Transiently Undead Enterocytes Mediate Homeostatic Tissue Turnover in the Adult Drosophila Midgut

We reveal surprising similarities between homeostatic cell turnover in adult Drosophila midguts and undead apoptosis-induced compensatory proliferation (AiP) in imaginal discs. During undead AiP, immortalized cells signal for AiP, allowing its analysis. Critical for undead AiP is the Myo1D-dependent localization of the initiator caspase Dronc to the plasma membrane. Here, we show that Myo1D functions in mature enterocytes (ECs) to control mitotic activity of intestinal stem cells (ISCs). In Myo1D mutant midguts, many signaling events involved in AiP (ROS generation, hemocyte recruitment, and JNK signaling) are affected. Importantly, similar to AiP, Myo1D is required for membrane localization of Dronc in ECs. We propose that ECs destined to die transiently enter an undead-like state through Myo1D-dependent membrane localization of Dronc, which enables them to generate signals for ISC activity and their replacement. The concept of transiently undead cells may be relevant for other stem cell models in flies and mammals

Tumor-promoting function of apoptotic caspases by an amplification loop involving ROS, macrophages and JNK in Drosophila

Apoptosis and its molecular mediators, the caspases, have long been regarded as tumor suppressors and one hallmark of cancer is \u27Evading Apoptosis\u27. However, recent work has suggested that apoptotic caspases can also promote proliferation and tumor growth under certain conditions. How caspases promote proliferation and how cells are protected from the potentially harmful action of apoptotic caspases is largely unknown. Here, we show that although caspases are activated in a well-studied neoplastic tumor model in Drosophila, oncogenic mutations of the proto-oncogene Ras (Ras(V12)) maintain tumorous cells in an \u27undead\u27-like condition and transform caspases from tumor suppressors into tumor promotors. Instead of killing cells, caspases now promote the generation of intra- and extracellular reactive oxygen species (ROS). One function of the ROS is the recruitment and activation of macrophage-like immune cells which in turn signal back to tumorous epithelial cells to activate oncogenic JNK signaling. JNK further promotes and amplifies caspase activity, thereby constituting a feedback amplification loop. Interfering with the amplification loop strongly reduces the neoplastic behavior of these cells and significantly improves organismal survival. In conclusion, Ras(V12)-modified caspases initiate a feedback amplification loop involving tumorous epithelial cells and macrophage-like immune cells that is necessary for uncontrolled tumor growth and invasive behavior

Autophagy-independent function of Atg1 for apoptosis-induced compensatory proliferation

BACKGROUND: ATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Apoptosis-induced proliferation (AiP) is a caspase-directed and JNK-dependent process which is involved in tissue repair and regeneration after massive stress-induced apoptotic cell loss. Under certain conditions, AiP can cause tissue overgrowth with implications for cancer. RESULTS: Here, we show that Atg1 in Drosophila (dAtg1) has a previously unrecognized function for both regenerative and overgrowth-promoting AiP in eye and wing imaginal discs. dAtg1 acts genetically downstream of and is transcriptionally induced by JNK activity, and it is required for JNK-dependent production of mitogens such as Wingless for AiP. Interestingly, this function of dAtg1 in AiP is independent of its roles in autophagy and in neuronal development. CONCLUSION: In addition to a role of dAtg1 in autophagy and neuronal development, we report a third function of dAtg1 for AiP

Non-apoptotic enteroblast-specific role of the initiator caspase Dronc for development and homeostasis of the Drosophila intestine

The initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc(+) in dronc mutant animals, suggesting that proper Dronc function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Dronc do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis

On the quantum, classical and total amount of correlations in a quantum state

We give an operational definition of the quantum, classical and total amount of correlations in a bipartite quantum state. We argue that these quantities can be defined via the amount of work (noise) that is required to erase (destroy) the correlations: for the total correlation, we have to erase completely, for the quantum correlation one has to erase until a separable state is obtained, and the classical correlation is the maximal correlation left after erasing the quantum correlations. In particular, we show that the total amount of correlations is equal to the quantum mutual information, thus providing it with a direct operational interpretation for the first time. As a byproduct, we obtain a direct, operational and elementary proof of strong subadditivity of quantum entropy.Comment: 12 pages ReVTeX4, 2 eps figures. v2 has some arguments clarified and references update

Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila

Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation

High photon energy spectroscopy of NiO: experiment and theory

We have revisited the valence band electronic structure of NiO by means of hard x-ray photoemission spectroscopy (HAXPES) together with theoretical calculations using both the GW method and the local density approximation + dynamical mean-field theory (LDA+DMFT) approaches. The effective impurity problem in DMFT is solved through the exact diagonalization (ED) method. We show that the LDA+DMFT method alone cannot explain all the observed structures in the HAXPES spectra. GW corrections are required for the O bands and Ni-s and p derived states to properly position their binding energies. Our results establish that a combination of the GW and DMFT methods is necessary for correctly describing the electronic structure of NiO in a proper ab-initio framework. We also demonstrate that the inclusion of photoionization cross section is crucial to interpret the HAXPES spectra of NiO.We argue that our conclusions are general and that the here suggested approach is appropriate for any complex transition metal oxide.Comment: 16 pages, 5 figure

All Inequalities for the Relative Entropy

The relative entropy of two n-party quantum states is an important quantity exhibiting, for example, the extent to which the two states are different. The relative entropy of the states formed by reducing two n-party to a smaller number $m$ of parties is always less than or equal to the relative entropy of the two original n-party states. This is the monotonicity of relative entropy. Using techniques from convex geometry, we prove that monotonicity under restrictions is the only general inequality satisfied by relative entropies. In doing so we make a connection to secret sharing schemes with general access structures. A suprising outcome is that the structure of allowed relative entropy values of subsets of multiparty states is much simpler than the structure of allowed entropy values. And the structure of allowed relative entropy values (unlike that of entropies) is the same for classical probability distributions and quantum states.Comment: 15 pages, 3 embedded eps figure

The CoESCA station at BESSY: Auger electron–photoelectron coincidences from surfaces demonstrated for Ag MNN

In this work, we present the CoESCA station for electron–electron coincidence spectroscopy from surfaces, built in a close collaboration between Uppsala University and Helmholtz-Zentrum Berlin at the BESSY II synchrotron facility in Berlin, Germany. We start with a detailed overview of previous work in the field of electron–electron coincidences, before we describe the CoESCA setup and its design parameters. The system is capable of recording shot-to-shot resolved 6D coincidence datasets, i.e. the kinetic energy and the two take off angles for both coincident electrons. The mathematics behind extracting and analysing these multi-dimensional coincidence datasets is introduced, with a focus on coincidence statistics, resulting in fundamental limits of the signal-to-noise ratio and its implications for acquisition times and the size of the raw data stream. The functionality of the CoESCA station is demonstrated for the example of Auger electron–photoelectron coincidences from silver surfaces for photoelectrons from the Ag 3d core levels and their corresponding MNN Auger electrons. The Auger spectra originating from the different core levels, 3d and 3d could be separated and further, the two-hole state energy distributions were determined for these Auger decay channels