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Article ; Online: Tangled up in blue: Contribution of short-wavelength sensitive cones in human circadian photoentrainment.

Buhr, Ethan D

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

2023 Volume 120, Issue 2, Page(s) e2219617120

MeSH term(s)	Humans ; Retinal Cone Photoreceptor Cells ; Circadian Rhythm ; Light
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2219617120
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Article ; Online: Molecular circadian rhythms in mammals: From angstroms to organisms.

Buhr, Ethan D

Seminars in cell & developmental biology

2021 Volume 126, Page(s) 1–2

MeSH term(s)	Animals ; Circadian Clocks ; Circadian Rhythm/genetics ; Mammals ; Suprachiasmatic Nucleus
Language	English
Publishing date	2021-10-01
Publishing country	England
Document type	Editorial
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2021.09.014
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Article ; Online: Melatonin Adjusts the Phase of Mouse Circadian Clocks in the Cornea Both Ex Vivo and In Vivo.

Huynh, Alex V / Buhr, Ethan D

Journal of biological rhythms

2021 Volume 36, Issue 5, Page(s) 470–482

Abstract: The presence of an endogenous circadian clock within most mammalian cells is associated with the amazing observation that within a given tissue, these clocks are largely in synchrony with each other. Different tissues use a variety of systemic or ... ...

Abstract	The presence of an endogenous circadian clock within most mammalian cells is associated with the amazing observation that within a given tissue, these clocks are largely in synchrony with each other. Different tissues use a variety of systemic or environmental cues to precisely coordinate the phase of these clocks. The cornea is a unique tissue in that it is largely isolated from the direct blood supply that most tissues experience, it is transparent to visible light, and it is exposed directly to environmental light and temperature. Melatonin is a hormone that has been implicated in regulation of the cornea's circadian clocks. Here, we analyze the ability of rhythmic melatonin to entrain corneas ex vivo, and analyze the phase of corneal circadian clocks in vivo both in light: dark cycles and in constant darkness. We find that the presence of a retina from a melatonin-proficient mouse strain, C3Sn, can photoentrain the circadian clocks of a co-cultured mouse cornea, but a retina from a melatonin-deficient strain, C57Bl/6, cannot. Furthermore, pharmacologic blockade of melatonin or use of a retina with advanced retinal degeneration,
MeSH term(s)	Animals ; Circadian Clocks/genetics ; Circadian Rhythm ; Cornea ; Light ; Melatonin/pharmacology ; Mice ; Mice, Inbred C57BL
Chemical Substances	Melatonin (JL5DK93RCL)
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/07487304211032385
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Article: Circadian Oscillations in the Murine Preoptic Area Are Reset by Temperature, but Not Light.

Díaz, Nicolás M / Gordon, Shannon A / Lang, Richard A / Buhr, Ethan D

Frontiers in physiology

2022 Volume 13, Page(s) 934591

Abstract: Mammals maintain their internal body temperature within a physiologically optimal range. This involves the regulation of core body temperature in response to changing environmental temperatures and a natural circadian oscillation of internal temperatures. ...

Abstract	Mammals maintain their internal body temperature within a physiologically optimal range. This involves the regulation of core body temperature in response to changing environmental temperatures and a natural circadian oscillation of internal temperatures. The preoptic area (POA) of the hypothalamus coordinates body temperature by responding to both external temperature cues and internal brain temperature. Here we describe an autonomous circadian clock system in the murine ventromedial POA (VMPO) in close proximity to cells which express the atypical violet-light sensitive opsin, Opn5. We analyzed the light-sensitivity and thermal-sensitivity of the VMPO circadian clocks
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.934591
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Article ; Online: 3D-printed assistive pipetting system for gel electrophoresis for technicians with low acuity vision.

Huynh, Alex Viqian / Stein, Phillip / Buhr, Ethan D

BioTechniques

2020 Volume 70, Issue 1, Page(s) 49–53

Abstract: In molecular biology laboratories, many tasks require fine motor control and high acuity vision. For example, lab technicians with visual impairment experience difficulty loading samples into the small wells of a horizontal agarose gel. We have developed ...

Abstract	In molecular biology laboratories, many tasks require fine motor control and high acuity vision. For example, lab technicians with visual impairment experience difficulty loading samples into the small wells of a horizontal agarose gel. We have developed a 3D-printable gel loading system which allows technicians with low-contrast vision to load gels correctly. It includes a casting tray, a bridge, and a modified comb. The system provides a high-contrast visual field to improve visibility, and the bridge allows pipette tips to be inserted at the correct location and only to the correct depth. The necessary computer files for printing this device are freely available to increase the accessibility of molecular biology laboratories to people with visual impairment.
MeSH term(s)	Electrophoresis/instrumentation ; Humans ; Printing, Three-Dimensional ; Vision Disorders
Language	English
Publishing date	2020-12-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
DOI	10.2144/btn-2020-0139
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Article ; Online: The molecular clockwork of mammalian cells.

Yi, Jonathan S / Díaz, Nicolás M / D'Souza, Shane / Buhr, Ethan D

Seminars in cell & developmental biology

2021 Volume 126, Page(s) 87–96

Abstract: Most organisms contain self-sustained circadian clocks. These clocks can be synchronized by environmental stimuli, but can also oscillate indefinitely in isolation. In mammals this is true at the molecular level for the majority of cell types that have ... ...

Abstract	Most organisms contain self-sustained circadian clocks. These clocks can be synchronized by environmental stimuli, but can also oscillate indefinitely in isolation. In mammals this is true at the molecular level for the majority of cell types that have been examined. A core set of "clock genes" form a transcriptional/translational feedback loop (TTFL) which repeats with a period of approximately 24 h. The exact mechanism of the TTFL differs slightly in various cell types, but all involve similar family members of the core cohort of clock genes. The clock has many outputs which are unique for different tissues. Cells in diverse tissues will convert the timing signals provided by the TTFL into uniquely orchestrated transcriptional oscillations of many clock-controlled genes and cellular processes.
MeSH term(s)	Animals ; Circadian Clocks/genetics ; Circadian Rhythm/genetics ; Humans ; Mammals/genetics ; Protein Processing, Post-Translational
Language	English
Publishing date	2021-03-31
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2021.03.012
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Article ; Online: Wounding Induces Facultative Opn5-Dependent Circadian Photoreception in the Murine Cornea.

Díaz, Nicolás M / Lang, Richard A / Van Gelder, Russell N / Buhr, Ethan D

Investigative ophthalmology & visual science

2020 Volume 61, Issue 6, Page(s) 37

Abstract: Purpose: Autonomous molecular circadian clocks are present in the majority of mammalian tissues. These clocks are synchronized to phases appropriate for their physiologic role by internal systemic cues, external environmental cues, or both. The ... ...

Abstract	Purpose: Autonomous molecular circadian clocks are present in the majority of mammalian tissues. These clocks are synchronized to phases appropriate for their physiologic role by internal systemic cues, external environmental cues, or both. The circadian clocks of the in vivo mouse cornea synchronize to the phase of the brain's master clock primarily through systemic cues, but ex vivo corneal clocks entrain to environmental light cycles. We evaluated the underlying mechanisms of this difference. Methods: Molecular circadian clocks of mouse corneas were evaluated in vivo and ex vivo for response to environmental light. The presence of opsins and effect of genetic deletion of opsins were evaluated for influence on circadian photoresponses. Opn5-expressing cells were identified using Opn5Cre;Ai14 mice and RT-PCR, and they were characterized using immunocytochemistry. Results: Molecular circadian clocks of the cornea remain in phase with behavioral circadian locomotor rhythms in vivo but are photoentrainable in tissue culture. After full-thickness incision or epithelial debridement, expression of the opsin photopigment Opn5 is induced in the cornea in a subset of preexisting epithelial cells adjacent to the wound site. This induction coincides with conferral of direct, short-wavelength light sensitivity to the circadian clocks throughout the cornea. Conclusions: Corneal circadian rhythms become photosensitive after wounding. Opn5 gene function (but not Opn3 or Opn4 function) is necessary for induced photosensitivity. These results demonstrate that opsin-dependent direct light sensitivity can be facultatively induced in the murine cornea.
MeSH term(s)	Animals ; Circadian Rhythm/physiology ; Cornea/metabolism ; Cornea/pathology ; Corneal Injuries/genetics ; Corneal Injuries/metabolism ; Corneal Injuries/physiopathology ; Disease Models, Animal ; Gene Expression Regulation ; Membrane Proteins/biosynthesis ; Membrane Proteins/genetics ; Mice ; Mice, Inbred C57BL ; Opsins/biosynthesis ; Opsins/genetics ; Photoperiod ; RNA/genetics ; Rod Opsins/metabolism
Chemical Substances	Membrane Proteins ; OPN5 protein, mouse ; Opsins ; Rod Opsins ; RNA (63231-63-0)
Language	English
Publishing date	2020-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.61.6.37
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Article: Toward an indoor lighting solution for social jet lag.

Neitz, Alex / Rice, Alicia / Casiraghi, Leandro / Bussi, Ivana L / Buhr, Ethan D / Neitz, Maureen / Neitz, Jay / de la Iglesia, Horacio O / Kuchenbecker, James A

Research square

2023

Abstract: There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focused on stimulating the intrinsic ... ...

Abstract	There is growing interest in developing artificial lighting that stimulates intrinsically photosensitive retinal ganglion cells (ipRGCs) to entrain circadian rhythms to improve mood, sleep, and health. Efforts have focused on stimulating the intrinsic photopigment, melanopsin; however, recently, specialized color vision circuits have been elucidated in the primate retina that transmit blue-yellow cone-opponent signals to ipRGCs. We designed a light that stimulates color-opponent inputs to ipRGCs by temporally alternating short and longer wavelength components that strongly modulate short-wavelength sensitive (S) cones. Two-hour exposure to this S-cone modulating light produced an average circadian phase advance of one hour and twenty minutes in 6 subjects (mean age = 30 years) compared to no phase advance for the subjects after exposure to a 500-lux white light equated for melanopsin effectiveness. These results are promising for developing artificial lighting that is highly effective in controlling circadian rhythms by invisibly modulating cone-opponent circuits.
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2649098/v1
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Article: Molecular components of the Mammalian circadian clock.

Buhr, Ethan D / Takahashi, Joseph S

Handbook of experimental pharmacology

2013 , Issue 217, Page(s) 3–27

Abstract: Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause ...

Abstract	Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases. Signals that can entrain these peripheral clocks include humoral signals, metabolic factors, and body temperature. At the level of individual tissues, thousands of genes are brought to unique phases through the actions of a local transcription/translation-based feedback oscillator and systemic cues. In this molecular clock, the proteins CLOCK and BMAL1 cause the transcription of genes which ultimately feedback and inhibit CLOCK and BMAL1 transcriptional activity. Finally, there are also other molecular circadian oscillators which can act independently of the transcription-based clock in all species which have been tested.
MeSH term(s)	ARNTL Transcription Factors/physiology ; Animals ; CLOCK Proteins/physiology ; Circadian Clocks/physiology ; Humans ; Suprachiasmatic Nucleus/physiology ; Temperature ; Transcription, Genetic
Chemical Substances	ARNTL Transcription Factors ; CLOCK Proteins (EC 2.3.1.48)
Language	English
Publishing date	2013-04-21
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/978-3-642-25950-0_1
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Article ; Online: Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins.

Upton, Brian A / Díaz, Nicolás M / Gordon, Shannon A / Van Gelder, Russell N / Buhr, Ethan D / Lang, Richard A

Journal of biological rhythms

2021 Volume 36, Issue 2, Page(s) 109–126

Abstract: Animals have evolved light-sensitive G protein-coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express ... ...

Abstract	Animals have evolved light-sensitive G protein-coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express them. While many unique patterns of evolution have been identified in mammals for rod and cone opsins, far less is known about the atypical mammalian opsins. Using genomic data from over 400 mammalian species from 22 orders, unique patterns of evolution for each mammalian opsins were identified, including photoisomerases, RGR-opsin (RGR) and peropsin (RRH), as well as atypical opsins, encephalopsin (OPN3), melanopsin (OPN4), and neuropsin (OPN5). The results demonstrate that OPN5 and rhodopsin show extreme conservation across all mammalian lineages. The cone opsins, SWS1 and LWS, and the nonvisual opsins, OPN3 and RRH, demonstrate a moderate degree of sequence conservation relative to other opsins, with some instances of lineage-specific gene loss. Finally, the photoisomerase, RGR, and the best-studied atypical opsin, OPN4, have high sequence diversity within mammals. These conservation patterns are maintained in human populations. Importantly, all mammalian opsins retain key amino acid residues important for conjugation to retinal-based chromophores, permitting light sensitivity. These patterns of evolution are discussed along with known functions of each atypical opsin, such as in circadian or metabolic physiology, to provide insight into the observed patterns of evolutionary constraint.
MeSH term(s)	Animals ; Circadian Rhythm/radiation effects ; Conserved Sequence ; Evolution, Molecular ; Humans ; Mammals/metabolism ; Mice ; Opsins/chemistry ; Opsins/genetics ; Opsins/metabolism ; Opsins/radiation effects ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Receptors, G-Protein-Coupled/radiation effects ; Retina/metabolism ; Retina/radiation effects ; Rhodopsin/chemistry ; Rhodopsin/genetics ; Rhodopsin/metabolism ; Rhodopsin/radiation effects
Chemical Substances	Opsins ; Receptors, G-Protein-Coupled ; Rhodopsin (9009-81-8)
Language	English
Publishing date	2021-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730421999870
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