Circadian clock-controlled genes isolated from Neurospora crassa are late night- to early morning-specific

SUMMARYIn the wild, when to go to sleep is a critical decision. Sleep onset is controlled by two processes: the circadian clock, and a homeostat measuring sleep drive [1, 2]. Environmental stimuli must also clearly intersect with the circadian clock and/or homeostat so that sleep is initiated only when appropriate. Yet how circadian, homeostatic and environmental cues are integrated at the circuit level is unclear. Recently, we found that DN1p clock neurons in Drosophila act to prolong morning wakefulness at elevated ambient temperatures [3]. Here we show that a subset of DN1p neurons exhibit temperature-sensitive increases in excitability, and define an output pathway linking DN1p neurons to downstream sleep-regulatory circuits. We show that DN1p neurons project axons to a subdomain of the Anterior Optic Tubercle (AOTU), and here make inhibitory synaptic connections with sleep-promoting tubercular-bulbar (TuBu) neurons. Using unbiased trans-synaptic labeling, we show that these TuBu neurons form synaptic connections with R-neurons innervating the ellipsoid body, subsets of which control homeostatic sleep drive [4]. DN1p excitability is clock-dependent, peaking in the late night and early morning [5]. Thus, integration of circadian and thermo-sensory information by DN1p neurons and subsequent inhibition of sleep-promoting TuBu neurons provides a mechanism by which an environmental stimulus can regulate sleep onset during a specific compartment of the day-night cycle. Furthermore, our results suggest that the AOTU functionally links circadian and sleep homeostat circuits in Drosophila.

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COMPLEMENTATION ANALYSIS OF LINKED CIRCADIAN CLOCK MUTANTS OF NEUROSPORA CRASSA

Genetics ◽

10.1093/genetics/82.1.9 ◽

1976 ◽

Vol 82 (1) ◽

pp. 9-17 ◽

Cited By ~ 3

Author(s):

Jerry F Feldman ◽

Marian N Hoyle

Keyword(s):

Linkage Group ◽

Circadian Clock ◽

Neurospora Crassa ◽

Period Length ◽

Complementation Analysis ◽

Wild Type ◽

The Right

ABSTRACT A fourth mutant of Neurospora crassa, designated frq-4, has been isolated in which the period length of the circadian conidiation rhythm is shortened to 19.3 ± 0.3 hours. This mutant is tightly linked to the three previously isolated frq mutants, and all four map to the right arm of linkage group VII about 10 map units from the centromere. Complementation tests suggest, but do not prove, that all four mutations are allelic, since each of the four mutants is co-dominant with the frq + allele—i.e., heterokaryons have period lengths intermediate between the mutant and wild-type—and since heterokaryons between pairs of mutants also have period lengths intermediate between those of the two mutants.

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Epistatic and Synergistic Interactions Between Circadian Clock Mutations in Neurospora crassa

Genetics ◽

10.1093/genetics/159.2.537 ◽

2001 ◽

Vol 159 (2) ◽

pp. 537-543

Author(s):

Louis W Morgan ◽

Jerry F Feldman

Keyword(s):

Circadian Clock ◽

Neurospora Crassa ◽

Mutant Strain ◽

Temperature Compensation ◽

Double Mutant ◽

Synergistic Interactions ◽

Long Period ◽

Double Mutant Strain ◽

Short Period ◽

Compensation Mechanisms

Abstract We identified a series of epistatic and synergistic interactions among the circadian clock mutations of Neurospora crassa that indicate possible physical interactions among the various clock components encoded by these genes. The period-6 (prd-6) mutation, a short-period temperature-sensitive clock mutation, is epistatic to both the prd-2 and prd-3 mutations. The prd-2 and prd-3 long-period mutations show a synergistic interaction in that the period length of the double mutant strain is considerably longer than predicted. In addition, the prd-2 prd-3 double mutant strain also exhibits overcompensation to changes in ambient temperature, suggesting a role in the temperature compensation machinery of the clock. The prd-2, prd-3, and prd-6 mutations also show significant interactions with the frq7 long-period mutation. These results suggest that the gene products of prd-2, prd-3, and prd-6 play an important role in both the timing and temperature compensation mechanisms of the circadian clock and may interact with the FRQ protein.

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Synchronizing the Neurospora crassa circadian clock with the rhythmic environment

Biochemical Society Transactions ◽

10.1042/bst0330949 ◽

2005 ◽

Vol 33 (5) ◽

pp. 949-952 ◽

Cited By ~ 4

Author(s):

N. Price-Lloyd ◽

M. Elvin ◽

C. Heintzen

Keyword(s):

Light Intensity ◽

Circadian Clock ◽

Neurospora Crassa ◽

Model Organism ◽

Circadian Clocks ◽

Current Understanding ◽

Signalling Pathways ◽

Selection Pressures ◽

The Earth ◽

Natural Cycles

The metronomic predictability of the environment has elicited strong selection pressures for the evolution of endogenous circadian clocks. Circadian clocks drive molecular and behavioural rhythms that approximate the 24 h periodicity of our environment. Found almost ubiquitously among phyla, circadian clocks allow preadaptation to rhythms concomitant with the natural cycles of the Earth. Cycles in light intensity and temperature for example act as important cues that couple circadian clocks to the environment via a process called entrainment. This review summarizes our current understanding of the general and molecular principles of entrainment in the model organism Neurospora crassa, a simple eukaryote that has one of the best-studied circadian systems and light-signalling pathways.

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4 From Genetics to Molecular Oscillations: The Circadian Clock in Neurospora crassa

Genetics and Biotechnology ◽

10.1007/978-3-030-49924-2_4 ◽

2020 ◽

pp. 77-103

Author(s):

Meaghan S. Jankowski ◽

Zachary A. Chase ◽

Jennifer M. Hurley

Keyword(s):

Circadian Clock ◽

Neurospora Crassa

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Nlrp3 Inflammasome Activation in Bone Marrow-Residing Innate Immunity Cells Governs Circadian Changes in the Number of Circulating Hematopoietic Stem/Progenitor Cells in Peripheral Blood

Blood ◽

10.1182/blood-2019-125853 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1033-1033

Author(s):

Mateusz Adamiak ◽

Andrzej Ciechanowicz ◽

Monika Cymer ◽

Marta Skoda ◽

Mariusz Z Ratajczak

Keyword(s):

Nlrp3 Inflammasome ◽

Early Morning ◽

Sterile Inflammation ◽

Circadian Oscillation ◽

Inflammasome Activation ◽

Hematopoietic Stem ◽

Circadian Changes ◽

Late Night ◽

Circulating Cells ◽

Nlrp3 Inflammasome Activation

Background. The number of hematopoietic stem/progenitor cells (HSPCs) in peripheral blood (PB) undergoes a circadian oscillation, with the peak occurring in the early morning hours and the nadir at night, and, as nicely demonstrated, this peak has been attributed to the enhanced tonus of the vegetative nervous system in the early morning hours (Nature 2008, 452, 442-447). Moreover, our group has demonstrated that release of HSPCs from bone marrow (BM) into PB is regulated during stress- or pharmacology-induced mobilization by activation of three ancient serum proteolytic cascades, the complement cascade (ComC), the coagulation cascade (CoaC), and the fibrynolytic cascade (FibC) (Stem Cell Rev. 2018; 14:677-685). Since it is known that the ComC, CoaC, and FibC show circadian activation at late night/early morning hours due to deep sleep hypoxia, regulation of the circadian oscillation of HSPC numbers in PB becomes more complex. Moreover, as we recently demonstrated, an important role in egress of HSPCs from BM into PB is played by purinergic signaling involving adenosine triphosphate (ATP) released from cells, which, as signaling mediators in the extracellular space, activate the Nlrp3 inflammasome in hematopoietic cells (Leukemia 2019; 33:815-825). Activation of the Nlrp3 inflammasome induces a state of sterile inflammation in the BM microenvironment and activates the ComC, CoaC, and FibC. Hypothesis. Since Nlrp3 inflammasome activation regulates egress of HSPCs from BM into PB by inducing BM sterile inflammation and activation of the ComC, CoaC, and FibC undergoes circadian activation, we became interested in whether Nlrp3 protein complex orchestrates circadian changes in the number of HSPCs circulating in PB.Materials and Methods. To address this important question, we studied the circadian oscillation in the number of circulating HSPCs in mice. Mice were accustomed to alternating periods of 12 hours light and 12 hours darkness. Light was turned on at 6 AM (ZT0), and the numbers of circulating white blood cells (WBCs), Sca-1+kit+Lin- HSCs, Sca-1+Lin-CD45+ HSCs, clonogenic CFU-GM progenitors, and non-hematopoietic Sca-1+Lin-CD45- cells (VSELs) were measured at 7 AM (ZT1), 11 AM (ZT5), 7 PM (ZT13), and 3 AM (ZT21). At the same time points, we evaluated expression of the Nlrp3 inflammasome at the mRNA level; Nlrp3 activation by measuring Nlrp3 inflammasome activation markers, such as interleukin-1beta, interleukin-18, and Hmgb1, at the mRNA and protein levels; ComC activation (by C5a ELISA); CoaC activation (by thrombin/antithrombin ELISA); and FibC activation (by plasmin/antiplasmin complex ELISA). To confirm the role of the Nlrp3 inflammasome in the circadian oscillation of HSPCs released into PB, we inhibited its activity by employing the specific small-molecule inhibitor MCC950. Results. We observed circadian changes in the expression and activation of the Nlrp3 inflammasome, with a peak in the early morning hours at ZT1 that preceded the peak in the number of circulating HSPCs at ZT5. This increase in activation of the Nlrp3 inflammasome and the number of circulating cells in WT animals was preceded by an increase in C5a concentration in PB at ZT1 as well as activation of the CoaC and FibC at ZT21. As expected, inhibition of the Nlrp3 inflammasome by MCC950 inhibited circadian oscillation of circulating HSPCs in PB. Conclusions. Our study confirms circadian activation of the Nlrp3 inflammsome due to the ComC, CoaC, and FibC in mice at late-night/early-morning hours preceding the release of HSPCs from BM into PB. The fact that we observed significant decrease in circadian changes in the number of circulating cells in PB in mice exposed to an Nlrp3 inflammasome inhibitor confirms its pivotal role in executing circadian release of HSPCs from BM into PB. Moreover, the fact that mice exposed to an Nlrp3 inhibitor show defective activation of the ComC and normal activation of the the CoaC and FibC indicates that, of the ancient proteolytic cascades tested, the ComC is the major player regulating Nlrp3 inflammasome-dependent circadian egress of HSPCs. Disclosures No relevant conflicts of interest to declare.

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Characteristics of Diurnal Rainfall over Peatland Area of South Sumatra, Indonesia

Science & Technology Indonesia ◽

10.26554/sti.2020.5.4.136-141 ◽

2020 ◽

Vol 5 (4) ◽

pp. 136

Author(s):

Puad Maulana Mandailing ◽

Wijaya Mardiansyah ◽

Muhammad Irfan ◽

Arsali Arsali ◽

Iskhaq Iskandar

Keyword(s):

Seasonal Variation ◽

Early Morning ◽

Temporal Variations ◽

In Situ Observation ◽

Peak Time ◽

The South ◽

Night Time ◽

Late Night ◽

Diurnal Rainfall

The peak time of rainfall occurrence over an area has certain characteristics in which the difference in time and intensity of rainfall varies depending on its location and distance from the sea. This variation can be determined based on the phase and amplitude obtained using harmonic analysis. In this study, combined data from in-situ observation, satellite remote sensing and reanalysis were used to analyze spatial and temporal variations of peak rainfall events over peatland area of the South Sumatra Province. The results show that most of the South Sumatra Province has a diurnal peak of rainfall during afternoon ranging from 16.00 to 19.00 Western Indonesian Time. In addition, the results also indicate that the analysis on the in situ data revealed seasonal variation both in amplitude and time of maximum diurnal rainfall, while the reanalysis data only indicated a weak seasonal variation on the amplitude of the diurnal rainfall. Furthermore, spatial analysis shows that the time of maximum diurnal rainfall has spatial variation. Over the ocean, the time of maximum diurnal rainfall occurs during night time/early morning. Over the lowland or coastal area, the time of maximum diurnal rainfall occurs during afternoon, while over the high altitude (mountain) it occurs during late night.

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Image Processing of Radar Mosaics for the Climatology of Convection Initiation in South China

Journal of Applied Meteorology and Climatology ◽

10.1175/jamc-d-19-0081.1 ◽

2020 ◽

Vol 59 (1) ◽

pp. 65-81 ◽

Cited By ~ 3

Author(s):

Lanqiang Bai ◽

Guixing Chen ◽

Ling Huang

Keyword(s):

South China ◽

Numerical Models ◽

Early Morning ◽

Moist Convection ◽

Late Night ◽

Morning Peak ◽

Spatial Modes ◽

Triggering Mechanisms ◽

Deep Moist Convection ◽

Convection Initiation

AbstractA dataset of convection initiation (CI) is of great value in studying the triggering mechanisms of deep moist convection and evaluating the performances of numerical models. In recent years, the data quality of the operationally generated radar mosaics over China has been greatly improved, which provides an opportunity to retrieve a CI dataset from that region. In this work, an attempt is made to reveal the potential of applying a simple framework of objective CI detection for the study of CI climatology in China. The framework was tested using radar mosaic maps in South China that were accessible online. The identified CI events were validated in both direct and indirect ways. On the basis of a direct manual check, nearly all of the identified CI cells had an organized motion. The precipitation echoes of the cells had a median duration of approximately 2.5 h. The CI occurrences were further compared with rainfall estimates to ensure physical consistency. The diurnal cycle of CI occurrence exhibits three major modes: a late-night-to-morning peak at the windward coasts and offshore, a noon-to-late-afternoon peak on the coastal land, and an evening-to-early-morning peak over the northwestern highland. These spatial modes agree well with those of rainfall, indirectly suggesting the reliability of the CI statistics. By processing radar mosaic maps, such a framework could be applied for studying CI climatology over China and other regions.

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Circadian Variation of Migraine Attack Onset: A Review of Clinical Studies

BioMed Research International ◽

10.1155/2019/4616417 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Daniel Baksa ◽

Kinga Gecse ◽

Sahel Kumar ◽

Zsuzsanna Toth ◽

Zsofia Gal ◽

...

Keyword(s):

Migraine Attack ◽

Circadian Variation ◽

Early Morning ◽

Sleep Stages ◽

Shift Workers ◽

Late Night ◽

Diurnal Distribution ◽

Pubmed Search ◽

Migraine Triggers ◽

The Moment

Several studies suggested that migraine attack onset shows a circadian variation; however, there has not been an overview and synthesis of these findings. A PubMed search with keywords “migraine” AND “circadian” resulted in ten studies directly investigating this topic. Results of these studies mostly show that migraine attacks follow a monophasic 24-hour cyclic pattern with an early morning or late night peak while other studies reported an afternoon peak and also a biphasic 24-hour cycle of attacks. The identified studies showed methodological variation including sample size, inclusion of medication use, comorbidities, and night or shift workers which could have contributed to the contradictory results. Several theories emerged explaining the diurnal distribution of migraine attacks suggesting roles for different phenomena including a morning rise in cortisol levels, a possible hypothalamic dysfunction, a circadian variation of migraine triggers, sleep stages, and a potentially different setting of the circadian pacemaker among migraineurs. At the moment, most studies show an early morning or late night peak of migraine attack onset, but a significant amount of studies reveals contradictory results. Further studies should investigate the arising hypotheses to improve our understanding of the complex mechanism behind the circadian variation of migraine attacks that can shed light on new targets for migraine therapy.

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Long-acting somatostatin analogue (Sandostatin) reduces late night insulinopenic ketogenesis in diabetic teenagers

Acta Endocrinologica ◽

10.1530/acta.0.115s045 ◽

1987 ◽

Vol 116 (4_Suppla) ◽

pp. S45-S53 ◽

Cited By ~ 6

Author(s):

R.S.R. Aarsen ◽

G.J. Bruining ◽

W.F.A. Grose ◽

R. van Strik ◽

S.W.J. Lamberts ◽

...

Keyword(s):

Blood Glucose ◽

Insulin Pump ◽

Movement Analysis ◽

Early Morning ◽

Insulin Pump Therapy ◽

Rank Test ◽

Somatostatin Analogue ◽

Late Night ◽

Free Insulin ◽

Long Acting

Abstract. Ten diabetic teenagers were admitted into our hospital for two nights, separated by one week. In a double-blind cross-over randomized study they received either 50 μg of the new long-acting somatostatin analogue Sandostatin sc or placebo. All patients were between 12 and 16 years of age, C-peptide negative with a duration of diabetes of at least four years. They had either conventional therapy or insulin pump therapy. Insulin doses and diets were kept unchanged. Blood samples were taken half hourly from 17.00 h until 09.30 h the next morning from an indwelling venous catheter. Hormonal and metabolic profiles on the two nights were evaluated by means of a distribution free time sequential co-movement analysis and by the paired Wilcoxon's signed rank test. After Sandostatin was given at 22.00 h, GH levels were significantly suppressed during 4 h. During that period blood glucose was slightly but significantly lower than after placebo. The free-insulin profiles from both nights were very comparable. Co-movement analysis showed a significant correlation between glucose and free insulin variations with a 30-min backward shift of the glucose curve. However, after Sandostatin administration this relation was lost in the period between 22.00 and 07.00 h, indicating a different effect of insulin on glucose levels during the nights Sandostatin was given. Early morning glucose rises were associated with free insulin levels below 20 mU/l. This association was not altered during the Sandostatin nights. Glucagon was not suppressed by Sandostatin except at 120 min after injection, and remained unchanged during the rest of the observation period. Triglyceride levels as well as 3-OH-butyrate values were significantly lower after Sandostatin. Plasma levels of FFA, free glycerol, alanine and cortisol were not significantly reduced. It is concluded that a single sc injection of 50 μg of Sandostatin given at 22.00 h is a potent GH inhibitor and lowers blood glucose concentrations for up to 4 h after injection. Early morning blood glucose rise is not prevented, but overnight hepatic ketogenesis as reflected by 3-OH--butyrate levels appears suppressed by Sandostatin up to the next morning injection of insulin.

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