Response to Therapeutic Sleep Deprivation: A Naturalistic Study of Clinical and Genetic Factors and Post-treatment Depressive Symptom Trajectory

Research has shown that therapeutic sleep deprivation (SD) has rapid antidepressant effects in the majority of depressed patients. Investigation of factors preceding and accompanying these effects may facilitate the identification of the underlying biological mechanisms. This exploratory study aimed to examine clinical and genetic factors predicting response to SD and determine the impact of SD on illness course. Mood during SD was also assessed via visual analogue scale. Depressed inpatients (n = 78) and healthy controls (n = 15) underwent ~36 h of SD. Response to SD was defined as a score of ≤ 2 on the Clinical Global Impression Scale for Global Improvement. Depressive symptom trajectories were evaluated for up to a month using self/expert ratings. Impact of genetic burden was calculated using polygenic risk scores for major depressive disorder. In total, 72% of patients responded to SD. Responders and non-responders did not differ in baseline self/expert depression symptom ratings, but mood differed. Response was associated with lower age (p = 0.007) and later age at life-time disease onset (p = 0.003). Higher genetic burden of depression was observed in non-responders than healthy controls. Up to a month post SD, depressive symptoms decreased in both patients groups, but more in responders, in whom effects were sustained. The present findings suggest that re-examining SD with a greater focus on biological mechanisms will lead to better understanding of mechanisms of depression

The waking brain: an update

Wakefulness and consciousness depend on perturbation of the cortical soliloquy. Ascending activation of the cerebral cortex is characteristic for both waking and paradoxical (REM) sleep. These evolutionary conserved activating systems build a network in the brainstem, midbrain, and diencephalon that contains the neurotransmitters and neuromodulators glutamate, histamine, acetylcholine, the catecholamines, serotonin, and some neuropeptides orchestrating the different behavioral states. Inhibition of these waking systems by GABAergic neurons allows sleep. Over the past decades, a prominent role became evident for the histaminergic and the orexinergic neurons as a hypothalamic waking center

Precision spectroscopy of helium in a magic wavelength optical dipole trap

Improvements in both theory and frequency metrology of few-electron systems such as hydrogen and helium have enabled increasingly sensitive tests of quantum electrodynamics (QED), as well as ever more accurate determinations of fundamental constants and the size of the nucleus. At the same time advances in cooling and trapping of neutral atoms have revolutionized the development of increasingly accurate atomic clocks. Here, we combine these fields to reach the highest precision on an optical tranistion in the helium atom to date by employing a Bose-Einstein condensate confined in a magic wavelength optical dipole trap. The measured transition accurately connects the ortho- and parastates of helium and constitutes a stringent test of QED theory. In addition we test polarizability calculations and ultracold scattering properties of the helium atom. Finally, our measurement probes the size of the nucleus at a level exceeding the projected accuracy of muonic helium measurements currently being performed in the context of the proton radius puzzle

Functional Promoter -31G>C Variant in Survivin Gene Is Associated with Risk and Progression of Renal Cell Cancer in a Chinese Population

BACKGROUND: Survivin is an inhibitor of apoptosis protein and is involved in the occurrence and progression of human malignancies. Recently, a functional polymorphism (-31G>C, rs9904341) in the promoter of survivin has been shown to influence its expression and confer susceptibility to different types of cancer. The present study was aimed to investigate whether the polymorphism also influences susceptibility and progression of renal cell cancer (RCC) in a Chinese population. METHODS: We genotyped this polymorphism using the TaqMan assay in a case-control study comprised of 710 RCC patients and 760 controls. The logistic regression was used to assess the genetic association with occurrence and progression of RCC. RESULTS: Compared with the genotypes containing G allele (GG and GC), we found a statistically significant increased occurrence of RCC associated with the CC genotype [P = 0.006, adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76]. The polymorphism was associated with risk of developing advanced stage (OR = 2.02, 95%CI = 1.34-3.07) and moderately differentiated (OR = 1.75; 95%CI = 1.20-2.54) RCC. Furthermore, the patients carrying the CC genotype had a significantly greater prevalence of high clinical stage disease (P(trend) = 0.003). Similar results were also observed when we restricted the analysis to clear cell RCC, a major histological type of RCC. CONCLUSIONS: Our results suggest that the functional -31G>C polymorphism in the promoter of survivin may influence the susceptibility and progression of RCC in the Chinese population. Large population-based prospective studies are required to validate our findings

A wake-active locomotion circuit depolarizes a sleep-active neuron to switch on sleep

Sleep-active neurons depolarize during sleep to suppress wakefulness circuits. Wake-active wake-promoting neurons in turn shut down sleep-active neurons, thus forming a bipartite flip-flop switch. However, how sleep is switched on is unclear because it is not known how wakefulness is translated into sleep-active neuron depolarization when the system is set to sleep. Using optogenetics in Caenorhabditis elegans, we solved the presynaptic circuit for depolarization of the sleep-active RIS neuron during developmentally regulated sleep, also known as lethargus. Surprisingly, we found that RIS activation requires neurons that have known roles in wakefulness and locomotion behavior. The RIM interneurons-which are active during and can induce reverse locomotion-play a complex role and can act as inhibitors of RIS when they are strongly depolarized and as activators of RIS when they are modestly depolarized. The PVC command interneurons, which are known to promote forward locomotion during wakefulness, act as major activators of RIS. The properties of these locomotion neurons are modulated during lethargus. The RIMs become less excitable. The PVCs become resistant to inhibition and have an increased capacity to activate RIS. Separate activation of neither the PVCs nor the RIMs appears to be sufficient for sleep induction; instead, our data suggest that they act in concert to activate RIS. Forward and reverse circuit activity is normally mutually exclusive. Our data suggest that RIS may be activated at the transition between forward and reverse locomotion states, perhaps when both forward (PVC) and reverse (including RIM) circuit activity overlap. While RIS is not strongly activated outside of lethargus, altered activity of the locomotion interneurons during lethargus favors strong RIS activation and thus sleep. The control of sleep-active neurons by locomotion circuits suggests that sleep control may have evolved from locomotion control. The flip-flop sleep switch in C. elegans thus requires an additional component, wake-active sleep-promoting neurons that translate wakefulness into the depolarization of a sleep-active neuron when the worm is sleepy. Wake-active sleep-promoting circuits may also be required for sleep state switching in other animals, including in mammals

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Two-particle azimuthal correlations in photonuclear ultraperipheral Pb plus Pb collisions at 5.02 TeV with ATLAS

Two-particle long-range azimuthal correlations are measured in photonuclear collisions using 1.7 nb − 1 of 5.02 TeV Pb + Pb collision data collected by the ATLAS experiment at the CERN Large Hadron Collider. Candidate events are selected using a dedicated high-multiplicity photonuclear event trigger, a combination of information from the zero-degree calorimeters and forward calorimeters, and from pseudorapidity gaps constructed using calorimeter energy clusters and charged-particle tracks. Distributions of event properties are compared between data and Monte Carlo simulations of photonuclear processes. Two-particle correlation functions are formed using charged-particle tracks in the selected events, and a template-fitting method is employed to subtract the nonflow contribution to the correlation. Significant nonzero values of the second- and third-order flow coefficients are observed and presented as a function of charged-particle multiplicity and transverse momentum. The results are compared with flow coefficients obtained in proton-proton and proton-lead collisions in similar multiplicity ranges, and with theoretical expectations. The unique initial conditions present in this measurement provide a new way to probe the origin of the collective signatures previously observed only in hadronic collision

Medium-Induced Modification of Z-Tagged Charged Particle Yields in Pb+Pb Collisions at 5.02 TeV with the ATLAS Detector

The yield of charged particles opposite to a Z boson with large transverse momentum ( p T ) is measured in 260     pb − 1 of p p and 1.7     nb − 1 of Pb + Pb collision data at 5.02 TeV per nucleon pair recorded with the ATLAS detector at the Large Hadron Collider. The Z boson tag is used to select hard-scattered partons with specific kinematics, and to observe how their showers are modified as they propagate through the quark-gluon plasma created in Pb + Pb collisions. Compared with p p collisions, charged-particle yields in Pb + Pb collisions show significant modifications as a function of charged-particle p T in a way that depends on event centrality and Z boson p T . The data are compared with a variety of theoretical calculations and provide new information about the medium-induced energy loss of partons in a p T regime difficult to measure through other channels

Search for pair production of third-generation scalar leptoquarks decaying into a top quark and a τ-lepton in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for pair production of third-generation scalar leptoquarks decaying into a top quark and a τ-lepton is presented. The search is based on a dataset of pp collisions at s√ = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Events are selected if they have one light lepton (electron or muon) and at least one hadronically decaying τ -lepton, or at least two light leptons. In addition, two or more jets, at least one of which must be identified as containing b-hadrons, are required. Six final states, defined by the multiplicity and flavour of lepton candidates, are considered in the analysis. Each of them is split into multiple event categories to simultaneously search for the signal and constrain several leading backgrounds. The signal-rich event categories require at least one hadronically decaying τ-lepton candidate and exploit the presence of energetic final-state objects, which is characteristic of signal events. No significant excess above the Standard Model expectation is observed in any of the considered event categories, and 95% CL upper limits are set on the production cross section as a function of the leptoquark mass, for different assumptions about the branching fractions into tτ and bν. Scalar leptoquarks decaying exclusively into tτ are excluded up to masses of 1.43 TeV while, for a branching fraction of 50% into tτ, the lower mass limit is 1.22 TeV

Search for bottom-squark pair production in pp collision events at √s=13 TeV with hadronically decaying τ-leptons, b-jets, and missing transverse momentum using the ATLAS detector

A search for pair production of bottom squarks in events with hadronically decaying τ -leptons, b -tagged jets, and large missing transverse momentum is presented. The analyzed dataset is based on proton-proton collisions at √ s = 13     TeV delivered by the Large Hadron Collider and recorded by the ATLAS detector from 2015 to 2018, and corresponds to an integrated luminosity of 139     fb − 1 . The observed data are compatible with the expected Standard Model background. Results are interpreted in a simplified model where each bottom squark is assumed to decay into the second-lightest neutralino ˜ χ 0 2 and a bottom quark, with ˜ χ 0 2 decaying into a Higgs boson and the lightest neutralino ˜ χ 0 1 . The search focuses on final states where at least one Higgs boson decays into a pair of hadronically decaying τ -leptons. This allows the acceptance and thus the sensitivity to be significantly improved relative to the previous results at low masses of the ˜ χ 0 2 , where bottom-squark masses up to 850 GeV are excluded at the 95% confidence level, assuming a mass difference of 130 GeV between ˜ χ 0 2 and ˜ χ 0 1 . Model-independent upper limits are also set on the cross section of processes beyond the Standard Model