Diurnal Oscillations Research Articles

A Systematic Review of Utilisation of Diurnal Timing Information in Clinical Trial Design for Long QT Syndrome

Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 h, and drug delivery. Despite guidelines having been issued around the analysis of 24-h ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.

Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice.

Selecting the most appropriate dosing time of PD-1/PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy.

Predicting resilience and stability of early second‐growth forests

AbstractIdentifying deforested areas with high potential for natural forest recovery can be used as an aid for ecological restoration projects at large‐scale. However, accurate predictions that infer the resilience (i.e. recovery rate after deforestation) and stability (i.e. the ability of the ecosystem to maintain its functions) of early second‐growth forests are scarce at a regional scale. Here, we investigated the effect of climate, soil and topography on the resilience and stability of 165 early second‐growth forests throughout the Brazilian Atlantic Forest. We also built prediction maps of potential resilience and stability to identify where reforestation could be optimized in the early stages of forest succession. We assessed the resilience and stability through an interannual plant primary productivity time series using a normalized difference vegetation index. Our analysis reveals that resilience was mainly associated with isothermality (i.e. diurnal temperature oscillation relative to the annual temperature oscillation) and precipitation of the warmest quarter. In turn, stability was mainly associated with the probability of bedrock occurrence, annual precipitation and precipitation seasonality. The prediction maps show a spatial pattern in which potential resilience and stability increase from north to south of the Atlantic Forest. Forest restoration can be optimized in regions with high potential resilience and stability, such as an isolated area on the north coast in the Bahia state and the southern region. However, restoration may require active practices and management in regions with low potential for both ecosystem properties, such as the north inland in the Bahia and Minas Gerais states. This ecosystemic approach can help achieve Atlantic Forest restoration commitments.

Plant Responses Underlying Timely Specialized Metabolites Induction of Brassica Crops.

A large subset of plant stress-signaling pathways, including those related with chemical defense production, exhibit diurnal or circadian oscillations. However the extent to which diurnal or circadian time influences the stress mediated accumulation of plant specialized metabolites remains largely unknown. Because plant responses to physical stress (e.g., wounding) is considered a common component of mounting a response against a broad range of environmental stresses, including herbivory, we have utilized mechanical wounding as the stress stimulus to determine the direct contribution of time of day on the induced defenses of Brassica crops. We analyzed glucosinolates (GSLs) from leaves of broccoli (Brassica oleracea) and turnip greens (Brassica rapa) following exposure to mechanical wounding at dawn (ZT0), mid-day (ZT4), and dusk (ZT8). Several GSLs differentially accumulated and their changes depended upon the time of day at wounding was performed. This response varied considerably between species. In a parallel experiment, we investigated whether diurnal activation of Brassica phytochemicals in response to wounding might prime plants against herbivore attack. Results showed that maximal response of plant chemical defense against larvae of the generalist pest Mamestra brassicae occurred at ZT0 in broccoli and ZT8 in turnip greens. Metabolome analysis for global trends of time dependent compounds showed that sulfur-containing phytochemicals, GSL hydrolysis products, auxin-signaling components, and other metabolites activators of plant disease resistance (nicotinamide and pipecolate) had important contributions to the responses of M. brassicae feeding behavior in broccoli at morning. Overall, the findings in this study highlight a significant role for time of day in the wound stress responsive metabolome, which can in turn affect plant-herbivore interactions.

6-Formylindolo[3,2-b]carbazole, a Potent Ligand for the Aryl Hydrocarbon Receptor Produced Both Endogenously and by Microorganisms, can Either Promote or Restrain Inflammatory Responses

The aryl hydrocarbon receptor (AHR) binds major physiological modifiers of the immune system. The endogenous 6-formylindolo[3,2-b]carbazole (FICZ), which binds with higher affinity than any other compound yet tested, including TCDD, plays a well-documented role in maintaining the homeostasis of the intestines and skin. The effects of transient activation of AHR by FICZ differ from those associated with continuous stimulation and, depending on the dose, include either differentiation into T helper 17 cells that express proinflammatory cytokines or into regulatory T cells or macrophages with anti-inflammatory properties. Moreover, in experimental models of human diseases high doses stimulate the production of immunosuppressive cytokines and suppress pathogenic autoimmunity. In our earlier studies we characterized the formation of FICZ from tryptophan via the precursor molecules indole-3-pyruvate and indole-3-acetaldehyde. In the gut formation of these precursor molecules is catalyzed by microbial aromatic-amino-acid transaminase ArAT. Interestingly, tryptophan can also be converted into indole-3-pyruvate by the amino-acid catabolizing enzyme interleukin-4 induced gene 1 (IL4I1), which is secreted by host immune cells. By thus generating derivatives of tryptophan that activate AHR, IL4I1 may have a role to play in anti-inflammatory responses, as well as in a tumor escape mechanism that reduces survival in cancer patients. The realization that FICZ can be produced from tryptophan by sunlight, by enzymes expressed in our cells (IL4I1), and by microorganisms as well makes it highly likely that this compound is ubiquitous in humans. A diurnal oscillation in the level of FICZ that depends on the production by the fluctuating number of microbes might influence not only intestinal and dermal immunity locally, but also systemic immunity.

Augmented early aged neutrophil infiltration contributes to late remodeling post myocardial infarction.

Neutrophils oscillate in number and phenotype after being released from bone marrow. Myocardial infarction (MI) outcome is associated with the time-of-day of ischemia onset. However, the underlying contributive factors of neutrophils to cardiac remodeling post MI remain unknown. We examined neutrophil infiltration into the heart and cardiac function and remodeling in C57BL/6J MI model created by permanent coronary ligation at different zeitgeber times (ZT). We found that cell surface markers (CD62L, CXCR2, CXCR4) of neutrophils in peripheral blood lost diurnal oscillation 24h post MI. Meanwhile, circadian gene Bmal1, Nr1d1, and Clock mRNA expression displayed disrupted diurnal patterns. Flow cytometry showed augmented aged neutrophil (CD11b+Ly6G+CD62Llow) infiltration into the heart along with increased circulating aged neutrophils in MI groups with more infiltration at ZT5 (p<0.05), but no difference for aged neutrophil infiltration at different ZT points in late stage. Infiltrated neutrophils had significantly higher CXCL2 and CXCR2 but lower CXCR4 gene expression (p<0.05). Mice that underwent ligation at ZT5 had high mortality rate and large infarct size. Echocardiography showed that those mice had significantly larger end diastolic and systolic volume and lower ejection fraction (p<0.05). Immunohistology revealed that those mice displayed more fibrosis, cardiomyocyte hypertrophy, and less angiogenesis compared to ZT13 or ZT21 group (p<0.05). However, treatment with anti-CXCL2 antibody significantly reduced LV dilatation, fibrosis, hypertrophy and improved cardiac function. These results indicate greater aged neutrophil infiltration into the heart contributes to cardiac hypertrophy, fibrosis, and dysfunction which suggests that blocking neutrophil aging may be a therapeutic alternative following acute myocardial infarction.

The connection of polymorphism and diurnal changes of the biological clock gene expression with the risk of progression of primary open-angle glaucoma

The purpose of this work is to study the connection betweengenetic factors (polymorphism and expression of key genes of the biological clock (KGBC), key genes controlled by KGBC, melatonin receptors) and the diurnal oscillation of melatonin in patients with stable and progressing primary open-angle glaucoma. Materials and methods. The study involved 115 patients aged 53–86 (averagely, 68.8 ± 7.9 years) with stable and progressive glaucoma. All patients underwent primary ophthalmological examination, tested for diurnal body temperature profile, intraocular pressure (IOP), melatonin (by the DLMO protocol) and were typed for key genes of the biological clock using the real-time polymerase chain reaction. We studied the sleep phase shift to later hours in carriers of the G-allele of the melatonin receptor gene during the progression of glaucoma. Results. The study of the clinical and genotypic features of the POAG course revealed phasal shifts of the circadian rhythms of body temperature, IOP, salivary melatonin levels and sleep phases which contributed to the progression of glaucomatous optic neuropathy. Certain polymorphic variants of genes contribute to individual frequent manifestations of desynchronosis. The clock rs1801260 and MTNR1B rs10830963 gene polymorphism was found to be related to disturbances in melatonin production and sleep phase. Conclusion. Complex manifestations of circadian desynchronization accompanying the progressive course of glaucoma are the late phase of rhythms and a decrease in sleep duration, body temperature, salivary melatonin and IOP, internal desynchronization between IOP and body temperature, IOP and sleep, evening dyslipidemia. The revealed patterns open up prospects for future studies of the relationship between polymorphism and daily changes of the expression of key genes in the biological clock with the risk of progression of primary open angle glaucoma.

Integrated water vapor during active and break spells of monsoon and its relationship with temperature, precipitation and precipitation efficiency over a tropical site

Global Positioning System (GPS) measurements of integrated water vapor (IWV) for two years (2014 and 2015) are presented in this paper. Variation of IWV during active and break spells of Indian summer monsoon has been studied for a tropical station Hyderabad (17.4° N, 78.46° E). The data is validated with ECMWF Re-Analysis (ERA) 91 level data. Relationships of IWV with other atmospheric variables like surface temperature, rain, and precipitation efficiency have been established through cross-correlation studies. A positive correlation coefficient is observed between IWV and surface temperature over two years. But the coefficient becomes negative when only summer monsoon months (June, July, August, and September) are considered. Rainfall during these months cools down the surface and could be the reason for this change in the correlation coefficient. Correlation studies between IWV- precipitation, IWV- precipitation efficiency (P.E), and precipitation-P.E show that coefficients are −0.05, −0.10 and 0.983 with 95% confidence level respectively, which proves that the efficacy of rain does not depend only on the level of water vapor. A proper dynamic mechanism is necessary to convert water vapor into the rain. The diurnal variations of IWV during active and break spells have been analyzed. The amplitudes of diurnal oscillation and its harmonics of individual spell do not show clear trends but the mean amplitudes of the break spells are approximately double than those of the active spells. The amplitudes of diurnal, semi-diurnal and ter-diurnal components during break spells are 1.08 kg/m2, 0.52 kg/m2 and 0.34 kg/m2 respectively. The corresponding amplitudes during active spells are 0.68 kg/m2, 0.41 kg/m2 and 0.23 kg/m2.

Oat Fiber Modulates Hepatic Circadian Clock via Promoting Gut Microbiota-Derived Short Chain Fatty Acids.

The biological alteration of circadian rhythm was found to be related to the development of metabolic disorders. Our previous studies reported that impaired lipid metabolism caused by a high-fat diet was improved by oat fiber, but did not attempt to answer whether the improvement is mechanistically linked to circadian rhythm. By focusing on circadian alteration, the present study aimed to elucidate the effect of gut microbiota-derived short chain fatty acids (SCFAs) on circadian rhythm in a high-fat diet experimental paradigm with and without dietary oat fiber feeding. The results showed that oat fiber prevented the production of obesity and dyslipidemia caused by a high-fat diet in C57BL/6 mice. From a circadian perspective specifically, a high-fat diet disrupted the hepatic circadian protein expressions of the liver clock genes, which were in parallel with the altered oscillation of serum triglycerides, low-density lipoprotein cholesterol, fasting insulin, and the homeostasis model assessment-insulin resistance index. Oat fiber, by contrast, reversed these disrupted diurnal oscillations. Most interestingly, what a high-fat diet induced and what oat fiber prevented were dictated in a close oscillation pattern resembling that of SCFA production facilitated by the intestinal microbiome. Given the results from the present study and from others that demonstrated the role played by SCFAs in regulating circadian rhythm, we conclude that the beneficial effects of oat fiber are likely mediated by complex processes involving multiple mechanisms including a signal transduction pathway of gut microbiota-derived SCFAs to hepatic circadian protein expression to lipid and other metabolic oscillations. The latter warrants more investigation to further determine whether the circadian rhythm pathway has any major and causal significance for the outcome measures in the prevention and treatment of metabolic disorders in humans.

Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging.

The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies.However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system’s regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear.Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.

Diurnal metabolic control in cyanobacteria requires perception of second messenger signaling molecule c-di-AMP by the carbon control protein SbtB.

Because of their photosynthesis-dependent lifestyle, cyanobacteria evolved sophisticated regulatory mechanisms to adapt to oscillating day-night metabolic changes. How they coordinate the metabolic switch between autotrophic and glycogen-catabolic metabolism in light and darkness is poorly understood. Recently, c-di-AMP has been implicated in diurnal regulation, but its mode of action remains elusive. To unravel the signaling functions of c-di-AMP in cyanobacteria, we isolated c-di-AMP receptor proteins. Thereby, the carbon-sensor protein SbtB was identified as a major c-di-AMP receptor, which we confirmed biochemically and by x-ray crystallography. In search for the c-di-AMP signaling function of SbtB, we found that both SbtB and c-di-AMP cyclase–deficient mutants showed reduced diurnal growth and that c-di-AMP–bound SbtB interacts specifically with the glycogen-branching enzyme GlgB. Accordingly, both mutants displayed impaired glycogen synthesis during the day and impaired nighttime survival. Thus, the pivotal role of c-di-AMP in day-night acclimation can be attributed to SbtB-mediated regulation of glycogen metabolism.

Limited changes in locomotor recovery and unaffected white matter sparing after spinal cord contusion at different times of day.

The circadian gene expression rhythmicity drives diurnal oscillations of physiological processes that may determine the injury response. While outcomes of various acute injuries are affected by the time of day at which the original insult occurred, such influences on recovery after spinal cord injury (SCI) are unknown. We report that mice receiving moderate, T9 contusive SCI at ZT0 (zeitgeber time 0, time of lights on) and ZT12 (time of lights off) showed similar hindlimb function recovery in the Basso mouse scale (BMS) over a 6 week post-injury period. In an independent study, no significant differences in BMS were observed after SCI at ZT18 vs. ZT6. However, the ladder walking test revealed modestly improved performance for ZT18 vs. ZT6 mice at week 6 after injury. Consistent with those minor effects on functional recovery, terminal histological analysis revealed no significant differences in white matter sparing at the injury epicenter. Likewise, blood-spinal cord barrier disruption and neuroinflammation appeared similar when analyzed at 1 week post injury at ZT6 or ZT18. Therefore, locomotor recovery after thoracic contusive SCI is not substantively modulated by the time of day at which the neurotrauma occurred.

Interplay between liver circadian rhythm and regeneration after PHx

Diurnal oscillations in gene expression are a hallmark of the liver internal clock and can be regulated by a variety of environmental stimuli. The circadian rhythm and liver regeneration (LR) are intimately linked. However, how they affect each other at the transcriptomic level is mainly unknown. Here, we revealed that partial hepatectomy (PHx)-induced LR led to reprogramming of rhythmic gene expression profiles as a consequence of disrupted BMAL1 occupation on the chromatin, while the rhythm of core clock genes remained robust. Furthermore, we demonstrated retarded LR when PHx was carried out in the evening, possibly due to the accumulation of DEC1. In summary, our data offer a broad perspective of the relationship between circadian rhythm and LR and suggest that the timing of PHx should be considered in the clinic application.

A new approach to study the long-term urban heat island evolution using time-dependent spectroscopy

This study presents a new approach to study long-term temperature and urban heat island intensity (UHII) evolution based on the method of time-depended spectroscopy on the example of Moscow megacity. In contrast to standard spectroscopy, this method allows analyzing the changes of the amplitude Fourier spectrum of the time series along the study period. Applying the novel method to the air temperature series for the period of 1977-2020, we demonstrate that ongoing changes of the mean temperature and UHII are accompanied by the changes of their spectra, including the spectral amplitudes corresponding to diurnal, annual and synoptic-scale oscillations. Such changes are complex, often non-linear, and seasonally asymmetric. Steady upward trends are found for summer season, for the spectral amplitudes of diurnal temperature and UHII oscillations, and synoptic-scale UHII oscillations. Spectral amplitudes of annual temperature and UHII oscillations experiences V-shaped dynamics with an increase since 1990th. For UHII such pattern reflects a switch between regimes with wintertime or summertime UHI maximum. Presented results provides an evidence that observed intensification of Moscow's UHI is forced not only by urban growth, but also by changing background meteorological conditions, which are becoming more favorable to UHI appearance in summer and less favorable in winter.

The Dominant Control of Relief on Soil Water Content Distribution During Wet‐Dry Transitions in Headwaters

AbstractThe redistribution of hillslope soil water during and after rainstorms is affected by soil properties and topography. Therefore, understanding how soil‐terrain attributes affect the soil volumetric water content (VWC) distribution under various catchment storages is a prerequisite for accurate hydrological modeling. Herein, the relationships between soil‐terrain attributes and soil VWC were examined in a steep (average slope = 60%), forested, zero‐order catchment. Detailed topography, soil properties, and runoff, and high frequency (6‐min) soil moisture data observed from July 2016 to November 2017 were employed along with resampled VWC data in three time‐steps (daily, hourly, and 6‐min intervals) for correlation analysis between soil‐terrain attributes and measured VWC. The results showed that daily aggregated data overlooked the highly heterogeneous flow conditions under dry‐wet transitions, leading to a constantly high correlation between VWC and the topographic wetness index (TWI). In comparison, the 6‐min data captured short‐lived flow processes, highlighting that, in reality, VWC‐TWI correlations fluctuated frequently as a function of catchment storages and precipitation characteristics, with four wetting patterns identified. Under wet‐dry transitions, the VWC‐TWI correlations increased significantly (from 0.3 to 0.6) as the hillslope gradually drained of lateral subsurface water. Soil water behavior consists of diurnal oscillations superimposed on a declining trend, which demonstrates the existence of unsaturated flow and which contributed to the increase in the strength of the correlations. Finally, through correlation analysis of all drying (n = 4) and wetting (n = 45) periods, we found that soil‐terrain attributes and VWC correlations can be used to identify the dominant soil water processes in various catchment storages.

Inhibition of 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE expression by brassinosteroid reduces carotenoid accumulation in Arabidopsis.

Unlike the indispensable function of the steroid hormone brassinosteroid (BR) in regulating plant growth and development, the metabolism of secondary metabolites regulated by BR is not well known. Here we show that BR reduces carotenoid accumulation in Arabidopsis seedlings. BR-deficient or BR-insensitive mutants accumulated higher content of carotenoids than wild-type plants, whereas BR treatment reduced carotenoid content. We demonstrated that BR transcriptionally suppresses 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE (HPPD) expression involved in carotenogenesis via plastoquinone production. We found that the expression of HPPD displays an oscillation pattern that is expressed more strongly in dark than in light conditions. Moreover, BR appeared to inhibit HPPD expression more strongly in darkness than in light, leading to suppression of a diurnal oscillation of HPPD expression. BR-responsive transcription factor BRASSINAZOLE RESISTANT 1 (BZR1) directly bound to the promoter of HPPD, and HPPD suppression by BR was increased in the bzr1-1D gain-of-function mutation. Interestingly, dark-induced HPPD expression did not cause carotenoid accumulation, due to down-regulation of other carotenoid biosynthetic genes in the dark. Our results suggest that BR regulates different physiological responses in dark and light through inhibition of HPPD expression.

Diurnal oscillations in gut bacterial load and composition eclipse seasonal and lifetime dynamics in wild meerkats

Circadian rhythms in gut microbiota composition are crucial for metabolic function, yet the extent to which they govern microbial dynamics compared to seasonal and lifetime processes remains unknown. Here, we investigate gut bacterial dynamics in wild meerkats (Suricata suricatta) over a 20-year period to compare diurnal, seasonal, and lifetime processes in concert, applying ratios of absolute abundance. We found that diurnal oscillations in bacterial load and composition eclipsed seasonal and lifetime dynamics. Diurnal oscillations were characterised by a peak in Clostridium abundance at dawn, were associated with temperature-constrained foraging schedules, and did not decay with age. Some genera exhibited seasonal fluctuations, whilst others developed with age, although we found little support for microbial senescence in very old meerkats. Strong microbial circadian rhythms in this species may reflect the extreme daily temperature fluctuations typical of arid-zone climates. Our findings demonstrate that accounting for circadian rhythms is essential for future gut microbiome research.

Physiological circadian rhythm of cardiac myosin-binding protein C (cMyC) and cardiac troponin

Abstract Introduction Cardiac myosin-binding protein C (cMyC) is a novel protein biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients with cardiac disease. Understanding the physiological diurnal oscillation of cMyC and cardiac troponin is important for the interpretation of single and serial measurements within the biomarker-assisted triage and risk stratification algorithms. Purpose In this study, we aim to assess and compare the physiological diurnal oscillation of cMyC and cardiac troponin cTnT and cTnI. Method Twenty-six consecutive hourly blood samples were drawn between 08.30 am and 09.30 am (+1 day) from normotensive 24 individuals without a recent history of acute myocardial infarction, for the measurement of cMyC, cardiac troponin T (Roche hs-cTnT) and I (Abbott hs-cTnI). Fitted cosinor sine regression model (with R, version 3.6.1) was used to assess the presence and significance of circadian oscillation of the biomarker, and to estimate the respective amplitude and acrophase (the time of peak activity). Amplitude and acrophase were compared across the biomarkers that exhibited significant circadian rhythm. Results Mean age was 72±7. 79% of participants (n=19) were men. All participants were free from renal disease. On population-mean cosinor analysis, hs-cTnI exhibited random diurnal oscillation, whereas significant circadian rhythm was detected for cMyC and hs-cTnT (p=0.015 and &amp;lt;0.001, respectively) (Figure 1). The circadian rhythm of cMyC is characterised by gradually increasing concentrations from early afternoon until early morning (acrophase 03:03 am, 95% CI 01:54–04:26 am) compared to hs-cTnT concentrations which exhibits delayed increase and a later peak (acrophase, 08:01, 95% CI 07:10–08:51 am), p=0.028 for acrophase difference (Figure 1). Diurnal rhythm remained significant after correction for possible posture-induced changes in plasma volume. To allow direct comparison between amplitudes, the measurements of cMyC and hs-TnT were normalised to the respective 08:30 am value, re-fitted cosinor model did not show significant difference between the amplitudes (amplitude ng/L, 0.12, 95% CI 0.07–0.15 vs 0.11, 95% CI 0.08–0.12, for normalised cMyC vs hs-cTnT, respectively; p=0.67). Conclusion Significant circadian rhythm exists for cMyC and hs-cTnT, with 5-hours phase difference between the two biomarkers (cMyC ahead of hs-cTnT). The cause of this rhythmic variation is unknown, but the phase difference is consistent with the previously described disparity in the release of cMyC and cTnT after iatrogenic myocardial injury, raising the possibility of an underlying diurnal variation in myocardial vulnerability. Studies are required to assess the impact of this physiological phenomenon on the performance of the biomarkers within unadjused diagnostic algorithms Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart FoundationStichting de Weijerhorst

Automation of the heated floor system in a room under the influence of ambient conditions

Energy consumption for cooling and heating buildings should be reduced in the future to maintain suitable indoor thermal comfort at a lower cost. Numerical simulation of heat transfer within building systems can help to design the energy-efficient buildings. This article presents a fundamental theoretical research done to understand the effect of automation of the underfloor heating system in a room under the influence of ambient conditions on heat transfer. The considered physical process has been described mathematically taking into account the turbulent natural convection and thermal surface radiation within an air filled enclosure having a panoramic window. Sinusoidal boundary condition has been applied to the external surface of panoramic window to model the possible diurnal ambient temperature oscillation. An automation of the underfloor heating system is determined by the heater volumetric heat flux that magnitude depends on the ambient conditions. The governing equations with boundary conditions have been solved numerically by the finite-difference method. The influence of the relevant parameters, viz., surface emissivity, length of underfloor heating system and ambient boundary conditions has been investigated in detail. Distributions of integral and local characteristics illustrating flow and thermal structures in the large-scale enclosure have been studied. The contribution of the thermal radiative mechanism to the overall heat transfer is close in magnitude to the convective heat transfer even under normal room conditions.

Dystrophin deficiency disrupts muscle clock expression and mitochondrial quality control in mdx mice.

Impaired oxidative capacity and mitochondrial function contribute to the dystrophic pathology in muscles of patients with Duchenne muscular dystrophy (DMD) and in relevant mouse models of the disease. Emerging evidence suggests an association between disrupted core clock expression and mitochondrial quality control, but this has not been established in muscles lacking dystrophin. We examined the diurnal regulation of muscle core clock and mitochondrial quality control expression in dystrophin-deficient C57BL/10ScSn-Dmdmdx (mdx) mice, an established model of DMD. Male C57BL/10 (BL/10; n = 18) and mdx mice (n = 18) were examined every 4 h beginning at the dark cycle. Throughout the entire light-dark cycle, extensor digitorum longus (EDL) muscles from mdx mice had decreased core clock mRNA expression (Arntl, Cry1, Cry2, Nr1d2; P < 0.05) and disrupted mitochondrial quality control mRNA expression related to biogenesis (decreased; Ppargc1a, Esrra; P < 0.05), fission (increased; Dnm1l; P < 0.01), fusion (decreased; Opa1, Mfn1; P < 0.05), and autophagy/mitophagy (decreased: Bnip3; P < 0.05; increased: Becn1; P < 0.05). Cosinor analysis revealed a decrease in the rhythmicity parameters mesor and amplitude for Arntl, Cry1, Cry2, Per2, and Nr1d1 (P < 0.001) in mdx mice. Diurnal oscillations in Esrra, Sirt1, Map1lc3b, and Sqstm1 were absent in mdx mice, along with decreased mesor and amplitude of Ppargc1a mRNA expression (P < 0.01). The expression of proteins involved in mitochondrial biogenesis (decreased: PPARGC1A, P < 0.05) and autophagy/mitophagy (increased: MAP1LC3BII, SQSTM1, BNIP3; P < 0.05) were also dysregulated in tibialis anterior muscles of mdx mice. These findings suggest that dystrophin deficiency in mdx mice impairs the regulation of the core clock and mitochondrial quality control, with relevance to DMD and related disorders.