to impaired evening function with excessive sleepiness and sleep-maintenance insomnia with early morning awakening. By contrast, delayed sleep-wake phase disorder is characterized by an inability to initiate sleep before the early morning hours, with subsequent delayed rise time, leading to clinical symptoms of severe sleep-onset insomnia coupled with excessive daytime sleepiness in the morning hours, as patients are unable to "sleep in" to attain sufficient sleep quantity. Irregular sleep-wake rhythm disorder is misentrainment with patches of brief sleep and wakefulness spread throughout the day, leading to unstable sleep and waking behavioral patterns and an entirely idiosyncratic sleep-wake schedule. Familiarity with these major circadian rhythm sleep-wake disorder phenotypes and their overlap with other neurologic disorders is essential for the neurologist so that clinicians may intervene and improve patient functioning and quality of life.

Circadian variations of adenosine and of its metabolism. Could adenosine be a molecular oscillator for circadian rhythms?

PubMed

Chagoya de Sánchez, V

1995-03-01

The present review describes the biological implications of the periodic changes of adenosine concentrations in different tissues of the rat. Adenosine is a purine molecule that could have been formed in the prebiotic chemical evolution and has been preserved. The rhythmicity of this molecule, as well as its metabolism and even the presence of specific receptors, suggests a regulatory role in eukaryotic cells and in multicellular organisms. Adenosine may be considered a chemical messenger and its action could take place at the level of the same cell (autocrine), the same tissue (paracrine), or on separate organs (endocrine). Exploration of the circadian variations of adenosine was planned considering the liver as an important tissue for purine formation, the blood as a vehicle among tissues, and the brain as the possible acceptor for hepatic adenosine or its metabolites. The rats used in these studies were adapted to a dark-light cycle of 12 h with an unrestrained feeding and drinking schedule. The metabolic control of adenosine concentration in the different tissues studied through the 24-h cycle is related to the activity of adenosine-metabolizing enzyme: 5'-nucleotidase adenosine deaminase, adenosine kinase, and S-adenosylhomocysteine hydrolase. Some possibilities of the factors modulating the activity of these enzymes are commented upon. The multiphysiological action of adenosine could be mediated by several actions: (i) by interaction with extracellular and intracellular receptors and (ii) through its metabolism modulating the methylation pathway, possibly inducing physiological lipoperoxidation, or participating in the energetic homeostasis of the cell. The physiological meaning of the circadian variations of adenosine and its metabolism was focused on: maintenance of the energetic homeostasis of the tissues, modulation of membrane structure and function, regulation of fasting and feeding metabolic pattern, and its participation in the sleep-wake cycle. From these considerations, we suggest that adenosine could be a molecular oscillator involved in the circadian pattern of biological activity in the rat.

Nanoscale patterning of a self-assembled monolayer by modification of the molecule-substrate bond.

PubMed

Shen, Cai; Buck, Manfred

2014-01-01

The intercalation of Cu at the interface of a self-assembled monolayer (SAM) and a Au(111)/mica substrate by underpotential deposition (UPD) is studied as a means of high resolution patterning. A SAM of 2-(4'-methylbiphenyl-4-yl)ethanethiol (BP2) prepared in a structural phase that renders the Au substrate completely passive against Cu-UPD, is patterned by modification with the tip of a scanning tunneling microscope. The tip-induced defects act as nucleation sites for Cu-UPD. The lateral diffusion of the metal at the SAM-substrate interface and, thus, the pattern dimensions are controlled by the deposition time. Patterning down to the sub-20 nm range is demonstrated. The difference in strength between the S-Au and S-Cu bond is harnessed to develop the latent Cu-UPD image into a patterned binary SAM. Demonstrated by the exchange of BP2 by adamantanethiol (AdSH) this is accomplished by a sequence of reductive desorption of BP2 in Cu free areas followed by adsorption of AdSH. The appearance of Au adatom islands upon the thiol exchange suggests that the interfacial structures of BP2 and AdSH SAMs are different.

Seasonal variation of temporal niche in wild owl monkeys (Aotus azarai azarai) of the Argentinean Chaco: a matter of masking?

PubMed

Erkert, Hans G; Fernandez-Duque, Eduardo; Rotundo, Marcelo; Scheideler, Angelika

2012-07-01

Among the more than 40 genera of anthropoid primates (monkeys, apes, and humans), only the South American owl monkeys, genus Aotus, are nocturnal. However, the southernmostly distributed species, Aotus azarai azarai, of the Gran Chaco may show considerable amounts of its 24-h activity during bright daylight. Due to seasonal changes in the duration of photophase and climatic parameters in their subtropical habitat, the timing and pattern of their daily activity are expected to show significant seasonal variation. By quantitative long-term activity recordings with Actiwatch AW4 accelerometer data logger devices of 10 wild owl monkeys inhabiting a gallery forest in Formosa, Argentina, the authors analyzed the seasonal variation in the temporal niche and activity pattern resulting from entrainment and masking of the circadian activity rhythm by seasonally and diurnally varying environmental factors. The owl monkeys always displayed a distinct bimodal activity pattern, with prominent activity bouts and peaks during dusk and dawn. Their activity rhythm showed distinct lunar and seasonal variations in the timing and daily pattern. During the summer, the monkeys showed predominantly crepuscular/nocturnal behavior, and a crepuscular/cathemeral activity pattern with similar diurnal and nocturnal activity levels during the cold winter months. The peak times of the evening and morning activity bouts were more closely related to the times of sunset and sunrise, respectively, than activity-onset and -offset. Obviously, they were better circadian markers for the phase position of the entrained activity rhythm than activity-onset and -offset, which were subject to more masking effects of environmental and/or internal factors. Total daily activity was lowest during the two coldest lunar months, and almost twice as high during the warmest months. Nighttime (21:00-06:00 h) and daytime (09:00-18:00 h) activity varied significantly across the year, but in an opposite manner. Highest nighttime activity occurred in summer and maximal daytime activity during the cold winter months. Dusk and dawn activity, which together accounted for 43% of the total daily activity, barely changed. The monkeys tended to terminate their nightly activity period earlier on warm and rainy days, whereas the daily amount of activity showed no significant correlation either with temperature or precipitation. These data are consistent with the dual-oscillator hypothesis of circadian regulation. They suggest the seasonal variations of the timing and pattern of daily activity in wild owl monkeys of the Argentinean Chaco result from a specific interplay of light entrainment of circadian rhythmicity and strong masking effects of various endogenous and environmental factors. Since the phase position of the monkeys' evening and morning activity peaks did not vary considerably over the year, the seasonal change from a crepuscular/nocturnal activity pattern in summer to a more crepuscular/cathemeral one in winter does not depend on a corresponding phase shift of the entrained circadian rhythm, but mainly on masking effects. Thermoregulatory and energetic demands and constraints seem to play a crucial role.

Molecular typing of Staphylococcus aureus based on coagulase gene.

PubMed

Javid, Faizan; Taku, Anil; Bhat, Mohd Altaf; Badroo, Gulzar Ahmad; Mudasir, Mir; Sofi, Tanveer Ahmad

2018-04-01

This study was conducted to study the coagulase gene-based genetic diversity of Staphylococcus aureus , isolated from different samples of cattle using restriction fragment length polymorphism (RFLP) and their sequence-based phylogenetic analysis. A total of 192 different samples from mastitic milk, nasal cavity, and pus from skin wounds of cattle from Military Dairy Farm, Jammu, India, were screened for the presence of S. aureus . The presumptive isolates were confirmed by nuc gene-based polymerase chain reaction (PCR). The confirmed S. aureus isolates were subjected to coagulase ( coa ) gene PCR. Different coa genotypes observed were subjected to RFLP using restriction enzymes Hae111 and Alu1 , to obtain the different restriction patterns. One isolate from each restriction pattern was sequenced. These sequences were aligned for maximum homology using the Bioedit softwareandsimilarity in the sequences was inferred with the help of sequence identity matrix. Of 192 different samples,39 (20.31%) isolates of S. aureus were confirmed by targeting nuc gene using PCR. Of 39 S. aureus isolates, 25 (64.10%) isolates carried coa gene. Four different genotypes of coa gene, i.e., 514 bp, 595 bp, 757 bp, and 802 bp were obtained. Two coa genotypes, 595 bp (15 isolates) and 802 bp (4 isolates), were observed in mastitic milk. 514 bp (2 isolates) and 757 bp (4 isolates) coa genotypes were observed from nasal cavity and pus from skin wounds, respectively. On RFLP using both restriction enzymes, four different restriction patterns P1, P2, P3, and P4 were observed. On sequencing, four different sequences having unique restriction patterns were obtained. The most identical sequences with the value of 0.810 were found between isolate S. aureus 514 (nasal cavity) and S. aureus 595 (mastitic milk), and thus, they are most closely related. While as the most distant sequences with the value of 0.483 were found between S. aureus 514 and S. aureus 802 isolates. The study, being localized to only one farm, yielded different RFLP patterns as observed from different sampling sites, which indicates that different S . aureus coagulase typeshave a site-specific predilection. Two coa patterns were observed in mastitic milk indicating multiple origins of infection, with 595 bp coa genotype being predominant in mastitic milk. The coa genotypes and their restriction patterns observed in the present study are novel, not published earlier. 514 and 595 coa variants of S. aureus are genetically most related.

Modeling study on the flow patterns of gas-liquid flow for fast decarburization during the RH process

NASA Astrophysics Data System (ADS)

Li, Yi-hong; Bao, Yan-ping; Wang, Rui; Ma, Li-feng; Liu, Jian-sheng

2018-02-01

A water model and a high-speed video camera were utilized in the 300-t RH equipment to study the effect of steel flow patterns in a vacuum chamber on fast decarburization and a superior flow-pattern map was obtained during the practical RH process. There are three flow patterns with different bubbling characteristics and steel surface states in the vacuum chamber: boiling pattern (BP), transition pattern (TP), and wave pattern (WP). The effect of the liquid-steel level and the residence time of the steel in the chamber on flow patterns and decarburization reaction were investigated, respectively. The liquid-steel level significantly affected the flow-pattern transition from BP to WP, and the residence time and reaction area were crucial to evaluate the whole decarburization process rather than the circulation flow rate and mixing time. A superior flow-pattern map during the practical RH process showed that the steel flow pattern changed from BP to TP quickly, and then remained as TP until the end of decarburization.

Dietary Patterns and Blood Pressure in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials12

PubMed Central

Tapsell, Linda C; Batterham, Marijka J

2016-01-01

Hypertension is a major risk factor for developing cardiovascular disease, stroke, and kidney disease. To lower blood pressure (BP), several lifestyle changes are recommended such as weight loss, exercise, and following a healthy diet. Investigating the effect of single nutrients may have positive results, but food is consumed as part of a whole diet, resulting in nutrient interactions. The aim of this systematic review and meta-analysis was to assess the effect of dietary patterns on BP in adults. Studies that were published between January 1999 and June 2014 were retrieved using Scopus, Web of Science, and the MEDLINE database. Seventeen randomized controlled trials were included in the meta-analysis. The results suggest that healthy dietary patterns such as the Dietary Approaches to Stop Hypertension diet, Nordic diet, and Mediterranean diet significantly lowered systolic BP and diastolic BP by 4.26 mm Hg and 2.38 mm Hg, respectively. These diets are rich in fruit, vegetables, whole grains, legumes, seeds, nuts, fish, and dairy and low in meat, sweets, and alcohol. Lifestyle factors such as exercise and weight loss in combination with dietary changes may also reduce BP. Further research is needed to establish the effect of dietary patterns on BP in different cultures other than those identified in this review. The review was registered on PROSPERO (International prospective register of systematic reviews) as CRD42015016272. PMID:26773016

Integrating Circadian Activity and Gene Expression Profiles to Predict Chronotoxicity of Drosophila suzukii Response to Insecticides

PubMed Central

Hamby, Kelly A.; Kwok, Rosanna S.; Zalom, Frank G.; Chiu, Joanna C.

2013-01-01

Native to Southeast Asia, Drosophila suzukii (Matsumura) is a recent invader that infests intact ripe and ripening fruit, leading to significant crop losses in the U.S., Canada, and Europe. Since current D. suzukii management strategies rely heavily on insecticide usage and insecticide detoxification gene expression is under circadian regulation in the closely related Drosophila melanogaster, we set out to determine if integrative analysis of daily activity patterns and detoxification gene expression can predict chronotoxicity of D. suzukii to insecticides. Locomotor assays were performed under conditions that approximate a typical summer or winter day in Watsonville, California, where D. suzukii was first detected in North America. As expected, daily activity patterns of D. suzukii appeared quite different between ‘summer’ and ‘winter’ conditions due to differences in photoperiod and temperature. In the ‘summer’, D. suzukii assumed a more bimodal activity pattern, with maximum activity occurring at dawn and dusk. In the ‘winter’, activity was unimodal and restricted to the warmest part of the circadian cycle. Expression analysis of six detoxification genes and acute contact bioassays were performed at multiple circadian times, but only in conditions approximating Watsonville summer, the cropping season, when most insecticide applications occur. Five of the genes tested exhibited rhythmic expression, with the majority showing peak expression at dawn (ZT0, 6am). We observed significant differences in the chronotoxicity of D. suzukii towards malathion, with highest susceptibility at ZT0 (6am), corresponding to peak expression of cytochrome P450s that may be involved in bioactivation of malathion. High activity levels were not found to correlate with high insecticide susceptibility as initially hypothesized. Chronobiology and chronotoxicity of D. suzukii provide valuable insights for monitoring and control efforts, because insect activity as well as insecticide timing and efficacy are crucial considerations for pest management. However, field research is necessary for extrapolation to agricultural settings. PMID:23861907

Integrating circadian activity and gene expression profiles to predict chronotoxicity of Drosophila suzukii response to insecticides.

PubMed

Hamby, Kelly A; Kwok, Rosanna S; Zalom, Frank G; Chiu, Joanna C

2013-01-01

Native to Southeast Asia, Drosophila suzukii (Matsumura) is a recent invader that infests intact ripe and ripening fruit, leading to significant crop losses in the U.S., Canada, and Europe. Since current D. suzukii management strategies rely heavily on insecticide usage and insecticide detoxification gene expression is under circadian regulation in the closely related Drosophila melanogaster, we set out to determine if integrative analysis of daily activity patterns and detoxification gene expression can predict chronotoxicity of D. suzukii to insecticides. Locomotor assays were performed under conditions that approximate a typical summer or winter day in Watsonville, California, where D. suzukii was first detected in North America. As expected, daily activity patterns of D. suzukii appeared quite different between 'summer' and 'winter' conditions due to differences in photoperiod and temperature. In the 'summer', D. suzukii assumed a more bimodal activity pattern, with maximum activity occurring at dawn and dusk. In the 'winter', activity was unimodal and restricted to the warmest part of the circadian cycle. Expression analysis of six detoxification genes and acute contact bioassays were performed at multiple circadian times, but only in conditions approximating Watsonville summer, the cropping season, when most insecticide applications occur. Five of the genes tested exhibited rhythmic expression, with the majority showing peak expression at dawn (ZT0, 6am). We observed significant differences in the chronotoxicity of D. suzukii towards malathion, with highest susceptibility at ZT0 (6am), corresponding to peak expression of cytochrome P450s that may be involved in bioactivation of malathion. High activity levels were not found to correlate with high insecticide susceptibility as initially hypothesized. Chronobiology and chronotoxicity of D. suzukii provide valuable insights for monitoring and control efforts, because insect activity as well as insecticide timing and efficacy are crucial considerations for pest management. However, field research is necessary for extrapolation to agricultural settings.

CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos.

PubMed

Houl, Jerry H; Ng, Fanny; Taylor, Pete; Hardin, Paul E

2008-12-18

The Drosophila circadian oscillator is composed of transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC) heterodimers activate their feedback regulators period (per) and timeless (tim) via E-box mediated transcription. These feedback loop oscillators are present in distinct clusters of dorsal and lateral neurons in the adult brain, but how this pattern of expression is established during development is not known. Since CLK is required to initiate feedback loop function, defining the pattern of CLK expression in embryos and larvae will shed light on oscillator neuron development. A novel CLK antiserum is used to show that CLK expression in the larval CNS and adult brain is limited to circadian oscillator cells. CLK is initially expressed in presumptive small ventral lateral neurons (s-LNvs), dorsal neurons 2 s (DN2s), and dorsal neuron 1 s (DN1s) at embryonic stage (ES) 16, and this CLK expression pattern persists through larval development. PER then accumulates in all CLK-expressing cells except presumptive DN2s during late ES 16 and ES 17, consistent with the delayed accumulation of PER in adult oscillator neurons and antiphase cycling of PER in larval DN2s. PER is also expressed in non-CLK-expressing cells in the embryonic CNS starting at ES 12. Although PER expression in CLK-negative cells continues in ClkJrk embryos, PER expression in cells that co-express PER and CLK is eliminated. These data demonstrate that brain oscillator neurons begin development during embryogenesis, that PER expression in non-oscillator cells is CLK-independent, and that oscillator phase is an intrinsic characteristic of brain oscillator neurons. These results define the temporal and spatial coordinates of factors that initiate Clk expression, imply that circadian photoreceptors are not activated until the end of embryogenesis, and suggest that PER functions in a different capacity before oscillator cell development is initiated.

Physical exercise, fitness and dietary pattern and their relationship with circadian blood pressure pattern, augmentation index and endothelial dysfunction biological markers: EVIDENT study protocol

PubMed Central

2010-01-01

Background Healthy lifestyles may help to delay arterial aging. The purpose of this study is to analyze the relationship of physical activity and dietary pattern to the circadian pattern of blood pressure, central and peripheral blood pressure, pulse wave velocity, carotid intima-media thickness and biological markers of endothelial dysfunction in active and sedentary individuals without arteriosclerotic disease. Methods/Design Design: A cross-sectional multicenter study with six research groups. Subjects: From subjects of the PEPAF project cohort, in which 1,163 who were sedentary became active, 1,942 were sedentary and 2,346 were active. By stratified random sampling, 1,500 subjects will be included, 250 in each group. Primary measurements: We will evaluate height, weight, abdominal circumference, clinical and ambulatory blood pressure with the Radial Pulse Wave Acquisition Device (BPro), central blood pressure and augmentation index with Pulse Wave Application Software (A-Pulse) and SphymgoCor System Px (Pulse Wave Analysis), pulse wave velocity (PWV) with SphymgoCor System Px (Pulse Wave Velocity), nutritional pattern with a food intake frequency questionnaire, physical activity with the 7-day PAR questionnaire and accelerometer (Actigraph GT3X), physical fitness with the cycle ergometer (PWC-170), carotid intima-media thickness by ultrasound (Micromax), and endothelial dysfunction biological markers (endoglin and osteoprotegerin). Discussion Determining that sustained physical activity and the change from sedentary to active as well as a healthy diet improve circadian pattern, arterial elasticity and carotid intima-media thickness may help to propose lifestyle intervention programs. These interventions could improve the cardiovascular risk profile in some parameters not routinely assessed with traditional risk scales. From the results of this study, interventional approaches could be obtained to delay vascular aging that combine physical exercise and diet. Trial Registration Clinical Trials.gov Identifier: NCT01083082 PMID:20459634

Intrinsic Patterns of Human Activity

NASA Astrophysics Data System (ADS)

Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

2003-03-01

Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly discovered patterns to a robust intrinsic multi-scale dynamic regulation of human activity that is independent of known extrinsic factors, and independent from the circadian and ultradian rhythms.

Circadian-Related Sleep Disorders and Sleep Medication Use in the New Zealand Blind Population: An Observational Prevalence Survey

PubMed Central

Warman, Guy R.; Pawley, Matthew D. M.; Bolton, Catherine; Cheeseman, James F.; Fernando, Antonio T.; Arendt, Josephine; Wirz-Justice, Anna

2011-01-01

Study Objectives To determine the prevalence of self-reported circadian-related sleep disorders, sleep medication and melatonin use in the New Zealand blind population. Design A telephone survey incorporating 62 questions on sleep habits and medication together with validated questionnaires on sleep quality, chronotype and seasonality. Participants Participants were grouped into: (i) 157 with reduced conscious perception of light (RLP); (ii) 156 visually impaired with no reduction in light perception (LP) matched for age, sex and socioeconomic status, and (iii) 156 matched fully-sighted controls (FS). Sleep Habits and Disturbances The incidence of sleep disorders, daytime somnolence, insomnia and sleep timing problems was significantly higher in RLP and LP compared to the FS controls (p<0.001). The RLP group had the highest incidence (55%) of sleep timing problems, and 26% showed drifting sleep patterns (vs. 4% FS). Odds ratios for unconventional sleep timing were 2.41 (RLP) and 1.63 (LP) compared to FS controls. For drifting sleep patterns, they were 7.3 (RLP) and 6.0 (LP). Medication Use Zopiclone was the most frequently prescribed sleep medication. Melatonin was used by only 4% in the RLP group and 2% in the LP group. Conclusions Extrapolations from the current study suggest that 3,000 blind and visually impaired New Zealanders may suffer from circadian-related sleep problems, and that of these, fewer than 15% have been prescribed melatonin. This may represent a therapeutic gap in the treatment of circadian-related sleep disorders in New Zealand, findings that may generalize to other countries. PMID:21789214

Brief psycho-education affects circadian variability in nicotine craving during cessation.

PubMed

Nosen, Elizabeth; Woody, Sheila R

2013-09-01

Nicotine cravings are a key target of smoking cessation interventions. Cravings demonstrate circadian variation during abstinence, often peaking during the morning and evening hours. Although some research has also shown diurnal variation in the efficacy of nicotine replacement medications, little research has examined how brief psychosocial interventions affect temporal patterns of craving during abstinence. The present study examined the impact of two brief psycho-education interventions on circadian variations in cravings during a 24-h period. 176 adult smokers interested in quitting participated in two lab sessions. During the first session, participants received (a) mindfulness psycho-education that encouraged acceptance of cravings as a normal, tolerable part of quitting that people should not expect to perfectly control, (b) standard cessation psycho-education, or (c) no psycho-education. Half the sample initiated a cessation attempt the following day. Dependent variables were assessed using ecological momentary assessment (24-h of monitoring, immediately after first lab session) and questionnaires four days later. Partially consistent with hypotheses, both forms of psycho-education were associated with differential diurnal variation in cravings during cessation. Relative to those receiving no psycho-education, standard smoking cessation psycho-education decreased morning cravings. Psycho-education encouraging acceptance of cravings was associated with lower craving in both the morning and evening, albeit only among successfully abstinent smokers. Results demonstrate that brief non-pharmacological interventions can affect circadian craving patterns during smoking cessation. Further investigation of mechanisms of change and of the impact of psycho-education on cessation outcomes is warranted. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Obstructive sleep apnea syndrome and hypertension: ambulatory blood pressure.

PubMed

Kario, Kazuomi

2009-06-01

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for hypertension and cardiovascular disease. OSAS is the frequent underlying disease of secondary hypertension and resistant hypertension. OSAS increases both daytime and night-time ambulatory blood pressures through the activation of various neurohumoral factors including the sympathetic nervous system and the renin-angiotensin-aldosterone system. In particular, OSAS predominantly increases ambulatory BP during sleep compared with the awake period, with the result that OSAS is likely to be associated with the non-dipping pattern (diminished nocturnal BP fall) or riser pattern (higher sleep BP than awake BP) of nocturnal BP. An additional characteristic of ABP in OSAS is increased BP variability. The newly developed non-invasive hypoxia-trigger BP-monitoring system detected marked midnight BP surges (ranging from around 10 to 100 mm Hg) during sleep in OSAS patients. The exaggerated BP surge may trigger OSAS-related cardiovascular events occurring during sleep. Clinically, as nocturnal hypoxia is the determinant of morning minus evening BP difference (ME difference), OSAS should be strongly suspected when morning BP cannot be controlled <135/85 mm Hg with increased ME difference even by the specific antihypertensive medications targeting morning hypertension such as bedtime dosing of antihypertensive drugs. Understanding the characteristics of OSAS-related hypertension is essentially important to achieve perfect BP control over a 24-h period, including the sleep period, for more effective prevention of cardiovascular disease.

Molecular Mechanisms of Circadian Regulation During Spaceflight

NASA Technical Reports Server (NTRS)

Zanello, Susana; Boyle, Richard

2011-01-01

Disruption of the regular environmental circadian cues in addition to stringent and demanding operational schedules are two main factors that undoubtedly impact sleep patterns and vigilant performance in the astronaut crews during spaceflight. Most research is focused on the behavioral aspects of the risk of circadian desynchronization, characterized by fatigue and health and performance decrement. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate this risk. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. The molecular clock consists of sets of proteins that perform different functions within the clock machinery: circadian oscillators (genes whose expression levels cycle during the day, keep the pass of cellular time and regulate downstream effector genes), the effector or output genes (those which impact the physiology of the tissue or organism), and the input genes (responsible for sensing the environmental cues that allow circadian entrainment). The main environmental cue is light. As opposed to the known photoreceptors (rods and cones), the non-visual light stimulus is received by a subset of the population of retinal ganglion cells called intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin (opsin 4 -Opn4-) as the photoreceptor. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight. To answer this question, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (animal enclosure module) mice were used as ground controls. Opn4 expression was analyzed by real time RT/qPCR and retinal sections were stained for Opn4 immunofluorescence. Opn4 was decreased (abrogated in one case) in retinas that concurrently showed higher evidence of oxidative stress. We propose that oxidative stress can lead to a decrease in melanopsin expression, likely via ipRGC loss or impairment, and thus, it can be a contributing factor to circadian disruption during spaceflight. Countermeasures contemplating the use of light should therefore be complemented with melanopsin expression maintenance and/or reduction in oxidative stress.

Preserved functional autonomic phenotype in adult mice overexpressing moderate levels of human alpha‐synuclein in oligodendrocytes

PubMed Central

Tank, Jens; da Costa‐Goncalves, Andrey C.; Kamer, Ilona; Qadri, Fatimunnisa; Ubhi, Kiren; Rockenstein, Edward; Diedrich, André; Masliah, Eliezer; Gross, Volkmar; Jordan, Jens

2014-01-01

Abstract Mice overexpressing human alpha‐synuclein in oligodendrocytes (MBP1‐α‐syn) recapitulate some key functional and neuropathological features of multiple system atrophy (MSA). Whether or not these mice develop severe autonomic failure, which is a key feature of human MSA, remains unknown. We explored cardiovascular autonomic regulation using long‐term blood pressure (BP) radiotelemetry and pharmacological testing. We instrumented 12 MBP1‐α‐syn mice and 11 wild‐type mice aged 9 months for radiotelemetry. Animals were tested with atropine, metoprolol, clonidine, and trimethaphan at 9 and 12 months age. We applied spectral and cross‐spectral analysis to assess heart rate (HR) and BP variability. At 9 months of age daytime BP (transgenic: 101 ± 2 vs. wild type: 99 ± 2 mmHg) and HR (497 ± 11 vs. 505 ± 16 beats/min) were similar. Circadian BP and HR rhythms were maintained. Nighttime BP (109 ± 2 vs. 108 ± 2 mmHg) and HR (575 ± 15 vs. 569 ± 14 beats/min), mean arterial BP responses to trimethaphan (−21 ± 8 vs. −10 ± 5 mmHg, P = 0.240) and to clonidine (−8 ± 3 vs. −5 ± 2 mmHg, P = 0.314) were similar. HR responses to atropine (+159 ± 24 vs. +146 ± 22 beats/min), and to clonidine (−188 ± 21 vs. −163 ± 33 beats/min) did not differ between strains. Baroreflex sensitivity (4 ± 1 vs. 4 ± 1 msec/mmHg) and HR variability (total power, 84 ± 17 vs. 65 ± 21 msec²) were similar under resting conditions and during pharmacological testing. Repeated measurements at 12 months of age provided similar results. In mice, moderate overexpression of human alpha‐synuclein in oligodendrocytes is not sufficient to induce overt autonomic failure. Additional mechanisms may be required to express the autonomic failure phenotype including higher levels of expression or more advanced age. PMID:25428949

Treating Insomnia Improves Mood State, Sleep, and Functioning in Bipolar Disorder: A Pilot Randomized Controlled Trial

PubMed Central

Harvey, Allison G.; Soehner, Adriane M.; Kaplan, Kate A.; Hein, Kerrie; Lee, Jason; Kanady, Jennifer; Rabe-Hesketh, Sophia; Neylan, Thomas C.; Li, Descartes; Ketter, Terence A.; Buysse, Daniel J.

2015-01-01

Objective To determine if a treatment for interepisode bipolar disorder I patients with insomnia improves mood state, sleep, and functioning. Method Alongside psychiatric care, interepisode bipolar disorder I participants with insomnia were randomly allocated to a bipolar disorder–specific modification of cognitive behavior therapy for insomnia (CBTI-BP; n = 30) or psychoeducation (PE; n = 28) as a comparison condition. Outcomes were assessed at baseline, the end of 8 sessions of treatment, and 6 months later. This pilot was conducted to determine initial feasibility and generate effect size estimates. Results During the 6-month follow-up, the CBTI-BP group had fewer days in a bipolar episode relative to the PE group (3.3 days vs. 25.5 days). The CBTI-BP group also experienced a significantly lower hypomania/mania relapse rate (4.6% vs. 31.6%) and a marginally lower overall mood episode relapse rate (13.6% vs. 42.1%) compared with the PE group. Relative to PE, CBTI-BP reduced insomnia severity and led to higher rates of insomnia remission at posttreatment and marginally higher rates at 6 months. Both CBTI-BP and PE showed statistically significant improvement on selected sleep and functional impairment measures. The effects of treatment were well sustained through follow-up for most outcomes, although some decline on secondary sleep benefits was observed. Conclusions CBTI-BP was associated with reduced risk of mood episode relapse and improved sleep and functioning on certain outcomes in bipolar disorder. Hence, sleep disturbance appears to be an important pathway contributing to bipolar disorder. The need to develop bipolar disorder–specific sleep diary scoring standards is highlighted. Public Health Significance This study suggests that an intervention to improve sleep and circadian functioning reduces risk of relapse and improves sleep and overall functioning among individuals who meet diagnostic criteria for bipolar disorder. PMID:25622197

Blood pressure and cerebral white matter share common genetic factors in Mexican Americans.

PubMed

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2011-02-01

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.

Autoregulation of cerebral blood flow in orthostatic hypotension

NASA Technical Reports Server (NTRS)

Novak, V.; Novak, P.; Spies, J. M.; Low, P. A.

1998-01-01

BACKGROUND AND PURPOSE: We sought to evaluate cerebral autoregulation in patients with orthostatic hypotension (OH). METHODS: We studied 21 patients (aged 52 to 78 years) with neurogenic OH during 80 degrees head-up tilt. Blood flow velocities (BFV) from the middle cerebral artery were continuously monitored with transcranial Doppler sonography, as were heart rate, blood pressure (BP), cardiac output, stroke volume, CO2, total peripheral resistance, and cerebrovascular resistance. RESULTS: All OH patients had lower BP (P<.0001), BFV_diastolic (P<.05), CVR (P<.007), and TPR (P<.02) during head-up tilt than control subjects. In control subjects, no correlations between BFV and BP were found during head-up tilt, suggesting normal autoregulation. OH patients could be separated into those with normal or expanded autoregulation (OH_NA; n=16) and those with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either no correlation between BFV and BP (n=8) or had a positive BFV/BP correlation (R2>.75) but with a flat slope. An expansion of the "autoregulated" range was seen in some patients. The OH_AF group was characterized by a profound fall in BFV in response to a small reduction in BP (mean deltaBP <40 mm Hg; R2>.75). CONCLUSIONS: The most common patterns of cerebral response to OH are autoregulatory failure with a flat flow-pressure relationship or intact autoregulation with an expanded autoregulated range. The least common pattern is autoregulatory failure with a steep flow-pressure relationship. Patients with patterns 1 and 2 have an enhanced capacity to cope with OH, while those with pattern 3 have reduced capacity.

Diural TSH variations in hypothyroidism.

PubMed

Weeke, J; Laurberg, P

1976-07-01

There is a circadian variation in serum TSH in euthyroid subjects. A similar diurnal variation has been demonstrated in patients with hypothyroidism. In the present study the 24-hour pattern of serum TSH was investigated in eight patients with hypothyroidism of varying severity and in five hypothyroid patients treated with thyroxine (T4). There was a circadian variation in serum TSH in patients with hypothyroidism of moderate degree, and in patients treated for severe hypothyrodism with thyroxine. The pattern was similar to that found in normal subjects, i.e., low TSH levels in the daytime and higher levels at night. In severely hypothyroid patients, no diurnal variation in serum TSH was observed. A practical consequence is that blood samples for TSH measurements in patients with moderately elevated TSH levels are best taken after 1100 h, when the low day levels are reached.

Comparative analysis of Pdf-mediated circadian behaviors between Drosophila melanogaster and D. virilis.

PubMed

Bahn, Jae Hoon; Lee, Gyunghee; Park, Jae H

2009-03-01

A group of small ventrolateral neurons (s-LN(v)'s) are the principal pacemaker for circadian locomotor rhythmicity of Drosophila melanogaster, and the pigment-dispersing factor (Pdf) neuropeptide plays an essential role as a clock messenger within these neurons. In our comparative studies on Pdf-associated circadian rhythms, we found that daily locomotor activity patterns of D. virilis were significantly different from those of D. melanogaster. Activities of D. virilis adults were mainly restricted to the photophase under light:dark cycles and subsequently became arrhythmic or weakly rhythmic in constant conditions. Such activity patterns resemble those of Pdf(01) mutant of D. melanogaster. Intriguingly, endogenous D. virilis Pdf (DvPdf) expression was not detected in the s-LN(v)-like neurons in the adult brains, implying that the Pdf(01)-like behavioral phenotypes of D. virilis are attributed in part to the lack of DvPdf in the s-LN(v)-like neurons. Heterologous transgenic analysis showed that cis-regulatory elements of the DvPdf transgene are capable of directing their expression in all endogenous Pdf neurons including s-LN(v)'s, as well as in non-Pdf clock neurons (LN(d)'s and fifth s-LN(v)) in a D. melanogaster host. Together these findings suggest a significant difference in the regulatory mechanisms of Pdf transcription between the two species and such a difference is causally associated with species-specific establishment of daily locomotor activity patterns.

Operational assessment of the 5-h on/10-h off watchstanding schedule on a US Navy ship: sleep patterns, mood and psychomotor vigilance performance of crewmembers in the nuclear reactor department.

PubMed

Shattuck, Nita Lewis; Matsangas, Panagiotis

2016-05-01

We assessed sleep patterns, psychomotor vigilance performance, work demands and mood of 77 crewmembers of USS NIMITZ (CVN-68) on the rotating 5-h on/10-h off (5/10) watchstanding schedule. Within the 3-day cycle of the 5/10, sleep occurred at distinctly different times each day. On two of these days, sailors typically received only brief, 4-h sleep episodes followed by periods of sustained wakefulness (approximately 22 and 20 h). Crewmembers received approximately seven hours of sleep daily, but reported excessive fatigue and dissatisfaction with their schedule. Crewmembers' mood worsened significantly over the course of the underway phase. Psychomotor vigilance performance (reaction times, lapses) was significantly degraded compared to performance when working circadian-aligned schedules. Overall, standing watch on the 5/10 schedule, combined with other work duties, resulted in poor sleep hygiene. Crewmembers on the 5/10 experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep. Practitioner summary: We assessed crewmembers' sleep patterns, psychomotor vigilance performance and work demands when working a rotating 5-h on/10-h off (5/10) watchstanding schedule. The 5/10, combined with other work duties, resulted in poor sleep hygiene. Crewmembers experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep.

Prevalence and tracking of back pain from childhood to adolescence

PubMed Central

2011-01-01

Background It is generally acknowledged that back pain (BP) is a common condition already in childhood. However, the development until early adulthood is not well understood and, in particular, not the individual tracking pattern. The objectives of this paper are to show the prevalence estimates of BP, low back pain (LBP), mid back pain (MBP), neck pain (NP), and care-seeking because of BP at three different ages (9, 13 and15 years) and how the BP reporting tracks over these age groups over three consecutive surveys. Methods A longitudinal cohort study was carried out from the years of 1997 till 2005, collecting interview data from children who were sampled to be representative of Danish schoolchildren. BP was defined overall and specifically in the three spinal regions as having reported pain within the past month. The prevalence estimates and the various patterns of BP reporting over time are presented as percentages. Results Of the 771 children sampled, 62%, 57%, and 58% participated in the three back surveys and 34% participated in all three. The prevalence estimates for children at the ages of 9, 13, and 15, respectively, were for BP 33%, 28%, and 48%; for LBP 4%, 22%, and 36%; for MBP 20%, 13%, and 35%; and for NP 10%, 7%, and 15%. Seeking care for BP increased from 6% and 8% at the two youngest ages to 34% at the oldest. Only 7% of the children who participated in all three surveys reported BP each time and 30% of these always reported no pain. The patterns of development differed for the three spinal regions and between genders. Status at the previous survey predicted status at the next survey, so that those who had pain before were more likely to report pain again and vice versa. This was most pronounced for care-seeking. Conclusion It was confirmed that BP starts early in life, but the patterns of onset and development over time vary for different parts of the spine and between genders. Because of these differences, it is recommended to report on BP in youngsters separately for the three spinal regions, and to differentiate in the analyses between the genders and age groups. Although only a small minority reported BP at two or all three surveys, tracking of BP (particularly NP) and care seeking was noted from one survey to the other. On the positive side, individuals without BP at a previous survey were likely to remain pain free at the subsequent survey. PMID:21575251

A mathematical model of communication between groups of circadian neurons in Drosophila melanogaster.

PubMed

Risau-Gusman, Sebastián; Gleiser, Pablo M

2014-12-01

In the fruit fly, circadian behavior is controlled by a small number of specialized neurons, whose molecular clocks are relatively well known. However, much less is known about how these neurons communicate among themselves. In particular, only 1 circadian neuropeptide, pigment-dispersing factor (PDF), has been identified, and most aspects of its interaction with the molecular clock remain to be elucidated. Furthermore, it is speculated that many other peptides should contribute to circadian communication. We have developed a relatively detailed model of the 2 main groups of circadian pacemaker neurons (sLNvs and LNds) to investigate these issues. We have proposed many possible mechanisms for the interaction between the synchronization factors and the molecular clock, and we have compared the outputs with the experimental results reported in the literature both for the wild-type and PDF-null mutant. We have studied how different the properties of each neuron should be to account for the observations reported for the sLNvs in the mutant. We have found that only a few mechanisms, mostly related to the slowing down of nuclear entry of a circadian protein, can synchronize neurons that present these differences. Detailed immunofluorescent recordings have suggested that, whereas in the mutant, LNd neurons are synchronized, in the wild-type, a subset of the LNds oscillate faster than the rest. With our model, we find that a more likely explanation for the same observations is that this subset is being driven outside its synchronization range and displays therefore a complex pattern of oscillation.

Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders.

PubMed

Williams, Wilbur P Trey; McLin, Dewey E; Dressman, Marlene A; Neubauer, David N

2016-09-01

Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non-24-hour sleep-wake disorder (or non-24). However, three additional commercially available melatonin receptor agonists-agomelatine, prolonged-release melatonin, and ramelteon-have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs. © 2016 Vanda Pharmaceuticals, Inc. Pharmacotherapy published by Wiley Periodicals, Inc. on behalf of Pharmacotherapy Publications, Inc.

Bidirectional interactions between circadian entrainment and cognitive performance

PubMed Central

Gritton, Howard J.; Kantorowski, Ana; Sarter, Martin; Lee, Theresa M.

2012-01-01

Circadian rhythms influence a variety of physiological and behavioral processes; however, little is known about how circadian rhythms interact with the organisms' ability to acquire and retain information about their environment. These experiments tested whether rats trained outside their endogenous active period demonstrate the same rate of acquisition, daily performance, and remote memory ability as their nocturnally trained counterparts in tasks of sustained attention and spatial memory. Furthermore, we explored how daily task training influenced circadian patterns of activity. We found that rats demonstrate better acquisition and performance on an operant task requiring attentional effort when trained during the dark-phase. Time of day did not affect acquisition or performance on the Morris water maze; however, when animals were retested 2 wk after their last day of training, they showed better remote memory if training originally occurred during the dark-phase. Finally, attentional, but not spatial, task performance during the light-phase promotes a shift toward diurnality and the synchronization of activity to the time of daily training; this shift was most robust when the demands on the cognitive control of attention were highest. Our findings support a theory of bidirectional interactions between cognitive performance and circadian processes and are consistent with the view that the circadian abnormalities associated with shift-work, aging, and neuropsychiatric illnesses may contribute to the deleterious effects on cognition often present in these populations. Furthermore, these findings suggest that time of day should be an important consideration for a variety of cognitive tasks principally used in psychological and neuroscience research. PMID:22383380

Association of sleep-wake habits in older people with changes in output of circadian pacemaker

NASA Technical Reports Server (NTRS)

Czeisler, C. A.; Dumont, M.; Duffy, J. F.; Steinberg, J. D.; Richardson, G. S.; Brown, E. N.; Sanchez, R.; Rios, C. D.; Ronda, J. M.

1992-01-01

Many elderly people complain of disturbed sleep patterns but there is not evidence that the need to sleep decreases with age; it seems rather that the timing and consolidation of sleep change. We tried to find out whether there is a concurrent change in the output of the circadian pacemaker with age. The phase and amplitude of the pacemaker's output were assessed by continuous measurement of the core body temperature during 40 h of sustained wakefulness under constant behavioural and environmental conditions. 27 young men (18-31 years) were compared with 21 older people (65-85 years; 11 men, 10 women); all were healthy and without sleep complaints. The mean amplitude of the endogenous circadian temperature oscillation (ECA) was 40% greater in young men than in the older group. Older men had a lower mean temperature ECA than older women. The minimum of the endogenous phase of the circadian temperature oscillation (ECP) occurred 1 h 52 min earlier in the older than in the young group. Customary bedtimes and waketimes were also earlier in the older group, as was their daily alertness peak. There was a close correlation between habitual waketime and temperature ECP in young men, which may lose precision with age, especially among women. These findings provide evidence for systematic age-related changes in the output of the human circadian pacemaker. We suggest that these changes may underlie the common complaints of sleep disturbance among elderly people. These changes could reflect the observed age-related deterioration of the hypothalamic nuclei that drive mammalian circadian rhythms.

The influence of environment, sex, and innate timing mechanisms on body temperature patterns of free-ranging black-tailed prairie dogs (Cynomys ludovicianus).

PubMed

Lehmer, Erin M; Bossenbroek, Jonathan M; Van Horne, Beatrice

2003-01-01

Mechanisms that influence body temperature patterns in black-tailed prairie dogs are not well understood. Previous research on both free-ranging and laboratory populations of black-tailed prairie dogs (Cynomys ludovicianus) has suggested that reductions in ambient temperature and food and water deprivation are the primary factors that stimulate torpor in this species. In other species, however, torpor has been shown to be influenced by a multitude of factors, including innate circadian and circannual timing mechanisms, energy status, and reproductive behaviors. Our objective was to clarify the influence of weather, sex, and intrinsic timing mechanisms on the body temperature patterns of free-ranging black-tailed prairie dogs. We monitored body temperatures of eight adult (>1 yr) prairie dogs from November 1999 to June 2000. Prairie dogs showed distinct daily and seasonal body temperature patterns, which reflected changes in ambient temperatures that occurred during these periods. These patterns of daily and seasonal heterothermy suggest that body temperature patterns of black-tailed prairie dogs may be driven by an innate timing mechanism. All prairie dogs entered torpor intermittently throughout winter and spring. Torpor bouts appeared to be influenced by precipitation and reductions in ambient temperature. Our results also suggest that reproductive behaviors and circadian timing may influence torpor in this species.

Validating and Verifying Biomathematical Models of Human Fatigue

NASA Technical Reports Server (NTRS)

Martinez, Siera Brooke; Quintero, Luis Ortiz; Flynn-Evans, Erin

2015-01-01

Airline pilots experience acute and chronic sleep deprivation, sleep inertia, and circadian desynchrony due to the need to schedule flight operations around the clock. This sleep loss and circadian desynchrony gives rise to cognitive impairments, reduced vigilance and inconsistent performance. Several biomathematical models, based principally on patterns observed in circadian rhythms and homeostatic drive, have been developed to predict a pilots levels of fatigue or alertness. These models allow for the Federal Aviation Administration (FAA) and commercial airlines to make decisions about pilot capabilities and flight schedules. Although these models have been validated in a laboratory setting, they have not been thoroughly tested in operational environments where uncontrolled factors, such as environmental sleep disrupters, caffeine use and napping, may impact actual pilot alertness and performance. We will compare the predictions of three prominent biomathematical fatigue models (McCauley Model, Harvard Model, and the privately-sold SAFTE-FAST Model) to actual measures of alertness and performance. We collected sleep logs, movement and light recordings, psychomotor vigilance task (PVT), and urinary melatonin (a marker of circadian phase) from 44 pilots in a short-haul commercial airline over one month. We will statistically compare with the model predictions to lapses on the PVT and circadian phase. We will calculate the sensitivity and specificity of each model prediction under different scheduling conditions. Our findings will aid operational decision-makers in determining the reliability of each model under real-world scheduling situations.

The circadian variation of cardiovascular stress levels and reactivity: relationship to individual differences in morningness/eveningness.

PubMed

Nebel, L E; Howell, R H; Krantz, D S; Falconer, J J; Gottdiener, J S; Gabbay, F H

1996-05-01

Two studies assessed the circadian variation of cardiovascular responses to stress in healthy and coronary artery disease (CAD) populations. In within-subjects designs, stressors were administered to healthy male subjects and male CAD patients both in the morning and afternoon, and subjects were classified as either morning or evening types using the Morningness-Eveningness Questionnaire (Horne & Ostberg, 1976, International Journal of Chronobiology, 4, 97-110). No consistent circadian variation in blood pressure or heart rate responses was observed in the aggregate sample of either healthy subjects or CAD patients. However, there were significant interactions between circadian type and time of day. In both populations, morning subjects exhibited higher cardiovascular levels during the morning session, and evening subjects exhibited higher levels during the afternoon session. Analyses of cardiovascular reactivity revealed less consistent evidence for this interaction. Self-reports of stress revealed interactions between time of day and morningness/eveningness only in the CAD sample. In CAD patients, preliminary analysis of myocardial wall function, an index of myocardial ischemia, did not reveal a significant interaction between morningness/eveningness and time of day, perhaps due to small sample size. The presence of differing circadian patterns in stress response based on individual differences in morningness/eveningness is discussed in terms of its methodological implications for psychophysiological research and in terms of the role of stress as an acute trigger of CAD.

Rhythmic Trafficking of TRPV2 in the Suprachiasmatic Nucleus is Regulated by Prokineticin 2 Signaling.

PubMed

Burton, Katherine J; Li, Xiaohan; Li, Jia-Da; Hu, Wang-Ping; Zhou, Qun-Yong

2015-04-01

The mammalian circadian clock is composed of single-cell oscillators. Neurochemical and electrical signaling among these oscillators is important for the normal expression of circadian rhythms. Prokineticin 2 (PK2), encoding a cysteine-rich secreted protein, has been shown to be a critical signaling molecule for the regulation of circadian rhythms. PK2 expression in the suprachiasmatic nucleus (SCN) is highly rhythmic, peaking during the day and being essentially absent during the night. Mice with disrupted PK2 gene or its receptor PKR2 display greatly reduced rhythmicity of broad circadian parameters such as locomotor activity, body temperature and sleep/wake patterns. PK2 has been shown to increase the firing rate of SCN neurons, with unknown molecular mechanisms. Here we report that TRPV2, an ion channel belonging to the family of TRP, is co-expressed with PKR2 in the SCN neurons. Further, TRPV2 protein, but not TRPV2 mRNA, was shown to oscillate in the SCN in a PK2-dependent manner. Functional studies revealed that TRPV2 enhanced signaling of PKR2 in calcium mobilization or ion current conductance, likely via the increased trafficking of TRPV2 to the cell surface. Taken together, these results indicate that TRPV2 is likely part of the downstream signaling of PK2 in the regulation of the circadian rhythms.

Rhythmic Trafficking of TRPV2 in the Suprachiasmatic Nucleus is Regulated by Prokineticin 2 Signaling

PubMed Central

Burton, Katherine J.; Li, Xiaohan; Li, Jia-Da; Hu, Wang-Ping

2015-01-01

The mammalian circadian clock is composed of single-cell oscillators. Neurochemical and electrical signaling among these oscillators is important for the normal expression of circadian rhythms. Prokineticin 2 (PK2), encoding a cysteine-rich secreted protein, has been shown to be a critical signaling molecule for the regulation of circadian rhythms. PK2 expression in the suprachiasmatic nucleus (SCN) is highly rhythmic, peaking during the day and being essentially absent during the night. Mice with disrupted PK2 gene or its receptor PKR2 display greatly reduced rhythmicity of broad circadian parameters such as locomotor activity, body temperature and sleep/wake patterns. PK2 has been shown to increase the firing rate of SCN neurons, with unknown molecular mechanisms. Here we report that TRPV2, an ion channel belonging to the family of TRP, is co-expressed with PKR2 in the SCN neurons. Further, TRPV2 protein, but not TRPV2 mRNA, was shown to oscillate in the SCN in a PK2-dependent manner. Functional studies revealed that TRPV2 enhanced signaling of PKR2 in calcium mobilization or ion current conductance, likely via the increased trafficking of TRPV2 to the cell surface. Taken together, these results indicate that TRPV2 is likely part of the downstream signaling of PK2 in the regulation of the circadian rhythms. PMID:27103928

Cloning and Functional Characterization of a β-Pinene Synthase from Artemisia annua That Shows a Circadian Pattern of Expression1

PubMed Central

Lu, Shan; Xu, Ran; Jia, Jun-Wei; Pang, Jihai; Matsuda, Seiichi P.T.; Chen, Xiao-Ya

2002-01-01

Artemisia annua plants produce a broad range of volatile compounds, including monoterpenes, which contribute to the characteristic fragrance of this medicinal species. A cDNA clone, QH6, contained an open reading frame encoding a 582-amino acid protein that showed high sequence identity to plant monoterpene synthases. The prokaryotically expressed QH6 fusion protein converted geranyl diphosphate to (−)-β-pinene and (−)-α-pinene in a 94:6 ratio. QH6 was predominantly expressed in juvenile leaves 2 weeks postsprouting. QH6 transcript levels were transiently reduced following mechanical wounding or fungal elicitor treatment, suggesting that this gene is not directly involved in defense reaction induced by either of these treatments. Under a photoperiod of 12 h/12 h (light/dark), the abundance of QH6 transcripts fluctuated in a diurnal pattern that ebbed around 3 h before daybreak (9th h in the dark phase) and peaked after 9 h in light (9th h in the light phase). The contents of (−)-β-pinene in juvenile leaves and in emitted volatiles also varied in a diurnal rhythm, correlating strongly with mRNA accumulation. When A. annua was entrained by constant light or constant dark conditions, QH6 transcript accumulation continued to fluctuate with circadian rhythms. Under constant light, advanced cycles of fluctuation of QH6 transcript levels were observed, and under constant dark, the cycle was delayed. However, the original diurnal pattern could be regained when the plants were returned to the normal light/dark (12 h/12 h) photoperiod. This is the first report that monoterpene biosynthesis is transcriptionally regulated in a circadian pattern. PMID:12226526

Xenobiotic metabolism in the fourth dimension: PARtners in time.

PubMed

Green, Carla B; Takahashi, Joseph S

2006-07-01

A significant portion of the transcriptome in mammals, including the PAR bZIP transcription factors DBP, HLF, and TEF, is under circadian clock control. In this issue of Cell Metabolism, Gachon and colleagues (Gachon et al., 2006) show that disruption of these three genes in mice alters gene expression patterns of many proteins involved in drug metabolism and in liver and kidney responses to xenobiotic agents. Triple mutant mice have severe physiological deficits, including increased hypersensitivity to xenobiotic agents and premature aging, highlighting the profound effect the circadian clock has on this important response system.

Effect of morning bright light on body temperature, plasma cortisol and wrist motility measured during 24 hour of constant conditions.

PubMed

Foret, J; Aguirre, A; Touitou, Y; Clodoré, M; Benoit, O

1993-06-11

Using 24 h constant conditions, time course of body temperature, plasma cortisol and wrist motility was measured in response to a 3 day morning 2 h bright light pulse. This protocol demonstrated that a 2000 lux illumination was sufficient to elicit a shift of about 2 h of temperature minimum and cortisol peak. In reference session, actimetric recordings showed a circadian time course, closely in relation with core temperature. Bright light pulse resulted in a decrease of amplitude and a disappearance of circadian pattern of actimetry.

NASA to study effects of jet lag on pilot performance

NASA Technical Reports Server (NTRS)

1980-01-01

Existing scientific literature on circadian rhythm was translated into lay terms and disseminated to the aviation community. The effects of rest, sleep, dietary, and drug use patterns of commercial airline crews were investigated.

Pollution patterns and underlying relationships of benzophenone-type UV-filters in wastewater treatment plants and their receiving surface water.

PubMed

Wu, Ming-Hong; Li, Jian; Xu, Gang; Ma, Luo-Dan; Li, Jia-Jun; Li, Jin-Song; Tang, Liang

2018-05-15

The environmental behaviors of emerging pollutants, benzophenone-type UV filters (BP-UV filters) and their derivatives were investigated in four wastewater treatment plants (WWTPs), and their receiving surface waters in Shanghai. The concentration level of selected BP-UV filters in the WWTPs was detected from ngL -1 to μgL -1 . BP (621-951ngL -1 ) and BP-3 (841-1.32 × 10 3 ngL -1 ) were the most abundant and highest detection frequency individuals among the target BP-UV filters in influents, whereas BP (198-400ngL -1 ), BP-4 (93.3-288ngL -1 ) and BP-3 (146-258ngL -1 ) were predominant in effluents. BP-UV filters cannot be completely removed and the total removal efficiency varied widely (-456% to 100%) during the treatment process. It can be inferred that the usage of BP and BP-3 are higher than other BP-UV filters in the study area. The lowest and highest levels were BP-2 (ND-7.66ngL -1 ) and BP-3 (68.5-5.01 × 10 3 ng L -1 ) in the receiving surface water, respectively. Interestingly, the seasonal variation of BP-3 is larger than those of other BP-UV filters in surface water from Shanghai. There is no obvious pollution pattern of BP-UV filters in the surface water from the cosmetic factory area. The correlation analysis of BP-UV filters between WWTPs effluents and nearby downstream water samples suggested that BP-UV filters emitted from some WWTPs might be the main source of receiving surface water. Preliminary risk assessment indicated that the levels of BP-UV filters detected by the effluent posed medium to high risk to fish as well as other aquatic organisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Diel time-courses of leaf growth in monocot and dicot species: endogenous rhythms and temperature effects.

PubMed

Poiré, Richard; Wiese-Klinkenberg, Anika; Parent, Boris; Mielewczik, Michael; Schurr, Ulrich; Tardieu, François; Walter, Achim

2010-06-01

Diel (24 h) leaf growth patterns were differently affected by temperature variations and the circadian clock in several plant species. In the monocotyledon Zea mays, leaf elongation rate closely followed changes in temperature. In the dicotyledons Nicotiana tabacum, Ricinus communis, and Flaveria bidentis, the effect of temperature regimes was less obvious and leaf growth exhibited a clear circadian oscillation. These differences were related neither to primary metabolism nor to altered carbohydrate availability for growth. The effect of endogenous rhythms on leaf growth was analysed under continuous light in Arabidopsis thaliana, Ricinus communis, Zea mays, and Oryza sativa. No rhythmic growth was observed under continuous light in the two monocotyledons, while growth rhythmicity persisted in the two dicotyledons. Based on model simulations it is concluded that diel leaf growth patterns in mono- and dicotyledons result from the additive effects of both circadian-clock-controlled processes and responses to environmental changes such as temperature and evaporative demand. Apparently very distinct diel leaf growth behaviour of monocotyledons and dicotyledons can thus be explained by the different degrees to which diel temperature variations affect leaf growth in the two groups of species which, in turn, depends on the extent of the leaf growth control by internal clocks.

Time of day of prednisolone administration in rheumatoid arthritis.

PubMed Central

Kowanko, I C; Pownall, R; Knapp, M S; Swannell, A J; Mahoney, P G

1982-01-01

Twelve patients with rheumatoid arthritis took low dosage prednisolone, mean 5.6 mg daily, at either 0800 h, 1300 h or 2300 h in a double-blind within-patient controlled trial. Each patient was studied on each of the 3 regimens to assess control of symptoms and side effects and also to examine circadian rhythms in signs and symptoms. For several days during each drug regimen patients collected urine at each micturition and self-assessed their signs and symptoms. Circadian rhythms of finger joint swelling and of grip strength were determined, and were similar on all regimens, with morning peaks of symptoms and signs. Subjective and objective assessments showed no differences in effectiveness between the 3 times of administration of prednisolone. Urinary excretion patterns were similar to those observed in untreated people. The quantity and circadian pattern of 11-hydroxycorticosteroids excreted were similar to those in healthy patients, providing no evidence of adrenal cortical suppression at the dose levels studied, even when this dose was taken in the evening. A single morning dose of prednisolone appears in many patients to be as effective as a single evening dose or divided doses. It is therefore reasonable to initiate therapy with a morning-only regimen, because adrenopituitary suppression should be minimised. PMID:6751242

Morning blood pressure surge and nighttime blood pressure in relation to nocturnal sleep pattern and arterial stiffness.

PubMed

Suh, Minhee; Barksdale, Debra J; Logan, Jeongok G

2014-01-01

The phenomenon of morning blood pressure (BP) surge (MBPS) is known to increase the risk for cardiovascular events and stroke. The purposes of this study were to explore associations between MBPS and nighttime BP and to examine arterial stiffness and sleep pattern in association with MBPS. This study included 30 healthy Korean American women aged 25 to 60 years. Ambulatory BP was monitored for 24 hours. To evaluate MBPS, maximum morning BP(power) was calculated. Arterial stiffness was measured by carotid-femoral pulse wave velocity, and sleep pattern was evaluated using an actigraphy. The participants (n = 8) in the upper quartile of MBPS had higher morning systolic BPs (SBPs; P = 0.015) and lower nighttime diastolic BPs (P = 0.031). The MBPS in SBP was significantly increased in the participants who had a more wakeful night (P = 0.038) and who slept longer at night (P = 0.041). Although MBPS was not significantly related to arterial stiffness, higher morning SBP (P = 0.005), morning diastolic BP (P = 0.048), and prewake SBP (P = 0.005) were associated with arterial stiffness. Our findings imply a possible link between disturbed sleep and MBPS. Clinicians should understand the importance of the modification of altered sleep pattern for reducing MBPS in nonhypertensive participants.

Effects of an isocaloric healthy Nordic diet on ambulatory blood pressure in metabolic syndrome: a randomized SYSDIET sub-study.

PubMed

Brader, L; Uusitupa, M; Dragsted, L O; Hermansen, K

2014-01-01

Dietary pattern is central in the prevention of hypertension and blood pressure (BP)-related diseases. A diet based on healthy Nordic foods may have a favourable impact on BP. The objective was to clarify whether a Nordic alternative for a healthy food pattern would have beneficial effects on ambulatory BP in subjects with metabolic syndrome (MetS). In total, 37 subjects were randomized to either a healthy Nordic diet or a control diet. A healthy Nordic diet embraced whole grains, rapeseed oil, berries, fruits, vegetables, fish, nuts and low-fat dairy products of Nordic origin. The mean nutrient intake in the Nordic countries formed the control diet, embracing wheat products, dairy fat-based spread and a lower intake of fruits, vegetables and fish. Diets were isoenergetic. Ambulatory BP was monitored and 24-h urine was collected before and after 12 weeks of intervention. After 12 weeks, ambulatory diastolic BP (-4.4 mm Hg; P=0.001) and mean arterial pressure (-4.2 mm Hg; P=0.006) were lowered by the healthy Nordic diet compared with the control diet, whereas changes in ambulatory systolic BP did not differ significantly between diets (-3.5 mm Hg; P=0.122). Heart rate tended to be lower in those on the healthy Nordic diet (P=0.057). Urinary sodium and potassium excretions were unaffected by diets and consequently not associated with the healthy Nordic diet-induced lowering of BP. Consumption of Nordic varieties of health-enhancing foods for 12 weeks decreased diastolic ambulatory BP and mean arterial pressure in subjects with features of MetS during weight-stable condition, suggesting beneficial effects of a healthy Nordic dietary pattern on ambulatory BP.

Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

PubMed Central

Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

2010-01-01

Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

Neuronal oscillations on an ultra-slow timescale: daily rhythms in electrical activity and gene expression in the mammalian master circadian clockwork.

PubMed

Belle, Mino D C; Diekman, Casey O

2018-02-03

Neuronal oscillations of the brain, such as those observed in the cortices and hippocampi of behaving animals and humans, span across wide frequency bands, from slow delta waves (0.1 Hz) to ultra-fast ripples (600 Hz). Here, we focus on ultra-slow neuronal oscillators in the hypothalamic suprachiasmatic nuclei (SCN), the master daily clock that operates on interlocking transcription-translation feedback loops to produce circadian rhythms in clock gene expression with a period of near 24 h (< 0.001 Hz). This intracellular molecular clock interacts with the cell's membrane through poorly understood mechanisms to drive the daily pattern in the electrical excitability of SCN neurons, exhibiting an up-state during the day and a down-state at night. In turn, the membrane activity feeds back to regulate the oscillatory activity of clock gene programs. In this review, we emphasise the circadian processes that drive daily electrical oscillations in SCN neurons, and highlight how mathematical modelling contributes to our increasing understanding of circadian rhythm generation, synchronisation and communication within this hypothalamic region and across other brain circuits. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Renal electrolyte circadian rhythms - Independence from feeding and activity patterns

NASA Technical Reports Server (NTRS)

Moore-Ede, M. C.; Herd, J. A.

1977-01-01

Experiments were conducted on six unanesthetized chair-acclimatized adult male squirrel monkeys (Saimiri sciureus) weighing 600-900 g to determine whether internal synchronization is the result of simple passive dependence of renal excretory rhythms on endogenous rhythms of those variable that influence electrolyte excretion such as dietary intake and muscular activity. Independence of the urinary rhythms from diurnal variations in feeding, drinking, and activity was secured by depriving the animals of food, water, and training them to perform a two-hourly schedule of feeding, drinking, and activity throughout day and night. Results indicate that the internal synchronization which is normally observed between the behavioral and urinary rhythms cannot be explained by any direct dependence of renal function on behavioral patterns. The most probable mechanism for circadian internal synchronization is that the various behavioral and renal rhythms are controlled by potentially independent separate oscillators which are normally kept in synchrony with one another.

Circadian rhythms and sleep patterns in urban Greek couples.

PubMed

Lee, Kathryn A; Beyene, Yewoubdar; Paparrigopoulos, Thomas J; Dikeos, Dimitris G; Soldatos, Constantin R

2007-07-01

A convenience sample of 14 adults (seven couples) who intentionally nap regularly was recruited to describe circadian rhythms and sleep patterns in a culture in which afternoon naps are routine. Participants wore a wrist actigraph for 48 hr during May to obtain two peaks and troughs of activity data. Peak activity, estimated by cosinor analysis (acrophase), occurred at 1542 hours for men and at 1600 hours for women. Compared to their male partners, women had a later acrophase and a significantly stronger 24-hr rhythm, despite similar nap and nighttime sleep schedules. Men had more awakenings during the night and slightly shorter naps than did women. For the 24-hr period, men averaged 6.8 +/- 1.0 hr of sleep and women averaged 7.4 +/- 1.1 hr. Results indicate that Greek adults delay sleep onset at night and awaken early in the morning. Among this small group, naps are an accepted cultural behavior.

Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

PubMed Central

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

2017-01-01

Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian circuit to generate robust 24-h rhythms. PMID:29075180

l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

PubMed

Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang-Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu

2017-12-01

Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before l-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of l-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: l-Serine administration enhanced light-induced phase shifts in mice (1.86-fold; P < 0.05). Both l-serine and its metabolite d-serine, a coagonist of N -methyl-d-aspartic acid (NMDA) receptors, exerted this effect, but d-serine concentrations in the hypothalamus did not increase after l-serine administration. The effect of l-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. l-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, l-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, l-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-l-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that l-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances. © 2017 American Society for Nutrition.

Extent and character of circadian gene expression in Drosophila melanogaster: identification of twenty oscillating mRNAs in the fly head.

PubMed

Van Gelder, R N; Bae, H; Palazzolo, M J; Krasnow, M A

1995-12-01

Although mRNAs expressed with a circadian rhythm have been isolated from many species, the extent and character of circadianly regulated gene expression is unknown for any animal. In Drosophila melanogaster, only the period (per) gene, an essential component of the circadian pacemaker, is known to show rhythmic mRNA expression. Recent work suggests that the encoded Per protein controls its own transcription by an autoregulatory feedback loop. Per might also control the rhythmic expression of other genes to generate circadian behavior and physiology. The goals of this work were to evaluate the extent and character of circadian control of gene expression in Drosophila, and to identify genes dependent on per for circadian expression. A large collection of anonymous, independent cDNA clones was used to screen for transcripts that are rhythmically expressed in the fly head. 20 of the 261 clones tested detected mRNAs with a greater than two-fold daily change in abundance. Three mRNAs were maximally expressed in the morning, whereas 17 mRNAs were most abundant in the evening--when per mRNA is also maximally expressed (but when the flies are inactive). Further analysis of the three 'morning' cDNAs showed that each has a unique dependence on the presence of a light-dark cycle, on timed feeding, and on the function of the per gene for its oscillation. These dependencies were different from those determined for per and for a novel 'evening' gene. Sequence analysis indicated that all but one of the 20 cDNAs identified previously uncloned genes. Diurnal control of gene expression is a significant but limited phenomenon in the fly head, which involves many uncharacterized genes. Diurnal control is mediated by multiple endogenous and exogenous mechanisms, even at the level of individual genes. A subset of circadianly expressed genes are predominantly or exclusively dependent on per for their rhythmic expression. The per gene can therefore influence the expression of genes other than itself, but for many rhythmically expressed genes, per functions in conjunction with external inputs to control their daily expression patterns.

Distal muscle activity alterations during the stance phase of gait in restless leg syndrome (RLS) patients.

PubMed

Dafkin, Chloe; Green, Andrew; Olivier, Benita; McKinon, Warrick; Kerr, Samantha

2018-05-01

To assess if there is a circadian variation in electromyographical (EMG) muscle activity during gait in restless legs syndrome (RLS) patients and healthy control participants. Gait assessment was done in 14 RLS patients and 13 healthy control participants in the evening (PM) and the morning (AM). Muscle activity was recorded bilaterally from the tibialis anterior (TA), lateral gastrocnemius (GL), rectus femoris (RF) and biceps femoris (BF) muscles. A circadian variation during the stance phase in only TA (PM > AM, p < 0.005) and BF (PM < AM, p = 0.008) activity was observed in control participants. Conversely no circadian variation was seen in any muscles in the RLS patients. RLS patients had an increased TA and GL activity (RLS > Controls, p < 0.05) during early stance and decreased GL activity (RLS < Controls, p < 0.01) during terminal stance in comparison to control participants in the evening. No other significant differences were noted between RLS patients and control participants. Activation of GL during the swing phase was noted in 79% of RLS patients and in 23% of control participants in the morning compared to 71% and 38% in the evening, respectively. EMG muscle activity shows no circadian variation in RLS patients. Evening differences in gait muscle activation patterns between RLS patients and control participants are evident. These results extend our knowledge about alterations in spinal processing during gait in RLS. A possible explanation for these findings is central pattern generator sensitization caused by increased sensitivity in cutaneous afferents in RLS patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Diel changes in plasma melatonin and corticosterone concentrations in tropical Nazca boobies (Sula granti) in relation to moon phase and age.

PubMed

Tarlow, Elisa M; Hau, Michaela; Anderson, David J; Wikelski, Martin

2003-10-01

We investigated the effects of moon phases and age on diel rhythms of plasma melatonin and corticosterone in free-living Nazca boobies (Sula granti) on the Galápagos Islands, Ecuador. Melatonin and corticosterone secretion are regulated by the circadian system and the two hormones play a role in the control of locomotor activity and foraging, which can be influenced by moon phases. These seabirds have a long life span and in many vertebrates circadian function deteriorates with age. The functioning of the circadian system under different environmental conditions and changes related to age are poorly understood and hardly studied in wild birds. Nazca boobies had generally low plasma melatonin concentrations but showed a diel variation with higher concentrations at 00:00 and 16:00h. The diel variations in melatonin concentrations disappeared during full moon, suggesting that natural light levels at night can suppress melatonin secretion in Nazca boobies. Maximal melatonin concentrations tended to decline in older birds (10-19 years). Birds showed a clear diel variation in basal plasma corticosterone with a peak in the early morning, before the active period begins, and low concentrations throughout the day. As with melatonin, there were no diel variations in corticosterone at full moon, which may be due to different activity patterns in response to food availability or changes in the circadian system. While other studies have found a relationship between corticosterone and melatonin, we found no such correlation in Nazca boobies. The lunar cycle appears to affect the hormone titers of Nazca boobies both directly and indirectly. First, melatonin rhythms can be directly affected by the light intensity associated with full moon. Second, prey availability may change foraging patterns and can therefore indirectly alter corticosterone secretion in Nazca boobies.

Thermal equilibrium of Nellore cattle in tropical conditions: an investigation of circadian pattern

USDA-ARS?s Scientific Manuscript database

The aim of this work was to evaluate the diurnal patterns of physiological responses and the thermal regulation of adult Nellore bulls. Six 30-mo-old Nellore bulls (669 ± 65 kg BW) were randomly assigned to four 6-h periods in a Latin Square design such that measurements of each animal cover a 24-h ...

Daily activity of four tropical intertidal hermit crabs from southeastern Brazil.

PubMed

Turra, A; Denadai, M R

2003-08-01

This study describes the daily activity in a simulated high tide situation of four species of hermit crabs (Pagurus criniticornis, Clibanarius antillensis, C. sclopetarius, and C. vittatus) that coexist in an intertidal flat in southeastern Brazil. Observations were done in two-hour intervals during two subsequent days (48 h) in three replicate pools with thirty crabs each. Among species (between and within genera) there was an evident variation in activity patterns, of which three could be distinguished. The circadian activity patterns of C. antillensis and C. vittatus could be characterized as evening and nocturnal, with resting peaks during the morning and afternoon. The circadian activity pattern of C. sclopetarius was characterized by two marked peaks of inactivity, corresponding to dawn and evening, which could represent an intrinsic association with the semi-lunar tidal cycles of the study area. Pagurus criniticornis showed high activity not influenced by day/night conditions during the entire observed period. These activity pattern variations of the studied hermit crabs should be taken into account in designing further experiments. More precise and accurate interspecific behavioral comparisons among species could be achieved in nocturnal experiments, the high activity period of all species.

A Computational Method to Quantify Fly Circadian Activity.

PubMed

Lazopulo, Andrey; Syed, Sheyum

2017-10-28

In most animals and plants, circadian clocks orchestrate behavioral and molecular processes and synchronize them to the daily light-dark cycle. Fundamental mechanisms that underlie this temporal control are widely studied using the fruit fly Drosophila melanogaster as a model organism. In flies, the clock is typically studied by analyzing multiday locomotor recording. Such a recording shows a complex bimodal pattern with two peaks of activity: a morning peak that happens around dawn, and an evening peak that happens around dusk. These two peaks together form a waveform that is very different from sinusoidal oscillations observed in clock genes, suggesting that mechanisms in addition to the clock have profound effects in producing the observed patterns in behavioral data. Here we provide instructions on using a recently developed computational method that mathematically describes temporal patterns in fly activity. The method fits activity data with a model waveform that consists of four exponential terms and nine independent parameters that fully describe the shape and size of the morning and evening peaks of activity. The extracted parameters can help elucidate the kinetic mechanisms of substrates that underlie the commonly observed bimodal activity patterns in fly locomotor rhythms.

The frequency of hippocampal theta rhythm is modulated on a circadian period and is entrained by food availability.

PubMed

Munn, Robert G K; Tyree, Susan M; McNaughton, Neil; Bilkey, David K

2015-01-01

The hippocampal formation plays a critical role in the generation of episodic memory. While the encoding of the spatial and contextual components of memory have been extensively studied, how the hippocampus encodes temporal information, especially at long time intervals, is less well understood. The activity of place cells in hippocampus has previously been shown to be modulated at a circadian time-scale, entrained by a behavioral stimulus, but not entrained by light. The experimental procedures used in the previous study of this phenomenon, however, necessarily conflated two alternative entraining stimuli, the exposure to the recording environment and the availability of food, making it impossible to distinguish between these possibilities. Here we demonstrate that the frequency of theta-band hippocampal EEG varies with a circadian period in freely moving animals and that this periodicity mirrors changes in the firing rate of hippocampal neurons. Theta activity serves, therefore, as a proxy of circadian-modulated hippocampal neuronal activity. We then demonstrate that the frequency of hippocampal theta driven by stimulation of the reticular formation also varies with a circadian period. Because this effect can be observed without having to feed the animal to encourage movement we were able to identify what stimulus entrains the circadian oscillation. We show that with reticular-activated recordings started at various times of the day the frequency of theta varies quasi-sinusoidally with a 25 h period and phase-aligned when referenced to the animal's regular feeding time, but not the recording start time. Furthermore, we show that theta frequency consistently varied with a circadian period when the data obtained from repeated recordings started at various times of the day were referenced to the start of food availability in the recording chamber. This pattern did not occur when data were referenced to the start of the recording session or to the actual time of day when this was not also related to feeding time. This double dissociation demonstrates that hippocampal theta is modulated with a circadian timescale, and that this modulation is strongly entrained by food. One interpretation of this finding is that the hippocampus is responsive to a food entrainable oscillator (FEO) that might modulate foraging behavior over circadian periods.

A software solution for recording circadian oscillator features in time-lapse live cell microscopy.

PubMed

Sage, Daniel; Unser, Michael; Salmon, Patrick; Dibner, Charna

2010-07-06

Fluorescent and bioluminescent time-lapse microscopy approaches have been successfully used to investigate molecular mechanisms underlying the mammalian circadian oscillator at the single cell level. However, most of the available software and common methods based on intensity-threshold segmentation and frame-to-frame tracking are not applicable in these experiments. This is due to cell movement and dramatic changes in the fluorescent/bioluminescent reporter protein during the circadian cycle, with the lowest expression level very close to the background intensity. At present, the standard approach to analyze data sets obtained from time lapse microscopy is either manual tracking or application of generic image-processing software/dedicated tracking software. To our knowledge, these existing software solutions for manual and automatic tracking have strong limitations in tracking individual cells if their plane shifts. In an attempt to improve existing methodology of time-lapse tracking of a large number of moving cells, we have developed a semi-automatic software package. It extracts the trajectory of the cells by tracking theirs displacements, makes the delineation of cell nucleus or whole cell, and finally yields measurements of various features, like reporter protein expression level or cell displacement. As an example, we present here single cell circadian pattern and motility analysis of NIH3T3 mouse fibroblasts expressing a fluorescent circadian reporter protein. Using Circadian Gene Express plugin, we performed fast and nonbiased analysis of large fluorescent time lapse microscopy datasets. Our software solution, Circadian Gene Express (CGE), is easy to use and allows precise and semi-automatic tracking of moving cells over longer period of time. In spite of significant circadian variations in protein expression with extremely low expression levels at the valley phase, CGE allows accurate and efficient recording of large number of cell parameters, including level of reporter protein expression, velocity, direction of movement, and others. CGE proves to be useful for the analysis of widefield fluorescent microscopy datasets, as well as for bioluminescence imaging. Moreover, it might be easily adaptable for confocal image analysis by manually choosing one of the focal planes of each z-stack of the various time points of a time series. CGE is a Java plugin for ImageJ; it is freely available at: http://bigwww.epfl.ch/sage/soft/circadian/.

24-h activity rhythm and sleep in depressed outpatients.

PubMed

Hori, Hiroaki; Koga, Norie; Hidese, Shinsuke; Nagashima, Anna; Kim, Yoshiharu; Higuchi, Teruhiko; Kunugi, Hiroshi

2016-06-01

Disturbances in sleep and circadian rest-activity rhythms are key features of depression. Actigraphy, a non-invasive method for monitoring motor activity, can be used to objectively assess circadian rest-activity rhythms and sleep patterns. While recent studies have measured sleep and daytime activity of depressed patients using wrist-worn actigraphy, the actigraphic 24-h rest-activity rhythm in depression has not been well documented. We aimed to examine actigraphically measured sleep and circadian rest-activity rhythms in depressed outpatients. Twenty patients with DSM-IV major depressive episode and 20 age- and sex-matched healthy controls participated in this study. Participants completed 7 consecutive days of all-day actigraphic activity monitoring while engaging in usual activities. For sleep parameters, total sleep time, wake after sleep onset, and sleep fragmentation index were determined. Circadian rhythms were estimated by fitting individual actigraphy data to a cosine curve of a 24-h activity rhythm using the cosinor method, which generated three circadian activity rhythm parameters, i.e., MESOR (rhythm-adjusted mean), amplitude, and acrophase. Subjective sleep was also assessed using a sleep diary and the Pittsburgh Sleep Quality Index. Patients showed significantly lower MESOR and more dampened amplitude along with significant sleep disturbances. Logistic regression analysis revealed that lower MESOR and more fragmented sleep emerged as the significant predictors of depression. Correlations between subjectively and actigraphically measured parameters demonstrated the validity of actigraphic measurements. These results indicate marked disturbances in sleep and circadian rest-activity rhythms of depression. By simultaneously measuring sleep and rest-activity rhythm parameters, actigraphy might serve as an objective diagnostic aid for depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Health consequences of electric lighting practices in the modern world: A report on the National Toxicology Program's workshop on shift work at night, artificial light at night, and circadian disruption.

PubMed

Lunn, Ruth M; Blask, David E; Coogan, Andrew N; Figueiro, Mariana G; Gorman, Michael R; Hall, Janet E; Hansen, Johnni; Nelson, Randy J; Panda, Satchidananda; Smolensky, Michael H; Stevens, Richard G; Turek, Fred W; Vermeulen, Roel; Carreón, Tania; Caruso, Claire C; Lawson, Christina C; Thayer, Kristina A; Twery, Michael J; Ewens, Andrew D; Garner, Sanford C; Schwingl, Pamela J; Boyd, Windy A

2017-12-31

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures. Published by Elsevier B.V.

Metabolic circadian rhythms in embryonic turtles.

PubMed

Loudon, Fiona Kay; Spencer, Ricky-John; Strassmeyer, Alana; Harland, Karen

2013-07-01

Oviparous species are model organisms for investigating embryonic development of endogenous physiological circadian rhythms without the influence of maternal biorhythms. Recent studies have demonstrated that heart rates and metabolic rates of embryonic turtles are not constant or always maximal and can be altered in response to the presence of embryos at a more advanced stage of development within the nest. A first step in understanding the physiological mechanisms underpinning these responses in embryonic ectothermic organisms is to develop metabolic profiles (e.g., heart rate) at different temperatures throughout incubation. Heart beat and rhythmic patterns or changes in development may represent important signals or cues within a nest and may be vital to coordinate synchronous hatching well in advance of the final stages of incubation. We developed baseline embryonic heart-rate profiles of embryos of the short-necked Murray River turtle (Emydura macquarii) to determine the stage of embryogenesis that metabolic circadian rhythms become established, if at all. Eggs were incubated at constant temperatures (26°C and 30°C) and heart rates were monitored at 6-h intervals over 24 h every 7-11 days until hatching. Circadian heart rate rhythms were detected at the mid-gestation period and were maintained until hatching. Heart rates throughout the day varied by up to 20% over 24 h and were not related to time of day. This study demonstrated that endogenous metabolic circadian rhythms in developing embryos in turtle eggs establish earlier in embryogenesis than those documented in other vertebrate taxa during embryogenesis. Early establishment of circadian rhythms in heart rates may be critical for communication among embryos and synchrony in hatching and emergence from the nest.

Limited evidence for affective and diurnal rhythm responses to dim light-at-night in male and female C57Bl/6 mice.

PubMed

Cleary-Gaffney, Michael; Coogan, Andrew N

2018-05-15

Circadian rhythms are recurring patterns in a range of behavioural, physiological and molecular parameters that display periods of near 24 h, and are underpinned by an endogenous biological timekeeping system. Circadian clocks are increasingly recognised as being key for health. Environmental light is the key stimulus that synchronises the internal circadian system with the external time cues. There are emergent health concerns regarding increasing worldwide prevalence of electric lighting, especially man-made light-at-night, and light's impact on the circadian system may be central to these effects. A number of previous studies have demonstrated increased depression-like behaviour in various rodent experimental models exposed to dim light-at-night. In this study we set out to study the impact of dim light-at-night on circadian and affective behaviours in C57Bl/6 mice. We set out specifically to examine the impact of sex on light at night's effects, as well as the impact of housing conditions. We report minimal impact of light-at-night on circadian and affective behaviours, as measured by the tail suspension test, the forced swim test, the sucrose preference test and the elevated plus maze. Light-at-night was also not associated with an increase in body weight, but was associated with a decrease in the cell proliferation marker Ki-67 in the dentate gyrus. In summary, we conclude that experimental contextual factors, such as model species or strain, may be considerable importance in the investigation of the impact of light at night on mood-related parameters. Copyright © 2018 Elsevier Inc. All rights reserved.

Macrophysical climate models and Holocene hunter-gatherer subsistence shifts in Central Texas, USA

NASA Astrophysics Data System (ADS)

Mauldin, R. P.; Munoz, C.

2013-12-01

We use stable carbon isotopic values from bone collagen, as well as carbon values from carbonate extracted from bone apatite from 69 prehistoric human skeletal samples to investigate past resource use and climate relationships over the Middle and Late Holocene in Central Texas. Bone samples come from seven archaeological sites and samples date from 6,900 BP to the close of the prehistoric sequence at about 350 BP. Carbon isotopes from these samples suggest four broad dietary trends. From 6,900 through about 3,800 BP, carbon isotopes suggest a gradual increase in the consumption of resources that ultimately use a C3 photosynthetic pathway. A decline in δ13C in both collagen and carbonate values follows, suggesting a decrease in C3 resource use through roughly 2,900 BP. A variable, but once again increasing pattern on C3 resource use by prehistoric hunter-gatherers is indicated in bone isotopes through about 1,000 BP. After that date, a decrease in C3 resource dependence, with hints at greater subsistence diversity, is suggested through the close of the sequence at 350 BP. To assess the impact of climate shifts on this isotopic pattern, we developed a series of macrophysical climate models (MCM) for several locations in Central Texas focusing on fall, winter, and early spring precipitation. This fall-spring rainfall should closely determine C3 production. If subsistence shifts are responding to climate-induced changes in resource availability, then the measured hunter-gatherer carbon isotope trends summarized above should pattern with C3 production as monitored by the modeled fall-spring precipitation values. For the Middle Holocene portion of the sequence, the precipitation models suggest increasing C3 production, consistent with increasing C3 dependence shown in the isotopic data. A decline in C3 production between 3,900 and 3,000 BP in the models is also consistent with the isotopic decline at that point. After 3,000 BP, however, the coupling between fall-spring rainfall pattern and the bone isotope patterns begin to break down. Precipitation models suggest an essentially flat or slightly increasing pattern of production, while the isotopic data show a rapid C3 increase, and then a decline. This divergence is especially the case late in the sequence, with isotopic patterns showing rapid decreases in C3 resource use that are not consistent with the macrophysical climate models. If the precipitation models are accurate, the Late Holocene pattern of resource use reflects additional elements (e.g., regional population density changes, mobility shifts, social alliances) that require investigation. Standardized values. Data point colors reflect distinct climate trends.

Circadian patterns of xylem sap properties and their covariation with plant hydraulic traits in hybrid aspen.

PubMed

Meitern, Annika; Õunapuu-Pikas, Eele; Sellin, Arne

2017-06-01

Physiological processes taking place in plants are subject to diverse circadian patterns but some of them are poorly documented in natural conditions. The daily dynamics of physico-chemical properties of xylem sap and their covariation with tree hydraulic traits were investigated in hybrid aspen (Populus tremula L.×P. tremuloides Michx) in field conditions in order to clarify which environmental drivers govern the daily variation in these parameters. K + concentration ([K + ]), electrical conductivity (σ sap ), osmolality (Osm) and pH of the xylem sap, as well as branch hydraulic traits, were measured in the field over 24-h cycles. All studied xylem sap properties and hydraulic characteristics including whole-branch (K wb ), leaf blade (K lb ) and petiole hydraulic conductances (K P ) showed clear daily dynamics. Air temperature (T A ) and photosynthetic photon flux density (PPFD), but also water vapour pressure deficit (VPD) and relative humidity (RH), had significant impacts on K wb K lb , K P , [K + ] and σ sap . Osm varied only with light intensity, while K B varied depending on atmospheric evaporative demand expressed as T A , VPD or RH. Xylem sap pH depended inversely on soil water potential (Ψ S ) and during daylight also on VPD. Although soil water content was close to saturation during the study period, Ψ S influenced also [K + ] and σ sap . The present study presents evidence of coupling between circadian patterns of xylem sap properties and plant hydraulic conductance providing adequate water supply to foliage under environmental conditions characterised by diurnal variation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis

PubMed Central

Sharma, Anupma; Wai, Ching Man; Ming, Ray

2017-01-01

Abstract Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. PMID:28922793

Chronobiologically Interpreted Ambulatory Blood Pressure Monitoring in Health and Disease

PubMed Central

Cornélissen, Germaine; Hillman, Dewayne; Beaty, Larry A.; Hong, Shiyu; Schwartzkopff, Othild; Watanabe, Yoshihiko; Otsuka, Kuniaki; Siegelova, Jarmila

2012-01-01

To detect vascular variability anomalies (VVAs), a blood pressure and heart rate profile around the clock for at least 7 days is a start. As a minimum, measurement every 60 or preferably 30 minutes for a week is needed, to be continued if abnormality is found, to assess the about 24-hour (circadian) variability that exists in all individuals. As a first dividend, one then also obtains a glimpse of 2 of the very many longer-than-circadian periodicities, the biological half-week and week. Certainly if we can have sensors and computer chips in our cars that continuously monitor the pressure over a tire's life, we should be able to do the same job for ourselves for diagnostic and therapeutic decisions. Healthcare today emphasizes wellness with recommendations for exercise and a proper diet, yet these evaluations may not be adequate. BP may be measured at a visit to the doctor or before an exercise session, along with measuring body weight and performing a physical exam. The seeds of disease are planted long before they are visible, and what appears to be normal from a conventional point of view may in fact be abnormal. Hidden alterations of physiological function, masked by the body's remarkable adaptive capabilities, may become visible through a new diagnostic and therapeutic realm—chronobiology—that reveals hitherto unseen abnormalities. The tools of chronobiology may yield additional dividends, such as the detection of physiological “loads” related to stress and stress relief and the undesirable effects of space weather upon personal events such as sudden cardiac death, societal events like terrorism and war, and natural disasters. Chronobiologically interpreted automatic ambulatory BP and heart rate (HR) monitoring (C-ABPM) may detect the antecedents of these types of events. C-ABPM is of interest in preventive cardiology, since it reveals new diagnoses as vascular variability anomalies (VVAs) and renders previous conventional diagnoses more reliable, such as that of an elevated BP. These VVAs include MESOR (midline-estimating statistic of rhythm)-hypertension, an elevation of the MESOR, which is diagnosed, like all other VVAs, only after 1 or preferably several replications of 7-day around-the-clock BP monitoring with available, affordable, and unobtrusive instrumentation. The recommendation for continuous C-ABPM recognizes several principles that constitute inseparably intertwined contributors to severe cardio-, cerebro- and renovascular diesase. C-ABPM gauges wear and tear of genetics, physical loads, and in particular mental stress placed upon individuals from “womb to tomb” by daily life, including weather in extraterrestrial space as well as that on earth, as a continuous surveillance paradigm preventing us from flying blind to a change from less than 5% to near 100% in the risk of a stroke within 6 years. PMID:23710422

Chronobiologically Interpreted Ambulatory Blood Pressure Monitoring in Health and Disease.

PubMed

Halberg, Franz; Mult, Hc; Cornélissen, Germaine; Hillman, Dewayne; Beaty, Larry A; Hong, Shiyu; Schwartzkopff, Othild; Watanabe, Yoshihiko; Otsuka, Kuniaki; Siegelova, Jarmila

2012-05-01

To detect vascular variability anomalies (VVAs), a blood pressure and heart rate profile around the clock for at least 7 days is a start. As a minimum, measurement every 60 or preferably 30 minutes for a week is needed, to be continued if abnormality is found, to assess the about 24-hour (circadian) variability that exists in all individuals. As a first dividend, one then also obtains a glimpse of 2 of the very many longer-than-circadian periodicities, the biological half-week and week. Certainly if we can have sensors and computer chips in our cars that continuously monitor the pressure over a tire's life, we should be able to do the same job for ourselves for diagnostic and therapeutic decisions. Healthcare today emphasizes wellness with recommendations for exercise and a proper diet, yet these evaluations may not be adequate. BP may be measured at a visit to the doctor or before an exercise session, along with measuring body weight and performing a physical exam. The seeds of disease are planted long before they are visible, and what appears to be normal from a conventional point of view may in fact actually be abnormal. Hidden alterations of physiological function, masked by the body's remarkable adaptive capabilities, may become visible through a new diagnostic and therapeutic realm-chronobiology-that reveals hitherto unseen abnormalities. The tools of chronobiology may yield additional dividends, such as the detection of physiological "loads" related to stress and stress relief and the undesirable effcts of space weather upon personal events such as sudden cardiac death, societal events like terrorism and war, and natural disasters. Chronobiologi cally interpreted automatic ambulatory BP and heart rate (HR) monitoring (C-ABPM) may detect the antecedents of these types of events. C-ABPM is of interest in preventive cardiology, since it reveals new diagnoses as vascular variability anomalies (VVAs) and renders previous conventional diagnoses more reliable, such as that of an elevated BP. These VVAs include MESOR (midline-estimating statistic of rhythm)-hypertension, an elevation of the MESOR, which is diagnosed, like all other VVAs, only after I or preferably several replications of 7-day around-the-clock BP monitoring with available, affordable, and unobtrusive instrumentation. The recommendation for continuous C-ABPM recognizes several principles that constitute inseparably intertwined contributors to severe cardio-, cerebro- and renovascular diease. C-ABPM gauges wear and tear of genetics, physical loads, and in particular mental stress placed upon individuals from "womb to tomb" by daily life, including weather in extraterrestrial space as well as that on earth, as a continuous surveillance paradigm preventing us from flying blind to a change from less than 5% to near 100% in the risk of a stroke within 6 years.

Congenital central hypoventilation syndrome (CCHS): Circadian temperature variation.

PubMed

Saiyed, Rehan; Rand, Casey M; Carroll, Michael S; Koliboski, Cynthia M; Stewart, Tracey M; Brogadir, Cindy D; Kenny, Anna S; Petersen, Emily K E; Carley, David W; Weese-Mayer, Debra E

2016-03-01

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy, which includes a control of breathing deficit and features of autonomic nervous system (ANS) dysregulation. In recognition of the fundamental role of the ANS in temperature regulation and rhythm and the lack of any prior characterization of circadian temperature rhythms in CCHS, we sought to explore peripheral and core temperatures and circadian patterning. We hypothesized that CCHS patients would exhibit lower peripheral skin temperatures (PST), variability, and circadian rhythmicity (vs. controls), as well as a disrupted relationship between core body temperature (CBT) and PST. PST was sampled every 3 min over four 24-hr periods in CCHS cases and similarly aged controls. CBT was sampled in a subset of these recordings. PST was recorded from 25 CCHS cases (110,664 measures/230 days) and 39 controls (78,772 measures/164 days). Simultaneous CBT measurements were made from 23 CCHS patients. In CCHS, mean PST was lower overall (P = 0.03) and at night (P = 0.02), and PST variability (interquartile range) was higher at night (P = 0.05) (vs. controls). PST circadian rhythm remained intact but the phase relationship of PST to CBT rhythm was extremely variable in CCHS. PST alterations in CCHS likely reflect altered autonomic control of peripheral vascular tone. These alterations represent a previously unreported manifestation of CCHS and may provide an opportunity for therapeutic intervention. The relationship between temperature dysregulation and CCHS may also offer insight into basic mechanisms underlying thermoregulation. © 2015 Wiley Periodicals, Inc.

Circadian and estral changes in the hypothalamic prostaglandin e content and [h]prostaglandin e binding in female rats.

PubMed

Bommelaer-Bayet, M C; Wisner, A; Renard, C A; Levi, F A; Dray, F

1990-04-01

Abstract Prostaglandin E(2), (PGE(2)) is involved in the luteinizing hormone-releasing hormone-stimulated luteinizing hormone surge in female rats and may act via specific membrane receptors. The following studies were performed to determine whether there were any changes in the hypothalamic PGE(2) binding and/or PGE(2) content which were specific to proestrus and not to the rest of the estrous cycle. Groups of female Wistar rats were sacrificed at 3-h intervals throughout the estrous cycle to determine both the circadian and circaestral changes in the hypothalamic PGE(2) content and [(3)H]PGE(2) binding. The hypothalamic PGE(2) content was maximal at 1700 h on each of the 4 consecutive days of the estrous cycle but was independent of the stage of the cycle. [(3)H]PGE(2) binding also displayed a circadian rhythm; the lowest binding occurred near the circadian peak of PGE(2), suggesting that the PGE(2) binding sites were occupied by endogenous PGE(2). Since such circadian rhythms were not observed in the hypothalamus of male rats, they may be under the control of ovarian steroids. Also, since PGE(2) binding and the PGE(2) content both exhibit a diurnal pattern independent of the day of the cycle, there may be changes in the PGE(2) receptor-mediated process coupled to an adenylyl cyclase which could explain the luteinizing hormone surge in proestrus.

Modeling Two-Oscillator Circadian Systems Entrained by Two Environmental Cycles

PubMed Central

Oda, Gisele A.; Friesen, W. Otto

2011-01-01

Several experimental studies have altered the phase relationship between photic and non-photic environmental, 24 h cycles (zeitgebers) in order to assess their role in the synchronization of circadian rhythms. To assist in the interpretation of the complex activity patterns that emerge from these “conflicting zeitgeber” protocols, we present computer simulations of coupled circadian oscillators forced by two independent zeitgebers. This circadian system configuration was first employed by Pittendrigh and Bruce (1959), to model their studies of the light and temperature entrainment of the eclosion oscillator in Drosophila. Whereas most of the recent experiments have restricted conflicting zeitgeber experiments to two experimental conditions, by comparing circadian oscillator phases under two distinct phase relationships between zeitgebers (usually 0 and 12 h), Pittendrigh and Bruce compared eclosion phase under 12 distinct phase relationships, spanning the 24 h interval. Our simulations using non-linear differential equations replicated complex non-linear phenomena, such as “phase jumps” and sudden switches in zeitgeber preferences, which had previously been difficult to interpret. Our simulations reveal that these phenomena generally arise when inter-oscillator coupling is high in relation to the zeitgeber strength. Manipulations in the structural symmetry of the model indicated that these results can be expected to apply to a wide range of system configurations. Finally, our studies recommend the use of the complete protocol employed by Pittendrigh and Bruce, because different system configurations can generate similar results when a “conflicting zeitgeber experiment” incorporates only two phase relationships between zeitgebers. PMID:21886835

Stochastic many-body problems in ecology, evolution, neuroscience, and systems biology

NASA Astrophysics Data System (ADS)

Butler, Thomas C.

Using the tools of many-body theory, I analyze problems in four different areas of biology dominated by strong fluctuations: The evolutionary history of the genetic code, spatiotemporal pattern formation in ecology, spatiotemporal pattern formation in neuroscience and the robustness of a model circadian rhythm circuit in systems biology. In the first two research chapters, I demonstrate that the genetic code is extremely optimal (in the sense that it manages the effects of point mutations or mistranslations efficiently), more than an order of magnitude beyond what was previously thought. I further show that the structure of the genetic code implies that early proteins were probably only loosely defined. Both the nature of early proteins and the extreme optimality of the genetic code are interpreted in light of recent theory [1] as evidence that the evolution of the genetic code was driven by evolutionary dynamics that were dominated by horizontal gene transfer. I then explore the optimality of a proposed precursor to the genetic code. The results show that the precursor code has only limited optimality, which is interpreted as evidence that the precursor emerged prior to translation, or else never existed. In the next part of the dissertation, I introduce a many-body formalism for reaction-diffusion systems described at the mesoscopic scale with master equations. I first apply this formalism to spatially-extended predator-prey ecosystems, resulting in the prediction that many-body correlations and fluctuations drive population cycles in time, called quasicycles. Most of these results were previously known, but were derived using the system size expansion [2, 3]. I next apply the analytical techniques developed in the study of quasi-cycles to a simple model of Turing patterns in a predator-prey ecosystem. This analysis shows that fluctuations drive the formation of a new kind of spatiotemporal pattern formation that I name "quasi-patterns." These quasi-patterns exist over a much larger range of physically accessible parameters than the patterns predicted in mean field theory and therefore account for the apparent observations in ecology of patterns in regimes where Turing patterns do not occur. I further show that quasi-patterns have statistical properties that allow them to be distinguished empirically from mean field Turing patterns. I next analyze a model of visual cortex in the brain that has striking similarities to the activator-inhibitor model of ecosystem quasi-pattern formation. Through analysis of the resulting phase diagram, I show that the architecture of the neural network in the visual cortex is configured to make the visual cortex robust to unwanted internally generated spatial structure that interferes with normal visual function. I also predict that some geometric visual hallucinations are quasi-patterns and that the visual cortex supports a new phase of spatially scale invariant behavior present far from criticality. In the final chapter, I explore the effects of fluctuations on cycles in systems biology, specifically the pervasive phenomenon of circadian rhythms. By exploring the behavior of a generic stochastic model of circadian rhythms, I show that the circadian rhythm circuit exploits leaky mRNA production to safeguard the cycle from failure. I also show that this safeguard mechanism is highly robust to changes in the rate of leaky mRNA production. Finally, I explore the failure of the deterministic model in two different contexts, one where the deterministic model predicts cycles where they do not exist, and another context in which cycles are not predicted by the deterministic model.

Descartes and His Peculiar Sleep Pattern.

PubMed

Damjanovic, Aleksandar; Milovanovic, Srdjan D; Trajanovic, Nikola N

2015-01-01

Rene Descartes (1596-1650) was a mathematician, philosopher, and scholar, whose work set a foundation for modern science. Among other interests, he focused on locating the "core and the seat of the soul" and concluded that the pineal gland was such a structure. Recent scientific findings validate Descartes' deep interest in pineal gland, appreciating its role as part of the circadian rhythm system. On the other hand, the biographical information suggests that Descartes had an aberration of the circadian rhythm (delayed sleep phase). Coincidentally, this meant that one of the most important things in his private life and one of the most significant areas of his research intersected in an overlooked way.

The Timing of the Circadian Clock and Sleep Differ between Napping and Non-Napping Toddlers.

PubMed

Akacem, Lameese D; Simpkin, Charles T; Carskadon, Mary A; Wright, Kenneth P; Jenni, Oskar G; Achermann, Peter; LeBourgeois, Monique K

2015-01-01

The timing of the internal circadian clock shows large inter-individual variability across the lifespan. Although the sleep-wakefulness pattern of most toddlers includes an afternoon nap, the association between napping and circadian phase in early childhood remains unexplored. This study examined differences in circadian phase and sleep between napping and non-napping toddlers. Data were collected on 20 toddlers (34.2±2.0 months; 12 females; 15 nappers). Children followed their habitual napping and non-napping sleep schedules (monitored with actigraphy) for 5 days before an in-home salivary dim light melatonin onset (DLMO) assessment. On average, napping children fell asleep during their nap opportunities on 3.6±1.2 of the 5 days before the DLMO assessment. For these napping children, melatonin onset time was 38 min later (p = 0.044; d = 0.93), actigraphically-estimated bedtime was 43 min later (p = 0.014; d = 1.24), sleep onset time was 59 min later (p = 0.006; d = 1.46), and sleep onset latency was 16 min longer (p = 0.030; d = 1.03) than those not napping. Midsleep and wake time did not differ by napping status. No difference was observed in the bedtime, sleep onset, or midsleep phase relationships with DLMO; however, the wake time phase difference was 47 min smaller for napping toddlers (p = 0.029; d = 1.23). On average, nappers had 69 min shorter nighttime sleep durations (p = 0.006; d = 1.47) and spent 49 min less time in bed (p = 0.019; d = 1.16) than non-nappers. Number of days napping was correlated with melatonin onset time (r = 0.49; p = 0.014). Our findings indicate that napping influences individual variability in melatonin onset time in early childhood. The delayed bedtimes of napping toddlers likely permits light exposure later in the evening, thereby delaying the timing of the clock and sleep. Whether the early developmental trajectory of circadian phase involves an advance associated with the decline in napping is a question necessitating longitudinal data as children transition from a biphasic to monophasic sleep-wakefulness pattern.

The Timing of the Circadian Clock and Sleep Differ between Napping and Non-Napping Toddlers

PubMed Central

Akacem, Lameese D.; Simpkin, Charles T.; Carskadon, Mary A.; Wright, Kenneth P.; Jenni, Oskar G.; Achermann, Peter; LeBourgeois, Monique K.

2015-01-01

The timing of the internal circadian clock shows large inter-individual variability across the lifespan. Although the sleep-wakefulness pattern of most toddlers includes an afternoon nap, the association between napping and circadian phase in early childhood remains unexplored. This study examined differences in circadian phase and sleep between napping and non-napping toddlers. Data were collected on 20 toddlers (34.2±2.0 months; 12 females; 15 nappers). Children followed their habitual napping and non-napping sleep schedules (monitored with actigraphy) for 5 days before an in-home salivary dim light melatonin onset (DLMO) assessment. On average, napping children fell asleep during their nap opportunities on 3.6±1.2 of the 5 days before the DLMO assessment. For these napping children, melatonin onset time was 38 min later (p = 0.044; d = 0.93), actigraphically-estimated bedtime was 43 min later (p = 0.014; d = 1.24), sleep onset time was 59 min later (p = 0.006; d = 1.46), and sleep onset latency was 16 min longer (p = 0.030; d = 1.03) than those not napping. Midsleep and wake time did not differ by napping status. No difference was observed in the bedtime, sleep onset, or midsleep phase relationships with DLMO; however, the wake time phase difference was 47 min smaller for napping toddlers (p = 0.029; d = 1.23). On average, nappers had 69 min shorter nighttime sleep durations (p = 0.006; d = 1.47) and spent 49 min less time in bed (p = 0.019; d = 1.16) than non-nappers. Number of days napping was correlated with melatonin onset time (r = 0.49; p = 0.014). Our findings indicate that napping influences individual variability in melatonin onset time in early childhood. The delayed bedtimes of napping toddlers likely permits light exposure later in the evening, thereby delaying the timing of the clock and sleep. Whether the early developmental trajectory of circadian phase involves an advance associated with the decline in napping is a question necessitating longitudinal data as children transition from a biphasic to monophasic sleep-wakefulness pattern. PMID:25915066

Determining the period, phase and anticipatory component of activity and temperature patterns in newborn rabbits that were maintained under a daily nursing schedule and fasting conditions.

PubMed

Trejo-Muñoz, Lucero; Navarrete, Erika; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

2012-07-16

During the last decade, lagomorphs have gained relevance as valuable models for the study of the development of circadian rhythmicity. This relevance is due to both the peculiar behavior of the lactating doe, in which maternal care is limited from 3 to 5 min per day, and the temporal organization that newborn rabbits exhibit during the early stages of development. In this study, we characterized the development of the temporal pattern of core body temperature and locomotor activity of newborn rabbits. This activity was recorded simultaneously for individual newborn rabbits and was maintained under constant light conditions, a 24-h nursing schedule and without access to the lactating doe. In addition, different mathematical algorithms were designed to determine the period, phase and anticipatory component of the time series obtained for the newborn rabbits. During the first two weeks of life, the average gross locomotor activity decreased as age increased; conversely however, the core body temperature exhibited a significant increment during the early stages of postnatal development. The newborn rabbits' circadian patterns of activity and temperature were consolidated as early as the first week of life. Similarly, the acrophase and nadir of both rhythms were settled by postnatal day 5, and the maximum activity consistently occurred approximately 2 h before the animals' maximum body temperature. The anticipation of nursing was evident from postnatal day 2 for both parameters, and the duration and intensity showed changes associated with the stage of development. In addition, the anticipatory component persisted with the same duration and intensity, even when nursing was omitted. The mathematical methods used in this study are suitable for producing unbiased analyses of the time series that are obtained from developing animals in situations during which biological signals generally show variability in frequencies and trends. By using these methods, it was possible to establish that circadian rhythmicity at the behavioral and physiological levels was evident during the first week of age in newborn rabbits. This circadian rhythmicity represents an endogenous rhythm because it persists throughout constant conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

Sleep/wake patterns and circadian typology in preschool children based on standardized parental self-reports.

PubMed

Doi, Yuriko; Ishihara, Kaneyoshi; Uchiyama, Makoto

2014-04-01

We studied the sleep/wake patterns and circadian typology of Japanese preschool children living in the Tokyo metropolitan area (193 boys and 190 girls, 4-6 years of age) from June to July 2012 based on a standardized parental self-reporting questionnaire. Our major findings are as follows: (1) sleep/wake timing was delayed, and the duration of nocturnal sleep (sleep period as well as time in bed) increased from that on scheduled days (weekdays) to that on free days (weekends) for all ages. (2) The duration of daily sleep (24 h), including daytime nap, was longer for 4-year-old children compared with that in 5- to 6-year-old children, but not significantly different between scheduled and free days within each age group. (3) The distribution of chronotypes was 36.3% for morning (M)-type, 48.8% for neither (N)-type and 11.2% for evening (E)-type, and this distribution was independent of sex or age. (4) Sleep/wake timing delays were observed from M-type and N-type to E-type during scheduled and free days. (5) The duration of nocturnal sleep decreased but increased for 24-h sleep time from M-type and N-type to E-type on scheduled days. (6) Sleep durations did not differ among chronotypes on free days. (7) Chronotypes were associated with parents' diurnal preferences, mealtimes and attendance at kindergartens or childcare centers but not with sex, age, season of birth, exposure to multimedia or exposure to morning sunlight in their bedrooms. When these results were compared with those for older children and adolescents, similar sleep/wake patterns and circadian typology were observed, although to a lesser degree, in children as young as 4-6 years of age. Napping may compensate, in part, for an accumulated weekday sleep deficit. The distribution of chronotypes was associated with differences in sleep/wake timing and duration and was influenced by the parents' diurnal preferences and lifestyles. Further research on preschool children is required to investigate whether circadian typology affects their behavioral, emotional and cognitive development.

Lack of circadian regulation of melatonin rhythms in the sockeye salmon (Oncorhynchus nerka) in vivo and in vitro.

PubMed

Iigo, Masayuki; Azuma, Teruo; Iwata, Munehico

2007-01-01

Melatonin profiles were determined in the plasma in vivo and in the pineal organ in vitro of the sockeye salmon (Oncorhynchus nerka) under various light conditions to test whether they are under circadian regulation. When serial blood samples were taken at 4-h intervals for 3 days via a cannula inserted into the dorsal aorta, plasma melatonin exhibited significant fluctuation under a light-dark cycle, with higher levels during the dark phase than during the light phase. No rhythmic fluctuations persisted under either constant dark or constant light, with constant low and high levels, respectively. Melatonin release from the pineal organ in flow-through culture exhibited a similar pattern in response to the change in light conditions, with high and low release associated with the dark and light phases, respectively. These results indicate that melatonin production in the sockeye salmon is driven by light and darkness but lacks circadian regulation.

Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA

PubMed Central

Mori, Tetsuya; Saveliev, Sergei V.; Xu, Yao; Stafford, Walter F.; Cox, Michael M.; Inman, Ross B.; Johnson, Carl H.

2002-01-01

KaiC from Synechococcus elongatus PCC 7942 (KaiC) is an essential circadian clock protein in cyanobacteria. Previous sequence analyses suggested its inclusion in the RecA/DnaB superfamily. A characteristic of the proteins of this superfamily is that they form homohexameric complexes that bind DNA. We show here that KaiC also forms ring complexes with a central pore that can be visualized by electron microscopy. A combination of analytical ultracentrifugation and chromatographic analyses demonstrates that these complexes are hexameric. The association of KaiC molecules into hexamers depends on the presence of ATP. The KaiC sequence does not include the obvious DNA-binding motifs found in RecA or DnaB. Nevertheless, KaiC binds forked DNA substrates. These data support the inclusion of KaiC into the RecA/DnaB superfamily and have important implications for enzymatic activity of KaiC in the circadian clock mechanism that regulates global changes in gene expression patterns. PMID:12477935

Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA.

PubMed

Mori, Tetsuya; Saveliev, Sergei V; Xu, Yao; Stafford, Walter F; Cox, Michael M; Inman, Ross B; Johnson, Carl H

2002-12-24

KaiC from Synechococcus elongatus PCC 7942 (KaiC) is an essential circadian clock protein in cyanobacteria. Previous sequence analyses suggested its inclusion in the RecADnaB superfamily. A characteristic of the proteins of this superfamily is that they form homohexameric complexes that bind DNA. We show here that KaiC also forms ring complexes with a central pore that can be visualized by electron microscopy. A combination of analytical ultracentrifugation and chromatographic analyses demonstrates that these complexes are hexameric. The association of KaiC molecules into hexamers depends on the presence of ATP. The KaiC sequence does not include the obvious DNA-binding motifs found in RecA or DnaB. Nevertheless, KaiC binds forked DNA substrates. These data support the inclusion of KaiC into the RecADnaB superfamily and have important implications for enzymatic activity of KaiC in the circadian clock mechanism that regulates global changes in gene expression patterns.

Activity pattern of medium and large sized mammals and density estimates of Cuniculus paca (Rodentia: Cuniculidae) in the Brazilian Pampa.

PubMed

Leuchtenberger, C; de Oliveira, Ê S; Cariolatto, L P; Kasper, C B

2018-02-22

Between July 2014 and April 2015, we conducted weekly inventories of the circadian activity patterns of mammals in Passo Novo locality, municipality of Alegrete, southern Brazil. The vegetation is comprised by a grassy-woody steppe (grassland). We used two camera traps alternately located on one of four 1 km transects, each separated by 1 km. We classified the activity pattern of species by the percentage of photographic records taken in each daily period. We identify Cuniculus paca individuals by differences in the patterns of flank spots. We then estimate the density 1) considering the area of riparian forest present in the sampling area, and 2) through capture/recapture analysis. Cuniculus paca, Conepatus chinga and Hydrochoerus hydrochaeris were nocturnal, Cerdocyon thous had a crepuscular/nocturnal pattern, while Mazama gouazoubira was cathemeral. The patterns of circadian activity observed for medium and large mammals in this Pampa region (southern grasslands) may reflect not only evolutionary, biological and ecological affects, but also human impacts not assessed in this study. We identified ten individuals of C. paca through skin spot patterns during the study period, which were recorded in different transects and months. The minimum population density of C. paca was 3.5 individuals per km2 (resident animals only) and the total density estimates varied from 7.1 to 11.8 individuals per km2, when considering all individuals recorded or the result of the capture/recapture analysis, respectively.

Fractal Patterns of Neural Activity Exist within the Suprachiasmatic Nucleus and Require Extrinsic Network Interactions

PubMed Central

Hu, Kun; Meijer, Johanna H.; Shea, Steven A.; vanderLeest, Henk Tjebbe; Pittman-Polletta, Benjamin; Houben, Thijs; van Oosterhout, Floor; Deboer, Tom; Scheer, Frank A. J. L.

2012-01-01

The mammalian central circadian pacemaker (the suprachiasmatic nucleus, SCN) contains thousands of neurons that are coupled through a complex network of interactions. In addition to the established role of the SCN in generating rhythms of ∼24 hours in many physiological functions, the SCN was recently shown to be necessary for normal self-similar/fractal organization of motor activity and heart rate over a wide range of time scales—from minutes to 24 hours. To test whether the neural network within the SCN is sufficient to generate such fractal patterns, we studied multi-unit neural activity of in vivo and in vitro SCNs in rodents. In vivo SCN-neural activity exhibited fractal patterns that are virtually identical in mice and rats and are similar to those in motor activity at time scales from minutes up to 10 hours. In addition, these patterns remained unchanged when the main afferent signal to the SCN, namely light, was removed. However, the fractal patterns of SCN-neural activity are not autonomous within the SCN as these patterns completely broke down in the isolated in vitro SCN despite persistence of circadian rhythmicity. Thus, SCN-neural activity is fractal in the intact organism and these fractal patterns require network interactions between the SCN and extra-SCN nodes. Such a fractal control network could underlie the fractal regulation observed in many physiological functions that involve the SCN, including motor control and heart rate regulation. PMID:23185285

Relative metabolic stability, but disrupted circadian cortisol secretion during the fasting month of Ramadan.

PubMed

Bahijri, Suhad; Borai, Anwar; Ajabnoor, Ghada; Abdul Khaliq, Altaf; AlQassas, Ibrahim; Al-Shehri, Dhafer; Chrousos, George

2013-01-01

Chronic feeding and sleep schedule disturbances are stressors that exert damaging effects on the organism. Practicing Muslims in Saudi Arabia go through strict Ramadan fasting from dawn till sunset for one month yearly. Modern era Ramadan practices in Saudi Arabia are associated with disturbed feeding and sleep patterns, namely abstaining from food and water and increasing daytime sleep, and staying awake and receiving food and water till dawn. Strict Ramadan practices in Saudi Arabia may influence metabolism, sleep and circadian cortisol secretion. Young, male Ramadan practitioners were evaluated before and two weeks into the Ramadan. Blood samples were collected at 9.00 am and 9.00 pm for measurements of metabolic parameters and cortisol. Saliva was collected serially during the day for cortisol determinations. Ramadan practitioners had relative metabolic stability or changes expected by the pattern of feeding. However, the cortisol circadian rhythm was abolished and circulating insulin levels and HOMA index were increased during this period. The flattening of the cortisol rhythm is typical of conditions associated with chronic stress or endogenous hypercortisolism and associated with insulin resistance. Modern Ramadan practices in Saudi Arabia are associated with evening hypercortisolism and increased insulin resistance. These changes might contribute to the high prevalence of chronic stress-related conditions, such as central obesity, hypertension, metabolic syndrome and diabetes mellitus type 2, and their cardiovascular sequelae observed in the Kingdom.

Aging and the circadian rhythm of melatonin: a cross-sectional study of Chinese subjects 30-110 yr of age.

PubMed

Zhao, Zi-Yan; Xie, Yi; Fu, Yue-Rong; Bogdan, André; Touitou, Yvan

2002-11-01

Although previous reports indicate that nocturnal plasma melatonin secretion declines with age, some recent findings do not support this point. In the present cross-sectional study, we documented serum melatonin concentrations at two time points, 02:00 and 08:00 h, in 144 persons aged 30-110 yr and found a significant age-related decline. It began around the age of 60 and reached a very significantly lower level in subjects in their 70s and over 80 yr of age (P < 0.01, when compared with age <60 yr). Nocturnal melatonin levels were higher among (post-menopausal only) women than men overall (P < 0.05). In the older age-groups, nocturnal melatonin levels did not differ between healthy controls and subjects with high blood pressure or ischemic heart disease. To further check these results, we also assessed the circadian pattern of serum melatonin in four subgroups of healthy men, aged 30-39, 40-49, 50-59, and 60-69 yr: blood samples were taken at 2 h intervals from 08:00 to 22:00 h and hourly from 22:00 to 08:00 h. Our results showed generally similar circadian melatonin patterns that peaked at night with very low levels during the daytime. No significant difference was found among the three younger groups, but nocturnal melatonin levels were significantly lower in the men in their 60s.

Actigraphy and motion analysis: new tools for psychiatry.

PubMed

Teicher, M H

1995-01-01

Altered locomotor activity is a cardinal sign of several psychiatric disorders. With advances in technology, activity can now be measured precisely. Contemporary studies quantifying activity in psychiatric patients are reviewed. Studies were located by a Medline search (1965 to present; English language only) cross-referencing motor activity and major psychiatric disorders. The review focused on mood disorders and attention-deficit hyperactivity disorder (ADHD). Activity levels are elevated in mania, agitated depression, and ADHD and attenuated in bipolar depression and seasonal depression. The percentage of low-level daytime activity is directly related to severity of depression, and change in this parameter accurately mirrors recovery. Demanding cognitive tasks elicit fidgeting in children with ADHD, and precise measures of activity and attention may provide a sensitive and specific marker for this disorder. Circadian rhythm analysis enhances the sophistication of activity measures. Affective disorders in children and adolescents are characterized by an attenuated circadian rhythm and an enhanced 12-hour harmonic rhythm (diurnal variation). Circadian analysis may help to distinguish between the activity patterns of mania (dysregulated) and ADHD (intact or enhanced). Persistence of hyperactivity or circadian dysregulation in bipolar patients treated with lithium appears to predict rapid relapse once medication is discontinued. Activity monitoring is a valuable research tool, with the potential to aid clinicians in diagnosis and in prediction of treatment response.

Biological clocks: their relevance to immune-allergic diseases.

PubMed

Paganelli, Roberto; Petrarca, Claudia; Di Gioacchino, Mario

2018-01-01

The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made in the past 15 years on the genetic and molecular mechanisms regulating many physiological functions, has renewed the attention to the importance of circadian rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus in the brain, photoentrained via direct connection with melanopsin containing, intrinsically light-sensitive retinal ganglion cells, and it projects to periphery, thus creating an inner circadian rhythm. This regulates several activities, including sleep, feeding times, energy metabolism, endocrine and immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal secretion and feeding, cause decrease in quality of life, as well as being involved in development of obesity, metabolic syndrome and neuropsychiatric disorders. Most immunological functions, from leukocyte numbers, activity and cytokine secretion undergo circadian variations, which might affect susceptibility to infections. The intensity of symptoms and disease severity show a 24 h pattern in many immunological and allergic diseases, including rheumatoid arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is accompanied by altered sleep duration and quality, a major determinant of quality of life. Shift work and travel through time zones as well as artificial light pose new health threats by disrupting the circadian rhythms. Finally, the field of chronopharmacology uses these concepts for delivering drugs in synchrony with biological rhythms.

Body weight gain in rats by a high-fat diet produces chronodisruption in activity/inactivity circadian rhythm.

PubMed

Bravo, Rafael; Cubero, Javier; Franco, Lourdes; Mesa, Mónica; Galán, Carmen; Rodríguez, Ana Beatriz; Jarne, Carlos; Barriga, Carmen

2014-04-01

In the last few decades, obesity has become one of the most important public health problems. Adipose tissue is an active endocrine tissue which follows a rhythmic pattern in its functions and may produce alterations in certain circadian rhythms. Our aim was to evaluate whether the locomotor activity circadian rhythm could be modified by a hypercaloric diet in rodents. Two groups were considered in the experiment: 16 rats were used as a control group and were fed standard chow; the other group comprised 16 rats fed a high-fat diet (35.8% fat, 35% glucides). The trial lasted 16 weeks. Body weight was measured every week, and a blood sample was extracted every two weeks to quantify triglyceride levels. The activity/inactivity circadian rhythm was logged through actimetry throughout the trial, and analysed using the DAS 24© software package. At the end of the experiment, the high-fat fed rats had obese-like body weights and high plasma triglyceride levels, and, compared with the control group, increased diurnal activity, decreased nocturnal activity, reductions in amplitude, midline estimating statistic of rhythm, acrophase and interdaily stability, and increases in intradaily variability of their activity rhythms. The results thus show how obesity can lead to symptoms of chronodisruption in the body similar to those of ageing.

Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

PubMed

Zhang, Beilin; Gao, Yanxia; Li, Yang; Yang, Jing; Zhao, Hua

2016-01-01

Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis.

Genome-wide binding site analysis of FAR-RED ELONGATED HYPOCOTYL3 reveals its novel function in Arabidopsis development.

PubMed

Ouyang, Xinhao; Li, Jigang; Li, Gang; Li, Bosheng; Chen, Beibei; Shen, Huaishun; Huang, Xi; Mo, Xiaorong; Wan, Xiangyuan; Lin, Rongcheng; Li, Shigui; Wang, Haiyang; Deng, Xing Wang

2011-07-01

FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1), two transposase-derived transcription factors, are key components in phytochrome A signaling and the circadian clock. Here, we use chromatin immunoprecipitation-based sequencing (ChIP-seq) to identify 1559 and 1009 FHY3 direct target genes in darkness (D) and far-red (FR) light conditions, respectively, in the Arabidopsis thaliana genome. FHY3 preferentially binds to promoters through the FHY3/FAR1 binding motif (CACGCGC). Interestingly, FHY3 also binds to two motifs in the 178-bp Arabidopsis centromeric repeats. Comparison between the ChIP-seq and microarray data indicates that FHY3 quickly regulates the expression of 197 and 86 genes in D and FR, respectively. FHY3 also coregulates a number of common target genes with PHYTOCHROME INTERACTING FACTOR 3-LIKE5 and ELONGATED HYPOCOTYL5. Moreover, we uncover a role for FHY3 in controlling chloroplast development by directly activating the expression of ACCUMULATION AND REPLICATION OF CHLOROPLASTS5, whose product is a structural component of the latter stages of chloroplast division in Arabidopsis. Taken together, our data suggest that FHY3 regulates multiple facets of plant development, thus providing insights into its functions beyond light and circadian pathways.

Abnormal blood pressure circadian rhythm in acute ischaemic stroke: are lacunar strokes really different?

PubMed

Castilla-Guerra, L; Espino-Montoro, A; Fernández-Moreno, M C; López-Chozas, J M

2009-08-01

A pathologically reduced or abolished circadian blood pressure variation has been described in acute stroke. However, studies on alterations of circadian blood pressure patterns after stroke and stroke subtypes are scarce. The objective of this study was to evaluate the changes in circadian blood pressure patterns in patients with acute ischaemic stroke and their relation to the stroke subtype. We studied 98 consecutive patients who were admitted within 24 h after ischaemic stroke onset. All patients had a detailed clinical examination, laboratory studies and a CT scan study of the brain on admission. To study the circadian rhythm of blood pressure, a continuous blood pressure monitor (Spacelab 90217) was used. Patients were classified according to the percentage fall in the mean systolic blood pressure or diastolic blood pressure at night compared with during the day as: dippers (fall> or =10-20%); extreme dippers (> or =20%); nondipper (<10%); and reverse dippers (<0%, that is, an increase in the mean nocturnal blood pressure compared with the mean daytime blood pressure). Data were separated and analysed in two groups: lacunar and nonlacunar infarctions. Statistical testing was conducted using the SSPS 12.0. Methods We studied 60 males and 38 females, mean age: 70.5+/-11 years. The patient population consisted of 62 (63.2%) lacunar strokes and 36 (36.8%) nonlacunar strokes. Hypertension was the most common risk factor (67 patients, 68.3%). Other risk factors included hypercholesterolaemia (44 patients, 44.8%), diabetes mellitus (38 patients, 38.7%), smoking (24 patients, 24.8%) and atrial fibrillation (19 patients, 19.3%). The patients with lacunar strokes were predominantly men (P=0.037) and had a lower frequency of atrial fibrillation (P=0.016) as compared with nonlacunar stroke patients. In the acute phase, the mean systolic blood pressure was 136+/-20 mmHg and diastolic blood pressure was 78.7+/-11.8. Comparing stroke subtypes, there were no differences in 24-h systolic blood pressure and 24-h diastolic blood pressure between patients with lacunar and nonlacunar infarction. However, patients with lacunar infarction showed a mean decline in day-night systolic blood pressure and diastolic blood pressure of approximately 4 mmHg [systolic blood pressure: 3.9 (SD 10) mmHg, P=0.003; diastolic blood pressure 3.7 (SD 7) mmHg, P=0.0001] compared with nonlacunar strokes. Nonlacunar strokes showed a lack of 24-h nocturnal systolic blood pressure and diastolic blood pressure fall. The normal diurnal variation in systolic blood pressure was abolished in 87 (88.9%) patients, and the variation in diastolic blood pressure was abolished in 76 (77.5%) patients. On comparing lacunar and nonlacunar strokes, we found that the normal diurnal variation in systolic blood pressure was abolished in 53 (85.4%) lacunar strokes and in 34 (94.4%) nonlacunar strokes (P=nonsignificant). In terms of diurnal variation in diastolic blood pressure, it was abolished in 43 (69.3%) lacunar strokes and in 33 (91.6%) nonlacunar strokes (P=0.026). Our results show clear differences in the blood pressure circadian rhythm of acute ischaemic stroke between lacunar and nonlacunar infarctions by means of 24-h blood pressure monitoring. The magnitude of nocturnal systolic and diastolic blood pressure dip was significantly higher in lacunar strokes. Besides, patients with lacunar strokes presented a higher percentage of dipping patterns in the diastolic blood pressure circadian rhythm. Therefore, one should consider the ischaemic stroke subtype when deciding on the management of blood pressure in acute stroke.

Preserved functional autonomic phenotype in adult mice overexpressing moderate levels of human alpha-synuclein in oligodendrocytes.

PubMed

Tank, Jens; da Costa-Goncalves, Andrey C; Kamer, Ilona; Qadri, Fatimunnisa; Ubhi, Kiren; Rockenstein, Edward; Diedrich, André; Masliah, Eliezer; Gross, Volkmar; Jordan, Jens

2014-11-01

Mice overexpressing human alpha-synuclein in oligodendrocytes (MBP1-α-syn) recapitulate some key functional and neuropathological features of multiple system atrophy (MSA). Whether or not these mice develop severe autonomic failure, which is a key feature of human MSA, remains unknown. We explored cardiovascular autonomic regulation using long-term blood pressure (BP) radiotelemetry and pharmacological testing. We instrumented 12 MBP1-α-syn mice and 11 wild-type mice aged 9 months for radiotelemetry. Animals were tested with atropine, metoprolol, clonidine, and trimethaphan at 9 and 12 months age. We applied spectral and cross-spectral analysis to assess heart rate (HR) and BP variability. At 9 months of age daytime BP (transgenic: 101 ± 2 vs. wild type: 99 ± 2 mmHg) and HR (497 ± 11 vs. 505 ± 16 beats/min) were similar. Circadian BP and HR rhythms were maintained. Nighttime BP (109 ± 2 vs. 108 ± 2 mmHg) and HR (575 ± 15 vs. 569 ± 14 beats/min), mean arterial BP responses to trimethaphan (-21 ± 8 vs. -10 ± 5 mmHg, P = 0.240) and to clonidine (-8 ± 3 vs. -5 ± 2 mmHg, P = 0.314) were similar. HR responses to atropine (+159 ± 24 vs. +146 ± 22 beats/min), and to clonidine (-188 ± 21 vs. -163 ± 33 beats/min) did not differ between strains. Baroreflex sensitivity (4 ± 1 vs. 4 ± 1 msec/mmHg) and HR variability (total power, 84 ± 17 vs. 65 ± 21 msec²) were similar under resting conditions and during pharmacological testing. Repeated measurements at 12 months of age provided similar results. In mice, moderate overexpression of human alpha-synuclein in oligodendrocytes is not sufficient to induce overt autonomic failure. Additional mechanisms may be required to express the autonomic failure phenotype including higher levels of expression or more advanced age. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Circadian rhythmicity of the urinary excretion of mercury, potassium and catecholamines in unconventional shift-work systems.

PubMed

Vokac, Z; Gundersen, N; Magnus, P; Jebens, E; Bakka, T

1980-09-01

The round the clock urinary excretion rates of mercury were assessed for two series of unconventional patterns of activity and sleep in subjects who were not exposed to occupational, medical, or other obvious sources of mercury. In the first series the urine was collected in 3-h periods from six subjects during the first and last 2 d of a four-week, continuous 6-h shift (car ferry, watches either 0800--1400 and 2000--0200 or 1400--2000 and 0200--0800). In the second series the urine was collected in 4-h periods from five subjects working an 8-h experimental rotation shift compressed into 5 d (work two mornings--8-h interval--work two nights--8-h interval--work two afternoons). The mean daily excretion rate of the 11 subjects (48 investigation days, 334 urine samples) was 14.5 pmol of mercury/min (range 5.5--24.4 pmol of mercury/min). The mercury excretion oscillated regularly during 24 h by +/- 20--25% of the individual's daily mean excretion rates. The peak excretion rates were found at 0652 in the first and 0642 in the second series (cosinor treatment). Due to the circadian rhythm the mean 24-h excretion rates were best represented (correlation coefficient 0.92) by analyses of urine produced around noon (spot samples, collection periods 1100--1400 and 1000-1400, respectively). The circadian oscillations of mercury excretion were not influenced by the widely different and varying activity-sleep patterns of the two series. The rhythmicity of potassium excretion (peaks at around 1400) was more irregular. The stable oscillations of mercury excretion contrasted most with the excretion of adrenaline and noradrenaline, which, without losing the basic 24-h rhythmicity, closely followed the unconventional patterns of activity and sleep.

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis.

PubMed

Sharma, Anupma; Wai, Ching Man; Ming, Ray; Yu, Qingyi

2017-09-01

Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Effect of Intraperitoneal Radiotelemetry Instrumentation on Voluntary Wheel Running and Surgical Recovery in Mice

DTIC Science & Technology

2012-09-01

affects body weight, food intake, water intake, circadian core temperature, activity , voluntary running patterns, and the health of internal organs and...temperature and activity patterns within 1 d after surgery, whereas activity was depressed in mice with large)ransmitters throughout experimentation. The...CD1 mice implanted with transmitter devices (approximately 11% of body weight), blood pressure, heart rate, and activity showed telemetry-associated

Calcium and cAMP directly modulate the speed of the Drosophila circadian clock.

PubMed

Palacios-Muñoz, Angelina; Ewer, John

2018-06-01

Circadian clocks impose daily periodicities to animal behavior and physiology. At their core, circadian rhythms are produced by intracellular transcriptional/translational feedback loops (TTFL). TTFLs may be altered by extracellular signals whose actions are mediated intracellularly by calcium and cAMP. In mammals these messengers act directly on TTFLs via the calcium/cAMP-dependent transcription factor, CREB. In the fruit fly, Drosophila melanogaster, calcium and cAMP also regulate the periodicity of circadian locomotor activity rhythmicity, but whether this is due to direct actions on the TTFLs themselves or are a consequence of changes induced to the complex interrelationship between different classes of central pacemaker neurons is unclear. Here we investigated this question focusing on the peripheral clock housed in the non-neuronal prothoracic gland (PG), which, together with the central pacemaker in the brain, controls the timing of adult emergence. We show that genetic manipulations that increased and decreased the levels of calcium and cAMP in the PG caused, respectively, a shortening and a lengthening of the periodicity of emergence. Importantly, knockdown of CREB in the PG caused an arrhythmic pattern of eclosion. Interestingly, the same manipulations directed at central pacemaker neurons caused arrhythmicity of eclosion and of adult locomotor activity, suggesting a common mechanism. Our results reveal that the calcium and cAMP pathways can alter the functioning of the clock itself. In the PG, these messengers, acting as outputs of the clock or as second messengers for stimuli external to the PG, could also contribute to the circadian gating of adult emergence.

Circadian preference is associated with emotional and affective temperaments.

PubMed

Ottoni, Gustavo L; Antoniolli, Eduardo; Lara, Diogo R

2012-07-01

Chronotype has long been associated with mental disorders and temperamental features. This study aims to investigate the association of circadian preference with a new model for emotional and affective temperament. In this Web survey, 6436 subjects (27.2% males) answered the Affective and Emotional Composite Temperament Scale (AFECTS), the Circadian Energy Scale (CIRENS), and questions on subjective sleep parameters for a sleep-based chronotype measure. Temperament was more strongly correlated with daily energy score than with chronotype. For emotional dimensions, Volition, Coping, and Control positively correlated with high and stable daily energy, contrary to Sensitivity. Evening types showed a less adaptive emotional profile than morning and intermediate types, who showed a relatively similar emotional pattern. Focus and order (facets of Control), energy (facet of Volition), caution (facet of Inhibition), and problem facing (facet of Coping) were distinctive for the three circadian types, being particularly low in evening types and high in morning types. Differences between affective temperaments were more pronounced for morning and afternoon than for evening scores. Cyclothymic and euphoric temperaments, which relate to bipolar disorders, and apathetic, volatile, and disinhibited temperaments, which relate to attention-deficit/hyperactivity disorder (ADHD), showed the latest chronotype (i.e., evening preference). In conclusion, temperament was more associated with absolute energy levels than with chronotype. Evening types had less emotional control, coping, volition, and caution, and more affective instability and externalization. The circadian daily energy profile can be very informative about human temperament and vice versa, and their combined assessment may be useful in the evaluation of psychiatric patients.

Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis.

PubMed

Kunz, D; Bes, F

2001-03-15

The etiology of Periodic Limb Movement Disorder (PLMD) as well as the precise role of melatonin in human physiology remains poorly understood. Inspired by a single case observation we performed the presented study in order to obtain first evidence for the hypothesis that exogenous melatonin would decrease PLM's and thereby improves symptoms of PLMD patients. N/A. N/A. Nine patients with first time diagnosis of PLMD without RLS were treated over a six-week period with 3 mg melatonin, taken between 10 and 11 p.m. N/A. Melatonin improved well-being in 7 of the 9 patients. Polysomnography, performed prior and at the end of melatonin treatment, demonstrated a significant reduction of investigated movement parameters, such as PLMs, PLM index, PLMs with arousals and PLM-arousal index. Actigraphy, measured over 14 nights prior and during the last 14 days of melatonin treatment, showed a significant reduction in movement rate and minutes with movements during Time in Bed. The temporal distribution of PLMs, as well as the coupling of PLMs with the phase position of circadian temperature curve, suggest an involvement of the circadian timing system in the pathophysiology of PLMD. Locomotor activity in animals clearly exhibits a circadian pattern and can be strongly influenced by exogenous melatonin. Results suggest a chronobiotic effect of exogenous melatonin in PLMD. More specifically, we hypothesize that the mode of action of melatonin in the presented PLMD patients might have been an increase of output-amplitude of the circadian timing system, thereby enhancing the circadian rhythmicity of locomotor activity with a reduction of sleep motor activity.

Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients

PubMed Central

Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J.; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz

2010-01-01

This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were VC = 27.7 l, VT = 801 l, and CLD = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65·(1 − 0.00714·(SBP − 135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC50 equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light–dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night–day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients. PMID:20544262

Circadian rhythms of body temperature and locomotor activity in the antelope ground squirrel, Ammospermophilus leucurus.

PubMed

Refinetti, Roberto; Kenagy, G J

2018-02-01

We studied circadian rhythms of body temperature and locomotor activity in antelope ground squirrels (Ammospermophilus leucurus) under laboratory conditions of a 12L:12D light-dark cycle and in constant darkness. Antelope ground squirrels are diurnally active and, exceptionally among ground squirrels and other closely related members of the squirrel family in general, they do not hibernate. Daily oscillations in body temperature consisted of a rise in temperature during the daytime activity phase of the circadian cycle and a decrease in temperature during the nighttime rest phase. The body temperature rhythms were robust (71% of maximal strength) with a daily range of oscillation of 4.6°C, a daytime mean of 38.7°C, and a nighttime mean of 34.1°C (24-h overall mean 36.4°C). The body temperature rhythm persisted in continuous darkness with a free-running period of 24.2h. This pattern is similar to that of hibernating species of ground squirrels but with a wave form more similar to that of non-hibernating rodents. Daily oscillations in body temperature were correlated with individual bouts of activity, but daytime temperatures were higher than nighttime temperatures even when comparing short episodes of nocturnal activity that were as intense as diurnal activity. This suggests that although muscular thermogenesis associated with locomotor activity can modify the level of body temperature, the circadian rhythm of body temperature is not simply a consequence of the circadian rhythm of activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronobiology of the neuroimmunoendocrine system and aging.

PubMed

Mate, Ianire; Madrid, Juan Antonio; De la Fuente, Mónica

2014-01-01

The health maintenance depends on the preservation of the homeostatic systems, such as nervous, endocrine and immune system, and a proper communication between them. In this regard, the circadian system, which promotes a better physiological system functions and thus well being, could be considered part of that homeostatic complex, since the neuroimmunoendocrine system possesses circadian patterns in most variables, as well as circannual or seasonal variations. With aging, an impairment of the homeostatic systems occurs and an alteration of circadian system regulation has been demonstrated. In the immune system, several function parameters, which are good markers of health and of the rate of aging, change not only with age (immunosenescence) but also throughout the day and year. Indeed, with advancing age there is a modification of immune cell circadian function especially in lymphocytes. Moreover, immune functions at early afternoon correspond to more aged values than at morning, especially in mature subjects (60-79 years of age). In addition, these mature men and women showed a significant impaired immune cell function, which is especially remarkable in the winter. It is noteworthy the role of immunomodulatory hormones, such as melatonin, in the regulation of biological rhythms and their involvement in the aging process. Furthermore, the evidence of a neuroimmune regulation of the circadian system and its disturbance with aging, highlights the importance of proinflammatory cytokines in this complex cross-talk. The biological rhythms disruption with age and some diseases (jet lag, cancer and seasonal affective disorder), could contribute increasing the immune system impairment and consequently the loss of health.

Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells.

PubMed

Sandbichler, Adolf M; Jansen, Bianca; Peer, Bettina A; Paulitsch, Monika; Pelster, Bernd; Egg, Margit

2018-01-01

Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly oxidized nocturnal cellular environment. Of note, circadian rhythms of cytosolic H2O2 remain unaltered, while the transcriptional clock is already attenuated, as it is known to occur also under chronic hypoxia. We therefor propose that the realignment of metabolic redox oscillations might initiate the observed hypoxia induced attenuation of the transcriptional clock, based on the reduced binding affinity of the CLOCK/BMAL complex to the DNA in an oxidized environment. © 2018 The Author(s). Published by S. Karger AG, Basel.

Circadian feeding patterns of 12-month-old infants.

PubMed

Wee, Poh Hui; Loy, See Ling; Toh, Jia Ying; Tham, Elaine Kwang Hsia; Cheung, Yin Bun; Godfrey, Keith M; Gluckman, Peter D; Saw, Seang Mei; Chong, Yap-Seng; Lek, Ngee; Chan, Jerry Kok Yen; Goh, Daniel Yam Thiam; Chong, Mary Foong-Fong; Yap, Fabian

2017-06-01

Early life nutrition and feeding practices are important modifiable determinants of subsequent obesity, yet little is known about the circadian feeding pattern of 12-month-old infants. We aimed to describe the 24-h feeding patterns of 12-month-old infants and examine their associations with maternal and infant characteristics. Mothers from a prospective birth cohort study (n 431) reported dietary intakes of their 12-month-old infants and respective feeding times using 24-h dietary recall. Based on their feeding times, infants were classified into post-midnight (00.00-05.59 hours) and pre-midnight (06.00-23.59 hours) feeders. Mean daily energy intake was 3234 (sd 950) kJ (773 (sd 227) kcal), comprising 51·8 (sd 7·8) % carbohydrate, 33·9 (sd 7·2) % fat and 14·4 (sd 3·2) % protein. Mean hourly energy intake and proportion of infants fed were lower during post-midnight than pre-midnight hours. There were 251 (58·2 %) pre-midnight and 180 (41·8 %) post-midnight feeders. Post-midnight feeders consumed higher daily energy, carbohydrate, fat and protein intakes than pre-midnight feeders (all P<0·001). The difference in energy intake originated from energy content consumed during the post-midnight period. Majority (n 173) of post-midnight feeders consumed formula milk during the post-midnight period. Using multivariate logistic regression with confounder adjustment, exclusively breast-feeding during the first 6 months of life was negatively associated with post-midnight feeding at 12 months (adjusted OR 0·31; 95 % CI 0·11, 0·82). This study provides new insights into the circadian pattern of energy intake during infancy. Our findings indicated that the timing of feeding at 12 months was associated with daily energy and macronutrient intakes, and feeding mode during early infancy.

A synoptic approach to weather conditions discloses a relationship with ambulatory blood pressure in hypertensives.

PubMed

Morabito, Marco; Crisci, Alfonso; Orlandini, Simone; Maracchi, Giampiero; Gensini, Gian F; Modesti, Pietro A

2008-07-01

Higher blood pressure (BP) values in cold than in hot months has been documented in hypertensives. These changes may potentially contribute to the observed excess winter cardiovascular mortality. However, the association with weather has always been investigated by considering the relationship with a single variable rather than considering the combination of ground weather variables characterizing a specific weather pattern (air mass (AM)). We retrospectively investigate in Florence (Italy) the relationship between BP and specific AMs in hypertensive subjects (n = 540) referred to our Hypertension Unit for 24-h ambulatory BP monitoring during the period of the year characterized by the highest weather variability (winter). Five different winter daily AMs were classified according to the combination of ground weather data (air temperature, cloud cover, relative humidity, atmospheric pressure, wind speed, and direction). Multiple variable analysis selected the AM as a significant predictor of mean 24-h BP (P < 0.01 for diastolic BP (DBP) and P < 0.05 for systolic BP (SBP)), daytime DBP (P < 0.001) and nighttime BP (P < 0.01 for both SBP and DBP), with higher BP values observed in cyclonic (unstable, cloudy, and mild weather) than in anticyclonic (settled, cloudless, and cold weather) days. When the association with 2-day sequences of AMs was considered, an increase in ambulatory BP followed a sudden day-to-day change of weather pattern going from anticyclonic to cyclonic days. The weather considered as a combination of different weather variables may affect BP. The forecast of a sudden change of AM could provide important information helpful for hypertensives during winter.

Potency of Melatonin in Living Beings

PubMed Central

Choi, Donchan

2013-01-01

Living beings are surrounded by various changes exhibiting periodical rhythms in environment. The environmental changes are imprinted in organisms in various pattern. The phenomena are believed to match the external signal with organisms in order to increase their survival rate. The signals are categorized into circadian, seasonal, and annual cycles. Among the cycles, the circadian rhythm is regarded as the most important factor because its periodicity is in harmony with the levels of melatonin secreted from pineal gland. Melatonin is produced by the absence of light and its presence displays darkness. Melatonin plays various roles in creatures. Therefore, this review is to introduce the diverse potential ability of melatonin in manifold aspects in living organism. PMID:25949131

Neonatal Alcohol Exposure Permanently Disrupts the Circadian Properties and Photic Entrainment of the Activity Rhythm in Adult Rats

PubMed Central

Allen, Gregg C.; West, James R.; Chen, Wei-Jung A.; Earnest, David J.

2009-01-01

Background Alcohol exposure during the period of rapid brain development produces structural damage in different brain regions, including the suprachiasmatic nucleus (SCN), that may have permanent neurobehavioral consequences. Thus, this study examined the long-term effects of neonatal alcohol exposure on circadian behavioral activity in adult rats. Methods Artificially reared Sprague-Dawley rat pups were exposed to alcohol (EtOH; 4.5 g/kg/day) or isocaloric milk formula (gastrostomy control; GC) on postnatal days 4–9. At 2 months of age, rats from the EtOH, GC, and suckle control (SC) groups were housed individually, and properties of the circadian rhythm in wheel-running behavior were continuously analyzed during exposure to a 12-hr light:12-hr dark photoperiod (LD 12:12) or constant darkness (DD). Results Neonatal alcohol exposure had distinctive effects on the rhythmic properties and quantitative parameters of adult wheel-running behavior. EtOH-treated animals were distinguished by unstable and altered entrainment to LD 12:12 such that their daily onsets of activity were highly variable and occurred at earlier times relative to control animals. In DD, circadian regulation of wheel-running behavior was altered by neonatal alcohol exposure such that the free-running period of the activity rhythm was shorter in EtOH-exposed rats than in control animals. Total amount of daily wheel-running activity in EtOH-treated rats was greater than that observed in the SC group. In addition, the circadian activity patterns of EtOH-exposed rats were fragmented such that the duration of the active phase and the number of activity bouts per day were increased. Conclusions These data indicate that neonatal alcohol exposure produces permanent changes in the circadian regulation of the rat activity rhythm and its entrainment to LD cycles. These long-term alterations in circadian behavior, along with the developmental alcohol-induced changes in SCN endogenous rhythmicity, may have important implications in clinical sleep-wake disturbances observed in neonates, children, and adults exposed to alcohol in utero. PMID:16269914

Possible molecular mechanism underlying cadmium-induced circadian rhythms disruption in zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Bo; Chen, Tian-Ming; Zhong, Yingbin

This study was aimed to explore the mechanisms underlying cadmium-induced circadian rhythms disruption. Two groups of zebrafish larvae treated with or without 5 ppm CdCl{sub 2} were incubated in a photoperiod of 14-h light/10-h dark conditions. The mRNA levels of clock1a, bmal1b, per2 and per1b in two groups were determined. Microarray data were generated in two group of samples. Differential expression of genes were identified and the changes in expression level for some genes were validated by RT-PCR. Finally, Gene Ontology functional and KEGG pathway enrichment analysis of differentially expressed genes (DEGs) were performed. In comparison with normal group, the mRNAmore » levels of clock1a, bmal1b, and per2 were significantly changed and varied over the circadian cycle in CdCl2-treated group. DEGs were obtained from the light (84 h, ZT12) and dark (88 h, ZT16) phase. In addition, G-protein coupled receptor protein signaling pathway and immune response were both enriched by DEGs in both groups. While, proteolysis and amino acid metabolism were found associated with DEGs in light phase, and Neuroactive ligand-receptor interaction and oxidation-reduction process were significantly enriched by DEGs in dark phase. Besides, the expression pattern of genes including hsp70l and or115-11 obtained by RT-PCR were consistent with those obtained by microarray analysis. As a consequence, cadmium could make significant effects on circadian rhythms through immune response and G protein-coupled receptor signaling pathway. Besides, between the dark and the light phase, the mechanism by which cadmium inducing disruption of circadian rhythms were different to some extent. - Highlights: • Cadmium could affect the expression levels of circadian rhythm-related genes. • Genes expression in microarray data were consistent with those in RT-PCR analysis. • Immune response and G protein-coupled receptor signaling pathway were identified. • Cadmium induces circadian rhythm disruption by different mechanism in day and night.« less

Genome-Wide Analysis of SREBP1 Activity around the Clock Reveals Its Combined Dependency on Nutrient and Circadian Signals

PubMed Central

Naldi, Aurélien; Baruchet, Michaël; Canella, Donatella; Le Martelot, Gwendal; Guex, Nicolas; Desvergne, Béatrice; Delorenzi, Mauro; Deplancke, Bart; Desvergne, Béatrice; Guex, Nicolas; Herr, Winship; Naef, Felix; Rougemont, Jacques; Schibler, Ueli; Deplancke, Bart; Guex, Nicolas; Herr, Winship; Guex, Nicolas; Andersin, Teemu; Cousin, Pascal; Gilardi, Federica; Gos, Pascal; Martelot, Gwendal Le; Lammers, Fabienne; Canella, Donatella; Gilardi, Federica; Raghav, Sunil; Fabbretti, Roberto; Fortier, Arnaud; Long, Li; Vlegel, Volker; Xenarios, Ioannis; Migliavacca, Eugenia; Praz, Viviane; Guex, Nicolas; Naef, Felix; Rougemont, Jacques; David, Fabrice; Jarosz, Yohan; Kuznetsov, Dmitry; Liechti, Robin; Martin, Olivier; Delafontaine, Julien; Sinclair, Lucas; Cajan, Julia; Krier, Irina; Leleu, Marion; Migliavacca, Eugenia; Molina, Nacho; Naldi, Aurélien; Rey, Guillaume; Symul, Laura; Guex, Nicolas; Naef, Felix; Rougemont, Jacques; Bernasconi, David; Delorenzi, Mauro; Andersin, Teemu; Canella, Donatella; Gilardi, Federica; Martelot, Gwendal Le; Lammers, Fabienne; Baruchet, Michaël; Raghav, Sunil

2014-01-01

In mammals, the circadian clock allows them to anticipate and adapt physiology around the 24 hours. Conversely, metabolism and food consumption regulate the internal clock, pointing the existence of an intricate relationship between nutrient state and circadian homeostasis that is far from being understood. The Sterol Regulatory Element Binding Protein 1 (SREBP1) is a key regulator of lipid homeostasis. Hepatic SREBP1 function is influenced by the nutrient-response cycle, but also by the circadian machinery. To systematically understand how the interplay of circadian clock and nutrient-driven rhythm regulates SREBP1 activity, we evaluated the genome-wide binding of SREBP1 to its targets throughout the day in C57BL/6 mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding pattern. In particular, different expression phases were observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. Binding sites for Hepatocyte Nuclear Factor 4 (HNF4) were specifically enriched in the close proximity of SREBP1 peaks of genes, whose expression was shifted by about 8 hours with respect to SREBP1 binding. Thus, the cross-talk between hepatic HNF4 and SREBP1 may underlie the expression timing of this subgroup of SREBP1 targets. Interestingly, the proper temporal expression profile of these genes was dramatically changed in Bmal1 −/− mice upon time-restricted feeding, for which a rhythmic, but slightly delayed, binding of SREBP1 was maintained. Collectively, our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity, strongly dependent from the circadian clock, exists. This system allows us to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved. PMID:24603613

Global Profiling of Rice and Poplar Transcriptomes Highlights Key Conserved Circadian-Controlled Pathways and cis-Regulatory Modules

PubMed Central

Filichkin, Sergei A.; Breton, Ghislain; Priest, Henry D.; Dharmawardhana, Palitha; Jaiswal, Pankaj; Fox, Samuel E.; Michael, Todd P.; Chory, Joanne; Kay, Steve A.; Mockler, Todd C.

2011-01-01

Background Circadian clocks provide an adaptive advantage through anticipation of daily and seasonal environmental changes. In plants, the central clock oscillator is regulated by several interlocking feedback loops. It was shown that a substantial proportion of the Arabidopsis genome cycles with phases of peak expression covering the entire day. Synchronized transcriptome cycling is driven through an extensive network of diurnal and clock-regulated transcription factors and their target cis-regulatory elements. Study of the cycling transcriptome in other plant species could thus help elucidate the similarities and differences and identify hubs of regulation common to monocot and dicot plants. Methodology/Principal Findings Using a combination of oligonucleotide microarrays and data mining pipelines, we examined daily rhythms in gene expression in one monocotyledonous and one dicotyledonous plant, rice and poplar, respectively. Cycling transcriptomes were interrogated under different diurnal (driven) and circadian (free running) light and temperature conditions. Collectively, photocycles and thermocycles regulated about 60% of the expressed nuclear genes in rice and poplar. Depending on the condition tested, up to one third of oscillating Arabidopsis-poplar-rice orthologs were phased within three hours of each other suggesting a high degree of conservation in terms of rhythmic gene expression. We identified clusters of rhythmically co-expressed genes and searched their promoter sequences to identify phase-specific cis-elements, including elements that were conserved in the promoters of Arabidopsis, poplar, and rice. Conclusions/Significance Our results show that the cycling patterns of many circadian clock genes are highly conserved across poplar, rice, and Arabidopsis. The expression of many orthologous genes in key metabolic and regulatory pathways is diurnal and/or circadian regulated and phased to similar times of day. Our results confirm previous findings in Arabidopsis of three major classes of cis-regulatory modules within the plant circadian network: the morning (ME, GBOX), evening (EE, GATA), and midnight (PBX/TBX/SBX) modules. Identification of identical overrepresented motifs in the promoters of cycling genes from different species suggests that the core diurnal/circadian cis-regulatory network is deeply conserved between mono- and dicotyledonous species. PMID:21694767

Ambulatory (24 h) blood pressure and arterial stiffness measurement in Marfan syndrome patients: a case control feasibility and pilot study.

PubMed

Hillebrand, Matthias; Nouri, Ghazaleh; Hametner, Bernhard; Parragh, Stephanie; Köster, Jelena; Mortensen, Kai; Schwarz, Achim; von Kodolitsch, Yskert; Wassertheurer, Siegfried

2016-05-06

The aim of this work is the investigation of measures of ambulatory brachial and aortic blood pressure and indices of arterial stiffness and aortic wave reflection in Marfan patients. A case-control study was conducted including patients with diagnosed Marfan syndrome following Ghent2 nosology and healthy controls matched for sex, age and daytime brachial systolic blood pressure. For each subject a 24 h ambulatory blood pressure and 24 h pulse wave analysis measurement was performed. All parameters showed a circadian pattern whereby pressure dipping was more pronounced in Marfan patients. During daytime only Marfan patients with aortic root surgery showed increased pulse wave velocity. In contrast, various nighttime measurements, wave reflection determinants and circadian patterns showed a significant difference. The findings of our study provide evidence that ambulatory measurement of arterial stiffness parameters is feasible and that these determinants are significantly different in Marfan syndrome patients compared to controls in particular at nighttime. Further investigation is therefore indicated.

Simultaneous monitoring of independent gene expression patterns in two types of cocultured fibroblasts with different color-emitting luciferases

PubMed Central

Noguchi, Takako; Ikeda, Masaaki; Ohmiya, Yoshihiro; Nakajima, Yoshihiro

2008-01-01

Background Luciferase assay systems enable the real-time monitoring of gene expression in living cells. We have developed a dual-color luciferase assay system in which the expression of multiple genes can be tracked simultaneously using green- and red-emitting beetle luciferases. We have applied the system to monitoring independent gene expressions in two types of cocultured fibroblasts in real time. Results Two Rat-1 cell lines were established that stably express either green- or red-emitting luciferases under the control of the mBmal1 promoter, a canonical clock gene. We cocultured these cell lines, and gene expression profiles in both were monitored simultaneously. The circadian rhythms of these cell lines are independent, oscillating following their intrinsic circadian phases, even when cocultured. Furthermore, the independent rhythms were synchronized by medium change as an external stimulus. Conclusion Using this system, we successfully monitored independent gene expression patterns in two lines of cocultured fibroblasts. PMID:18416852

Blood Pressure and Cerebral White Matter Share Common Genetic Factors in Mexican-Americans

PubMed Central

Kochunov, Peter; Glahn, David C; Lancaster, Jack; Winkler, Anderson; Karlsgodt, Kathrin; Olvera, Rene L; Curran, Joanna E; Carless, Melanie A; Dyer, Thomas D; Almasy, Laura; Duggirala, Ravi; Fox, Peter T; Blangero, John

2010-01-01

Elevated arterial pulse pressure (PP) and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially due to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy (FA) of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican-Americans. The patterns of whole-brain and regional genetic overlap between BP and FA were interpreted in the context the pulse-wave encephalopathy (PWE) theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7×1.7×3mm, 55 directions) diffusion tensor imaging (DTI) data were analyzed for 332 (202 females; mean age=47.9±13.3years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements [PP, systolic (SBP) and diastolic (DBP)] and FA (whole-brain and regional values). Intersubject variance in PP and SBP exhibited a significant genetic overlap with variance in whole-brain FA values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=−.75, p=0.01). The pattern of genetic overlap between BP and WM integrity was generally in-agreement with the PWE theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development suggesting a possible role for genotype-by-age interactions. PMID:21135356

Chronic Artificial Blue-Enriched White Light Is an Effective Countermeasure to Delayed Circadian Phase and Neurobehavioral Decrements

PubMed Central

Najjar, Raymond P.; Wolf, Luzian; Taillard, Jacques; Schlangen, Luc J. M.; Salam, Alex

2014-01-01

Studies in Polar Base stations, where personnel have no access to sunlight during winter, have reported circadian misalignment, free-running of the sleep-wake rhythm, and sleep problems. Here we tested light as a countermeasure to circadian misalignment in personnel of the Concordia Polar Base station during the polar winter. We hypothesized that entrainment of the circadian pacemaker to a 24-h light-dark schedule would not occur in all crew members (n = 10) exposed to 100–300 lux of standard fluorescent white (SW) light during the daytime, and that chronic non-time restricted daytime exposure to melanopsin-optimized blue-enriched white (BE) light would establish an a stable circadian phase, in participants, together with increased cognitive performance and mood levels. The lighting schedule consisted of an alternation between SW lighting (2 weeks), followed by a BE lighting (2 weeks) for a total of 9 weeks. Rest-activity cycles assessed by actigraphy showed a stable rest-activity pattern under both SW and BE light. No difference was found between light conditions on the intra-daily stability, variability and amplitude of activity, as assessed by non-parametric circadian analysis. As hypothesized, a significant delay of about 30 minutes in the onset of melatonin secretion occurred with SW, but not with BE light. BE light significantly enhanced well being and alertness compared to SW light. We propose that the superior efficacy of blue-enriched white light versus standard white light involves melanopsin-based mechanisms in the activation of the non-visual functions studied, and that their responses do not dampen with time (over 9-weeks). This work could lead to practical applications of light exposure in working environment where background light intensity is chronically low to moderate (polar base stations, power plants, space missions, etc.), and may help design lighting strategies to maintain health, productivity, and personnel safety. PMID:25072880

Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis.

PubMed

Manoharan, Shanmugam; Panjamurthy, Kuppusamy; Balakrishnan, Subramanian; Vasudevan, Kalaiarasan; Vellaichamy, Lakshmanan

2009-01-01

Circadian time-dependent treatment with chemotherapeutic drugs (chronotherapy) optimizes the therapeutic index by maximizing treatment efficacy and minimizing toxicity. The circadian time-dependent chemopreventive and anti-lipid peroxidative efficacy of withaferin-A in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis was investigated in the present study. We induced oral squamous cell carcinoma in the buccal pouches of golden Syrian hamsters during the day (4:00, 8:00, 12:00, 16:00, 20:00 and 24:00) by application of DMBA three times per week for 14 weeks. The circadian time-dependent tumor incidence, volume and burden were observed in hamsters treated with either DMBA alone or DMBA + withaferin-A. The circadian pattern of lipid peroxidation by-products, as measured by the formation of thiobarbituric acid reactive substances (TBARS) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], was also analyzed in the buccal mucosa of DMBA-treated hamsters. We found the highest incidence of tumor formation at 24.00 h in hamsters treated with DMBA alone as compared to other experimental groups. Circadian dysregulation of lipid peroxidation and antioxidant status was observed in DMBA-treated animals as compared to control animals. Oral (po) administration of withaferin-A (20 mg/kg) completely prevented the formation of tumors between 8.00 h and 12.00 h and synchronized the status of lipid peroxidation and antioxidants in the buccal mucosa of hamsters treated with DMBA alone. Also, oral administration of withaferin-A to DMBA-treated animals significantly reduced the formation of tumors and synchronized the status of lipid peroxidation and antioxidants in the rest of the time intervals. Our study thus suggests that withaferin-A has significant chemopreventive and anti-lipid peroxidative potential in DMBA-induced oral carcinogenesis, probably by interfering with DMBA-induced abnormal cell proliferation in the buccal mucosa.

A circadian rhythm of conidiation in Neurospora crassa (L-12)

NASA Technical Reports Server (NTRS)

Miyoshi, Yashuhiro

1993-01-01

Two fungi growth chambers containing six growth tubes each are used in this experiment. One chamber is for the space experiment; the other is for the simultaneous ground control experiment. The hyphae of Neurospora crassa band A mutant are inoculated at one end of each tube. Both the chambers are kept at 3 C plus or minus 1.5 C to stop hyphae growth until the Spacelab is activated. After the activation, each chamber is transferred simultaneously to the Spacelab and a phytotron in KSC and kept in continuous light at the same temperature. After about 24 hours of light exposure, each chamber is inserted into a growth chamber bag to keep it in constant darkness. The circadian rhythm of conidiation is initiated by this light to dark transition. After the dark incubation for 5 days at room temperature, both the growth chambers are kept at 3 C plus or minus 1.5 C to stop growth of the hyphae. After the space shuttle lands, both conidiation patterns are compared and analyzed. It has been known that numerous physiological phenomena show circadian rhythms. They are characterized by the fact that the oscillation can persist under constant conditions of light and temperature. Therefore, it has been accepted by most investigators that the generation mechanism of the circadian rhythm is endogeneous. However, one cannot reject the possibility that these rhythms are caused by some geophysical exogeneous factor having a 24-hour period, such as atmospheric pressure, gravity, or electromagnetic radiation. We use Neurospora crassa band A mutual which shows an obvious circadian rhythm in its spore-forming (conidiation) on the ground, and we intend to attempt the conidation of this mutant in the Spacelab where 24-hour periodicity is severely attenuated and to elucidate the effect of the geophysical exogeneous factor in the generation mechanism of the circadian rhythm.

Cocaine Modulates Mammalian Circadian Clock Timing by Decreasing Serotonin Transport in the SCN

PubMed Central

Prosser, Rebecca A.; Stowie, Adam; Amicarelli, Mario; Nackenoff, Alex G.; Blakely, Randy D.; Glass, J. David

2014-01-01

Cocaine abuse disrupts reward and homeostatic processes through diverse processes, including those involved in circadian clock regulation. Recently we showed that cocaine administration to mice disrupts nocturnal photic phase resetting of the suprachiasmatic (SCN) circadian clock, whereas administration during the day induces non-photic phase shifts. Importantly, the same effects are seen when cocaine is applied to the SCN in vitro, where it blocks photic-like (glutamate-induced) phase shifts at night and induces phase advances during the day. Furthermore, our previous data suggest that cocaine acts in the SCN by enhancing serotonin (5-HT) signaling. For example, the in vitro actions of cocaine mimic those of 5-HT and are blocked by the 5-HT antagonist, metergoline, but not the dopamine receptor antagonist, fluphenazine. Although our data are consistent with cocaine acting through enhance 5-HT signaling, the nonselective actions of cocaine as an antagonist of monoamine transporters raises the question of whether inhibition of the 5-HT transporter (SERT) is key to its circadian effects. Here we investigate this issue using transgenic mice expressing a SERT that exhibits normal 5-HT recognition and transport but significantly reduced cocaine potency (SERT Met172). Circadian patterns of SCN behavioral and neuronal activity did not differ between WT and SERT Met172 mice, nor did they differ in the ability of the 5-HT1A,2,7 receptor agonist, 8-OH-DPAT to reset SCN clock phase, consistent with the normal SERT expression and activity in the transgenic mice. However, 1) cocaine administration does not induce phase advances when administered in vivo or in vitro in SERT Met172 mice; 2) cocaine does not block photic or glutamate-induced (phase shifts in SERT Met172 mice; and 3) cocaine does not induce long-term changes in free-running period in SERT Met172 mice. We conclude that SERT antagonism is required for the phase shifting of the SCN circadian clock induced by cocaine. PMID:24950119

Early sound patterns in the speech of two Brazilian Portuguese speakers.

PubMed

Teixeira, Elizabeth Reis; Davis, Barbara L

2002-06-01

Sound patterns in the speech of two Brazilian-Portuguese speaking children are compared with early production patterns in English-learning children as well as English and Brazilian-Portuguese (BP) characteristics. The relationship between production system effects and ambient language influences in the acquisition of early sound patterns is of primary interest, as English and BP are characterized by differing phonological systems. Results emphasize the primacy of production system effects in early acquisition, although even the earliest word forms show evidence of perceptual effects from the ambient language in both BP children. Use of labials and coronals and low and midfront vowels in simple syllable shapes is consistent with acquisition data for this period across languages. However, potential ambient language influences include higher frequencies of dorsals, use of multisyllabic words, and different phone types in syllable-offset position. These results suggest that to fully understand early acquisition of sound systems one must account for both production system effects and perceptual effects from the ambient language.

Tailored lighting intervention improves measures of sleep, depression, and agitation in persons with Alzheimer’s disease and related dementia living in long-term care facilities

PubMed Central

Figueiro, Mariana G; Plitnick, Barbara A; Lok, Anna; Jones, Geoffrey E; Higgins, Patricia; Hornick, Thomas R; Rea, Mark S

2014-01-01

Background Light therapy has shown great promise as a nonpharmacological method to improve symptoms associated with Alzheimer’s disease and related dementias (ADRD), with preliminary studies demonstrating that appropriately timed light exposure can improve nighttime sleep efficiency, reduce nocturnal wandering, and alleviate evening agitation. Since the human circadian system is maximally sensitive to short-wavelength (blue) light, lower, more targeted lighting interventions for therapeutic purposes, can be used. Methods The present study investigated the effectiveness of a tailored lighting intervention for individuals with ADRD living in nursing homes. Low-level “bluish-white” lighting designed to deliver high circadian stimulation during the daytime was installed in 14 nursing home resident rooms for a period of 4 weeks. Light–dark and rest–activity patterns were collected using a Daysimeter. Sleep time and sleep efficiency measures were obtained using the rest–activity data. Measures of sleep quality, depression, and agitation were collected using standardized questionnaires, at baseline, at the end of the 4-week lighting intervention, and 4 weeks after the lighting intervention was removed. Results The lighting intervention significantly (P<0.05) decreased global sleep scores from the Pittsburgh Sleep Quality Index, and increased total sleep time and sleep efficiency. The lighting intervention also increased phasor magnitude, a measure of the 24-hour resonance between light–dark and rest–activity patterns, suggesting an increase in circadian entrainment. The lighting intervention significantly (P<0.05) reduced depression scores from the Cornell Scale for Depression in Dementia and agitation scores from the Cohen–Mansfield Agitation Inventory. Conclusion A lighting intervention, tailored to increase daytime circadian stimulation, can be used to increase sleep quality and improve behavior in patients with ADRD. The present field study, while promising for application, should be replicated using a larger sample size and perhaps using longer treatment duration. PMID:25246779

A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

PubMed

Nolasco, Nahum; Juárez, Claudia; Morgado, Elvira; Meza, Enrique; Caba, Mario

2012-01-01

Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h) or day (10:00 h), and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

Cross-correlation of instantaneous phase increments in pressure-flow fluctuations: Applications to cerebral autoregulation

NASA Astrophysics Data System (ADS)

Chen, Zhi; Hu, Kun; Stanley, H. Eugene; Novak, Vera; Ivanov, Plamen Ch.

2006-03-01

We investigate the relationship between the blood flow velocities (BFV) in the middle cerebral arteries and beat-to-beat blood pressure (BP) recorded from a finger in healthy and post-stroke subjects during the quasisteady state after perturbation for four different physiologic conditions: supine rest, head-up tilt, hyperventilation, and CO2 rebreathing in upright position. To evaluate whether instantaneous BP changes in the steady state are coupled with instantaneous changes in the BFV, we compare dynamical patterns in the instantaneous phases of these signals, obtained from the Hilbert transform, as a function of time. We find that in post-stroke subjects the instantaneous phase increments of BP and BFV exhibit well-pronounced patterns that remain stable in time for all four physiologic conditions, while in healthy subjects these patterns are different, less pronounced, and more variable. We propose an approach based on the cross-correlation of the instantaneous phase increments to quantify the coupling between BP and BFV signals. We find that the maximum correlation strength is different for the two groups and for the different conditions. For healthy subjects the amplitude of the cross-correlation between the instantaneous phase increments of BP and BFV is small and attenuates within 3-5 heartbeats. In contrast, for post-stroke subjects, this amplitude is significantly larger and cross-correlations persist up to 20 heartbeats. Further, we show that the instantaneous phase increments of BP and BFV are cross-correlated even within a single heartbeat cycle. We compare the results of our approach with three complementary methods: direct BP-BFV cross-correlation, transfer function analysis, and phase synchronization analysis. Our findings provide insight into the mechanism of cerebral vascular control in healthy subjects, suggesting that this control mechanism may involve rapid adjustments (within a heartbeat) of the cerebral vessels, so that BFV remains steady in response to changes in peripheral BP.

Cross-correlation of instantaneous phase increments in pressure-flow fluctuations: applications to cerebral autoregulation.

PubMed

Chen, Zhi; Hu, Kun; Stanley, H Eugene; Novak, Vera; Ivanov, Plamen Ch

2006-03-01

We investigate the relationship between the blood flow velocities (BFV) in the middle cerebral arteries and beat-to-beat blood pressure (BP) recorded from a finger in healthy and post-stroke subjects during the quasisteady state after perturbation for four different physiologic conditions: supine rest, head-up tilt, hyperventilation, and CO2 rebreathing in upright position. To evaluate whether instantaneous BP changes in the steady state are coupled with instantaneous changes in the BFV, we compare dynamical patterns in the instantaneous phases of these signals, obtained from the Hilbert transform, as a function of time. We find that in post-stroke subjects the instantaneous phase increments of BP and BFV exhibit well-pronounced patterns that remain stable in time for all four physiologic conditions, while in healthy subjects these patterns are different, less pronounced, and more variable. We propose an approach based on the cross-correlation of the instantaneous phase increments to quantify the coupling between BP and BFV signals. We find that the maximum correlation strength is different for the two groups and for the different conditions. For healthy subjects the amplitude of the cross-correlation between the instantaneous phase increments of BP and BFV is small and attenuates within 3-5 heartbeats. In contrast, for post-stroke subjects, this amplitude is significantly larger and cross-correlations persist up to 20 heartbeats. Further, we show that the instantaneous phase increments of BP and BFV are cross-correlated even within a single heartbeat cycle. We compare the results of our approach with three complementary methods: direct BP-BFV cross-correlation, transfer function analysis, and phase synchronization analysis. Our findings provide insight into the mechanism of cerebral vascular control in healthy subjects, suggesting that this control mechanism may involve rapid adjustments (within a heartbeat) of the cerebral vessels, so that BFV remains steady in response to changes in peripheral BP.

Gestational dietary patterns are not associated with blood pressure changes during pregnancy and early postpartum in a Brazilian prospective cohort.

PubMed

Eshriqui, Ilana; Vilela, Ana Amélia Freitas; Rebelo, Fernanda; Farias, Dayana Rodrigues; Castro, Maria Beatriz Trindade; Kac, Gilberto

2016-02-01

To identify gestational dietary patterns and evaluate the association between these patterns and the blood pressure (BP) rate of change during pregnancy and the postpartum. Prospective cohort study composed of 191 healthy pregnant women. Systolic BP (SBP) and diastolic BP (DBP) were obtained at the 5th-13th, 20th-26th, 30th-36th gestational weeks, and with 30-45 days postpartum. A food frequency questionnaire administered at the 30th-36th gestational week was used to measure dietary intake during pregnancy. Principal component analysis was performed to identify the dietary patterns. A longitudinal linear mixed-effects regression model was used to evaluate the association between the dietary patterns and BP (adjusted for time elapsed after conception and the women's age, education, parity, body mass index and total energy intake). Three gestational dietary patterns were identified: healthy, common-Brazilian and processed. SBP/DBP mean values (SD) were 110.1 (9.0)/66.9 (7.5), 108.7 (9.0)/64.9 (6.7), 111.3 (9.2)/67.0 (6.9) and 115.0 (10.7)/73.7 (8.6) mmHg at the first, second and third gestational trimesters and postpartum, respectively. Women with higher/lower adherence to the processed pattern presented SBP of 117.9 and 113.0 mmHg (P = 0.037), respectively, during postpartum. No association was found between any of the three dietary patterns and SBP in the multiple longitudinal linear regression models, whereas 1 SD increase in the common-Brazilian pattern was associated with a small change of DBP (β = 0.0006; 95% CI 4.66e-06, 0.001; P = 0.048). The three dietary patterns identified revealed no association with changes of SBP and DBP levels during pregnancy and at early postpartum in this sample of healthy Brazilian women.

Sleep patterning and behaviour in cats with pontine lesions creating REM without atonia.

PubMed

Sanford; Morrison; Mann; Harris; Yoo; Ross

1994-12-01

Lesions of the dorsal pontine tegmentum release muscle tone and motor behaviour, much of it similar to orienting during wakefulness, into rapid eye movement sleep (REM), a state normally characterized by paralysis. Sleep after pontine lesions may be altered, with more REM-A episodes of shorter duration compared to normal REM. We examined behaviour, ponto-geniculo-occipital (PGO) waves (which may be central markers of orienting) and sleep in lesioned cats: (i) to characterize the relationship of PGO waves to behaviour in REM-A; (ii) to determine whether post-lesion changes in the timing and duration of REM-A episodes were due to activity-related awakenings: and (iii) to determine whether alterations in sleep changed the circadian sleep/wake cycle in cats. Behavioural release in REM-A was generally related to episode length, but episode length was not necessarily shorter than normal REM in cats capable of full locomotion in REM-A. PGO wave frequency was reduced overall during REM-A, but was higher during REM-A with behaviour than during quiet REM-A without overt behaviour. Pontine lesions did not significantly alter the circadian sleep/wake cycle: REM-A had approximately the same Light/Dark distribution as normal REM. Differences in the patterning of normal REM and REM-A within sleep involve more than mere movement-induced awakenings. Brainstem lesions that eliminate the atonia of REM may damage neural circuitry involved in REM initiation and maintenance; this circuitry is separate from circadian control mechanisms.

Treating hypertension with a device that slows and regularises breathing: a randomised, double-blind controlled study.

PubMed

Schein, M H; Gavish, B; Herz, M; Rosner-Kahana, D; Naveh, P; Knishkowy, B; Zlotnikov, E; Ben-Zvi, N; Melmed, R N

2001-04-01

To examine the efficacy of a new device, which slows and regularises breathing, as a non-pharmacological treatment of hypertension and thus to evaluate the contribution of breathing modulation in the blood pressure (BP) reduction. Randomised, double-blind controlled study, carried out in three urban family practice clinics in Israel. Sixty-five male and female hypertensives, either receiving antihypertensive drug therapy or unmedicated. Four patients dropped out at the beginning of the study. Self treatment at home, 10 minutes daily for 8 consecutive weeks, using either the device (n = 32), which guides the user towards slow and regular breathing using musical sound patterns, or a Walkman, with which patients listened to quiet music (n = 29). Medication was unchanged 2 months prior to and during the study period. Systolic BP, diastolic BP and mean arterial pressure (MAP) changes from baseline. BP reduction in the device group was significantly greater than a predetermined 'clinically meaningful threshold' of 10.0, 5.0 and 6.7 mm Hg for the systolic BP, diastolic BP and MAP respectively (P = 0.035, P = 0.0002 and P = 0.001). Treatment with the device reduced systolic BP, diastolic BP and MAP by 15.2, 10.0 and 11.7 mm Hg respectively, as compared to 11.3, 5.6 and 7.5 mm Hg (P = 0.14, P = 0.008, P = 0.03) with the Walkman. Six months after treatment had stopped, diastolic BP reduction in the device group remained greater than the 'threshold' (P < 0.02) and also greater than in the walkman group (P = 0.001). The device was found to be efficacious in reducing high BP during 2 months of self-treatment by patients at home. Breathing pattern modification appears to be an important component in this reduction.

Trajectories of Childhood Blood Pressure and Adult Left Ventricular Hypertrophy: The Bogalusa Heart Study.

PubMed

Zhang, Tao; Li, Shengxu; Bazzano, Lydia; He, Jiang; Whelton, Paul; Chen, Wei

2018-07-01

This longitudinal study aims to characterize longitudinal blood pressure (BP) trajectories from childhood and examine the impact of level-independent childhood BP trajectories on adult left ventricular hypertrophy (LVH) and remodeling patterns. The longitudinal cohort consisted of 1154 adults (787 whites and 367 blacks) who had repeated measurements of BP 4 to 15 times from childhood (4-19 years) to adulthood (20-51 years) and assessment of echocardiographic LV dimensions in adulthood. Model-estimated levels and linear slopes of BP at childhood age points were calculated in 1-year intervals using the growth curve parameters and their first derivatives, respectively. Linear and nonlinear curve parameters of BP showed significant race and sex differences from age 15 years onwards. Adults with LVH had higher long-term BP levels than adults with normal LVM in race-sex groups. Linear and nonlinear slope parameters of BP differed consistently and significantly between LVH and normal groups. Associations of level-independent linear slopes of systolic BP with adult LVH were significantly inverse (odds ratio=0.75-0.82; P =0.001-0.015) in preadolescent children of 4 to 9 years but significantly positive (odds ratio=1.29-1.46; P =0.001-0.008) in adolescents of 13 to 19 years, adjusting for covariates. These associations were consistent across race-sex groups. Of note, the association of childhood BP linear slopes with concentric LVH was significantly stronger than that with eccentric LVH during the adolescence period of 12 to 19 years. These observations indicate that the impact of BP trajectories on adult LVH and geometric patterns originates in childhood. Adolescence is a crucial period for the development of LVH in later life, which has implications for early prevention. © 2018 American Heart Association, Inc.

Morningness-eveningness, sex, and the Alternative Five Factor Model of personality.

PubMed

Muro, Anna; Gomà-i-Freixanet, Montserrat; Adan, Ana

2009-08-01

Recent research on personality and circadian typology indicates that evening-type subjects are more extraverted, impulsive, and novelty-seeking, while morning ones tend to be more introverted, conscientious, agreeable, and emotionally stable. The purpose of this study was to examine the differences between circadian typologies on the Zuckerman's Alternative Five Factor Model of personality (AFFM), which has a strong biological basis, controlling for sex and age. A sample of 533 university students (168 men) participated in the study. Results showed that morning-type subjects had significant higher scores than evening-type and neither-type subjects in Activity, and in its subscales General Activity and Work Activity. A significant interaction between circadian typology and sex was found for Neuroticism-Anxiety: morning-type men showed higher scores than evening-type and neither-type, who had the lowest scores. Women presented the opposite pattern: neither-type obtained the highest scores, while morning-type showed the lowest. This is the first time the AFFM has been used in the context of circadian rhythms research. The results suggest that activity is the only trait related to extraversion associated with morningness, while Neuroticism-Anxiety was modulated by sex. These results might help highlight previous results on the association between morningness-eveningness and other models of personality assessment, and they offer new data that calls for further research.

Circadian, day-of-week, and seasonal variability in myocardial infarction: comparison between working and retired patients.

PubMed

Spielberg, C; Falkenhahn, D; Willich, S N; Wegscheider, K; Völler, H

1996-09-01

The circadian, day-of-week, and seasonal distributions of acute myocardial infarction and its association with the patients' working status were analyzed in a regionally defined population (n = 103, 322) monitored from 1980 to 1988. Included were 2906 consecutive patients (1746 [60.1%] men and 1160 [39.9%] women; mean age 67.8 years) with confirmed diagnosis (by standardized diagnostic criteria in hospitalized patients and autopsy results in out-of-hospital deaths). The time of myocardial infarction on the basis of onset of symptoms was known in 1901 cases. Myocardial infarction occurred more frequently (p < 0.05) during the morning from 7:00 to 10:00 AM, on Mondays, and during the winter from January to March compared with other times of day, days of the week, and seasons. Compared with retired patients, working patients (32%) had a second circadian peak, in the afternoon at 4:00 PM (p < 0.05), and a trend toward an additional seasonal peak in September (p value not significant), whereas the day-of-week pattern was similar in the two subgroups. The occurrence of myocardial infarction demonstrates marked circadian, day-of-week, and seasonal variations, with some differences between working and retired patients. Further investigation of possible triggering events may aid in identifying underlaying mechanisms and perhaps in improving prevention of the disease.

Subjective alertness rhythms in elderly people

NASA Technical Reports Server (NTRS)

Monk, T. H.; Buysse, D. J.; Reynolds, C. F. 3rd; Kupfer, D. J.; Houck, P. R.

1996-01-01

The aim of this study was to evaluate age-related changes in the circadian rhythm of subjective alertness and to explore the circadian mechanisms underlying such changes. Using a visual analogue scale (VAS) instrument, 25 older men and women (71 y and older; 15 female, 10 male) rated their subjective alertness about 7 times per day during 5 baseline days of temporal isolation during which habitual bedtimes and waketimes were enforced. Comparisons were made with 13 middle-aged men (37-52 y) experiencing the same protocol. Advancing age (particularly in the men) resulted in less rhythmic alertness patterns, as indicated by lower amplitudes and less reliability of fitted 24-h sinusoids. This appeared in spite of the absence of any reliable age-related diminution in circadian temperature rhythm amplitude, thus suggesting the effect was not due to SCN weakness per se, but to weakened transduction of SCN output. In a further experiment, involving 36 h of constant wakeful bedrest, differences in the amplitude of the alertness rhythm were observed between 9 older men (79 y+), 7 older women (79 y+), and 17 young controls (9 males, 8 females, 19-28 y) suggesting that with advancing age (particularly in men) there is less rhythmic input into subjective alertness from the endogenous circadian pacemaker. These results may explain some of the nocturnal insomnia and daytime hypersomnia that afflict many elderly people.

Influence of temperature on the liver circadian clock in the ruin lizard Podarcis sicula.

PubMed

Malatesta, Manuela; Frigato, Elena; Baldelli, Beatrice; Battistelli, Serafina; Foà, Augusto; Bertolucci, Cristiano

2007-07-01

Reptiles represent an interesting animal model to investigate the influence of temperature on molecular circadian clocks. The ruin lizard Podarcis sicula lives in a continental climate and it is subjected to wide range of environmental temperatures during the course of the year. As consequence, ruin lizard daily activity pattern includes either the hibernation or periods of inactivity determined by hypothermia. Here we showed the rhythmic expression of two clock genes, lPer2 and lClock, in the liver of active lizards exposed to summer photo-thermoperiodic conditions. Interestingly, the exposition of lizards to hypothermic conditions, typical of winter season, induced a strong dampening of clock genes mRNA rhythmicity with a coincident decrease of levels. We also examined the qualitative and quantitative distribution of lPER2 and lCLOCK protein in different cellular compartments during the 24-h cycle. In the liver of active lizards both proteins showed a rhythmic expression profile in all cellular compartments. After 3 days at 6 degrees C, some temporal fluctuations of the lCLOCK and lPER2 are still detectable, although, with some marked modifications in respect to the values detected in the liver of active lizards. Besides demonstrating the influence of low temperature on the lizard liver circadian oscillators, present results could provide new essential information for comparative studies on the influence of temperature on the circadian system across vertebrate classes.

The Circadian Clock Modulates Global Daily Cycles of mRNA Ribosome Loading[OPEN

PubMed Central

Missra, Anamika; Ernest, Ben; Jia, Qidong; Ke, Kenneth

2015-01-01

Circadian control of gene expression is well characterized at the transcriptional level, but little is known about diel or circadian control of translation. Genome-wide translation state profiling of mRNAs in Arabidopsis thaliana seedlings grown in long day was performed to estimate ribosome loading per mRNA. The experiments revealed extensive translational regulation of key biological processes. Notably, translation of mRNAs for ribosomal proteins and mitochondrial respiration peaked at night. Central clock mRNAs are among those subject to fluctuations in ribosome loading. There was no consistent phase relationship between peak translation states and peak transcript levels. The overlay of distinct transcriptional and translational cycles can be expected to alter the waveform of the protein synthesis rate. Plants that constitutively overexpress the clock gene CCA1 showed phase shifts in peak translation, with a 6-h delay from midnight to dawn or from noon to evening being particularly common. Moreover, cycles of ribosome loading that were detected under continuous light in the wild type collapsed in the CCA1 overexpressor. Finally, at the transcript level, the CCA1-ox strain adopted a global pattern of transcript abundance that was broadly correlated with the light-dark environment. Altogether, these data demonstrate that gene-specific diel cycles of ribosome loading are controlled in part by the circadian clock. PMID:26392078

Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio)

NASA Astrophysics Data System (ADS)

Zhao, Yanbin; Fent, Karl

2016-02-01

Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals.

Real World Home Blood Pressure Variability in Over 56,000 Individuals With Nearly 17 Million Measurements.

PubMed

Kim, Kwang-Il; Nikzad, Nima; Quer, Giorgio; Wineinger, Nathan E; Vegreville, Matthieu; Normand, Alexis; Schmidt, Nicolas; Topol, Eric J; Steinhubl, Steven

2018-04-13

Using the data from 56,365 individuals, from 185 countries, and a Nokia Health Wireless blood pressure (BP) monitor, we investigated real-world characteristics of BP variability (BPV). All included individuals self-measured and uploaded their BP using Bluetooth at least 20 times over a period of ≥1 month at a frequency and duration of their choosing. In total, 16,904,844 BP measurements were analyzed, with a median of 146 measurements per person (interquartile range [IQR] 73-321) over a median of 14 months (IQR 7-31). SD, coefficient of variation, maximum BP, and maximum minus minimum BP difference were all calculated as measures of BPV. BPV showed a distinct pattern, influenced by season of year, day of week, and time of day. BPV index was higher in females compared with males (P < 0.001) and increased with age (P < 0.001). Compared to the weekend, the weekday BPV index was significantly higher, and this finding was more prominent in females (P = 0.001). In multivariate analysis, BPV index were significantly associated with age, gender, geographic location, and mean BP values. Using the largest BP data set we are aware of, with the benefits and limitations of real-world measurement, we could show the pattern of BPV and provide reference values that may be helpful in understanding the nature of BPV as self-measurement at home becomes more common, and help guide individualized management.

A circadian rhythm in skill-based errors in aviation maintenance.

PubMed

Hobbs, Alan; Williamson, Ann; Van Dongen, Hans P A

2010-07-01

In workplaces where activity continues around the clock, human error has been observed to exhibit a circadian rhythm, with a characteristic peak in the early hours of the morning. Errors are commonly distinguished by the nature of the underlying cognitive failure, particularly the level of intentionality involved in the erroneous action. The Skill-Rule-Knowledge (SRK) framework of Rasmussen is used widely in the study of industrial errors and accidents. The SRK framework describes three fundamental types of error, according to whether behavior is under the control of practiced sensori-motor skill routines with minimal conscious awareness; is guided by implicit or explicit rules or expertise; or where the planning of actions requires the conscious application of domain knowledge. Up to now, examinations of circadian patterns of industrial errors have not distinguished between different types of error. Consequently, it is not clear whether all types of error exhibit the same circadian rhythm. A survey was distributed to aircraft maintenance personnel in Australia. Personnel were invited to anonymously report a safety incident and were prompted to describe, in detail, the human involvement (if any) that contributed to it. A total of 402 airline maintenance personnel reported an incident, providing 369 descriptions of human error in which the time of the incident was reported and sufficient detail was available to analyze the error. Errors were categorized using a modified version of the SRK framework, in which errors are categorized as skill-based, rule-based, or knowledge-based, or as procedure violations. An independent check confirmed that the SRK framework had been applied with sufficient consistency and reliability. Skill-based errors were the most common form of error, followed by procedure violations, rule-based errors, and knowledge-based errors. The frequency of errors was adjusted for the estimated proportion of workers present at work/each hour of the day, and the 24 h pattern of each error type was examined. Skill-based errors exhibited a significant circadian rhythm, being most prevalent in the early hours of the morning. Variation in the frequency of rule-based errors, knowledge-based errors, and procedure violations over the 24 h did not reach statistical significance. The results suggest that during the early hours of the morning, maintenance technicians are at heightened risk of "absent minded" errors involving failures to execute action plans as intended.

Not All Trees Sleep the Same—High Temporal Resolution Terrestrial Laser Scanning Shows Differences in Nocturnal Plant Movement

PubMed Central

Zlinszky, András; Molnár, Bence; Barfod, Anders S.

2017-01-01

Circadian leaf movements are widely known in plants, but nocturnal movement of tree branches were only recently discovered by using terrestrial laser scanning (TLS), a high resolution three-dimensional surveying technique. TLS uses a pulsed laser emitted in a regular scan pattern for rapid measurement of distances to the targets, thus producing three dimensional point cloud models of sub-centimeter resolution and accuracy in a few minutes. Here, we aim to gain an overview of the variability of circadian movement of small trees across different taxonomic groups, growth forms and leaf anatomies. We surveyed a series of 18 full scans over a 12-h night period to measure nocturnal changes in shape simultaneously for an experimental setup of 22 plants representing different species. Resulting point clouds were evaluated by comparing changes in height percentiles of laser scanning points belonging to the canopy. Changes in crown shape were observed for all studied trees, but clearly distinguishable sleep movements are apparently rare. Ambient light conditions were continuously dark between sunset (7:30 p.m.) and sunrise (6:00 a.m.), but most changes in movement direction occurred during this period, thus most of the recorded changes in crown shape were probably not controlled by ambient light. The highest movement amplitudes, for periodic circadian movement around 2 cm were observed for Aesculus and Acer, compared to non-periodic continuous change in shape of 5 cm for Gleditschia and 2 cm for Fargesia. In several species we detected 2–4 h cycles of minor crown movement of 0.5–1 cm, which is close to the limit of our measurement accuracy. We present a conceptual framework for interpreting observed changes as a combination of circadian rhythm with a period close to 12 h, short-term oscillation repeated every 2–4 h, aperiodic continuous movement in one direction and measurement noise which we assume to be random. Observed movement patterns are interpreted within this framework, and connections with morphology and taxonomy are proposed. We confirm the existence of overnight “sleep” movement for some trees, but conclude that circadian movement is a variable phenomenon in plants, probably controlled by a complex combination of anatomical, physiological, and morphological factors. PMID:29104583

Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients

NASA Technical Reports Server (NTRS)

Jewett, M. E.; Rimmer, D. W.; Duffy, J. F.; Klerman, E. B.; Kronauer, R. E.; Czeisler, C. A.

1997-01-01

Fifty-six resetting trials were conducted across the subjective day in 43 young men using a three-cycle bright-light (approximately 10,000 lx). The phase-response curve (PRC) to these trials was assessed for the presence of a "dead zone" of photic insensitivity and was compared with another three-cycle PRC that had used a background of approximately 150 lx. To assess possible transients after the light stimulus, the trials were divided into 43 steady-state trials, which occurred after several baseline days, and 13 consecutive trials, which occurred immediately after a previous resetting trial. We found that 1) bright light induces phase shifts throughout subjective day with no apparent dead zone; 2) there is no evidence of transients in constant routine assessments of the fitted temperature minimum 1-2 days after completion of the resetting stimulus; and 3) the timing of background room light modulates the resetting response to bright light. These data indicate that the human circadian pacemaker is sensitive to light at virtually all circadian phases, implying that the entire 24-h pattern of light exposure contributes to entrainment.

Phase shifting two coupled circadian pacemakers - Implications for jet lag

NASA Technical Reports Server (NTRS)

Gander, P. H.; Kronauer, R. E.; Graeber, R. C.

1985-01-01

Two Van der Pol oscillators with reciprocal linear velocity coupling are utilized to model the response of the human circadian timing system to abrupt displacements of the environmental time cues (zeitgebers). The core temperature rhythm and sleep-wake cycle simulated by the model are examined. The relationship between the masking of circadian rhythms by environmental variables and behavioral and physiological events and the rates of resynchronization is studied. The effects of zeitgeber phase shifts and zeitgeber strength on the resynchronization rates are analyzed. The influence of intrinsic pacemakers periods and coupling strength on resynchronization are investigated. The simulated data reveal that: resynchronization after a time zone shift depends on the magnitude of the shift; the time of day of the shift has little influence on resynchronization; the strength of zeitgebers affects the rate and direction of the resynchronization; the intrinsic pacemaker periods have a significant effect on resynchronization; and increasing the coupling between the oscillators results in an increase in the rate of resynchronization. The model data are compared to transmeridian flight studies data and similar resynchronization patterns are observed.

Agomelatine, an innovative pharmacological response to unmet needs.

PubMed

Le Strat, Y; Gorwood, P

2008-09-01

Most of the available antidepressants, with different pharmacological profiles, such as inhibitors of serotonin reuptake (SSRIs) or norepinephrine reuptake (NRIs) or both (SNRIs), have limitations leading some patients to drop out of treatment. Another direction of research has therefore been undertaken, based initially on the fact that affective disorders are most often characterized by abnormal patterns of circadian rhythms. This consideration has led to the synthesis of agomelatine, a novel antidepressant combining melatonergic MT(1) and MT(2) agonism and serotonergic 5-HT(2C) antagonism. The antidepressant effects of agomelatine have been investigated in different animal models, including chronic mild stress, forced swimming, learned helplessness and psychosocial stress. All studies reported an antidepressant-like effect of agomelatine. A resynchronizing activity of agomelatine was seen in animal models for delayed sleep phase syndrome and in several original models of circadian disturbance, such as rodents infected by trypanosome or old hamsters. This activity of agomelatine on circadian rhythms was further confirmed in humans. Furthermore, several randomized, double-blind, placebo-controlled and comparator-controlled studies of agomelatine in the treatment of major depressive disorder indicate that agomelatine is effective and well tolerated.

Biochronometry; Proceedings of the Symposium, Friday Harbor, Wash., September 4-6, 1969.

NASA Technical Reports Server (NTRS)

Menaker, M.

1971-01-01

Topics discussed include circadian activity rhythms in birds and man, variation of circadian rhythms in monkeys, resetting of circadian eclosion rhythm in fruitflies, the effectiveness of mathematical models of circadian rhythms, the influence of ac electric fields on circadian rhythms in man, the relation between changes in the metabolic rate and circadian periodicity of the resistance of pocket mice to ionizing radiation, the relation between circadian organization and the photoperiodic time measurement in moths, the circadian rhythm of optic nerve potentials in the isolated eye of the sea hare, phasing of circadian temperature rhythms in the pocket mouse by specific spectral regions, the phase-shifting effect of light on circadian rhymicity in the fruifly, hormonal control of circadian rhythms in the fruitfly, metabolically controlled temperature compensation in the circadian rhythm of algae, and circadian rhythms in the chloroplasts of algae. Individual items are abstracted in this issue.

Circadian Rhythm and Sleep During Prolonged Antarctic Residence at Chinese Zhongshan Station.

PubMed

Chen, Nan; Wu, Quan; Xiong, Yanlei; Chen, Guang; Song, Dandan; Xu, Chengli

2016-12-01

Residence at Zhongshan Station (69°22'24″S, 76°22'40″E) for over 1 year exposes winter-over members to marked changes of light-dark cycle, ranging from the constant daylight of polar days to the constant darkness of polar nights, in addition to geographic and social isolation. This extreme photoperiodic environment may increase the risk of sleep disturbances and circadian desynchrony. The aim of this study was to investigate the circadian rhythm and sleep phase of Chinese winter-over expeditioners at Zhongshan Station. This study was conducted on 17 healthy male participants before departure from Shanghai and during residence at Zhongshan Station for 1 year (before winter, mid-winter, and end of winter). Sequential urine samples over 48 hours were obtained, 6-sulphatoxymelatonin in urine was assessed, and the circadian rhythm was analyzed by a cosine curve-fitting method. Participants' sleep parameters were obtained from wrist actigraphy and sleep logs. Morningness-Eveningness Questionnaire and Seasonal Pattern Assessment Questionnaire were completed. The acrophase of 6-sulphatoxymelatonin rhythm, sleep onset, sleep offset, and mid-sleep time were delayed significantly (P < .05) in Antarctica relative to departure values. The subjects had greater eveningness preference (P < .05) in mid-winter in Antarctica. The Global Seasonality Score and the prevalence of subsyndromal seasonal affective disorder increased (P < .05) during winter. Our results indicate that during polar nights Chinese expeditioners experienced the following problems: delayed circadian rhythm and sleep phase, later chronotype, and incidence of subsyndromal seasonal affective disorder. An appropriate combination of artificial bright light during dark winter months and a strict social schedule are recommended in a winter-over station in Antarctica. Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.

PubMed

Samulin Erdem, Johanna; Skare, Øivind; Petersen-Øverleir, Marte; Notø, Heidi Ødegaard; Lie, Jenny-Anne S; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

2017-01-01

Shift work has been suggested to be associated with breast cancer risk, and circadian disruption in shift workers is hypothesized as one of the mechanisms of increased cancer risk. There is, however, insufficient molecular evidence supporting this hypothesis. Using the quantitative methodology of pyrosequencing, epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK , BMAL1 , CRY1, PER1 and PER2 in female nurses working night shift work (278 breast cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium exposure to night work was associated with increased methylation levels of the CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with controls. Within the cases, analysis of the effects of shift work on the methylation patterns showed that methylation of CRY1 was lower in those who had worked night shift and had a high exposure (p=0.006) compared with cases that had worked only days. For cases with a medium exposure to night work, an increase in BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day working (unexposed) cases. The methylation levels of the five core circadian genes were also analyzed in relation to the estrogen and progesterone receptors status of the tumors in the cases, and no correlations were observed. Furthermore, nineteen polymorphisms in the five circadian genes were assessed for their effects on the methylation levels of the respective genes, but no associations were found. In summary, our data suggest that epigenetic regulation of CLOCK , BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers.

Conserved and divergent rhythms of crassulacean acid metabolism-related and core clock gene expression in the cactus Opuntia ficus-indica.

PubMed

Mallona, Izaskun; Egea-Cortines, Marcos; Weiss, Julia

2011-08-01

The cactus Opuntia ficus-indica is a constitutive Crassulacean acid metabolism (CAM) species. Current knowledge of CAM metabolism suggests that the enzyme phosphoenolpyruvate carboxylase kinase (PPCK) is circadian regulated at the transcriptional level, whereas phosphoenolpyruvate carboxylase (PEPC), malate dehydrogenase (MDH), NADP-malic enzyme (NADP-ME), and pyruvate phosphate dikinase (PPDK) are posttranslationally controlled. As little transcriptomic data are available from obligate CAM plants, we created an expressed sequence tag database derived from different organs and developmental stages. Sequences were assembled, compared with sequences in the National Center for Biotechnology Information nonredundant database for identification of putative orthologs, and mapped using Kyoto Encyclopedia of Genes and Genomes Orthology and Gene Ontology. We identified genes involved in circadian regulation and CAM metabolism for transcriptomic analysis in plants grown in long days. We identified stable reference genes for quantitative polymerase chain reaction and found that OfiSAND, like its counterpart in Arabidopsis (Arabidopsis thaliana), and OfiTUB are generally appropriate standards for use in the quantification of gene expression in O. ficus-indica. Three kinds of expression profiles were found: transcripts of OfiPPCK oscillated with a 24-h periodicity; transcripts of the light-active OfiNADP-ME and OfiPPDK genes adapted to 12-h cycles, while transcript accumulation patterns of OfiPEPC and OfiMDH were arrhythmic. Expression of the circadian clock gene OfiTOC1, similar to Arabidopsis, oscillated with a 24-h periodicity, peaking at night. Expression of OfiCCA1 and OfiPRR9, unlike in Arabidopsis, adapted best to a 12-h rhythm, suggesting that circadian clock gene interactions differ from those of Arabidopsis. Our results indicate that the evolution of CAM metabolism could be the result of modified circadian regulation at both the transcriptional and posttranscriptional levels.

Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

PubMed

Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

2017-10-01

In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.

Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts

PubMed Central

Samulin Erdem, Johanna; Skare, Øivind; Petersen-Øverleir, Marte; Notø, Heidi Ødegaard; Lie, Jenny-Anne S.; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

2017-01-01

Shift work has been suggested to be associated with breast cancer risk, and circadian disruption in shift workers is hypothesized as one of the mechanisms of increased cancer risk. There is, however, insufficient molecular evidence supporting this hypothesis. Using the quantitative methodology of pyrosequencing, epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK, BMAL1, CRY1, PER1 and PER2 in female nurses working night shift work (278 breast cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium exposure to night work was associated with increased methylation levels of the CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with controls. Within the cases, analysis of the effects of shift work on the methylation patterns showed that methylation of CRY1 was lower in those who had worked night shift and had a high exposure (p=0.006) compared with cases that had worked only days. For cases with a medium exposure to night work, an increase in BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day working (unexposed) cases. The methylation levels of the five core circadian genes were also analyzed in relation to the estrogen and progesterone receptors status of the tumors in the cases, and no correlations were observed. Furthermore, nineteen polymorphisms in the five circadian genes were assessed for their effects on the methylation levels of the respective genes, but no associations were found. In summary, our data suggest that epigenetic regulation of CLOCK, BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers. PMID:28928877

Associations of pineal volume, chronotype and symptom severity in adults with attention deficit hyperactivity disorder and healthy controls.

PubMed

Bumb, Jan Malte; Mier, Daniela; Noelte, Ingo; Schredl, Michael; Kirsch, Peter; Hennig, Oliver; Liebrich, Luisa; Fenske, Sabrina; Alm, Barbara; Sauer, Carina; Leweke, Franz Markus; Sobanski, Esther

2016-07-01

The pineal gland, as part of the human epithalamus, is the main production site of peripheral melatonin, which promotes the modulation of sleep patterns, circadian rhythms and circadian preferences (morningness vs. eveningness). The present study analyses the pineal gland volume (PGV) and its association with circadian preferences and symptom severity in adult ADHD patients compared to healthy controls. PGV was determined manually using high-resolution 3T MRI (T1-magnetization prepared rapid gradient echo) in medication free adult ADHD patients (N=74) compared to healthy controls (N=86). Moreover, the Morningness-Eveningness Questionnaire (MEQ), the ADHD Diagnostic Checklist and the Wender-Utah Rating Scale were conducted. PGV differed between both groups (patients: 59.9±33.8mm(3); healthy controls: 71.4±27.2mm(3), P=0.04). In ADHD patients, more eveningness types were revealed (patients: 29%; healthy controls: 17%; P=0.05) and sum scores of the MEQ were lower (patients: 45.8±11.5; healthy controls 67.2±10.1; P<0.001). Multiple regression analyses indicated a positive correlation of PGV and MEQ scores in ADHD (β=0.856, P=0.003) but not in healthy controls (β=0.054, P=0.688). Patients' MEQ scores (β=-0.473, P=0.003) were negatively correlated to ADHD symptoms. The present results suggest a linkage between the PGV and circadian preference in adults with ADHD and an association of the circadian preference to symptom severity. This may facilitate the development of new chronobiological treatment approaches for the add-on treatment in ADHD. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans.

PubMed

Won, Jinyoung; Jin, Yunho; Choi, Jeonghyun; Park, Sookyoung; Lee, Tae Ho; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2017-06-20

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation ( fmr ) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

PubMed Central

Won, Jinyoung; Jin, Yunho; Choi, Jeonghyun; Park, Sookyoung; Lee, Tae Ho; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2017-01-01

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (fmr) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm. PMID:28632163

Titanium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells.

PubMed

Hassan, Nathaniel; McCarville, Kirstin; Morinaga, Kenzo; Mengatto, Cristiane M; Langfelder, Peter; Hokugo, Akishige; Tahara, Yu; Colwell, Christopher S; Nishimura, Ichiro

2017-01-01

Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated. The Ti biomaterials, which reduced Per1 expression and upregulated Npas2, were further examined with BMSCs harvested from Per1::luc transgenic rats. Next, we addressed the regulatory relationship between Per1 and Npas2 using BMSCs from Npas2 knockout mice. The Npas2 knockout mutation did not rescue the Ti biomaterial-induced Per1 suppression and did not affect Per2, Per3, Bmal1 and Clock expression, suggesting that the Ti biomaterial-induced Npas2 overexpression was likely an independent phenomenon. Previously, vitamin D deficiency was reported to interfere with Ti biomaterial osseointegration. The present study demonstrated that vitamin D supplementation significantly increased Per1::luc expression in BMSCs, though the presence of Ti biomaterials only moderately affected the suppressed Per1::luc expression. Available in vivo microarray data from femurs exposed to Ti biomaterials in vitamin D-deficient rats were evaluated by weighted gene co-expression network analysis. A large co-expression network containing Npas2, Bmal1, and Vdr was observed to form with the Ti biomaterials, which was disintegrated by vitamin D deficiency. Thus, the aberrant BMSC peripheral circadian rhythm may be essential for the integration of Ti biomaterials into bone.

Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits

PubMed Central

Navarrete, Erika; Ortega-Bernal, Juan Roberto; Trejo-Muñoz, Lucero; Díaz, Georgina; Montúfar-Chaveznava, Rodrigo; Caldelas, Ivette

2016-01-01

Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb. PMID:27305041

Chronobiology of death in heart failure.

PubMed

Ribas, Nuria; Domingo, Maite; Gastelurrutia, Paloma; Ferrero-Gregori, Andreu; Rull, Pilar; Noguero, Mariana; Garcia, Carmen; Puig, Teresa; Cinca, Juan; Bayes-Genis, Antoni

2014-05-01

In the general population, heart events occur more often during early morning, on Mondays, and during winter. However, the chronobiology of death in heart failure has not been analyzed. The aim of this study was to determine the circadian, day of the week, and seasonal variability of all-cause mortality in chronic heart failure. This was an analysis of all consecutive heart failure patients followed in a heart failure unit from January 2003 to December 2008. The circadian moment of death was analyzed at 6-h intervals and was determined by reviewing medical records and by information provided by the relatives. Of 1196 patients (mean [standard deviation] age, 69 [13] years; 62% male), 418 (34.9%) died during a mean (standard deviation) follow-up of 29 (21) months. Survivors were younger, had higher body mass index, left ventricular ejection fraction, glomerular filtration rate, hemoglobin and sodium levels, and lower Framingham risk scores, amino-terminal pro-B type natriuretic peptide, troponin T, and urate values. They were more frequently treated with angiotensin receptor blockers, beta-blockers, mineralocorticoids receptor antagonists, digoxin, nitrates, hydralazine, statins, loop diuretics, and thiazides. The analysis of the circadian and weekly variability did not reveal significant differences between the four 6-h intervals or the days of the week. Mortality occurred more frequently during the winter (30.6%) compared with the other seasons (P = .024). All cause mortality does not follow a circadian pattern, but a seasonal rhythm in patients with heart failure. This finding is in contrast to the circadian rhythmicity of cardiovascular events reported in the general population. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Endogenous circadian regulation of carbon dioxide exchange in terrestrial ecosystems

Treesearch

Victor Resco de Dios; Michael L. Goulden; Kiona Ogle; Andrew D. Richardson; David Y. Hollinger; Eric A. Davidson; Josu G. Alday; Greg A. Barron-Gafford; Arnaud Carrara; Andrew S. Kowalski; Walt C. Oechel; Borja R. Reverter; Russell L. Scott; Ruth K. Varner; Ruben Diaz-Sierra; Jose M. Moreno

2012-01-01

It is often assumed that daytime patterns of ecosystem carbon assimilation are mostly driven by direct physiological responses to exogenous environmental cues. Under limited environmental variability, little variation in carbon assimilation should thus be expected unless endogenous plant controls on carbon assimilation, which regulate photosynthesis in time, are active...

Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1.

PubMed

Tamura, M; Kanno, Y; Chuma, S; Saito, T; Nakatsuji, N

2001-04-01

Mammalian sex-determination and differentiation are controlled by several genes, such as Sry, Sox-9, Dax-1 and Mullerian inhibiting substance (MIS), but their upstream and downstream genes are largely unknown. Ad4BP/SF-1, encoding a zinc finger transcription factor, plays important roles in gonadogenesis. Disruption of this gene caused disappearance of the urogenital system including the gonad. Ad4BP/SF-1, however, is also involved in the sex differentiation of the gonad at later stages, such as the regulation of steroid hormones and MIS. Pod-1/Capsulin, a member of basic helix-loop-helix transcription factors, is expressed in a pattern closely related but mostly complimentary to that of the Ad4BP/SF-1 expression in the developing gonad. In the co-transfection experiment using cultured cells, overexpression of Pod-1/Capsulin repressed expression of a reporter gene that carried the upstream regulatory region of the Ad4BP/SF-1 gene. Furthermore, forced expression of Pod-1/Capsulin repressed expression of Ad4BP/SF-1 in the Leydig cell-derived I-10 cells. These results suggest that Pod-1/Capsulin may play important roles in the development and sex differentiation of the mammalian gonad via transcriptional regulation of Ad4BP/SF-1.

The Effects of Dietary Factors on Blood Pressure.

PubMed

Appel, Lawrence J

2017-05-01

Evidence supports that multiple dietary factors affect blood pressure (BP). Dietary changes that effectively lower BP are weight loss, reduced sodium intake, increased potassium intake, moderation of alcohol intake, and Dietary Approaches to Stop Hypertension-style and vegetarian dietary patterns. In view of the increasing levels of BP in children and adults and the continuing epidemic of BP-related cardiovascular and renal diseases, efforts to reduce BP in both nonhypertensive and hypertensive individuals are warranted. The challenge to health care providers, researchers, government officials, and the general public is developing and implementing clinical and public health strategies that lead to sustained dietary changes. Copyright © 2016 Elsevier Inc. All rights reserved.

Holocene Activity of the Quelccaya Ice Cap: A Working Model

NASA Astrophysics Data System (ADS)

Lowell, T. V.; Smith, C. A.; Kelly, M. A.; Stroup, J. S.

2012-12-01

The patterns and magnitudes of past climate change in the topics are still under discussion. We contribute here by reporting on patterns of glacier length changes of the largest glacier in the tropics, Quelccaya Ice Cap (~13.9°S, 70.9°W, summit at 5645 m). This ice cap has several local domes that may have different patterns of length changes because of differing elevations of the domes (high to the north, lower to the south). Prior work (Mark et al. 2003, Abbott et al., 2004; Thompson et al., 2005; Buffen, et al., 2009), new radiocarbon ages, and stratigraphic and geomorphic relationships are used to determine the general pattern of length changes for the outlets from this ice cap. We exploit geomorphic relationships and present new radiocarbon ages on interpreted stratigraphic sections to determine the pattern of length changes for this ice cap. Ice retreated during late glacial times (Rodbell and Seltzer, 2000; Kelly et al., in press). By 11,400 yr BP it had reached a position ~1.2 km beyond its present (2000 AD) extent. While length during the early Holocene is problematic, present evidence permits, but does not prove, extents of 0.5 to 1.0 km down-valley from the present margin. Between 6400 and 4400 yr BP the ice cap was smaller than present, but it advanced multiple times during the late Holocene. Lengths of up to 1 km beyond present were achieved at 3400 yr BP and ~500 yr BP. Additionally, the ice advanced to 0.8 km beyond its present margin at 1600 yr BP. Because these glaciers were temperate, we take these lengths to represent primarily changes in temperature. This may suggest that lowering insolation values in the northern hemisphere during the Holocene provide a first order control on tropical temperatures. Alternatively, it may be that major reorganization of the topical circulation belts about 5000 yr BP yields two configurations of the QIC and hence Holocene temperatures - one at the present ice margin and and the second about 1 km beyond the present ice margin. In either case, the pulsating glacier lengths indicate a dynamic Holocene climate.

Extensive circadian and light regulation of the transcriptome in the malaria mosquito Anopheles gambiae

PubMed Central

2013-01-01

Background Mosquitoes exhibit 24 hr rhythms in flight activity, feeding, reproduction and development. To better understand the molecular basis for these rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized microarray analysis on time-of-day specific collections of mosquitoes over 48 hr to explore the coregulation of gene expression rhythms by the circadian clock and light, and compare these with the 24 hr rhythmic gene expression in the diurnal Aedes aegypti dengue vector mosquito. Results In time courses from An. gambiae head and body collected under light:dark cycle (LD) and constant dark (DD) conditions, we applied three algorithms that detect sinusoidal patterns and an algorithm that detects spikes in expression. This revealed across four experimental conditions 393 probes newly scored as rhythmic. These genes correspond to functions such as metabolic detoxification, immunity and nutrient sensing. This includes glutathione S-transferase GSTE5, whose expression pattern and chromosomal location are shared with other genes, suggesting shared chromosomal regulation; and pulsatile expression of the gene encoding CYP6M2, a cytochrome P450 that metabolizes pyrethroid insecticides. We explored the interaction of light and the circadian clock and highlight the regulation of odorant binding proteins (OBPs), important components of the olfactory system. We reveal that OBPs have unique expression patterns as mosquitoes make the transition from LD to DD conditions. We compared rhythmic expression between An. gambiae and Ae. aegypti heads collected under LD conditions using a single cosine fitting algorithm, and report distinct similarities and differences in the temporal regulation of genes involved in tRNA priming, the vesicular-type ATPase, olfaction and vision between the two species. Conclusions These data build on our previous analyses of time-of-day specific regulation of the An. gambiae transcriptome to reveal additional rhythmic genes, an improved understanding of the co-regulation of rhythms in gene expression by the circadian clock and by light, and an understanding of the time-of-day specific regulation of some of these rhythmic processes in comparison with a different species of mosquito. Improved understanding of biological timing at the molecular level that underlies key physiological aspects of mosquito vectors may prove to be important to successful implementation of established and novel insect control methods. PMID:23552056

Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and Peripheral Blood of Patients with Bullous Pemphigoid.

PubMed

Engmann, Judith; Rüdrich, Urda; Behrens, Georg; Papakonstantinou, Eleni; Gehring, Manuela; Kapp, Alexander; Raap, Ulrike

2017-04-06

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more common in elderly individuals. The aim of this study was to determine the functional activity of eosinophils in patients with BP compared with healthy donors. Blood, skin and blister-derived eosinophils were strongly activated in patients with BP, seen by increased surface expression of CD69 compared with controls. CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1×106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1α in BP blister fluids. Apoptosis in cultivated BP eosinophils was increased and accompanied by enhanced surface externalization of CD95. Caspase 3 positive eosinophils in lesional BP skin and blister fluid also showed the initiation of apoptosis. These results reveal novel pathophysiological aspects of BP, with a strong activation pattern and increased apoptosis of eosinophils in the peripheral blood, skin and blister fluids.

24-h actigraphic monitoring of motor activity, sleeping and eating behaviors in underweight, normal weight, overweight and obese children.

PubMed

Martoni, Monica; Carissimi, Alicia; Fabbri, Marco; Filardi, Marco; Tonetti, Lorenzo; Natale, Vincenzo

2016-12-01

Within a chronobiological perspective, the present study aimed to describe 24 h of sleep-wake cycle, motor activity, and food intake patterns in different body mass index (BMI) categories of children through 7 days of actigraphic recording. Height and weight were objectively measured for BMI calculation in a sample of 115 Italian primary schoolchildren (10.21 ± 0.48 years, 62.61 % females). According to BMI values, 2.60 % were underweight, 61.70 % were of normal weight, 29.60 % were overweight and 6.10 % were obese. Participants wore a wrist actigraph continuously for 7 days to record motor activity and describe sleep-wake patterns. In addition, participants were requested to push the event-marker button of the actigraph each time they consumed food to describe their circadian eating patterns. BMI group differences were found for sleep quantity (i.e. midpoint of sleep and amplitude), while sleep quality, 24-h motor activity and food intake patterns were similar between groups. Regression analyses showed that BMI was negatively predicted by sleep duration on schooldays. BMI was also predicted by motor activity and by food intake frequencies recorded at particular times of day during schooldays and at the weekend. The circadian perspective seems to provide promising insight into childhood obesity, but this aspect needs to be further explored.

Revisiting the daily human birth pattern: time of delivery at Casa de Maternidad in Madrid (1887-1892).

PubMed

Varea, Carlos; Fernández-Cerezo, Susana

2014-01-01

Among the ancestral characteristics of the primate group to which Homo sapiens belongs we find a pattern of daytime physical activity, but one notable exception is birthing which usually begins with night-time labor. In populations with a moderate or high level of medicalized labor, there is evidence that the medical preferences interfere with the underlying biological mechanism for the circadian pattern of human birth. This study analyses the hourly patterns of 4,599 single live births in the House of Maternity in Madrid between 1887 and 1892, a period of very limited obstetric intervention and without the influence of artificial lighting. In order to determine the influence of natural light on labor, two periods of maximum and minimum light have been established around the summer and winter solstices of the years in question. A clear circadian pattern of births emerges, with very early morning and early morning births dominating, and a sharp drop from midday until nightfall. The hourly distribution on both solstices follows this pattern, but with a clear peak shift: in winter, there is a greater concentration of deliveries in the early morning, whereas in the summer, the highest concentration is between 8 and 12 in the morning. The results confirm that non-intervened human birth has a clear diurnal cycle, with a higher incidence of deliveries in the early morning or morning. The shift in distribution during the winter and summer solstices seems to confirm the effect of light on the labor process. © 2014 Wiley Periodicals, Inc.

Enterprise Pattern: integrating the business process into a unified enterprise model of modern service company

NASA Astrophysics Data System (ADS)

Li, Ying; Luo, Zhiling; Yin, Jianwei; Xu, Lida; Yin, Yuyu; Wu, Zhaohui

2017-01-01

Modern service company (MSC), the enterprise involving special domains, such as the financial industry, information service industry and technology development industry, depends heavily on information technology. Modelling of such enterprise has attracted much research attention because it promises to help enterprise managers to analyse basic business strategies (e.g. the pricing strategy) and even optimise the business process (BP) to gain benefits. While the existing models proposed by economists cover the economic elements, they fail to address the basic BP and its relationship with the economic characteristics. Those proposed in computer science regardless of achieving great success in BP modelling perform poorly in supporting the economic analysis. Therefore, the existing approaches fail to satisfy the requirement of enterprise modelling for MSC, which demands simultaneous consideration of both economic analysing and business processing. In this article, we provide a unified enterprise modelling approach named Enterprise Pattern (EP) which bridges the gap between the BP model and the enterprise economic model of MSC. Proposing a language named Enterprise Pattern Description Language (EPDL) covering all the basic language elements of EP, we formulate the language syntaxes and two basic extraction rules assisting economic analysis. Furthermore, we extend Business Process Model and Notation (BPMN) to support EPDL, named BPMN for Enterprise Pattern (BPMN4EP). The example of mobile application platform is studied in detail for a better understanding of EPDL.

A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation

PubMed Central

Fan, Zenghua; Zhao, Meng; Joshi, Parth D.; Li, Ping; Zhang, Yan; Guo, Weimin; Xu, Yichi; Wang, Haifang; Zhao, Zhihu

2017-01-01

Abstract Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα. These circadian lncRNAs showed similar circadian phases with their nearby genes. The extent of their nuclear localization is higher than protein coding genes but less than enhancer RNAs. The association between enhancer and circadian lncRNAs is also observed in tissues other than liver. Comparative analysis between mouse and rat circadian liver transcriptomes showed that circadian transcription at lncRNA loci tends to be conserved despite of low sequence conservation of lncRNAs. One such circadian lncRNA termed lnc-Crot led us to identify a super-enhancer region interacting with a cluster of genes involved in circadian regulation of metabolism through long-range interactions. Further experiments showed that lnc-Crot locus has enhancer function independent of lnc-Crot's transcription. Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. PMID:28335007

Altered cropping pattern and cultural continuation with declined prosperity following abrupt and extreme arid event at ~4,200 yrs BP: Evidence from an Indus archaeological site Khirsara, Gujarat, western India.

PubMed

Pokharia, Anil K; Agnihotri, Rajesh; Sharma, Shalini; Bajpai, Sunil; Nath, Jitendra; Kumaran, R N; Negi, Bipin Chandra

2017-01-01

Archaeological sites hold important clues to complex climate-human relationships of the past. Human settlements in the peripheral zone of Indus culture (Gujarat, western India) are of considerable importance in the assessment of past monsoon-human-subsistence-culture relationships and their survival thresholds against climatic stress exerted by abrupt changes. During the mature phase of Harappan culture between ~4,600-3,900yrsBP, the ~4,100±100yrsBP time slice is widely recognized as one of the major, abrupt arid-events imprinted innumerous well-dated palaeo records. However, the veracity of this dry event has not been established from any archaeological site representing the Indus (Harappan) culture, and issues concerning timing, changes in subsistence pattern, and the likely causes of eventual abandonment (collapse) continue to be debated. Here we show a significant change in crop-pattern (from barley-wheat based agriculture to 'drought-resistant' millet-based crops) at ~4,200 yrs BP, based on abundant macrobotanical remains and C isotopes of soil organic matter (δ13CSOM) in an archaeological site at Khirsara, in the Gujarat state of western India. The crop-change appears to be intentional and was likely used as an adaptation measure in response to deteriorated monsoonal conditions. The ceramic and architectural remains of the site indicate that habitation survived and continued after the ~4,200yrsBP dry climatic phase, but with declined economic prosperity. Switching to millet-based crops initially helped inhabitants to avoid immediate collapse due to climatic stresses, but continued aridity and altered cropping pattern led to a decline in prosperity levels of inhabitants and eventual abandonment of the site at the end of the mature Harappan phase.

Ovo-vegetarian diet is associated with lower systemic blood pressure in Taiwanese women.

PubMed

Ho, C P; Yu, J H; Lee, T J F

2017-12-01

This study was designed to investigate blood pressure (BP) profiles among Taiwanese women with different dietary patterns. Cross-sectional study. A total of 269 non-hypertensive Taiwanese women, 40 years of age or older, were surveyed using structured questionnaires, and measurements of BP and physiological parameters were made. To assess differences among vegans, ovo-vegetarians, and meat eaters in terms of BP, demographic, and health behavior data, the chi-squared and Fisher's exact tests were employed for categorical variables, and analysis of variance and independent t-tests were performed for continuous variables. Multiple regression analysis was used to examine the relationship between BP and dietary patterns while controlling for potential confounding factors. A significant difference was found among the three test groups in terms of age, education, employment, stress, and waist-hip ratio. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly differed among the three groups. After controlling for age, body weight, waist circumference, and hip circumference, the three groups were observed to be a significant risk factor of the SBP and DBP. The SBP and DBP of the ovo-vegetarian group were significantly lower than those of the meat-eater group. No significant differences were found between the vegan and meat-eater groups in terms of SBP and DBP. Dietary pattern is a likely risk factor for SBP and DBP outcomes in Taiwanese women. In particular, the SBP and DBP of ovo-vegetarians are the lowest among the values observed for all dietary patterns. This finding suggests that an ovo-vegetarian diet is beneficial for long-term BP control and prevention of hypertension in females. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Hypothesis driven single cell dual oscillator mathematical model of circadian rhythms

PubMed Central

S, Shiju

2017-01-01

Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations. Understanding of dual oscillator dynamics in a single cell at molecular level may provide insight about the circadian mechanisms that encodes day length variations and its response to external zeitgebers. We present here a realistic dual oscillator model of circadian rhythms based on the series of hypotheses proposed by Daan et al., in which they conjectured that the circadian genes per1/cry1 track dawn while per2/cry2 tracks dusk and they together constitute the morning and evening oscillators (dual oscillator). Their hypothesis also provides explanations about the encoding of day length in terms of molecular mechanisms of per/cry expression. We frame a minimal mathematical model with the assumption that per1 acts a morning oscillator and per2 acts as an evening oscillator and to support and interpret this assumption we fit the model to the experimental data of per1/per2 circadian temporal dynamics, phase response curves (PRC's), and entrainment phenomena under various light-dark conditions. We also capture different patterns of splitting phenomena by coupling two single cell dual oscillators with neuropeptides vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) as the coupling agents and provide interpretation for the occurrence of splitting in terms of ME oscillators, though they are not required to explain the morning and evening oscillators. The proposed dual oscillator model based on Daan's hypothesis supports per1 and per2 playing the role of morning and evening oscillators respectively and this may be the first step towards the understanding of the core molecular mechanism responsible for encoding the day length. PMID:28486525

Hypothesis driven single cell dual oscillator mathematical model of circadian rhythms.

PubMed

S, Shiju; Sriram, K

2017-01-01

Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations. Understanding of dual oscillator dynamics in a single cell at molecular level may provide insight about the circadian mechanisms that encodes day length variations and its response to external zeitgebers. We present here a realistic dual oscillator model of circadian rhythms based on the series of hypotheses proposed by Daan et al., in which they conjectured that the circadian genes per1/cry1 track dawn while per2/cry2 tracks dusk and they together constitute the morning and evening oscillators (dual oscillator). Their hypothesis also provides explanations about the encoding of day length in terms of molecular mechanisms of per/cry expression. We frame a minimal mathematical model with the assumption that per1 acts a morning oscillator and per2 acts as an evening oscillator and to support and interpret this assumption we fit the model to the experimental data of per1/per2 circadian temporal dynamics, phase response curves (PRC's), and entrainment phenomena under various light-dark conditions. We also capture different patterns of splitting phenomena by coupling two single cell dual oscillators with neuropeptides vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) as the coupling agents and provide interpretation for the occurrence of splitting in terms of ME oscillators, though they are not required to explain the morning and evening oscillators. The proposed dual oscillator model based on Daan's hypothesis supports per1 and per2 playing the role of morning and evening oscillators respectively and this may be the first step towards the understanding of the core molecular mechanism responsible for encoding the day length.

Circadian and longitudinal variation of serum C-telopeptide, osteocalcin, and skeletal alkaline phosphatase in C3H/HeJ mice.

PubMed

Srivastava, A K; Bhattacharyya, S; Li, X; Mohan, S; Baylink, D J

2001-10-01

Inbred strains of mice are increasingly being used as an animal model to investigate skeletal disorders relevant to humans. In the bone field, one of the most convenient endpoints for evaluating genetic, physiological, or pharmaceutical perturbations is the use of biochemical markers. To apply biochemical markers in an effective manner, it is of key importance to establish the biological variation and appropriate sampling time. In this study, we evaluate two components: (i) circadian changes, and (ii) longitudinal variation for three serum markers, osteocalcin, C-telopeptide, and skeletal alkaline phosphatase (sALP), using 6-week-old C3H/HeJ (C3H) mice. To study circadian rhythms, the mice were randomly divided into eight groups of 15 mice each. Blood was collected at 3 h intervals, starting at 9:00 A.M. and continuing until 6:00 A.M. the next day. To determine whether circadian rhythm is intrinsically regulated or influenced by restricted food intake, it was also studied after a 12 h fasting period. Serum osteocalcin and C-telopeptide levels were measured by enzyme-linked immunoassay (ELISA) and skeletal alkaline phosphatase by a kinetic assay. The results demonstrated significant circadian variations in osteocalcin and C-telopeptide levels with a peak value between 0900 and 1200 h during daytime and a nadir between 15:00 and 18:00 h. The peak levels of C-telopeptide and osteocalcin were 26%-66% higher as compared with 24 h mean values. The pattern of the circadian variation of C-telopeptide and osteocalcin was similar in female and male animals and was not significantly affected by restricted food intake. The sALP levels were only marginally affected by the circadian rhythm. Longitudinal variations, expressed as coefficient of variation (CV), for osteocalcin, C-telopeptide, and sALP concentrations were 17%, 14%, and 16%, respectively. In addition, the longitudinal variations were not significantly influenced by the time of blood collection in sALP and osteocalcin levels, whereas C-telopeptide levels showed significantly higher within-subject day-to-day variation in morning samples, as compared with blood samples collected in the afternoon. The results highlight the importance of: (i) the timing of sample collection for appropriate interpretation of the bone marker data; and (ii) using the appropriate number of samples based on the variance obtained herein.

Blood Pressure Levels and Mortality Risk among Hemodialysis Patients: Results from the Dialysis Outcomes and Practice Patterns Study

PubMed Central

Robinson, Bruce M.; Tong, Lin; Zhang, Jinyao; Wolfe, Robert A.; Goodkin, David A.; Greenwood, Roger N.; Kerr, Peter G.; Morgenstern, Hal; Li, Yun; Pisoni, Ronald L.; Saran, Rajiv; Tentori, Francesca; Akizawa, Tadao; Fukuhara, Shunichi; Port, Friedrich K.

2014-01-01

KDOQI practice guidelines recommend pre-dialysis blood pressure (BP) <140/90 mm Hg. However, most prior hemodialysis studies found elevated mortality with low, not high, systolic blood pressure (SBP), possibly due to unmeasured confounders affecting BP and mortality such as severity of comorbidities. To lessen this bias, we analyzed facility-level BP practices, relating patient-level survival to the fraction of patients in BP categories at each dialysis facility in Cox regression models adjusted for patient and facility characteristics. Analyses included 24,525 patients in the Dialysis Outcomes and Practice Patterns Study. Compared with pre-dialysis SBP 130–159 mm Hg, mortality was 13% higher in facilities with 20% more patients at SBP 110–129 mm Hg and 16% higher in facilities with 20% more patients at SBP ≥160 mm Hg. For patient-level SBP, mortality was elevated at low (<130 mm Hg), not high (up to ≥180 mm Hg) SBP. For pre-dialysis diastolic BP, mortality was lowest at 60–99 mm Hg, a wide range suggesting less chance to improve outcomes. Higher mortality at SBP <130 mm Hg is consistent with prior studies and may be due to excessive BP-lowering during dialysis. The lowest risk facility SBP range of 130–159 mm Hg indicates this range may be optimal, but may have been influenced by unmeasured facility practices. While additional study is needed, the findings contrast with KDOQI BP targets, and provide guidance on optimal BP range in absence of definitive clinical trial data. PMID:22718187

Short sleep duration as an independent predictor of cardiovascular events in Japanese patients with hypertension.

PubMed

Eguchi, Kazuo; Pickering, Thomas G; Schwartz, Joseph E; Hoshide, Satoshi; Ishikawa, Joji; Ishikawa, Shizukiyo; Shimada, Kazuyuki; Kario, Kazuomi

2008-11-10

It is not known whether short duration of sleep is a predictor of future cardiovascular events in patients with hypertension. To test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD), we performed ambulatory blood pressure (BP) monitoring in 1255 subjects with hypertension (mean [SD] age, 70.4 [9.9] years) and followed them for a mean period of 50 (23) months. Short sleep duration was defined as less than 7.5 hours (20th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio and 95% confidence interval (CI) for short sleep duration. A riser pattern was defined when mean nighttime systolic BP exceeded daytime systolic BP. The end point was a cardiovascular event: stroke, fatal or nonfatal myocardial infarction (MI), and sudden cardiac death. In multivariable analyses, short duration of sleep (<7.5 hours) was associated with incident CVD (hazard ratio [HR], 1.68; 95% CI, 1.06-2.66; P = .03). A synergistic interaction was observed between short sleep duration and the riser pattern (P = .09). When subjects were classified according to their sleep time and a riser vs nonriser pattern, the group with shorter sleep duration plus the riser pattern had a substantially and significantly higher incidence of CVD than the group with predominant normal sleep duration plus the nonriser pattern (HR, 4.43; 95% CI, 2.09-9.39; P < .001), independent of covariates. Short duration of sleep is associated with incident CVD risk and the combination of the riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of patients with hypertension.

Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures

PubMed Central

Gómez-Abellán, Purificación; Díez-Noguera, Antoni; Madrid, Juan A.; Luján, Juan A.; Ordovás, José M.; Garaulet, Marta

2012-01-01

Aims to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression. Subjects and Methods VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m2) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR. Results CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues. Conclusions 24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure. PMID:23251369

Prevalence of poor glycemic and blood pressure control and pattern of drug use among primary health-care outpatients in Al Ahsa Saudi Arabia

PubMed Central

Emeka, Promise M.; Mukalaf, Ahmed Al; Helal, Hussien Al; Khan, Tahir M.; Almukalf, Mishial A.

2017-01-01

Objectives: To assess drug use pattern and the effect on glycemic and blood pressure (BP) control in type 2 diabetes mellitus (T2DM) and hypertensive patients. Furthermore, to evaluate the duration of drug use and antecedence in diagnosis. Methodology: A cross-sectional study design, comprising interview/questionnaire targeting outpatients attending primary health centers in Al Ahsa was adopted. During the interview, their fasting blood glucose, weight, and height were measured, along with their BP. Time and duration of drug use were recorded. The history, sociodemographic data and the presence of any other disease conditions were also documented. Results: The highest number of uncontrolled BP and poor glycemic control was among the age group of 45 and 49 years. Significant number of the patients (92.9%) had body mass index >30 kg/m2. The prevalence of developing hypertension before T2DM among participants was 59.9%. A significant number (84%) had uncontrolled hypertension, and 67.3% had uncontrolled T2DM. Drug use pattern revealed single or combinations according to clinical guidelines initially but did not follow through in meeting targets. Majority received angiotensin converting enzyme inhibitors, amlodipine or atenolol for BP control and metformin for T2DM. Patients diagnosed between 1 and 5 years displayed significant poor glycemic and BP control. Significantly, most patients appeared to have been on same prescriptions for a longer time without review. Conclusion: Poor glycemic and BP controls observed in this study could be due to deficient treatment strategy among others. Patients were, however, not adequately managed in line with prescribed clinical guidelines. PMID:28936150

[Hypertension and prehypertension in children and adolescents with diabetes type 1].

PubMed

Machnica, Lukasz; Deja, Grazyna; Jarosz-Chobot, Przemysława

2008-01-01

The aim of the study was to evaluate the prevalence of hypertension, prehypertension and circadian blood pressure rhythm disturbances with the analysis of chosen cardio-vascular risk factors in children and adolescents with diabetes type 1 (T1DM). The study group comprised 100 type 1 diabetic children (51 girls) with the mean age 15.4+/-2.58 years and mean diabetes duration 7.02+/-2.93 years. All subjects had an ambulatory blood pressure measurement (ABPM) as well as HbA1c, blood lipids and microalbuminuria assessment performed. 30 (30%) patients during the day period and 26 (26%) during the night period had their mean systolic BP (SBP) elevated beyond the 95-th percentile (for sex, age and height) in more than 40% of measurements. Corresponding diastolic BP (DBP) elevation occurred during the day in 3 (3%) and during the night in 2 (2%) patients. Prehypertension was revealed in 39 (39%) patients. Lack of physiological BP decrease during the night (Non-dipper) appeared in 48 (48%) subjects. A negative correlation between HDL and mean 24-hour SBP (r=-0.412, p<0.05) as well as mean night SBP (r=-0.520, p<0.01) in the group with hypertension was found. There was also a positive correlation between triglycerides (TG) level and mean 24-hour DBP (r=0.443, p<0.05) as well as mean night SBP (r=0.467, p<0.05) in the same group. The hypertension group presented with significantly lower mean HbA1c than the subjects without elevated BP (8.42+/-2.09% vs. 7.16+/-1.06%, p<0.05). Subjects with blunted 24-hour blood pressure variation (Non-dippers) had significantly higher BMI (p<0.05) and TG concentrations (p<0.05) and significantly lower HDL (p<0.05). Both hypertension and prehypertension are common disorders in young patients with T1DM. Lack of physiological BP decrease during the night seems to be connected with higher BMI and triglycerides and with lower HDL cholesterol.

Blood Pressure, Sleep Quality and Fatigue in Shift Working Police Officers: Effects of a Twelve Hour Roster System on Cardiovascular and Sleep Health.

PubMed

Elliott, Jaymen L; Lal, Sara

2016-01-29

Police officers have been reported to exhibit a high incidence of pathologies, which present prematurely in an otherwise healthy population. Shift work has also been associated with an increased risk of cardiovascular and sleep disorders, attributable to its propensity for circadian rhythm dysfunction. However, contention exists as to whether shift work has a direct effect upon blood pressure (BP) regulation. This cross-sectional study sought to determine changes in BP and associations with the overall sleep quality and fatigue in 206 general duties police officers (n = 140 males) of the New South Wales Police Force in Australia. The subjects' BP was assessed before and after their twelve hour shift, during which time they also completed the Lifestyle Appraisal Questionnaire, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale and Fatigue Severity Scale (FSS). Poor sleep quality (PSQI) and fatigue severity (FSS) were found to predominate in the sample (69% and 51% respectively). Although there was no change in BP for male participants, female officers' systolic blood pressure (SBP) was found to increase significantly across the shift (p < 0.001), but with no change found in females' diastolic blood pressure (DBP). Finally, higher pre and post-shift SBP (r = -0.26, p = 0.001; r = -0.25, p = 0.001, respectively) and DBP (r = -0.26, p = 0.001; r = -0.26, p = 0.001, respectively) were significantly correlated with lower FSS scores after accounting for age, waist-hip ratio and lifestyle risk factors. Based on these preliminary findings, there was a significant increase in SBP of female police officers after shift work, while BP and fatigue levels in all police officers were strongly related. Moreover, the predominating poor sleep quality and impact of fatigue in this sample remain a concern. Further research is required to ensure the physiological welfare of police officers, while strategies must be implemented to manage the detrimental effects shift work may be having upon their cardiovascular and sleep health.

Differentially expressed proteins of soybean (Glycine max) pulvinus in light and dark conditions

USDA-ARS?s Scientific Manuscript database

Soybean leaves (Glycine max) both track and avoid the sun through turgor changes of the pulvinus tissue at the base of leaves. Pulvinar response is known to be affected by both diurnally varying environmental factors and circadian patterns. Differential expression of the proteins between light and d...