Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

Mechanisch-technologische Eigenschaften generativ gefertigter Bauteile in Abhängigkeit von der Bauteilorientierung

In dem Artikel wird eine Versuchsreihe vorgestellt und ausgewertet, die zur Ermittlung orientungsabhängiger mechanisch-technologischer Eigenschaften von generativ gefertigten Bauteilen, am Institut für Konstruktionstechnik, durchgeführt wurde. Es wird gezeigt, dass Zugfestigkeit und Bruchdehnung deutlich unter denen des Ausgangsmaterials liegen und sehr stark von der Orientierung des Bauteils abhängen.

Social-Software-Portfolios im Einsatz

Die Dissertationsschrift widmet sich der Erforschung des Online-Lernens mittels Weblogs unter Anwendung der E-Portfolio Methode als einer seit mehreren Jahren verstärkt aufkommenden Lern- und Präsentationsform im Bildungskontext. Über mehrere Lehrveranstaltungen des Studiengangs "Angewandte Medien- und Kommunikationswissenschaft" an der Technischen Universität Ilmenau hinweg wurden drei Fallstudien gebildet. Innerhalb dieser wurde das Führen von eigenen E-Portfolio Blogs durch Studierende über einen Zeitraum von etwa drei Jahren evaluiert. Als Evaluationsziel wurde anhand spezifischer Fragestellungen ermittelt, wie das damit einhergehende selbstgesteuert-konnektive Lernen zu entsprechendem Erfolg führen kann. Hierbei wurde insbesondere die Teildimension Medienkompetenz im Spannungsfeld von Lernaktivität, Wissenserwerb und Informations-/Wissensmanagement betrachtet sowie weitere intervenierende Variablen, wie zum Beispiel Aufwand oder Akzeptanz, berücksichtigt. Inhaltlich wurden zunächst begriffliche Grundlagen dargestellt, die Nutzung von E-Portfolios in Theorie und Praxis beschrieben, Medienkompetenz-Ansätze detailliert aufgezeigt sowie in den Kontext von E-Portfolios gebracht und schließlich eine umfangreiche Analyse des Forschungsstandes aufbereitet. Diese gingen mit Erkenntnissen aus einer qualitativen Vorstudie in Form von fünf leitfadengestützten Experteninterviews einher. Die darauf aufbauende Hauptstudie widmete sich anschließend der Erhebung und Auswertung quantitativer Daten anhand von Online-Befragungen mit den Studierenden zu fünf Zeitpunkten aus intra- und interindividueller Perspektive. Als markanteste empirische Erkenntnis der Arbeit kann festgehalten werden, dass es durch das selbstgesteuert-konnektive Lernen mit E-Portfolio Blogs zu einer nachhaltigen Förderung der Medienkompetenz kommt, die sich auch in signifikanten Zusammenhängen mit den anderen Teildimensionen und intervenierenden Variablen widerspiegelt. Darüber hinaus bieten sich aber auch Potenziale für eine steigende Lernaktivität, einen ansteigenden Wissenserwerb und ein verbessertes Informations-/Wissensmanagement, die es aber noch weiterführend zu erforschen gilt. Demgegenüber können allerdings der entstehende und kontinuierlich hohe Aufwand sowie die erforderliche (Eigen-) Motivation als entscheidende Herausforderungen dieser Lernmethode identifiziert werden.

Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodal metastasis after surgery

INTRODUCTION Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. AIMS AND METHODS Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated. RESULTS The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22-0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance. CONCLUSION This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.

Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors

Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC)-specific p53 deletion, we demonstrate that loss of p53 alone is insufficient to initiate intestinal tumorigenesis but markedly enhances carcinogen-induced tumor incidence and leads to invasive cancer and lymph node metastasis. Whereas p53 controls DNA damage and IEC survival during the initiation stage, loss of p53 during tumor progression is associated with increased intestinal permeability, causing formation of an NF-κB-dependent inflammatory microenvironment and the induction of epithelial-mesenchymal transition. Thus, we propose a p53-controlled tumor-suppressive function that is independent of its well-established role in cell-cycle regulation, apoptosis, and senescence.

Item Sum: A New Technique for Asking Quantitative Sensitive Questions

This article contributes to an ongoing debate about how to measure sensitive topics in population surveys. We propose a novel technique that can be applied to the measurement of quantitative sensitive variables: the item sum technique (IST). This method is closely related to the item count technique, which was developed for the measurement of dichotomous sensitive items. First, we provide a description of our new technique and discuss how data collected by the IST can be analyzed. Second, we present the results of a CATI survey on undeclared work in Germany, in which the IST has been applied. Using an experimental design, we compare the IST to direct questioning. Our empirical results indicate that the IST is a promising data-collection technique for sensitive questions. We conclude by discussing the limitations of the new technique and outlining possible improvements for future studies.

Jüdisches Ceremoniel : das ist: allerhand jüdische Gebräuche, welche die Juden in und ausser dem Tempel, bey allen und jeden Fest-Tägen, im Gebet, im Opfern ... pflegen in acht zu nehmen

aufgesetzt u. auf d. neue verm. von Paul Christian Kirchner

Jüdisches Ceremoniel oder: Beschreibung derjenigen jüdische Gebräuche, welche die Jüden so wol inn - als ausser dem Templ ... in acht zu nehmen pflegen : nunmehro aber bey dieser neuen Aufl. mit accuraten Kupfern versehen ...

Paul Christian Kirchner

Jejunitis and brown bowel syndrome with multifocal carcinogenesis of the small bowel

This is the first report describing a case where prolonged, severe malabsorption from brown bowel syndrome progressed to multifocally spread small bowel adenocarcinoma. This case involves a female patient who was initially diagnosed with chronic jejunitis associated with primary diffuse lymphangiectasia at the age of 26 years. The course of the disease was clinically, endoscopically, and histologically followed for 21 years until her death at the age 47 due to multifocal, metastasizing adenocarcinoma of the small bowel. Multiple lipofuscin deposits (so-called brown bowel syndrome) and severe jejunitis were observed microscopically, and sections of the small bowel showed dense lymphoplasmacytic infiltration of the lamina propria as well as blocked lymphatic vessels. After several decades, multifocal nests of adenocarcinoma cells and extensive, flat, neoplastic mucosal proliferations were found only in the small bowel, along with a loss of the mismatch repair protein MLH1 as a long-term consequence of chronic jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis colon carcinoma syndrome. This article demonstrates for the first time multifocal carcinogenesis in the small bowel in a malabsorption syndrome in an enteritis-dysplasia-carcinoma sequence.

Preoperative Glucagon-like peptide-1 receptor imaging reduces surgical trauma and pancreatic tissue loss in insulinoma patients: a report of three cases

BACKGROUND Insulinomas are rare tumors, in the majority of cases best treated by surgical resection. Preoperative localization of insulinoma is challenging. The more precise the preoperative localization the less invasive and safer is the resection. The purpose of the study is to check the impact of a new technique to localize insulinoma on the surgical strategy. FINDINGS We present exact preoperative localization with Glucagon-like peptide-1 receptor (GLP-1R) imaging. This allows a more precise resection thereby reducing surgical access trauma, loss of healthy pancreatic tissue and increasing safety and quality of the surgical intervention. CONCLUSION With the help of precise preoperative localization of insulinoma with GLP-1R imaging the surgeon is able to minimize the amount of resected healthy pancreatic tissue. We hypothesize that GLP-1R imaging will become a preoperative diagnostic tool to be used for many patients scheduled for open or laparoscopic insulinoma resection.

Lebensgeschichte der Blütenpflanzen Mitteleuropas : spezielle Ökologie der Blütenpflanzen Deutschlands, Österreichs und der Schweiz

von O. von Kirchner; E. Loew; C. Schröter