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Summary 1.In nature, the fruit fly Drosophila melanogaster is attracted to fermenting fruit. Micro‐organisms like Saccharomyces yeasts growing on fruit occupy a commonly overlooked trophic level between fruit and insects. Although the dietary quality of yeast is well established for D. melanogaster, the individual contribution of fruit and yeast on host finding and reproductive success has not been established. 2.Here, we show that baker's yeast Saccharomyces cerevisiae on its own is sufficient for fruit fly attraction, oviposition and larval development. In contrast, attraction and oviposition were significantly lower if non‐fermented grape juice or growth media were used, and yeast‐free grapes did not support larval development either. 3.Despite a strong preference for fermented substrates, moderate attraction to and oviposition on unfermented fruit might be adaptive in view of the fly's capacity to vector yeast. 4.Signals emitted by fruit were only of secondary importance because fermenting yeast without fruit induced the same fly behaviour as yeast fermenting on fruit. We identified a synthetic mimic of yeast odour, comprising ethanol, acetic acid, acetoin, 2‐phenyl ethanol and 3‐methyl‐1‐butanol, which was as attractive for the fly as fermenting grape juice or fermenting yeast minimal medium. 5.Yeast odours represent the critical signal to establish the fly–fruit–yeast relationship. The traditional plant–herbivore niche concept needs to be updated, to accommodate for the role of micro‐organisms in insect–plant interactions.

Genetic and epigenetic plasticity allows tumors to evade single-targeted treatments. Here we direct Bcl2-specific short interfering RNA (siRNA) with 5'-triphosphate ends (3p-siRNA) against melanoma. Recognition of 5'-triphosphate by the cytosolic antiviral helicase retinoic acid-induced protein I (Rig-I, encoded by Ddx58) activated innate immune cells such as dendritic cells and directly induced expression of interferons (IFNs) and apoptosis in tumor cells. These Rig-I-mediated activities synergized with siRNA-mediated Bcl2 silencing to provoke massive apoptosis of tumor cells in lung metastases in vivo. The therapeutic activity required natural killer cells and IFN, as well as silencing of Bcl2, as evidenced by rescue with a mutated Bcl2 target, by site-specific cleavage of Bcl2 messenger RNA in lung metastases and downregulation of Bcl-2 protein in tumor cells in vivo. Together, 3p-siRNA represents a single molecule-based approach in which Rig-I activation on both the immune- and tumor cell level corrects immune ignorance and in which gene silencing corrects key molecular events that govern tumor cell survival.

For the Ruhr River, bathing has been prohibited for decades. However, along with significant improvements of the hygienic water quality, there is an increasing demand of using the river for recreational purposes, in particular for bathing. In the "Safe Ruhr" interdisciplinary research project, demands, options and chances for lifting the bathing ban for the Ruhr River were investigated. As being the prominent reason for persisting recreational restrictions, microbiological water quality was in the focus of interest. Not only the faecal indicator organisms (FIOs) as required by the European Bathing Water Directive were considered, but also pathogens such as Salmonella, Pseudomonas aeruginosa, Legionella pneumophila, Campylobacter, Leptospira, enteroviruses and protozoan parasites. In this introductory paper, we firstly relate current recreational desires to historical experiences of river bathing. After recapitulating relevant microbial river contamination sources (predominantly sewage treatment plants, combined sewer overflows, and surface runoffs), we review existing knowledge about the relationships of FIOs and pathogens in rivers designated for recreational purposes, and then trace the evolution, rationale and validity of recreational freshwater quality criteria which are, despite obvious uncertainties, mostly relying on the FIO paradigm. In particular, the representativeness of FIOs is critically discussed. The working programme of Safe Ruhr, aiming at initiating and facilitating a process towards legalisation of Ruhr River bathing, is outlined. Sources of contamination can be technically handled which leaves the actual measures to political decisions. As contaminations are transient, only occasionally exceeding legal limits, a flexible bathing site management, warning bathers of non-safe situations, may amend technical interventions and offer innovative solutions. As a result, a situation-adapted system for lifting of the bathing ban for Ruhr River appears realistic.

We report the combination of "click chemistry" with PCR by using alkyne-modified triphosphates for efficient and homogeneous labeling of DNA. A series of modified PCR products of different lengths (300, 900, and 2000 base pairs) were prepared by using a variety of alkyne- and azide-containing triphosphates and different polymerases. After intensive screening of real-time PCR methods, protocols were developed that allow the amplification of genes by using these modified triphosphates with similar efficiency to that of standard PCR. The click reaction on the highly modified PCR fragments provided conversion rates above 90 % and resulted in the functionalization of hundreds of alkynes on large DNA fragments with superb selectivity and efficiency.

Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1\beta. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications., Comment: The manuscript includes 23 pages, 6 figures, 1 table

A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core–shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core–shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid–based cell targeting.

Die neonatologische Pflegeforschung der Universitätskinderklinik und Poliklinik Heidelberg beschäftigt sich seit 1994 mit der Haut- und Körperpflege bei Früh- und Neugeborenen. Aufgrund von positiven Erfahrungen mit der Anwendung von Hydrokolloidplatten bei der Versorgung von Frühgeborenen mit Wundsein im Genitalbereich wurde in einer randomisierten Untersuchung der Frage nachgegangen, ob die Behandlung nach Standard oder mit Hydrokolloidplatten die Wundheilung beschleunigt. Mit Hilfe eines neu entwickelten Erhebungsbogens wurden über einen Zeitraum von 19 Monaten die Daten von insgesamt 27 Kindern erhoben. Die Ergebnisse zeigen, dass die Dauer der Wundheilung in der Gruppe der Behandlung mit einer Hydrokolloidplatte kürzer war als bei der Behandlung nach Standard. Weitere Studienfragen, zum Einfluss der Ernährung auf die Wundheilung, konnten nicht bearbeitet werden. Gründe hierfür werden in den strukturellen Rahmenbedingungen bei der Durchführung der Studie gesehen sowie in der Studienplanung. Diese Erkenntnisse zur praktischen Durchführung von Studien im Klinikalltag werden als wichtige Ergebnisse der vorliegenden Studie angesehen und diskutiert.

Título en ingles: Micropropagation of papaya plants in temporary immersion recipients from axilary shootsTítulo corto: Micropropagación de lechosa en recipientes de inmersión temporal.Resumen: Se estandarizaron las condiciones de iniciación, multiplicación, enraizamiento y aclimatización de plantas hermafroditas de lechosa cv Maradol provenientes de brotes axilares, producidos en recipientes de inmersión temporal RITA®. En cada envase, contentivo de 200 ml de medio de cultivo líquido de Fitch, se colocaron cuatro brotes de 2 a 3 cm de longitud. Los biorreactores se conectaron a tres líneas de inmersión de 5, 2 y 1 min cada 4h y se colocaron 6 envases en promedio por línea, en condiciones de fotoperíodo de 16 h. Transcurridos 30 a 45 días, se cuantificaron los brotes y se clasificaron de acuerdo al tamaño: < 2 cm (pequeños), entre 2 a 3 cm (medianos), ˃ 3 cm con y sin raíz (grandes). Los dos primeros tipos de brotes se continuaron multiplicando en los mismos medios; y los más elongados se aclimatizaron utilizando el Sistema Autotrófico Hidropónico (SAH). Se determinó la sanidad y la fidelidad de las plantas producidas mediante pruebas de ELISA y RAPD, respectivamente. Durante un periodo de 6 meses se reciclaron un total de 47 recipientes, los cuales produjeron 1.091 brotes: 377 pequeños; 482 medianos; 175 grandes sin raíz y 57 con raíz. Usando el SAH se obtuvo 89,5% de plantas aclimatizadas cuando se usaron brotes enraizados, y 41,6% a partir de brotes sin raíces. Con la combinación de las técnicas RITA y SAH se logró un sistema continuo y eficiente de producción de plantas sanas y fieles al tipo, en comparación con los métodos convencionales de micropropagación y aclimatización.Palabras clave: Carica papaya, RITA®, sistema autotrófico, estabilidad genética.Abstract: We standardized initiation, multiplication, rooting and acclimatization conditions of papaya cv Maradol hermaphrodite plants from axillary buds produced in temporary immersion reactor RITA®. Recipients contained 200 ml of Fitch liquid culture medium, and four shoots of 2 to 3 cm. in length were placed in each. The bioreactors were connected to three different immersion lines of 5, 2, and 1 min each 4h, with 6 containers per line on average, in 16 h photoperiod. After 30 to 45 days, the shoots produced were quantified and classified according to size: 3 cm with or without roots (large). The first two types of shoots were multiplied in the same culture media, and more elongated shoots were acclimatized using Autotrophic Hydroponic System (AHS). The sanity and fidelity of the produced plants were determined using ELISA and RAPD, respectively. For a period of six months 47 vessels were recycled and 1,091 shoots were produced: 377 small; 482 medium; 175 large without roots and 57 rooted shoots. Using AHS, 89.5% acclimatized plants were obtained when rooted shoots were used, and 41.6% from rootless shoots. With the combination of RITA and AHS techniques we achieved a continuous and efficient production of healthy and true to type papaya plants, in comparison to conventional micropropagation and acclimatization procedures.Key words: Carica papaya, RITA®, autotrophic system, genetic stability.Recibido: mayo 16 de 2014 Aprobado: abril 21 de 2015

Im Beitrag wird die Familie als informelles Lern- und Bildungsfeld fur Heranwachsende thematisiert. Dafur wird zum einen Bezug genommen auf die, vor allem bildungspolitisch diskutierten Anforderungen und Erwartungen an Eltern heute, die sich gleichsam im Konzept der ‚Bildungsarrangeure‘ bundeln lassen. Unter der Perspektive der in der Familie potenziell angesiedelten Lern- und Bildungsprozesse werden zunachst die Grundlinien des aktuellen padagogischen Diskurses nachgezeichnet. Diskutiert werden dafur die Entwurfe spezifischer Kompetenzprofile sowie die sozialen und kulturellen ‚Vererbungsprozesse‘ in der Familie im Kontext familialer Habitusformation. In Erweiterung der so skizzierten Perspektiven auf das Lern- und Bildungsfeld Familie wird schlieslich in das kindheitswissenschaftliche Akteurskonzept (agency) eingefuhrt, um am Beispiel der sog. young carers zu diskutieren, inwiefern die agency von Kindern, verstanden als Ergebnis einer reflexiven Selbstverstandigung und spezifischen Positionierung zu ihren je konkreten Lebensrealitaten, auch Bildungspotenziale birgt, die moglicherweise im gegenwartigen bildungstheoretischen Diskurs noch vernachlassigt werden.

In der Diskussion um die Qualitat der Fruhen Bildung ruckt die Thematik der Professionalisierung der PadagogInnen verstarkt in den Fokus. Wer positive, anregende Interaktionen mit Kindern gestaltet, tragt zur Qualitatssteigerung der Einrichtung bei. Der Beitrag widmet sich der Frage, was eine professionelle Interaktion ausmacht und wie sie in der Weiterbildung entwickelt werden kann.

The structural elucidation of four phloroglucinol derivatives isolated from the ethanolic extract of the brown alga Carpophyllum angustifolium after peracetylation is described. Three of them, trihydroxyheptaphlorethol-A octadecaacetate, trihydroxyoctaphlorethol-A eicosaacetate and trihydroxyoctaphlorethol-B eicosaacetate, are described for the first time. Characterized by three additional hydroxyl groups and two 1,2-diphenoxylated 3,4,5-triacetoxybenzene rings directly linked by an ether bond they are called trihydroxyphlorethols as a novel group of phlorotannins. The structural elucidation was carried out on the basis of spectral data.

Mesoporous nanoparticles for drug delivery would benefit significantly from further improvements in targeting efficiency and endosomal release. We present a system based on colloidal mesoporous silica nanoparticles with targeting-ligands and a red-light photosensitizer. This nanoparticle system provides spatial and temporal control of the release of drugs into the cytosol of cancer cells. Furthermore, the system presents a general platform since it can be loaded with different cargos and adapted for targeting of multiple cell types.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. Adjuvant radiation increases survival in advanced stages, but efficacy in stage I disease is unknown. A retrospective review included all patients treated for stage I MCC during a 15-year period at Vanderbilt University Medical Center. Among 42 patients, 26 (62%) had a negative sentinel lymph node biopsy (stage IA) and 16 (38%) had clinically negative lymph nodes (stage IB) at the time of resection. Analysis using Cox regression revealed that higher stage and absence of adjuvant radiation are associated with increased disease recurrence (hazard ratio, 6.29; P=0.003 and hazard ratio, 4.69; P=0.013, respectively). Controlling for stage, radiation therapy significantly increased disease-free survival among patients with stage IB disease (P=0.0026) in a log-rank test comparing Kaplan-Meier curves. These findings support adjuvant radiation therapy in stage IB MCC patients with clinically negative lymph nodes who do not undergo sentinel lymph node biopsy.

We investigated uptake and individual endosome lysis events in fibroblast, normal, and carcinoma cell lines using a colloidal mesoporous silica (CMS) nanoparticle (NP)-based reporter system with a covalently attached photosensitizer. Endosome lysis was induced through the activation of protoporphyrin IX (PpIX). Surprisingly, this release-on-demand system resulted in more broadly distributed lysis times than expected, particularly for Renca, a renal carcinoma cell line. An analysis of the NP load per endosome, endosome size, and uptake characteristics indicate that Renca cells not only take up a lower amount of NPs in comparison with the fibroblast cells but also have larger endosomes and a lower NP load per endosome. We then created a stochastic model detailing steps downstream of uptake to understand how much factors that cannot be directly measured, such as variations in the PpIX load per NP, affect the lysis time distributions. Model results indicate that the distributions are primarily determined by the endosome properties, rather than variations across NPs.

Different bioactive molecules are released into living cells from lipid-covered mesoporous silica nanoparticles. The release is triggered by light, as the particles feature covalently attached photosensitizers as membrane-opening agents. It is demonstrated that the particles achieve endosomal escape and that they release their cargo into the cytosol.

Olfactory studies have expanded beyond the study of single compound odor perception to explore the processing of complex mixtures and blends. The spatiotemporal presentation of blend stimuli is a challenging task requiring volatiles with diverse chemical and physical properties to be presented as a unified stimulus. This not only necessitates accurate control of the timing and homogeneity of the odor stream, but requires attention to the concentration of each blend component presented. We have developed a novel, multicomponent stimulus system for use in olfactory experiments that is capable of presenting up to 8 different odors simultaneously or in sequence at defined concentrations and time scales. Each odor is separated to minimize physical or chemical interactions, and stimulations are performed from a saturated headspace of the odor solution. Stimulus concentrations can be measured empirically or estimated using common gas laws. Photoionization detector measurements show that stimuli could be presented as cohesive blends or single components at frequencies of at least 10Hz without leakage or contamination. Solid phase microextraction measurements also show that the concentration of each component could be equilibrated through regulation of each component line's flow rate based on the different partial vapor pressures of the odorants. This device provides a unique method for introducing complex volatile mixtures for olfactory studies in a variety of animal taxa and allows for accurate control of odor intensities in both time and space.

Since 1994 the neonatal care research of the Division of Neonatology, Department of Pediatrics, University of Heidelberg has been occupying itself with skin damage and skin hygiene in newborn and pre-term infants. Due to positive practical experiences when applying a hydrocolloid to pre-term infants with skin damage in genitalia, a randomized controlled study was conducted to investigate whether the application of the hydrocolloid or the valid guideline would promote the healing of the damaged skin. A protocol was developed and data was collected over a period of 19 months. The results show, that the length of time needed for skin recovery was shorter when applying a hydrocolloid in comparison to the guideline. A number of further issues were anticipated to be investigated, however could not be evaluated. Reasons for this are in the structural circumstances/conditions while executing/performing the study as well as the study design. These important discoveries, regarding the execution of studies during everyday clinical practice are regarded as important results/findings in this study.

Firms increasingly aim to combat climate change. For corporate managers,the question whether a related strategy affects financial performance arises. Sinceempirical research on this topic is rather sparse, this study investigates whetherpursuing a corporate climate change strategy leads to better corporate financialperformance. By applying paired samples t-tests, a sample of 62 companies fromthe electric utilities sector matched in pairs is investigated over a five-year timespan. Results indicate that firms with a comprehensive climate change strategypredominantly perform significantly better than their competitors without such astrategy. These findings might contribute to promoting climate change strategies ina corporate context.