Temperature Entrainment Research Articles

The Reindeer Circadian Clock Is Rhythmic and Temperature-compensated But Shows Evidence of Weak Coupling Between the Secondary and Core Molecular Clock Loops.

Circadian rhythms synchronize the internal physiology of animals allowing them to anticipate daily changes in their environment. Arctic habitats may diminish the selective advantages of circadian rhythmicity by relaxing daily rhythmic environmental constraints, presenting a valuable opportunity to study the evolution of circadian rhythms. In reindeer, circadian control of locomotor activity and melatonin release is weak or absent, and the molecular clockwork is reportedly non-functional. Here we present new evidence that the circadian clock in cultured reindeer fibroblasts is rhythmic and temperature-compensated. Compared with mouse fibroblasts, however, reindeer fibroblasts have a short free-running period, and temperature cycles have an atypical impact on clock gene regulation. In reindeer cells, Per2 and Bmal1 reporters show rapid responses to temperature cycles, with a disintegration of their normal antiphasic relationship. The antiphasic Per2-Bmal1 relationship re-emerges immediately after release from temperature cycles, but without complete temperature entrainment and with a marked decline in circadian amplitude. Experiments using Bmal1 promoter reporters with mutated RORE sites showed that a reindeer-like response to temperature cycles can be mimicked in mouse or human cell lines by decoupling Bmal1 reporter activity from ROR/REV-ERB-dependent transcriptional regulation. We suggest that weak coupling between core and secondary circadian feedback loops accounts for the observed behavior of reindeer fibroblasts in vitro. Our findings highlight diversity in how the thermal environment affects the temporal organization of mammals living under different thermoenergetic constraints.

Mathematical modeling of temperature-induced circadian rhythms

The central circadian pacemaker in the suprachiasmatic nuclei (SCN) aligns the phase and period of autonomous molecular oscillators in peripheral cells to daily light/dark cycles via physiological, neuronal, hormonal, and metabolic signals. Among different entrainment factors, temperature entrainment has been proposed as an essential alternative for inducing and sustaining circadian rhythms in vitro. While the synchronization mechanisms for hormones such as glucocorticoids have been widely studied, little is known about the crucial role of body temperature as a systemic cue. In this work, we develop a semi-mechanistic mathematical model describing the entrainment of peripheral clocks to temperature rhythms. The model incorporates a temperature sensing-transduction cascade involving a heat shock transcription factor-1 (HSF1) and heat shock response (HSR) pathway to simulate the entrainment of clock genes. The model is used to investigate the mammalian temperature entrainment and synchronization of cells subject to temperature oscillations of different amplitudes and magnitudes and examine the effects of transitioning between temperature schedules. Our computational analyses of the system’s dynamic responses reveal that 1) individual cells gradually synchronize to the rhythmic temperature signal by resetting their intrinsic phases to achieve coherent dynamics while oscillations are abolished in the absence of temperature rhythmicity; 2) alterations in the amplitude and period of temperature rhythms impact the peripheral synchronization behavior; 3) personalized synchronization strategies allow for differential, adaptive responses to temperature rhythms. Our results demonstrate that temperature can be a potent entrainer of circadian rhythms. Therefore, in vitro systems subjected to temperature modulation can serve as a potential tool for studying the adjustment or disruption of circadian rhythms.

Effect of initial generating eddy height on temperature, velocity and air entrainment of fire whirl

In this paper, we present an experimental effort to reveal the effect of the initially generated eddy height on the thermal, velocity, and air entrainment properties of the fire vortex plume. Experiments were performed by a fixed-frame facility with variable channel wall height (h), using propane as the fuel (20 cm in burner exit diameter, 50.0–100.0 kW in heat release rate). Results show that the growth rates of centerline excess temperature and axial velocity tend to increase with h in the continuous flame below h. It is found that the radial distribution of excess temperature is always of hump-type and little affected by h at lower levels, while the radial profile of axial velocity changes from the plateau-type into the hump-type as h is increased. In the upper continuous and intermittent flames, the radial profile of excess temperature evolves from the hump type into the unimodal type, and that of axial velocity develops into the unimodal type from the plateau type as h is increased. The growth rates of excess temperature radius and axial velocity radius with the normalized height decrease with h for the continuous and intermittent flames. The axial position corresponding to the significant increase in the growth rate moves upstream with the increase of the heat release rate (Q˙). Under small h, the tangential velocity within the vortex core decreases with height, suggesting that the rotational strength becomes weakened. It is found that the air entrainment is weak at the flame bottom within the initial generating eddy height, and the entrained air is insufficient for complete combustion. The axial mass flow rate increases obviously as the channel wall disappears. With the increase of h, turbulence suppression is enhanced, and its role in flame elongation becomes more significant. The reduction of flame height is probably attributed to the greater turbulent mixing length under lower initial generating eddy height.

The impact of ambient pressure on the gas temperature near the ceiling and air entrainment caused by two fires in a tunnel

The tunnel is a typical underground building. Estimating the heat released by the fire sources to the surrounding environment, as well as providing rapid emergency response, requires a thorough comprehension of the properties of gas temperature and air entrainment beneath tunnel ceilings. Numerical works are performed to explore the impact of pressure on the gas distribution, velocity field distribution, temperature field distribution, and air entrainment rate induced by dual interacting fires with various heat release rates in a tunnel building. The findings indicate that as the distance between fires increases, two flames undergo a transition from merging together to not merging (S/D ≥ 2). The rise in atmospheric pressure leads to an augmentation in the air intake of two fires, ultimately diminishing the intensity at which the flames merge. As the spacing or pressure decreases, the area of flame expansion on the tunnel ceiling grows. The oxygen level in the extra space between the two flames gradually rises as the ambient pressure rises. This leads to a reduction in the local gas speed and temperature. The constraint factor is utilized to describe the maximum strength of air entrainment, revealing that the air entrainment constraint factor (β) for two tunnel fires ranges from 0 to 0.2. The maximum temperature rise of ceiling gas (ΔTmax) is reached at zero fire spacing, which is about 900 °C. For two fires with large spacings (S/D ≥ 2), ΔTmax is mainly determined by ambient pressure and heat release rate. Given that less cryogenic air entrainment into the ceiling gas, a higher ΔTmax is achieved at lower ambient pressure. A segmented correlation to correlate ΔTmax of two fires is developed and well-verified using literature data, and the forecast error is within ±30%.

Temperature compensation and entrainment in cyanobacteria circadian rhythm

ABSTRACT Circadian rhythm is an endogenous rhythmic behavior of organisms used to adapt to the external environment. Although most biochemical reactions accelerate with increasing temperature, the period of circadian rhythms remains relatively stable across a range of temperature, a phenomenon known as temperature compensation. Meanwhile, circadian rhythms can be reset by environmental signals, such as daily periodic light or temperature, a phenomenon known as entrainment. Cyanobacteria are the simplest organisms to have circadian rhythms. The effect of light on cyanobacteria circadian rhythm has been widely studied with mathematical models. However, the effect of temperature on cyanobacteria circadian rhythm and the mechanisms of temperature compensation and entrainment are far from clear. In this paper, we apply a recent model to incorporate temperature dependence by Van’t Hoff rule. With numerical simulation, we study the temperature compensation and entrainment in detail. The results show that the system can exhibit temperature compensation when the post-transcription process is insensitive to temperature. The temperature compensation is caused by the cancellation of the increase of amplitude and the acceleration of speed, resulting in the stable period, when the temperature rises. The system can also exhibit temperature entrainment in constant light in a very limited temperature range. When the periodic light is added simultaneously to simulate more realistic environment, the temperature range of entrainment is greatly improved. The results also suggest that long-day condition is conducive to entrainment. The findings of this paper provide a theoretical reference for biological research and help us understand the dynamical mechanisms of cyanobacteria circadian rhythm.

COLD REGULATED GENE 27 and 28 Antagonize the Transcriptional Activity of the RVE8/LNK1/LNK2 Circadian Complex.

Many molecular and physiological processes in plants occur at a specific time of day. These daily rhythms are coordinated in part by the circadian clock, a timekeeper that uses daylength and temperature to maintain rhythms of approximately 24 hours in various clock-regulated phenotypes. The circadian MYB-like transcription factor REVEILLE 8 (RVE8) interacts with its transcriptional coactivators NIGHT LIGHT INDUCIBLE AND CLOCK REGULATED 1 (LNK1) and LNK2 to promote the expression of evening-phased clock genes and cold tolerance factors. While genetic approaches have commonly been used to discover connections within the clock and between clock elements and other pathways, here we used affinity purification coupled with mass spectrometry to identify time-of-day-specific protein interactors of the RVE8-LNK1/LNK2 complex in Arabidopsis (Arabidopsis thaliana). Among the interactors of RVE8/LNK1/LNK2 were COLD REGULATED GENE 27 (COR27) and COR28, which coprecipitated in an evening-specific manner. In addition to COR27 and COR28, we found an enrichment of temperature-related interactors that led us to establish a previously uncharacterized role for LNK1 and LNK2 in temperature entrainment of the clock. We established that RVE8, LNK1, and either COR27 or COR28 form a tripartite complex in yeast (Saccharomyces cerevisiae) and that the effect of this interaction in planta serves to antagonize transcriptional activation of RVE8 target genes, potentially through mediating RVE8 protein degradation in the evening. Together, these results illustrate how a proteomic approach can be used to identify time-of-day-specific protein interactions. Discovery of the RVE8-LNK-COR protein complex indicates a previously unknown regulatory mechanism for circadian and temperature signaling pathways.

Nanoplastics exposure disrupts circadian rhythm associated with dysfunction of the endolysosomal pathway and autophagy in Caenorhabditis elegans

Nanoplastics (NPs), an emerging pollutant, have raised great safety concerns due to their widespread applications and continuous release into the environment, which lead to potential human and environmental risks. Recently, polystyrene NPs (100 nm; 100 mg/L) exposure has been reported to disrupt circadian rhythms under five days temperature entrainment and be associated with stress resistance decline in Caenorhabditis elegans. This study explored the possible relationship between circadian rhythm disruption and endocytosis and autophagy under polystyrene NPs exposure in C. elegans. We show that the disrupted circadian rhythm induced by NPs exposure reduced stress resistance via endocytosis and autophagy impairment. Furthermore, we found that most NPs taken up by intestinal cells were localized to early endosomes, late endosomes, and lysosomes and delivered to autophagosomes. In addition, the disruption of circadian rhythm inhibited NPs localization to these organelles. These findings indicate that NPs exposure disrupts circadian rhythm and alters its subcellular trafficking, leading to enhanced toxicity in C. elegans. Our results shed light on the prominent role of NPs exposure in circadian rhythm disruption associated with endocytosis and autophagy impairments, which may be conserved in higher animals such as humans.

Effects of decay heat and cooling condition on the reactor pool natural circulation under RVACS operation in a water 2-D slab model

The temperature distribution of the reactor pool under natural circulation induced by the RVACS operation was experimentally studied. According to the Bo’ based similarity law, which could reproduce the temperature distribution of the working fluid under natural circulation, SINCRO-2D facility was designed based on the PGSFR. It was reduced to 1 : 25 in length scale, having water as a simulant of the sodium, which is the original working fluid. In general, temperature was stratified, however, effect of the natural circulation flow could be observed by the entrainment of the stratified temperature. Relative cooling contribution of the upper plenum (narrow gap) and lower plenum was approximately 0.2 and 0.8, respectively. In the range of decay heat from 0.2% to 1.0%, only the magnitude of the temperature was changed, while the normalized temperature maintained. Boundary temperature distribution change made a global temperature offset of the pool, without a significant local change. Therefore, the decay heat and cooling boundary condition had no significant effect on temperature distribution characteristics of the pool within the given range of the decay heat and boundary temperature distribution.

Methodology for the optimization of artificial lighting considering both visual and non-visual effects

The effect of light on human physiology as well as its non-image forming effects have been known for several years. An important milestone in understanding the non-visual effects of light was the discovery of a new type of photoreceptor namely the intrinsically photosensitive retinal ganglion cells, or ipRGCs which play a vital role in the human circadian system. The non-visual effects of light are the following: regulation of melatonin secretion, circadian entrainment and modification of body temperature. With the advent of solid-state lighting, it is possible to precisely regulate the spectral power distribution of artificial lighting, so as to favour the human circadian rhythm. The scope of this paper is to present a conceptual methodology for the evaluation of artificial lighting systems with regards to visual, circadian effects and their energy consumption. In other words, this paper aims to outline an assessment process for lighting designers by elaborating not only on the visual aspects of each lighting system but also the melanopic effects and its energy efficiency.

An experimental investigation of ejector employed a dual-evaporator vapor compression refrigeration system under various entrainment ratios using R134a as the refrigerant

Today, vapor compression refrigeration (VCR) systems are commonly used for cooling and heating in buildings, industrial and many other applications. Given the high-energy costs, it is essential to use highly efficient VCR systems. This study presents an experimental performance analysis of a refrigeration cycle with a dual evaporator ejector system (DEES). For this aim, an experimental system was designed and established on a laboratory scale. DEES system was organized for regarding different and possible applications via operating the individual evaporators with different heat sources as air and water. Within the scope of the work performed in this study, the DEES was tested by varying the condensing temperature and ejector Entrainment Ratio (ER) values. The investigated DEES was also contrasted with a conventional vapor compression refrigeration cycle as a baseline system considering different operating conditions. The findings obtained in this study showed that a 13.24% enhancement in coefficient of performance (COP) was achieved when comparing with the baseline system. The highest exergy destruction rate for the compressor in ER#3 was 0.79 kW, but the total cooling capacity significantly improved compared to the baseline system. Additionally, the total exergy destruction rate of the baseline system was the lowest compared to the other modes, while the cooling capacity of this mode was always the lowest. It was also found that when the ER value varied from ER#3 to ER#1, the total cooling capacity increased by up to 11.79%. The results show that the ejector works more efficiently at low ER values and condenser temperatures.

The analysis of temperature and air entrainment rate for the turbulence diffusion jet flame of propane and carbon dioxide gas mixture

A few of studies have investigated the temperature profile and air entrainment of the turbulent jet diffusion flame produced by the combustion of a gas mixture. In this study, the air entrainment rate and temperature distribution along the axis of a turbulent jet diffusion flame of propane mixed with different concentrations of carbon dioxide were therefore investigated, which using a series of experiments conducted with 2, 3, and 4 mm nozzles. The results show that the flame temperature increased in the continuous flame region and decreased in fire plume region as the carbon dioxide concentration increased under the same heat release rate. A virtual origin model was then developed to analyze the relationship between carbon dioxide concentration and flame temperature. The air entrainment rate of the fire plume region was influenced by the gas flow speed from the nozzles, and the total air entrainment rate was inversely proportional to the carbon dioxide concentration. A correlation among the flame temperature, carbon dioxide concentration, and air entrainment rate was then established, providing a valuable resource for the risk assessment of turbulent jet diffusion flames.

Analysis of spray/wall impingement using an ECN single-hole injector and a controlled-temperature wall under realistic engine conditions

Spray–wall interactions (SWI) directly affect fuel–air mixture and emissions formation. Therefore, they are considered among the most critical physical processes in engine research nowadays. However, the physics of the wall film formation, propagation, and breakup is not fully understood yet. This work aims to use a thermoregulated steel wall to study the spray–wall interaction phenomenon and its influence on the macroscopic spray behavior. A single-hole injector known as “Spray D” in the Engine Combustion Network was used. n-Dodecane was employed as fuel and the wall has been positioned in four different configurations, varying angle and distance respect to the injector tip. For this work, not only diesel combustion is reproduced in the test rig due to ambient gas engine-like thermodynamic conditions, but wall temperature has been controlled to emulate characteristic values that could be found in the piston of an internal combustion engine. This implies that the spray–wall heat transfer is simulated and its effects on ignition and spray development can be analyzed. Heat flux was measured by employing high-speed thermocouples fitted in the wall and by the use of an one-dimensional transient wall heat model. Three high speed cameras were simultaneously used to observe the SWI, one for the Schlieren optical technique which allows to study the vapor phase of the spray and to determine the ignition delay, another one to observe the natural luminosity of the flame, and finally, an intensified camera was used to determine the lift-off length by observing the chemiluminescence of the OH*. An interesting finding obtained in this work was a boundary layer formation due to the thermal diffusion that contributes to cool down the spray and to delay the high-temperature chemical reactions. Results show a substantial increment of the heat flux and the wall temperature variation with both ambient temperature and density by increasing the flame temperature and gas entrainment. The exposure to the cold wall affects the ignition delay variation with the injection pressure and the wall distance. It was found that the wall temperature (in the range of tested conditions) did not affect the lift-off length location. • The exposure to the cold wall delayed the ignition. • Flame thickness around the wall undergoes a narrowing at lower wall temperatures. • The injection pressure increments the convective coefficient. • A boundary layer due to thermal diffusion was formed on the wall.

The Analysis of Temperature and Air Entrainment Rate for the Turbulence Diffusion Flame of Propane and Carbon Dioxide Gas Mixture

The Analysis of Temperature and Air Entrainment Rate for the Turbulence Diffusion Flame of Propane and Carbon Dioxide Gas Mixture

Principles underlying the complex dynamics of temperature entrainment by a circadian clock

SummaryAutonomously oscillating circadian clocks resonate with daily environmental (zeitgeber) rhythms to organize physiology around the solar day. Although entrainment properties and mechanisms have been studied widely and in great detail for light-dark cycles, entrainment to daily temperature rhythms remains poorly understood despite that they are potent zeitgebers. Here we investigate the entrainment of the chronobiological model organism Neurospora crassa, subject to thermocycles of different periods and fractions of warm versus cold phases, mimicking seasonal variations. Depending on the properties of these thermocycles, regularly entrained rhythms, period-doubling (frequency demultiplication) but also irregular aperiodic behavior occurs. We demonstrate that the complex nonlinear phenomena of experimentally observed entrainment dynamics can be understood by molecular mathematical modeling.

Arabidopsis EARLY FLOWERING 3 controls temperature responsiveness of the circadian clock independently of the evening complex.

Daily changes in light and temperature are major entrainment cues that enable the circadian clock to generate internal biological rhythms that are synchronized with the external environment. With the average global temperature predicted to keep increasing, the intricate light-temperature coordination that is necessary for clock functionality is expected to be seriously affected. Hence, understanding how temperature signals are perceived by the circadian clock has become an important issue. In Arabidopsis, the clock component EARLY FLOWERING 3 (ELF3) not only serves as a light Zeitnehmer, but also functions as a thermosensor participating in thermomorphogenesis. However, the role of ELF3 in temperature entrainment of the circadian clock is not fully understood. Here, we report that ELF3 is essential for delivering temperature input to the clock. We demonstrate that in the absence of ELF3, the oscillator is unable to respond to temperature changes, resulting in an impaired gating of thermoresponses. Consequently, clock-controlled physiological processes such as rhythmic growth and cotyledon movement were disturbed. Genetic analyses suggest that the evening complex is not required for ELF3-controlled thermoresponsiveness. Together, our results reveal that ELF3 is an essential Zeitnehmer for temperature sensing of the oscillator, and thereby for coordinating the rhythmic control of thermoresponsive physiological outputs.

Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies.

Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30–40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of “clock genes” and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low-amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.

Molecular mechanisms of Evening Complex activity in Arabidopsis

The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment, acting as an important environmental sensor and conveying this information to growth and developmental pathways. However, the molecular basis for EC DNA binding specificity and temperature-dependent activity were not known. Here, we solved the structure of the DNA binding domain of LUX in complex with DNA. Residues critical for high-affinity binding and direct base readout were determined and tested via site-directed mutagenesis in vitro and in vivo. Using extensive in vitro DNA binding assays of LUX alone and in complex with ELF3 and ELF4, we demonstrate that, while LUX alone binds DNA with high affinity, the LUX-ELF3 complex is a relatively poor binder of DNA. ELF4 restores binding to the complex. In vitro, the full EC is able to act as a direct thermosensor, with stronger DNA binding at 4 °C and weaker binding at 27 °C. In addition, an excess of ELF4 is able to restore EC binding even at 27 °C. Taken together, these data suggest that ELF4 is a key modulator of thermosensitive EC activity.

Affectations in photic and thermic circadian entrainment of the locomotor activity rhythm in obese volcano mouse Neotomodon alstoni

ABSTRACT Obesity affects the ability of both photic and non-photic entrainment of the locomotor activity's circadian rhythm in the volcano mouse Neotomodon alstoni. The present study aimed to recognize differences in the synchronization of semi-natural, artificial, and periods other than 24 h light cycles between lean and obese mice. Also, the entrainment to temperature cycles was explored. The results obtained indicate that the activity profiles show discrete differences in the amplitude according to the type of lighting; when exposed to 22 or 26 h photic cycles, obese mice manifest more difficulty in the entrainment of the circadian rhythm. Changes in the free-running period produced by temperature cycles were larger in lean mice than in obese mice, with variability among organisms. The above confirms that photic entrainment is more difficult in obese mice, and that temperature entrainment suggest a decreased sensibility to temperature cycles in obese mice.

Temperature Entrainment of Circadian Locomotor and Transcriptional Rhythms in the Cricket, Gryllus bimaculatus.

Most animals exhibit circadian rhythms in various physiological and behavioral functions regulated by circadian clock that resides in brain and in many peripheral tissues. Temperature cycle is an important time cue for entrainment, even in mammals, since the daily change in body temperature is thought to be used for phase regulation of clocks in peripheral tissues. However, little is known about the mechanisms by which temperature resets the clock. In the present study, we investigated the effect of temperature on circadian activity rhythm and clock gene transcription by using the cricket, Gryllus bimaculatus. We show that temperature cycle can entrain both behavioral and transcriptional rhythms of clock genes, such as period, timeless, cryptochrome2 and cycle in the circadian pacemaker tissue, optic lobe. Under temperature cycle, phase of evening peak of locomotor activity occurred 1 h before the warm-to-cold phase transition, which is associated with earlier peaks of mRNA expression rhythm of the clock genes than that under light/dark cycles. When the temperature cycle was advanced by 6 h, behavioral rhythms re-entrained to newly phased temperature cycle after ∼16 transient cycles. The mRNA oscillation of period and timeless gained stable rhythm under phase advanced temperature cycles with a lesser number of transient cycles than cryptochrome2 and cycle. These results suggest that temperature cycle can entrain behavioral and molecular rhythms in cricket and clock genes vary in sensitivity to temperature. It is thus likely that clock genes play differential roles in resetting the clock with environmental temperature changes.

Entrainment of Circadian Rhythms to Temperature Reveals Amplitude Deficits in Fibroblasts from Patients with Bipolar Disorder and Possible Links to Calcium Channels

Bipolar disorder (BD) is characterized by recurrent mood episodes, and circadian rhythm disturbances. Past studies have identified calcium channel genes as risk loci for BD. CACNA1C encodes an L-type calcium channel (LTCC) involved in the entrainment of circadian rhythms to light. Another calcium channel, i.e., the ryanodine receptor (RYR), is involved in ­circadian phase delays. It is unknown whether variants in CACNA1C or other calcium channels contribute to the circadian phenotype in BD. We hypothesized that, by using temperature cycles, we could model circadian entrainment in fibroblasts from BD patients and controls to interrogate the circadian functions of LTCCs. Using Per2-luc, a bioluminescent reporter, we verified that cells entrain to temperature rhythms in vitro. Under constant temperature conditions, the LTCC antagonist verapamil shortened the circadian period, and the RYR antagonist dantrolene lengthened the period. However, neither drug affected temperature entrainment. Fibroblasts from BD patients and controls also entrained to temperature. In cells from BD patients, the rhythm amplitude was lower under entrained, but not constant, conditions. Temperature entrainment was otherwise similar between BD and control cells. However, the CACNA1C genotype among BD cells predicted the degree to which cells entrained. We conclude that assessment of rhythms under entrained conditions reveals additional rhythm abnormalities in BD that are not observable under constant temperature conditions.