PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, filterJournals=PLoSONE, q=subject:"Chronobiology"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&unformattedQuery=subject:%22Chronobiology%22&sort=Date,+newest+first&filterJournals=PLoSONEAll PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-29T05:10:16ZIntrauterine and early-life malnutrition in rats disrupts the circadian rhythm programming of energy metabolites through adulthoodDulce Jocelyn Bustamante-ValdezMartin Alejandro Fuentes-CanoJesus Salvador Gonzalez-RuanoAlonso Martinez-CanabalRene Cardenas-VazquezPilar Duran10.1371/journal.pone.02995542024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Dulce Jocelyn Bustamante-Valdez, Martin Alejandro Fuentes-Cano, Jesus Salvador Gonzalez-Ruano, Alonso Martinez-Canabal, Rene Cardenas-Vazquez, Pilar Duran</p>
Maternal malnutrition plays a crucial role in functional development, resulting in behavioral, cognitive, and metabolic abnormalities and disturbances. “Cafeteria diet” has been linked to obesity, metabolic syndrome, diabetes, and other metabolic disruptions in the mammalian lifespan. However, there are very few reports about the effect of intrauterine and early postnatal malnutrition on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental for correct interaction with the environment and physiological regulation. Exposure to malnutrition during development imprints metabolic programming throughout life on the central nervous system and peripheral systems. Lifespan studies exploring the effect of high fat/low protein diet administered during critical periods of development are scarce. The present study explored the effect of intrauterine and perinatal malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators controlling glucose, insulin, and triglycerides in rats at 40 and 90 days of age. We evaluated plasma glucose and triglyceride levels in 6 Zeitgeber times, in addition to an intraperitoneal glucose tolerance test (IpTGT) and homeostasis model assessment of insulin resistance (HOMA-IR) at two time-points over 24h. Our results show that offspring of malnourished dams fed cafeteria diet present alterations in circadian rhythmicity of glucose and triglycerides associated with a change in glucose tolerance and insulin sensibility differentially regulated at the development stage and time of day. Intrauterine and early malnutrition due to a cafeteria diet produces maladaptive responses and programs energetic metabolism at several developmental stages during the lifespan.Moonlight-driven biological choruses in Hawaiian coral reefsDaniel DuaneSimon FreemanLauren Freeman10.1371/journal.pone.02999162024-03-20T14:00:00Z2024-03-20T14:00:00Z<p>by Daniel Duane, Simon Freeman, Lauren Freeman</p>
Sounds from fish and invertebrates in coral reefs can create persistent cacophonies that can be recorded for ecosystem monitoring, including during nighttime hours where visual surveys are typically not feasible. Here we use soundscape measurements in Hawaii to demonstrate that multiple coral reef communities are rapidly responsive to shifts in nighttime ambient light, with sustained changes in biological sound between moonrise and moonset. High frequency pulse train sounds from fish (0.5-1.5 kHz) are found to increase during moonlight hours, while low frequency fish vocalizations (0.1-0.3 kHz) and invertebrate sounds (2-20 kHz) are found to decrease during moonlight hours. These discoveries suggest that the rising and setting of the moon triggers regular shifts in coral reef ecosystem interactions. Future acoustic monitoring of reef health may be improved by comparing soundscapes during moonlight and non-moonlight hours, which may provide early indicators of shifts in the relative abundance of separate reef communities.Moonless night sky increases <i>Isistius</i> species (cookiecutter shark) and live human contactSteven MinagliaMelodee Liegl10.1371/journal.pone.02918522024-02-21T14:00:00Z2024-02-21T14:00:00Z<p>by Steven Minaglia, Melodee Liegl</p>
The nocturnal feeding behavior and zoogeographical habitat of cookiecutter sharks <i>Isistius brasiliensis</i> and <i>Isistius plutodus</i> (<i>Isistius spp</i>.) greatly reduces interaction of this species with live humans. Attacks on live humans are exceedingly rare with 7 cases reported worldwide, 6 of them in Hawaiʻi, and 5 of these occuring among channel swimmers. Published research suggests that periods of bright moonlight may increase <i>Isistius spp</i>. contact with live humans and does not otherwise identify significant trends or risk factors. Yet 5 of the 6 <i>Isistius spp</i>. bites on live humans in Hawaiʻian waters occurred with the moon set and after nautical twilight end and before nautical twilight start. From 1961–2023 in Hawaiʻi, 129 successful solo channel crosses and 5 <i>Isistius spp</i>. related injuries in the habitat of cookiecutter sharks were analyzed across two groups: one where both the moon and sun were set (dark group) and one where the moon and/or sun was in the sky (light group). There was a significant difference for swimmers bitten by <i>Isistius spp</i>. in the dark 4 (12%) versus light groups 1 (1%), p = 0.012, RR 12.6 (95% confidence interval: 1.5–108.9). Swim start time and year was also significant (Pearson correlation 0.566, p <0.001). Swimmer gender and use of shark deterrent devices and artificial illumination were not significant. The growing popularity of channel swimming in Hawaiʻi and swim start times have contributed to an increasing likelihood of live human and <i>Isistius spp</i>. contact and a moonless night sky is a significant risk factor for this interaction.Survival of hibernating little brown bats that are unaffected by white-nose syndrome: Using thermal cameras to understand arousal behaviorHaley J. GmutzaRodney W. FosterJonathan M. GmutzaGerald G. CarterAllen Kurta10.1371/journal.pone.02978712024-02-06T14:00:00Z2024-02-06T14:00:00Z<p>by Haley J. Gmutza, Rodney W. Foster, Jonathan M. Gmutza, Gerald G. Carter, Allen Kurta</p>
White-nose syndrome is a fungal disease that has decimated hibernating bats from multiple North American species. In 2014, the invasive fungus arrived at a hibernaculum of little brown bats (<i>Myotis lucifugus</i>) inside the spillway of Tippy Dam, located near Wellston, Michigan, USA, yet surprisingly, this population has not experienced the declines seen elsewhere. Unlike a typical subterranean hibernaculum, light enters the spillway through small ventilation holes. We hypothesized that this light causes the hibernating bats to maintain a circadian rhythm, thereby saving energy via social thermoregulation during synchronous arousals. To test this idea, we used high-resolution thermal cameras to monitor arousals from October 2019 to April 2020. We found that arousals followed a circadian rhythm, peaking after sunset, and that most observed arousals (>68%) occurred within a cluster of bats allowing for social thermoregulation. These findings are consistent with the hypothesis that light-induced synchronized arousals contribute to the unprecedented absence of mass mortality from white-nose syndrome in this large population. Using light to maintain a circadian rhythm in bats should be tested as a potential tool for mitigating mortality from white-nose syndrome. More generally, studying populations that have been largely unaffected by white-nose syndrome may provide insight into mitigation strategies for protecting the remaining populations.Road extraction through Yangwang-1 nighttime light data: A case study in Wenzhou, ChinaAnfeng ZhuJun HaoXu GangHao ZhangXiaoyu LongLuyao Wang10.1371/journal.pone.02971522024-01-19T14:00:00Z2024-01-19T14:00:00Z<p>by Anfeng Zhu, Jun Hao, Xu Gang, Hao Zhang, Xiaoyu Long, Luyao Wang</p>
The extraction of roadways from remote sensing imagery constitutes a pivotal task, with far-reaching implications across diverse domains such as urban planning, management of transportation systems, emergency response initiatives, and environmental monitoring endeavors. Satellite images captured during daytime have customarily served as the primary resource for this extraction process. However, the emergence of Nighttime Light (NTL) remote sensing data introduces an innovative dimension to this arena. The exploration of NTL data for road extraction remains in its nascent stage, and this study seeks to bridge this gap. We present a refined U-Net model (CA U-Net) integrated with Cross-Attention Mechanisms, meticulously designed to extract roads from Yangwang-1 NTL images. This model incorporates several enhancements, thereby improving its proficiency in identifying and delineating road networks. Through extensive experimentation conducted in the urban landscape of Wenzhou City, the model delivers highly accurate results, achieving an F1 score of 84.46%. These outcomes significantly surpass the performance benchmarks set by Support Vector Machines (SVM) and the Optimal Threshold (OT) method. This promising development paves the way towards maximizing the utility of NTL data for comprehensive mapping and analysis of road networks. Furthermore, the findings underscore the potential of utilizing Yangwang-1 data as a reliable source for road extraction and reaffirm the viability of deploying deep learning frameworks for road extraction tasks utilizing NTL data.Does darkness increase the risk of certain types of crime? A registered report protocolJim UttleyRosie CanwellJamie SmithSarah FalconerYichong MaoSteve A. Fotios10.1371/journal.pone.02919712024-01-19T14:00:00Z2024-01-19T14:00:00Z<p>by Jim Uttley, Rosie Canwell, Jamie Smith, Sarah Falconer, Yichong Mao, Steve A. Fotios</p>
Evidence about the relationship between lighting and crime is mixed. Although a review of evidence found that improved road / street lighting was associated with reductions in crime, these reductions occurred in daylight as well as after dark, suggesting any effect was not due only to changes in visual conditions. One limitation of previous studies is that crime data are reported in aggregate and thus previous analyses were required to make simplifications concerning types of crimes or locations. We will overcome that by working with a UK police force to access records of individual crimes. We will use these data to determine whether the risk of crime at a specific time of day is greater after dark than during daylight. If no difference is found, this would suggest improvements to visual conditions after dark through lighting would have no effect. If however the risk of crime occurring after dark was greater than during daylight, quantifying this effect would provide a measure to assess the potential effectiveness of lighting in reducing crime risk after dark. We will use a case and control approach to analyse ten years of crime data. We will compare counts of crimes in ‘case’ hours, that are in daylight and darkness at different times of the year, and ‘control’ hours, that are in daylight throughout the year. From these counts we will calculate odds ratios as a measure of the effect of darkness on risk of crime, using these to answer three questions: 1) Is the risk of overall crime occurring greater after dark than during daylight? 2) Does the risk of crime occurring after dark vary depending on the category of crime? 3) Does the risk of crime occurring after dark vary depending on the geographical area?LimoRhyde2: Genomic analysis of biological rhythms based on effect sizesDora ObodoElliot H. OutlandJacob J. Hughey10.1371/journal.pone.02920892023-12-14T14:00:00Z2023-12-14T14:00:00Z<p>by Dora Obodo, Elliot H. Outland, Jacob J. Hughey</p>
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.Investigating automated regression models for estimating left ventricular ejection fraction levels in heart failure patients using circadian ECG featuresSona M. Al YounisLeontios J. HadjileontiadisAamna M. Al ShehhiCesare StefaniniMohanad AlkhodariStergios SoulaidopoulosPetros ArsenosIoannis DoundoulakisKonstantinos A. GatzoulisKonstantinos TsioufisAhsan H. Khandoker10.1371/journal.pone.02956532023-12-11T14:00:00Z2023-12-11T14:00:00Z<p>by Sona M. Al Younis, Leontios J. Hadjileontiadis, Aamna M. Al Shehhi, Cesare Stefanini, Mohanad Alkhodari, Stergios Soulaidopoulos, Petros Arsenos, Ioannis Doundoulakis, Konstantinos A. Gatzoulis, Konstantinos Tsioufis, Ahsan H. Khandoker</p>
Heart Failure (HF) significantly impacts approximately 26 million people worldwide, causing disruptions in the normal functioning of their hearts. The estimation of left ventricular ejection fraction (LVEF) plays a crucial role in the diagnosis, risk stratification, treatment selection, and monitoring of heart failure. However, achieving a definitive assessment is challenging, necessitating the use of echocardiography. Electrocardiogram (ECG) is a relatively simple, quick to obtain, provides continuous monitoring of patient’s cardiac rhythm, and cost-effective procedure compared to echocardiography. In this study, we compare several regression models (support vector machine (SVM), extreme gradient boosting (XGBOOST), gaussian process regression (GPR) and decision tree) for the estimation of LVEF for three groups of HF patients at hourly intervals using 24-hour ECG recordings. Data from 303 HF patients with preserved, mid-range, or reduced LVEF were obtained from a multicentre cohort (American and Greek). ECG extracted features were used to train the different regression models in one-hour intervals. To enhance the best possible LVEF level estimations, hyperparameters tuning in nested loop approach was implemented (the outer loop divides the data into training and testing sets, while the inner loop further divides the training set into smaller sets for cross-validation). LVEF levels were best estimated using rational quadratic GPR and fine decision tree regression models with an average root mean square error (RMSE) of 3.83% and 3.42%, and correlation coefficients of 0.92 (p<0.01) and 0.91 (p<0.01), respectively. Furthermore, according to the experimental findings, the time periods of midnight-1 am, 8–9 am, and 10–11 pm demonstrated to be the lowest RMSE values between the actual and predicted LVEF levels. The findings could potentially lead to the development of an automated screening system for patients with coronary artery disease (CAD) by using the best measurement timings during their circadian cycles.Density and population size estimates of the endangered northern yellow-cheeked crested gibbon <i>Nomascus annamensis</i> in selectively logged Veun Sai-Siem Pang National Park in Cambodia using acoustic spatial capture-recapture methodsSarah J. McGrathJing LiuBen C. StevensonAlison M. Behie10.1371/journal.pone.02923862023-11-27T14:00:00Z2023-11-27T14:00:00Z<p>by Sarah J. McGrath, Jing Liu, Ben C. Stevenson, Alison M. Behie</p>
Many gibbon species are threatened with extinction, including the endangered northern yellow-cheeked crested gibbon, <i>Nomascus annamensis</i>. Assessing gibbon populations and understanding how human disturbances and environmental factors impact these populations is vital for effective conservation planning. In 2010, auditory surveys revealed that Veun Sai-Siem Pang National Park (VSSP) in Cambodia contains one of the largest known <i>N</i>. <i>annamensis</i> populations in the world, with an estimated 456 (95% CI 421–490) gibbon groups. Illegal selective logging is common in the park, but the impact of continued logging on the gibbon population has not been investigated. To determine any change in the <i>N</i>. <i>annamensis</i> population since 2010, between January and April 2019 we conducted auditory surveys at 13 sites that were at least 4 km apart. We surveyed each site for three days, each day recording the gibbon calls heard over 3.25 hours from three listening posts located 500 m apart. At the same sites, we assessed the logging intensity using transects and ecological plots. Gibbon densities can be influenced by various environmental factors such as canopy height and forest type. Therefore, in addition to investigating the relationship between the density of <i>N</i>. <i>annamensis</i> groups and logging, we included five additional environmental variables in our acoustic spatial capture-recapture models. Our best fit model with the lowest AIC value included canopy height, forest type, distance to villages, and logging. We estimate that there are 389 (95% CI 284–542) <i>N</i>. <i>annamensis</i> groups currently in VSSP. Selective logging is widespread in the park, primarily targeting four tree species. The estimated felling time of these logged trees, together with previous reports, indicate that the species most targeted in VSSP varies over time. To conserve the <i>N</i>. <i>annamensis</i> population in VSSP, it is crucial that action is taken to reduce illegal logging.Manatees display diel trends in acoustic activity at two microhabitats in BelizeBeth BradyCarly SarbackerJake Andrew LasalaMaria Maust-MohlKristi Ashley CollomLinda SearleLaura J. May-ColladoEric Angel Ramos10.1371/journal.pone.02946002023-11-17T14:00:00Z2023-11-17T14:00:00Z<p>by Beth Brady, Carly Sarbacker, Jake Andrew Lasala, Maria Maust-Mohl, Kristi Ashley Collom, Linda Searle, Laura J. May-Collado, Eric Angel Ramos</p>
Many marine mammals exhibit diel trends in vocal production, which can provide information on habitat use and behavioral activity. In Belize, Antillean manatees (<i>Trichechus manatus manatus</i>) commonly inhabit small depressions in the substrate or deep-water coves known as “resting holes”. Determining if manatees exhibit diel temporal trends in their call production rate and call types between microhabitats can provide insights into their diurnal and nocturnal activity patterns. Here, we investigate the diel vocalization patterns of wild Antillean manatees in two adjacent resting holes off of St. George’s Caye, Belize. Recordings of manatees were made using a bottom-mounted hydrophone located near a reef barrier reef for nine days in July of 2017 and ten days in January of 2018. To explore if and how manatee acoustic activity differs between sites, we compared the number of calls per hour, the number of manatee positive hours, the number of tonal and atonal sounds, and the number of boats detected across sites. A total of 370 hours of acoustic recordings were analyzed resulting in the detection of 3,262 calls. There were no significant differences in the number of manatee calls produced per hour between sites. The average number of calls produced by manatees decreased over the course of several days. The proportion of tonal calls decreased with hours after sunset and increased in boat presence. These results suggest manatees in this region may exhibit different diel activity patterns which appear to be influenced by the characteristics of the environment. These findings can support ongoing conservation and management efforts to safeguard species in Belize.Associations between sleep habits, quality, chronotype and depression in a large cross-sectional sample of Swedish adolescentsTheresa LemkeSebastian HökbyDanuta WassermanVladimir CarliGergö Hadlaczky10.1371/journal.pone.02935802023-11-02T14:00:00Z2023-11-02T14:00:00Z<p>by Theresa Lemke, Sebastian Hökby, Danuta Wasserman, Vladimir Carli, Gergö Hadlaczky</p>
Objective <p>To investigate behavioral sleep habits, self-perceived quality of sleep, and chronotype, and to examine their association with clinically relevant levels of depression in Swedish adolescents.</p> Method <p>Questionnaire data were obtained from a representative sample of Swedish adolescents (n = 8449; 50.8% girls; aged 12–16). Depression was defined as >13 BDI-II scores. Logistic regression modelling estimated the effects of sleep duration, sleep quality, and chronotype on depression, adjusted for socio-demographic factors.</p> Results <p>On weekdays, approximately 46% of adolescents slept less than the recommended length of eight hours per night (depressed: 68%, non-depressed: 40%). On weekends, however, only 17% slept shorter than recommended. Short weekday sleep duration was more common among girls than boys (53% vs. 38%) and girls reported worse sleep quality. The regression model showed that depression was predicted by weekday sleep duration (OR = 0.773, p < .0001), sleep quality (OR = 0.327, p < .0001), and late chronotype (OR = 1.126, p = .0017), but not by weekend sleep duration. A 30-minute increase in weekday sleep duration was associated with about 10% lower odds of depression.</p> Conclusions <p>A substantial proportion of Swedish adolescents do not seem to meet the sleep recommendations of eight hours per night. Short sleep duration on weekdays, poor sleep quality, and late chronotype were associated with increased risk of depression. Interventions promoting longer weekday sleep duration (e.g., later school start times) seem relevant in this context, but further research is needed to investigate the directionality and underlying mechanisms of these associations.</p>Sex and age-dependent characterization of the circadian clock as a potential biomarker for physical performance: A prospective study protocolMüge YalçinAngela Relógio10.1371/journal.pone.02932262023-10-24T14:00:00Z2023-10-24T14:00:00Z<p>by Müge Yalçin, Angela Relógio</p>
Introduction <p>Circadian rhythms (CR) regulate daily cycles in behavior, physiology and molecular processes. CRs are endogenous and vary across individuals. Seasonal changes can influence CR. Accordingly, rhythms with different characteristics (amplitude, phase) are depicted during the summer months, as compared to winter. Increasing evidence points to an influence of circadian regulation on physical performance. Here, we aim to obtain a comprehensive circadian gene expression profile for physically active individuals, which can potentially be used for the identification of optimal time intervals for physical exercise.</p> Methods and analysis <p>To explore these different aspects, we propose a study where we will carry out a molecular analysis of CR by measuring the expression of specific clock and clock-controlled genes, based on a non-invasive approach using RNA extracted from saliva in physically active, healthy participants. We will collect data across two seasons and use computational algorithms to integrate the molecular data with hormonal data (cortisol and melatonin), and generate a profile of CR in healthy individuals of different sex and age groups. Finally, we will use computational tools to predict optimal time intervals for physical performance based on the above-described data, thereby retrieving valuable data on the circadian clock as a key factor for health maintenance and optimization.</p>Light and dark cycles modify the expression of clock genes in the ovaries of <i>Aedes aegypti</i> in a noncircadian mannerLeo Nava Piorsky Dominici CruzRayane Teles-de-FreitasMaria Eduarda Barreto ResckAndresa Borges de Araujo FonsecaKarine Pedreira PadilhaLuana Cristina FarnesiLuciana Ordunha AraripeRafaela Vieira Bruno10.1371/journal.pone.02872372023-10-19T14:00:00Z2023-10-19T14:00:00Z<p>by Leo Nava Piorsky Dominici Cruz, Rayane Teles-de-Freitas, Maria Eduarda Barreto Resck, Andresa Borges de Araujo Fonseca, Karine Pedreira Padilha, Luana Cristina Farnesi, Luciana Ordunha Araripe, Rafaela Vieira Bruno</p>
Circadian oscillators (<i>i</i>.<i>e</i>., circadian clocks) are essential to producing the circadian rhythms observed in virtually all multicellular organisms. In arthropods, many rhythmic behaviors are generated by oscillations of the central pacemaker, specific groups of neurons of the protocerebrum in which the circadian oscillator molecular machinery is expressed and works; however, oscillators located in other tissues (<i>i</i>.<i>e</i>., peripheral clocks) could also contribute to certain rhythms, but are not well known in non-model organisms. Here, we investigated whether eight clock genes that likely constitute the <i>Aedes aegypti</i> clock are expressed in a circadian manner in the previtellogenic ovaries of this mosquito. Also, we asked if insemination by conspecific males would alter the expression profiles of these clock genes. We observed that the clock genes do not have a rhythmic expression profile in the ovaries of virgin (VF) or inseminated (IF) females, except for <i>period</i>, which showed a rhythmic expression profile in ovaries of IF kept in light and dark (LD) cycles, but not in constant darkness (DD). The mean expression of seven clock genes was affected by the insemination status (VF or IF) or the light condition (LD 12:12 or DD), among which five were affected solely by the light condition, one solely by the insemination status, and one by both factors. Our results suggest that a functional circadian clock is absent in the ovaries of <i>A</i>. <i>aegypti</i>. Still, their differential mean expression promoted by light conditions or insemination suggests roles other than circadian rhythms in this mosquito’s ovaries.Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulationRoman MoravčíkSoňa OlejárováJana ZlackáIveta Herichová10.1371/journal.pone.02928802023-10-13T14:00:00Z2023-10-13T14:00:00Z<p>by Roman Moravčík, Soňa Olejárová, Jana Zlacká, Iveta Herichová</p>
The small non-coding RNA miR-34a is a p53-regulated miRNA that acts as a tumour suppressor of colorectal cancer (CRC). Oncogenesis is also negatively influenced by deregulation of the circadian system in many types of tumours with various genetic backgrounds. As the clock gene <i>per2</i> was recently recognized as one of the target genes of miR-34a, we focused on the miR-34a-mediated influence on the circadian oscillator in CRC cell lines DLD1 and LoVo, which differ in their p53 status. Previously, a sex-dependent association between the expression of <i>per2</i> and that of miR-34a was demonstrated in CRC patients. Therefore, we also investigated the effect of 17β-estradiol (E2) on miR-34a oncostatic functions. miR-34a mimic caused a pronounced inhibition of <i>per2</i> expression in both cell lines. Moreover, miR-34a mimic significantly inhibited <i>bmal1</i> expression in LoVo and <i>rev-erbα</i> expression in DLD1 cells and induced <i>clock</i> gene expression in both cell lines. miR-34a mimic caused a pronounced decrease in <i>sirt1</i> and <i>cyclin D1</i> expression, which may be related to the inhibition of proliferation observed after mir-34a administration in DLD1 cells. E2 administration inhibited the migration and proliferation of DLD1 cells. E2 and miR-34a, when administered simultaneously, did not potentiate each other’s effects. To conclude, miR-34a strongly influences the expression of components of the circadian oscillator without respect to p53 status and exerts its oncostatic effects via inhibition of <i>sirt1</i> and <i>cyclin D1</i> mRNA expression. E2 administration inhibits the growth of DLD1 cells; however, this effect seems to be independent of miR-34a-mediated action. With respect to the possible use of miR-34a in cancer treatment, clock genes can be considered as off-target genes, as changes in their expression induced by miR-34a treatment do not contribute to the oncostatic functions of miR-34a. Possible ambiguous oncogenic characteristics should be taken into consideration in future clinical studies focused on miR-34a.Blue light exposure-dependent improvement in robustness of circadian rest-activity rhythm in aged ratsEryck Holmes A. SilvaNelyane Nayara M. SantanaNarita Renata M. SeixasLyzandro Lucas F. BezerraMaria Milena O. SilvaSâmarah F. SantosJeferson S. CavalcanteMário A. Leocadio-MiguelRovena Clara Engelberth10.1371/journal.pone.02923422023-10-04T14:00:00Z2023-10-04T14:00:00Z<p>by Eryck Holmes A. Silva, Nelyane Nayara M. Santana, Narita Renata M. Seixas, Lyzandro Lucas F. Bezerra, Maria Milena O. Silva, Sâmarah F. Santos, Jeferson S. Cavalcante, Mário A. Leocadio-Miguel, Rovena Clara Engelberth</p>
The aging effects on circadian rhythms have diverse implications including changes in the pattern of rhythmic expressions, such as a wide fragmentation of the rhythm of rest-activity and decrease in amplitude of activity regulated by the suprachiasmatic nucleus (SCN). The study of blue light on biological aspects has received great current interest due, among some aspects, to its positive effects on psychiatric disorders in humans. This study aims to evaluate the effect of blue light therapy on the SCN functional aspects, through the evaluation of the rest-activity rhythm, in aging rats. For this, 33 sixteen-months-old male Wistar rats underwent continuous records of locomotor activity and were exposed to periods of 6 hours of blue light during the first half of the light phase (Zeitgeber times 0–6) for 14 days. After this, the rats were maintained at 12h:12h light:dark cycle to check the long-term effect of blue light for 14 days. Blue light repeated exposure showed positive effects on the rhythmic variables of locomotor activity in aged rats, particularly the increase in amplitude, elevation of rhythmic robustness, phase advance in acrophase, and greater consolidation of the resting phase. This effect depends on the presence of daily blue light exposure. In conclusion, our results indicate that blue light is a reliable therapy to reduce circadian dysfunctions in aged rats, but other studies assessing how blue light modulates the neural components to modulate this response are still needed.