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Article ; Online: Functional Analyses of Four Cryptochromes From Aquatic Organisms After Heterologous Expression in

Chen, Chenghao / Tamai, T Katherine / Xu, Min / Petrone, Libero / Oliveri, Paola / Whitmore, David / Stanewsky, Ralf

2024 , Page(s) 7487304241228617

Abstract: Cryptochromes (Crys) represent a multi-facetted class of proteins closely associated with circadian clocks. They have been shown to function as photoreceptors but also to fulfill light-independent roles as transcriptional repressors within the negative ... ...

Abstract	Cryptochromes (Crys) represent a multi-facetted class of proteins closely associated with circadian clocks. They have been shown to function as photoreceptors but also to fulfill light-independent roles as transcriptional repressors within the negative feedback loop of the circadian clock. In addition, there is evidence for Crys being involved in light-dependent magneto-sensing, and regulation of neuronal activity in insects, adding to the functional diversity of this cryptic protein class. In mammals, Crys are essential components of the circadian clock, but their role in other vertebrates is less clear. In invertebrates, Crys can function as circadian photoreceptors, or as components of the circadian clock, while in some species, both light-receptive and clock factor roles coexist. In the current study, we investigate the function of Cry proteins in zebrafish (
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/07487304241228617
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Article: Molecular and Neuroendocrine Mechanisms of Avian Seasonal Reproduction.

Tamai, T Katherine / Yoshimura, Takashi

Advances in experimental medicine and biology

2017 Volume 1001, Page(s) 125–136

Abstract: ... within the mediobasal hypothalamus. This local bioactive TH, triiodothyronine (T ...

Abstract	Animals living outside tropical zones experience seasonal changes in the environment and accordingly, adapt their physiology and behavior in reproduction, molting, and migration. Subtropical birds are excellent models for the study of seasonal reproduction because of their rapid and dramatic response to changes in photoperiod. For example, testicular weight typically changes by more than a 100-fold. In birds, the eyes are not necessary for seasonal reproduction, and light is instead perceived by deep brain photoreceptors. Functional genomic analysis has revealed that long day (LD)-induced thyrotropin from the pars tuberalis of the pituitary gland causes local thyroid hormone (TH) activation within the mediobasal hypothalamus. This local bioactive TH, triiodothyronine (T
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-10-3975-1_8
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Article: Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington's disease.

Whittaker, Daniel S / Tamai, T Katherine / Bains, Raj S / Villanueva, Sophia Anne Marie / Luk, Shu Hon Christopher / Dell'Angelica, Derek / Block, Gene D / Ghiani, Cristina A / Colwell, Christopher S

Frontiers in nutrition

2022 Volume 9, Page(s) 1034743

Abstract: Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington's disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine ... ...

Abstract	Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington's disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate the symptoms and delay disease progression in the BACHD mouse model of HD. Adult WT and BACHD male mice were fed a normal or a ketogenic diet (KD) for 3 months. The KD evoked a robust rhythm in serum levels of β-hydroxybutyrate and dramatic changes in the microbiome of male WT and BACHD mice. NanoString analysis revealed transcriptional changes driven by the KD in the striatum of both WT and BACHD mice. Disturbances in sleep/wake cycles have been reported in mouse models of HD and are common among HD patients. Having established that the KD had effects on both the WT and mutant mice, we examined its impact on sleep/wake cycles. KD increased daytime sleep and improved the timing of sleep onset, while other sleep parameters were not altered. In addition, KD improved activity rhythms, including rhythmic power, and reduced inappropriate daytime activity and onset variability. Importantly, KD improved motor performance on the rotarod and challenging beam tests. It is worth emphasizing that HD is a genetically caused disease with no known cure. Life-style changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of diet-based treatment strategies in a pre-clinical model of HD.
Language	English
Publishing date	2022-11-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2022.1034743
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Article ; Online: Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process.

Laranjeiro, Ricardo / Tamai, T Katherine / Letton, William / Hamilton, Noémie / Whitmore, David

Journal of biological rhythms

2018 Volume 33, Issue 2, Page(s) 137–150

Abstract: ... under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up ... in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles. ...

Abstract	Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles.
MeSH term(s)	Animals ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cell Line ; Circadian Clocks ; Circadian Rhythm/physiology ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Light ; Photoperiod ; Single-Cell Analysis ; Zebrafish/genetics ; Zebrafish/physiology
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p21
Language	English
Publishing date	2018-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730418755583
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Article ; Online: Mapping brain gene coexpression in daytime transcriptomes unveils diurnal molecular networks and deciphers perturbation gene signatures.

Neuron

2022 Volume 110, Issue 20, Page(s) 3318–3338.e9

Abstract: Brain tissue transcriptomes may be organized into gene coexpression networks, but their underlying biological drivers remain incompletely understood. Here, we undertook a large-scale transcriptomic study using 508 wild-type mouse striatal tissue samples ... ...

Abstract	Brain tissue transcriptomes may be organized into gene coexpression networks, but their underlying biological drivers remain incompletely understood. Here, we undertook a large-scale transcriptomic study using 508 wild-type mouse striatal tissue samples dissected exclusively in the afternoons to define 38 highly reproducible gene coexpression modules. We found that 13 and 11 modules are enriched in cell-type and molecular complex markers, respectively. Importantly, 18 modules are highly enriched in daily rhythmically expressed genes that peak or trough with distinct temporal kinetics, revealing the underlying biology of striatal diurnal gene networks. Moreover, the diurnal coexpression networks are a dominant feature of daytime transcriptomes in the mouse cortex. We next employed the striatal coexpression modules to decipher the striatal transcriptomic signatures from Huntington's disease models and heterozygous null mice for 52 genes, uncovering novel functions for Prkcq and Kdm4b in oligodendrocyte differentiation and bipolar disorder-associated Trank1 in regulating anxiety-like behaviors and nocturnal locomotion.
MeSH term(s)	Animals ; Mice ; Transcriptome ; Protein Kinase C-theta/genetics ; Gene Regulatory Networks ; Huntington Disease/genetics ; Brain
Chemical Substances	Protein Kinase C-theta (EC 2.7.11.13)
Language	English
Publishing date	2022-10-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2022.09.028
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen.

Mosser, Eric A / Chiu, Cindy N / Tamai, T Katherine / Hirota, Tsuyoshi / Li, Suna / Hui, May / Wang, Amy / Singh, Chanpreet / Giovanni, Andrew / Kay, Steve A / Prober, David A

Scientific reports

2019 Volume 9, Issue 1, Page(s) 12405

Abstract: The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we ... ...

Abstract	The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.
MeSH term(s)	Animals ; Animals, Genetically Modified/physiology ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Casein Kinase I/antagonists & inhibitors ; Casein Kinase I/metabolism ; Circadian Rhythm/drug effects ; Larva/drug effects ; Larva/physiology ; Protein Kinase Inhibitors/pharmacology ; Receptors, Glycine/agonists ; Receptors, Glycine/metabolism ; Small Molecule Libraries/pharmacology ; Taurine/pharmacology ; Zebrafish/growth & development ; Zebrafish/physiology ; Zebrafish Proteins/antagonists & inhibitors ; Zebrafish Proteins/metabolism
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Protein Kinase Inhibitors ; Receptors, Glycine ; Small Molecule Libraries ; Zebrafish Proteins ; Taurine (1EQV5MLY3D) ; Casein Kinase I (EC 2.7.11.1)
Language	English
Publishing date	2019-08-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-48914-7
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Article ; Online: Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior.

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 17, Page(s) 9594–9603

Abstract: Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like ... ...

Abstract	Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an
MeSH term(s)	Animals ; Behavior, Animal/physiology ; Depression/metabolism ; Dimethyl Sulfoxide/toxicity ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Genome ; Mutation ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Oryzias/physiology ; Seasons
Chemical Substances	NF-E2-Related Factor 2 ; Dimethyl Sulfoxide (YOW8V9698H)
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2000278117
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Zs.A 1148: Show issues

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Article ; Online: Light acts on the zebrafish circadian clock to suppress rhythmic mitosis and cell proliferation.

Tamai, T Katherine / Young, Lucy C / Cox, Catherine A / Whitmore, David

Journal of biological rhythms

2012 Volume 27, Issue 3, Page(s) 226–236

Abstract: A fundamental role of the circadian clock is to control biochemical and physiological processes such that they occur an optimal time of day. One of the most significant clock outputs from a clinical as well as basic biological standpoint is the timing of ...

Abstract	A fundamental role of the circadian clock is to control biochemical and physiological processes such that they occur an optimal time of day. One of the most significant clock outputs from a clinical as well as basic biological standpoint is the timing of the cell cycle. Here we show that the circadian clock regulates the timing of mitosis in a light-responsive, clock-containing zebrafish cell line. Disrupting clock function, using a CLOCK1 dominant-negative construct or constant light, blocks the gating of cell division, demonstrating that this mitotic rhythm is cell autonomous and under control of the circadian pacemaker. Quantitative PCR reveals that several key mitotic genes, including Cyclin B1, Cyclin B2, and cdc2, are rhythmically expressed and clock-controlled. Peak expression of these genes occurs at a critical phase required to gate mitosis to the late night/early morning. Using clock and cell cycle luminescent reporter zebrafish cell lines, we show that light strongly represses not only circadian clock function, but also mitotic gene expression, and consequently slows cell proliferation.
MeSH term(s)	Animals ; Aphidicolin/pharmacology ; CDC2 Protein Kinase/metabolism ; Cell Proliferation ; Circadian Rhythm ; Cyclin B1/biosynthesis ; Cyclin B2/biosynthesis ; Flow Cytometry/methods ; Genes, Reporter ; Histones/chemistry ; Luminescence ; Mitosis ; Models, Biological ; Polymerase Chain Reaction/methods ; Zebrafish/physiology
Chemical Substances	Cyclin B1 ; Cyclin B2 ; Histones ; Aphidicolin (38966-21-1) ; CDC2 Protein Kinase (EC 2.7.11.22)
Language	English
Publishing date	2012-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730412440861
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Article ; Online: Identification of circadian clock modulators from existing drugs.

Tamai, T Katherine / Nakane, Yusuke / Ota, Wataru / Kobayashi, Akane / Ishiguro, Masateru / Kadofusa, Naoya / Ikegami, Keisuke / Yagita, Kazuhiro / Shigeyoshi, Yasufumi / Sudo, Masaki / Nishiwaki-Ohkawa, Taeko / Sato, Ayato / Yoshimura, Takashi

EMBO molecular medicine

2018 Volume 10, Issue 5

Abstract: Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is ... ...

Abstract	Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cells, Cultured ; Circadian Clocks/drug effects ; Circadian Clocks/physiology ; Circadian Rhythm/drug effects ; Circadian Rhythm/physiology ; Drug Repositioning/methods ; Embryo, Mammalian/cytology ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Humans ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Pharmaceutical Preparations/administration & dosage ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/metabolism
Chemical Substances	Pharmaceutical Preparations ; Protein Kinase Inhibitors ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2018-04-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.201708724
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Zs.A 6784: Show issues

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Article ; Online: Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen

Eric A. Mosser / Cindy N. Chiu / T. Katherine Tamai / Tsuyoshi Hirota / Suna Li / May Hui / Amy Wang / Chanpreet Singh / Andrew Giovanni / Steve A. Kay / David A. Prober

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 14

Abstract: Abstract The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we ...

Abstract	Abstract The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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