Search

Background: We examined associations between dog ownership, morning dog walking and its timing and duration, and depression risk in female nurses, exploring effect modification by chronotype. We hypothesized that dog ownership and morning walking with the dog are associated with lower odds of depression, and that the latter is particularly beneficial for evening chronotypes by helping them to synchronize their biological clock with the solar system. Methods: 26,169 depression-free US women aged 53–72 from the Nurses' Health Study 2 (NHS2) were prospectively followed from 2017–2019. We used age- and multivariable-adjusted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for depression according to dog ownership, and morning dog walking, duration, and timing. Results: Overall, there was no association between owning a dog (ORvs_no_pets = 1.12, 95%CI = 0.91–1.37), morning dog walking (ORvs_not = 0.87, 95%CI = 0.64–1.18), or the duration (OR>30min vs. ≤15mins = 0.68, 95%CI = 0.35–1.29) or timing of morning dog walks (ORafter9am vs. before7am = 1.06, 95%CI = 0.54–2.05) and depression. Chronotype of dog owners appeared to modify these associations. Compared to women of the same chronotype but without pets, dog owners with evening chronotypes had a significantly increased odds of depression (OR = 1.60, 95%CI = 1.12–2.29), whereas morning chronotypes did not (OR = 0.94, 95%CI = 0.71–1.23). Further, our data suggested that evening chronotypes benefited more from walking their dog themselves in the morning (OR = 0.75, 95%CI = 0.46–1.23, Pintx = 0.064;) than morning chronotypes. Conclusions: Overall, dog ownership was not associated with depression risk though it was increased among evening chronotypes. Walking their dog in the morning might help evening chronotypes to lower their odds of depression, though more data are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Platynereis dumerilii, a marine annelid, is a model animal that has gained popularity in various fields such as developmental biology, biological rhythms, nervous system organization and physiology, behaviour, reproductive biology, and epigenetic regulation. The transparency of P. dumerilii tissues at all developmental stages makes it easy to perform live microscopic imaging of all cell types. In addition, the slow-evolving genome of P. dumerilii and its phylogenetic position as a representative of the vast branch of Lophotrochozoans add to its evolutionary significance. Although P. dumerilii is amenable to transgenesis and CRISPR-Cas9 knockouts, its relatively long and indefinite life cycle, as well as its semelparous reproduction have been hindrances to its adoption as a reverse genetics model. To overcome this limitation, an adapted culturing method has been developed allowing much faster life cycling, with median reproductive age at 13–14 weeks instead of 25–35 weeks using the traditional protocol. A low worm density in boxes and a strictly controlled feeding regime are important factors for the rapid growth and health of the worms. This culture method has several advantages, such as being much more compact, not requiring air bubbling or an artificial moonlight regime for synchronized sexual maturation and necessitating only limited water change. A full protocol for worm care and handling is provided. [ABSTRACT FROM AUTHOR]

Genome-scale data have revealed daily rhythms in various species and tissues. However, current methods to assess rhythmicity largely restrict their focus to quantifying statistical significance, which may not reflect biological relevance. To address this limitation, we developed a method called LimoRhyde2 (the successor to our method LimoRhyde), which focuses instead on rhythm-related effect sizes and their uncertainty. For each genomic feature, LimoRhyde2 fits a curve using a series of linear models based on periodic splines, moderates the fits using an Empirical Bayes approach called multivariate adaptive shrinkage (Mash), then uses the moderated fits to calculate rhythm statistics such as peak-to-trough amplitude. The periodic splines capture non-sinusoidal rhythmicity, while Mash uses patterns in the data to account for different fits having different levels of noise. To demonstrate LimoRhyde2's utility, we applied it to multiple circadian transcriptome datasets. Overall, LimoRhyde2 prioritized genes having high-amplitude rhythms in expression, whereas a prior method (BooteJTK) prioritized "statistically significant" genes whose amplitudes could be relatively small. Thus, quantifying effect sizes using approaches such as LimoRhyde2 has the potential to transform interpretation of genomic data related to biological rhythms. [ABSTRACT FROM AUTHOR]

Valvometry techniques used to monitor bivalve gaping activity have elucidated numerous relationships with environmental fluctuations, along with biological rhythms ranging from sub-daily to seasonal. Thus, a precise understanding of the natural activity of bivalves (i.e., not exposed to stressful environmental variations) is necessary as a baseline for detecting abnormal behaviors (deviations). This knowledge is also needed to reliably interpret observations of bivalve gaping behavior and associated biological processes (e.g., respiration, nutrition) acquired over time-limited periods. With this in mind, we investigated the natural daily gaping activity of the great scallop (Pecten maximus) by continuously monitoring 35 individuals in several individual tanks and in situ (Bay of Saint-Brieuc, Brittany, France) using fully autonomous Hall effect sensors. Our results revealed a circadian cycle (τ = 24.0h) in scallop gaping activity. Despite significant inter-individual variability in mean opening and cycle amplitude, almost all individuals (87.5%) exhibited nocturnal activity, with valves more open at night than during the day. A shift in light regime in the tanks triggered an instantaneous change in opening pattern, indicating that light levels strongly determine scallop activity. Based on the opening status of scallops, we also identified several gaping behaviors deviating from the regular daily pattern (lack of rhythmicity, high daytime opening), potentially reflecting physiological weakness. While further long-term studies are required to fully understand the natural activity of scallops, these findings pave the way for studies focused on the scallop response to external factors and introduce further research into the detection of abnormal behaviors. Coupling observations of diel valve gaping cycles with other daily variations in organismal and environmental parameters could help explain mechanisms driving the growth patterns of scallops observed in their shell striations. From a technical perspective, our field-based monitoring demonstrates the suitability of autonomous valvometry sensors for studying mobile subtidal bivalve activity in remote offshore environments. [ABSTRACT FROM AUTHOR]

Previous studies have reported correlates of bodily self-illusions such as the rubber hand in signatures of rhythmic brain activity. However, individual studies focused on specific variations of the rubber hand paradigm, used different experimental setups to induce this, or used different control conditions to isolate the neurophysiological signatures related to the illusory state, leaving the specificity of the reported illusion-signatures unclear. We here quantified correlates of the rubber hand illusion in EEG-derived oscillatory brain activity and asked two questions: which of the observed correlates are robust to the precise nature of the control conditions used as contrast for the illusory state, and whether such correlates emerge directly around the subjective illusion onset. To address these questions, we relied on two experimental configurations to induce the illusion, on different non-illusion conditions to isolate neurophysiological signatures of the illusory state, and we implemented an analysis directly focusing on the immediate moment of the illusion onset. Our results reveal a widespread suppression of alpha and beta-band activity associated with the illusory state in general, whereby the reduction of beta power prevailed around the immediate illusion onset. These results confirm previous reports of a suppression of alpha and beta rhythms during body illusions, but also highlight the difficulties to directly pinpoint the precise neurophysiological correlates of the illusory state. [ABSTRACT FROM AUTHOR]

Objective: When facing major emergency public accidents, men and women may react differently. Our research aimed to assess the influence of gender difference on social support, information preference, biological rhythm, psychological distress, and the possible interaction among these factors during the COVID-19 pandemic. Methods: In this cross-sectional study, 3,237 respondents aged 12 years and older finished the online survey. Levels of social support, information preference, biological rhythm, and psychological distress were assessed using validated scales. A path analysis was conducted to explore possible associations among these variables. Results: The path analysis indicated that women with high levels of social support had a lower possibility of biological rhythm disorders and lower levels of somatization symptoms of psychological distress during the COVID-19 pandemic. The influence of social support on somatization symptoms was exerted via biological rhythm. Women tended to believe both negative and positive information, while men preferred more extreme information. Conclusion: Our results highlighted gender difference in study variables during the COVID-19 pandemic and the importance of social support in alleviating psychological distress and biological rhythm disorders. Moreover, we confirmed that information preference differed significantly by somatization symptoms of psychological distress, suggesting extra efforts to provide more individualized epidemic information. Longitudinal research is required to further explore casual inferences. [ABSTRACT FROM AUTHOR]

Biological rhythms regulate innumerable physiological processes, yet little is known of factors that regulate many of these rhythms. Disruption in the timing of these rhythms can have devastating impacts on population sustainability. We hypothesized that the timing of the molt infradian rhythm in the crustacean Daphnia magna is regulated by the joint action of the protein E75 and nitric oxide. Further, we hypothesized that disruption of the function of E75 would adversely impact several physiological processes related to growth and reproduction. Analysis of mRNA levels of several genes, involved in regulating the molt cycle in insects, revealed the sequential accumulation of E75, its dimer partner HR3, FTZ-F1, and CYP18a1 during the molt cycle. Exposure to the nitric oxide donor sodium nitroprusside early in the molt cycle had no effect on E75 or HR3 mRNA levels, but delayed the peak accumulation of FTZ-F1 and CYP18a1 mRNA. The subsequent exuviation was also delayed consistent with the delay in peak accumulation of FTZ-F1 and CYP18a1. These results supported our assertion that nitric oxide binds E75 rendering it incapable of binding HR3. Excess HR3 protein then enhanced the accumulation of the downstream products FTZ-F1 and CYP18a1. Similarly, suppression of E75 mRNA levels, using siRNA, had no effect on mRNA levels of HR3 but elevated mRNA levels of FTZ-F1. Consistent with these molecular responses, the suppression of E75 using siRNA increased the duration of the molt cycle and reduced the number of offspring produced. We conclude that the molt cycle of daphnids is regulated in a manner similar to insects and disruption of E75 results in a lengthening of the molt cycle and a reduction the release of viable offspring. [ABSTRACT FROM AUTHOR]

The temporal modulation structure of speech plays a key role in neural encoding of the speech signal. Amplitude modulations (AMs, quasi-rhythmic changes in signal energy or intensity) in speech are encoded by neuronal oscillations (rhythmic variations in neural excitability in large cell networks) that oscillate at matching temporal rates. To date, however, all neural studies have investigated adult-directed speech (ADS) as produced and perceived by highly literate adults. Whether temporal features of ADS vary with the skills of the speaker, for example literacy skills, is currently unknown. Here we analyse the temporal structure of ADS spoken by illiterate, low literate (≤ 4 years of literacy) and highly literate (≥ 12 years of literacy) adults. We find that illiterates produce speech differently. Spontaneous conversational speech produced by illiterate adults showed significantly less synchronised coupling between AM bands (less phase synchronisation) than conversational speech produced by low literate and highly literate adults, and contained significantly fewer syllables per second. There was also a significant relationship between years of literacy and the amount of theta-band energy in conversational speech. When asked to produce rhythmic proverbs learned in childhood, all groups could produce speech with similar AM phase synchronisation, suggesting that the differences in spontaneous conversational speech were not caused by physiological constraints. The data suggest that the temporal modulation structure of spoken language changes with the acquisition of cultural skills like literacy that are usually a product of schooling. There is a cultural effect on the temporal modulation structure of spoken language. [ABSTRACT FROM AUTHOR]

Aquaculture is currently a major source of fish and has the potential to become a major source of protein in the future. These demands require efficient aquaculture. The intestinal microbiota plays an integral role that benefits the host, providing nutrition and modulating the immune system. Although our understanding of microbiota in fish gut has increased, comprehensive studies examining fish microbiota and host metabolism remain limited. Here, we investigated the microbiota and host metabolism in the coral leopard grouper, which is traded in Asian markets as a superior fish and has begun to be produced via aquaculture. We initially examined the structural changes of the gut microbiota using next-generation sequencing and found that the composition of microbiota changed between fasting and feeding conditions. The dominant phyla were Proteobacteria in fasting and Firmicutes in feeding; interchanging the dominant bacteria required 12 hours. Moreover, microbiota diversity was higher under feeding conditions than under fasting conditions. Multivariate analysis revealed that Proteobacteria are the key bacteria in fasting and Firmicutes and Fusobacteria are the key bacteria in feeding. Subsequently, we estimated microbiota functional capacity. Microbiota functional structure was relatively stable throughout the experiment; however, individual function activity changed according to feeding conditions. Taken together, these findings indicate that the gut microbiota could be a key factor to understanding fish feeding conditions and play a role in interactions with host metabolism. In addition, the composition of microbiota in ambient seawater directly affects the fish; therefore, it is important to monitor the microbiota in rearing tanks and seawater circulating systems. [ABSTRACT FROM AUTHOR]

A major challenge in systems biology is to infer the parameters of regulatory networks that operate in a noisy environment, such as in a single cell. In a stochastic regime it is hard to distinguish noise from the real signal and to infer the noise contribution to the dynamical behavior. When the genetic network displays oscillatory dynamics, it is even harder to infer the parameters that produce the oscillations. To address this issue we introduce a new estimation method built on a combination of stochastic simulations, mass action kinetics and ensemble network simulations in which we match the average periodogram and phase of the model to that of the data. The method is relatively fast (compared to Metropolis-Hastings Monte Carlo Methods), easy to parallelize, applicable to large oscillatory networks and large (~2000 cells) single cell expression data sets, and it quantifies the noise impact on the observed dynamics. Standard errors of estimated rate coefficients are typically two orders of magnitude smaller than the mean from single cell experiments with on the order of ~1000 cells. We also provide a method to assess the goodness of fit of the stochastic network using the Hilbert phase of single cells. An analysis of phase departures from the null model with no communication between cells is consistent with a hypothesis of Stochastic Resonance describing single cell oscillators. Stochastic Resonance provides a physical mechanism whereby intracellular noise plays a positive role in establishing oscillatory behavior, but may require model parameters, such as rate coefficients, that differ substantially from those extracted at the macroscopic level from measurements on populations of millions of communicating, synchronized cells. [ABSTRACT FROM AUTHOR]

Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, “Exploration of Distinctive CREs and CRMs” (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, “CRM Network Generator” (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression. [ABSTRACT FROM AUTHOR]

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels control cardiac and neuronal rhythmicity. HCN channels contain cyclic nucleotide-binding domain (CNBD) in their C-terminal region linked to the pore-forming transmembrane segment with a C-linker. The C-linker couples the conformational changes caused by the direct binding of cyclic nucleotides to the HCN pore opening. Recently, cyclic dinucleotides were shown to antagonize the effect of cyclic nucleotides in HCN4 but not in HCN2 channels. Based on the structural analysis and mutational studies it has been proposed that cyclic dinucleotides affect HCN4 channels by binding to the C-linker pocket (CLP). Here, we first show that surface plasmon resonance (SPR) can be used to accurately measure cyclic nucleotide binding affinity to the C-linker/CNBD of HCN2 and HCN4 channels. We then used SPR to investigate cyclic dinucleotide binding in HCN channels. To our surprise, we detected no binding of cyclic dinucleotides to the isolated monomeric C-linker/CNBDs of HCN4 channels with SPR. The binding of cyclic dinucleotides was further examined with isothermal calorimetry (ITC), which indicated no binding of cyclic dinucleotides to both monomeric and tetrameric C-linker/CNBDs of HCN4 channels. Taken together, our results suggest that interaction of the C-linker/CNBD with other parts of the channel is necessary for cyclic-dinucleotide binding in HCN4 channels. [ABSTRACT FROM AUTHOR]

Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations. Understanding of dual oscillator dynamics in a single cell at molecular level may provide insight about the circadian mechanisms that encodes day length variations and its response to external zeitgebers. We present here a realistic dual oscillator model of circadian rhythms based on the series of hypotheses proposed by Daan et al., in which they conjectured that the circadian genes per1/cry1 track dawn while per2/cry2 tracks dusk and they together constitute the morning and evening oscillators (dual oscillator). Their hypothesis also provides explanations about the encoding of day length in terms of molecular mechanisms of per/cry expression. We frame a minimal mathematical model with the assumption that per1 acts a morning oscillator and per2 acts as an evening oscillator and to support and interpret this assumption we fit the model to the experimental data of per1/per2 circadian temporal dynamics, phase response curves (PRC's), and entrainment phenomena under various light-dark conditions. We also capture different patterns of splitting phenomena by coupling two single cell dual oscillators with neuropeptides vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) as the coupling agents and provide interpretation for the occurrence of splitting in terms of ME oscillators, though they are not required to explain the morning and evening oscillators. The proposed dual oscillator model based on Daan's hypothesis supports per1 and per2 playing the role of morning and evening oscillators respectively and this may be the first step towards the understanding of the core molecular mechanism responsible for encoding the day length. [ABSTRACT FROM AUTHOR]

Molecular clock system constitutes the origin of biological rhythms that allow organisms to anticipate cyclic environmental changes and adapt their behavior and physiology. Components of the molecular clock are largely conserved across a broad range of species but appreciable diversity in clock structure and function is also present especially in invertebrates. The present work aimed at identify and characterize molecular clockwork components in relationship with the monitoring of valve activity behavior in the oyster Crassostrea gigas. Results provided the characterization of most of canonical clock gene including clock, bmal/cycle, period, timeless, vertebrate-type cry, rev-erb, ror as well as other members of the cryptochrome/photolyase family (plant-like cry, 6–4 photolyase). Analyses of transcriptional variations of clock candidates in oysters exposed to light / dark regime and to constant darkness led to the generation of a putative and original clockwork model in C. gigas, intermediate of described systems in vertebrates and insects. This study is the first characterization of a mollusk clockwork. It constitutes essential bases to understand interactions of the different components of the molecular clock in C. gigas as well as the global mechanisms associated to the generation and the synchronization of biological rhythms in oysters. [ABSTRACT FROM AUTHOR]

Non-verbal communication has important implications for inter-individual relationships and negotiation success. However, to what extent humans can spontaneously use rhythm and prosody as a sole communication tool is largely unknown. We analysed human ability to resolve a conflict without verbal dialogs, independently of semantics. We invited pairs of subjects to communicate non-verbally using whistle sounds. Along with the production of more whistles, participants unwittingly used a subtle prosodic feature to compete over a resource (ice-cream scoops). Winners can be identified by their propensity to accentuate the first whistles blown when replying to their partner, compared to the following whistles. Naive listeners correctly identified this prosodic feature as a key determinant of which whistler won the interaction. These results suggest that in the absence of other communication channels, individuals spontaneously use a subtle variation of sound accentuation (prosody), instead of merely producing exuberant sounds, to impose themselves in a conflict of interest. We discuss the biological and cultural bases of this ability and their link with verbal communication. Our results highlight the human ability to use non-verbal communication in a negotiation process. [ABSTRACT FROM AUTHOR]

Leishmania amazonensis is one of the major etiological agents of the neglected, stigmatizing disease termed american cutaneous leishmaniasis (ACL). ACL is a zoonosis and rodents are the main reservoirs. Most cases of ACL are reported in Brazil, Bolivia, Colombia and Peru. The biological cycle of the parasite is digenetic because sand fly vectors transmit the motile promastigote stage to the mammalian host dermis during blood meal intakes. The amastigote stage survives within phagocytes of the mammalian host. The purpose of this study is detection and identification of changes in protein abundance by 2DE/MALDI-TOF/TOF at the main growth phases of L. amazonensis promastigotes in axenic culture and the differentiation process that takes place simultaneously. The average number of proteins detected per gel is 202 and the non-redundant cumulative number is 339. Of those, 63 are differentially abundant throughout growth and simultaneous differentiation of L. amazonensis promastigotes. The main finding is that certain proteins involved in resistance to nitrosative and oxidative stress are more abundant at the last stages of growth and differentiation of cultured L. amazonensis promastigotes. These proteins are the arginase, a light variant of the tryparedoxin peroxidase, the iron superoxide dismutase, the regulatory subunit of the protein kinase A and a light HSP70 variant. These data taken together with the decrease of the stress-inducible protein 1 levels are additional evidence supporting the previously described pre-adaptative hypothesis, which consists of preparation in advance towards the amastigote stage. [ABSTRACT FROM AUTHOR]

Background: Knowledge of atrial electrophysiological properties is crucial for clinical intervention of atrial arrhythmias and the investigation of the underlying mechanism. This study aims to evaluate the feasibility of a novel noninvasive cardiac electrical imaging technique in imaging bi-atrial activation sequences from body surface potential maps (BSPMs). Methods: The study includes 7 subjects, with 3 atrial flutter patients, and 4 healthy subjects with normal atrial activations. The subject-specific heart-torso geometries were obtained from MRI/CT images. The equivalent current densities were reconstructed from 208-channel BSPMs by solving the inverse problem using individual heart-torso geometry models. The activation times were estimated from the time instant corresponding to the highest peak in the time course of the equivalent current densities. To evaluate the performance, a total of 32 cycles of atrial flutter were analyzed. The imaged activation maps obtained from single beats were compared with the average maps and the activation maps measured from CARTO, by using correlation coefficient (CC) and relative error (RE). Results: The cardiac electrical imaging technique is capable of imaging both focal and reentrant activations. The imaged activation maps for normal atrial activations are consistent with findings from isolated human hearts. Activation maps for isthmus-dependent counterclockwise reentry were reconstructed on three patients with typical atrial flutter. The method was capable of imaging macro counterclockwise reentrant loop in the right atrium and showed inter-atria electrical conduction through coronary sinus. The imaged activation sequences obtained from single beats showed good correlation with both the average activation maps (CC = 0.91±0.03, RE = 0.29±0.05) and the clinical endocardial findings using CARTO (CC = 0.70±0.04, RE = 0.42±0.05). Conclusions: The noninvasive cardiac electrical imaging technique is able to reconstruct complex atrial reentrant activations and focal activation patterns in good consistency with clinical electrophysiological mapping. It offers the potential to assist in radio-frequency ablation of atrial arrhythmia and help defining the underlying arrhythmic mechanism. [ABSTRACT FROM AUTHOR]

In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods. [ABSTRACT FROM AUTHOR]

A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup´s growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation. [ABSTRACT FROM AUTHOR]

Variations in the temporal structure of an interval can lead to remarkable differences in perceived duration. For example, it has previously been shown that isochronous intervals, that is, intervals filled with temporally regular stimuli, are perceived to last longer than intervals left empty or filled with randomly timed stimuli. Characterizing the extent of such distortions is crucial to understanding how duration perception works. One account to explain effects of temporal structure is a non-linear accumulator-counter mechanism reset at the beginning of every subinterval. An alternative explanation based on entrainment to regular stimulation posits that the neural response to each filler stimulus in an isochronous sequence is amplified and a higher neural response may lead to an overestimation of duration. If entrainment is the key that generates response amplification and the distortions in perceived duration, then any form of predictability in the temporal structure of interval fillers should lead to the perception of an interval that lasts longer than a randomly filled one. The present experiments confirm that intervals filled with fully predictable rhythmically grouped stimuli lead to longer perceived duration than anisochronous intervals. No general over- or underestimation is registered for rhythmically grouped compared to isochronous intervals. However, we find that the number of stimuli in each group composing the rhythm also influences perceived duration. Implications of these findings for a non-linear clock model as well as a neural response magnitude account of perceived duration are discussed. [ABSTRACT FROM AUTHOR]

Skeletal histology supports the hypothesis that primate life histories are regulated by a neuroendocrine rhythm, the Havers-Halberg Oscillation (HHO). Interestingly, subfossil lemurs are outliers in HHO scaling relationships that have been discovered for haplorhine primates and other mammals. We present new data to determine whether these species represent the general lemur or strepsirrhine condition and to inform models about neuroendocrine-mediated life history evolution. We gathered the largest sample to date of HHO data from histological sections of primate teeth (including the subfossil lemurs) to assess the relationship of these chronobiological measures with life history-related variables including body mass, brain size, age at first female reproduction, and activity level. For anthropoids, these variables show strong correlations with HHO conforming to predictions, though body mass and endocranial volume are strongly correlated with HHO periodicity in this group. However, lemurs (possibly excepting Daubentonia) do not follow this pattern and show markedly less variability in HHO periodicity and lower correlation coefficients and slopes. Moreover, body mass is uncorrelated, and brain size and activity levels are more strongly correlated with HHO periodicity in these animals. We argue that lemurs evolved this pattern due to selection for risk-averse life histories driven by the unpredictability of the environment in Madagascar. These results reinforce the idea that HHO influences life history evolution differently in response to specific ecological selection regimes. [ABSTRACT FROM AUTHOR]

Daily rhythms in Drosophila under semi-natural conditions (or SN) have received much recent attention. One of the striking differences in the behaviour of wild type flies under SN is the presence of an additional peak of activity in the middle of the day. This is referred to as the afternoon peak (A-peak) and is absent under standard laboratory regimes using gated light and temperature cues. Although previous reports identified the physical factors that contribute towards the A-peak there is no evidence for underlying molecular mechanisms or pathways that control A-peak. We report that the A-peak is mediated by thermosensitive dTRPA1 (drosophila Transient Receptor Potential- A1) ion channels as this peak is absent in dTRPA1 null mutants. Further, when natural cycles of light and temperature are simulated in the lab, we find that the amplitude of the A-peak is dTRPA1-dependent. Although a few circadian neurons express dTRPA1, we show that modulation of A-peak is primarily influenced by non-CRY dTRPA1 expressing neurons. Hence, we propose that A-peak of activity observed under SN is a temperature sensitive response in flies that is elicited through dTRPA1 receptor signalling. [ABSTRACT FROM AUTHOR]

When sounds occur with temporally structured patterns, we can feel a rhythm. To memorize a rhythm, perception of its temporal patterns and organization of them into a hierarchically structured sequence are necessary. On the other hand, rhythm perception can often cause unintentional body movements. Thus, we hypothesized that rhythm information can be manifested in two different ways; temporal and motor representations. The motor representation depends on effectors, such as the finger or foot, whereas the temporal representation is effector-independent. We tested our hypothesis with a working memory paradigm to elucidate neuronal correlates of temporal or motor representation of rhythm and to reveal the neural networks associated with these representations. We measured brain activity by fMRI while participants memorized rhythms and reproduced them by tapping with the right finger, left finger, or foot, or by articulation. The right inferior frontal gyrus and the inferior parietal lobule exhibited significant effector-independent activations during encoding and retrieval of rhythm information, whereas the left inferior parietal lobule and supplementary motor area (SMA) showed effector-dependent activations during retrieval. These results suggest that temporal sequences of rhythm are probably represented in the right fronto-parietal network, whereas motor sequences of rhythm can be represented in the SMA-parietal network. [ABSTRACT FROM AUTHOR]

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample. [ABSTRACT FROM AUTHOR]

West Nile Virus (WNV) is a globally important mosquito borne virus, with significant implications for human and animal health. The emergence and spread of new lineages, and increased pathogenicity, is the cause of escalating public health concern. Pinpointing the environmental conditions that favour WNV circulation and transmission to humans is challenging, due both to the complexity of its biological cycle, and the under-diagnosis and reporting of epidemiological data. Here, we used remote sensing and GIS to enable collation of multiple types of environmental data over a continental spatial scale, in order to model annual West Nile Fever (WNF) incidence across Europe and neighbouring countries. Multi-model selection and inference were used to gain a consensus from multiple linear mixed models. Climate and landscape were key predictors of WNF outbreaks (specifically, high precipitation in late winter/early spring, high summer temperatures, summer drought, occurrence of irrigated croplands and highly fragmented forests). Identification of the environmental conditions associated with WNF outbreaks is key to enabling public health bodies to properly focus surveillance and mitigation of West Nile virus impact, but more work needs to be done to enable accurate predictions of WNF risk. [ABSTRACT FROM AUTHOR]

Present study was designed to examine daily and seasonal variability in the innate immune responses of splenocytes in the fresh water snake, Natrix piscator. Animals were mildly anesthetized and spleen was aseptically isolated and processed for macrophage phagocytosis, NBT reduction, nitrite production, splenocyte proliferation and serum lysozyme activity. Samples were collected at seven time points, viz., 0000, 0400, 0800, 1200, 1600, 2000 and 0000 h during three different seasons, namely summer, winter and spring. Cosinor analysis revealed that percent phagocytosis had a significant 24-h rhythm during summer and spring seasons. The peaks of rhythms in NBT reduction and nitrite release occurred in the morning hours at 10.88 h and 8.31 h, respectively, in winter. A significant 24-h rhythm was also observed in lysozyme concentration and splenocyte proliferation (both Basal and Concanavalin A stimulated) in all three seasons. A significant phase shift in splenocyte proliferation was obtained with a trend of delayed phase shift from winter to spring and from spring to summer. Of the nine variables, significant annual (seasonal) rhythms were detected in almost all variables, excluding phagocytic and splenosomatic indices. All rhythmic variables, except spleen cellularity, exhibited tightly synchronized peaks coinciding with the progressive and recrudescence phases of annual reproductive cycle. It is concluded that the snake synchronizes its daily and seasonal immune activity with the corresponding external time cues. The enhancement of immune function coinciding with one of its crucial reproductive phases might be helping it to cope with the seasonal stressors, including abundance of pathogens, which would otherwise jeopardize the successful reproduction and eventual survival of the species. [ABSTRACT FROM AUTHOR]

Recent studies have emphasized the importance of multiplex networks – interdependent networks with shared nodes and different types of connections – in systems primarily outside of neuroscience. Though the multiplex properties of networks are frequently not considered, most networks are actually multiplex networks and the multiplex specific features of networks can greatly affect network behavior (e.g. fault tolerance). Thus, the study of networks of neurons could potentially be greatly enhanced using a multiplex perspective. Given the wide range of temporally dependent rhythms and phenomena present in neural systems, we chose to examine multiplex networks of individual neurons with time scale dependent connections. To study these networks, we used transfer entropy – an information theoretic quantity that can be used to measure linear and nonlinear interactions – to systematically measure the connectivity between individual neurons at different time scales in cortical and hippocampal slice cultures. We recorded the spiking activity of almost 12,000 neurons across 60 tissue samples using a 512-electrode array with 60 micrometer inter-electrode spacing and 50 microsecond temporal resolution. To the best of our knowledge, this preparation and recording method represents a superior combination of number of recorded neurons and temporal and spatial recording resolutions to any currently available in vivo system. We found that highly connected neurons (“hubs”) were localized to certain time scales, which, we hypothesize, increases the fault tolerance of the network. Conversely, a large proportion of non-hub neurons were not localized to certain time scales. In addition, we found that long and short time scale connectivity was uncorrelated. Finally, we found that long time scale networks were significantly less modular and more disassortative than short time scale networks in both tissue types. As far as we are aware, this analysis represents the first systematic study of temporally dependent multiplex networks among individual neurons. [ABSTRACT FROM AUTHOR]

The current study investigated the rhythmic coordination between vocalization and whole-body movement. Previous studies have reported that spatiotemporal stability in rhythmic movement increases when coordinated with a rhythmic auditory stimulus or other effector in a stable coordination pattern. Therefore, the present study conducted two experiments to investigate (1) whether there is a stable coordination pattern between vocalization and whole-body movement and (2) whether a stable coordination pattern reduces variability in whole-body movement and vocalization. In , two coordination patterns between vocalizations and whole-body movement (hip, knee, and ankle joint flexion-on-the-voice vs. joint extension-on-the-voice) in a standing posture were explored at movement frequencies of 80, 130, and 180 beats per minute. At higher movement frequencies, the phase angle in the extension-on-the-voice condition deviated from the intended phase angle. However, the angle of the flexion-on-the-voice was maintained even when movement frequency increased. These results suggest that there was a stable coordination pattern in the flexion-on-the-voice condition. In , variability in whole-body movement and voice-onset intervals was compared between two conditions: one related to tasks performed in the flexion-on-the-voice coordination (coordination condition) that was a stable coordination pattern, and the other related to tasks performed independently (control condition). The results showed that variability in whole-body movement and voice-onset intervals was smaller in the coordination condition than in the control condition. Overall, the present study revealed mutual stabilization between rhythmic vocalization and whole-body movement via coordination within a stable pattern, suggesting that coupled action systems can act as a single functional unit or coordinative structure. [ABSTRACT FROM AUTHOR]

Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson’s disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients’ walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent α. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and α. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and α to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn–Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, α differentiated obvious-PRD from mild-PRD. Considering α reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have potential to evaluate the symptoms of PD. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR) plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR) and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA) was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1–6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), cholic acid (CA) as well as ursodeoxycholic acid (UDCA) at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO) as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC), Inspiratory time (TI), Expiratory Time (TE) and Integral Amplitude (IA) were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids. [ABSTRACT FROM AUTHOR]

SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor. [ABSTRACT FROM AUTHOR]

Background: In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF), a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. Methods: Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD). Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test). Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. Results: The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1α expression and promoted gastric contractility changes. Conclusions: This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and immune-related gastrointestinal disorders among shift workers. [ABSTRACT FROM AUTHOR]

Background: The arginine vasopressin receptor (AVPR) and oxytocin receptor (OXTR) genes have been demonstrated to contribute to prosocial behavior. Recent research has focused on the manner by which these simple receptor genes influence prosociality, particularly with regard to the AVP system, which is modulated by the clock gene. The clock gene is responsible for regulating the human biological clock, affecting sleep, emotion and behavior. The current study examined in detail whether the influences of the OXTR and AVPR1b genes on prosociality are dependent on the clock gene. Methodology/Principal Findings: This study assessed interactions between the clock gene (rs1801260, rs6832769) and the OXTR (rs1042778, rs237887) and AVPR1b (rs28373064) genes in association with individual differences in prosociality in healthy male Chinese subjects (n = 436). The Prosocial Tendencies Measure (PTM-R) was used to assess prosociality. Participants carrying both the GG/GA variant of AVPR1b rs28373064 and the AA variant of clock rs6832769 showed the highest scores on the Emotional PTM. Carriers of both the T allele of OXTR rs1042778 and the C allele of clock rs1801260 showed the lowest total PTM scores compared with the other groups. Conclusions: The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality. [ABSTRACT FROM AUTHOR]

Circadian rhythms of behavior and physiology are driven by the biological clock that operates endogenously but can also be entrained to the light-dark cycle of the environment. In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN), which is composed of individual cellular oscillators that are driven by a set of core clock genes interacting in transcriptional/translational feedback loops. Light signals can trigger molecular events in the SCN that ultimately impact on the phase of expression of core clock genes to reset the master pacemaker. While transcriptional regulation has received much attention in the field of circadian biology in the past, other mechanisms including targeted protein degradation likely contribute to the clock timing and entrainment process. In the present study, proteome-wide screens of the murine SCN led to the identification of ubiquitin protein ligase E3 component N-recognin 4 (UBR4), a novel E3 ubiquitin ligase component of the N-end rule pathway, as a time-of-day-dependent and light-inducible protein. The spatial and temporal expression pattern of UBR4 in the SCN was subsequently characterized by immunofluorescence microscopy. UBR4 is expressed across the entire rostrocaudal extent of the SCN in a time-of-day-dependent fashion. UBR4 is localized exclusively to arginine vasopressin (AVP)-expressing neurons of the SCN shell. Upon photic stimulation in the early subjective night, the number of UBR4-expressing cells within the SCN increases. This study is the first to identify a novel E3 ubiquitin ligase component, UBR4, in the murine SCN and to implicate the N-end rule degradation pathway as a potential player in regulating core clock mechanisms and photic entrainment. [ABSTRACT FROM AUTHOR]

In the widely used mouse model of retinal degeneration, rd1, the loss of photoreceptors leads to rhythmic electrical activity of around 10–16 Hz in the remaining retinal network. Recent studies suggest that this oscillation is formed within the electrically coupled network of AII amacrine cells and ON-bipolar cells. A second mouse model, rd10, displays a delayed onset and slower progression of degeneration, making this mouse strain a better model for human retinitis pigmentosa. In rd10, oscillations occur at a frequency of 3–7 Hz, raising the question whether oscillations have the same origin in the two mouse models. As rd10 is increasingly being used as a model to develop experimental therapies, it is important to understand the mechanisms underlying the spontaneous rhythmic activity. To study the properties of oscillations in rd10 retina we combined multi electrode recordings with pharmacological manipulation of the retinal network. Oscillations were abolished by blockers for ionotropic glutamate receptors and gap junctions. Frequency and amplitude of oscillations were modulated strongly by blockers of inhibitory receptors and to a lesser extent by blockers of HCN channels. In summary, although we found certain differences in the pharmacological modulation of rhythmic activity in rd10 compared to rd1, the overall pattern looked similar. This suggests that the generation of rhythmic activity may underlie similar mechanisms in rd1 and rd10 retina. [ABSTRACT FROM AUTHOR]

The NEPTUNE cabled observatory network hosts an ecological module called TEMPO-mini that focuses on hydrothermal vent ecology and time series, granting us real-time access to data originating from the deep sea. In 2011–2012, during TEMPO-mini’s first deployment on the NEPTUNE network, the module recorded high-resolution imagery, temperature, iron (Fe) and oxygen on a hydrothermal assemblage at 2186 m depth at Main Endeavour Field (North East Pacific). 23 days of continuous imagery were analysed with an hourly frequency. Community dynamics were analysed in detail for Ridgeia piscesae tubeworms, Polynoidae, Pycnogonida and Buccinidae, documenting faunal variations, natural change and biotic interactions in the filmed tubeworm assemblage as well as links with the local environment. Semi-diurnal and diurnal periods were identified both in fauna and environment, revealing the influence of tidal cycles. Species interactions were described and distribution patterns were indicative of possible microhabitat preference. The importance of high-resolution frequencies (<1 h) to fully comprehend rhythms in fauna and environment was emphasised, as well as the need for the development of automated or semi-automated imagery analysis tools. [ABSTRACT FROM AUTHOR]

Motion of the upper limbs is often coupled to that of the lower limbs in human bipedal locomotion. It is unclear, however, whether the functional coupling between upper and lower limbs is bi-directional, i.e. whether arm movements can affect the lumbosacral locomotor circuitry. Here we tested the effects of voluntary rhythmic arm movements on the lower limbs. Participants lay horizontally on their side with each leg suspended in an unloading exoskeleton. They moved their arms on an overhead treadmill as if they walked on their hands. Hand-walking in the antero-posterior direction resulted in significant locomotor-like movements of the legs in 58% of the participants. We further investigated quantitatively the responses in a subset of the responsive subjects. We found that the electromyographic (EMG) activity of proximal leg muscles was modulated over each cycle with a timing similar to that of normal locomotion. The frequency of kinematic and EMG oscillations in the legs typically differed from that of arm oscillations. The effect of hand-walking was direction specific since medio-lateral arm movements did not evoke appreciably leg air-stepping. Using externally imposed trunk movements and biomechanical modelling, we ruled out that the leg movements associated with hand-walking were mainly due to the mechanical transmission of trunk oscillations. EMG activity in hamstring muscles associated with hand-walking often continued when the leg movements were transiently blocked by the experimenter or following the termination of arm movements. The present results reinforce the idea that there exists a functional neural coupling between arm and legs. [ABSTRACT FROM AUTHOR]

The tuco-tuco Ctenomys aff. knighti is a subterranean rodent which inhabits a semi-arid area in Northwestern Argentina. Although they live in underground burrows where environmental cycles are attenuated, they display robust, 24 h locomotor activity rhythms that are synchronized by light/dark cycles, both in laboratory and field conditions. The underground environment also poses energetic challenges (e.g. high-energy demands of digging, hypoxia, high humidity, low food availability) that have motivated thermoregulation studies in several subterranean rodent species. By using chronobiological protocols, the present work aims to contribute towards these studies by exploring day-night variations of thermoregulatory functions in tuco-tucos, starting with body temperature and its temporal relationship to locomotor activity. Animals showed daily, 24 h body temperature rhythms that persisted even in constant darkness and temperature, synchronizing to a daily light/dark cycle, with highest values occurring during darkness hours. The range of oscillation of body temperature was slightly lower than those reported for similar-sized and dark-active rodents. Most rhythmic parameters, such as period and phase, did not change upon removal of the running wheel. Body temperature and locomotor activity rhythms were robustly associated in time. The former persisted even after removal of the acute effects of intense activity on body temperature by a statistical method. Finally, regression gradients between body temperature and activity were higher in the beginning of the night, suggesting day-night variation in thermal conductance and heat production. Consideration of these day-night variations in thermoregulatory processes is beneficial for further studies on thermoregulation and energetics of subterranean rodents. [ABSTRACT FROM AUTHOR]

Biorhythm is a fundamental property of human physiology. Changes in the extracellular space induced by cell swelling in response to the neural activity enable the in vivo characterization of cerebral microstructure by measuring the water diffusivity using diffusion tensor imaging (DTI). To study the diurnal microstructural alterations of human brain, fifteen right-handed healthy adult subjects were recruited for DTI studies in two repeated sessions (8∶30 AM and 8∶30 PM) within a 24-hour interval. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial (λ//) and radial diffusivity (λ⊥) were compared pixel by pixel between the sessions for each subject. Significant increased morning measurements in FA, ADC, λ// and λ⊥ were seen in a wide range of brain areas involving frontal, parietal, temporal and occipital lobes. Prominent evening dominant λ⊥ (18.58%) was detected in the right inferior temporal and ventral fusiform gyri. AM-PM variation of λ⊥ was substantially left side hemisphere dominant (p<0.05), while no hemispheric preference was observed for the same analysis for ADC (p = 0.77), λ// (p = 0.08) or FA (p = 0.25). The percentage change of ADC, λ//, λ⊥, and FA were 1.59%, 2.15%, 1.20% and 2.84%, respectively, for brain areas without diurnal diffusivity contrast. Microstructural variations may function as the substrates of the phasic neural activities in correspondence to the environment adaptation in a light-dark cycle. This research provided a baseline for researches in neuroscience, sleep medicine, psychological and psychiatric disorders, and necessitates that diurnal effect should be taken into account in following up studies using diffusion tensor quantities. [ABSTRACT FROM AUTHOR]

Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine the impacts of light pollution on nocturnal mammals an experimental study was conducted on a nocturnal primate, the grey mouse lemur Microcebus murinus. Male mouse lemurs (N = 8) were exposed 14 nights to moonlight treatment and then exposed 14 nights to light pollution treatment. For both treatments, chronobiological parameters related to locomotor activity and core temperature were recorded using telemetric transmitters. In addition, at the end of each treatment, the 14th night, nocturnal and feeding behaviors were explored using an infrared camera. Finally, throughout the study, body mass and daily caloric food intake were recorded. For the first time in a nocturnal primate, light pollution was demonstrated to modify daily rhythms of locomotor activity and core temperature especially through phase delays and increases in core temperature. Moreover, nocturnal activity and feeding behaviors patterns were modified negatively. This study suggests that light pollution induces daily desynchronization of biological rhythms and could lead to seasonal desynchronization with potential deleterious consequences for animals in terms of adaptation and anticipation of environmental changes. [ABSTRACT FROM AUTHOR]

The biological clock plays an important role in integrating nutrient and energy metabolism with other cellular processes. Previous studies have demonstrated that core clock genes are rhythmically expressed in peripheral tissues, including the liver, skeletal muscle, pancreatic islets, and white and brown adipose tissues. These peripheral clocks are entrained by physiological cues, thereby aligning the circadian pacemaker to tissue functions. The mechanisms that regulate brown adipose tissue clock in response to physiological signals remain poorly understood. Here we found that the expression of core clock genes is highly responsive to cold exposure in brown fat, but not in white fat. This cold-inducible regulation of the clock network is mediated by adrenergic receptor activation and the transcriptional coactivator PGC-1α. Brown adipocytes in mice lacking a functional clock contain large lipid droplets accompanied by dysregulation of genes involved in lipid metabolism and adaptive thermogenesis. Paradoxically, the “clockless” mice were competent in maintaining core body temperature during cold exposure. These studies elucidated the presence of adrenergic receptor/clock crosstalk that appears to be required for normal thermogenic gene expression in brown fat. [ABSTRACT FROM AUTHOR]

Light influences the daily patterning of behavior by entraining circadian rhythms and through its acute effects on activity levels (masking). Mechanisms of entrainment are quite similar across species, but masking can be very different. Specifically, in diurnal species, light generally increases locomotor activity (positive masking), and in nocturnal ones, it generally suppresses it (negative masking). The intergeniculate leaflet (IGL), a subdivision of the lateral geniculate complex, receives direct retinal input and is reciprocally connected with the primary circadian clock, the suprachiasmatic nucleus (SCN). Here, we evaluated the influence of the IGL on masking and the circadian system in a diurnal rodent, the Nile grass rat (Arvicanthis niloticus), by determining the effects of bilateral IGL lesions on general activity under different lighting conditions. To examine masking responses, light or dark pulses were delivered in the dark or light phase, respectively. Light pulses at Zeitgeber time (ZT) 14 increased activity in control animals but decreased it in animals with IGL lesions. Dark pulses had no effect on controls, but significantly increased activity in lesioned animals at ZT0. Lesions also significantly increased activity, primarily during the dark phase of a 12:12 light/dark cycle, and during the subjective night when animals were kept in constant conditions. Taken together, our results suggest that the IGL plays a vital role in the maintenance of both the species-typical masking responses to light, and the circadian contribution to diurnality in grass rats. [ABSTRACT FROM AUTHOR]

We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent in vitro circadian clock formation assay that recapitulates in vivo circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking Casein Kinase I delta (CKIδ) induced ∼3 hours longer period-length of circadian rhythm than the wild type, which was compatible with recently reported results using CKIδ null mice. In addition, this assay system also revealed that a Casein Kinase 2 alpha subunit (CK2α) homozygous mutant ES cell line developed significantly longer (about 2.5 hours) periods of circadian clock oscillations after in vitro or in vivo differentiation. Moreover, revertant ES cell lines in which mutagenic vector sequences were deleted showed nearly wild type periods after differentiation, indicating that the abnormal circadian period of the mutant ES cell line originated from the mutation in the CK2α gene. Since CK2α deficient mice are embryonic lethal, this in vitro assay system represents the genetic evidence showing an essential role of CK2α in the mammalian circadian clock. This assay was successfully applied for the phenotype analysis of homozygous mutant ES cells, demonstrating that an ES cell-based in vitro assay is available for circadian genetic screening. [ABSTRACT FROM AUTHOR]

Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II). We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice. [ABSTRACT FROM AUTHOR]

Serotonin in blood plasma is primarily synthesized in the duodenum, as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD). Analysis of the duodenum and blood plasma showed that the amount of serotonin in the duodenum varies across the day and that serotonin profiles in blood plasma are also rhythmic in LD, but were not rhythmic in constant darkness. Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function. The diurnal regulation of plasma serotonin may also serve as an additional biochemical signal in the blood encoding time and could be used by target tissues to indicate the status of nutrient absorption. [ABSTRACT FROM AUTHOR]

Fiddler crabs (Uca spp., Decapoda: Ocypodidae) are commonly found forming large aggregations in intertidal zones, where they perform rhythmic waving displays with their greatly enlarged claws. While performing these displays, fiddler crabs often synchronize their behavior with neighboring males, forming the only known synchronized visual courtship displays involving reflected light and moving body parts. Despite being one of the most conspicuous aspects of fiddler crab behavior, little is known about the mechanisms underlying synchronization of male displays. In this study we develop a spatially explicit model of fiddler crab waving displays using coupled logistic map equations. We explored two alternative models in which males either direct their attention at random angles or preferentially toward neighbors. Our results indicate that synchronization is possible over a fairly large region of parameter space. Moreover, our model was capable of generating local synchronization neighborhoods, as commonly observed in fiddler crabs under natural conditions. [ABSTRACT FROM AUTHOR]

Collective rhythmic dynamics from neurons is vital for cognitive functions such as memory formation but how neurons self-organize to produce such activity is not well understood. Attractor-based computational models have been successfully implemented as a theoretical framework for memory storage in networks of neurons. Additionally, activity-dependent modification of synaptic transmission is thought to be the physiological basis of learning and memory. The goal of this study is to demonstrate that using a pharmacological treatment that has been shown to increase synaptic strength within in vitro networks of hippocampal neurons follows the dynamical postulates theorized by attractor models. We use a grid of extracellular electrodes to study changes in network activity after this perturbation and show that there is a persistent increase in overall spiking and bursting activity after treatment. This increase in activity appears to recruit more “errant” spikes into bursts. Phase plots indicate a conserved activity pattern suggesting that a synaptic potentiation perturbation to the attractor leaves it unchanged. Lastly, we construct a computational model to demonstrate that these synaptic perturbations can account for the dynamical changes seen within the network. [ABSTRACT FROM AUTHOR]

In the current event-related potential (ERP) study, we investigated how speech rhythm impacts speech segmentation and facilitates the resolution of syntactic ambiguities in auditory sentence processing. Participants listened to syntactically ambiguous German subject- and object-first sentences that were spoken with either regular or irregular speech rhythm. Rhythmicity was established by a constant metric pattern of three unstressed syllables between two stressed ones that created rhythmic groups of constant size. Accuracy rates in a comprehension task revealed that participants understood rhythmically regular sentences better than rhythmically irregular ones. Furthermore, the mean amplitude of the P600 component was reduced in response to object-first sentences only when embedded in rhythmically regular but not rhythmically irregular context. This P600 reduction indicates facilitated processing of sentence structure possibly due to a decrease in processing costs for the less-preferred structure (object-first). Our data suggest an early and continuous use of rhythm by the syntactic parser and support language processing models assuming an interactive and incremental use of linguistic information during language processing. [ABSTRACT FROM AUTHOR]

Period1 (PER1) is an important core clock gene, which regulates normal cell proliferations and physiological rhythms of human beings. Recent studies have showed aberrant expressions and altered rhythms of PER1 were highly correlated to the carcinogenesis and development of malignant tumors. However, there is no study on the correlation of aberrant expressions and altered rhythms of PER1 with the growth, proliferation and metastasis of buccal squamous cell carcinoma (BSCC). In this study, PER1 and MMP-2 expression in the cancerous and adjacent noncancerous tissues of 38 patients with BSCC and its correlations with patients' clinical pathologic characteristics were investigated. A mouse model of BSCC was also established and mice were sacrificed at 4 different time points in a period of 24 hours. Xenografted tumor weight, proliferation index (PI), and mitotic index (MI) of tumors in the 4 time groups were detected. Results showed that PER1 expression was significantly down-regulated in cancerous tissues of patients with BSCC (P<0.05). PER1 expression was significantly down-regulated in patients of T3∼T4 staging and those with lymph node metastasis compared to that of T1∼T2 staging and those without lymph node metastasis (P<0.05), respectively. PER1 mRNA expression, MI and tumor weight had significant differences among the 4 time groups, which PI all confirmed to circadian rhythms. MI, PI, MMP-2 mRNA and tumor weight had negative correlation with PER1 mRNA expression. Peak value of PER1 mRNA expression and trough values of MI, PI and tumor weight all appeared in middle activity phase, whereas trough value of PER1 mRNA expression and peak values of MI, PI and tumor weight all occurred in middle rest phase. Our study suggested that aberrant expression of PER1 had significant correlation with the growth, proliferation and metastasis of BSCC and it might act as an anti-oncogene. [ABSTRACT FROM AUTHOR]

Psychological stressors prominently affect diurnal rhythms, including locomotor activity, sleep, blood pressure, and body temperature, in humans. Here, we found that a novel continuous stress imposed by the perpetual avoidance of water on a wheel (PAWW) affected several physiological diurnal rhythms in mice. One week of PAWW stress decayed robust circadian locomotor rhythmicity, while locomotor activity was evident even during the light period when the mice are normally asleep. Daytime activity was significantly upregulated, whereas nighttime activity was downregulated, resulting in a low amplitude of activity. Total daily activity gradually decreased with increasing exposure to PAWW stress. The mice could be exposed to PAWW stress for over 3 weeks without adaptation. Furthermore, continuous PAWW stress enhanced food intake, but decreased body weight and plasma leptin levels, indicating that sleep loss and PAWW stress altered the energy balance in these mice. The diurnal rhythm of corticosterone levels was not severely affected. The body temperature rhythm was diurnal in the stressed mice, but significantly dysregulated during the dark period. Plasma catecholamines were elevated in the stressed mice. Continuous PAWW stress reduced the duration of daytime sleep, especially during the first half of the light period, and increased nighttime sleepiness. Continuous PAWW stress also simultaneously obscured sleep/wake and locomotor activity rhythms compared with control mice. These sleep architecture phenotypes under stress are similar to those of patients with insomnia. The stressed mice could be entrained to the light/dark cycle, and when they were transferred to constant darkness, they exhibited a free-running circadian rhythm with a timing of activity onset predicted by the phase of their entrained rhythms. Circadian gene expression in the liver and muscle was unaltered, indicating that the peripheral clocks in these tissues remained intact. [ABSTRACT FROM AUTHOR]