BTK Modulates p53 Activity to Enhance Apoptotic and Senescent Responses

p53 is a tumor suppressor that prevents the emergence of transformed cells by inducing apoptosis or senescence, among other responses. Its functions are regulated tightly by posttranslational modifications. Here we show that Bruton's tyrosine kinase (BTK) is a novel modulator of p53. We found that BTK is induced in response to DNA damage and p53 activation. BTK induction leads to p53 phosphorylation, which constitutes a positive feedback loop that increases p53 protein levels and enhances the transactivation of its target genes in response to stress. Inhibiting BTK reduced both p53-dependent senescence and apoptosis. Further, BTK expression also upregulated DNA damage signals and apoptosis. We conclude that despite being involved in oncogenic signals in blood malignancies, BTK has antineoplastic properties in other contexts, such as the enhancement of p53's tumor suppressor responses. Along with evidence that BTK expression correlates with good prognosis in some epithelial tumors, our findings may encourage a reevaluation of the clinical uses of BTK inhibitors in cancer therapy

Laser-assisted decay spectroscopy for the ground states of 180,182Au^180,182Au

status: publishe

Hyperfine anomaly in gold and magnetic moments of Ipi=11/2−I^pi=11/2^- gold isomers

status: publishe

Laser-assisted decay spectroscopy and mass spectrometry of 178Au^178Au

A comprehensive study of the isotope 178Au has been made at the CERN-ISOLDE facility, using resonance laser ionization. Two long-lived states in 178Au were identified—a low-spin ground state and a high-spin isomer—each of which were produced as pure beams. Using the ISOLTRAP precision Penning trap, the excitation energy of the isomeric state in 178Au was determined to be E∗=189(14)keV. The α-decay fine structure patterns of the two states were studied using the Windmill decay station, providing information on the low-lying states in the daughter nucleus 174Ir. Nuclear spin assignments of I(178Aug)=(2,3) and I(178Aum)=(7,8) are made based on the observed β-decay feeding and hyperfine structure intensity patterns. These spin assignments are used for fitting the hyperfine structures of the two states from which values for the magnetic dipole moments are extracted. The extracted moments are compared with calculations using additivity relations to establish the most probable configurations for 178Aug,m

Laser-assisted nuclear decay spectroscopy of 176,177,179Au

A study of the laser-ionized and mass-separated neutron-deficient isotopes Au-176,Au-177,Au-179 was performed using the Resonance Ionization Laser Ion Source and the Windmill detection setup at ISOLDE, CERN. New and improved data on complex fine-structure alpha decays of the three isotopes were deduced, providing insight into the low-lying levels in the daughter nuclei Ir-172,Ir-173,Ir-175. New information on the properties of beta-decay daughter products Pt-177,Pt-179 was also obtained. From the first in-source laser spectroscopy measurements of the hyperfine structure in the atomic 267.6-nm transition of Au-176, the nuclear magnetic moments for both high- and low-spin alpha-decaying states were deduced. Together with the values determined from the additivity relations, they were used to propose the most probable spins and configurations for both states. The a-decay branching ratios were determined as b(alpha)(Au-176(1s)) = 58(5)% and b(alpha)(Au-176(hs)) = 29 (5)%

Laser Spectroscopy of Neutron-Rich 207,208Hg Isotopes : Illuminating the Kink and Odd-Even Staggering in Charge Radii across the N =126 Shell Closure

International audienceThe mean-square charge radii of Hg207,208 (Z=80, N=127, 128) have been studied for the first time and those of Hg202,203,206 (N=122, 123, 126) remeasured by the application of in-source resonance-ionization laser spectroscopy at ISOLDE (CERN). The characteristic kink in the charge radii at the N=126 neutron shell closure has been revealed, providing the first information on its behavior below the Z=82 proton shell closure. A theoretical analysis has been performed within relativistic Hartree-Bogoliubov and nonrelativistic Hartree-Fock-Bogoliubov approaches, considering both the new mercury results and existing lead data. Contrary to previous interpretations, it is demonstrated that both the kink at N=126 and the odd-even staggering (OES) in its vicinity can be described predominately at the mean-field level and that pairing does not need to play a crucial role in their origin. A new OES mechanism is suggested, related to the staggering in the occupation of the different neutron orbitals in odd- and even-A nuclei, facilitated by particle-vibration coupling for odd-A nuclei

Change in structure between the I = 1/2 states in 181Tl and 177,179Au

The first accurate measurements of the α-decay branching ratio and half-life of the Iπ=1/2+ ground state in 181Tl have been made, along with the first determination of the magnetic moments and I=1/2 spin assignments of the ground states in 177,179Au. The results are discussed within the complementary systematics of the reduced α-decay widths and nuclear g factors of low-lying, Iπ=1/2+ states in the neutron-deficient lead region. The findings shed light on the unexpected hindrance of the 1/2+→1/2+, 181Tl→g177Aug α decay, which is explained by a mixing of π3s1/2 and π2d3/2 configurations in 177Aug, whilst 181Tlg remains a near-pure π3s1/2. This conclusion is inferred from the g factor of 177Aug which has an intermediate value between those of π3s1/2 and π2d3/2 states. A similar mixed configuration is proposed for the Iπ=1/2+ ground state of 179Au. This mixing may provide evidence for triaxial shapes in the ground states in these nuclei

Charge radii, moments, and masses of mercury isotopes across the N=126N=126 shell closure

Combining laser spectroscopy in a Versatile Arc Discharge and Laser Ion Source, with Penning-trap mass spectrometry at the CERN-ISOLDE facility, this work reports on mean-square charge radii of neutron-rich mercury isotopes across the $N = 126$ shell closure, the electromagnetic moments of $^{207}$Hg and more precise mass values of $^{206-208}$Hg. The odd-even staggering (OES) of the mean square charge radii and the kink at $N = 126$ are analyzed within the framework of covariant density functional theory (CDFT), with comparisons between different functionals to investigate the dependence of the results on the underlying single-particle structure. The observed features are defined predominantly in the particle-hole channel in CDFT, since both are present in the calculations without pairing. However, the magnitude of the kink is still affected by the occupation of the $1i_{11/2}$ and $2g_{9/2}$ orbitals with a dependence on the relative energies as well as pairing.Comment: 20 pages, 12 figures, Phys. Rev. C in pres

Shape staggering of midshell mercury isotopes from in-source laser spectroscopy compared with density-functional-theory and Monte Carlo shell-model calculations

Neutron-deficient 177−185Hg isotopes were studied using in-source laser resonance-ionization spectroscopy at the CERN-ISOLDE radioactive ion-beam facility in an experiment combining different detection methods tailored to the studied isotopes. These include either α-decay tagging or multireflection time-of-flight gating for isotope identification. The endpoint of the odd-even nuclear shape staggering in mercury was observed directly by measuring for the first time the isotope shifts and hyperfine structures of 177−180Hg. Changes in the mean-square charge radii for all mentioned isotopes, magnetic dipole, and electric quadrupole moments of the odd-A isotopes and arguments in favor of I=7/2 spin assignment for 177,179Hg were deduced. Experimental results are compared with density functional theory (DFT) and Monte Carlo shell model (MCSM) calculations. DFT calculations using Skyrme parametrizations predict a jump in the charge radius around the neutron N=104 midshell, with an odd-even staggering pattern related to the coexistence of nearly degenerate oblate and prolate minima. This near-degeneracy is highly sensitive to many aspects of the effective interaction, a fact that renders perfect agreement with experiments out of reach for current functionals. Despite this inherent difficulty, the SLy5s1 and a modified UNEDF1SO parametrization predict a qualitatively correct staggering that is off by two neutron numbers. MCSM calculations of states with the experimental spins and parities show good agreement for both electromagnetic moments and the observed charge radii. A clear mechanism for the origin of shape staggering within this context is identified: a substantial change in occupancy of the proton πh9/2 and neutron νi13/2 orbitals

Characterization of the shape-staggering effect in mercury nuclei

In rare cases, the removal of a single proton (Z) or neutron (N) from an atomic nucleus leads to a dramatic shape change. These instances are crucial for understanding the components of the nuclear interactions that drive deformation. The mercury isotopes (Z = 80) are a striking example1,2: their close neighbours, the lead isotopes (Z = 82), are spherical and steadily shrink with decreasing N. The even-mass (A = N + Z) mercury isotopes follow this trend. The odd-mass mercury isotopes 181,183,185Hg, however, exhibit noticeably larger charge radii. Due to the experimental difficulties of probing extremely neutron-deficient systems, and the computational complexity of modelling such heavy nuclides, the microscopic origin of this unique shape staggering has remained unclear. Here, by applying resonance ionization spectroscopy, mass spectrometry and nuclear spectroscopy as far as 177Hg, we determine 181Hg as the shape-staggering endpoint. By combining our experimental measurements with Monte Carlo shell model calculations, we conclude that this phenomenon results from the interplay between monopole and quadrupole interactions driving a quantum phase transition, for which we identify the participating orbitals. Although shape staggering in the mercury isotopes is a unique and localized feature in the nuclear chart, it nicely illustrates the concurrence of single-particle and collective degrees of freedom at play in atomic nuclei