Time Cues Research Articles

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.

Amplification of input differences by dynamic heterogeneity in the spiral ganglion.

A defining feature of type I primary auditory afferents that compose ∼95% of the spiral ganglion is their intrinsic electrophysiological heterogeneity. This diversity is evident both between and within unitary, rapid, and slow adaptation (UA, RA, and SA) classes indicative of specializations designed to shape sensory receptor input. But to what end? Our initial impulse is to expect the opposite: that auditory afferents fire uniformly to represent acoustic stimuli with accuracy and high fidelity. Yet this is clearly not the case. One explanation for this neural signaling strategy is to coordinate a system in which differences between input stimuli are amplified. If this is correct, then stimulus disparity enhancements within the primary afferents should be transmitted seamlessly into auditory processing pathways that utilize population coding for difference detection. Using sound localization as an example, one would expect to observe separately regulated differences in intensity level compared with timing or spectral cues within a graded tonotopic distribution. This possibility was evaluated by examining the neuromodulatory effects of cAMP on immature neurons with high excitability and slow membrane kinetics. We found that electrophysiological correlates of intensity and timing were indeed independently regulated and tonotopically distributed, depending on intracellular cAMP signaling level. These observations, therefore, are indicative of a system in which differences between signaling elements of individual stimulus attributes are systematically amplified according to auditory processing constraints. Thus, dynamic heterogeneity mediated by cAMP in the spiral ganglion has the potential to enhance the representations of stimulus input disparities transmitted into higher level difference detection circuitry.NEW & NOTEWORTHY Can changes in intracellular second messenger signaling within primary auditory afferents shift our perception of sound? Results presented herein lead to this conclusion. We found that intracellular cAMP signaling level systematically altered the kinetics and excitability of primary auditory afferents, exemplifying how dynamic heterogeneity can enhance differences between electrophysiological correlates of timing and intensity.

Gesture and reference to objects in the here-and-now: Listeners' use of gesture cues in quiet and in noise.

In face-to-face interaction, speakers spontaneously produce manual gestures that can facilitate listeners' comprehension of spoken language. The present study explores the factors affecting the uptake and influence of gesture cues in situations where a speaker is referring to objects visible to the listener. In this context, the listener's attention must be distributed across various scene regions, potentially reducing the ability to draw on and apply gesture cues in real time. In two experiments, the instruction provided by a speaker (e.g., "pick up the candy") was accompanied by an iconic grasp gesture (produced alongside the verb) that reflected the size/shape of the intended target. Effects on listeners' comprehension were compared with a no-gesture condition. Experiment 1 (audiovisual gating task) showed that, under simplified processing circumstances, gesture cues allowed earlier identification of intended targets. Experiment 2 (eye tracking) explored whether this facilitation is found in real-time comprehension, and whether attention to gesture information is influenced by the acoustic environment (quiet vs. background noise). Measures of gaze position showed that although the speaker's gesturing hand was rarely fixated directly, gestures did facilitate comprehension, particularly when the target object was smaller relative to alternatives. The magnitude of the gesture effect was greater in quiet than in noise, suggesting that the latter did not provoke listeners to increase attention to gesture to compensate for the challenging auditory signal. Together, the findings clarify how situational factors influence listeners' attention to visual information during real-time comprehension. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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The circadian clock, an internal time‐keeping mechanism, drives many physiological processes during the 24‐h day. The core oscillators respond to the resetting of environmental timing cues. The rhythmic outputs include leaves and petals movement, sunflower heliotropism, stomatal opening and closing, oscillation of cytosolic free calcium, and the resistance responses to biotic and abiotic stresses, etc (Page 792–811).

Is returning a product worth my time? The impact of time cues on consumer product returns

AbstractConsidering that returning a purchased product involves time costs to consumers, we posit that making a time cue salient will influence their likelihood of returning a product. Four studies reveal that consumers primed with time cues are less willing to return a product. Specifically, presenting time cues can reduce product returns by amplifying consumers' perception of time pressure and alleviating their psychological discomfort. Furthermore, private self‐awareness is found to moderate the time‐cue effect through perceived discomfort. The results are replicated even when time pressure and psychological discomfort are directly manipulated, supporting the causal account. This study contributes to the literature on consumer product returns by proposing the time‐cue effect and its psychological mechanisms and helps retailers manage product returns using various time cues.

MTOR-AKT Signaling in Cellular Clock Resetting Triggered by Osmotic Stress.

Aims: The circadian clock oscillates in a cell-autonomous manner with a period of ∼24 h, and the phase is regulated by various time cues such as light and temperature through multiple clock input pathways. We previously found that osmotic and oxidative stress strongly affected the circadian period and phase of cellular rhythms, and triple knockout of apoptosis signal-regulating kinase (ASK) family members, Ask1, Ask2, and Ask3, abolished the phase shift (clock resetting) induced by hyperosmotic pulse treatment. We aimed at exploring a key molecule(s) and signaling events in the clock input pathway dependent on ASK kinases. Results: The phase shift of the cellular clock induced by the hyperosmotic pulse treatment was significantly reduced by combined deficiencies of the clock(-related) genes, Dec1, Dec2, and E4 promoter-binding protein 4 (also known as Nfil3) (E4bp4). In addition, liquid chromatography mass/mass spectrometry (LC-MS/MS)-based proteomic analysis identified hyperosmotic pulse-induced phosphorylation of circadian locomotor output cycles caput (CLOCK) Ser845 in an AKT-dependent manner. We found that AKT kinase was phosphorylated at Ser473 (i.e., activated) in response to the hyperosmotic pulse experiments. Inhibition of mechanistic target of rapamycin (mTOR) kinase by Torin 1 treatment completely abolished the AKT activation, suppressed the phosphorylation of CLOCK Ser845, and blocked the clock resetting induced by the hyperosmotic pulse treatment. Innovation and Conclusions: We conclude that mTOR-AKT signaling is indispensable for the CLOCK Ser845 phosphorylation, which correlates with the clock resetting induced by the hyperosmotic pulse treatment. Immediate early induction of the clock(-related) genes and CLOCK carboxyl-terminal (C-terminal) region containing Ser845 also play important roles in the clock input pathway through redox-sensitive ASK kinases. Antioxid. Redox Signal. 37, 631-646.

Circadian clock in plants: Linking timing to fitness.

Endogenous circadian clock integrates cyclic signals of environment and daily and seasonal behaviors of organisms to achieve spatiotemporal synchronization, which greatly improves genetic diversity and fitness of species. This review addresses recent studies on the plant circadian system in the field of chronobiology, covering topics on molecular mechanisms, internal and external Zeitgebers, and hierarchical regulation of physiological outputs. The architecture of the circadian clock involves the autoregulatory transcriptional feedback loops, post-translational modifications of core oscillators, and epigenetic modifications of DNA and histones. Here, light, temperature, humidity, and internal elemental nutrients are summarized to illustrate the sensitivity of the circadian clock to timing cues. In addition, the circadian clock runs cell-autonomously, driving independent circadian rhythms in various tissues. The core oscillators responds to each other with biochemical factors including calcium ions, mineral nutrients, photosynthetic products, and hormones. We describe clock components sequentially expressed during a 24-h day that regulate rhythmic growth, aging, immune response, and resistance to biotic and abiotic stresses. Notably, more data have suggested the circadian clock links chrono-culture to key agronomic traits in crops.

Perception of Fortis and Lenis Stops of English in Word-Initial Position in Terms of VOT

The purpose of this study was to investigate the differences between the responses of native Korean and English listeners to voice onset time (VOT) cues when distinguishing word-initial fortis and lenis stops in English. Additionally, this study examined the effects of the place of articulation and the height and backness of the following vowels. The first finding of the study is that the native Korean listeners needed a longer VOT to differentiate fortis from lenis stops. Second, the VOT boundary was the lowest for bilabial stops, while there was no statistically significant difference between alveolar and velar stops. Third, the boundary was found to be the highest for high vowels, the second highest for mid vowels, and lowest for low vowels. Finally, the boundary of high vowels was formed at a greater value than that of low vowels.

Towards an Understanding of Circatidal Clocks.

Circadian clocks are an intrinsic element of life that orchestrate appropriately timed daily physiological and behavioural rhythms entrained to the solar cycle, thereby conferring increased fitness. However, it is thought that the first archaic ‘proto-clocks’ evolved in ancient cyanobacteria in a marine environment, where the dominant time cues (zeitgebers) probably would have been lunar-driven and included tidal cycles. To date, non-circadian ‘marine clocks’ have been described with circatidal (~12.4 h), circasemilunar (~14.8 days), and circalunar (~29.5 days) periodicity, mostly studied in accessible but temporally complex intertidal habitats. In contrast to the well-described circadian clock, their molecular machinery is poorly understood, and fundamental mechanisms remain unclear. We propose that a multi-species approach is the most apposite strategy to resolve the divergence that arose from non-circadian clockwork forged in an evolutionary environment with multiple zeitgebers. We review circatidal clock models with a focus on intertidal organisms, for which robust behavioural, physiological, or genetic underpinnings have been explicated, and discuss their relative experimental merits. Developing a comprehensive mechanistic understanding of circatidal clocks should be a priority because it will ultimately contribute to a more holistic understanding of the origins and evolution of chronobiology itself.

Speech timing cues reveal deceptive speech in social deduction board games.

The faculty of language allows humans to state falsehoods in their choice of words. However, while what is said might easily uphold a lie, how it is said may reveal deception. Hence, some features of the voice that are difficult for liars to control may keep speech mostly, if not always, honest. Previous research has identified that speech timing and voice pitch cues can predict the truthfulness of speech, but this evidence has come primarily from laboratory experiments, which sacrifice ecological validity for experimental control. We obtained ecologically valid recordings of deceptive speech while observing natural utterances from players of a popular social deduction board game, in which players are assigned roles that either induce honest or dishonest interactions. When speakers chose to lie, they were prone to longer and more frequent pauses in their speech. This finding is in line with theoretical predictions that lying is more cognitively demanding. However, lying was not reliably associated with vocal pitch. This contradicts predictions that increased physiological arousal from lying might increase muscular tension in the larynx, but is consistent with human specialisations that grant Homo sapiens sapiens an unusual degree of control over the voice relative to other primates. The present study demonstrates the utility of social deduction board games as a means of making naturalistic observations of human behaviour from semi-structured social interactions.

How to Effectively Display Sponsorship Information: The Influences of External Time Cues and Information Type on Individuals' Evaluations.

Time, an important, yet scarce resource in daily living, affects cognition, decision-making, and behavior in various ways. For instance, in marketing practice, time-bound strategies are often employed to influence consumer behavior. Thus, understanding and mastering a target market from a temporal perspective can contribute to the ease with which marketers and businesses formulate marketing strategies. Accordingly, this research conducts three studies to explore the influence of temporal framing as an external time cue on the evaluation of sponsorship-linked marketing campaigns. The studies show that future-framed participants adopted a global processing style. In this context, providing information about the sponsoring brand and sponsored event induced a more positive evaluation of future campaigns. However, in a past-frame context, participants were less likely to adopt a global processing style. Here, providing brand sponsor information alone increased the likelihood of a positive evaluation of past campaigns. Ultimately, the findings provide a theoretical basis for decision-making utilizing the influence of activities and events to enhance brand image.

Photic Entrainment of the Circadian System.

Circadian rhythms are essential for the survival of all organisms, enabling them to predict daily changes in the environment and time their behaviour appropriately. The molecular basis of such rhythms is the circadian clock, a self-sustaining molecular oscillator comprising a transcriptional–translational feedback loop. This must be continually readjusted to remain in alignment with the external world through a process termed entrainment, in which the phase of the master circadian clock in the suprachiasmatic nuclei (SCN) is adjusted in response to external time cues. In mammals, the primary time cue, or “zeitgeber”, is light, which inputs directly to the SCN where it is integrated with additional non-photic zeitgebers. The molecular mechanisms underlying photic entrainment are complex, comprising a number of regulatory factors. This review will outline the photoreception pathways mediating photic entrainment, and our current understanding of the molecular pathways that drive it in the SCN.

Advantages of Pulse Rate Compared to Modulation Frequency for Temporal Pitch Perception in Cochlear Implant Users.

Most cochlear implants encode the fundamental frequency of periodic sounds by amplitude modulation of constant-rate pulsatile stimulation. Pitch perception provided by such stimulation strategies is markedly poor. Two experiments are reported here that consider potential advantages of pulse rate compared to modulation frequency for providing stimulation timing cues for pitch. The first experiment examines beat frequency distortion that occurs when modulating constant-rate pulsatile stimulation. This distortion has been reported on previously, but the results presented here indicate that distortion occurs for higher stimulation rates than previously reported. The second experiment examines pitch resolution as provided by pulse rate compared to modulation frequency. The results indicate that pitch discrimination is better with pulse rate than with modulation frequency. The advantage was large for rates near what has been suggested as the upper limit of temporal pitch perception conveyed by cochlear implants. The results are relevant to sound processing design for cochlear implants particularly for algorithms that encode fundamental frequency into deep envelope modulations or into precisely timed pulsatile stimulation.

Studying Circadian Clock Entrainment by Hormonal Signals.

In mammals, molecular circadian clocks not only exist in the suprachiasmatic nucleus (SCN) but in almost all organ systems. Intriguingly, tissue clocks can operate in both isolated tissues and cell lines with endocrine signals mediating the circadian expression of local transcriptomes. This can be demonstrated by treating tissue explants with endocrine cues in a phase- and dose-dependent manner. In this chapter we provide an overview of methods to study the effects of candidate hormonal time cues on tissue clock resetting. We propose an experimental procedure based on an in vitro setup consisting of several consecutive steps in which organotypic tissue cultures or cells can be used. Our approach targets the potential resetting mechanism at three levels: the hormone, the direct clock gene target, and the tissue clock response.

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

The Processing Mechanisms of Two Types of Mixed Prospective Memory.

Mixed prospective memory (MPM) needs to be executed when both external time and event cues appear. According to the clarity of time cues, MPM can be further divided into two types: time-point MPM and time-period MPM. There is no research on these two types of MPM. Whether existing theories of EBPM can explain its processing mechanisms is worth exploring. The current study was aimed at examining the differences in attentional allocation characteristics between these two types of MPM and EBPM under different difficult ongoing tasks. The results showed that the attention consumption of the two types of MPM groups was less than that of the EBPM group in the early and middle stages of high cognitive load, but there was no difference between the three groups in the later stage of the task. The attention distribution of time-point MPM and time-period MPM displayed dynamic changes: the time-point MPM only had attention consumption in the later stage, while the time-period MPM also existed in the early and middle stages. These results support dynamic multiprocess theory.

Estimations of the Passing Height of Approaching Objects.

Limited optical cues associated with ball flight were inadequate to estimate the vertical passing distance of approaching balls. These results suggest that these optical cues either must be integrated with contextual and kinematic cues or must be of larger amplitude to contribute to estimates of vertical passing distance. To intercept or avoid approaching objects, individuals must estimate both when and where the object will arrive. The purpose of this experiment was to determine whether individuals could estimate the vertical passing height of a ball approaching at different linear speeds when vertical angular retinal image velocity and cues for time to contact were minimized. Twenty participants stood 40 feet from a pitching machine that projected tennis balls toward observers at six random speeds from 56 to 80 mph. The flight of the balls was stopped after 9 feet. The actual passing height ranged from about 35 (lowest speed) to 136 cm (highest speed). Observers indicated the height at which they expected the balls to arrive. Overall, the height estimates increased as ball speed increased (means, 121 ± 13 cm [lowest speed] and 131 ± 10 cm [highest speed]). However, only at the higher speeds were the absolute height estimates close to the actual height of the ball. At the higher ball speeds, estimates for participants with some experience in baseball or softball were more accurate (86.4% correct at the highest speed) than estimates for participants with no experience. Overall, estimates of vertical passing distance were inaccurate particularly at the lower speeds. Underestimates of vertical drop at lower speeds may have resulted from overestimates of ball speeds. At short exposure durations, optical cues associated with ball flight were inadequate for predictions of vertical passing distance at all speeds for the no-experience group and at lower speeds for the experienced group.

Rapid-acting antidepressants and the circadian clock.

A growing number of epidemiological and experimental studies has established that circadian disruption is strongly associated with psychiatric disorders, including major depressive disorder (MDD). This association is becoming increasingly relevant considering that modern lifestyles, social zeitgebers (time cues) and genetic variants contribute to disrupting circadian rhythms that may lead to psychiatric disorders. Circadian abnormalities associated with MDD include dysregulated rhythms of sleep, temperature, hormonal secretions, and mood which are modulated by the molecular clock. Rapid-acting antidepressants such as subanesthetic ketamine and sleep deprivation therapy can improve symptoms within 24 h in a subset of depressed patients, in striking contrast to conventional treatments, which generally require weeks for a full clinical response. Importantly, animal data show that sleep deprivation and ketamine have overlapping effects on clock gene expression. Furthermore, emerging data implicate the circadian system as a critical component involved in rapid antidepressant responses via several intracellular signaling pathways such as GSK3β, mTOR, MAPK, and NOTCH to initiate synaptic plasticity. Future research on the relationship between depression and the circadian clock may contribute to the development of novel therapeutic strategies for depression-like symptoms. In this review we summarize recent evidence describing: (1) how the circadian clock is implicated in depression, (2) how clock genes may contribute to fast-acting antidepressants, and (3) the mechanistic links between the clock genes driving circadian rhythms and neuroplasticity.