The cell cycle and the circadian clock are essential cyclic cellular processes often synchronous in healthy cells. In this work, we use previously developed mathematical models of the mammalian cell ...cycle and circadian cellular clock in order to investigate their dynamical interactions. Firstly, we study unidirectional cell cycle → clock coupling by proposing a mechanism of mitosis promoting factor (MPF)-controlled REV-ERB
degradation. Secondly, we analyse a bidirectional coupling configuration, where we add the CLOCK : BMAL1-mediated MPF repression via the WEE1 kinase to the first system. Our simulations reproduce ratios of clock to cell cycle period in agreement with experimental observations and give predictions of the system's synchronization state response to a variety of control parameters. Specifically, growth factors accelerate the coupled oscillators and dexamethasone (Dex) drives the system from a 1 : 1 to a 3 : 2 synchronization state. Furthermore, simulations of a Dex pulse reveal that certain time regions of pulse application drive the system from 1 : 1 to 3 : 2 synchronization while others have no effect, revealing the existence of a responsive and an irresponsive system's phase, a result we contextualize with observations on the segregation of Dex-treated cells into two populations.
The low-lying structure of 15C has been investigated via the neutron-removal 16C(d,t) reaction. Along with the known bound neutron sd-shell states, unbound p-shell hole states have been observed. The ...excitation energies and the deduced spectroscopic factors of the cross-shell states are an important measure of the (p)−1(sd)2 neutron configurations in 15C. Our results show a very good agreement with shell-model calculations using the SFO-tls interaction for 15C. However, this same interaction predicted energies that were too low for the corresponding hole states in the N=9 isotone 17O and adjustment of the p-sd and sd-sd monopole terms was required to match the 17O energies. In addition, the excitation energies and spectroscopic factors have been compared to the first calculations of 15C with the ab initio self-consistent Green's function method employing the NNLOsat interaction. The results show the sensitivity to the size of the N=8 shell gap and highlight the need to go beyond the current truncation scheme.
The purpose of this work was to study PuGa 1 at.% alloy behavior from martensitic transformation to the whole reversion process. The relevant phase transformations were investigated as a function of ...temperature via in situ X-ray diffraction and dilatometry analyses carried out at low and high temperatures. The results show that the delta-to-alpha' martensitic transformation occurring at low temperatures is direct and does not involve any intermediate y1 phase. They also reveal that the reverse transformation of the two-phase delta + alpha' alloy during heating involves two competing modes, namely direct and indirect reversion. The latter is associated with a Ga diffusion process that governs the ratio between these reversion modes. More precisely, our study demonstrates that the indirect reversion process consists of a Ga-enrichment of the remaining delta phase as well as the emergence of the beta and gamma phases of pure plutonium. Every stage of indirect reversion has been discussed in relation to the equilibrium phase diagram of the Pu-Ga binary system.
REV-ERBα has been shown to regulate adipogenesis and lipid metabolism as well as to link the circadian timing system to whole body metabolic homeostasis. We thus tested whether polymorphisms in ...REV-ERBα could be associated with metabolic phenotypes in human population samples.
We analyzed the associations between 5 REV-ERBα polymorphisms and anthropometric (body weight, body mass index (BMI), waist and hip circumferences), biochemical (plasma lipid, glucose and insulin levels) and clinical (systolic and diastolic blood pressure) variables in three population-based studies (MONICA Lille n=1155 adults, MONA LISA Lille n=1170 adults and HELENA n=1155 adolescents). We assessed in vitro, the potential influence of one REV-ERBα polymorphism in transient transfection assays using two different cell lines.
We observed significant and consistent associations between the T minor allele of the REV-ERBα rs2071427 polymorphism (located in intron 1) and higher BMI (mean allele effect=+0.33 kg m(-2)) in the MONICA Lille (P=0.02), MONA LISA (P=0.02) and HELENA (P=0.03) studies. The odds ratios for obesity associated with this allele were 1.67 (1.00-2.79) (P=0.05) in MONICA Lille, 1.29 (1.01-1.65) (P=0.04) in MONA LISA Lille and the odds ratio for overweight was 1.48 (1.08-2.03) (P=0.01) in HELENA. In transfection experiments in human hepatocyte-derived cell lines, the REV-ERBα intron 1 directed the transcription of a luciferase reporter gene independently of the rs2071427 polymorphism.
Our results suggest that the REV-ERBα rs2071427 polymorphism modulates body fat mass in both adult and young people.
Abstract Adipose tissue is an abundant source of various cell types including not only adipocytes, but also progenitor and endothelial cells from thestroma. Interest in adipose tissue has surged ...since the identification in 2001 of adipose-derived stem cells (ADSCs) and of the stromal vascular fraction (SVF) obtained from adipose tissue by enzymatic digestion and centrifugation. SVF has been proven effective in ensuring tissue regeneration, thus improving tissue trophicityand vascularisation. These effects have generated strong interest among both physicians and surgeons, particularly in the field of hand surgery. Several applications have been developed and used, for instance to treat Dupuytren's contracture,systemic sclerosis-related hand lesions, and skin ageing at the hand. Other uses are being evaluated in clinical or animal studies. The objective of this article is to review the capabilities of adipose tissue and their current and potential applications in hand surgery.
Unbound states in C17 were investigated via one-neutron removal from a C18 beam at an energy of 245 MeV/nucleon on a carbon target. The energy spectrum of C17, above the single-neutron decay ...threshold, was reconstructed using invariant mass spectroscopy from the measured momenta of the C16 fragment and neutron, and was found to exhibit resonances at Er=0.52(2), 0.77(2), 1.36(1), 1.91(1), 2.22(3) and 3.20(1) MeV. The resonance at Er=0.77(2) MeV Ex=1.51(3) MeV was provisionally assigned as the second 5/2+ state. The two resonances at Er=1.91(1) and 3.20(1) MeV Ex=2.65(2) and 3.94(2) MeV were identified, through comparison of the energies, cross sections and momentum distributions with shell-model and eikonal reaction calculations, as p-shell hole states with spin-parities 1/21− and 3/21−, respectively. A detailed comparison was made with the results obtained using a range of shell-model interactions. The YSOX shell-model Hamiltonian, the cross-shell part of which is based on the monopole-based universal interaction, was found to provide a very good description of the present results and those for the neighbouring odd-A carbon isotopes – in particular for the negative parity cross-shell states.
The physiological effects of estrogens are mediated by two intracellular transcription factors, the estrogen receptors (ERs), that regulate transcription of target genes through binding to specific ...DNA target sequences. Here we describe alterations in cellular responses to different ER agonists and to the anti-estrogenic compound tamoxifen resulting from co-expression of the two ERs in transient co-transfection experiments. Our results demonstrate that ERbeta can act as a negative or positive dominant regulator of ER activity. This is manifested through reduced transcriptional activity at low concentrations of estradiol (E2); increased antagonistic effects of tamoxifen on E2 stimulated activity; and enhanced agonistic action of the phytoestrogenic compound genistein. Furthermore, using chimeric proteins lacking the N-terminal activation function 1 (AF-1), we show that the differential responses of ERalpha and ERbeta to different agonists and antagonists are primarily dictated by inherent differences in the C-terminal ligand-binding domains of the receptors, whereas the magnitude of transcriptional activity is influenced by ERalpha AF-1, but not ERbeta AF-1. The ERalpha AF-1 activity appears to be modulated upon co-expression of both ERs. The alterations in transcriptional activity resulting from co-expression of ERalpha and ERbeta are probably due to the formation of alpha/beta heterodimeric complexes. This study demonstrates that co-localization and subsequent heterodimerization of ERalpha and ERbeta may result in receptor activity distinct from that of ER homodimers.
The isovector and isoscalar components of neutron-proton pairing are investigated in the N=Z unstable nuclei of the fp-shell through the two-nucleon transfer reaction (p,3He) in inverse kinematics. ...The combination of particle and gamma-ray detection with radioactive beams of 56Ni and 52Fe, produced by fragmentation at the GANIL/LISE facility, made it possible to carry out this study for the first time in a closed and an open-shell nucleus in the fp-shell. The transfer cross-sections for ground-state to ground-state (J=0+, T=1) and to the first (J=1+, T=0) state were extracted for both cases together with the transfer cross-section ratios σ(0+,T=1)/σ(1+,T=0). They are compared with second-order distorted-wave born approximation (DWBA) calculations. The enhancement of the ground-state to ground-state pair transfer cross-section close to mid-shell, in 52Fe, points towards a superfluid phase in the isovector channel. For the “deuteron-like” transfer, very low cross-sections to the first (J=1+, T=0) state were observed both for 56Ni(p,3He) and 52Fe(p,3He) and are related to a strong hindrance of this channel due to spin-orbit effect. No evidence for an isoscalar deuteron-like condensate is observed.
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