Coupling between the circadian clock and cell cycle oscillators : implication for healthy cells and malignant growth

Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer

Age-structured cell population model to study the influence of growth factors on cell cycle dynamics.

17 pagesInternational audienceCell proliferation is controlled by many complex regulatory networks. Ourpurpose is to analyse, through mathematical modeling, the effects of growth factors on the dynamics of the division cycle in cell populations. Our work is based on an age-structured PDE model of the cell division cycle within a population of cells in a common tissue. Cell proliferation is at its first stages exponential and is thus characterised by its growth exponent, the first eigenvalue of the linear system we consider here, a growth exponent that we will explicitly evaluate from biological data. Moreover, this study relies on recent and innovative imaging data (fluorescence microscopy) that make us able to experimentally determine the parameters of the model and to validate numerical results. This model has allowed us to study the degree of simultaneity of phase transitions within a proliferating cell population and to analyse the role of an increased growth factor concentration in this process. This study thus aims at helping biologists to elicit the impact of growth factor concentration on cell cycle regulation, at making more precise the dynamics of key mechanisms controlling the division cycle in proliferating cell populations, and eventually at establishing theoretical bases for optimised combined anticancer treatments

Model-based Investigation of the Coupling between the Cell Cycle and the Circadian Clock in Mouse Embryonic Fibroblasts

Experimental observations have put in evidence autonomous self-sustained cir-cadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the milieu is enriched in FBS, the absence of such acceleration in confluent cells, and the absence of any period doubling phenomena. In order to explain these observations, we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective inhibition of Bmal1 transcription, or the selective activation of RevErb-α at the end of the mitosis phase, allow us to fit the experimental data, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on some further $ This article is the extended revision of a preliminary communication published in [1]. Email addresses: [email protected] (Pauline Traynard), [email protected] (Céline Feillet), [email protected] (Sylvain Soliman), [email protected] (Franck Delaunay), [email protected] (François Fages) Preprint submitted to Elsevier December 19, 2015 predictions of the model

Irreversible transformation of ferromagnetic ordered stripe domains in single-shot IR pump - resonant X-ray scattering probe experiments

The evolution of a magnetic domain structure upon excitation by an intense, femtosecond Infra-Red (IR) laser pulse has been investigated using single-shot based time-resolved resonant X-ray scattering at the X-ray Free Electron laser LCLS. A well-ordered stripe domain pattern as present in a thin CoPd alloy film has been used as prototype magnetic domain structure for this study. The fluence of the IR laser pump pulse was sufficient to lead to an almost complete quenching of the magnetization within the ultrafast demagnetization process taking place within the first few hundreds of femtoseconds following the IR laser pump pulse excitation. On longer time scales this excitation gave rise to subsequent irreversible transformations of the magnetic domain structure. Under our specific experimental conditions, it took about 2 nanoseconds before the magnetization started to recover. After about 5 nanoseconds the previously ordered stripe domain structure had evolved into a disordered labyrinth domain structure. Surprisingly, we observe after about 7 nanoseconds the occurrence of a partially ordered stripe domain structure reoriented into a novel direction. It is this domain structure in which the sample's magnetization stabilizes as revealed by scattering patterns recorded long after the initial pump-probe cycle. Using micro-magnetic simulations we can explain this observation based on changes of the magnetic anisotropy going along with heat dissipation in the film.Comment: 16 pages, 6 figure

Evaluation of heat transfer at the cavity-polymer interface in microinjection moulding based on experimental and simulation study

YesIn polymer melt processing, the heat transfer coefficient (HTC) determines the heat flux across the interface of the polymer melt and the mould wall. The HTC is a dominant parameter in cooling simulations especially for microinjection moulding, where the high surface to volume ratio of the part results in very rapid cooling. Moreover, the cooling rate can have a significant influence on internal structure, morphology and resulting physical properties. HTC values are therefore important and yet are not well quantified. To measure HTC in micromoulding, we have developed an experimental setup consisting of a special mould, and an ultra-high speed thermal camera in combination with a range of windows. The windows were laser machined on their inside surfaces to produce a range of surface topographies. Cooling curves were obtained for two materials at different processing conditions, the processing variables explored being melt and mould temperature, injection speed, packing pressure and surface topography. The finite element package Moldflow was used to simulate the experiments and to find the HTC values that best fitted the cooling curves, so that HTC is known as a function of the process variables explored. These results are presented and statistically analysed. An increase in HTC from the standard value of 2500 W/m2C to values in the region 7700 W/m2C was required to accurately model the observations.EPSR

Coupling between the circadian clock and cell cycle oscillators: Implication for healthy cells and malignant growth

Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer

Extracting the spectral signature of alpha-clustering in 44,48,52Ti using the continuous wavelet transform

A novel technique has been developed, making use of the continuous wavelet transform to identify α-clustered states from resonant scattering measurements in regions of high nuclear state density. This technique expedites the investigation of α-clustering in medium mass and heavy nuclei, where the role that α-clustering plays in the structure of the nucleus is poorly understood. Here we report the application of this technique to measurements of the 4He(40,44,48Ca,α) resonant reactions, leading to an assessment of the α-cluster structure of 44,48,52Ti. Alpha-clustering was identified in 44Ti and 52Ti, but was observed to break down in 48Ti. The implications of these results are discussed

Widely tunable two-colour seeded free-electron laser source for resonant-pump resonant-probe magnetic scattering

International audienceThe advent of free-electron laser (FEL) sources delivering two synchronized pulses of different wavelengths (or colours) has made available a whole range of novel pump–probe experiments. This communication describes a major step forward using a new configuration of the FERMI FEL-seeded source to deliver two pulses with different wavelengths, each tunable independently over a broad spectral range with adjustable time delay. The FEL scheme makes use of two seed laser beams of different wavelengths and of a split radiator section to generate two extreme ultraviolet pulses from distinct portions of the same electron bunch. The tunability range of this new two-colour source meets the requirements of double-resonant FEL pump/FEL probe time-resolved studies. We demonstrate its performance in a proof-of-principle magnetic scattering experiment in Fe–Ni compounds, by tuning the FEL wavelengths to the Fe and Ni 3p resonances

The identification of α -clustered doorway states in 44, 48, 52 Ti using machine learning

Abstract: A novel experimental analysis method has been developed, making use of the continuous wavelet transform and machine learning to rapidly identify α-clustering in nuclei in regions of high nuclear state density. This technique was applied to resonant scattering measurements of the 4He(40,44,48Ca,α) resonant reactions, allowing the α-cluster structure of 44,48,52Ti to be investigated. Fragmented α-clustering was identified in 44Ti and 52Ti, while the results for 48Ti were less conclusive, but suggest no such clustering

Alpha clustering in Ti isotopes: 40, 44, 48Ca+ α resonant scattering

Measurements were made of the 4He(40,44,48Ca,α) resonant scattering reactions at 180° and up to Ec.m. ~ 11.5MeV, using the Thick Target Inverse Kinematics technique. These measurements are discussed, with a focus on assessing their usefulness for investigating α-clustering in medium mass 44,48,52Ti nuclei