University of Duisburg-Essen

About: University of Duisburg-Essen is a education organization based out in Essen, Nordrhein-Westfalen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 16072 authors who have published 39972 publications receiving 1109199 citations.

γ-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin

Abstract: DNA double-strand breaks (DSBs) are extremely dangerous lesions with severe consequences for cell survival and the maintenance of genomic stability. In higher eukaryotic cells, DSBs in chromatin promptly initiate the phosphorylation of the histone H2A variant, H2AX, at Serine 139 to generate gamma-H2AX. This phosphorylation event requires the activation of the phosphatidylinositol-3-OH-kinase-like family of protein kinases, DNA-PKcs, ATM, and ATR, and serves as a landing pad for the accumulation and retention of the central components of the signaling cascade initiated by DNA damage. Regions in chromatin with gamma-H2AX are conveniently detected by immunofluorescence microscopy and serve as beacons of DSBs. This has allowed the development of an assay that has proved particularly useful in the molecular analysis of the processing of DSBs. Here, we first review the role of gamma-H2AX in DNA damage response in the context of chromatin and discuss subsequently the use of this modification as a surrogate marker for mechanistic studies of DSB induction and processing. We conclude with a critical analysis of the strengths and weaknesses of the approach and present some interesting applications of the resulting methodology.

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.

Abstract: Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.

EAE/ASE Recommendations for Image Acquisition and Display Using Three-Dimensional Echocardiography

Abstract: CRT : Cardiac resynchronization therapy ECG : Electrocardiographic LV : Left ventricular RV : Right ventricular SDI : Systolic dyssynchrony index TEE : Transesophageal echocardiographic 3D : Three-dimensional 3DE : Three-dimensional echocardiographic TTE : Transthoracic echocardiographic TV : Tricuspid valve 2D : Two-dimensional Three-dimensional (3D) echocardiographic (3DE) imaging represents a major innovation in cardiovascular ultrasound. Advancements in computer and transducer technologies permit real-time 3DE acquisition and presentation of cardiac structures from any spatial point of view. The usefulness of 3D echocardiography has been demonstrated in (1) the evaluation of cardiac chamber volumes and mass, which avoids geometric assumptions; (2) the assessment of regional left ventricular (LV) wall motion and quantification of systolic dyssynchrony; (3) presentation of realistic views of heart valves; (4) volumetric evaluation of regurgitant lesions and shunts with 3DE color Doppler imaging; and (5) 3DE stress imaging. However, for 3D echocardiography to be implemented in routine clinical practice, a full understanding of its technical principles and a systematic approach to image acquisition and analysis are required. The main goal of this document is to provide a practical guide on how to acquire, analyze, and display the various cardiac structures using 3D echocardiography, as well as limitations of the technique. In addition, this document describes the current and potential clinical applications of 3D echocardiography along with their strengths and weaknesses. ### a. Fully Sampled Matrix-Array Transducers An important milestone in the history of real-time 3D echocardiography was reached shortly after the year 2000, with the development of fully sampled matrix-array transducers. These transducers provided excellent real-time imaging of the beating heart in three dimensions and required significant technological developments in both hardware and software, including transducer design, microelectronic techniques, and computing. Currently, 3DE matrix-array transducers are composed of nearly 3,000 piezoelectric elements with operating frequencies ranging from 2 to 4 MHz and from 5 to 7 MHz for transthoracic echocardiographic (TTE) and transesophageal echocardiographic (TEE) imaging, respectively. These piezoelectric elements are arranged in a matrix configuration within the transducer and require a large number of digital channels for these fully sampled elements to be connected. To reduce both …

Coordination of Rho GTPase activities during cell protrusion

Abstract: The GTPases Rac1, RhoA and Cdc42 act together to control cytoskeleton dynamics. Recent biosensor studies have shown that all three GTPases are activated at the front of migrating cells, and biochemical evidence suggests that they may regulate one another: Cdc42 can activate Rac1 (ref. 8), and Rac1 and RhoA are mutually inhibitory. However, their spatiotemporal coordination, at the seconds and single-micrometre dimensions typical of individual protrusion events, remains unknown. Here we examine GTPase coordination in mouse embryonic fibroblasts both through simultaneous visualization of two GTPase biosensors and using a 'computational multiplexing' approach capable of defining the relationships between multiple protein activities visualized in separate experiments. We found that RhoA is activated at the cell edge synchronous with edge advancement, whereas Cdc42 and Rac1 are activated 2 micro-m behind the edge with a delay of 40 s. This indicates that Rac1 and RhoA operate antagonistically through spatial separation and precise timing, and that RhoA has a role in the initial events of protrusion, whereas Rac1 and Cdc42 activate pathways implicated in reinforcement and stabilization of newly expanded protrusions.

Max Weber, Wirtschaft und Gesellschaft. Grundriss der verstehenden Soziologie, Tübingen 1922

Abstract: „Wirtschaft und Gesellschaft“ ist eine Zusammenstellung von Schriften Max Webers, die seine Frau Marianne 1922 aus dem Nachlass veroffentlichte. Weber hatte vor dem Ersten Weltkrieg eine gewaltige wissenschaftliche Kollektivanstrengung initiiert und herausgegeben, die unter dem Titel „Grundriss der Sozialokonomik“ im Bereich von Politik, Wirtschaft und Gesellschaft alle hierfur relevanten normativen, theoretischen und empirischen Aspekte verbinden wollte. Max Webers eigener Beitrag war als erster Band fur die III. Abteilung mit dem Titel „Wirtschaft und Gesellschaft“ gedacht. Er sollte „Die Wirtschaft und ihre gesellschaftlichen Ordnungen und Machte“ heisen. Die heutige Gestalt beruht auf der Neuausgabe Johannes Winckelmanns. Er versuchte, den Stoff in der von Weber moglicherweise intendierten Gliederung vorzulegen und erganzte die fur „Wirtschaft und Gesellschaft“ noch nicht ausgefuhrten Abschnitte um Stucke aus anderen Veroffentlichungen Webers.