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In mammals, including humans, nearly all physiological processes are subject to daily oscillations that are governed by a circadian timing system with a complex hierarchical structure. The central pacemaker, residing in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus, is synchronized daily by photic cues transmitted from the retina to SCN neurons via the retinohypothalamic tract. In turn, the SCN must establish phase coherence between self-sustained and cell-autonomous oscillators present in most peripheral cell types. The synchronization signals (Zeitgebers) can be controlled more or less directly by the SCN. In mice and rats, feeding-fasting rhythms, which are driven by the SCN through rest-activity cycles, are the most potent Zeitgebers for the circadian oscillators of peripheral organs. Signaling through the glucocorticoid receptor and the serum response factor also participate in the phase entrainment of peripheral clocks, and these two pathways are controlled by the SCN independently of feeding-fasting rhythms. Body temperature rhythms, governed by the SCN directly and indirectly through rest-activity cycles, are perhaps the most surprising cues for peripheral oscillators. Although the molecular makeup of circadian oscillators is nearly identical in all cells, these oscillators are used for different purposes in the SCN and in peripheral organs.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus which is thought to set the phase of slave oscillators in virtually all body cells. However due to the lack of appropriate in vivo recording technologies it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT Biolumicorder which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.

Des oscillateurs moléculaires générant des rythmes circadiens sont présents dans chaque cellule et contrôlent de nombreux aspects de la physiologie. Ces oscillateurs restent synchronisés grâce à une horloge centrale, dans l'hypothalamus, qui règle la phase des oscillateurs périphériques dans le reste du corps. En utilisant des reporteurs circadiens bioluminescents, nous avons montré que des cycles de température peuvent synchroniser les oscillateurs des fibroblastes en culture et que le facteur de transcription HSF1 est requis durant ce processus. Ceci suggère que le rythme de température corporelle, lui-même régulé par l'horloge centrale, pourrait participer à la synchronisation des oscillateurs périphériques. Nous avons établi un système permettant de visualiser l'expression circadienne de reporteurs bioluminescents dans le foie de souris. Ceci nous a permis de montrer que l'horloge centrale est nécessaire pour coordonner la phase des oscillateurs individuels hépatiques et pour empêcher que cette phase ne change abruptement suite à un rythme alimentaire contradictoire.

The mammalian circadian timing system is composed of a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain and subsidiary oscillators in most peripheral cell types. While oscillators in SCN neurons are known to function in a self-sustained fashion, peripheral oscillators have been thought to damp rapidly when disconnected from the control exerted by the SCN. Using two reporter systems, we monitored circadian gene expression in NIH3T3 mouse fibroblasts in real time and in individual cells. In conjunction with mathematical modeling and cell co-culture experiments, these data demonstrated that in vitro cultured fibroblasts harbor self-sustained and cell-autonomous circadian clocks similar to those operative in SCN neurons. Circadian gene expression in fibroblasts continues during cell division, and our experiments unveiled unexpected interactions between the circadian clock and the cell division clock. Specifically, the circadian oscillator gates cytokinesis to defined time windows, and mitosis elicits phase shifts in circadian cycles.

In the 90’s, the discovery of high concentrations of plastic debris in the oceans generated interest and concern of general public as well as scientific community. Since, the accumulation of plastic debris in the North Pacific and North Atlantic gyres has been widely reported. Surprisingly, only few quantitative studies exist concerning the Mediterranean Sea. The purpose of this study was to examine the distribution, abundance and characteristics of surface micro (size 0.33 – 5.0 mm) and meso (size 5.0 – 50 mm) plastic debris, as compared to the abundance of organic material, in the western Mediterranean Sea. 41 samples have been collected during 2 cruises in September 2011 and August 2012 in regions distributed between positions 38-44°N and 001-010°E (Gulf of Lion, Eastern Spanish coast, Balearic Islands, Sardinia, Corsica). Sample collection was performed using a surface net tow of 330 μm mesh size. Samples were sieved to separate particles smaller than 5 mm from larger ones; plastic pieces were extracted from the plankton and organic matter, and sorted in 6 categories: fragments, pellets, thin films, foams, lines and others (tar, etc.). Each were counted and weighted, as was the organic matter once dried. The concentrations of micro-plastic debris were measured in term of particles number and particles mass per surface unit. The average values of 130’000 parts/km2 and 58’000 mg/km2, respectively were measured, with highest concentrations reaching values superior to 420’000 parts/km2 and 140’000 mg/km2. A qualitative analysis mainly revealed the presence of fragments (77% in mass), but also thin films (13%), foams (7%), pellets (2%) and lines (2%). The average ratio of micro-plastic mass to dry organic material mass has been measured at 1.04. A fraction of the samples was collected in low wind conditions (u10 < 4 m/s), while the other part was collected under medium wind conditions (4 ≤ u10 ≤ 11 m/s). As the vertical distribution of micro-plastic is known to be highly sensitive to wind stress, the values have been corrected and re-interpreted using the methodology proposed by Kukulka & al. 2012. The resulting corrected values suggest that the employed sampling process underestimated the surface micro-plastic concentration by an average factor of 1.55. The average concentrations of meso-plastic debris reached the number of 5’500 parts/km2 and the mass of 120’000 mg/km2, mostly fragments (57%) and thin films (34%). The results revealed that (1) plastic marine debris are widely distributed in western Mediterranean sea, (2) plastic debris concentrations in the Mediterranean Sea are of the same order of magnitude than those measured in the North Atlantic or North Pacific subtropical gyres and (3) plastic debris concentrations are about the same order of magnitude than dry organic material, arguing in favor of the hypothesis of potential misinterpretation and ingestion of these particles by plankton feeders in the sea. Kukulka T, Proskurowski G, Moret-Ferguson S, Meyer D, Lavender Law K, 2012. Geophysical Research Letters, vol 39.

Aim: The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. Methods: To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis. Results: Lipid homeostasis was strongly altered in a disease- and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. The high amounts of non-canonical 1-deoxyceramide present in human adipose tissue most likely come from cell-autonomous synthesis because 1-deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. Conclusion: Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.