Sleep Loss Reduces the DNA-Binding of BMAL1, CLOCK, and NPAS2 to Specific Clock Genes in the Mouse Cerebral Cortex

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), −6, −12, and −18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and −6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven

Gradient-free quantum optimization on NISQ devices

Variational Quantum Eigensolvers (VQEs) have recently attracted considerable attention. Yet, in practice, they still suffer from the efforts for estimating cost function gradients for large parameter sets or resource-demanding reinforcement strategies. Here, we therefore consider recent advances in weight-agnostic learning and propose a strategy that addresses the trade-off between finding appropriate circuit architectures and parameter tuning. We investigate the use of NEAT-inspired algorithms which evaluate circuits via genetic competition and thus circumvent issues due to exceeding numbers of parameters. Our methods are tested both via simulation and on real quantum hardware and are used to solve the transverse Ising Hamiltonian and the Sherrington-Kirkpatrick spin model.Comment: 13 pages, 6 figures, comments welcome

Depriving Mice of Sleep also Deprives of Food.

Both sleep-wake behavior and circadian rhythms are tightly coupled to energy metabolism and food intake. Altered feeding times in mice are known to entrain clock gene rhythms in the brain and liver, and sleep-deprived humans tend to eat more and gain weight. Previous observations in mice showing that sleep deprivation (SD) changes clock gene expression might thus relate to altered food intake, and not to the loss of sleep per se. Whether SD affects food intake in the mouse and how this might affect clock gene expression is, however, unknown. We therefore quantified (i) the cortical expression of the clock genes Per1, Per2, Dbp, and Cry1 in mice that had access to food or not during a 6 h SD, and (ii) food intake during baseline, SD, and recovery sleep. We found that food deprivation did not modify the SD-incurred clock gene changes in the cortex. Moreover, we discovered that although food intake during SD did not differ from the baseline, mice lost weight and increased food intake during subsequent recovery. We conclude that SD is associated with food deprivation and that the resulting energy deficit might contribute to the effects of SD that are commonly interpreted as a response to sleep loss

No intolerance of errors:The effect of intolerance of uncertainty on performance monitoring revisited

Errors have been conceptualized as internal forms of threat that can cause harm in unpredictable ways. An index of error processing is the error-related negativity (ERN), an event-related potential reflecting variability in the sensitivity to errors. Prior work has shown the relationship between psychopathology symptoms and the ERN is unclear, and may be moderated by intolerance of uncertainty (IU), a trait that captures how people react to unpredictability. IU includes two subfactors of prospective IU (active seeking of predictability) and inhibitory IU (behavioral paralysis). In the present study, 188 undergraduates performed an Eriksen flanker task designed to elicit the ERN, while brain activity was recorded using electroencephalography (EEG). Participants completed the Intolerance of Uncertainty Scale, Short Form (IUS-12), and other measures of anxiety, depression and worry. Total IU explained 5 % of the variance in correct-response negativity (CRN), but was not associated with the ERN in our sample. In contrast to previous findings, the IU subfactors did not predict the ERN or post-error slowing (PES), nor did total IU and depression interact to predict the ERN. Exploratory analyses also showed that total IU did not moderate the relationship between trait anxiety and the ERN. Small samples may have previously exaggerated the links between self-reported IU and the ERN. As such, further high-powered replications are required to confirm if, and how, they are related

Potential of Mycobacterium tuberculosis resuscitation-promoting factors as antigens in novel tuberculosis sub-unit vaccines

n/

COVID-19: Experience of a tertiary children’s hospital in Western Cape Province, South Africa

The COVID-19 pandemic necessitated rapid changes in healthcare systems and at Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, South Africa. Paediatric services in particular required adjustment, not only for the paediatric patients but also for their carers and the staff looking after them. Strategies were divided into streams, including the impact of COVID-19 on the hospital and the role of RCWMCH in Western Cape Province, communication strategies, adaptation of clinical services at the hospital, specifically with a paediatric-friendly approach, and staff engagement. Interventions utilised: (i) Specific COVID-19 planning was required at a children’s hospital, and lessons were learnt from other international children’s hospitals. A similar number of patients and staff were infected by the virus (244 patients and 212 staff members by 21 December 2020). (ii) Measures were put in place to assist creation of capacity at metro hospitals’ adult services by accepting children with emergency issues directly to RCWMCH, as well as accepting adolescents up to age 18 years. (iii) The communication strategy was improved to include daily engagement with heads of departments/supervisors by earlymorning structured information meetings. There were also changes in the methods of communication with staff using media such as Zoom, MS Teams and WhatsApp. Hospital-wide information and discussion sessions were held both on social platforms and in the form of smallgroup physical meetings with senior hospital administrators (with appropriate distancing). Labour union representatives were purposefully directly engaged to assess concerns. (iv) Clinical services at the hospital were adapted. These included paediatric-friendly services and physical changes to the hospital environment. (v) Staff engagement was particularly important to assist in allaying staff anxiety, developing a staff screening programme, and provision and training in use of personal protective equipment, as well as focusing on staff wellness. In conclusion, visible management and leadership has allowed for flexibility and adaptability to manage clinical services in various contexts. It is important to utilise staff in different roles during a crisis and to consider the different perspectives of people involved in the services. The key to success, that included very early adoption of the above measures, has been hospital staff taking initiative, searching for answers and identifying and implementing solutions, effective communication, and leadership support. These lessons are useful in dealing with second and further waves of the COVID-19 pandemic

Perpustakaan UMP anjur NCOAL

Kuantan 17 Mac - Seramai 70 peserta dari Perpustakaan awam dan swasta yang menyertai Persidangan Kebangsaan Perpustakaan Akademik (NCOAL) 2015 selama dua hari bertempat di Hotel MS Garden, Kuantan

PO-0891: Clinical implementation and experience with real-time anatomy tracking and gating during MR-IGRT

Cardiolog

Beyond the Front Page: Measuring Third Party Dynamics in the Field

In the modern Web, service providers often rely heavily on third parties to run their services. For example, they make use of ad networks to finance their services, externally hosted libraries to develop features quickly, and analytics providers to gain insights into visitor behavior. For security and privacy, website owners need to be aware of the content they provide their users. However, in reality, they often do not know which third parties are embedded, for example, when these third parties request additional content as it is common in real-time ad auctions. In this paper, we present a large-scale measurement study to analyze the magnitude of these new challenges. To better reflect the connectedness of third parties, we measured their relations in a model we call third party trees, which reflects an approximation of the loading dependencies of all third parties embedded into a given website. Using this concept, we show that including a single third party can lead to subsequent requests from up to eight additional services. Furthermore, our findings indicate that the third parties embedded on a page load are not always deterministic, as 50% of the branches in the third party trees change between repeated visits. In addition, we found that 93% of the analyzed websites embedded third parties that are located in regions that might not be in line with the current legal framework. Our study also replicates previous work that mostly focused on landing pages of websites. We show that this method is only able to measure a lower bound as subsites show a significant increase of privacy-invasive techniques. For example, our results show an increase of used cookies by about 36% when crawling websites more deeply

Cortical miR-709 links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD) altered; while the rapid-eye-movement sleep (REMS) rebound was compromised in both, the increase in EEG delta (1 to 4 Hz) power during non-REMS (NREMS) was smaller in cKO mice and larger in icKO mice compared to controls. We subsequently investigated the effects of SD on the forebrain miRNA transcriptome and found that the expression of 48 miRNAs was affected, and in particular that of the activity-dependent miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75 to 1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates genes involved in glutamatergic neurotransmission. A subset of these genes was also affected in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal activity during wakefulness to brain synchrony during sleep through the regulation of glutamatergic signaling