Many-body effects in x-ray absorption and magnetic circular dichroism spectra within the LSDA+DMFT framework

The theoretical description of photoemission spectra of transition metals was greatly improved recently by accounting for the correlations between the d electrons within the local spin density approximation (LSDA) plus dynamical mean field theory (DMFT). We assess the improvement of the LSDA+DMFT over the plain LSDA in x-ray absorption spectroscopy, which --- unlike the photoemission spectroscopy --- is probing unocccupied electronic states. By investigating the L2,3-edge x-ray absorption near-edge structure (XANES) and x-ray magnetic circular dichroism (XMCD) of Fe, Co, and Ni, we find that the LSDA+DMFT improves the LSDA results, in particular concerning the asymmetry of the L3 white line. Differences with respect to the experiment, nevertheless, remain --- particularly concerning the ratio of the intensities of the L3 and L2 peaks. The changes in the XMCD peak intensities invoked by the use of the LSDA+DMFT are a consequence of the improved description of the orbital polarization and are consistent with the XMCD sum rules. Accounting for the core hole within the final state approximation does not generally improve the results. This indicates that to get more accurate L2,3-edge XANES and XMCD spectra, one has to treat the core hole beyond the final state approximation.Comment: 4 figures, 1 table, 8 page

Potentiating vascular-targeted photodynamic therapy through CSF-1R modulation of myeloid cells in a preclinical model of prostate cancer

Vascular-targeted photodynamic therapy (VTP) induces rapid destruction of targeted tissues and is a promising therapy for prostate cancer. However, the resulting immune response, which may play an important role in either potentiating or blunting the effects of VTP, is still incompletely understood. Myeloid cells such as myeloid-derived suppressor cells (MDSCs) and macrophages are often found in tumors and are widely reported to be associated with cancer angiogenesis, tissue remodeling, and immunosuppression. These cells are also known to play a critical role in wound-healing, which is induced by rapid tissue destruction. In this study, we investigated the effects of VTP on the recruitment of tumor-infiltrating myeloid cells, specifically MDSCs and tumor-associated macrophages (TAMs), in the Myc-Cap and TRAMP C2 murine prostate cancer models. We report that VTP increased the infiltration of myeloid cells into the tumors, as well as their expression of CSF1R, a receptor required for myeloid differentiation, proliferation, and tumor migration. As anti-CSF1R treatment has previously been used to deplete these cells types in other murine models of prostate cancer, we hypothesized that combining anti-CSF1R with VTP therapy would lead to decreased tumor regrowth and improved survival. Importantly, we found that targeting myeloid cells using anti-CSF1R in combination with VTP therapy decreased the number of tumor MDSCs and TAMs, especially M2 macrophages, as well as increased CD8 T cell infiltration, decreased tumor growth and improved overall survival. These results suggest that targeting myeloid cells via CSF1R targeting is a promising strategy to potentiate the anti-tumor effects of VTP

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Anisotropy of the orbital methods and the magnetic dipole term TzT_z in CrO2{\rm CrO_2}: An {\it ab-initio} studt

A systematic study is performed by the {\it ab-initio} density functional theory of the anisotropy of the orbital moments $$and the magnetic dipole term$$ in bulk ${\rm CrO_2}$. Two different band-structure techniques are used (FLAPW and LMTO-ASA), and the electronic correlations are treated by the local-spin-density approximation (LSDA), the LSDA+ orbital polarization method, and the LSDA+$U$ method. The calculated anisotropies of $$and$$ are very large compared to Fe, Ni and Co but still a factor of 5 and 2 smaller than the anisotropies obtained from a recently suggested analysis of the X-ray magnetic circular dichroism spectra for a thick layer of ${\rm CrO_2}$

The interplay of local electron correlations and ultrafast spin dynamics in fcc Ni

The complex electronic structure of metallic ferromagnets is determined by a balance between exchange interaction, electron hopping leading to band formation, and local Coulomb repulsion. The interplay between the respective terms of the Hamiltonian is of fundamental interest, since it produces most, if not all, of the exotic phenomena observed in the solid state. By combining high energy and temporal resolution in femtosecond time-resolved X-ray absorption spectroscopy with ab initio time-dependent density functional theory we analyze the electronic structure in fcc Ni on the time scale of these interactions in a pump-probe experiment. We distinguish transient broadening and energy shifts in the absorption spectra, which we demonstrate to be caused by electron repopulation and correlation-induced modifications of the electronic structure, respectively. Importantly, the theoretical description of this experimental result hence requires to take the local Coulomb interaction into account, revealing a temporal interplay between band formation, exchange interaction, and Coulomb repulsion

Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells

Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induced cell death in melanoma. ESOM rapidly induced accumulation of reactive oxygen species (ROS) through mitochondrial dysfunctions and involvement of NADPH oxidase. The ROS scavenger N-acetyl--cysteine (NAC) and inhibition of NADPH oxidase significantly reduced ESOM-induced cell death, consistent with inhibition of cytosolic acidification. Autophagy, a cellular catabolic pathway leading to lysosomal degradation and recycling of proteins and organelles, represents a defence mechanism in cancer cells under metabolic stress. ESOM induced the early accumulation of autophagosomes, at the same time reducing the autophagic flux, as observed by WB analysis of LC3-II accumulation and by fluorescence microscopy. Moreover, ESOM treatment decreased mammalian target of rapamycin signalling, as reduced phosphorylation of p70-S6K and 4-EBP1 was observed. Inhibition of autophagy by knockdown of Atg5 and Beclin-1 expression significantly increased ESOM cytotoxicity, suggesting a protective role for autophagy in ESOM-treated cells. The data presented suggest that autophagy represents an adaptive survival mechanism to overcome drug-induced cellular stress and cytotoxicity, including alteration of pH homeostasis mediated by proton pump inhibition

Detection of Light Images by Simple Tissues as Visualized by Photosensitized Magnetic Resonance Imaging

In this study, we show how light can be absorbed by the body of a living rat due to an injected pigment circulating in the blood stream. This process is then physiologically translated in the tissue into a chemical signature that can be perceived as an image by magnetic resonance imaging (MRI). We previously reported that illumination of an injected photosynthetic bacteriochlorophyll-derived pigment leads to a generation of reactive oxygen species, upon oxygen consumption in the blood stream. Consequently, paramagnetic deoxyhemoglobin accumulating in the illuminated area induces changes in image contrast, detectable by a Blood Oxygen Level Dependent (BOLD)-MRI protocol, termed photosensitized (ps)MRI. Here, we show that laser beam pulses synchronously trigger BOLD-contrast transients in the tissue, allowing representation of the luminous spatiotemporal profile, as a contrast map, on the MR monitor. Regions with enhanced BOLD-contrast (7-61 fold) were deduced as illuminated, and were found to overlap with the anatomical location of the incident light. Thus, we conclude that luminous information can be captured and translated by typical oxygen exchange processes in the blood of ordinary tissues, and made visible by psMRI (Fig. 1). This process represents a new channel for communicating environmental light into the body in certain analogy to light absorption by visual pigments in the retina where image perception takes place in the central nervous system. Potential applications of this finding may include: non-invasive intra-operative light guidance and follow-up of photodynamic interventions, determination of light diffusion in opaque tissues for optical imaging and possible assistance to the blind