Contribution of the rest–activity circadian rhythm to quality of life in cancer patients

Quality of life (QoL) is estimated from patients scores to items related to everyday life, including rest and activity. The rest–activity rhythm reflects endogenous circadian clock function. The relation between the individual rhythm in activity and QoL was investigated in 200 patients with metastatic colorectal cancer. Patients wore a wrist actigraph (Ambulatory Monitoring Inc., New York, NY) for 3–5 d before chronotherapy, and completed a QoL questionnaire developed by the European Organization for Research and Treatment of Cancer (QLQ-C30) plus the Hospital Anxiety and Depression Scale. The rest–activity circadian rhythm was characterized by the mean activity level (m), autocorrelation coefficient at 24h (r24), and the dichotomy index (I<O), a ratio between the amount of activity while in and out of bed. The distribution of the rest–activity cycle parameters and that of QoL scores was independent of sex, age, primary tumor, number of metastatic sites, and prior treatment. Both the 24h rhythm indicators were positively correlated with global QoL score as well as physical, emotional, and social functioning. Negative correlations were found between m, r24, or I<O and fatigue, appetite loss, and nausea. The rest–activity circadian rhythm appeared to be an objective indicator of physical welfare and QoL. This analysis suggests that circadian function may be one of the biological determinants of QoL in cancer patients.     

Duration of activity and period of circadian activity–rest rhythm in a photoperiod-dependent primate,Microcebus murinus

Under free-running conditions, the grey lesser mouse lemur expresses a circadian activity–rest rhythm with a period particularly short (22.50 ± 0.6 h) for a mammal. Light exerts a strong suppressive effect upon activity. After transfer from nycthemeral to free-running conditions the duration of activity was systematically increased. This extension took place in the first cycle and was characterized by both a phase advance in activity onset and an even larger phase delay in activity offset. This phenomenon was more pronounced after long day entrainment. Any shift of the light–dark cycle was followed the next day by a corresponding shift in activity onset. The phase response curve pattern was similar to that already described for nocturnal mammals. Due to the strength of light as a zeitgeber and the plasticity of the response to photic conditions, the mouse lemur appears as a convenient species for chronobiological studies on non-human primates.     

Reactions of d-glyceraldehyde 3-phosphate dehydrogenase facilitated by oxidized nicotinamide–adenine dinucleotide

Transient kinetic methods have been used to study the influence of NAD(+) on the rate of elementary processes of the reversible oxidative phosphorylation of d-glyceraldehyde 3-phosphate catalysed by d-glyceraldehyde 3-phosphate dehydrogenase. In the pH range 5-8 NAD(+) is bound to the enzyme during the following elementary processes of the mechanism: phosphorolysis of the acyl-enzyme, its formation from 1,3-diphosphoglycerate and the enzyme and the formation and breakdown of the glyceraldehyde 3-phosphate-enzyme complex. The rates of these four elementary processes only equal or exceed the turnover rate of the enzyme when NAD(+) is bound and are as much as 10(4) times the rates in the absence of NAD(+). Autocatalysis of the reductive dephosphorylation of 1,3-diphosphoglycerate occurs when glyceraldehyde 3-phosphate release is rate determining because NAD(+) is a reaction product. An important feature of the enzyme mechanism is that the negative-free-energy change of a chemical reaction, acyl-enzyme formation, is linked in a simple way to the positive-free-energy change of a dissociation reaction, NAD(+) release.     

Is there a circadian rhythm of postural control and perception of the vertical?

Daytime activity is largely regulated by the day/night pattern. Various physiological and cognitive functions display a variation during the diurnal period, where individuals manage their balance, spatial orientation and consequently their perception of the vertical. However, findings concerning daytime changes of postural control quality remain contradictory, mainly due to methodogical considerations. The aim of our study is to evaluate the effect of time of day on postural control and perception of the vertical.

Fifteen male subjects underwent six test sessions over a 24-hour period. Each session involved a postural balance test (static/dynamic; eyes open/closed) and a subjective evaluation of sleepiness, fatigue and subjective visual vertical (SVV) (light stick tilted from 10 to 40°; eight trials). No time-of-day effect was observed on postural balance. However, perception of the vertical fluctuates during the day and is better at 10 a.m. than at 10 p.m. Despite the gradual perception of the vertical deterioration over the day, postural balance does not show any fluctuation. This postural balance consistency throughout the day may be the result of compensation mechanisms.     

Importance of ornithine-δ-aminotransferase to proline accumulation caused by water stress in detached rice leaves

Proline is synthesized either from glutamate or from ornithine in plants. Relatively little is known about the contribution of the pathway from ornithine to proline biosynthesis. In this paper we investigated the contribution of ornithine--aminotransterase (OAT), an enzyme responsible for ornithine pathway, to proline accumulation in water-stressed detached rice leaves. Although OAT activity increased with the increase of water stress duration, a pattern similar to that obtained for proline accumulation, the ornithine pathway in rice leaves seems to contribute little, if any, to proline accumulation under water stress condition. This conclusion was based on the observations that (a) gabaculine (50 M), an inhibitor of OAT, inhibited about 75% OAT activity caused by water stress but reduced only 20% of proline content and (b) cycloheximide, a protein synthesis inhibitor, had no effect on OAT activity induced by water stress but significantly reduced proline accumulation.     

Can dim light melatonin onset be predicted by the timing of sleep in patients with possible circadian sleep-wake rhythm disorders?

Dim Light Melatonin Onset (DLMO) is a reliable marker of the endogenous circadian rhythm. To determine if sleep timing can predict DLMO, we investigated the relationship between sleep timing and DLMO in patients in various circadian sleep-wake rhythm disorders (CSWRDs), ages and genders. We found that correlations were only moderate between DLMO and sleep-onset in the complete data-set, but they increased in patients with delayed sleep-wake phase disorder (DSWPD), DSWPD patients with a regular sleep pattern and patients with advanced sleep-wake phase disorder (ASWPD); the levels of correlation were r = 0.542, 0.657, 0.728 and 0.814, respectively. In DSWPD patients with a regular sleep pattern, mid-sleep strongly correlated (r = 0.839) with DLMO. Correlation in other CSRWDs was not significant. DLMO, sleep-onset and age were most discriminated factors between the various CSRWDs. Estimation of DLMO is only possible in patients with ASWPD and in DSWPD patients with a regular sleep pattern.     

Free‐running circadian rhythm of plastid movements in individual cells of pyrocystis lunula (dinophyta)

Abstract

Pyrocystis lunula, a dinoflagellate lacking periodicity in spontaneous bio‐luminescence, shows a characteristic circadian rhythm of plastid movements which can be monitored photographically in individual cells. The rhythm persists under free‐running conditions in constant dim light (40–50 Ix), but is damped out already in LL of 100 lx.     

The oxidative stress and the mitochondrial dysfunction caused by endotoxemia are prevented by α-lipoic acid

The aims of this work were to study the mitochondrial function and to evaluate (a) the oxidative stress in real time in an acute model of endotoxemia and (b) the effect of α-lipoic acid (LA, 100 mg/kg) as a therapeutic strategy to be considered. In rats treated with lipopolisaccharide (LPS, 10 mg/kg), a 1.4-fold increase was observed in in situ skeletal muscle chemiluminescence. Experimental sepsis increased oxygen consumption in tissue cubes (1 mm³) by 30% for heart and diaphragm and impaired state 3 mitochondrial respiration rate in the three organs (liver, diaphragm and heart) studied. Only complex I activity in heart and diaphragm and complex IV activity in diaphragm were found impaired in this septic model. The production of NO by submitochondrial membranes was found increased by 80% in the diaphragm and by 35% in the heart of septic rats. The treatment with LA prevented the oxidative stress and mitochondrial dysfunction observed in this model.     

Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy–causing mutations

Lamin filaments are major components of the nucleoskeleton that bind LINC complexes and many nuclear membrane proteins. The tail domain of lamin A directly binds 21 known partners, including actin, emerin, and SREBP1, but how these interactions are regulated is unknown. We report small ubiquitin-like modifier 1 (SUMO1) as a major new posttranslational modification of the lamin A tail. Two SUMO1 modification sites were identified based on in vitro SUMOylation assays and studies of Cos-7 cells. One site (K420) matches the SUMO1 target consensus; the other (K486) does not. On the basis of the position of K486 on the lamin A Ig-fold, we hypothesize the SUMO1 E2 enzyme recognizes a folded structure–dependent motif that includes residues genetically linked to familial partial lipodystrophy (FPLD). Supporting this model, SUMO1-modification of the lamin A tail is reduced by two FPLD-causing mutations, G465D and K486N, and by single mutations in acidic residues E460 and D461. These results suggest a novel mode of functional control over lamin A in cells.     

Modulation of mammalian circadian rhythms by tumor necrosis factor-α

Systemic low doses of the endotoxin lipopolysaccharide (LPS, 100?µg/kg) administered during the early night induce phase-delays of locomotor activity rhythms in mice. Our aim was to evaluate the role of tumor necrosis factor (Tnf)-alpha and its receptor 1/p55 (Tnfr1) in the modulation of LPS-induced circadian effects on the suprachiasmatic nucleus (SCN). We observed that Tnfr1-defective mice (Tnfr1 KO), although exhibiting similar circadian behavior and light response to that of control mice, did not show LPS-induced phase-delays of locomotor activity rhythms, nor LPS-induced cFos and Per2 expression in the SCN and Per1 expression in the paraventricular hypothalamic nucleus (PVN) as compared to wild-type (WT) mice. We also analyzed Tnfr1 expression in the SCN of WT mice, peaking during the early night, when LPS has a circadian effect. Peripheral inoculation of LPS induced an increase in cytokine/chemokine levels (Tnf, Il-6 and Ccl2) in the SCN and in the PVN. In conclusion, in this study, we show that LPS-induced circadian responses are mediated by Tnf. Our results also suggest that this cytokine stimulates the SCN after LPS peripheral inoculation; and the time-related effect of LPS (i.e. phase shifts elicited only at early night) might depend on the increased levels of Tnfr1 expression. We also confirmed that LPS modulates clock gene expression in the SCN and PVN in WT but not in Tnfr1 KO mice.

Highlights: We demonstrate a fundamental role for Tnf and its receptor in circadian modulation by immune stimuli at the level of the SCN biological clock.     

Chronobiological study on the circadian rhythm of blood gastrin in non‐synchronized young healthy males as tested by different statistical methods

Abstract

In this study, the day course of blood gastrin was investigated in a group of 15 students whose eating habits had not been synchronized. A significant 24‐h pattern could be found. Because of the discrepancy between the rhythm parameters obtained by Cosinor analysis and the visual inspection of the original data, a new method of testing the suitability of the Cosinor model was applied. On analysis of our data we came to the conclusion that the circadian rhythm of blood gastrin could have an endogenous as well as an exogenous component.     

Redundancy of stomatal control for the circadian photosynthetic rhythm in Kalanchoë daigremontiana Hamet et Perrier

In continuous light, the Crassulacean acid metabolism plant Kalanchoe daigremontiana Hamet et Perrier has a circadian rhythm of gas exchange with peaks occurring during the subjective night. The rhythm of gas exchange is coupled to a weak, reverse phased rhythm of quantum yield of photosystem II (Phi (PSII)). To test if the rhythm of Phi (PSII) persists in the absence of stomatal control, leaves were coated with a thin layer of translucent silicone grease which prevented CO2 and H2O exchange. In spite of this treatment, the rhythm of Phi (PSII) occurred with close to normal phase timing and with a much larger amplitude than in uncoated leaves. The mechanism underlying the Phi (PSII) rhythm in coated leaves can be explained by a circadian activity of phosphoenolpyruvate carboxylase (PEPC). At peaks of PEPC activity, the small amount of CO2 contained in the coated leaf could have become depleted, preventing the carboxylase activity of Rubisco and causing decreases in electron transport rates (observed as deep troughs of Phi (PSII) at 23-h in LL and at ca. 24-h intervals afterwards). Peaks of Phi (PSII) would be caused by a downregulation of PEPC leading to improved supply of CO2 to Rubisco. Substrate limitation of photochemistry at 23 h (trough of Phi (PSII)) was also suggested by the weak response of ETR in coated leaves to stepwise light enhancement. These results show that photosynthetic rhythmicity in K. daigremontiana is independent of stomatal regulation and may originate in the mesophyll.     

Might cardiac catheterization influence diurnal rhythm of the steroid stress hormones secretion?

Glucocorticoids (GCs) are steroid hormones produced by the adrenal cortex in reaction to stress stimuli. GCs production is not stable over a 24-hour period; the plasma concentration peaks in the morning (approximately upon awakening) and then the plasma levels decrease, reaching the nadir in the evening. In our experiments, the levels of cortisol, cortisone, DHEA and DHEAS were tested in young female pigs (n=23) during heart catheterization at two different day times (in the morning and in the afternoon). The non-parametric Mann-Whitney test for statistical analysis was used. We found only minimal statistical differences in studied markers between the morning and afternoon group (p>0.05). The absence of circadian variation in GCs levels could originate either at an early age of our experimental pigs, or in stressful conditions on the experiment day, or most likely the day before (e.g. social isolation, fasting, transport, and catheterization), respectively. We can conclude there is no difference in the stress load between morning and afternoon experiments, and therefore we can assume the stress load is not a limiting factor for the timing when catheterization should be preferably performed.