bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of nontarget prey, Tetranychus truncatus, affected the predation by Neoseiulus bicaudus on Tetranychus turkestani
Authors: Hu Hengxiao , Tang Siqiong , Fang Chen , Mu Kaiqin , Su Jie , Zhang Jianping
Published: May 2023

Neoseiulus bicaudus (Wainstein) (Acari: Phytoseiidae) is a generalist predatory mite that consumes several pest species, including Tetranychus turkestani (Ugarov et Nikolskii) (Acari: Tetranychidae) in the Xinjiang Uygur Autonomous Region. The release numbers of predatory mites are based on the populations of target pests and their ability to control them. Populations of T. turkestani and T. truncatus Ehara (Acari: Tetranychidae) often coexist and damage many crops. To determine whether the presence of the non-target prey T. truncatus affects the ability of N. bicaudus to control the target prey T. turkestani. The study evaluated the predation rate and functional response of N. bicaudus to 4 stages of T. turkestani in the presence of T. truncatus. The consumption of T. turkestani by N. bicaudus gradually decreased as the proportion of T. truncatus increased. The functional response of N. bicaudus to T. turkestani was not changed when T. truncatus was presented, which was consistent with a type II response. The attack rate of N. bicaudus on the egg, larva, and nymph of T. turkestani was significantly decreased and the handling time of N. bicaudus on T. turkestani was significantly extended when T. truncatus was presented. The preference index showed that the preference of N. bicaudus for eggs and female adults of T. turkestani decreased with increasing density of T. turkestani in the same proportion as T. truncatus. The presence of T. truncatus can negatively affect the predation of T. turkestani by N. bicaudus. We suggest that the number of N. bicaudus released to control T. turkestani should be increased when T. truncatus coexist.
Seasonal patterns of beneficial phytochemical availability in honey and stored pollen from honey bee colonies in large apiaries
Authors: Bernklau Elisa , Arathi H S
Published: May 2023

Honey bees (Apis mellifera L.; Hymenoptera, Apidae) are the most efficient pollinators in agroecosystems, responsible for the successful production of fruits, nuts, and vegetables, but they continue to face debilitating challenges. One of the major factors leading to these challenges could be linked to poor nutrition that results in weakening the colony, increasing susceptibility to pests and pathogens, and reducing the ability of bees to adapt to other abiotic stresses. Extensively used for commercial pollination, honey bee colonies regularly face exposure to limited diversity in their pollen diet as they are placed in flowering monocrops. Lack of access to diverse plant species compromises the availability of plant secondary compounds (phytochemicals), which, in small amounts, provide significant benefits to honey bee health. We analyzed the beneficial phytochemical content of honey and stored pollen (bee bread) samples from colonies in large apiaries through the active bee season. Samples were evaluated for 4 beneficial phytochemicals (caffeine, kaempferol, gallic acid, and p-coumaric acid), which have previously been shown to improve honey bee health. Our results, as relevant to the apiary locations in the study, indicated that p-coumaric acid is uniformly available throughout the season. Caffeine is completely absent, and gallic acid and kaempferol are not regularly available. Our results suggest the need to explore the potential to deliver beneficial phytochemicals as nutritional supplements to improve bee health. It may be vital for the pollination industry to consider such targeted dietary supplementation as beekeepers strive to meet the increasing demand for crop pollination services.
Thulium laser vaporesection of prostates with volume exceeding 100 cm3 as an alternative to HoLEP and ThuLEP
Authors: Paesano Nahuel , Castañeda Gonzalo , Maccagno Alicia , Caldas Paulo , Chechile Gilberto
Published: May 2023

The aim of this study is to evaluate the outcomes of thulium laser vaporesection of prostates with volume exceeding 100 cm3. In the present prospective study, patients with infra-vesical urinary obstruction due to a prostate with volume exceeding 100 cm3 underwent endoscopic vaporesection using thulium laser. In this procedure, prostate chips were resected without morcellation. The technical aspects of surgery, admission time, post-operative catheter time and post-operative complications were analyzed. Flowmetry was performed combined with prostatic ultrasound in the follow-up. Between March 2010 and November 2018, 156 cases with benign prostatic hyperplasia (BPH; volume >100 cm3) were treated. The mean patient age was 67.8 years (48.4–86.6 years), and the mean prostatic volume was 137 cm3 (100–436 cm3). The mean length of hospitalization was 1.48 days (1–8 days), and the mean post-operative catheter time was 5.1 (1–17). Three cases (1.9%) required readmission due to hematuria. The mean follow-up time was 31.2 months (standard deviation = 27.7). Urethral stricture was observed in 14 cases (9%), with bulbar urethra being the most frequent finding. Urinary tract infection was observed in 11 cases (7.1%), and urinary incontinence was observed in 5 cases. The mean peak urinary flow at 12 and 24 months was 26.9 ± 12.5 and 23.9 ± 11.7 ml/s, respectively, and the mean urinary flow during the final follow-up at 41 months was 21.6 ml/s. Thulium laser vaporesection is a valid alternative to open prostatectomy, HoLEP and ThuLEP in patients with large BPH. Urinary flow remained elevated throughout the follow-up.
Non-specific LIPID TRANSFER PROTEIN 1 enhances immunity against tobacco mosaic virus in Nicotiana benthamiana
Authors: Zhu Feng , Cao Meng-Yao , Zhu Peng-Xiang , Zhang Qi-Ping , Lam Hon-Ming
Published: May 2023

Plant non-specific lipid transfer proteins (nsLTPs) are small, cysteine-rich proteins that play significant roles in biotic and abiotic stress responses; however, the molecular mechanism of their functions against viral infections remains unclear. In this study, we employed virus-induced gene-silencing and transgenic overexpression to functionally analyse a type-I nsLTP in Nicotiana benthamiana, NbLTP1, in the immunity response against tobacco mosaic virus (TMV). NbLTP1 was inducible by TMV infection, and its silencing increased TMV-induced oxidative damage and the production of reactive oxygen species (ROS), compromised local and systemic resistance to TMV, and inactivated the biosynthesis of salicylic acid (SA) and its downstream signaling pathway. The effects of NbLTP1-silencing were partially restored by application of exogenous SA. Overexpressing NbLTP1 activated genes related to ROS scavenging to increase cell membrane stability and maintain redox homeostasis, confirming that an early ROS burst followed by ROS suppression at the later phases of pathogenesis is essential for resistance to TMV infection. The cell-wall localization of NbLTP1 was beneficial to viral resistance. Overall, our results showed that NbLTP1 positively regulates plant immunity against viral infection through up-regulating SA biosynthesis and its downstream signaling component, NONEXPRESSOR OF PATHOGENESIS-RELATED 1 (NPR1), which in turn activates pathogenesis-related genes, and by suppressing ROS accumulation at the later phases of viral pathogenesis.
Whole-exome sequencing reveals a likely pathogenic LMNA variant causing hypertrophic cardiomyopathy
Authors: Mahdavi Mohammad , Mohsen-Pour Neda , Maleki Majid , Ghasemi Serwa , Tabib Avisa , Houshmand Golnaz , Naderi Niloofar , Masoumi Tannaz , Pouraliakbar Hamidreza , Kalayinia Samira
Published: May 2023

Objective

We studied the clinical and molecular features of a family with hypertrophic cardiomyopathy (HCM).

Background

A very heterogeneous disease affecting the heart muscle, HCM is mostly caused by variants in the proteins of sarcomeres. The detection of HCM pathogenic variants can affect the handling of patients and their families.

Methods

Whole-exome sequencing (WES) was performed to assess the genetic cause(s) of HCM in a consanguineous Iranian family.

Results

Missense likely pathogenic variant c.1279C>T (p.Arg427Cys) within exon 7 of the LMNA gene (NM_170707) was found. The segregations were confirmed by polymerase chain reaction–based Sanger sequencing.

Conclusions

Variant c.1279C>T (p.Arg427Cys) in the LMNA gene seemed to have been the cause of HCM in the family. A few LMNA gene variants related to HCM phenotypes have been recognized so far. Identifying HCM genetic basis confers significant opportunities to understand how the disease can develop and, by extension, how this progression can be arrested. Our study supports WES effectiveness for first-tier variant screening of HCM in a clinical setting.
A rapid protocol for ribosome profiling of low input samples
Authors: Meindl Andreas , Romberger Markus , Lehmann Gerhard , Eichner Norbert , Kleemann Leon , Wu Jie , Danner Johannes , Boesl Maria , Mesitov Mikhail , Meister Gunter , König Julian , Leidel Sebastian Andreas , Medenbach Jan
Published: May 2023

Ribosome profiling provides quantitative, comprehensive, and high-resolution snapshots of cellular translation by the high-throughput sequencing of short mRNA fragments that are protected by ribosomes from nucleolytic digestion. While the overall principle is simple, the workflow of ribosome profiling experiments is complex and challenging, and typically requires large amounts of sample, limiting its broad applicability. Here, we present a new protocol for ultra-rapid ribosome profiling from low-input samples. It features a robust strategy for sequencing library preparation within one day that employs solid phase purification of reaction intermediates, allowing to reduce the input to as little as 0.1 pmol of ∼30 nt RNA fragments. Hence, it is particularly suited for the analyses of small samples or targeted ribosome profiling. Its high sensitivity and its ease of implementation will foster the generation of higher quality data from small samples, which opens new opportunities in applying ribosome profiling.
sfkit: a web-based toolkit for secure and federated genomic analysis
Authors: Mendelsohn Simon , Froelicher David , Loginov Denis , Bernick David , Berger Bonnie , Cho Hyunghoon
Published: May 2023

Advances in genomics are increasingly depending upon the ability to analyze large and diverse genomic data collections, which are often difficult to amass due to privacy concerns. Recent works have shown that it is possible to jointly analyze datasets held by multiple parties, while provably preserving the privacy of each party’s dataset using cryptographic techniques. However, these tools have been challenging to use in practice due to the complexities of the required setup and coordination among the parties. We present sfkit, a secure and federated toolkit for collaborative genomic studies, to allow groups of collaborators to easily perform joint analyses of their datasets without compromising privacy. sfkit consists of a web server and a command-line interface, which together support a range of use cases including both auto-configured and user-supplied computational environments. sfkit provides collaborative workflows for the essential tasks of genome-wide association study (GWAS) and principal component analysis (PCA). We envision sfkit becoming a one-stop server for secure collaborative tools for a broad range of genomic analyses. sfkit is open-source and available at: https://sfkit.org.
0005 A circadian-informed lighting intervention markedly improves vigilance in a simulated night shift setting
Authors: Scott Hannah , Stuart Nicole , Manners Jack , Guyett Alisha , Kemps Eva , Lechat Bastien , Lack Leon , Lovato Nicole , Vakulin Andrew , Banks Siobhan , Dorrian Jill , Adams Robert , Eckert Danny , Catcheside Peter
Published: May 2023

Introduction

Due to misalignment between circadian timing and the work/rest schedule, cognitive performance during night shift-work is often poor. This study tested a circadian-informed lighting strategy designed to improve on-shift cognitive performance through alerting effects, faster circadian adjustment to the shift-work schedule and promoting more sleep off-shift, compared to standard lighting.

Methods

A randomised controlled, within-subjects, counter-balanced cross-over study was performed to examine circadian-informed versus standard lighting on cognitive performance during a simulated 8-day night shift-work schedule. Nineteen healthy sleepers (12 males/7 females, mean±SD aged 28.7±10.4 years) underwent two separate 8-day experimental conditions in the sleep laboratory. The standard lighting condition mimicked current lighting on submarines (largely dim, blue-depleted light), while the circadian-informed lighting administered bright, blue-enriched and dim, blue-depleted lighting at times estimated to facilitate rapid circadian delay. After an adaptation sleep opportunity from 22:00 – 07:00 (day 1), participants remained awake for 27 hours to transition to sleeping during the day (10:00 - 19:00) and undertaking simulated night shift-work (00:00 - 08:00) at night on days 3-7. The primary performance outcome was the number of lapses (>500ms responses) on the psychomotor vigilance task (PVT), administered six times across each simulated work shift. Median reaction time and other PVT outcomes were also compared between lighting conditions.

Results

There were significant day-by-condition interactions on PVT lapses, p< 0.05. The circadian-informed lighting intervention resulted in ~50% fewer lapses by the final day compared to standard lighting (mean±SD 7.4±5.0 vs. 15.6±6.1 lapses). Similar effects were observed across other PVT outcomes.

Conclusion

Circadian-informed lighting resulted in markedly better vigilance than standard lighting under simulated night shift-work conditions. These findings indicate the considerable potential for automated lighting interventions to improve performance and safety in shift-workers.

Support (if any)

This research is supported by the Commonwealth of Australia as represented by the Defence Science and Technology Group of the Department of Defence through the Research Network for Undersea Decision Superiority (research agreement number: 9334), with additional financial support from Flinders University and lighting provision support from REDARC.
0009 Circadian Athletic Performance Variations When Travelling in the Canadian Football League
Authors: Bourgon Vincent , Duval Félix Gabriel , Beauchamp Karolane , Forest Geneviève
Published: May 2023

Introduction

Previous studies have shown a circadian disadvantage in professional sports with teams traveling westward. This effect has been attributed to the circadian clock, core body temperature and associated decline in sports performance in the evening. Compared to the National Football League (NFL) teams, Canadian Football League (CFL) teams often travel longer distances and play at later times. As such, the objective of the present study was to investigate the circadian disadvantage in the CFL.

Methods

Data from 5 years of CFL regular season games were extracted from online databases (2016-2021). Wins, score differentials, first downs, average total, passing, penalty, and kickoff yards, pass completion percentages, interceptions, fumbles, sacks, and time of possession were extracted for both the offense (made) and defense (allowed) for every away evening game (after 6pm; n=387) as well as the direction of the travel (eastward, same time-zone, westward). Two-way ANOVAs of Direction of Travel (eastwards, same time-zone, westwards) on each performance variable were computed to study the circadian effect. Linear regression analyses were done to investigate the effect of the distance travelled by the away team (longitude travelled) on each performance variable.

Results

Significant effects of travel were found for team variables: score differentials (F[2,386]=3.86, p=.02) and time of possession (F[2,386]=5.42, p=.005). Significant results were also found for offensive variables: first downs (F(2,386)=2.91, p=.06), average kickoff return yards (F[2,386]=3.54, p=.03), fumbles (F[2,386]=2.38, p=.09), and for defensive variables: first downs allowed (F[2,386]=2.79, p=.06), average yards per play (F[2,386]=4.83, p=.008), average passing yards allowed (F[2,386]=3.14, p=.04), average kickoff yards allowed (F[2,386]=3.37, p=.04). Each significant post-hoc t-test revealed a circadian disadvantage to teams travelling westwards and a circadian advantage for teams travelling eastwards. Linear regression analyses showed that traveling westward predicts worst performances on some variables, with an increasing effect with distance travelled.

Conclusion

These results are consistent with previous findings showing that professional sports teams travelling westward show important challenges in evening games. In addition, our results highlight the fact that this disadvantage may affect not only the result of the games, but also the performance of players at a more individual level.

Support (if any)
0011 Daily verses circadian amplitude of the distal-proximal skin temperature gradient
Authors: Ballell Lidia , Ritchie Hannah K , Knauer Oliver A , Guerin Molly K , Stothard Ellen , Wright Kenneth
Published: May 2023

Introduction

Sleep, circadian rhythms, and thermoregulatory physiology are highly integrated and impact each other. The daily rhythm in the distal-proximal skin temperature gradient (DPG) is wider/more negative during wakefulness, and narrower/closer to zero during sleep. The circadian rhythm in the DPG is wider during the biological day and narrower during the biological night. Here we aimed to quantify and compare the amplitude of the daily rhythm in the DPG under wakefulness-sleep conditions versus the amplitude of the circadian rhythm in the DPG under sleep deprivation conditions to examine associations and magnitude differences.

Methods

Eleven [5 females] healthy adults [aged 27.6±10.2y, BMI 23.1±2.2 (mean±SD)] participated. After one week of at-home ambulatory monitoring with 8h per night sleep opportunities at habitual bedtimes, participants were studied in the laboratory for three days under controlled dim light (< 8 lux maximum) and ambient temperature conditions (22-24°C). Participants arrived in the afternoon, were kept awake 4h later than typical and scheduled to a 4h sleep opportunity. The next day, participants were sleep deprived for 28h followed by recovery sleep. Skin temperature was assessed every min with iButtons placed subclavicular (proximal skin temperature) and foot palmar (distal skin temperature). The DPG was calculated as difference between proximal and distal skin temperatures. A three-harmonic regression model was used to fit DPG data and derive daily and circadian rhythm amplitudes, and percent difference in amplitude was calculated. Pearson correlations were calculated between daily and circadian rhythm DPG amplitudes.

Results

DPG amplitude was significantly greater for daily versus circadian rhythm (p < 0.05). Percent difference analyses showed daily DPG rhythm was 57% larger than circadian DPG rhythm (SD 30%, range 22-134%). A significant correlation was found between daily and circadian rhythm DPG amplitudes (r = 0.71, p< 0.05).

Conclusion

The amplitudes of daily and circadian rhythms of the DPG are associated, but the daily rhythm amplitude is larger. Additional research is needed to compare the relative importance of daily versus circadian skin temperature amplitudes for sleep and circadian relevant outcomes.

Support (if any)

CurAegis Technologies Inc., Fundacio Joan Riera I Gubau, Undergraduate Research Opportunities Program University of Colorado Boulder
0012 Night Owls and Morning Birds Fly Over the Gym: Circadian Misalignment Does Not Predict Physical Activity in Adolescents
Authors: Wright Isabella , Lee Lindsey , Kamhout Sarah , York Nicholas , Rugh Kathleen , Duraccio Kara
Published: May 2023

Introduction

Given that obesity rates have reached epidemic-level proportions in the U.S., it is more important than ever to identify preventative interventions to reduce obesity risk. Many aspects of sleep have been associated with obesity through their relationship to physical activity. Circadian misalignment is an area of sleep that is yet understudied but that may be especially relevant given the rapid biological and social changes in sleep timing seen in adolescence. This study examined the relationship between circadian misalignment and physical activity among adolescents.

Methods

Fifty adolescents completed an 11-day protocol that began with a baseline appointment where study staff measured participants’ height and weight. Over the next 10 days, participants wore waist accelerometers that measured physical activity and completed manual sleep diaries. After 10 days, participants completed a six-hour appointment in a dimly lit room (lux level < 5) where study staff collected saliva samples every 30 minutes to measure the onset of participants’ melatonin levels. In this preliminary analysis, circadian misalignment was calculated by subtracting the timing of melatonin onset from the average bedtime noted in participants’ sleep diaries; lower scores are reflective of greater circadian misalignment.

Results

Adolescents engaged in 12,038.77 minutes (SD=1737.62) of sedentary activity, 767.29 minutes (SD=260.93) of light physical activity, and 1,263 (SD= 411.89) of moderate-to-vigorous physical activity across this ten-day monitoring period. We conducted multiple regression analyses with circadian misalignment as a predictor of sedentary, light, and moderate-to-vigorous physical activity levels. Circadian misalignment was not a statistically significant predictor of sedentary physical activity (p=.85), light physical activity (p=.70), or moderate-to-vigorous physical activity (p=.30).

Conclusion

In our study, circadian misalignment did not predict sedentary, light, or moderate-to-vigorous physical activity levels. Current literature on other facets of sleep suggests that sleep duration and quality is related to physical activity. However, our results suggest that improving circadian alignment may not be a viable intervention to increase physical activity. Further studies are needed to validate these results as well as to explore the effects of circadian alignment on other aspects of obesity risk.

Support (if any)
0016 Influence of Circadian Preference on Sleep, Depression, and Anxiety in Canadian Student-Athletes
Authors: Cook Jesse , Charest Jonathan , Plante David , Werthner Penny , Horsnell Matthew , Samuels Charles
Published: May 2023

Introduction

Student-athletes face unique demands that heighten vulnerability to both sleep and mental health problems. Circadian preference (CP) describes an individuals’ preferred timing for sleep and wake activity, with this conceived as a continuum between the extremes of morningness and eveningness. CP has been shown to influence both sleep and mental health, with greater eveningness preference generally associating with worse outcomes. However, these relationships are understudied in student-athletes. Thus, this investigation was designed to assess the influence of CP on sleep, depression, and anxiety in Canadian student-athletes.

Methods

Data were obtained throughout the academic semester from Canadian institutions, with student-athletes completing the Athlete Sleep Screening Questionnaire (ASSQ), General Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire (PHQ-9). ASSQ captured sleep health characteristics and CP, while GAD-7 and PHQ-9 assessed anxiety and depressive symptoms, respectively. ASSQ CP response options were Definitely-Morning, Morning, Evening, or Definitely-Evening as response options, and was coded on a 0-3 scale, with higher values representing increasing eveningness preference. Linear regression estimated associations of CP with sleep, depression, and anxiety. Adjusted regressions controlled for age, gender, race/ethnicity, and sport type.

Results

Sample included 559 Canadian student-athletes (Average Age = 18.9 ± 3.21 years; Percentage Women = 53%; Percentage White = 79.1%) from eight different sports. Regarding CP, 11.4% reported Definitely-Morning, 27.0% reported Morning, 41.8% reported Evening, and 19.8% reported Definitely-Evening. Greater eveningness preference significantly associated with worse overall sleep difficulties (padjusted < 0.0001), longer sleep latency (padjusted < 0.0001), reduced sleep satisfaction (padjusted < 0.0001), more prolonged sleep inertia (padjusted < 0.0001), more daytime naps (padjusted = 0.01), and more severe depressive symptomatology (padjusted = 0.0006).

Conclusion

Greater eveningness in a sample of Canadian student-athletes associated with worse sleep and psychological characteristics, including overall sleep difficulty, sleep latency, sleep satisfaction, sleep inertia, daytime napping, and depressive symptom severity. The results of this study provide compelling evidence that eveningness CP may predict poor mental and sleep health outcomes in student-athletes. Thus, further attention to circadian characteristics of student-athletes is warranted. Additionally, modifications to training schedules and team routines could be considered as preventative strategies for mental and sleep health problems.

Support (if any)

Mitacs #IT23469
0018 Perils of the nighttime: impact of behavioral timing and preference on mental and physical health
Authors: Zeitzer Jamie , Lok Renske , Weed Lara , Winer Joseph
Published: May 2023

Introduction

Both chronotype and the actual timing of sleep have been associated with mental and physical health outcomes. While these often align, life often intervenes and causes a misalignment between desired and actual timing of sleep. The impact of such a misalignment has not been well investigated.

Methods

Community-dwelling (n=73,888) adults participating in the UK Biobank were monitored with wrist actigraphy for one week. Timing of behavioral patterns was derived from calculation of L5 (onset of lowest five hours of activity) and parsed into quartiles (Q1: early, Q2-3: intermediate, Q4: late). Chronotype was determined by a single question and parsed into quartiles (Q1: morning-type, Q2-3: intermediate, Q4: evening-type). Mental (mental, behavioral, and neurodevelopmental disorders, generalized anxiety disorder, depression) and physical (including metabolic disorder, diabetes, obesity, hypertension, circulatory disorder, digestive disorder, respiratory disorder, all-cause cancer) health status was determined with ICD-10 codes. Prevalence and likelihood (odds ratios) of disorders were calculated and adjusted for common demographic variables (sex, age, body mass index, material deprivation) and sleep duration.

Results

As compared to morning-type individuals who went to sleep early (aligned), morning-type individuals who went to sleep late (misaligned) had increased likelihood of both mental (OR=1.52±0.06, p< 0.001) and physical (OR=1.45±0.03, p< 0.001) health disorders. As compared to evening-type individuals who went to sleep late (aligned), evening-type individuals who went to sleep early (aligned) had decreased likelihood of both mental (OR=0.85±0.06, p=0.002) and physical (OR=0.66±0.03, p< 0.001) health disorders.

Conclusion

Going to sleep early, irrespective of natural proclivity and potential circadian misalignment, is associated with better mental and physical health.

Support (if any)

Mental Illness Research Education and Clinical Center, Department of Veterans Affairs
0020 Associations between bedtime and waketime variability and sleep outcomes in autistic children
Authors: McGovney Kevin , Hayse Braden , Stearns Melanie , Mazurek Micah , Curtis Ashley , Nair Neetu , Beversdorf David , Sohl Kristen , Davis Beth , McCrae Christina
Published: May 2023

Introduction

Up to 80% of autistic children experience sleep disturbances. Sleep hygiene guidelines advise patients to maintain consistent bedtimes and waketimes for the purpose of regulating one’s circadian rhythm. However, the relationship between bedtime and waketime variability and sleep outcomes in autistic children is unclear, and so the current study examines these associations.

Methods

One hundred thirty autistic children (Mage = 8.81 yrs, SD = 1.92 yrs, range = 6-12 yrs, 71% male) completed two weeks of daily sleep diaries with parental assistance and concurrently wore actigraphic wrist watches (Actiwatch-2, Respironics). Rest intervals in Actiware software were set using visual inspection while referencing self-reported bed/waketime. Boundaries of rest intervals were defined as the time when the child first attempted sleep to the time when the child vacated bed. Subjective and objective estimates of bedtime, waketime, total wake time during attempted sleep periods, and total sleep time were obtained. Bayesian multi-level models obtained individual estimates of average variability in bedtime and waketime. Multiple linear regressions were then used to examine associations between subjective and objective bedtime and waketime variability and total wake time and total sleep time, controlling for age and average levels of bed/waketime variability. Models were separated out by subjective/objective sleep outcomes (i.e., subjective waketime variability predicting subjective total sleep time).

Results

Greater objective waketime variability was associated with less objective total sleep time (B=-38.80, p<.001, partial eta-squared = .071). Greater subjective waketime variability was associated with longer subjective total wake time (B = 18.58, p=.02, partial eta-squared = .058) and shorter subjective total sleep time (B=-70.60, p<.001, partial eta-squared = 0.227).

Conclusion

While results do not possess causal implications, greater subjective and objective waketime variability are associated with poorer sleep outcomes in autistic children. Effect sizes ranged from approximately medium to large. Results suggest that bedtime variability may not be related to sleep outcomes in autistic children. Future studies should examine whether reductions in waketime variability mediate the effect of behavioral insomnia interventions on improved sleep in autistic children.

Support (if any)

MU Research Board Grant (McCrae, PI); Department of Defense Autism Research Program (McCrae, PI; W81XWH2010399); Thompson Center for Autism and Neurodevelopmental Disorders.
0025 Effects of NLS-4 (Lauflumide) and modafinil in a rat model of circadian rhythm and chronic severe fatigue
Authors: Bizot Jean-Charles , Massé Fabienne , Combeau Julie , Lacerda-Queiroz Norinne , David Sabrina , Benel Laurent , Apostol George , Konofal Eric
Published: May 2023

Introduction

The chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by easy fatigability, feverishness, diffuse pains, and depression. Many COVID-19 patients expressed a long-term effect of coronavirus (long-COVID), with some characteristics typically found in CFS. To examine the efficacy of NLS-4 (Lauflumide), in comparison with a positive control, modafinil, which has been shown to improve recovery from CFS in human, to improve recovery from severe fatigue in rats.

Methods

Male 7-8 weeks old Sprague-Dawley rats were subjected to a fatigue procedure for seven consecutive days. Their locomotor activity in home cage was then recorded for 3 days following the end of the fatigue procedure. A Sham group was subjected to the same measurement of circadian activity but without the fatigue procedure. Rats were divided into different groups which received, before the start of the dark period, three daily administrations of NLS-4, modafinil or vehicle (Control and Sham groups).

Results

The fatigue procedure induced an impairment in the circadian activity, that is a decrease in motor activity during the dark period and an increase in motor activity during the period of light. Accordingly, the difference of distance travelled between the dark period and the light period was lower in the Control group than in the Sham group. This impairment was still present 3 days after the end of the fatigue procedure. modafinil and NLS-4 dose-dependently increased locomotor activity during the dark phase and, to a lesser extent, during the light phase. The increase in activity during the dark phase was significant at doses of 16, 32 and 64 mg/kg with NLS-4 and at doses 64 and 128 mg/kg with modafinil but the effect of NLS-4 was more sustainable than that of modafinil.

Conclusion

This study suggests that the impairment of circadian rhythm induced by a fatigue procedure was reduced to a similar magnitude by modafinil (64 mg/kg) and NLS-4 (16 mg/kg). Since modafinil has been shown to improve recovery from chronic fatigue in human, these results show that NLS-4 could improve recovery from CFS in human at doses four times lower than that used for modafinil.

Support (if any)

NLS Pharmaceutics
0027 Ravaged Rat Rhythms: Circadian Rhythm Influence on Mecamylamine-Induced Nicotine Withdrawal
Authors: Garcia Cristian Douglas Sales , Prince Attaira , Schwartz Eric E J
Published: May 2023

Introduction

Mecamylamine (Mec) is a nicotinic acetylcholine receptor (nAChR) antagonist, serving as an important piece of nicotine addiction cessation therapies. When co-administered with nicotine, Mec blocks the positive reinforcing effects of the substance of abuse and may promote a lessened desire to perpetuate an addictive cycle. On the other hand, the magnitude of the withdrawal symptoms caused by this co-administration may reinforce addiction as users can choose to terminate the process of quitting.

Methods

The present study uses Sprague-Dawley rats to examine if the time of withdrawal onset in relation to circadian rhythms impacts the magnitude of the relevant aversive symptoms. We hypothesized that Mec injected during the rat’s dark period show significantly less aversive symptoms when compared to when it’s done during their light period. For this, we injected rats (n=3 per group) twice a day for thirteen days subcutaneously, with either saline or nicotine, a validated protocol to induce addiction. To measure aversive symptoms of nicotine precipitated withdrawal in light vs dark periods, we used a conditioned place aversion (CPA) behavioral assay in which the rats were either tested mid-light or mid-dark periods. In CPA, the rats were first introduced to the two distinct chambers and allowed to freely move in between them (day 10, for 15 minutes), while time spent in each one was analyzed. Then, they were conditioned to associate one chamber with saline and the other with Mec (days 11-12, for 30 minutes each). Finally, they were placed again in freedom, and the time spent in the mecamylamine-paired chamber was detracted from pre-conditioning to give us the results of aversion (day 13, for 15 minutes).

Results

We predicted that in the aftermath, the light-period rats on nicotine addiction schedule would show the shortest change in time in Mec-paired chamber, while saline-scheduled rats across both periods would show a change of zero—or no impact of Mec. Results indicated no significant differences between group averages for time spent in the Mec-paired chamber, but they showed saline-scheduled rats to be similarly aversive to it.

Conclusion

This result indicates the potential need for a study with a more selective nicotine blocker.

Support (if any)
0029 The Effect of BMAL1 Expression on Autophagy Activity in Astrocytes
Authors: Campbell Connor
Published: May 2023

Introduction

Circadian rhythm disruption is an established symptom of neurodegenerative disease, however, there is mounting evidence that circadian systems drive early pathogenesis. The core circadian clock gene, BMAL1, mediates daily oscillations in transcription for homeostatic processes. Furthermore, the deletion of BMAL1 renders tissue transcriptionally arrhythmic and influences non-circadian genes, which causes reactive astrogliosis, oxidative stress, and neuronal injury in the brain. We have recently observed in-vitro that BMAL1 knockout astrocytes exhibit increases in the pH-sensitive lysosomal dye lysotracker. This suggests that the clock potentially modulates an even broader array of cellular processes, like autophagy, which maintains cellular homeostasis by delivering proteins to lysosomes for degradation. Given that deficits in the clearance of stable protein aggregates is characteristic of many neurodegenerative disorders, the manipulation of autophagic machinery displays therapeutic potential. Therefore, the purpose of this project is to evaluate whether autophagy activity in astrocytes is regulated rhythmically by circadian clocks or through non-rhythmic genes linked to BMAL1 expression.

Methods

Through employing the fluorescent (RFP)-EGFP-LC3 reporter, we can detect differential organelle pH values to reveal the autophagy dynamics. Specifically, the RFP:EGFP signal ratio represents the progression from the autophagosome to the acidic autolysosome, thereby quantitatively illustrating the protein degradation arising from autophagy machinery.

Results

When comparing astrocyte-specific BMAL1 knockout mice to the wildtype littermates, there are significant increases for EGFP and RFP channels within the white matter. Furthermore, the greater RFP:EGFP value exhibits upregulated protein degradation, which validates that BMAL1 deletion can modulate autophagy activity. Upon establishing the baseline fluorescence for wildtypes across the 24-hour cycle, the EGFP and RFP signals suggested rhythmic activity for the light-stimulated groups. Nevertheless, the insignificant sinusoidal patterns among the dark-only counterparts reduces the probability that circadian clocks regulate autophagy activity.

Conclusion

The effect of BMAL1 deletion on autophagosomes in white matter tissue likely originates from other glial cell types that are uniquely susceptible to dysfunction in non-rhythmic pathways related to BMAL1 expression in astrocytes. Ultimately, investigating how BMAL1 protects against neurodegeneration will reveal therapeutic approaches for manipulating the autophagy machinery to promote pathology clearance, along with emphasizing the importance for maintaining sleeping patterns.

Support (if any)
0031 Whole genome sequence analyses for Excessive Daytime Sleepiness in the NHLBI TOPMed Program
Authors: Zhang Yiyan , Kurniansyah Nuzulul , Nagarajan Pavithra , Chen Han , Purcell Shaun , Saxena Richa , Zhu Xiaofeng , Cade Brian , Sofer Tamar , Redline Susan , Wang Heming , Zhang Yiyan
Published: May 2023

Introduction

Excessive daytime sleepiness is associated with multiple sleep, cardiometabolic, and neuropsychiatric disorders. Previous genome-wide association studies (GWAS) of daytime sleepiness using a single question in European population revealed associations for multiple genes in central nervous pathways. However, findings are still limited and may not be generalizable to other populations. In this study, we performed the first whole-genome sequence (WGS) analyses for Epworth Sleepiness Scale (ESS) in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program.

Methods

This study includes 15,201 individuals of diverse race and ethnic backgrounds from seven cohorts in the TOPMed. We performed GWAS of single common variants (MAF>0.01) and gene-based burden tests of low-frequency and rare functional variants (loss of function and missense; MAF< 0.05). We adjusted for age, sex, body mass index (BMI), study, race/ethnicity, and genetic relatedness using linear mixed effects models implemented in the GENESIS R package.

Results

This sample included 43.8% males with a mean age of 54.9 years and BMI 29.6kg/m2, of whom 21.3% were classified with excessive daytime sleepiness (ESS>=10). In single variant test, we identified one novel genomic locus at rs60249969 (on CELF2) significantly associated with ESS (p-value=3.91x10-8). Suggestive significant associations were observed at 5 novel loci that overlapped with PDE7A/DNAJC5B, AHI1/PDE7B, KCNH7, F5, and FBXL17 (p< 1x10-7). In gene-based burden test, we did not identify any gene significantly associated with the ESS after correcting for multiple comparisons (p< 2x10-6). Suggestive significant evidence was observed at OR1A2 (consisting of 41 missense variants; p-value=1.65x10-5), an olfactory receptor gene differentially expressed in choroid plexus in the brain implicated in neurodegenerative diseases.

Conclusion

In our investigation of common and rare variant associations with excessive daytime sleepiness as assessed by the ESS, we identified one significant and several suggestive novel loci that mapped to genes highly expressed in brain tissues, which may have implications on sleep wake control system. Our next step will include replication analyses using independent imputed samples.

Support (if any)

R01HL153814 (to H.W.), NHLBI R35HL135818 (to S.R.).
0034 Genetic Variants for Obstructive Sleep Apnea Identified after Modeling Interactions with Daytime Sleepiness
Authors: Nagarajan Pavithra , Chen Han , Zhang Yiyan , Kurniansyah Nuzulul , Purcell Shaun , Saxena Richa , Zhu Xiaofeng , Cade Brian , Sofer Tamar , Redline Susan , Wang Heming ,   TOPMed Sleep Working Group
Published: May 2023

Introduction

Obstructive sleep apnea (OSA) is a complex sleep disorder that presents with a range of symptoms, including excessive daytime sleepiness (EDS), postulated to represent a more severe subtype. Despite significant heritability and past GWASs, genetic mechanisms of the disorder remain unclear. Given that EDS often reflects chronic sleep insufficiency and a pro-inflammatory state, we reasoned it may interact with genetic variants to modify risk for OSA. We tested this hypothesis by investigating gene by sleepiness interaction analysis of OSA.

Methods

Whole-genome sequencing data of 11,619 individuals of diverse race and ethnic backgrounds from the NHLBI Trans-Omics for Precision Medicine program was used, with the outcome being Apnea-Hypopnea Index (AHI) and the exposure Epworth Sleepiness Scale (>10: EDS, <=10: non-EDS). GENESIS R package was used to perform 2-stage rank normalization, adjusting for age, sex, BMI, ancestral PCs, cohort, and genetic relatedness, and rescaling residuals to a unit variance, separately in each study/ancestry group. GEM software was used to perform gene-EDS interaction analyses, including 1 df tests of marginal SNP effect and interaction effect of SNPxEDS on AHI, respectively, and 2 df test of joint significance of both. Robust standard errors were used, with a significance threshold of p< 5x10-8.

Results

The 1 df test of marginal SNP effect identified one novel locus (rs35370454) that mapped to IFRD1, whose overexpression has been associated with sleep restriction, and hypomethylation with narcolepsy. The 1 df test of interaction effect identified two novel loci (rs13118183, rs281851) that mapped to genes MARCHF1 and CCDC3. The 2 df joint test did not reveal additional novel loci. CCDC3 has shown to repress inflammatory activity of TNF-alpha, a cytokine postulated to be involved in sleep regulation. MARCHF1 has shown to inhibit cellular insulin sensitivity as well as promote NF-KB, with degree of activation positively correlating with OSA severity.

Conclusion

By modeling the modification effect of EDS on OSA we identified 3 novel loci. This approach may be useful in understanding the genetic factors that vary across OSA subtypes. For next steps, we seek to conduct replication analysis using independent imputed samples.

Support (if any)

NHLBI, R01HL153814 (H.W.), R35HL135818 (S.R.).
0036 ARC Genotype Modulates REM EEG Spectral Power Following Total Sleep Deprivation
Authors: Satterfield Brieann , Finlay Myles , Skeiky Lillian , Fluke Sofia , Van Dongen Hans
Published: May 2023

Introduction

EEG spectral power in the alpha range is indicative of a wake-like state, with alpha power typically high during wakefulness and reduced during sleep. We previously reported that a single nucleotide polymorphism (SNP) of the activity-regulated cytoskeleton associated protein (ARC) gene modulates non-REM theta and alpha spectral power. Here we sought to determine whether ARC genotype is also associated with phenotypic differences in EEG spectral power during REM sleep.

Methods

43 healthy adults (27.6±4.8y; 23 females) participated in one of two in-laboratory studies. Each participant had a 10h baseline sleep opportunity (22:00–08:00), 38h TSD, and 10h recovery sleep opportunity (22:00–08:00). Sleep periods were recorded polysomnographically and visually scored according to AASM criteria. Genomic DNA was assayed for the ARC c.*742 + 58C>T non-coding SNP, rs35900184. Log-transformed EEG spectral power (C3-M3 derivation) for REM sleep over 0.2 Hz frequency bins in each of four frequency bands – delta (0.8–4.0 Hz), theta (4.2–8.0 Hz), alpha (8.2–12.0 Hz), and beta (12.2–16.0 Hz) – was analyzed by band using mixed-effects ANOVA with fixed effects for ARC genotype, night (baseline, recovery), frequency bin, and their interactions. Analyses included study and age as covariates and a random effect over subjects on the intercept.

Results

The genotype distribution in this sample was 28 C/C homozygotes, 10 C/T heterozygotes, and 5 T/T homozygotes. There was a significant genotype by night interaction in the alpha band (F2,1560=23.80, p< 0.001). Compared to baseline sleep, T/T homozygotes had 13.0% more alpha power during post-TSD recovery sleep, whereas C/C homozygotes had 1.2% less alpha power and C/T heterozygotes had 3.2% less alpha power. This differential TSD effect for the ARC genotypes was not seen in the other spectral bands.

Conclusion

Our results show that ARC genotype mediates the REM sleep EEG response to TSD, with T/T homozygotes displaying a pronounced increase in REM alpha power following sleep deprivation. The ARC SNP has been associated with schizophrenia, a psychiatric disorder with known sleep disturbances. As such, the ARC-mediated increase in REM EEG alpha power for T/T homozygotes might be a marker of a psychosis-like predisposition.

Support (if any)

ONR N00014-13-1-0302; NIH R21CA167691; USAMRDC W81XWH-18-1-0100; ARO W911NF2210223