The Circadian-clock Regulates the Arabidopsis Gravitropic Response

Abstract For long-term space missions, it is necessary to understand how organisms respond to changes in gravity. Plant roots are positively gravitropic; the primary root grows parallel to gravity's pull even after being turned away from the direction of gravity. We examined if this gravitropic response varies depending on the time of day reorientation occurs. When plants were reoriented in relation to the gravity vector or placed in simulated microgravity, the magnitude of the root gravitropic response varied depending on the time of day the initial change in gravity occurred. The response was greatest when plants were reoriented at dusk, just before a period of rapid growth, and were minimal just before dawn as the plants entered a period of reduced root growth. We found that this variation in the magnitude of the gravitropic response persisted in constant light (CL) suggesting the variation is circadian-regulated. Gravitropic responses were disrupted in plants with disrupted circadian clocks, including plants overexpressing Circadian-clock Associated 1 (CCA1) and elf3-2, in the reorientation assay and on a 2D clinostat. These findings indicate that circadian-regulated pathways modulate the gravitropic responses, thus, highlighting the importance of considering and recording the time of day gravitropic experiments are performed.

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Loss of Circadian Protection in Adults Exposed to Neonatal Hyperoxia

10.1101/2020.07.10.197277 ◽

2020 ◽

Author(s):

Yasmine Issah ◽

Amruta Naik ◽

Soon Y Tang ◽

Kaitlyn Forrest ◽

Thomas G Brooke ◽

...

Keyword(s):

Circadian Clock ◽

Early Life ◽

Influenza A ◽

Negative Impact ◽

Influenza Infection ◽

Time Of Day ◽

Long Term Effects ◽

Neonatal Hyperoxia ◽

Early Life Exposures

AbstractAdverse early life exposures having a lasting negative impact on health. For examples, neonatal hyperoxia which is a risk factor for chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) confers susceptibility to respiratory infections like Influenza A (IAV) later in life. Given our previous findings that the circadian clock exerts a protective effect on injury from IAV, we asked if the long-term impact of neonatal hyperoxia includes disruption of circadian rhythms. We show here that neonatal hyperoxia abolishes the circadian clock mediated time of day protection from IAV, not through the regulation of viral burden, but through host tolerance pathways. We further discovered that that this dysregulation is mediated through the intrinsic clock in the lung, rather than through central or immune system clocks. Loss of circadian protein, Bmal1, in AT2 cells of the lung recapitulates the increased mortality, loss of temporal gating and other key features of hyperoxia-exposed animals. Taken together, our data suggest a novel role for the circadian clock in AT2 clock in mediating long-term effects of early life exposures to the lungs.Brief SummaryNeonatal hyperoxia abrogates the circadian protection from Influenza infection in recovered adults.

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The circadian clock contributes to the long-term water use efficiency of Arabidopsis

10.1101/583526 ◽

2019 ◽

Author(s):

Noriane M. L. Simon ◽

Calum A. Graham ◽

Nicholas E. Comben ◽

Alistair M. Hetherington ◽

Antony N. Dodd

Keyword(s):

Circadian Clock ◽

Water Use Efficiency ◽

Water Use ◽

Biomass Accumulation ◽

Time Of Day ◽

Circadian Oscillator ◽

Circadian Regulation ◽

Use Efficiency ◽

The Impact

AbstractIn plants, water use efficiency is a complex trait derived from numerous physiological and developmental characteristics. Here, we investigated the involvement of circadian regulation in long-term water use efficiency. Circadian rhythms are generated by the circadian oscillator, which provides a cellular measure of the time of day. In plants, the circadian oscillator contributes to the regulation of many aspects of physiology, including stomatal opening, the rate of photosynthesis, carbohydrate metabolism and developmental processes. We investigated in Arabidopsis the impact of the misregulation of genes encoding a large number of components of the circadian oscillator upon whole plant, long-term water use efficiency. From this, we identified a role for the circadian oscillator in water use efficiency. This appears to be due to contributions of the circadian clock to the control of transpiration and biomass accumulation. We also identified that the circadian oscillator within guard cells can contribute to long-term water use efficiency. Our experiments indicate that knowledge of circadian regulation will be important for developing future crops that use water more efficiently.One-sentence summaryThe circadian clock in Arabidopsis makes an important contribution to long-term water use efficiency.

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Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates

eLife ◽

10.7554/elife.61241 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yasmine Issah ◽

Amruta Naik ◽

Soon Y Tang ◽

Kaitlyn Forrest ◽

Thomas G Brooks ◽

...

Keyword(s):

Circadian Clock ◽

Early Life ◽

Influenza A ◽

Negative Impact ◽

Influenza Infection ◽

Time Of Day ◽

Alveolar Type ◽

Neonatal Hyperoxia ◽

Early Life Exposures

Adverse early-life exposures have a lasting negative impact on health. Neonatal hyperoxia that is a risk factor for bronchopulmonary dysplasia confers susceptibility to influenza A virus (IAV) infection later in life. Given our previous findings that the circadian clock protects against IAV, we asked if the long-term impact of neonatal hyperoxia vis-à-vis IAV infection includes circadian disruption. Here, we show that neonatal hyperoxia abolishes the clock-mediated time of day protection from IAV in mice, independent of viral burden through host tolerance pathways. We discovered that the lung intrinsic clock (and not the central or immune clocks) mediated this dysregulation. Loss of circadian protein, Bmal1, in alveolar type 2 (AT2) cells recapitulates the increased mortality, loss of temporal gating, and other key features of hyperoxia-exposed animals. Our data suggest a novel role for the circadian clock in AT2 cells in mediating long-term effects of early-life exposures to the lungs.

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Using supraglottic airways by paramedics for airway management in analogue microgravity increases speed and success of ventilation

Scientific Reports ◽

10.1038/s41598-021-88008-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jochen Hinkelbein ◽

Anton Ahlbäck ◽

Christine Antwerber ◽

Lisa Dauth ◽

James DuCanto ◽

...

Keyword(s):

Airway Management ◽

Success Rate ◽

Simulated Microgravity ◽

Laryngeal Tube ◽

Space Missions ◽

Airway Device ◽

Future Space ◽

Secondary Endpoints ◽

Present Trial

AbstractIn the next few years, the number of long-term space missions will significantly increase. Providing safe concepts for emergencies including airway management will be a highly challenging task. The aim of the present trial is to compare different airway management devices in simulated microgravity using a free-floating underwater scenario. Five different devices for airway management [laryngeal mask (LM), laryngeal tube (LT), I-GEL, direct laryngoscopy (DL), and video laryngoscopy (VL)] were compared by n = 20 paramedics holding a diving certificate in a randomized cross-over setting both under free-floating conditions in a submerged setting (pool, microgravity) and on ground (normogravity). The primary endpoint was the successful placement of the airway device. The secondary endpoints were the number of attempts and the time to ventilation. A total of 20 paramedics (3 female, 17 male) participated in this study. Success rate was highest for LM and LT and was 100% both during simulated microgravity and normogravity followed by the I-GEL (90% during microgravity and 95% during normogravity). However, the success rate was less for both DL (60% vs. 95%) and VL (20% vs. 60%). Fastest ventilation was performed with the LT both in normogravity (13.7 ± 5.3 s; n = 20) and microgravity (19.5 ± 6.1 s; n = 20). For the comparison of normogravity and microgravity, time to ventilation was shorter for all devices on the ground (normogravity) as compared underwater (microgravity). In the present study, airway management with supraglottic airways and laryngoscopy was shown to be feasible. Concerning the success rate and time to ventilation, the optimum were supraglottic airways (LT, LM, I-GEL) as their placement was faster and associated with a higher success rate. For future space missions, the use of supraglottic airways for airway management seems to be more promising as compared to tracheal intubation by DL or VL.

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Circadian clock protein Rev-erbα regulates neuroinflammation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1812405116 ◽

2019 ◽

Vol 116 (11) ◽

pp. 5102-5107 ◽

Cited By ~ 36

Author(s):

Percy Griffin ◽

Julie M. Dimitry ◽

Patrick W. Sheehan ◽

Brian V. Lananna ◽

Chun Guo ◽

...

Keyword(s):

Circadian Clock ◽

Microglial Activation ◽

Time Of Day ◽

Resting State Functional Connectivity ◽

Promoter Regions ◽

Clock Component ◽

Glial Cultures ◽

Inflammatory Phenotype

Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, a nuclear receptor and circadian clock component, is a mediator of microglial activation and neuroinflammation. We observed time-of-day oscillation in microglial immunoreactivity in the hippocampus, which was disrupted in Rev-erbα−/− mice. Rev-erbα deletion caused spontaneous microglial activation in the hippocampus and increased expression of proinflammatory transcripts, as well as secondary astrogliosis. Transcriptomic analysis of hippocampus from Rev-erbα−/− mice revealed a predominant inflammatory phenotype and suggested dysregulated NF-κB signaling. Primary Rev-erbα−/− microglia exhibited proinflammatory phenotypes and increased basal NF-κB activation. Chromatin immunoprecipitation revealed that Rev-erbα physically interacts with the promoter regions of several NF-κB–related genes in primary microglia. Loss of Rev-erbα in primary astrocytes had no effect on basal activation but did potentiate the inflammatory response to lipopolysaccharide (LPS). In vivo, Rev-erbα−/− mice exhibited enhanced hippocampal neuroinflammatory responses to peripheral LPS injection, while pharmacologic activation of Rev-erbs with the small molecule agonist SR9009 suppressed LPS-induced hippocampal neuroinflammation. Rev-erbα deletion influenced neuronal health, as conditioned media from Rev-erbα–deficient primary glial cultures exacerbated oxidative damage in cultured neurons. Rev-erbα−/− mice also exhibited significantly altered cortical resting-state functional connectivity, similar to that observed in neurodegenerative models. Our results reveal Rev-erbα as a pharmacologically accessible link between the circadian clock and neuroinflammation.

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Long-term throughfall exclusion decreases soil organic phosphorus associated with reduced plant roots and soil microbial biomass in a subtropical forest

Geoderma ◽

10.1016/j.geoderma.2021.115309 ◽

2021 ◽

Vol 404 ◽

pp. 115309

Author(s):

Yuexin Fan ◽

Shengxu Lu ◽

Min He ◽

Liuming Yang ◽

Weifang Hu ◽

...

Keyword(s):

Microbial Biomass ◽

Soil Microbial Biomass ◽

Organic Phosphorus ◽

Subtropical Forest ◽

Plant Roots ◽

Soil Microbial ◽

Soil Organic Phosphorus ◽

Throughfall Exclusion

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A54 THE CIRCADIAN CLOCK INFLUENCES JAK/STAT SIGNALING AND GUT PERMEABILITY

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.052 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 11-12

Author(s):

K Parasram ◽

D Bachetti ◽

P Karpowicz

Keyword(s):

Circadian Clock ◽

Clock Cycle ◽

Intestinal Barrier ◽

Fruit Fly ◽

Cell Types ◽

Time Of Day ◽

Acute Injury ◽

Intestinal Barrier Function ◽

Intestinal Immunity ◽

Stat Signaling

Abstract Background The circadian clock is a 24-hour feedback loop that drives rhythms in behaviours and physiological processes. This molecular timekeeper consists of the transcription factors, Clock-Cycle, that drive expression of thousands of clock-controlled genes, with two of these, Period and Timeless, acting as negative regulators of Clock-Cycle. This fundamental mechanism was initially characterized in the fruit fly, Drosophila melanogaster (Nobel Prize in Physiology & Medicine, 2017), and is highly conserved in humans. The intestine, or midgut, of Drosophila, is also similar to the human small intestine consisting of similar cellular lineage, signaling pathways, and physiological functions. The lineage of the Drosophila intestine contains the same four cell types as humans: intestinal stem cells (ISCs), progenitors called enteroblasts, enterocytes and enteroendocrine cells. This simplified lineage as well as the genetic tools available, make Drosophila an ideal model for intestinal regeneration in health and disease. We have previously shown that the circadian clock is active in ISCs, EBs and ECs during both homeostatic and regenerating conditions. Furthermore, the circadian clock regulates the mitosis of ISCs under regenerating conditions. Aims We sought to uncover if Jak/STAT signaling, one of the key pathways involved in ISC proliferation in the Drosophila intestine, shows a circadian rhythm and if there is a time-of-day difference in the regenerative response. Methods To test whether the clock regulates Jak/STAT during acute injury, we developed an irradiation assay that does not affect survival but acutely disrupts intestinal barrier function. Results Using a dynamic reporter of Jak/STAT activity we show that Period circadian clock mutants have low Jak/STAT signaling and a leaky gut phenotype. Wildtype controls show time-dependent gut leakiness upon irradiation, which is higher and time-independent in Period mutants. The level of Jak/STAT response differs depending on the time of irradiation in the controls, but is higher at all times in the mutants. Conclusions The Jak/Stat pathway regulates intestinal immunity and epithelial cell proliferation in humans, thus playing a role in colorectal cancer and inflammatory bowel disease. Our results suggest Jak/Stat is controlled by the circadian clock, which has implications for intestinal recovery following medical treatments, including radiation therapy. Funding Agencies NRC

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Circadian Timekeeping in Anticancer Therapeutics: An Emerging Vista of Chronopharmacology Research

Current Drug Metabolism ◽

10.2174/1389200222666211119103422 ◽

2021 ◽

Vol 22 ◽

Author(s):

Alekhya Puppala ◽

Sourbh Rankawat ◽

Sandipan Ray

Keyword(s):

Drug Metabolism ◽

Circadian Clock ◽

Cancer Cells ◽

Anticancer Drugs ◽

Cancer Biology ◽

Anticancer Therapy ◽

Time Of Day ◽

Circadian Regulation ◽

Cancer Management ◽

Anticancer Therapeutics

Background: Intrinsic rhythms in host and cancer cells play an imperative role in tumorigenesis and anticancer therapy. Circadian medicine in cancer is principally reliant on the control of growth and development of cancer cells or tissues by targeting the molecular clock and implementing time-of-day-based anticancer treatments for therapeutic improvements. In recent years, based on extensive high-throughput studies, we witnessed the arrival of several drugs and drug-like compounds that can modulate circadian timekeeping for therapeutic gain in cancer management. Objective: This perspective article intends to illustrate the current trends in circadian medicine in cancer, focusing on clock-modulating pharmacological compounds and circadian regulation of anticancer drug metabolism and efficacy. Scope and Approach: Considering the critical roles of the circadian clock in metabolism, cell signaling, and apoptosis, chronopharmacology research is exceedingly enlightening for understanding cancer biology and improving anticancer therapeutics. In addition to reviewing the relevant literature, we investigated the rhythmic expression of molecular targets for many anticancer drugs frequently used to treat different cancer types. Key Findings and Conclusion: There are adequate empirical pieces of evidence supporting circadian regulation of drug metabolism, transport, and detoxification. Administration of anticancer drugs at specific dosing times can improve their effectiveness and reduce the toxic effects. Moreover, pharmacological modulators of the circadian clock could be used for targeted anticancer therapeutics such as boosting circadian rhythms in the host can markedly reduce the growth and viability of tumors. All in all, precision chronomedicine can offer multiple advantages over conventional anticancer therapy.

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