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

Associations of Depressive Symptoms, COVID-19-Related Stressors, and Coping Strategies. A Comparison Between Cities and Towns in Germany

Background: The COVID-19 pandemic has led to a wide range of stressors related to depressive symptoms. Prevention measures like physical distancing have burdened the general population, especially in highly urbanized areas. However, little is known about the associations between pandemic-related stressors, coping strategies, and depressive symptoms in highly urbanized vs. less urbanized environments. Methods: Participants were recruited in a cross-sectional online survey in Germany. Propensity score matching yielded a matched sample of city (n = 453) and town (n = 453) inhabitants. Depressive symptoms, COVID-19-related stressors, and coping strategies were compared between cities and towns. Multiple regression analysis was performed to determine associations between pandemic-related stressors and depressive symptoms for the two groups separately. Results: City inhabitants showed significantly higher depression scores than town inhabitants (t = 2.11, df = 897.95, p = 0.035). Seven coping strategies were more often used by the city sample. Depressive symptoms were associated with “restricted physical social contact” and “difficult housing conditions” (adjusted R2= 0.19, F[9,443] = 12.52, p < 0.001) in city inhabitants, and with “fear of infection” and “difficult housing conditions” (adjusted R2= 0.20, F[9,443] = 13.50, p < 0.001) in town inhabitants. Limitations: The data were collected at the end of the first wave and represent a snapshot without causal inferences. Pandemic-related stressors were measured with a newly developed scale. Conclusion: Depressive symptoms, perceived stressors, and approach/avoidance coping strategies differed between city vs. town inhabitants. These differences should be considered in policy-making and mental health care

Stainless steel made to rust: a robust water-splitting catalyst with benchmark characteristics

The oxygen evolution reaction (OER) is known as the efficiency-limiting step for the electrochemical cleavage of water mainly due to the large overpotentials commonly used materials on the anode side cause. Since Ni–Fe oxides reduce overpotentials occurring in the OER dramatically they are regarded as anode materials of choice for the electrocatalytically driven water-splitting reaction. We herewith show that a straightforward surface modification carried out with AISI 304, a general purpose austenitic stainless steel, very likely, based upon a dissolution mechanism, to result in the formation of an ultra-thin layer consisting of Ni, Fe oxide with a purity >99%. The Ni enriched thin layer firmly attached to the steel substrate is responsible for the unusual highly efficient anodic conversion of water into oxygen as demonstrated by the low overpotential of 212 mV at 12 mA cm−2 current density in 1 M KOH, 269.2 mV at 10 mA cm−2 current density in 0.1 M KOH respectively. The Ni, Fe-oxide layer formed on the steel creates a stable outer sphere, and the surface oxidized steel samples proved to be inert against longer operating times (>150 ks) in alkaline medium. In addition Faradaic efficiency measurements performed through chronopotentiometry revealed a charge to oxygen conversion close to 100%, thus underpinning the conclusion that no “inner oxidation” based on further oxidation of the metal matrix below the oxide layer occurs. These key figures achieved with an almost unrivalled-inexpensive and unrivalled-accessible material, are among the best ever presented activity characteristics for the anodic water-splitting reaction at pH 13

Flexible Features of the Compact Storage Ring in the cSTART Project at Karlsruhe Institute of Technology

Within the cSTART project (compact storage ring for accelerator research and technology), a Very Large Acceptance compact Storage Ring (VLA-cSR) will be realized at the Institute for Beam Physics and Technology (IBPT) of the Karlsruhe Institute of Technology. (KIT). A modified geometry of a compact storage ring operating at 50 MeV energy range has been studied and main features of the new model are described here. The new design, based on 45° bending magnets, is suitable to store a wide momentum spread beam as well as ultra-short electron bunches in the sub-ps range injected from the plasma cell as well as from the Ferninfrarot Linac- Und Test Experiment (FLUTE). The DBA lattice of the VLA-cSR with different settings and relaxed parameters, split elements and higher order optics of tolerable strength allows to improve the dynamic aperture and momentum acceptance to an acceptable level. This contribution discusses the lattice features in detail, expected lifetime, injection, tolerances and different possible operation schemes of the ring

Role of NOD2/CARD15 in coronary heart disease

<p>Abstract</p> <p>Background:</p> <p>Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion. Genetic variation in the <it>CARD15 </it>gene, which encodes NOD2, was previously shown to result in a barrier defect that causes chronic inflammatory disorders (e.g. Crohn disease). In the present study, we investigated the possible involvement of NOD2/<it>CARD15 </it>in the pathology of CHD by <it>i) </it>analyzing the local expression of NOD2 in atherectomy versus healthy tissue (n = 5 each) using histochemical immunofluorescence and <it>ii) </it>by testing the three major functional <it>CARD15 </it>variants (R702W, G908R and 1007fs) for association with early-onset CHD in 900 German patients and 632 healthy controls.</p> <p>Results:</p> <p>In atherectomy tissue of CHD patients, NOD2 was detected in inflammatory cells at the luminal sides of the lesions. However, the allele and genotype frequencies of the three major <it>CARD15 </it>polymorphisms did not differ between CHD patients and controls.</p> <p>Conclusion:</p> <p>The NOD2 up-regulation in atheroma lesions indicates an involvement of this protein in the pathology of CHD. Although NOD2 could be important in local immune response mechanisms, none of the analyzed <it>CARD15 </it>variants seem to play a significant role in the etiology of CHD.</p

Numerical Implementation of the QuEST Function

This paper deals with certain estimation problems involving the covariance matrix in large dimensions. Due to the breakdown of finite-dimensional asymptotic theory when the dimension is not negligible with respect to the sample size, it is necessary to resort to an alternative framework known as large-dimensional asymptotics. Recently, Ledoit and Wolf (2015) have proposed an estimator of the eigenvalues of the population covariance matrix that is consistent according to a mean-square criterion under large-dimensional asymptotics. It requires numerical inversion of a multivariate nonrandom function which they call the QuEST function. The present paper explains how to numerically implement the QuEST function in practice through a series of six successive steps. It also provides an algorithm to compute the Jacobian analytically, which is necessary for numerical inversion by a nonlinear optimizer. Monte Carlo simulations document the effectiveness of the code.Comment: 35 pages, 8 figure

Decay constants of charm and beauty pseudoscalar heavy-light mesons on fine lattices

We compute decay constants of heavy-light mesons in quenched lattice QCD with a lattice spacing of a ~ 0.04 fm using non-perturbatively O(a) improved Wilson fermions and O(a) improved currents. We obtain f_{D_s} = 220(6)(5)(11) MeV, f_D = 206(6)(3)(22) MeV, f_{B_s} = 205(7)(26)(17) MeV and f_B = 190(8)(23)(25) MeV, using the Sommer parameter r_0 = 0.5 fm to set the scale. The first error is statistical, the second systematic and the third from assuming a +-10% uncertainty in the experimental value of r_0. A detailed discussion is given in the text. We also present results for the meson decay constants f_K and f_\pi and the \rho meson mass.Comment: 13 pages, 7 figures. Replaced version contains analysis in terms of improved quark masses instead of bare quark masses, result for f_B changed by 1 MeV. Several typos corrected, in particular error bars in table 4. Version accepted in PL