Search NASA⌕ Search

SEARCH · Search NASA

Results for “circadian rhythms”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12

From primordial clocks to circadian oscillators

Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator1. The evolutionary history of the three Kai proteins indicates that KaiC is the oldest member and a central component of the clock. Subsequent additions of KaiB and KaiA regulate the phosphorylation state of KaiC for time synchronization. The canonical KaiABC system in cyanobacteria is well understood but little is known about more ancient systems that only possess KaiBC. However, there are reports that they might exhibit a basic, hourglass-like timekeeping mechanism. Here we investigate the primordial circadian clock in Rhodobacter sphaeroides , which contains only KaiBC, to elucidate its inner workings despite missing KaiA. Using a combination of X-ray crystallography and cryogenic electron microscopy, we find a new dodecameric fold for KaiC, in which two hexamers are held together by a coiled-coil bundle of 12 helices. This interaction is formed by the carboxy-terminal extension of KaiC and serves as an ancient regulatory moiety that is later superseded by KaiA. A coiled-coil register shift between daytime and night-time conformations is connected to phosphorylation sites through a long-range allosteric network that spans over 140 Å. Our kinetic data identify the difference in the ATP-to-ADP ratio between day and night as the environmental cue that drives the clock. They also unravel mechanistic details that shed light on the evolution of self-sustained oscillators.

59 BASIC BIOLOGICAL SCIENCES↗

Skylab SO71/SO72 circadian periodicity experiment

The circadian rhythm hardware activities from 1965 through 1973 are considered. A brief history of the programs leading to the development of the combined Skylab SO71/SO72 Circadian Periodicity Experiment (CPE) is given. SO71 is the Skylab experiment number designating the pocket mouse circadian experiment, and SO72 designates the vinegar gnat circadian experiment. Final design modifications and checkout of the CPE, integration testing with the Apollo service module CSM 117 and the launch preparation and support tasks at Kennedy Space Center are reported.

Fairchild, M. K.↗

Research on the Effects of Fatigue within the Corporate/Business Aircraft Environment

In 1980, responding to a Congressional request, NASA Ames Research Center created a program to examine whether 'there is a safety problem of uncertain magnitude, due to transmeridian flying and a potential problem due to fatigue in association with various factors found in air transport operations.' The NASA Ames Fatigue/Jet Lag Program was created to collect systematic, scientific information on fatigue, sleep, circadian rhythms, and performance in flight operations. Three Program goals were established and continue to guide research efforts to: (1) determine the extent of fatigue, sleep loss, and circadian disruption in flight operations; (2) determine the impact of these factors on flight crew performance; (3) develop and evaluate countermeasures to mitigate the adverse effects of these factors and maximize flight crew performance and alertness. Since 1980, studies have been conducted in a variety of aviation environments, in controlled laboratory environments, as well as in a full-mission flight simulation. Early studies included investigations of short-haul, long-haul, and overnight cargo flight crews. In 1991, the name of the program was changed to the Fatigue Countermeasures Program to provide a greater emphasis on the development and evaluation of countermeasures. More recent work has examined the effects of planned cockpit rest as an operational countermeasure and provided analyses of the pertinent sleep/duty factors preceding an aviation accident at Guantanamo Bay, Cuba. The Short-Haul study examined the extent of sleep loss, circadian disruption, and fatigue engendered by flying commercial short-haul air transport operations (flight legs less than eight hours). This was one of the first field studies conducted by the NASA program and provided unique insight into the physiological and subjective effects of flying commercial short-haul operations. It demonstrated that a range of measures could be obtained in an operational environment without disturbing the regular performance of duties. The Long-Haul study examined how long-haul flight crews organized their sleep during a variety of international trip patterns and examined how duty requirements, local time, and the circadian system affected the timing, duration, and quality of sleep. Duty requirements and local time can be viewed as external/environmental constraints on time available for sleep, while the internal circadian system is a major physiological modulator of sleep duration and quality. The Overnight Cargo study documented the psychophysiological effects of flying overnight cargo operations. The data collected clearly demonstrated that overnight cargo operations, like other night work, involve physiological disruption not found in comparable daytime operations.

Neri, David F.↗

Circadian rhythmicity of amyloid‐beta‐related molecules is disrupted in the choroid plexus of a female Alzheimer's disease mouse model

Abstract The choroid plexus (CP) is part of the blood‐cerebrospinal fluid barrier (BCSFB) and was recently described as an important component of the circadian clock system. It is the principal source of cerebrospinal fluid (CSF) and responsible for the synthesis and secretion of various neuroprotective peptides including those involved in amyloid‐β (Aβ) transport/degradation, contributing to Aβ homeostasis. Inadequate Aβ metabolic clearance and transport across the BCSFB have been associated with circadian dysfunctions in Alzheimer's disease (AD) patients. To investigate whether AD pathology influences Aβ scavengers circadian expression, we collected CP at different time points from an AD mouse model (APP/PS1) (female and male animals, aged 6‐ and 12‐months‐old) and analyzed their mRNA expression by Real‐time RT‐PCR. Only angiotensin‐converting enzyme (Ace) expression in 6‐month‐old female wild‐type mice and transthyretin (Ttr) expression in 12‐month‐old female wild‐type mice presented significant rhythmicity. The circadian rhythmicity of Ace and Ttr, prompt us to analyze the involvement of circadian rhythm in Aβ uptake. A human CP papilloma (HIBCPP) cell line was incubated with Aβ‐488 and uptake was evaluated at different time points using flow cytometry. Aβ uptake displayed circadian rhythmicity. Our results suggest that AD might affect Aβ scavengers rhythmicity and that Aβ clearance is a rhythmic process possibly regulated by the rhythmic expression of Aβ scavengers.

Furtado, André↗

Thermoregulatory responses of rhesus monkeys during spaceflight

This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union. Additional control studies were performed in the United States to examine the possible role of metabolic heat production in the T(ax) response observed during the spaceflight. All monkeys were exposed to a 24-h light-dark cycle (LD 16:8) throughout these studies. During weightlessness, T(ax) in both flight animals was lower than on earth. The largest difference (0.75 degree C) occurred during the night. There was a reduction in mean heart rate and Tsk during flight. This suggests a reduction in both heat loss and metabolic rate during spaceflight. Although the circadian rhythms in all variables were present during flight, some differences were noted. For example, the amplitude of the rhythms in Tsk and activity were attenuated. Furthermore, the T(ax) and activity rhythms did not have precise 24.0 hour periods and may have been externally desynchronized from the 24-h LD cycle. These data suggest a weakening of the coupling between the internal circadian pacemaker and the external LD synchronizer.

Sulzman, F. M.↗

Circadian and Fatigue Effects on the Dynamics of the Pupillary Light Reflex

The pupillary light reflex (PLR) is known to be driven by the photo-entrainment of intrinsically-photosensitive retinal ganglion cells. These ganglion cells are known to have retino-hypothalamic projections to the suprachiasmatic nuclei (SCN), which regulates circadian rhythms, and bilateral retinal projections to the pretectal area, which mediates the PLR (Dacey et al., 2005; Hattar et al., 2002, 2006). The magnitude of the PLR has previously been shown to show circadian variation (Mnch et al., 2012). In this study, we used a constant routine protocol (Mills et al., 1978) to examine circadian and fatigue effects on the dynamics of the PLR. We characterized the PLR (pupil size as a function of time) in response to a square-wave change in the luminance of a white display background, at ten different times over a single circadian cycle. Twelve subjects participated in three daytime baseline runs followed by 7 nighttime runs each separated by an hour (17 23 hours after awakening). The constriction and dilation phases of the PLR waveform were fit separately with a single exponential model (Longtin Milton, 1988; Milton Longtin, 1990) with time constants estimated using a least-squares method. The dilation time constant exhibited a distinct sinusoidal modulation across the circadian cycle and, after 23 hours of wakefulness, decreased on average by 82 ms (paired t-test, p 0.05) relative to baseline (mean: 543 ms). The constriction time constant however, did not show an overall decrease with increased wakefulness. We conclude that the dynamics of the PLR show circadian variation and that, in addition, the briskness of the dilation response to a step-decrease in luminance shows a homeostatic enhancement with increased wakefulness.

human performance↗

Cardiovascular tissues contain independent circadian clocks

Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

Non-NASA Center↗

Aircrew fatigue and circadian rhythmicity

Recent statistical and experimental studies on the role of circadian rhythms in aircrew fatigue and aviation accidents are reviewed from a human-factors perspective, and typical data are presented in extensive graphs. Consideration is given to the biological clock and the limits of endurance, circadian desynchronization, sleep and sleepiness, short-haul and long-haul operational studies, and the potential advantages of cockpit automation.

Graeber, R. Curtis↗

Lighting for Health and Wellness Recommendations in Offices: A Circadian Lighting Pilot Project in Chicago, IL

In 2019 Cook County initiated a request for proposals for a pilot project aimed at designing and specifying an advanced tunable lighting system for government offices in Chicago, Illinois. The primary goal of the project was to replace the existing tubular LED (TLED) lighting system with a lighting system that supported the circadian rhythms and wellbeing their office employees. A secondary goal was to evaluate the potential impacts of the new lighting system, informing Cook County’s internal workplace design standards. Schuler Shook, a Chicago-based lighting design firm, was awarded the Circadian Lighting Pilot Project in October 2019 and invited Pacific Northwest National Laboratory (PNNL) to contribute as a research partner. Based on the initial project goals, Schuler Shook and PNNL established design objectives that would enable a human factors study in the office spaces, investigating the benefits and drawbacks of using a tunable LED lighting system to meet existing recommendations for lighting and health. The following report details the lighting design process through design development, with summaries of the relevant circadian lighting metrics, simulation tools, energy considerations, and research plan for the Circadian Lighting Pilot Project.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Advanced Solid State Lighting for AES Deep Space Hab Project

The advanced Solid State Lighting (SSL) assemblies augmented 2nd generation modules under development for the Advanced Exploration Systems Deep Space Habitat in using color therapy to synchronize crew circadian rhythms. Current RGB LED technology does not produce sufficient brightness to adequately address general lighting in addition to color therapy. The intent is to address both through a mix of white and RGB LEDs designing for fully addressable alertness/relaxation levels as well as more dramatic circadian shifts.

Technology Portfolio System↗

Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

NASA Discipline Space Human Factors↗

Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection?

Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (T(b)), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in T(b) and an attenuated T(b) circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice (P < 0.0001). In contrast, the het mice did not exhibit a decrease in mean T(b) and only a slight decrease in T(b) circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

NASA Discipline Regulatory Physiology↗

Genomic profiles of four novel cyanobacteria MAGs from Lake Vanda, Antarctica: insights into photosynthesis, cold tolerance, and the circadian clock

Cyanobacteria in polar environments face environmental challenges, including cold temperatures and extreme light seasonality with small diurnal variation, which has implications for polar circadian clocks. However, polar cyanobacteria remain underrepresented in available genomic data, and there are limited opportunities to study their genetic adaptations to these challenges. This paper presents four new Antarctic cyanobacteria metagenome-assembled genomes (MAGs) from microbial mats in Lake Vanda in the McMurdo Dry Valleys in Antarctica. The four MAGs were classified as Leptolyngbya sp. BulkMat.35, Pseudanabaenaceae cyanobacterium MP8IB2.15, Microcoleus sp. MP8IB2.171, and Leptolyngbyaceae cyanobacterium MP9P1.79. The MAGs contain 2.76 Mbp – 6.07 Mbp, and the bin completion ranges from 74.2–92.57%. Furthermore, the four cyanobacteria MAGs have average nucleotide identities (ANIs) under 90% with each other and under 77% with six existing polar cyanobacteria MAGs and genomes. This suggests that they are novel cyanobacteria and demonstrates that polar cyanobacteria genomes are underrepresented in reference databases and there is continued need for genome sequencing of polar cyanobacteria. Analyses of the four novel and six existing polar cyanobacteria MAGs and genomes demonstrate they have genes coding for various cold tolerance mechanisms and most standard circadian rhythm genes with the Leptolyngbya sp. BulkMat.35 and Leptolyngbyaceae cyanobacterium MP9P1.79 contained kaiB3, a divergent homolog of kaiB.

59 BASIC BIOLOGICAL SCIENCES↗

A Summary Of: Collecting Sleep, Circadian, Fatigue, and Performance Data in Complex Operational Environments

Sleep loss and circadian misalignment contribute to a meaningful proportion of operational accidents and incidents. Countermeasures and work scheduling designs aimed at mitigating fatigue are typically evaluated in controlled laboratory environments, but the effectiveness of translating such strategies to operational environments can be challenging to assess. This manuscript summarizes an approach for collecting sleep, circadian, fatigue, and performance data in a complex operational environment. We studied 44 airline pilots over 34 days while they flew a fixed schedule, which included a baseline data collection with 5 days of mid-morning flights, four early flights, four high-workload mid-day flights, and four late flights that landed after midnight. Each work block was separated by 3-4 days of rest. To assess sleep, participants wore a wrist-worn research-validated activity monitor continuously and completed daily sleep diaries. To assess the circadian phase, pilots were asked to collect all urine produced in four or eight hourly bins during the 24 h after each duty block for the assessment of 6-sulfatoxymelatonin (aMT6s), which is a biomarker of the circadian rhythm. To assess subjective fatigue and objective performance, participants were provided with a touchscreen device used to complete the Samn-Perelli Fatigue Scale and Psychomotor Vigilance Task (PVT) during and after each flight, and at wake-time, mid-day, and bedtime. Using these methods, it was found that sleep duration was reduced during early starts and late finishes relative to baseline. Circadian phase shifted according to duty schedule, but there was a wide range in the aMT6s peak between individuals on each schedule. PVT performance was worse on the early, high-workload, and late schedules relative to baseline. Overall, the combination of these methods was practical and effective for assessing the influence of sleep loss and circadian phase on fatigue and performance in a complex operational environment.

Arsintescu, Lucica↗

Photic and circadian regulation of retinal melatonin in mammals

Several studies have established that melatonin synthesis occurs in the retina of vertebrates, including mammals. In mammals, a subpopulation of photoreceptors (probably the cones) synthesize melatonin. Melatonin synthesis in the retina is elevated at night and reduced during the day in a fashion similar to events in the pineal gland. Both the MT1 and MT2 melatonin receptors are present in the retina and retinal melatonin does not contribute to circulating levels, suggesting that retinal melatonin acts locally as a neurohormone and/or neuromodulator. Melatonin synthesis in the retina of mammals is under the control of a circadian oscillator, and circadian rhythms in melatonin synthesis and/or release have been described for several species of mammals. These rhythms are present in vivo, persist in vitro, are entrained by light and are temperature compensated. The cloning of the gene responsible for the synthesis of the enzyme arylalkylamine N-acetyltransferase (the key enzyme in the melatonin biosynthetic pathway) has allowed studies of the molecular mechanisms responsible for the generation of retinal melatonin rhythmicity. The present review focuses on the cellular and molecular mechanisms that regulate melatonin synthesis. In particular, we discuss how the photic environment and the circadian clock interact in determining melatonin levels, in addition to the role that melatonin plays in retinal physiology.

NASA Discipline Space Human Factors↗

Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing

Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.

59 BASIC BIOLOGICAL SCIENCES↗

Validating and Verifying Biomathematical Models of Human Fatigue

Airline pilots experience acute and chronic sleep deprivation, sleep inertia, and circadian desynchrony due to the need to schedule flight operations around the clock. This sleep loss and circadian desynchrony gives rise to cognitive impairments, reduced vigilance and inconsistent performance. Several biomathematical models, based principally on patterns observed in circadian rhythms and homeostatic drive, have been developed to predict a pilots levels of fatigue or alertness. These models allow for the Federal Aviation Administration (FAA) and commercial airlines to make decisions about pilot capabilities and flight schedules. Although these models have been validated in a laboratory setting, they have not been thoroughly tested in operational environments where uncontrolled factors, such as environmental sleep disrupters, caffeine use and napping, may impact actual pilot alertness and performance. We will compare the predictions of three prominent biomathematical fatigue models (McCauley Model, Harvard Model, and the privately-sold SAFTE-FAST Model) to actual measures of alertness and performance. We collected sleep logs, movement and light recordings, psychomotor vigilance task (PVT), and urinary melatonin (a marker of circadian phase) from 44 pilots in a short-haul commercial airline over one month. We will statistically compare with the model predictions to lapses on the PVT and circadian phase. We will calculate the sensitivity and specificity of each model prediction under different scheduling conditions. Our findings will aid operational decision-makers in determining the reliability of each model under real-world scheduling situations.

fatigue↗

San Francisco Bar Pilot Fatigue Study

The purpose of this study was to evaluate the extent of fatigue among San Francisco Bar Pilots (Maritime Pilots) and its potential impact on safety, and to make recommendations concerning how the risk of fatigue could be managed. Information was gathered via a literature review, observations of Bar Pilots at work, surveys, a task analysis, and an analysis of dispatch records.The work of San Francisco Bar Pilots involves an unusual mix of activities and job demands. Their work calls for situational awareness, reasoning, communication, and perceptual abilities comparable to those required by airline pilots and air traffic controllers. Errors can have severe consequences for public safety and the environment, as well as significant financial costs. Fatigue is increasingly recognized as a hazard that must be managed by the transportation industry. The reduced sleep quality and quantity experienced by personnel who work at night, in conjunction with human circadian rhythms can lead to an operationally significant level of cognitive impairment. The cognitive impact of fatigue includes functions that are critical to safe maritime piloting, such as vigilance, judgment, reaction time and communication. The surveys distributed to Bar Pilots did not uncover evidence of widespread fatigue. The survey results also suggested that fatigue was not a major concern of Bar Pilots. Bar Pilots had overall low scores on the subjective fatigue measures used in the survey, and generally assessed the safety risk due to fatigue as low. Compared to air traffic controllers, Bar Pilots gave significantly lower ratings on questions concerning the prevalence and impact of fatigue. The application of fatigue modeling software to Bar Pilot dispatch records identified that in most cases, pilot's cognitive effectiveness was predicted to be acceptable during their duty periods. However, these results could not be verified with objective data.The study identified a number of fatigue issues that deserve attention. These include Bar Pilot work periods that frequently infringe on the circadian low, consecutive work periods without a significant break, consecutive periods of night work, unpredictable work schedules, start time variability, the potential for sleep inertia, and the number of pilots on the board at any given time.

fatigue↗