Involvement of the RNA-binding protein ARE/poly(U)-binding factor 1 (AUF1) in the cytotoxic effects of proinflammatory cytokines on pancreatic beta cells

Aims/hypothesis: Chronic exposure of pancreatic beta cells to proinflammatory cytokines leads to impaired insulin secretion and apoptosis. ARE/poly(U)-binding factor 1 (AUF1) belongs to a protein family that controls mRNA stability and translation by associating with adenosine- and uridine-rich regions of target messengers. We investigated the involvement of AUF1 in cytokine-induced beta cell dysfunction. Methods: Production and subcellular distribution of AUF1 isoforms were analysed by western blotting. To test for their role in the control of beta cell functions, each isoform was overproduced individually in insulin-secreting cells. The contribution to cytokine-mediated beta cell dysfunction was evaluated by preventing the production of AUF1 isoforms by RNA interference. The effect of AUF1 on the production of potential targets was assessed by western blotting. Results: MIN6 cells and human pancreatic islets were found to produce four AUF1 isoforms (p42>p45>p37>p40). AUF1 isoforms were mainly localised in the nucleus but were partially translocated to the cytoplasm upon exposure of beta cells to cytokines and activation of the ERK pathway. Overproduction of AUF1 did not affect glucose-induced insulin secretion but promoted apoptosis. This effect was associated with a decrease in the production of the anti-apoptotic proteins, B cell leukaemia/lymphoma 2 (BCL2) and myeloid cell leukaemia sequence 1 (MCL1). Silencing of AUF1 isoforms restored the levels of the anti-apoptotic proteins, attenuated the activation of the nuclear factor-κB (NFκB) pathway, and protected the beta cells from cytokine-induced apoptosis. Conclusions/interpretation: Our findings point to a contribution of AUF1 to the deleterious effects of cytokines on beta cell functions and suggest a role for this RNA-binding protein in the early phases of type 1 diabete

Hochbegabte Underachiever: Verkannte Schwerarbeiter

Es gibt Schülerinnen und Schüler, die trotz höchster Intelligenzwerte nur dürftige oder ungenügende schulische Leistungen erbringen. Welche Hinweise zu den Gründen solchen Verhaltens liefern die Neurowissenschaften? Und: Welche Ansätze adäquater Förderung lassen sich daraus ableiten? Der vorliegende Artikel resümiert eine schriftliche Arbeit, in deren Rahmen sich Forschungsresultate der Neurowissenschaften, Ergebnisse aus Hochbegabtenstudien und Modelle der Emotionspsychologie zu einer Antwort verdichten. Eine entscheidende Rolle bei Minderleistung Hochbegabter spielen demnach bestimmte dysfunktionale Prozesse der Emotionsverarbeitung. Als logische Konsequenz postuliert der Autor zur adäquaten Förderung Hochbegabter Underachiever Ansätze, in deren Fokus die Verbesserung der Funktionalität eben dieser emotionsverarbeitenden Prozesse liegt

Clinical, Radiological, and Pathological Investigation of Asbestosis

By the radiological examination, differential diagnosis of asbestosis from chronic interstitial pneumonia such as IPF/UIP is difficult. The pathological features of asbestosis show the peribronchiolar fibrosis which suggest that asbestos fibers cause the inflammation of bronchioli. Therefore, the criteria for pathological diagnosis of asbestosis in 2010, contain the finding of peribronchiolar fibrosis again. Chest CT scanning including HRCT for total of 38 cases clinically diagnosed asbestosis were reviewed by 3 radiologists and one pulmonologist. On the other hand, the histology of lung tissues obtained by surgery or autopsy were examined by 4 pulmonological pathologists. Furthermore, the content of asbestos bodies in the lung was counted by phase-contrast microscopy. Thirteen cases were definitely diagnosed of asbestosis in the image including HRCT and 17 cases were diagnosed by the histopathological examination showing lung fibrosis with peribronchiolar fibrosis. Only 10 cases were indicated asbestosis by both the radiological and histopathological examinations. The mean value of asbestos bodies for these cases, was 2,133,255 per gram of dry lung tissue

Microprobe Analysis in Human Pathology

This tutorial paper reviews the literature on the application of microprobe analysis to practical problems in diagnostic human pathology. The goal is to allow the reader ready access to the literature on specific clinical problems. Specimen preparation and commonly encountered artifacts are also considered. It is concluded that energy dispersive x-ray microanalysis and backscattered electron imaging are at present the most generally useful microprobe techniques for clinical work, and are no longer solely research tools. The findings often have diagnostic, therapeutic, and/or legal implications

New techniques for imaging and analyzing lung tissue.

The recent technological revolution in the field of imaging techniques has provided pathologists and toxicologists with an expanding repertoire of analytical techniques for studying the interaction between the lung and the various exogenous materials to which it is exposed. Analytical problems requiring elemental sensitivity or specificity beyond the range of that offered by conventional scanning electron microscopy and energy dispersive X-ray analysis are particularly appropriate for the application of these newer techniques. Electron energy loss spectrometry, Auger electron spectroscopy, secondary ion mass spectrometry, and laser microprobe mass analysis each offer unique advantages in this regard, but also possess their own limitations and disadvantages. Diffraction techniques provide crystalline structural information available through no other means. Bulk chemical techniques provide useful cross-checks on the data obtained by microanalytical approaches. It is the purpose of this review to summarize the methodology of these techniques, acknowledge situations in which they have been used in addressing problems in pulmonary toxicology, and comment on the relative advantages and disadvantages of each approach. It is necessary for an investigator to weigh each of these factors when deciding which technique is best suited for any given analytical problem; often it is useful to employ a combination of two or more of the techniques discussed. It is anticipated that there will be increasing utilization of these technologies for problems in pulmonary toxicology in the decades to come

Züchtung auf Resistenz gegen Anthraknose bei Weisser Lupine

1. Hintergrund 2. Lupinen: Potential und Probleme 3. Anthraknose bei Lupinen 4. Resistenzzüchtung: Stand international 5. FiBL – Lupinenprojekt: Ziele, Massnahmen, erste Ergebnisse, Ausblic