Few biological systems are as ubiquitous as the circadian rhythm, a distributed yet inter-connected “system of systems” that coordinates the timing of physiological processes via a self-regulating, flexible network present at every level of biological organization, from cells to cities. Its functional role as the interface between time-dependent internal processes and external environmental cues exposes the circadian rhythm to disruption if these drift out of synchrony. This is especially common in industrialized human societies, where the abun-dance of resources – in combination with the fact that anthropogenic calendars have largely supplanted the sun as the primary determinant of our daily cycles of rest, activity, and sleep – disrupts the circadian rhythm’s ability to synchronize biological processes with each other and the geophysical solar day. Humans are now beholden to two increasingly disconnected clocks, and the ever-accelerating curve of human progress suggests our biological and so-cial times will only grow more disconnected. Longitudinal “out-of-clinic” monitoring is an ecologically valid alternative to well-controlled laboratory studies that can provide insight into how human circadian and behav-ioral rhythms exist in day-to-day life, and so has great potential to provide contextual data for translating chronobiological science into clinical intervention. However, methodological diversity, inconsistent terminology, insufficient reporting, and the sheer number of potential factors has slowed progress. Herein is presented scientific work focused on detecting and quantifying some of these factors, particularly “sociogenic” determinants such as the seven-day week. Through rhythmometric analysis of longitudinal in-home actigraphy, weekly be-havioral patterns were observed in both young adult males (n = 24, mean age = 23.46 years) and older adults with Parkinson’s disease (n = 13 [7 male], mean age = 60.62 years, mean Hoehn & Yahr Stage = 2.31) that evince a seven-day “circaseptan” rhythm of circadi-an and sleep disruption. This is hypothesized to be dependent upon the seven-day calendar week, particularly the regular and abrupt shifts in timing between work and rest days. These perturbations vary by chronotype in young adults, and by disease severity in Parkin-son’s disease. Collectively, these results contribute to the growing evidence that our daily rhythms are shaped by sociogenic factors in addition to well-documented environmental and biological mechanisms. Moreover, the study of these subtle infradian patterns presents serious – yet surmountable – methodological challenges that must be overcome in order to accurately monitor, quantify, analyze, report, and apply findings from observational studies of naturalistic human behavior to scientific and clinical problems.

La plupart des êtres vivants possèdent une horloge circadienne (période de 24heures). Elle leur permet notamment d’anticiper les changements quotidiens (lumière,température) imposés par la rotation de la terre et d’y adapter leur comportement et leurphysiologie. L’horloge est présente dans la plupart des cellules et repose sur deux boucles derégulation transcriptionnelle négative qui génèrent des oscillations d’ARNm des gènesd’horloge. Un délai entre l’accumulation des ARNm et celle des protéines assure lefonctionnement de la boucle de rétroaction. Ce délai est dû à des modifications posttraductionnellesdes protéines PERIOD et TIMELESS. Les oscillations protéiques sontnotamment contrôlées par leur phosphorylation, l’ubiquitination et la dégradation via leprotéasome. L’ubiquitine ligase SCFSlmb induit la dégradation circadienne de PER et de TIM.SCFJetlag contrôle la dégradation de TIM par la lumière, cette dernière intervenant dans lasynchronisation de l’oscillateur.Au cours de notre étude, nous avons identifié une nouvelle ubiquitine ligase, uncomplexe Cul-3, qui contrôle principalement la stabilité de TIM. Nos résultats indiquent queCul-3 contrôle surtout la stabilité de TIM peu phosphorylé, de façon indépendante de PER,tandis que Slmb contrôle principalement la stabilité de TIM phosphorylé. Nous proposons unmodèle dans l'oscillation de TIM régie par deux systèmes d'ubiquitination: Cul-3 pourretarder l'accumulation nocturne de la protéine, et Slmb pour précipiter sa disparition en finde nuit. / Most living organisms possess a circadian clock (24 hours period). This internal clockallows them to anticipate the daily changes (light, temperature) due to the rotation of theearth and consequently adapt their behavior and physiology. The molecular clock relies ontwo negative feedback loops that generate oscillations of the clock gene mRNA. A delaybetween the accumulation of the mRNAs and the proteins is required for the feedback loop,and is generated by post-translational modifications of PERIOD and TIMELESS. The proteinoscillations are controlled by their phosphorylation, ubiquitination and proteasomedependentdegradation. The ubiquitin ligase SCFSlmb induces the circadian degradation ofPER and TIM. SCFJetlag controls the light-dependent degradation of TIM, which is involved inthe resetting of the clock.In our study, we have identified Cul-3, as a new clock ubiquitin ligase that controlsTIM stability. Our results indicate that Cul-3 mostly controls the stability ofhypophosphorylated TIM, independently of PER, whereas SLMB controls the stability ofphosphorylated TIM. We propose a model where TIM oscillations are regulated by twoubiquitination process. Cul-3 delays the night accumulation of TIM, whereas Slmbprecipitates its degradation at the end of the night.