Senescent cells, formed in response to physiological and oncogenic stresses, facilitate protection from tumourigenesis and aid in tissue repair. However, accumulation of such cells in tissues contributes to age-related pathologies. Resistance of senescent cells to apoptotic stimuli may contribute to their accumulation, yet the molecular mechanisms allowing their prolonged viability are poorly characterized. Here we show that senescent cells upregulate the anti-apoptotic proteins BCL-W and BCL-XL. Joint inhibition of BCL-W and BCL-XL by siRNAs or the small-molecule ABT-737 specifically induces apoptosis in senescent cells. Notably, treatment of mice with ABT-737 efficiently eliminates senescent cells induced by DNA damage in the lungs as well as senescent cells formed in the epidermis by activation of p53 through transgenic p14ARF. Elimination of senescent cells from the epidermis leads to an increase in hair-follicle stem cell proliferation. The finding that senescent cells can be eliminated pharmacologically paves the way to new strategies for the treatment of age-related pathologies.
10 A possible explanation of the role of ATP in the transformation of II to III is that it gives rise to additional phosphorylated products, which, however, are too rapidly converted to III to be detected.
The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S-2S transition by Hänsch 1 to a precision of a few parts in 10 15 . Recent technological advances have allowed us to focus on antihydrogen-the antimatter equivalent of hydrogen 2-4 . The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today's Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S-2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 × 10 −10 .
I953 2. After injection of 82p into young rats the specific activity of the free glycerylphosphorylethanolamine after short periods was always greater than that of the phosphatidylethanolamine. This suggests that glycerylphosphorylethanolamine is not an in vivo breakdown product of phosphatidylethanolamine, although other considerations indicate that it does not lie on the main synthetic pathway. 3. The specific activity of a combined form of glycerylphosphorylethanolamine labile to 10% trichloroacetic acid at 40 was always identical with that of phosphatidylethanolamine. The specific activity of the ethanolamine-containing acetal-, phospholipid was also similar. 4. The synthesis of radioactive glycerylphosphorylethanolamine by minced rat brain has been accomplished. No invitro synthesis ofphosphatidylethanolarnine could be demonstrated.
In 1928, Dirac published an equation that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented a class of hitherto unobserved and unimagined particles-antimatter. The existence of particles of antimatter was confirmed with the discovery of the positron (or anti-electron) by Anderson in 1932, but it is still unknown why matter, rather than antimatter, survived after the Big Bang. As a result, experimental studies of antimatter, including tests of fundamental symmetries such as charge-parity and charge-parity-time, and searches for evidence of primordial antimatter, such as antihelium nuclei, have high priority in contemporary physics research. The fundamental role of the hydrogen atom in the evolution of the Universe and in the historical development of our understanding of quantum physics makes its antimatter counterpart-the antihydrogen atom-of particular interest. Current standard-model physics requires that hydrogen and antihydrogen have the same energy levels and spectral lines. The laser-driven 1S-2S transition was recently observed in antihydrogen. Here we characterize one of the hyperfine components of this transition using magnetically trapped atoms of antihydrogen and compare it to model calculations for hydrogen in our apparatus. We find that the shape of the spectral line agrees very well with that expected for hydrogen and that the resonance frequency agrees with that in hydrogen to about 5 kilohertz out of 2.5 × 10 hertz. This is consistent with charge-parity-time invariance at a relative precision of 2 × 10-two orders of magnitude more precise than the previous determination -corresponding to an absolute energy sensitivity of 2 × 10 GeV.
The observation of hyperfine structure in atomic hydrogen by Rabi and co-workers 1-3 and the measurement 4 of the zero-field groundstate splitting at the level of seven parts in 10 13 are important achievements of mid-twentieth-century physics. The work that led to these achievements also provided the first evidence for the anomalous magnetic moment of the electron 5-8 , inspired Schwinger's relativistic theory of quantum electrodynamics 9,10 and gave rise to the hydrogen maser 11 , which is a critical component of modern navigation, geo-positioning and very-long-baseline interferometry systems. Research at the Antiproton Decelerator at CERN by the ALPHA collaboration extends these enquiries into the antimatter sector. Recently, tools have been developed that enable studies of the hyperfine structure of antihydrogen 12 -the antimatter counterpart of hydrogen. The goal of such studies is to search for any differences that might exist between this archetypal pair of atoms, and thereby to test the fundamental principles on which quantum field theory is constructed. Magnetic trapping of antihydrogen atoms 13,14 provides a means of studying them by combining electromagnetic interaction with detection techniques that are unique to antimatter 12,15 . Here we report the results of a microwave spectroscopy experiment in which we probe the response of antihydrogen over a controlled range of frequencies. The data reveal clear and distinct signatures of two allowed transitions, from which we obtain a direct, magneticfield-independent measurement of the hyperfine splitting. From a set of trials involving 194 detected atoms, we determine a splitting of 1,420.4 ± 0.5 megahertz, consistent with expectations for atomic hydrogen at the level of four parts in 10 4 . This observation of the detailed behaviour of a quantum transition in an atom of antihydrogen exemplifies tests of fundamental symmetries such as charge-parity-time in antimatter, and the techniques developed here will enable more-precise such tests.In an earlier experiment 12 using the original ALPHA apparatus 16 , we demonstrated microwave-induced spin flips in trapped antihydrogen. The current work was carried out using the second-generation ALPHA-2 device (Fig.
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