Diurnal Oscillations Research Articles

Determining groundwater recharge and vapor flow in dune sediments using a weighable precision meteo lysimeter

Dune belts are crucial for the recharge of coastal aquifers. In spite of their hydrological relevance for the maintenance of precious natural wetland and wildlife environments and a range of other ecosystem services, only limited knowledge of soil water dynamics in dune belts is currently available. This study presents soil water balance components measured during one hydrological year using a high precision meteo-lysimeter with lower boundary control installed in a coastal dune belt under a dry subhumid climate in southern Spain close to the Atlantic Ocean. The site is equipped with a cylindrical lysimeter of 1 m2 surface and 1.50 m height (METER Group, Inc. USA) and a weighing resolution of 10 g, 2 SC650 soil moisture sensors (Campbell Scientific, Logan, UT) and 1 automatic meteorological station. The lower boundary condition at the bottom of the lysimeter is controlled at 1.4 m depth by a bidirectional peristaltic pump to maintain field conditions. Results show a recharge rate of 64% of the precipitation measured by the lysimeter. Diurnal oscillations of the measured upper boundary flow during days without rainfall represented vapor adsorption and real evaporation rates ranging between 0.3 and 0.4 mm/day and 0.4 and 0.6 mm/day, respectively throughout the whole year summing up an annual vapor adsorption of 77 mm. The measured precipitation of the lysimeter exceeded pluviometer data by 13% as a result of vapor adsorption. The presented results provide a precise balance of soil water components in a coastal dune belt including the relevant contribution of vapor flow.

Diurnal protein oscillation profiles in Drosophila head.

Circadian clocks control daily rhythms in physiology, metabolism and behaviour in most organisms. Proteome-wide analysis of protein oscillations is still lacking in Drosophila. In this study, the total protein and phosphorylated protein in Drosophila heads in a 24-h daily time-course were assayed by using the isobaric tags for relative and absolute quantitation (iTRAQ) method, and 10 and 7 oscillating proteins as well as 19 and 22 oscillating phosphoproteins in the w1118 control and ClkJrk mutant strains were separately identified. Lastly, we performed a mini screen to investigate the functions of some oscillating proteins in circadian locomotion rhythms. This study provides the first proteomic profiling of diurnally oscillating proteins in fly heads, thereby providing a basis for further mechanistic studies of these proteins in circadian rhythm.

The circadian clock regulates the diurnal levels of microbial short-chain fatty acids and their rhythmic effects on colon contractility in mice.

The microbiota shows diurnal oscillations that are synchronized by the host's circadian clock and feeding rhythms. Short-chain fatty acids (SCFAs) produced by the microbiota are possible synchronizers of peripheral circadian clocks. We aimed to investigate whether faecal SCFAs show a diurnal rhythm that regulates the rhythm of SCFA receptor expression (FFAR2/3, OLFR78, HCAR2) and SCFA-induced colonic contractility. The role of the circadian clock was studied in mice lacking the core clock gene Bmal1. Mice were sacrificed at 4-hour intervals. Faecal SCFA concentrations and SCFA receptor expression were determined. The effect of increasing concentrations of a SCFA mix on electrical field-induced neural responses in colon strips was measured isometrically. Diurnal fluctuations in faecal SCFA concentrations (peak 4hours after lights on) were observed that were in phase with the rhythm of Ffar2/3 expression in the colonic muscle layer. Olfr78 expression was not diurnal and Hcar2 was not detectable. The inhibitory effect of a SCFA mix on neural contractions in colonic smooth muscle strips showed a diurnal rhythm and oscillated in phase with faecal SCFA concentrations and Ffar2/3 expression. In contrast, neither excitatory neural responses nor acetylcholine-induced smooth muscle contractions showed a diurnal rhythm. In Bmal1-/- mice, no fluctuations in faecal SCFA levels, Ffar3 expression and neural responses to SCFAs were observed. Diurnal microbial SCFA levels regulate the rhythm of Ffar3 expression in the colonic myenteric plexus, which causes rhythmicity in SCFA-induced colonic motility. Deletion of Bmal1 abolishes rhythmicity of SCFA levels and their downstream effects.

Effects of calcium particle films and natural shading on ecophysiological parameters of conilon coffee

Conilon coffee (Coffea canephora Pierre ex A. Froehner) is an important agricultural crop in Brazil due to its high economic value. This plant species is sensitive to the effects of high levels of solar radiation and temperature, which could limit its wide cultivation in the Brazilian Northeast region. However, management practices such as shading could increase the feasibility of its cultivation. This study aimed to evaluate the effects of different shading methods and the use of calcium particle films on the conilon coffee ecophysiological parameters in the coastal flatland the State of Sergipe, Brazil. The field experiment was carried out as randomized block design with four treatments: i) Natural shading (intercropping coffee and banana plants), ii) Artificial shading with 10% w/v CaCO3 particle films; iii) Artificial shading with 20% w/v CaO particle films; and iv) and control (without shading), and four replicates. Measurements were performed 7, 21 and 35 days after film application at 9:00 h and 12:00 h. Individual parameters, gas exchange efficiency, chlorophyll a fluorescence and maintenance of film coverage on leaves were evaluated. Artificial shading with particle films promoted greater physiological stability of the coffee plants during diurnal meteorological oscillations as compared to the control, resulting in higher rates of liquid photosynthesis (A), better control on stomatal conductance (gs) and transpiration (E). Improvement was also observed in the plant water use efficiency (WUE and IWUE) and in the reduction of leaf temperature. Calcium particle films were more efficient in providing protection to the photosystems and improving photochemical efficiency and energy conversion for photophosphorylation than natural shading. However, the results were more pronounced at 21 days after film application and more persistent for treatment with 20% CaO film. Therefore, calcium particle films are useful tools to alleviate coffee plants stress under adverse climate conditions.

Long-term observation of midlatitude quasi 2-day waves by a water vapor radiometer

Abstract. A mesospheric water vapor data set obtained by the middle atmospheric water vapor radiometer (MIAWARA) close to Bern, Switzerland (46.88∘ N, 7.46∘ E) during October 2010 to September 2017 is investigated to study the long-term evolution and variability of quasi 2-day waves (Q2DWs). We present a climatological overview and an insight on the dynamical behavior of these waves with the occurring spectrum of periods as seen from a midlatitude observation site. Such a large and nearly continuous measurement data set as ours is rare and of high scientific value. The core results of our investigation indicate that the activity of the Q2DW manifests in burst-like events and is higher during winter months (November–February) than during summer months (May–August) for the altitude region of the mesosphere (up to 0.02 hPa in winter and up to 0.05 hPa in summer) accessible for the instrument. Single Q2DW events reach at most about 0.8 ppm in the H2O amplitudes. Further, monthly mean Q2DW amplitude spectra are presented and reveal a high-frequency variability between different months. A large fraction of identified Q2DW events (20 %) develop periods between 38 and 40 h. Further, we show the temporal evolution of monthly mean Q2DW oscillations continuously for all months and separated for single months over 7 years. The analysis of autobicoherence spectra gives evidence that Q2DWs are sometimes phase coupled to diurnal oscillations to a high degree and to waves with a period close to 18 h.

A Simple Model for the Anomalous Counterclockwise Turning of the Surface Wind with Time over the Great Plains of the United States

AbstractA recent study found that surface hodographs over the Great Plains of the United States turn in a counterclockwise direction with time. This observed turning is opposite of the clockwise turning observed (and expected, based on theory) at higher altitudes. Using a mesoscale forecast model, the same study shows that it has the same hodograph behavior as found in the observations. The study further shows that the reason for this anomalous counterclockwise turning is the decoupling of the surface layer from the boundary layer after sunset and its recoupling after sunrise. The present paper presents a simple model for this behavior by extending a recent analytical model for the diurnal oscillation to include the surface-layer effect. In addition, selected solution features are analyzed in terms of several of the nondimensional input parameters.

Abstract 488: Clock Regulates Autophagy and Cell Survival of Cardiac Myocytes During Hypoxia Stress

Circadian rhythms play a fundamental role in cell metabolism and tissue homeostasis and are influenced by the diurnal oscillation of cellular circadian clock genes. Zeitgebers influence the activation of the circadian rhythm by serving as molecular switches for the intrinsic cellular clock. Herein, we provide new evidence that hypoxia is a Zietgeber for the circadian rhythm and regulator of clock gene expression in cardiac myocytes. We further show that clock gene regulation promotes survival of cardiac myocytes by a mechanism that bi-directionally influences autophagy. Cardiac myocytes exhibited phasic oscillations in clock gene expression under basal conditions. Interestingly, in contrast to control cells, a marked time dependent decline in clock gene transcription was observed in cardiac myocytes subjected to hypoxia with maximal decline occurring at 18hrs. This coincided with a reciprocal increase in mitochondrial autophagy genes including beclin-1 . Loss of function mutations of clock that disrupted nuclear localization or DNA binding promoted wide-spread cell death. Hence, the findings of the present study provide the first direct evidence that hypoxia is a Zeitgeber for regulating Clock gene expression and cell survival of cardiac myocytes during hypoxic injury.

Diurnal oscillations in human salivary microRNA and microbial transcription: Implications for human health and disease.

The microbiome plays a vital role in human health and disease. Interaction between human hosts and the microbiome occurs through a number of mechanisms, including transcriptomic regulation by microRNA (miRNA). In animal models, circadian variations in miRNA and microbiome elements have been described, but patterns of co-expression and potential diurnal interaction in humans have not. We investigated daily oscillations in salivary miRNA and microbial RNA to explore relationships between these components of the gut-brain-axis and their implications in human health. Nine subjects provided 120 saliva samples at designated times, on repeated days. Samples were divided into three sets for exploration and cross-validation. Identification and quantification of host miRNA and microbial RNA was performed using next generation sequencing. Three stages of statistical analyses were used to identify circadian oscillators: 1) a two-way analysis of variance in the first two sample sets identified host miRNAs and microbial RNAs whose abundance varied with collection time (but not day); 2) multivariate modeling identified subsets of these miRNAs and microbial RNAs strongly-associated with collection time, and evaluated their predictive ability in an independent hold-out sample set; 3) regulation of circadian miRNAs and microbial RNAs was explored in data from autistic children with disordered sleep (n = 77), relative to autistic peers with typical sleep (n = 63). Eleven miRNAs and 11 microbial RNAs demonstrated consistent diurnal oscillation across sample sets and accurately predicted collection time in the hold-out set. Associations among five circadian miRNAs and four circadian microbial RNAs were observed. We termed the 11 miRNAs CircaMiRs. These CircaMiRs had 1,127 predicted gene targets, with enrichment for both circadian gene targets and metabolic signaling processes. Four CircaMiRs had “altered” expression patterns among children with disordered sleep. Thus, novel and correlated circadian oscillations in human miRNA and microbial RNA exist and may have distinct implications in human health and disease.

Circadian clock component PERIOD2 regulates diurnal expression of Na+/H+ exchanger regulatory factor-1 and its scaffolding function

A number of diverse cell-surface proteins are anchored to the cytoskeleton via scaffold proteins. Na+/H+ exchanger regulatory factor-1 (NHERF1), encoded by the Slc9a3r1 gene, functions as a scaffold protein, which is implicated in the regulation of membrane expression of various cell-surface proteins. Here, we demonstrate that the circadian clock component PERIOD2 (PER2) modulates transcription of the mouse Slc9a3r1 gene, generating diurnal accumulation of NHERF1 in the mouse liver. Basal expression of Slc9a3r1 was dependent on transcriptional activation by p65/p50. PER2 bound to p65 protein and prevented p65/p50-mediated transactivation of Slc9a3r1. The time-dependent interaction between PER2 and p65 underlay diurnal oscillation in the hepatic expression of Slc9a3r1/NHERF1. The results of immunoprecipitation experiments and liquid chromatography-mass spectrometry analysis of mouse liver revealed that NHERF1 time-dependently interacted with fatty acid transport protein-5 (FATP5). Temporary accumulation of NHERF1 protein stabilized plasmalemmal localization of FATP5, thereby enhancing hepatic uptake of fatty acids at certain times of the day. Our results suggest an unacknowledged role for PER2 in regulating the diurnal expression of NHERF1 in mouse liver. This machinery also contributed to diurnal changes in the ability of hepatic cells to uptake fatty acids.

Accumulation of sorbitol in the sciatic nerve modulates circadian properties of diabetes-induced neuropathic pain hypersensitivity in a diabetic mouse model

The intensity of pain in diabetic neuropathy varies in a circadian time-dependent manner. It is well known that diabetes has two distinct types, which are differentiated based on the cause of the disease. Previous studies have yet to compare the circadian properties of the pain intensity of diabetic neuropathy between type I and type II diabetes. In this study, we demonstrated that the pain intensity of diabetic peripheral neuropathy in a db/db mouse model of type II diabetes showed a significant diurnal oscillation, but such time-dependent oscillation was not detected in a streptozotocin (STZ)-induced type I diabetic mouse model. The polyol pathway-induced accumulation of sorbitol in peripheral nerve cells suppresses Na+/K+-ATPase activity, which is associated with the intensity of pain in diabetic neuropathy. In db/db mice, this accumulation of sorbitol in peripheral nerve cells showed significant diurnal oscillation. In addition, pain intensity and Na+/K+-ATPase activity were decreased at the peak time of sorbitol accumulation in these mice. Although STZ-induced diabetic mice also showed sorbitol accumulation and Na+/K+-ATPase dysfunction, these measures did not oscillate in a time-dependent manner. These findings reveal differences in the circadian properties of pain hypersensitivity in mouse models of type I and type II diabetes, and also provide ideas for developing novel approaches to the management of diabetic neuropathy.

Light exposure influences the diurnal oscillation of gut microbiota in mice

The gut microbiota exhibit diurnal compositional and functional oscillations that influence the host homeostasis. However, the upstream factors that affect the microbial oscillations remain elusive. Here, we focused on the potential impact of light exposure, the main factor that affects the host circadian oscillation, on the diurnal oscillations of intestinal microflora to explore the upstream factor that governs the fluctuations of the gut microbes. The gut microbiota of the mice that were underwent regular light/dark (LD) cycles exhibited a robust rhythm at both compositional and functional level, in all parts of the intestine. Comparably, constant darkness (Dark-Dark, DD) led to the loss of the rhythmic oscillations in almost all parts of the intestine. Additionally, the abundance of Clostridia in DD conditions was dramatically enhanced in the small intestine. Our data indicated light exposure is the upstream factor that governs the regular diurnal fluctuations of gut microbiota in vivo.

Circadian rhythms, refractive development, and myopia.

Despite extensive research, mechanisms regulating postnatal eye growth and those responsible for ametropias are poorly understood. With the marked recent increases in myopia prevalence, robust and biologically-based clinical therapies to normalize refractive development in childhood are needed. Here, we review classic and contemporary literature about how circadian biology might provide clues to develop a framework to improve the understanding of myopia etiology, and possibly lead to rational approaches to ameliorate refractive errors developing in children. Increasing evidence implicates diurnal and circadian rhythms in eye growth and refractive error development. In both humans and animals, ocular length and other anatomical and physiological features of the eye undergo diurnal oscillations. Systemically, such rhythms are primarily generated by the 'master clock' in the surpachiasmatic nucleus, which receives input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) through the activation of the photopigment melanopsin. The retina also has an endogenous circadian clock. In laboratory animals developing experimental myopia, oscillations of ocular parameters are perturbed. Retinal signaling is now believed to influence refractive development; dopamine, an important neurotransmitter found in the retina, not only entrains intrinsic retinal rhythms to the light:dark cycle, but it also modulates refractive development. Circadian clocks comprise a transcription/translation feedback control mechanism utilizing so-called clock genes that have now been associated with experimental ametropias. Contemporary clinical research is also reviving ideas first proposed in the nineteenth century that light exposures might impact refraction in children. As a result, properties of ambient lighting are being investigated in refractive development. In other areas of medical science, circadian dysregulation is now thought to impact many non-ocular disorders, likely because the patterns of modern artificial lighting exert adverse physiological effects on circadian pacemakers. How, or if, such modern light exposures and circadian dysregulation contribute to refractive development is not known. The premise of this review is that circadian biology could be a productive area worthy of increased investigation, which might lead to the improved understanding of refractive development and improved therapeutic interventions.

A proteomics landscape of circadian clock in mouse liver

As a circadian organ, liver executes diverse functions in different phase of the circadian clock. This process is believed to be driven by a transcription program. Here, we present a transcription factor (TF) DNA-binding activity-centered multi-dimensional proteomics landscape of the mouse liver, which includes DNA-binding profiles of different TFs, phosphorylation, and ubiquitylation patterns, the nuclear sub-proteome, the whole proteome as well as the transcriptome, to portray the hierarchical circadian clock network of this tissue. The TF DNA-binding activity indicates diurnal oscillation in four major pathways, namely the immune response, glucose metabolism, fatty acid metabolism, and the cell cycle. We also isolate the mouse liver Kupffer cells and measure their proteomes during the circadian cycle to reveal a cell-type resolved circadian clock. These comprehensive data sets provide a rich data resource for the understanding of mouse hepatic physiology around the circadian clock.

Effects of sleeve gastrectomy on the composition and diurnal oscillation of gut microbiota related to the metabolic improvements

BackgroundDisruptions of the composition and diurnal oscillation of gut microbiota are involved in metabolic disorders. ObjectivesTo identify alterations in both the composition and diurnal oscillation of gut microbiota after high-fat diet (HFD) feeding and sleeve gastrectomy (SG) related to host metabolic status. SettingUniversity laboratories. MethodsTwenty-one 6-week-old male C57 BL/6 J mice were randomized on an HFD (n = 14) or normal chow (NC, n = 7). After 14 weeks of feeding, HFD-induced obese mice were randomized to receive either SG or sham surgery (n = 7 in each group). Fecal samples were collected every 6 hours over a 24-hour period at 14 weeks of NC or HFD feeding and subsequently 8 weeks after surgery. The composition and diurnal oscillation of gut microbiota were characterized using next-generation Illumina sequencing of 16 S rDNA. ResultsHFD feeding led to adiposity, disrupted composition, and impaired diurnal oscillation of gut microbiota relative to NC. After surgery, SG mice had considerable weight loss, improved glucose tolerance, and insulin sensitivity compared with sham mice. SG restored the reduced richness and disruptions in the composition of gut microbiota. The diminished diurnal oscillation of gut microbiota was improved after SG. ConclusionSG not only changed the disrupted composition of gut microbiota toward that of NC feeding, but also improved the dampened diurnal oscillation of gut microbiota due to HFD feeding.

NRF2 regulates core and stabilizing circadian clock loops, coupling redox and timekeeping in Mus musculus.

Diurnal oscillation of intracellular redox potential is known to couple metabolism with the circadian clock, yet the responsible mechanisms are not well understood. We show here that chemical activation of NRF2 modifies circadian gene expression and rhythmicity, with phenotypes similar to genetic NRF2 activation. Loss of Nrf2 function in mouse fibroblasts, hepatocytes and liver also altered circadian rhythms, suggesting that NRF2 stoichiometry and/or timing of expression are important to timekeeping in some cells. Consistent with this concept, activation of NRF2 at a circadian time corresponding to the peak generation of endogenous oxidative signals resulted in NRF2-dependent reinforcement of circadian amplitude. In hepatocytes, activated NRF2 bound specific enhancer regions of the core clock repressor gene Cry2, increased Cry2 expression and repressed CLOCK/BMAL1-regulated E-box transcription. Together these data indicate that NRF2 and clock comprise an interlocking loop that integrates cellular redox signals into tissue-specific circadian timekeeping.

Meal-related oscillations in the serum serotonin levels in healthy young men.

Serotonin acts as a neurotransmitter in the central and enteric nervous systems, modulating psychological, metabolic and gastrointestinal functions. Serotonin is also found in the serum or plasma, indicating its potential role as a hormone. We aimed to assess the 24-hour diurnal profile of serum serotonin in relation to meal ingestion in healthy adult men. Ten healthy (5 lean and 5 obese) male subjects were enrolled in this study. Blood samples were drawn every 30-60minutes throughout a 24-hour period to determine the serotonin levels. Three meals were provided on a fixed schedule. To confirm the effect of meal intake on serum serotonin levels, 4 subjects underwent fasting until 1500h and were then provided a meal without notice. Serum serotonin levels had distinct diurnal variations, with the highest levels early in the morning and the lowest levels in the midafternoon and during sleep. Notably, these diurnal oscillations were markedly reduced in obese subjects. Fluctuations in serum serotonin levels were associated with meal intake, and the levels peaked 30minutes before meals and exhibited a trough during the postprandial period. Fasting blunted the meal-related oscillations in serum serotonin levels. Moreover, unexpected meal intake did not lead to a premeal increase in serum serotonin levels. Serum serotonin levels displayed meal-related diurnal oscillations, which were disrupted by fasting and obesity. These findings suggest the possibility that circulating serotonin modulates metabolic function in humans.

Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4

Glucocorticoids are steroid hormones with strong anti-inflammatory and immunosuppressive effects that are produced in a diurnal fashion. Although glucocorticoids have the potential to induce interleukin-7 receptor (IL-7R) expression in Tcells, whether they control Tcell homeostasis and responses at physiological concentrations remains unclear. We found that glucocorticoid receptor signaling induces IL-7R expression in mouse Tcells by binding to an enhancer of the IL-7Rα locus, with a peak at midnight and a trough at midday. This diurnal induction of IL-7R supported the survival of Tcells and their redistribution between lymph nodes, spleen, and blood by controlling expression of the chemokine receptor CXCR4. In mice, Tcell accumulation in the spleen at night enhanced immune responses against soluble antigens and systemic bacterial infection. Our results reveal the immunoenhancing role of glucocorticoids in adaptive immunity and provide insight into how immune function is regulated by the diurnal rhythm.

Open-circuit potential of a Pt electrode immersed in different aqueous solutions

The aim of this study is to investigate the multi-day behavior of the electromotive force (EMF) between Pt and reference Ag/AgCl, KClsat. electrodes immersed in various aqueous systems (deionized water, 1 × 10−3 M H2SO4 solution and 0.15 M KCl solution) at 32 °C and also at ambient temperature, without oxygen removal and redox species introduction. The control test of EMF behavior in the presence of redox species was performed with cyanide complexes of Fe2+ and Fe3+ ions at ambient temperature. In experiments with deionized water, systems were protected against the influence of daylight and static electricity. The results have shown diurnal oscillations of EMF in all investigated systems with amplitudes in the range ≈ 1 to 25 mV depending on applied experimental conditions. EMF oscillations in deionized water were independent on the applied temperature and yielded amplitudes of 15–25 mV in daylight regime, and only a few mV when protected from its influence. The effect of electrostatic electricity was not observed. Diurnal EMF oscillations with the amplitudes ≤ 5 mV were observed individually in 0.15 M KCl solution, redox system and after 4 days of investigation in H2SO4 solution. Results presented in this work pointed out that the behavior of Pt–oxygen electrode is specific and very complex, even in the simplest system such as deionized water. To investigate the origin of the observed EMF oscillations and the application of Pt–oxygen electrode in in situ multi-day dynamics studies under open-circuit potential condition, additional theoretical and experimental methods and particularly electrochemical ones, must be applied.

Genetic deletion of the circadian clock transcription factor BMAL1 and chronic alcohol consumption differentially alter hepatic glycogen in mice.

Multiple metabolic pathways exhibit time-of-day-dependent rhythms that are controlled by the molecular circadian clock. We have shown that chronic alcohol is capable of altering the molecular clock and diurnal oscillations in several elements of hepatic glycogen metabolism ( 19 , 44 ). Herein, we sought to determine whether genetic disruption of the hepatocyte clock differentially impacts hepatic glycogen content in chronic alcohol-fed mice. Male hepatocyte-specific BMAL1 knockout (HBK) and littermate controls were fed control or alcohol-containing diets for 5 wk to alter hepatic glycogen content. Glycogen displayed a significant diurnal rhythm in livers of control genotype mice fed the control diet. While rhythmic, alcohol significantly altered the diurnal oscillation of glycogen in livers of control genotype mice. The glycogen rhythm was mildly altered in livers of control-fed HBK mice. Importantly, glycogen content was arrhythmic in livers of alcohol-fed HBK mice. Consistent with these changes in hepatic glycogen content, we observed that some glycogen and glucose metabolism genes were differentially altered by chronic alcohol consumption in livers of HBK and littermate control mice. Diurnal rhythms in glycogen synthase (mRNA and protein) were significantly altered by alcohol feeding and clock disruption. Alcohol consumption significantly altered Gck, Glut2, and Ppp1r3g rhythms in livers of control genotype mice, with diurnal rhythms of Pklr, Glut2, Ppp1r3c, and Ppp1r3g further disrupted (dampened or arrhythmic) in livers of HBK mice. Taken together, these findings show that chronic alcohol consumption and hepatocyte clock disruption differentially influence the diurnal rhythm of glycogen and various key glycogen metabolism-related genes in the liver. NEW & NOTEWORTHY We report that circadian clock disruption exacerbates alcohol-mediated alterations in hepatic glycogen. We observed differential responsiveness in diurnal rhythms of glycogen and glycogen metabolism genes and proteins in livers of hepatocyte-specific BMAL1 knockout and littermate control mice fed alcohol. Our findings provide new insights into potential mechanisms by which alcohol alters glycogen, an important energy source for liver and other organs.

Abstract 20933: Regulation of Hypoxia Induced Cardiac Cell Death by the Intrinsic Circadian Clock

Circadian rhythms play a fundamental role in cell metabolism and tissue homeostasis and are influenced by the diurnal oscillation of cellular circadian clock genes. Zeitgebers influence the activation of the circadian rhythm by serving as molecular switches for the intrinsic cellular clock. Herein, we provide new evidence that hypoxia is a Zietgeber for the circadian rhythm and regulator of clock gene expression in cardiac myocytes. We further show that clock gene regulation promotes survival of cardiac myocytes by a mechanism that bi-directionally influences the inducible death protein Bnip3. Cardiac myocytes exhibited phasic oscillations in clock gene expression under basal conditions. Interestingly, in contrast to control cells, a marked time dependent decline in clock gene transcription was observed in cardiac myocytes subjected to hypoxia with maximal decline occurring at 18hrs. This coincided with a reciprocal increase in the expression of the mitochondrial autophagy protein Bnip3 and cell death. Given that Bnip3 is transcriptionally repressed under basal conditions, we reasoned that clock may promote cell survival by negatively regulating Bnip3 gene transcription. While Bnip3 transcription was markedly increased in cardiac myocytes subjected to hypoxia, gain of function of clock suppressed Bnip3 gene activation and cell death of cardiac myocytes. Hence, the findings of the present study provide the first direct evidence that hypoxia is a circadian Zeitgeber for circadian rhythm in cardiac myocytes. We further show that circadian protein Clock regulates cell survival during hypoxic injury by a mechanism that involves the transcriptional repression of Bnip3.