CXCL16 and oxLDL are induced in the onset of diabetic nephropathy

Diabetic nephropathy (DN) is a major cause of end-stage renal failure worldwide. Oxidative stress has been reported to be a major culprit of the disease and increased oxidized low density lipoprotein (oxLDL) immune complexes were found in patients with DN. In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL. In contrast, in primary tubular cells CD36 was mainly involved in the uptake of oxLDL. We further demonstrate that oxLDL down-regulated α3-integrin expression and increased the production of fibronectin in human podocytes. In addition, oxLDL uptake induced the production of reactive oxygen species (ROS) in human podocytes. Inhibition of oxLDL uptake by CXCL16 blocking antibodies abrogated the fibronectin and ROS production and restored α3 integrin expression in human podocytes. Furthermore we present evidence that hyperglycaemic conditions increased CXCL16 and reduced ADAM10 expression in podocytes. Importantly, in streptozotocin-induced diabetic mice an early induction of CXCL16 was accompanied by higher levels of oxLDL. Finally immunofluorescence analysis in biopsies of patients with DN revealed increased glomerular CXCL16 expression, which was paralleled by high levels of oxLDL. In summary, regulation of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of DN and therefore all three proteins may represent potential new targets for diagnosis and therapeutic intervention in DN

Dynamical Mean-Field Theory and Its Applications to Real Materials

Dynamical mean-field theory (DMFT) is a non-perturbative technique for the investigation of correlated electron systems. Its combination with the local density approximation (LDA) has recently led to a material-specific computational scheme for the ab initio investigation of correlated electron materials. The set-up of this approach and its application to materials such as (Sr,Ca)VO_3, V_2O_3, and Cerium is discussed. The calculated spectra are compared with the spectroscopically measured electronic excitation spectra. The surprising similarity between the spectra of the single-impurity Anderson model and of correlated bulk materials is also addressed.Comment: 20 pages, 9 figures, invited paper for the JPSJ Special Issue "Kondo Effect - 40 Years after the Discovery"; final version, references adde

The Kondo Resonance in Electron Spectroscopy

The Kondo resonance is the spectral manifestation of the Kondo properties of the impurity Anderson model, and also plays a central role in the dynamical mean-field theory (DMFT) for correlated electron lattice systems. This article presents an overview of electron spectroscopy studies of the resonance for the 4f electrons of cerium compounds, and for the 3d electrons of V_2O_3, including beginning efforts at using angle resolved photoemission to determine the k-dependence of the resonance. The overview includes the comparison and analysis of spectroscopy data with theoretical spectra as calculated for the impurity model and as obtained by DMFT, and the Kondo volume collapse calculation of the cerium alpha-gamma phase transition boundary, with its spectroscopic underpinnings.Comment: 32 pages, 11 figures, 151 references; paper for special issue of J. Phys. Soc. Jpn. on "Kondo Effect--40 Years after the Discovery

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions - a pilot study

Background: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Methods: Four adult warmblood horses received a unilateral injection of 10 × 106 autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. Results: AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Conclusions: Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 106 AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low-field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT

On the relationship between individual and population health

The relationship between individual and population health is partially built on the broad dichotomization of medicine into clinical medicine and public health. Potential drawbacks of current views include seeing both individual and population health as absolute and independent concepts. I will argue that the relationship between individual and population health is largely relative and dynamic. Their interrelated dynamism derives from a causally defined life course perspective on health determination starting from an individual’s conception through growth, development and participation in the collective till death, all seen within the context of an adaptive society. Indeed, it will become clear that neither individual nor population health is identifiable or even definable without informative contextualization within the other. For instance, a person’s health cannot be seen in isolation but must be placed in the rich contextual web such as the socioeconomic circumstances and other health determinants of where they were conceived, born, bred, and how they shaped and were shaped by their environment and communities, especially given the prevailing population health exposures over their lifetime. We cannot discuss the “what” and “how much” of individual and population health until we know the cumulative trajectories of both, using appropriate causal language