Time Cues Research Articles

O022 Response of Sleep and the Circadian System to a Long Summer Photoperiod at High Latitude

Abstract The light-dark cycle is the primary time cue for the synchronization of the internal human circadian system with the external world. Our previous research has shown the capacity of the circadian system to adapt to seasonal variations in the light-dark cycle at latitude ~40oN in the Rocky Mountains following curtailment of artificial light exposure. In the current study, we examined the circadian response to a longer photoperiod in summer by measuring melatonin timing before and after a week of camping outdoors in Sweden. Actigraphy-derived (Actiwatch Spectrum) assessments of sleep, activity and light exposure were carried out for 2 weeks. Week 1 was under modern urban living conditions with exposure to natural and artificial light in Stockholm, Sweden (~59oN; 18 hr 37 min: 5 hr 23 min light-dark cycle). Week 2 was spent rough camping in nature with exposure to only natural light at the Swedish High Coast (~63oN; 20 hr 40 min: 3 hr 20 min). Dim-light melatonin onset (DLMO) assessments were conducted in laboratory over two 24 hr periods immediately before and after camping to assess melatonin levels in hourly saliva samples. On average, participants’ (n = 10) melatonin midpoint and offset advanced ~0.7 and ~1.3 hr (p < 0.01), respectively, with no change in onset (p = 0.45). As sleep duration, and timing were similar between environments (p > 10), melatonin offset occurred closer to sleep offset after camping. Consistent with prior findings, the end of biological night is timed closer to waketime in the natural environment.

Input integration by the circadian clock exhibits nonadditivity and fold-change detection

Circadian clocks are synchronized by external timing cues to align with one another and the environment. Various signaling pathways have been shown to independently reset the phase of the clock. However, in the body, circadian clocks are exposed to a multitude of potential timing cues with complex temporal dynamics, raising the question of how clocks integrate information in response to multiple signals. To investigate different modes of signal integration by the circadian clock, we used Circa-SCOPE, a method we recently developed for high-throughput phase resetting analysis. We found that simultaneous exposure to different combinations of known pharmacological resetting agents elicits a diverse range of responses. Often, the response was nonadditive and could not be readily predicted by the response to the individual signals. For instance, we observed that dexamethasone is dominant over other tested inputs. In the case of signals administered sequentially, the background levels of a signal attenuated subsequent resetting by the same signal, but not by signals acting through a different pathway. This led us to examine whether the circadian clock is sensitive to relative rather than absolute levels of the signal. Importantly, our analysis revealed the involvement of a signal-specific fold-change detection mechanism in the clock response. This mechanism likely stems from properties of the signaling pathway that are upstream to the clock. Overall, our findings elucidate modes of input integration by the circadian clock, with potential relevance to clock resetting under both physiological and pathological conditions.

Testing beat perception without sensory cues to the beat: the Beat-Drop Alignment Test (BDAT)

Beat perception can serve as a window into internal time-keeping mechanisms, auditory–motor interactions, and aspects of cognition. One aspect of beat perception is the covert continuation of an internal pulse. Of the several popular tests of beat perception, none provide a satisfying test of this faculty of covert continuation. The current study proposes a new beat-perception test focused on covert pulse continuation: The Beat-Drop Alignment Test (BDAT). In this test, participants must identify the beat in musical excerpts and then judge whether a single probe falls on or off the beat. The probe occurs during a short break in the rhythmic components of the music when no rhythmic events are present, forcing participants to judge beat alignment relative to an internal pulse maintained in the absence of local acoustic timing cues. Here, we present two large (N > 100) tests of the BDAT. In the first, we explore the effect of test item parameters (e.g., probe displacement) on performance. In the second, we correlate scores on an adaptive version of the BDAT with the computerized adaptive Beat Alignment Test (CA-BAT) scores and indices of musical experience. Musical experience indices outperform CA-BAT score as a predictor of BDAT score, suggesting that the BDAT measures a distinct aspect of beat perception that is more experience-dependent and may draw on cognitive resources such as working memory and musical imagery differently than the BAT. The BDAT may prove useful in future behavioral and neural research on beat perception, and all stimuli and code are freely available for download.

The intestinal clock drives the microbiome to maintain gastrointestinal homeostasis

Diurnal (i.e., 24-hour) oscillations of the gut microbiome have been described in various species including mice and humans. However, the driving force behind these rhythms remains less clear. In this study, we differentiate between endogenous and exogenous time cues driving microbial rhythms. Our results demonstrate that fecal microbial oscillations are maintained in mice kept in the absence of light, supporting a role of the host’s circadian system rather than representing a diurnal response to environmental changes. Intestinal epithelial cell-specific ablation of the core clock gene Bmal1 disrupts rhythmicity of microbiota. Targeted metabolomics functionally link intestinal clock-controlled bacteria to microbial-derived products, in particular branched-chain fatty acids and secondary bile acids. Microbiota transfer from intestinal clock-deficient mice into germ-free mice altered intestinal gene expression, enhanced lymphoid organ weights and suppressed immune cell recruitment. These results highlight the importance of functional intestinal clocks for microbiota composition and function, which is required to balance the host’s gastrointestinal homeostasis.

What you are getting and what you will be getting: Testing whether verb tense affects intertemporal choices.

Prior research has shown that the way information is communicated can impact decisions, consistent with some forms of the Sapir-Whorf hypothesis that language shapes thought. In particular, language structure-specifically the form of verb tense in that language-can predict savings behaviors among speakers of different languages. We test the causal effect of language structure encountered during financial decision-making, by manipulating the verb tense (within a single language) used to communicate intertemporal tradeoffs. We find that verb tense can significantly shift choices between options, owing to tense-based inferences about timing. However, the spontaneous use of verb tense when making choices occurs only in the complete absence of other timing cues and is eliminated if even ambiguous or nondiagnostic time cues are present, although prompted timing inferences persist. We test between multiple competing accounts for how verb tense differentially impacts timing inferences and choices. We find evidence for a cue-based account, such that the presence of other cues blocks the spontaneous use of verb tense in making intertemporal decisions, consistent with the "Good Enough" proposal in psycholinguistics. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Detection of dynamic changes in interaural delay by older adults (L).

The ability of older adults (48 to 72) with relatively intact low-frequency hearing to detect the motion of an acoustic source was investigated using dynamically varying interaural delays. Thresholds were measured using a single-interval two-alternative forced-choice task in which listeners determined if the sound source was moving or stationary. Motion thresholds were significantly larger than stationary localization thresholds. No correlation was observed between age and motion-detection ability for the age range tested. An interesting finding was that there were similar thresholds for older and younger adults. Results suggest reliance on dominant low-frequency binaural timing cues unaffected by high-frequency hearing loss in older adults.

Studying food entrainment: Models, methods, and musings.

The ability to tell time relative to predictable feeding opportunities has a long history of research, going back more than 100 years with behavioral observations of honeybees and rats. Animals that have access to food at a particular time of day exhibit “food anticipatory activity” (FAA), which is a preprandial increase in activity and arousal thought to be driven by food entrained circadian oscillator(s). However, the mechanisms behind adaptation of behavior to timed feeding continue to elude our grasp. Methods used to study circadian entrainment by food vary depending on the model system and the laboratory conducting the experiments. Most studies have relied on rodent model systems due to neuroanatomical tools and genetic tractability, but even among studies of laboratory mice, methods vary considerably. A lack of consistency within the field in experimental design, reporting, and definition of food entrainment, or even FAA, makes it difficult to compare results across studies or even within the same mutant mouse strain, hindering interpretation of replication studies. Here we examine the conditions used to study food as a time cue and make recommendations for study design and reporting.

Oscillations of the circadian clock protein, BMAL-1, align to daily cycles of mechanical stimuli: a novel means to integrate biological time within predictive in vitro model systems

PurposeIn vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems.MethodsQuiescent bovine chondrocytes were entrained for 3 days by daily 12-h bouts of cyclic biaxial tensile strain (10%, 0.33 Hz, Flexcell) before sampling during free-running conditions. The core clock protein, BMAL-1, was quantified from normalised Western Blot signal intensity and the temporal oscillations characterised by Cosinor linear fit with 24-h period.ResultsFollowing entrainment, the cell-autonomous oscillations of the molecular clock protein, BMAL-1, exhibited circadian (24 h) periodicity (p < 0.001) which aligned to the diurnal mechanical stimuli. A 6-h phase shift in the mechanical entrainment protocol resulted in an equivalent shift of the circadian clockwork. Thus, repeated daily mechanical stimuli synchronised circadian rhythmicity of chondrocytes in vitro.ConclusionThis work demonstrates that daily mechanical stimulation can act as a timing cue that is sufficient to entrain the peripheral circadian clock in vitro. This discovery may be exploited to induce and sustain circadian physiology within into predictive in vitro model systems, including OOAC systems. Integration of the circadian clock within these systems will enhance their potential to accurately recapitulate human diurnal physiology and hence augment their predictive value as drug testing platforms and as realistic models of human (patho)physiology.

Auditory feedback control in adults who stutter during metronome-paced speech II. Formant Perturbation

PurposePrior work has shown that Adults who stutter (AWS) have reduced and delayed responses to auditory feedback perturbations. This study aimed to determine whether external timing cues, which increase fluency, resolve auditory feedback processing disruptions. MethodsFifteen AWS and sixteen adults who do not stutter (ANS) read aloud a multisyllabic sentence either with natural stress and timing or with each syllable paced at the rate of a metronome. On random trials, an auditory feedback formant perturbation was applied, and formant responses were compared between groups and pacing conditions. ResultsDuring normally paced speech, ANS showed a significant compensatory response to the perturbation by the end of the perturbed vowel, while AWS did not. In the metronome-paced condition, which significantly reduced the disfluency rate, the opposite was true: AWS showed a significant response by the end of the vowel, while ANS did not. ConclusionThese findings indicate a potential link between the reduction in stuttering found during metronome-paced speech and changes in auditory motor integration in AWS.

Expression and Neurotransmitter Association of the Synaptic Calcium Sensor Synaptotagmin in the Avian Auditory Brain Stem.

In the avian auditory brain stem, acoustic timing and intensity cues are processed in separate, parallel pathways via the two divisions of the cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Differences in excitatory and inhibitory synaptic properties, such as release probability and short-term plasticity, contribute to differential processing of the auditory nerve inputs. We investigated the distribution of synaptotagmin, a putative calcium sensor for exocytosis, via immunohistochemistry and double immunofluorescence in the embryonic and hatchling chick brain stem (Gallus gallus). We found that the two major isoforms, synaptotagmin 1 (Syt1) and synaptotagmin 2 (Syt2), showed differential expression. In the NM, anti-Syt2 label was strong and resembled the endbulb terminals of the auditory nerve inputs, while anti-Syt1 label was weaker and more punctate. In NA, both isoforms were intensely expressed throughout the neuropil. A third isoform, synaptotagmin 7 (Syt7), was largely absent from the cochlear nuclei. In nucleus laminaris (NL, the target nucleus of NM), anti-Syt2 and anti-Syt7 strongly labeled the dendritic lamina. These patterns were established by embryonic day 18 and persisted to postnatal day 7. Double-labeling immunofluorescence showed that Syt1 and Syt2 were associated with vesicular glutamate transporter 2 (VGluT2), but not vesicular GABA transporter (VGAT), suggesting that these Syt isoforms were localized to excitatory, but not inhibitory, terminals. These results suggest that Syt2 is the major calcium binding protein underlying excitatory neurotransmission in the timing pathway comprising NM and NL, while Syt2 and Syt1 regulate excitatory transmission in the parallel intensity pathway via cochlear nucleus NA.

Motor engagement enhances incidental memory for task-irrelevant items.

Actions shape what we see and memorize. A previous study suggested the interaction between motor and memory systems by showing that memory encoding for task-irrelevant items was enhanced when presented with motor-response cues. However, in the studies on the attentional boost effect, it has been revealed that detection of the target stimulus can lead to memory enhancement without requiring overt action. Thus, the direct link between the action and memory remains unclear. To exclude the effect of the target detection process as a potential confounder, this study assessed the benefit of action for memory by separating items from the response cue in time. In our pre-registered online experiment (N = 142), participants responded to visual Go cues by pressing a key (i.e., motor task) or counting (i.e., motor-neutral cognitive task) while ignoring No-go cues. In each trial, two task-irrelevant images were sequentially presented after the cue disappearance. After encoding the Go/No-go tasks, participants performed a surprise recognition memory test for those images. Importantly, we quantified the impact of overt execution of the action by comparing memories with and without motor response and the impact of covert motor processes (e.g., preparation and planning of action) by comparing memory between the motor and cognitive tasks. The results showed no memory differences between Go and No-go trials in the motor task. This means that the execution itself was not critical for memory enhancement. However, the memory performance in the motor No-go trials was higher than that in the cognitive No-go trials, only for the items presented away from the cues in time. Therefore, engaging the motor task itself could increase incidental memory for the task-irrelevant items compared to a passive viewing situation. We added empirical evidence on the online interaction between action and memory encoding. These memory advantages could be especially brought in action preparation and planning. We believe this fact may expand our present understanding of everyday memory, such as active learning.

Drosophila Populations Reared Under Tropical Semi-natural Conditions Evolve Season-dependent Differences in Timing of Eclosion.

Circadian clocks are considered an evolutionary adaptation to environmental cycles, helping organisms to adapt to daily and seasonal changes. However, most studies on the evolution of circadian rhythms have been carried out in controlled laboratory conditions; hence evolution of circadian clocks and rhythms in organisms reared under the influence of naturally varying time cues is not well understood. To address this, we reared large outbred fly populations in an outdoor enclosure on our institutional grounds in Bengaluru, southern India for about 150 generations, at the same time maintaining their ancestral control populations under standard laboratory conditions. Studying their rhythms in eclosion, a vital behavior for Drosophila, in the laboratory and semi-natural environments revealed that flies reared under semi-natural conditions differed in the timing of eclosion under semi-natural conditions in a season-dependent manner from their laboratory-reared counterparts. These differences were manifested under harsh semi-natural environments but not under mild ones or in standard laboratory conditions. Further analysis revealed that this phenotype might be responsive to seasonal changes in temperature cycles which was confirmed in the laboratory with simulated light and temperature cycles that approximated semi-natural conditions. Our results highlight key intricacies on the relative impact of intensity and timing of environmental cues for predicting the timing of Drosophila eclosion under tropical naturalistic conditions. Overall, our research uncovers previously unexplored aspects of adaptive circadian timekeeping in complex natural conditions, offering valuable insight into the evolution of clocks.

Circadian molecular clock disruption in chronic pulmonary diseases.

The circadian clock is the biochemical oscillator with a near 24-h period that is responsible for generating the circadian rhythms in peripheral organs including the lung. Mounting evidence suggests that circadian clock disruption during chronic lung diseases plays an essential role in augmented oxidative stress, inflammatory response, metabolic imbalances, hypoxia/hyperoxia, mucus secretion, dysregulated autophagy, and alters pulmonary function. Here, we review circadian clock disruption and discuss candidate clock genes that are altered at the transcriptional or translational level in chronic pulmonary diseases. This review aims to provide the current knowledge and understanding of the circadian molecular clock disruption in chronic pulmonary diseases which will further advance the development of novel clock-based therapeutics in the future.

Sunshine with a Chance of Smiles: How Does Weather Impact Sentiment on Social Media?

The environment we are in can affect our mood and behavior. One environmental factor is weather, which is linked to sentiment as expressed on social media. However, less is known about how integrating changes in weather, along with time and location contextual cues, can improve sentiment detection and understanding. In this paper, we explore the effects of three contextual features--weather, location, and time--on expressed sentiment in social media. Leveraging a large Snapchat dataset, we provide extensive experimental evidence that including contextual features in addition to textual features significantly improves textual sentiment detection performance by 3% over transformer-based language models. Our results also generalize cross-domain to Twitter. Ablation studies indicate the relative importance of weather compared to location and time. We also conduct correlation analyses on 8 million Snapchat posts to highlight the link between past weather and current sentiment, showing that weather has a lasting impact on mood. Users generally exhibit more positive sentiment in better weather conditions as well as in improved weather conditions. Additionally, we show that temperature's link with mood holds after controlling for time or population density, but there exist geographical differences in how temperature affects mood. Our work demonstrates the effectiveness of including external contexts in linguistic tasks and carries design implications for researchers and designers of social media.

Dynamic lighting schedules to facilitate circadian adaptation to shifted timing of sleep and wake.

Circadian adaptation to shifted sleep/wake schedules may be facilitated by optimizing the timing, intensity and spectral characteristics of light exposure, which is the principal time cue for mammalian circadian pacemaker, and possibly by strategically timing nonphotic time cues such as exercise. Therefore, circadian phase resetting by light and exercise was assessed in 44 healthy participants (22 females, mean age [±SD] 36.2 ± 9.2 years), who completed 8-day inpatient experiments simulating night shiftwork, which included either an 8 h advance or 8 h delay in sleep/wake schedules. In the advance protocol (n = 18), schedules were shifted either gradually (1.6 h/day across 5 days) or abruptly (slam shift, 8 h in 1 day and maintained across 5 days). Both advance protocols included a dynamic lighting schedule (DLS) with 6.5 h exposure of blue-enriched white light (704 melanopic equivalent daylight illuminance [melEDI] lux) during the day and dimmer blue-depleted light (26 melEDI lux) for 2 h immediately before sleep on the shifted schedule. In the delay protocol (n = 26), schedules were only abruptly delayed but included four different lighting conditions: (1) 8 h continuous room-light control; (2) 8 h continuous blue-enriched light; (3) intermittent (7 × 15 min pulses/8 h) blue-enriched light; (4) 8 h continuous blue-enriched light plus moderate intensity exercise. In the room-light control, participants received dimmer white light for 30 min before bedtime, whereas in the other three delay protocols participants received dimmer blue-depleted light for 30 min before bedtime. Both the slam and gradual advance protocols induced similar shifts in circadian phase (3.28 h ± 0.37 vs. 2.88 h ± 0.31, respectively, p = .43) estimated by the change in the timing of timing of dim light melatonin onset. In the delay protocol, the continuous 8 h blue-enriched exposure induced significantly larger shifts than the room light control (-6.59 h ± 0.43 vs. -4.74 h ± 0.62, respectively, p = .02). The intermittent exposure induced ~60% of the shift (-3.90 h ± 0.62) compared with 8 h blue-enriched continuous light with only 25% of the exposure duration. The addition of exercise to the 8 h continuous blue-enriched light did not result in significantly larger phase shifts (-6.59 h ± 0.43 vs. -6.41 h ± 0.69, p = .80). Collectively, our results demonstrate that, when attempting to adapt to an 8 h overnight work shift, delay shifts are more successful, particularly when accompanied by a DLS with high-melanopic irradiance light stimulus during wake.

0210 Social rhythm regularity: Associations with sleep, circadian, mental health, and alcohol use outcomes in adolescents

Abstract Introduction Circadian rhythms and sleep regularity relate to a range of negative health outcomes, such as mental illness and substance abuse including binge drinking. According to the social zeitgeber hypothesis, the timing of key modifiable daily behaviors serves as time cues that entrain circadian rhythms, ostensibly stabilizing them and thereby improving health. The cross-day stability in timing of these behaviors (i.e., social rhythm regularity) is measured by SRM5; however, studies have not tested whether SRM5 correlates with circadian rhythm regularity based on physiological measures, such as dim light melatonin onset (DLMO). The current study examined whether SRM5 was associated with: (1) the regularity of circadian rhythms and/or sleep regularity metrics, and (2) sleep quality, depression, and binge drinking. Methods Late adolescents aged 18 to 22 years old who drink alcohol (n = 36; 61.1% female, Mage = 21.26) completed a self-reported sleep diary (including SRM5 items for first contact, start work, and dinner time), wore a wrist actigraph for 14 days, and completed 2 overnight visits to assess DLMO. We used the self-reported data to calculate SRM5 and standard deviation (StDev); actigraphy data to calculate composite phase deviation (CPD), social jet lag (SJL), and interdaily stability (IS); and DLMO data to calculate the stability of the circadian phase (Sunday minus Thursday). Participants also completed surveys that assessed global sleep quality, depressive symptoms, and frequency of binge drinking. Correlational analysis and hierarchical linear regression modeling were used. Results Higher SRM5 scores (i.e., higher social rhythm regularity) were associated with higher regularities of mid-sleep timing (r = –.48, p &amp;lt; .001) and total sleep duration (r = –.41, p = .01) based on StDev metrics but were not associated with IS (r = 13, p = .45), CPD (r = –.19, p = .28), SJL (r = –.07, p = .68), and stability of DLMO (r = –.003, p = .99). A post-hoc analysis found that higher stability of the “out of bed” item of SRM5 was related to higher stability of DLMO (b = –.11, se = .05, p = .03, r2 = .33). Higher SRM5 scores were associated with better sleep quality (b = –.73, se = .30, p = .02, r2 = .21), but were not with depressive symptoms or binge drinking Conclusion In contrast with the social zeitgeber hypothesis, SRM5 was not associated with circadian rhythm regularity measured by DLMO. However, social rhythm regularity is an important factor in predicting better sleep quality. This study provides a foundation for future research with better power to determine the extent to which social rhythms influence circadian stability and to better understand why social rhythm regularity relates to sleep quality. Support (If Any) This research was supported by the NIH NIAAA (R21AA023209-02 ), NHLBI (T32HL082610), and NIMH (T32MH019986)

0003 On the Same Wavelength? Quantifying the Associations between Eating Timing and Rest-Activity Rhythms in Free-Living Adults

Abstract Introduction Misalignment between the central circadian clock and daily behaviors increases cardiometabolic morbidity and mortality risk, likely due to internal misalignment between central and peripheral circadian rhythms. Experimental studies suggest food intake may act as a time cue (‘zeitgeber’) for resetting circadian rhythms, representing a potential behavioral target to ameliorate circadian misalignment and associated health consequences. However, the extent to which eating timing relates to circadian rhythms in free-living adults is unclear. Therefore, we tested the associations between eating timing with 24-h rest-activity-rhythms (RAR), a free-living proxy for endogenous circadian rhythms, in non-shift-working adults. Methods Adults without chronic health conditions or sleep disorders completed 14 days of 24/7 wrist accelerometry to evaluate RAR variables of interdaily stability (IS; day-to-day stability in RAR), intradaily variability (IV; within-day fragmentation of RAR), relative amplitude (RA; difference between peak vs. trough activity), L5 onset time (5-h period with lowest activity), and M10 onset time (10-h period with highest activity). Concurrently, time-stamped image-assisted diet records were obtained to generate average eating timing variables, including daily eating onset (time of first caloric intake after awakening), offset (last caloric intake time), duration (time elapsed between eating onset and offset), and caloric midpoint (time at which 50% of daily kcals were consumed), and variables illustrating irregularity in eating timing (standard deviation of eating timing variables). Pearson’s correlations quantified the associations between RAR and eating timing variables. Results Participants (N=30) were 28.0±6.6 years, 57% female, with a BMI of 23.8±2.5 kg/m2. Higher IS was correlated with lower irregularity in both eating onset (r=-0.55, p&amp;lt;0.01) and duration (r=-0.51, p&amp;lt;0.01). Higher RA correlated with earlier eating onset (r=-0.47, p&amp;lt;0.01), longer eating duration (r=0.53, p&amp;lt;0.01), and lower eating onset irregularity (r=-0.37, p&amp;lt;0.05). Later L5 correlated with later eating onset (r=0.67, p&amp;lt;0.001), offset (r=0.58, p&amp;lt;0.001), caloric midpoint (r=0.56, p&amp;lt;0.01), and greater eating offset irregularity (r=0.53, p&amp;lt;0.01). Later M10 correlated with later eating offset (r=0.40, p&amp;lt;0.05). Conclusion Preliminary findings indicate that eating timing and RAR are moderately correlated in free-living adults. Earlier eating timing, increased eating regularity, and longer daily eating duration may represent behavioral targets for improving circadian rhythms and subsequent cardiometabolic outcomes. Support (If Any): Support provided by the American Heart Association (#831488) and a University of Delaware Research Fund-Strategic Initiative Award.

Intestinal inflammation alters the antigen-specific immune response to a skin commensal.

SUMMARYResident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.

A fixed single meal in the subjective day prevents free-running of the human sleep-wake cycle but not of the circadian pacemaker under temporal isolation.

Effects of a fixed single meal per day were examined on the circadian pacemaker and sleep-wake cycle in subjects under temporal isolation. When the time of single meal was allowed to take at any time of day (ad-lib meal), the sleep-wake cycle as well as the circadian rhythms in plasma melatonin, cortisol, and core body temperature were significantly phase-delayed in 8 days. On the other hand, when the time of meal was fixed at 1800 h in local time (RF meal), the phase-shift of sleep-wake cycle was not significant while those of the circadian rhythms were significant. The differential effects of a fixed single meal schedule were confirmed in most individual subjects. There was no evidence for the prefeeding increase in plasma cortisol and leptin levels under the fixed single meal schedule. The plasma ghrelin level was apparently high before meal in both ad-lib and RF meal groups, which was, however, likely sculptured by a nonspecific prandial drop and gradual increase after meal intake. Single meal augmented the prandial increase of plasma insulin levels by four to five times. These findings indicate that a single meal at a fixed time of the day during the subjective day failed to prevent the human circadian pacemaker but prevented the sleep-wake cycle from free running for at least 8 days under temporal isolation, suggesting that mealtime was a potent nonphotic time cue for the human sleep-wake cycle.

Effect of different assistive systems on elderly pedestrians’ road-crossing decisions

ABSTRACT This study seeks to explore the road-crossing behavior of elderly pedestrians and whether time cues can effectively reduce the risk of crossing. Past studies on road-crossing decision-making mostly focus on the increased risk in older pedestrians due to diminished cognitive functions but often overlooked the impact of providing information about time. Therefore, this study examined the effects of assistive systems providing two different types of time information, namely, remaining time and arriving time, on road-crossing in older pedestrians under different traffic situations. The results showed that both assistive systems reduced the road-crossing response time and collision rate in older adults. In general, the “remaining time system” was more effective, especially in the combination of short vehicle gap and high vehicle speed. Remaining time was found to be more intuitive for road-crossing decision-making. These findings contribute to effective ways to reduce the risk of road crossing in elderly pedestrians.