In peripheral tissues circadian gene expression can be driven either by local oscillators or by cyclic systemic cues controlled by the master clock in the brain's suprachiasmatic nucleus. In the latter case, systemic signals can activate immediate early transcription factors (IETFs) and thereby control rhythmic transcription. In order to identify IETFs induced by diurnal blood-borne signals, we developed a novel and unbiased experimental strategy, dubbed Synthetic TAndem Repeat PROMoter (STAR-PROM) screening. This technique relies on the observation that most transcription factor binding sites exist at a relatively high frequency in random DNA sequences. Using STAR-PROM we identified serum response factor (SRF) as an IETF responding to oscillating signaling proteins present in human and rodent sera. Our data suggest that in mouse liver SRF is regulated via dramatic diurnal changes of actin dynamics, leading to the rhythmic translocation of the SRF coactivator Myocardin-related transcription factor–B (MRTF-B) into the nucleus.
Contributors:Deiber Ibanez, Marie-Pierre
The present thesis explores the electroencephalographic (EEG) patterns associated with attention and working memory functions in normal aging and in patients with moderate cognitive decline possibly precursor of Alzheimer’s disease. Across five studies published between 2009 and 2015, we examine the surface EEG fluctuations generated by visual perception and cognitive processing in the form of 1) event-related potentials (ERPs), reflecting postsynaptic potentials of cortical neural populations, and 2) patterns of brain oscillations between 4 and 30 Hz, including theta (4-7.5 Hz), alpha (8-13 Hz) and beta (14-30 Hz) frequency bands, corresponding to rhythmic synchronizations of neuronal discharges in specific cell assemblies. Overall, these studies evidence various specific functional perturbations associated with cognitive activation in older adults and patients with cognitive deficits, demonstrating the capacity of electrophysiological indices to provide sensitive measures of brain function in normal aging and cognitive decline.
Counting statistics investigates the probability P(n,t) that a number n of electrons traverse a nano-scale conductor during a time span t. It is equivalent to consider the zero frequency charge or current correlators, the so-called moments and cumulants, in principle up to infinite order. In this thesis we investigate several aspects of electronic correlations due to interactions. First we investigate the influence of interactions on the counting statistics, considering a generic two-terminal conductor. We show that if the factorial cumulants oscillate as functions of any system parameter or time, then the electrons must be interacting. This statement may be verified in Coulomb blockaded quantum dots, where it is possible to monitor the traversal of electrons in real-time. Moreover, we use a Markovian master equation to describe the first experiment on counting statistics of Andreev events, where two electrons tunnel accross a tunnel barrier between a superconducting lead and a normal metallic island. The statistics are strongly super-Poissonian, reflecting that Andreev events occur in avalanches of different sizes. Finally, we consider finite frequency current noise and show that the noise spectra are in general asymmetric in the applied bias voltage. Using a higher order fluctuation relation, which is an extension of the fluctuation dissipation relation to the non-equilibrium transport regime, we show that this asymmetry is due to a broken electron-hole symmetry, resulting in a finite rectification. We point out that this can occur either due to an asymmetrically applied bias, but more importantly, due to interactions and an inherent chirality of the conductor.
In this thesis, we used three approaches to investigate the neural correlates of the processing of relevant stimuli using electroencephalography (EEG). Time-frequency transforms performed on a cortically blind patient showed frontal slow wave oscillations in response to faces and scrambled faces, supporting the existence of a singular pathway for processing visual stimuli in this neurological condition. Analyses performed on intracranial data revealed that in this case emotion does not modulate the parts of the amygdala that were targeted and that the orbitofrontal cortex seems to better reflect the processing of emotion and stimulus awareness. Finally, we used a cueing paradigm in healthy participants to show that when they are not consciously perceived, emotional faces do not capture attention. Taken together, these findings support previous evidence for a subcortical processing route. However, we also showed that top-down processing cannot be triggered if the cue is not consciously perceived in healthy participants.