NK Cells of Kidney Transplant Recipients Display an Activated Phenotype that Is Influenced by Immunosuppression and Pathological Staging

To explore phenotype and function of NK cells in kidney transplant recipients, we investigated the peripheral NK cell repertoire, capacity to respond to various stimuli and impact of immunosuppressive drugs on NK cell activity in kidney transplant recipients. CD56(dim) NK cells of kidney transplanted patients displayed an activated phenotype characterized by significantly decreased surface expression of CD16 (p=0.0003), CD226 (p<0.0001), CD161 (p=0.0139) and simultaneously increased expression of activation markers like HLA-DR (p=0.0011) and CD25 (p=0.0015). Upon in vitro stimulation via Ca++-dependent signals, down-modulation of CD16 was associated with induction of interferon (IFN)-gamma expression. CD16 modulation and secretion of NFAT-dependent cytokines such as IFN-gamma, TNF-alpha, IL-10 and IL-31 were significantly suppressed by treatment of isolated NK cells with calcineurin inhibitors but not with mTOR inhibitors. In kidney transplant recipients, IFN-gamma production was retained in response to HLA class I-negative target cells and to non-specific stimuli, respectively. However, secretion of other cytokines like IL-13, IL-17, IL-22 and IL-31 was significantly reduced compared to healthy donors. In contrast to suppression of cytokine expression at the transcriptional level, cytotoxin release, i.e. perforin, granzyme A/B, was not affected by immunosuppression in vitro and in vivo in patients as well as in healthy donors. Thus, immunosuppressive treatment affects NK cell function at the level of NFAT-dependent gene expression whereby calcineurin inhibitors primarily impair cytokine secretion while mTOR inhibitors have only marginal effects. Taken together, NK cells may serve as indicators for immunosuppression and may facilitate a personalized adjustment of immunosuppressive medication in kidney transplant recipients.

Miriam Hellrung: Lehrerhandeln im individualisierten Unterricht, Entwicklungsaufgaben und ihre Bewältigung. Opladen / Farmington Hills: Verlag Barbara Budrich 2010 [Rezension]

Rezension von: Miriam Hellrung: Lehrerhandeln im individualisierten Unterricht, Entwicklungsaufgaben und ihre Bewältigung, Opladen / Farmington Hills: Verlag Barbara Budrich 2010 (276 S.; ISBN 978-3-86649-338-4)

Artificial Skin - Culturing of Different Skin Cell Lines for Generating an Artificial Skin Substitute on Cross-Weaved Spider Silk Fibres

Background: In the field of Plastic Reconstructive Surgery the development of new innovative matrices for skin repair is in urgent need. The ideal biomaterial should promote attachment, proliferation and growth of cells. Additionally, it should degrade in an appropriate time period without releasing harmful substances, but not exert a pathological immune response. Spider dragline silk from Nephila spp meets these demands to a large extent. Methodology/Principal Findings: Native spider dragline silk, harvested directly out of Nephila spp spiders, was woven on steel frames. Constructs were sterilized and seeded with fibroblasts. After two weeks of cultivating single fibroblasts, keratinocytes were added to generate a bilayered skin model, consisting of dermis and epidermis equivalents. For the next three weeks, constructs in co-culture were lifted on an originally designed setup for air/liquid interface cultivation. After the culturing period, constructs were embedded in paraffin with an especially developed program for spidersilk to avoid supercontraction. Paraffin cross-sections were stained in Haematoxylin & Eosin (H&E) for microscopic analyses. Conclusion/Significance: Native spider dragline silk woven on steel frames provides a suitable matrix for 3 dimensional skin cell culturing. Both fibroblasts and keratinocytes cell lines adhere to the spider silk fibres and proliferate. Guided by the spider silk fibres, they sprout into the meshes and reach confluence in at most one week. A well-balanced, bilayered cocultivation in two continuously separated strata can be achieved by serum reduction, changing the medium conditions and the cultivation period at the air/liquid interphase. Therefore spider silk appears to be a promising biomaterial for the enhancement of skin regeneration.

Interactions between Spider Silk and Cells - NIH/3T3 Fibroblasts Seeded on Miniature Weaving Frames

Background: Several materials have been used for tissue engineering purposes, since the ideal matrix depends on the desired tissue. Silk biomaterials have come to focus due to their great mechanical properties. As untreated silkworm silk has been found to be quite immunogenic, an alternative could be spider silk. Not only does it own unique mechanical properties, its biocompatibility has been shown already in vivo. In our study, we used native spider dragline silk which is known as the strongest fibre in nature. Methodology/Principal Findings: Steel frames were originally designed and manufactured and woven with spider silk, harvesting dragline silk directly out of the animal. After sterilization, scaffolds were seeded with fibroblasts to analyse cell proliferation and adhesion. Analysis of cell morphology and actin filament alignment clearly revealed adherence. Proliferation was measured by cell count as well as determination of relative fluorescence each after 1, 2, 3, and 5 days. Cell counts for native spider silk were also compared with those for trypsin-digested spider silk. Spider silk specimens displayed less proliferation than collagen-and fibronectin-coated cover slips, enzymatic treatment reduced adhesion and proliferation rates tendentially though not significantly. Nevertheless, proliferation could be proven with high significance (p<0.01). Conclusion/Significance: Native spider silk does not require any modification to its application as a biomaterial that can rival any artificial material in terms of cell growth promoting properties. We could show adhesion mechanics on intracellular level. Additionally, proliferation kinetics were higher than in enzymatically digested controls, indicating that spider silk does not require modification. Recent findings concerning reduction of cell proliferation after exposure could not be met. As biotechnological production of the hierarchical composition of native spider silk fibres is still a challenge, our study has a pioneer role in researching cellular mechanics on native spider silk fibres.

Präsenzunterricht, Fernunterricht: Die Suche nach dem optimalen Mix

Bei der Beurteilung von Projekten des Swiss Virtual Campus (SVC; Virtueller Campus Schweiz, Campus Virtuel Suisse, Campus Virtuale Svizzero), eines Programms des Bundes zur Förderung der neuen Informations- und Kommunikationstechnologien in der Hochschullehre, gilt es auch auf den optimalen Mix von Präsenzunterricht und Fernunterricht zu achten. Welche Arten von Szenarien sind vorstellbar, und wie beeinflusst die Art des Szenarios die optimale Verteilung von Präsenz- und Fernunterricht? Welche technischen Hilfsmittel sind für welches Szenario sinnvoll? Der Swiss Virtual Campus ist grundsätzlich nicht als Online-Universität geplant und nicht auf Fernstudien ausgerichtet. Es ist jedoch denkbar, dass manche Projekte des Swiss Virtual Campus künftig den Weg in Fernstudienangebote finden werden, obwohl sie nicht dafür konzipiert wurden. Einige Projekte von Fachhochschulen wurden bereits als Fernstudium konzipiert. In gewissen Aspekten funktionieren sie nach anderen Regeln als für Präsenzunterricht konzipierte Kurse.(DIPF/Orig.)

Lobbying in a transatlantic comparison: opportunity structures and lobbying content in the US and the EU

Despite vast literatures on interest representation in the United States (US) and the European Union (EU), few studies have tried to compare lobbying across the two cases. Those who do are interested primarily in the existence of different lobbying styles and distinguish between an aggressive pressure group approach in the US and a more consensus oriented informational lobbying in the EU. However, the origins of these differences have received little attention and references most often point to different political “cultures” and lobbying traditions. This paper takes issue with this cultural explanation and links the observed lobbying styles with differences in the design of the political institutions that private actors have to interact with. It argues that divided policy authority in the US allows for interest group bargaining while shared policy competencies in the EU constrain not only policy-makers but also lobbyists to adopt a more consensus-oriented approach. The effect of political institutions on the form of lobbying, in turn, can have important implications for the comparison of different policy areas across countries, because the policy stances of private actors cannot always be assumed to be exogenous to the policy process in which they are active.

Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells

Following cultivation of distinct mesenchymal stem cell (MSC) populations derived from human umbilical cord under hypoxic conditions (between 1.5% to 5% oxygen (O-2)) revealed a 2- to 3-fold reduced oxygen consumption rate as compared to the same cultures at normoxic oxygen levels (21% O-2). A simultaneous measurement of dissolved oxygen within the culture media from 4 different MSC donors ranged from 15 mu mol/L at 1.5% O-2 to 196 mu mol/L at normoxic 21% O-2. The proliferative capacity of the different hypoxic MSC populations was elevated as compared to the normoxic culture. This effect was paralleled by a significantly reduced cell damage or cell death under hypoxic conditions as evaluated by the cellular release of LDH whereby the measurement of caspase 3/7 activity revealed little if any differences in apoptotic cell death between the various cultures. The MSC culture under hypoxic conditions was associated with the induction of hypoxia-inducing factor-alpha (HIF-1 alpha) and an elevated expression of energy metabolism-associated genes including GLUT-1, LDH and PDK1. Concomitantly, a significantly enhanced glucose consumption and a corresponding lactate production could be observed in the hypoxic MSC cultures suggesting an altered metabolism of these human stem cells within the hypoxic environment.

Composite Medicago truncatula plants harbouring Agrobacterium rhizogenes-transformed roots reveal normal mycorrhization by Glomus intraradices

Composite plants consisting of a wild-type shoot and a transgenic root are frequently used for functional genomics in legume research. Although transformation of roots using Agrobacterium rhizogenes leads to morphologically normal roots, the question arises as to whether such roots interact with arbuscular mycorrhizal (AM) fungi in the same way as wild-type roots. To address this question, roots transformed with a vector containing the fluorescence marker DsRed were used to analyse AM in terms of mycorrhization rate, morphology of fungal and plant subcellular structures, as well as transcript and secondary metabolite accumulations. Mycorrhization rate, appearance, and developmental stages of arbuscules were identical in both types of roots. Using Mt16kOLI1Plus microarrays, transcript profiling of mycorrhizal roots showed that 222 and 73 genes exhibited at least a 2-fold induction and less than half of the expression, respectively, most of them described as AM regulated in the same direction in wild-type roots. To verify this, typical AM marker genes were analysed by quantitative reverse transcription-PCR and revealed equal transcript accumulation in transgenic and wild-type roots. Regarding secondary metabolites, several isoflavonoids and apocarotenoids, all known to accumulate in mycorrhizal wild-type roots, have been found to be up-regulated in mycorrhizal in comparison with non-mycorrhizal transgenic roots. This set of data revealed a substantial similarity in mycorrhization of transgenic and wild-type roots of Medicago truncatula, validating the use of composite plants for studying AM-related effects.

p-BioSPRE-an information and communication technology framework for transnational biomaterial sharing and access

Biobanks represent key resources for clinico-genomic research and are needed to pave the way to personalised medicine. To achieve this goal, it is crucial that scientists can securely access and share high-quality biomaterial and related data. Therefore, there is a growing interest in integrating biobanks into larger biomedical information and communication technology (ICT) infrastructures. The European project p-medicine is currently building an innovative ICT infrastructure to meet this need. This platform provides tools and services for conducting research and clinical trials in personalised medicine. In this paper, we describe one of its main components, the biobank access framework p-BioSPRE (p-medicine Biospecimen Search and Project Request Engine). This generic framework enables and simplifies access to existing biobanks, but also to offer own biomaterial collections to research communities, and to manage biobank specimens and related clinical data over the ObTiMA Trial Biomaterial Manager. p-BioSPRE takes into consideration all relevant ethical and legal standards, e.g., safeguarding donors’ personal rights and enabling biobanks to keep control over the donated material and related data. The framework thus enables secure sharing of biomaterial within open and closed research communities, while flexibly integrating related clinical and omics data. Although the development of the framework is mainly driven by user scenarios from the cancer domain, in this case, acute lymphoblastic leukaemia and Wilms tumour, it can be extended to further disease entities.

Determinants of transfer of training: A comprehensive literature review

Investments in training measures can only be considered effective if the transfer of the learned contents to practical situations is continuously successful. In this context the scientific and professional discourse regarding the effectiveness of further education, especially regarding training transfer, has intensified considerably. This analysis provides a systematic and comprehensive overview of the current state of international empirical research regarding major influencing factors of learning transfer in the context of formalized further vocational training. Our review of literature differentiates the most important influencing factors on the micro-level of the specific individual characteristics of the participants, the meso-level of measure-specific characteristics of the field of learning, as well as institutional characteristics of the work environment at the macro-level. Decades of transfer research brings forth a wealth of information regarding factors which influence the learning transfer. The current analysis systematizes these results and clarifies that the current state of research regarding the determinants of the process of learning transfer shows clear trends. But there are also some inconsistent findings. Thus the question of which factors positively influence the success of learning transfer is well-studied for the micro-level in particular. The article shows that there is still a research deficit concerning the major determinants of learning transfer at the meso- and macro-level. Finally, in this context this article identifies promising directions for future research. (DIPF/Orig.)

(Appendix A) Sedimentation rate, geochemical and environmental magnetic proxies of the samples of the Metochia section, on the island of Gavdos, south of Crete

The upper Tortonian Metochia marls on the island of Gavdos provide an ideal geological archive to trace variations in Aegean sediment supply as well as changes in the North African monsoon system. A fuzzy-cluster analysis on the multiproxy geochemical and rock magnetic dataset of the astronomically tuned sedimentary succession shows a dramatic shift in the dominance of 'Aegean tectonic' clusters to 'North African climate' clusters. The tectonic signature, traced by the starvation of the Cretan sediment, now enables to date the late Tortonian basin foundering on Crete, related to the tectonic break-up of the Aegean landmass, at c. 8.2 Ma. The synchronous decrease in the North African climate proxies is interpreted to indicate a change in the depositional conditions of the sink rather than a climatic change in the African source. This illustrates that interpretations of climate proxies require a multiproxy approach which also assesses possible contributions of regional tectonism.

Cognitive processing in non-communicative patients:what can event-related potentials tell us?

Event-related potentials (ERP) have been proposed to improve the differential diagnosis of non-responsive patients. We investigated the potential of the P300 as a reliable marker of conscious processing in patients with locked-in syndrome (LIS). Eleven chronic LIS patients and 10 healthy subjects (HS) listened to a complex-tone auditory oddball paradigm, first in a passive condition (listen to the sounds) and then in an active condition (counting the deviant tones). Seven out of nine HS displayed a P300 waveform in the passive condition and all in the active condition. HS showed statistically significant changes in peak and area amplitude between conditions. Three out of seven LIS patients showed the P3 waveform in the passive condition and five of seven in the active condition. No changes in peak amplitude and only a significant difference at one electrode in area amplitude were observed in this group between conditions. We conclude that, in spite of keeping full consciousness and intact or nearly intact cortical functions, compared to HS, LIS patients present less reliable results when testing with ERP, specifically in the passive condition. We thus strongly recommend applying ERP paradigms in an active condition when evaluating consciousness in non-responsive patients.

“Alguien que cuide de mí” Para una lectura crítica sobre los discursos de igualdad de género

"Este trabajo plantea la pregunta por las causas de las resistencias femeninas a la recepción de los discursos de igualdad de género. En su hipótesis central afirma que tales resistencias obedecen a límites propios del discurso y que, en consecuencia, éste no puede ser considerado como universalmente aceptable. Los límites que se identifican en el texto se centran en las condiciones sociales y económicas de posibilidad, en las barreras que genera el discurso victimizante, en la pervivencia del privilegio de seguridad y en las consecuencias que sobre las estructuras sociales resultan del proceso de asimilación de los nuevos roles de género."

Estimation of the Traffic Intensity in a Piecewise-stationary Mt/Gt/1 Queue with Probing

We use a probing strategy to estimate the time dependent traffic intensity in an Mt/Gt/1 queue, where the arrival rate and the general service-time distribution change from one time interval to another, and derive statistical properties of the proposed estimator. We present a method to detect a switch from a stationary interval to another using a sequence of probes to improve the estimation. At the end, we compare our results with two estimators proposed in the literature for the M/G/1 queue.