Lithium Impacts on the Amplitude and Period of the Molecular Circadian Clockwork

Lithium salt has been widely used in treatment of Bipolar Disorder, a mental disturbance associated with circadian rhythm disruptions. Lithium mildly but consistently lengthens circadian period of behavioural rhythms in multiple organisms. To systematically address the impacts of lithium on circadian pacemaking and the underlying mechanisms, we measured locomotor activity in mice in vivo following chronic lithium treatment, and also tracked clock protein dynamics (PER2::Luciferase) in vitro in lithium-treated tissue slices/cells. Lithium lengthens period of both the locomotor activity rhythms, as well as the molecular oscillations in the suprachiasmatic nucleus, lung tissues and fibroblast cells. In addition, we also identified significantly elevated PER2::LUC expression and oscillation amplitude in both central and peripheral pacemakers. Elevation of PER2::LUC by lithium was not associated with changes in protein stabilities of PER2, but instead with increased transcription of Per2 gene. Although lithium and GSK3 inhibition showed opposing effects on clock period, they acted in a similar fashion to up-regulate PER2 expression and oscillation amplitude. Collectively, our data have identified a novel amplitude-enhancing effect of lithium on the PER2 protein rhythms in the central and peripheral circadian clockwork, which may involve a GSK3-mediated signalling pathway. These findings may advance our understanding of the therapeutic actions of lithium in Bipolar Disorder or other psychiatric diseases that involve circadian rhythm disruptions

Stochastic backgrounds of relic gravitons: a theoretical appraisal

Stochastic backgrounds or relic gravitons, if ever detected, will constitute a prima facie evidence of physical processes taking place during the earliest stages of the evolution of the plasma. The essentials of the stochastic backgrounds of relic gravitons are hereby introduced and reviewed. The pivotal observables customarily employed to infer the properties of the relic gravitons are discussed both in the framework of the $\Lambda$CDM paradigm as well as in neighboring contexts. The complementarity between experiments measuring the polarization of the Cosmic Microwave Background (such as, for instance, WMAP, Capmap, Quad, Cbi, just to mention a few) and wide band interferometers (e.g. Virgo, Ligo, Geo, Tama) is emphasized. While the analysis of the microwave sky strongly constrains the low-frequency tail of the relic graviton spectrum, wide-band detectors are sensitive to much higher frequencies where the spectral energy density depends chiefly upon the (poorly known) rate of post-inflationary expansion.Comment: 94 pages, 32 figure

Photoperiod differentially regulates circadian oscillators in central and peripheral tissues of the Syrian hamster.

In many seasonally breeding rodents, reproduction and metabolism are activated by long summer days (LD) and inhibited by short winter days (SD). After several months of SD, animals become refractory to this inhibitory photoperiod and spontaneously revert to LD-like physiology. The suprachiasmatic nuclei (SCN) house the primary circadian oscillator in mammals. Seasonal changes in photic input to this structure control many annual physiological rhythms via SCN-regulated pineal melatonin secretion, which provides an internal endocrine signal representing photoperiod. We compared LD- and SD-housed animals and show that the waveform of SCN expression for three circadian clock genes (Per1, Per2, and Cry2) is modified by photoperiod. In SD-refractory (SD-R) animals, SCN and melatonin rhythms remain locked to SD, reflecting ambient photoperiod, despite LD-like physiology. In peripheral oscillators, Per1 and Dbp rhythms are also modified by photoperiod but, in contrast to the SCN, revert to LD-like, high-amplitude rhythms in SD-R animals. Our data suggest that circadian oscillators in peripheral organs participate in photoperiodic time measurement in seasonal mammals; however, circadian oscillators operate differently in the SCN. The clear dissociation between SCN and peripheral oscillators in refractory animals implicates intermediate factor(s), not directly driven by the SCN or melatonin, in entrainment of peripheral clocks

Photoperiod differentially regulates circadian oscillators in central and peripheral tissues of the Syrian hamster.

In many seasonally breeding rodents, reproduction and metabolism are activated by long summer days (LD) and inhibited by short winter days (SD). After several months of SD, animals become refractory to this inhibitory photoperiod and spontaneously revert to LD-like physiology. The suprachiasmatic nuclei (SCN) house the primary circadian oscillator in mammals. Seasonal changes in photic input to this structure control many annual physiological rhythms via SCN-regulated pineal melatonin secretion, which provides an internal endocrine signal representing photoperiod. We compared LD- and SD-housed animals and show that the waveform of SCN expression for three circadian clock genes (Per1, Per2, and Cry2) is modified by photoperiod. In SD-refractory (SD-R) animals, SCN and melatonin rhythms remain locked to SD, reflecting ambient photoperiod, despite LD-like physiology. In peripheral oscillators, Per1 and Dbp rhythms are also modified by photoperiod but, in contrast to the SCN, revert to LD-like, high-amplitude rhythms in SD-R animals. Our data suggest that circadian oscillators in peripheral organs participate in photoperiodic time measurement in seasonal mammals; however, circadian oscillators operate differently in the SCN. The clear dissociation between SCN and peripheral oscillators in refractory animals implicates intermediate factor(s), not directly driven by the SCN or melatonin, in entrainment of peripheral clocks

A steady-state model for predicting hygrothermal conditions in beds in relation to house dust mite requirements

This paper describes the development, testing and validation of a simple steady- state hygrothermal bed model (BED) which predicts conditions of temperature and relative humidity within the bed core (the occupied space between mattress and covering), given the temperature and relative humidity of the bedroom. BED is the second of three simple steady-state models that in combination allow the impact of modifying bedroom hygrothermal conditions on dust mite populations to be assessed. The first of the trio is Condensation Targeter II, an existing validated model that predicts average monthly conditions of temperature and relative humidity within the bedroom. These conditions are then used as boundary conditions for the BED model which predicts hygrothermal conditions within the bed core. Finally, these outputs are in turn used as inputs to a simple Mite Population Index (MPI) model (to be described elsewhere) that predicts their likely effect on house dust mite population growth in the bed. As reported here, BED has been validated using monitored bedroom and bed data for a full year in three dwellings and the results show that the steady state model predicts monthly bed hygrothermal conditions with a reasonable degree of accuracy. Using Condensation Targeter II and BED in combination, a sensitivity study has been carried out to assess the impact of changes in input parameters of both models on hygrothermal conditions in the bed core. This highlights the importance that the design of the fabric and services of the building has on the hygrothermal conditions in a bed. The impact of climate change has also been assessed using future climate change scenarios. Practical application: This paper describes in detail a simple steady-state model, (BED) which is used to predict the monthly average temperature and relative humidity within a bed, given the ambient conditions within the bedroon. The input parameters, output parameters and the model formulae are provided so that the model can be easily implemented. BED is the second of three simple models that are used to predict, first the bedroon conditions (Condensation Targeter II), second the bed conditions (BED) and finally the likely effect on house dust mite population growth using a simple Mite Population Index (MPI). The Condensation Targeter II and MPI models are described in detail elsewhere. The suite of models allows the testing of the impact of dwelling design and occupant use on likely mite population growth and therefore the health risks of the occupants. It also allows the impact of climate change to be analysed

Low transmission rate of 2009 H1N1 Influenza during a long-distance bus trip

Current data on the risk of transmission of 2009 H1N1 Influenza in public transportation systems (e.g., public trains, busses, airplanes) are conflicting. The main transmission route of this virus is thought to be via droplets, but airborne transmission has not been completely ruled out