Einfluss von Catechingallat auf Proliferation und TRAIL-vermittelte Apoptose von Pankreastumorzellen

Das duktale Adenokarzinom des Pankreas ist eine hochmaligne Erkrankung mit hoher Letalität. Die therapeutischen Optionen begrenzen sich häufig auf eine palliative Chemotherapie und Radiatio. Gegen die mithilfe dieser Therapien induzierte Apoptose zeigen Pankreastumorzellen im Gegensatz zu anderen soliden Karzinomen eine erhöhte Resistenz. Ein Grund dafür ist eine Proteindysregulation der Apoptosekaskade auf molekularer Ebene durch Proteine der BcL-2 Familie, IAPs sowie NF-κB und TRAF-2. Sowohl epidemiologisch als auch unter in-vitro Bedingungen konnten antikarzinogene Effekte von Catechinen des grünen Tees nachgewiesen werden. In der vorliegenden Arbeit wurde das antikarzinogene Potential des Catechins Catechingallat (CG) unter in vitro Bedingungen auf die Pankreastumorzelllinien BxPC3 und PancTuI analysiert. Zunächst konnte nachgewiesen werden, dass CG die Proliferation von BxPC3 und PancTuI in vitro verlangsamt. Insbesondere bei einer Konzentration von 80 µM CG zeigte sich die Proliferationsrate der Pankreastumorzellen verringert. Auch die Inkorporation des Proliferationsmarkers [3H]-Thymidin war nach Behandlung mit 80 µM CG deutlich reduziert. Ein phasenspezifischer Zellzyklusarrest oder Induktion von Apoptose konnte in der daraufhin durchgeführten durchflusszytometrischen Zellzyklusanalyse nicht nachgewiesen werde. Die Proliferation wird durch Sezernierung von autokrin wirkenden Zytokinen durch die Pankreastumorzellen reguliert. Hierbei zeigten sich aufgrund einer bei beiden Tumorzelllinien gleichgerichteten Regulationstendenz nach CG-Behandlung die Zytokine MDC, HCC-4, CXCL-16, PDGF-AA, Amphiregulin, IL-6R sowie IL-9 möglicherweise verantwortlich für die antiproliferativen Effekt von CG. Nachdem unter alleinigem CG-Einfluss eine Proliferationsverlangsamung nachgewiesen werden konnte, wurde nun eine mögliche Sensibilisierung der Pankreastumorzellen für die ligandeninduzierte Apoptose durch TRAIL untersucht. Hierbei zeigte sich eine gegenüber der Kontrolle erhöhte Sensibilität für TRAIL-vermittelte Apoptose nach Vorbehandlung mit 80 µM CG. Die Proteine BID, Caspase-3 und Caspase-8 der Apoptosekaskade selbst zeigten keine erheblichen Veränderungen. Bei den apoptoseregulierenden IAPs cIAP-2 und insbesondere Survivin konnte unter Einfluss von CG eine deutliche Minderung des Proteinspiegels nachgewiesen werden. Auch das Protein der BcL-2-Familie BcL-XL, welches eine Apoptoseresistenz bei Pankreastumorzellen anzeigt, war nach Behandlung mit 80 µM CG herunterreguliert. Der Transkriptionsfaktor NF-κB ist über die Regulation der IAPs und der BcL-2 Proteine an antiapoptotischen Signalkaskaden im Rahmen von TRAIL-vermittelter Apoptose beteiligt. Nach Vorbehandlung mit 80 µM CG und anschließender Apoptosestimulation mit TRAIL konnte eine deutliche Verminderung der DNA-Bindungsaktivität von NF-κB gegenüber alleiniger TRAIL-Stimulation gezeigt werden. Das an der NF-κB-Signalgebung beteiligte TRAF-2 war unter CG Einfluss unverändert. Insgesamt erwies sich das grüne Tee Polyphenol Catechingallat als eine vielversprechende Substanz sowohl im Hinblick auf eine Proliferationsinhibition als auch hinsichtlich einer Sensitivierung für TRAIL-vermittelte Apoptose von Pankreastumorzellen

A three-marker DNA barcoding approach for ecological studies of xerothermic plants and herbivorous insects from central Europe

The DNA barcoding technique developed for species identification has recently been adapted for ecological studies (e.g. host plant identification). Comprehensive barcode databases, covering most species inhabiting areas, habitats or communities of interest are essential for reliable and efficient identification of plants. Here we present a three-barcode (plastid rbcL and matK genes and the trnL intron) database for xerothermic plant species from central Europe. About 85% of the xerothermic plant species (126 out of c. 150) known to be associated with xerothermic habitats were collected and barcoded. The database contains barcodes for 117 (rbcL and trnL) and 96 (matK) species. Interspecific nucleotide distances were in the ranges 0–17.9% (0–3.2% within genera) for rbcL, 0–44.4% (0–3.1%) for trnL and 0–52.5% (0–10.9%) for matK. Blast-searching of each sequence in the database against the entire database showed that species-level identification is possible for 89.6% (rbcL), 98.4% (trnL) and 96.4% (matK) of examined plant species. The utility of the presented database for identification of host plants was demonstrated using two insect species associated with xerothermic habitats: the oligophagous leaf-beetle Cheilotoma musciformis (for which two host plants in Fabaceae were identified) and the polyphagous weevil Polydrusus inustus (which was found to feed on 14 host plants, mostly Rosaceae, Asteraceae and Fabaceae). The developed database will be useful in various applications, including biodiversity, phylogeography, conservation and ecolog

Chandra observations of the bursting X-ray transient SAX J1747.0-2853 during low-level accretion activity

We present Chandra/ACIS observations of the bursting X-ray transient SAX J1747.0-2853 performed on 18 July 2001. We detected a bright source at the position of R.A = 17^h 47^m 02.60^s and Dec. = -28 52' 58.9'' (J2000.0; with a 1 sigma error of ~0.7 arcseconds), consistent with the BeppoSAX and ASCA positions of SAX J1747.0-2853 and with the Ariel V position of the transient GX +0.2,-0.2, which was active during the 1970's. The 0.5-10 keV luminosity of the source during our observations was ~3 x 10^{35} erg/s (assuming a distance of 9 kpc) demonstrating that the source was in a low-level accretion state. We also report on the long-term light curve of the source as observed with the all sky monitor aboard the Rossi X-ray Timing Explorer. After the initial 1998 outburst, two more outbursts (in 2000 and 2001) were detected with peak luminosities about two orders of magnitude larger than our Chandra luminosity. Our Chandra observation falls in-between those two outbursts, making the outburst history for SAX J1747.0-2853 complex. Those bright 2000 and 2001 outbursts combined with the likely extended period of low level activity in-between those outbursts strongly suggest that the classification of SAX J1747.0-2853 as a faint X-ray transient was premature. It might be possible that the other faint X-ray transients also can exhibit bright, extended outbursts which would eliminate the need for a separate sub-class of X-ray transients. We discuss our results also in the context of the behavior of X-ray binaries accreting at low levels with luminosities around 10^{35} erg/s, a poorly studied accretion rate regime.Comment: Accepte for publication in ApJ, 11 July 200

'I trap her with a CD, then tomorrow find her with a big old man who bought her a smart phone'. Constructions of masculinities and transactional sex: a qualitative study from North-Western Tanzania.

Men's role in transactional sex is relatively unexplored, limiting initiatives to prevent exploitative transactional sex and its negative health implications for girls and women. We addressed this literature gap by conducting eight focus group discussions and twenty in-depth-interviews with boys and men aged 14?-?49?years in 2015 in Tanzania. We employed a novel combination of theoretical perspectives - gender and masculinities, and social norms - to understand how transactional sex participation contributes to perpetuating gendered hierarchies, and how reference groups influence men's behaviour. Findings signal two gender norms that men display within transactional sex: the expectation of men's provision in sexual relationships, and the expectation that men should exhibit heightened sexuality and sexual prowess. Adherence to these expectations in transactional sex relationships varied between older and younger men and created hierarchies among men and between men and women and girls. We found that approval of transactional sex was contested. Although young men were likely to object to transactional sex, they occupied a structurally weaker position than older men. Findings suggest that interventions should employ gender synchronised and gender transformative approaches and should prioritise the promotion of alternative positive norms over preventing the exchange of gifts or money in relationships

Products as Affective Modifiers of Identities

© The Author(s) 2015. Are salesclerks seen as better, more powerful, or more active when they drive Mustangs? What about entrepreneurs? What about driving a mid-sized car? Intuitively, we have ideas about these, but much of the research on the affective nature of products is on purchasing, desires, and self-fulfillment. Drawing on symbolic interactionism, we argue that people's association with products has some basis in the impression management of their identity. For this to occur, there must be some cultural consensus about the way that products modify identities. Drawing on affect control theory's (ACT) methodology and equations, we measure the goodness, powerfulness, and activeness of several products, identities, and the associated product-modified identities to explore how products function as affective modifiers of identities. We find consistent effects across several types of technology products, whereby products pull the modified identity in the direction of the products' affective qualities. Support is established for the ACT equations that predict how traits modify identities as also having utility for predicting how products modify identities. This suggests that the opening questions can be answered empirically by measuring cultural-specific sentiments of the identity and the product and by developing equations to predict the identity modification process

A randomized controlled trial

Objective We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. Methods This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. Results 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). Conclusions In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation

Vaccine-induced skewing of T cell responses protects against Chikungunya virus disease

Chikungunya virus (CHIKV) infections can cause severe and debilitating joint and muscular pain that can be long lasting. Current CHIKV vaccines under development rely on the generation of neutralizing antibodies for protection; however, the role of T cells in controlling CHIKV infection and disease is still unclear. Using an overlapping peptide library, we identified the CHIKV-specific T cell receptor epitopes recognized in C57BL/6 infected mice at 7 and 14 days post-infection. A fusion protein containing peptides 451, 416, a small region of nsP4, peptide 47, and an HA tag (CHKVf5) was expressed using adenovirus and cytomegalovirus-vectored vaccines. Mice vaccinated with CHKVf5 elicited robust T cell responses to higher levels than normally observed following CHIKV infection, but the vaccine vectors did not elicit neutralizing antibodies. CHKVf5-vaccinated mice had significantly reduced infectious viral load when challenged by intramuscular CHIKV injection. Depletion of both CD

Animal Models of Chikungunya Virus Infection and Disease

Chikungunya virus (CHIKV) is a reemerging alphavirus that causes acute febrile illness and severe joint pain in humans. Although acute symptoms often resolve within a few days, chronic joint and muscle pain can be long lasting. In the last decade, CHIKV has caused widespread outbreaks of unprecedented scale in the Americas, Asia, and the Indian Ocean island regions. Despite these outbreaks and the continued expansion of CHIKV into new areas, mechanisms of chikungunya pathogenesis and disease are not well understood. Experimental animal models are indispensable to the field of CHIKV research. The most commonly used experimental animal models of CHIKV infection are mice and nonhuman primates; each model has its advantages for studying different aspects of CHIKV disease. This review will provide an overview of animal models used to study CHIKV infection and disease and major advances in our understanding of chikungunya obtained from studies performed in these models