IER2-induced senescence drives melanoma invasion through osteopontin

Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence

Electronic Quantum Coherence in Glycine Molecules Probed with Ultrashort X-ray Pulses in Real Time

Structural changes in nature and technology are driven by charge carrier motion. A process such as charge-directed reactivity that can be operational in radiobiology is more efficient, if energy transfer and charge motion proceeds along well-defined quantum mechanical pathways keeping the coherence and minimizing dissipation. The open question is: do long-lived electronic quantum coherences exist in complex molecules? Here, we use x-rays to create and monitor electronic wave packets in the amino acid glycine. The outgoing photoelectron wave leaves behind a positive charge formed by a superposition of quantum mechanical eigenstates. Delayed x-ray pulses track the induced electronic coherence through the photoelectron emission from the sequential double photoionization processes. The observed sinusoidal modulation of the detected electron yield as a function of time clearly demonstrates that electronic quantum coherence is preserved for at least 25 femtoseconds in this molecule of biological relevance. The surviving coherence is detected via the dominant sequential double ionization channel, which is found to exhibit a phase shift as a function of the photoelectron energy. The experimental results agree with advanced ab-initio simulations.Comment: 54 pages, 11 figure

Charge induced chemical dynamics in glycine probed with time resolved Auger electron spectroscopy

In the present contribution, we use x rays to monitor charge induced chemical dynamics in the photoionized amino acid glycine with femtosecond time resolution. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x ray pulses track the induced coherence through resonant x ray absorption that induces Auger decay. Temporal modulation of the Auger electron signal correlated with specific ions is observed, which is governed by the initial electronic coherence and subsequent vibronic coupling to nuclear degrees of freedom. In the time resolved x ray absorption measurement, we monitor the time frequency spectra of the resulting many body quantum wave packets for a period of 175 fs along different reaction coordinates. Our experiment proves that by measuring specific fragments associated with the glycine dication as a function of the pump probe delay, one can selectively probe electronic coherences at early times associated with a few distinguishable components of the broad electronic wave packet created initially by the pump pulse in the cation. The corresponding coherent superpositions formed by subsets of electronic eigenstates and evolving along parallel dynamical pathways show different phases and time periods in the range of amp; 8722;0.3 0.1 amp; 120587; amp; 8804; amp; 120601; amp; 8804; 0.1 0.2 amp; 120587; and 18.2 1.7 amp; 8722;1.4 amp; 8804; amp; 119879; amp; 8804;23.9 1.2 amp; 8722;1.1 fs. Furthermore, for long delays, the data allow us to pinpoint the driving vibrational modes of chemical dynamics mediating charge induced bond cleavage along different reaction coordinate

Electronic quantum coherence in glycine molecules probed with ultrashort x ray pulses in real time

Here, we use x rays to create and probe quantum coherence in the photoionized amino acid glycine. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x ray pulses track the induced coherence through resonant x ray absorption that induces Auger decay and by photoelectron emission from sequential double photoionization. Sinusoidal temporal modulation of the detected signal at early times 0 to 25 fs is observed in both measurements. Advanced ab initio many electron simulations allow us to explain the first 25 fs of the detected coherent quantum evolution in terms of the electronic coherence. In the kinematically complete x ray absorption measurement, we monitor its dynamics for a period of 175 fs and observe an evolving modulation that may implicate the coupling of electronic to vibronic coherence at longer time scales. Our experiment provides a direct support for the existence of long lived electronic coherence in photoionized biomolecule

Auger electron wave packet interferometry on extreme timescales with coherent soft x rays

Wave packet interferometry provides benchmark information on light-induced electronic quantum states by monitoring their relative amplitudes and phases during coherent excitation, propagation,and decay. The relative phase control of soft x-ray pulse replicas on the single-digit attosecond timescale achieved in our experiments makes this method a powerful tool to probe ultrafast quantum phenomena such as the excitation of Auger shake-up states with sub-cycle precision. In this contribution we present first results obtained for different Auger decay channels upon generating L-shell vacancies in argon atoms using Michelson-type all-reflective interferometric autocorrelation at a central free-electron laser photon energy of 274.7 eV