scholarly journals Nitric Oxide Mediates Neuro-Glial Interaction that Shapes Drosophila Circadian Behavior

2019 ◽  
Author(s):  
Anatoly Kozlov ◽  
Emi Nagoshi
Keyword(s):  
Nitric Oxide ◽  
Circadian Rhythms ◽  
Neural Circuit ◽  
Critical Role ◽  
Constant Darkness ◽  
Molecular Clocks ◽  
Loss Of Function ◽  
Pacemaker Neurons ◽  
Circadian Behavior ◽  
First Time

AbstractDrosophila circadian behavior relies on the network of heterogeneous groups of clock neurons. Short -and long-range signaling within the pacemaker circuit coordinates molecular and neural rhythms of clock neurons to generate coherent behavioral output. The neurochemistry of circadian behavior is complex and remains incompletely understood. Here we demonstrate that the gaseous messenger nitric oxide (NO) is a signaling molecule linking circadian pacemaker to rhythmic locomotor activity. We show that two independent mutants lacking nitric oxide synthase (NOS) have severely disturbed locomotor behavior both in light-dark cycles and constant darkness, although molecular clocks in the main pacemaker neurons are unaffected. Behavioral phenotypes are due in part to the malformation of neurites of the main pacemaker neurons, s-LNvs. Using cell-type selective and stage-specific gain -and loss-of-function of NOS, we demonstrate that NO secreted from diverse cellular clusters non-cell-autonomously affect molecular and behavioral rhythms. We further identify glia as a major source of NO that regulates circadian locomotor output. These results reveal for the first time the critical role of NO signaling in the Drosophila circadian system and highlight the importance of neuro-glial interaction in the neural circuit output.Author summaryCircadian rhythms are daily cycles of physiological and behavioral processes found in most plants and animals on our planet from cyanobacteria to humans. Circadian rhythms allow organisms to anticipate routine daily and annual changes of environmental conditions and efficiently adapt to them. Fruit fly Drosophila melanogaster is an excellent model to study this phenomenon, as its versatile toolkit enables the study of genetic, molecular and neuronal mechanisms of rhythm generation. Here we report for the first time that gasotransmitter nitric oxide (NO) has a broad, multi-faceted impact on Drosophila circadian rhythms, which takes place both during the development and the adulthood. We also show that one of the important contributors of NO to circadian rhythms are glial cells. The second finding highlights that circadian rhythms of higher organisms are not simply controlled by the small number of pacemaker neurons but are generated by the system that consists of many different players, including glia.

Daily exposure to a running wheel entrains circadian rhythms in mice in parallel with development of an increase in spontaneous movement prior to running-wheel access

2013 ◽  
Vol 305 (11) ◽  
pp. R1367-R1375 ◽  
Author(s):  
Yujiro Yamanaka ◽  
Sato Honma ◽  
Ken-ichi Honma
Keyword(s):  
Circadian Rhythms ◽  
Fixed Time ◽  
Time Of Day ◽  
Constant Darkness ◽  
Spontaneous Movement ◽  
Running Wheel ◽  
Daily Exposure ◽  
Free Running ◽  
Nonphotic Entrainment ◽  
Circadian Behavior

Entrainment of circadian behavior rhythms by daily exposure to a running wheel was examined in mice under constant darkness. Spontaneous movement was individually monitored for more than 6 mo by a thermal sensor. After establishment of steady-state free running, mice were placed in a different cage equipped with a running-wheel for 3 h once per day at 6 AM. The daily exchange was continued for 80 days. The number of wheel revolutions during exposure to the running wheel was also measured simultaneously with spontaneous movement. In 13 out of 17 mice, circadian behavior rhythm was entrained by daily wheel exposure, showing a period indistinguishable from 24 h. The entrainment occurred in parallel with an increase in spontaneous movement immediately prior to the daily wheel exposure. A similar preexposure increase was observed in only one of four nonentrained mice. The preexposure increase appeared in 19.5 days on average after the start of daily wheel exposure and persisted for 36 days on average after the termination of the exposure schedule. The preexposure increase was detected only when daily wheel exposure came into the activity phase of the circadian behavior rhythm, which was accompanied by an increase in the number of wheel revolutions. These findings indicate that a novel oscillation with a circadian period is induced in mice by daily exposure to a running wheel at a fixed time of day and suggest that the oscillation is involved in the nonphotic entrainment of circadian rhythms in spontaneous movement.

scholarly journals miR-263b Controls Circadian Behavior and the Structural Plasticity of Pacemaker Neurons by Regulating the LIM-Only Protein Beadex

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 923 ◽  
Author(s):  
Xiaoge Nian ◽  
Wenfeng Chen ◽  
Weiwei Bai ◽  
Zhangwu Zhao ◽  
Yong Zhang
Keyword(s):  
Circadian Rhythms ◽  
Environmental Changes ◽  
Structural Plasticity ◽  
Underlying Mechanism ◽  
Molecular Characteristics ◽  
Constant Darkness ◽  
Loss Of Function ◽  
Physiological Importance ◽  
Important Regulator ◽  
Locomotor Rhythms

Circadian clocks drive rhythmic physiology and behavior to allow adaption to daily environmental changes. In Drosophila, the small ventral lateral neurons (sLNvs) are primary pacemakers that control circadian rhythms. Circadian changes are observed in the dorsal axonal projections of the sLNvs, but their physiological importance and the underlying mechanism are unclear. Here, we identified miR-263b as an important regulator of circadian rhythms and structural plasticity of sLNvs in Drosophila. Depletion of miR-263b (miR-263bKO) in flies dramatically impaired locomotor rhythms under constant darkness. Indeed, miR-263b is required for the structural plasticity of sLNvs. miR-263b regulates circadian rhythms through inhibition of expression of the LIM-only protein Beadex (Bx). Consistently, overexpression of Bx or loss-of-function mutation (BxhdpR26) phenocopied miR-263bKO and miR-263b overexpression in behavior and molecular characteristics. In addition, mutating the miR-263b binding sites in the Bx 3′ UTR using CRISPR/Cas9 recapitulated the circadian phenotypes of miR-263bKO flies. Together, these results establish miR-263b as an important regulator of circadian locomotor behavior and structural plasticity.

scholarly journals Zebrafish Mutants Carrying Leptin a (lepa) Gene Deficiency Display Obesity, Anxiety, Less Aggression and Fear, and Circadian Rhythm and Color Preference Dysregulation

2018 ◽  
Vol 19 (12) ◽  
pp. 4038 ◽  
Author(s):  
Gilbert Audira ◽  
Sreeja Sarasamma ◽  
Jung-Ren Chen ◽  
Stevhen Juniardi ◽  
Bonifasius Sampurna ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Critical Role ◽  
Color Preference ◽  
Loss Of Function ◽  
Coding Region ◽  
Transcription Activator ◽  
Zebrafish Model ◽  
Biochemical Assays ◽  
First Time ◽  
The Brain

Leptin, a hormone secreted by peripheral adipose tissues, regulates the appetite in animals. Recently, evidence has shown that leptin also plays roles in behavioral response in addition to controlling appetite. In this study, we examined the potential function of leptin on non-appetite behaviors in zebrafish model. By using genome editing tool of Transcription activator-like effector nuclease (TALEN), we successfully knocked out leptin a (lepa) gene by deleting 4 bp within coding region to create a premature-translation stop. Morphological and appetite analysis showed the lepa KO fish display a phenotype with obese, good appetite and elevation of Agouti-related peptide (AgRP) and Ghrelin hormones, consistent with the canonical function of leptin in controlling food intake. By multiple behavior endpoint analyses, including novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm, and color preference assay, we found the lepa KO fish display an anxiogenic phenotype showing hyperactivity with rapid swimming, less freezing time, less fear to predator, loose shoaling area forming, and circadian rhythm and color preference dysregulations. Using biochemical assays, melatonin, norepinephrine, acetylcholine and serotonin levels in the brain were found to be significantly reduced in lepa KO fish, while the levels of dopamine, glycine and cortisol in the brain were significantly elevated. In addition, the brain ROS level was elevated, and the anti-oxidative enzyme catalase level was reduced. Taken together, by performing loss-of-function multiple behavior endpoint testing and biochemical analysis, we provide strong evidence for a critical role of lepa gene in modulating anxiety, aggression, fear, and circadian rhythm behaviors in zebrafish for the first time.

scholarly journals Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

2021 ◽  
Vol 12 ◽  
Author(s):  
Edouard Jaumouillé ◽  
Rafael Koch ◽  
Emi Nagoshi
Keyword(s):  
Constant Darkness ◽  
Molecular Clocks ◽  
Pacemaker Neurons ◽  
Molecular Oscillator ◽  
Neural Communication ◽  
Theoretical Predictions ◽  
Neural Transmission ◽  
Free Running ◽  
Locomotor Rhythms ◽  
Central Pacemaker

Studies of circadian locomotor rhythms in Drosophila melanogaster gave evidence to the preceding theoretical predictions on circadian rhythms. The molecular oscillator in flies, as in virtually all organisms, operates using transcriptional-translational feedback loops together with intricate post-transcriptional processes. Approximately150 pacemaker neurons, each equipped with a molecular oscillator, form a circuit that functions as the central pacemaker for locomotor rhythms. Input and output pathways to and from the pacemaker circuit are dissected to the level of individual neurons. Pacemaker neurons consist of functionally diverse subclasses, including those designated as the Morning/Master (M)-oscillator essential for driving free-running locomotor rhythms in constant darkness and the Evening (E)-oscillator that drives evening activity. However, accumulating evidence challenges this dual-oscillator model for the circadian circuit organization and propose the view that multiple oscillators are coordinated through network interactions. Here we attempt to provide further evidence to the revised model of the circadian network. We demonstrate that the disruption of molecular clocks or neural output of the M-oscillator during adulthood dampens free-running behavior surprisingly slowly, whereas the disruption of both functions results in an immediate arrhythmia. Therefore, clocks and neural communication of the M-oscillator act additively to sustain rhythmic locomotor output. This phenomenon also suggests that M-oscillator can be a pacemaker or a downstream path that passively receives rhythmic inputs from another pacemaker and convey output signals. Our results support the distributed network model and highlight the remarkable resilience of the Drosophila circadian pacemaker circuit, which can alter its topology to maintain locomotor rhythms.

A critical role of iNOS-derived Nitric Oxide (NO) and progesterone in implantation

1998 ◽  
Vol 5 (1) ◽  
pp. 115A-115A
Author(s):  
K CHWALISZ ◽  
E WINTERHAGER ◽  
T THIENEL ◽  
R GARFIELD
Keyword(s):  
Nitric Oxide ◽  
Critical Role

Non-Plasmonic SERS with Silicon: Is It Really Safe? New Insights into Opto-Thermics of Core/Shell Microbeads

2018 ◽  
Author(s):  
Nicolò Bontempi ◽  
Irene Vassalini ◽  
Stefano Danesi ◽  
Matteo Ferroni ◽  
Paolo Colombi ◽  
...  
Keyword(s):  
Critical Role ◽  
Raman Laser ◽  
Core Shell ◽  
Thermal Coupling ◽  
Melting Points ◽  
Experimental Proof ◽  
Weakly Coupled ◽  
Light Management ◽  
Laser Sources ◽  
First Time

<p>Here we investigate for the first time the opto-thermal behavior of SiO<sub>2</sub>/Si core/shell microbeads (Si-rex) irradiated with three common Raman laser sources (lambda=532, 633, 785 nm) under real working conditions. We obtained an experimental proof of the critical role played by bead size and aggregation in heat and light management, demonstrating that in the case of strong opto-thermal coupling the temperature can exceed that of the melting points of both core and shell components. In addition, we also show that weakly coupled beads can be utilized as stable substrates for plasmon-free SERS experiments.</p>

Circadian Rhythms of Endothelial Nitric Oxide Synthase and Toll-like Receptors 2 Production in Females with Rheumatoid Arthritis Depending on NOS3 Gene Polymorphism

2020 ◽  
Vol 15 (2) ◽  
pp. 145-151
Author(s):  
Kateryna Zaichko ◽  
Nataliia Zaichko ◽  
Oleksandr Maievskyi ◽  
Oleksandr Korotkyi ◽  
Tetyana Falalyeyeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Circadian Rhythms ◽  
Gene Polymorphism ◽  
Endothelial Nitric Oxide Synthase ◽  
Toll Like Receptors ◽  
Nos3 Gene ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background: Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism. Methods: We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results. Results: Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively). Conclusion: RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.

scholarly journals Plastid phylogenomics resolves ambiguous relationships within the orchid family and provides a solid timeframe for biogeography and macroevolution

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Alejandra Serna-Sánchez ◽  
Oscar A. Pérez-Escobar ◽  
Diego Bogarín ◽  
María Fernanda Torres-Jimenez ◽  
Astrid Catalina Alvarez-Yela ◽  
...  
Keyword(s):  
Phylogenetic Relationships ◽  
Divergence Times ◽  
Molecular Clocks ◽  
Phylogenetic Placement ◽  
Plastid Genomes ◽  
Phylogenetic Reconstructions ◽  
A Genome ◽  
Tree Models ◽  
Phylogenomic Analyses ◽  
First Time

AbstractRecent phylogenomic analyses based on the maternally inherited plastid organelle have enlightened evolutionary relationships between the subfamilies of Orchidaceae and most of the tribes. However, uncertainty remains within several subtribes and genera for which phylogenetic relationships have not ever been tested in a phylogenomic context. To address these knowledge-gaps, we here provide the most extensively sampled analysis of the orchid family to date, based on 78 plastid coding genes representing 264 species, 117 genera, 18 tribes and 28 subtribes. Divergence times are also provided as inferred from strict and relaxed molecular clocks and birth–death tree models. Our taxon sampling includes 51 newly sequenced plastid genomes produced by a genome skimming approach. We focus our sampling efforts on previously unplaced clades within tribes Cymbidieae and Epidendreae. Our results confirmed phylogenetic relationships in Orchidaceae as recovered in previous studies, most of which were recovered with maximum support (209 of the 262 tree branches). We provide for the first time a clear phylogenetic placement for Codonorchideae within subfamily Orchidoideae, and Podochilieae and Collabieae within subfamily Epidendroideae. We also identify relationships that have been persistently problematic across multiple studies, regardless of the different details of sampling and genomic datasets used for phylogenetic reconstructions. Our study provides an expanded, robust temporal phylogenomic framework of the Orchidaceae that paves the way for biogeographical and macroevolutionary studies.

Synthesis of an azadioxa-planar triphenylborane and investigation of its structural and photophysical properties

2021 ◽  
Author(s):  
Y. Kitamoto ◽  
K. Oda ◽  
K. Ogino ◽  
K. Hiyama ◽  
H. Kita ◽  
...  
Keyword(s):  
Photophysical Properties ◽  
Critical Role ◽  
Molecular Properties ◽  
Bridging Groups ◽  
First Time

An azadioxa-planar triphenylborane was synthesized for the first time and it was found that bridging groups have a critical role in changing its molecular properties.

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