A non-circadian role for clock-genes in sleep homeostasis:a strain comparison

BACKGROUND: We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound. RESULTS: In all three strains per expression was increased when animals were kept awake but the rate of increase during the SD as well as the relative increase in per after 6 h SD were highest in the strain for which the sleep rebound was smallest; i.e., DBA/2J (D2). Moreover, whereas in the other two strains per1 and per2 reverted to control levels with recovery sleep, per2 expression specifically, remained elevated in D2 mice. dbp expression increased during the light period both during baseline and during SD although levels were reduced during the latter condition compared to baseline. In contrast to per2, dbp expression reverted to control levels with recovery sleep in D2 only, whereas in the two other strains expression remained decreased. CONCLUSION: These findings support and extend our previous findings that clock genes in the forebrain are implicated in the homeostatic regulation of sleep and suggest that sustained, high levels of per2 expression may negatively impact recovery sleep

Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice

Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour) induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period.Down Syndrome Research and Treatment FoundationResearch Down Syndrome Organizatio

Pumilio-2 Function in the Mouse Nervous System

Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2) has been found to play a role in the mammalian nervous system, in particular in regulating morphology, arborization and excitability of neuronal dendrites, in vitro. However, the role of Pum2 in vivo remains unclear. Here, we report our investigation of the functional and molecular consequences of Pum2 disruption in vivo using an array of neurophysiology, behavioral and gene expression profiling techniques. We used Pum2-deficient mice to monitor in vivo brain activity using EEG and to study behavior traits, including memory, locomotor activity and nesting capacities. Because of the suspected role of Pum2 in neuronal excitability, we also examined the susceptibility to seizure induction. Finally, we used a quantitative gene expression profiling assay to identify key molecular partners of Pum2. We found that Pum2-deficient mice have abnormal behavioral strategies in spatial and object memory test. Additionally, Pum2 deficiency is associated with increased locomotor activity and decreased body weight. We also observed environmentally-induced impairment in nesting behavior. Most importantly, Pum2-deficient mice showed spontaneous EEG abnormalities and had lower seizure thresholds using a convulsing dosage of pentylenetetrazole. Finally, some genes, including neuronal ion channels, were differentially expressed in the hippocampus of Pum2-deficient mice. These findings demonstrate that Pum2 serves key functions in the adult mammalian central nervous system encompassing neuronal excitability and behavioral response to environmental challenges

The Ursinus Weekly, May 3, 1965

Y retreat emphasizes creation of ideal college • Stage set for Fenwickian mouse • Ferguson, Dawson report $1,700 for Campus Chest • Psych Club elects officers • Bishop\u27s Players present An enemy of the people • Waiters\u27 banquet • Starvation: Paradox of plenty • Bali Ha\u27i theme for annual Spring Festival • Active electioneering marks class elections • Editorial: MSGA election; UC traditions and manners • Letters to the editor • One language for the world • Nine overseas students enrolled at Ursinus • Admissions dilemma • Injured thinclads bow at PMC; Win triangular meet at Hopkins • UC nine wins two: Beat F&M, Lebanon Valley • UC girls drop match to W.C. • Lacrosse team whips W. Chester • Greek gleanings • Advertising and PR seminarhttps://digitalcommons.ursinus.edu/weekly/1248/thumbnail.jp

Quenched hadron spectroscopy with improved staggered quark action

We investigate light hadron spectroscopy with an improved quenched staggered quark action. We compare the results obtained with an improved gauge plus an improved quark action, an improved gauge plus standard quark action, and the standard gauge plus standard quark action. Most of the improvement in the spectroscopy results is due to the improved gauge sector. However, the improved quark action substantially reduces violations of Lorentz invariance, as evidenced by the meson dispersion relations.Comment: New references adde

Science and the Liberal Arts at Ursinus College

Science trend: Moving beyond industrialism • Founders\u27 Day address: Small colleges nurture young scientists well • Physics mentor changed a life • Complex world a challenge for scientists • In government, chemist finds his niche • Ursinus helps non standard student bloom • Ursinus let him explore inner space • Finding the problem is scientist\u27s hardest task • Most wanted: Insatiable curiosity • Real research: Practical or esoteric? • Flexibility is a matter of degree • Liberal arts education prepares minds • The way to encourage young scientistshttps://digitalcommons.ursinus.edu/founders_programs/1053/thumbnail.jp

Ursinus College Alumni Journal, November 1965

First words • From the President • Planning for the future at Ursinus College • Start of a four-year celebration • Guide to Centennial giving • Soviet portfolio: Rise and fall of the literary temperature; Evgeny Yevtushenko, Siberian pastorale; Memories of a Russian honeymoon • Founders Day is Ladies Day • Alumni come home to Ursinus • The many lives of Wismer Hall • Matching gifts lift industry & academia • Found: Preacher Mack • On Peace Corps duty in Thailand • The war trap • Lengthening list • Sporting scene • Campus clippings • Letters • Profiles: Four Ursinus men of distinction • Class notebook • Weddings • Births • In memoriam • A tribute to J. Allen Minnich • End quotes: The measles principle of educationhttps://digitalcommons.ursinus.edu/alumnijournal/1083/thumbnail.jp

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Tactile Stimulation of the Human Head for Information Display

A series of three studies was conducted to explore the use of tactile stimulation or light tapping of the human head to inform a pilot of possible threats or other situations in the flight environment. Study I confirmed that subjects could achieve 100% detection of the tactile stimuli. Localization performance, measured in Study 2, depended on the number of different stimulus sites and ranged from 93% accuracy for 6 sites to 47% accuracy for 12 sites across the parietal meridian of the head. In Study 3 we investigated the effect of performing the localization task simultaneously with a dual memory/tracking task or an air combat simulation task. These studies demonstrated that tactile information display could be an integral contributor to improved situation awareness, but not without cost to other task performance. The results of Study 3 were also examined with reference to popular models of attention and workload.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Beyond the Symptom: The Biology of Fatigue

A workshop titled Beyond the Symptom: The Biology of Fatigue was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them