Der Interleukin-1-Genkomplex in der Schizophrenie

Es gilt heute als gesichert, dass eine starke genetische Komponente in der Ätiologie der Schizophrenie vorliegt. In der vorliegenden Arbeit wurden in einer Fall-Kontroll-Assoziationsstudie drei genetische Polymorphismen in Genen des Interleukin-1-Genkomplexes auf eine mögliche Assoziation mit Schizophrenie untersucht: die Gene, die für die proinflammatorischen Interleukine Interleukin-1 alpha und Interleukin-1 beta kodieren, sowie das Gen, welches für den antiinflammatorischen Interleukin-1-Rezeptorantagonist kodiert. Dieser ist der natürlich vorkommende, endogene Gegenspieler von Interleukin-1. Seine biologische Funktion scheint in der Kontrolle des Ausmaßes der proinflammatorischen Interleukine zu liegen. Die in der vorliegenden Arbeit untersuchten Gene liegen innerhalb einer Genregion auf Chromosom 2p12-q22.1, die in einer groß angelegten Meta-Analyse als einziger Genabschnitt eine genomweite signifikante Kopplung erreichte (Lewis et al. 2003). Daher sind die Gene des Interleukin-1-Genkomplexes positionelle Kandidatengene in der Pathogenese der Schizophrenie. Außerdem sind die Interleukine deswegen sehr interessante Proteine für die Schizophrenie, da sie den Metabolismus von Neurotransmittern und die Hirnentwicklung beeinflussen sowie Informationen zwischen Zellen des peripheren Immunsystems und des zentralen Nervensystems vermitteln können. Im Blut, in der Zerebrospinalflüssigkeit sowie im präfrontalen Cortex schizophrener Patienten konnten veränderte Konzentrationen von IL-1 und IL-1RA im Vergleich zu Kontrollen beobachtet werden. Dies weist auf eine Dysregulation der Interleukine in der Schizophrenie hin. Da Anomalien bei der Hirnentwicklung, den Neurotransmittersystemen und dem Immunsystem als mögliche Pathomechanismen der Schizophrenie betrachtet werden, ist es durchaus vorstellbar, dass eine genetisch bedingte Störung in dem sensitiven Gleichgewicht zwischen pro- und antiinflammatorischen Interleukinen in der Schizophrenie zumindest teilweise krankheitsauslösend oder -beeinflussend sein kann. Für diese Fragestellung wurden Allel- und Genotypfrequenzen eines C-889T-Basenaustauschpolymorphismus im Promotor des Interleukin-1 alpha-Gens, eines C-511T-Basenaustauschpolymorphismus im Promotor des Interleukin-1 beta-Gens sowie eines variable number of tandem repeats (VNTR) -Polymorphismus im zweiten Intron des Interleukin-1-Rezeptorantagonist-Gens untersucht. In der vorliegenden Arbeit konnte keine Assoziation zwischen den untersuchten Polymorphismen der Gene des Interleukin-1 alpha und beta mit der Diagnose Schizophrenie festgestellt werden. Bei dem untersuchten Polymorphismus des IL-1RN konnte ein Trend in Richtung einer selteneren Häufigkeit des Allels 2 bei Schizophrenen nachgewiesen werden. Die Analyse von Haplotypen des IL-1-Genkomplexes auf Assoziation mit Schizophrenie ergab keinen Zusammenhang. Die vorliegenden Ergebnisse sprechen dafür, dass das seltenere Vorkommen des Allels 2 des IL-1RA bei den Schizophrenen einen Einfluss auf das Entstehungsrisiko der Schizophrenie haben könnte, indem es zu einer Verschiebung der sensitiven Balance des Interleukin-1-Genkomplexes zwischen pro- und antiinflammatorischen Interleukinen zugunsten der proinflammatorischen Interleukine führt. Dieser Befund bekräftigt die Hypothese, dass eine überschießende Aktivierung des Immunsystems in der Pathogenese der Schizophrenie eine Rolle spielen könnte. Außerdem weist er darauf hin, dass die Dysregulation der Interleukine bei den Schizophrenen zumindest teilweise genetisch bedingt sein könnte. Die Ergebnisse sprechen somit für eine mögliche schützende Rolle des Allels 2 des Interleukin-1-Rezeptorantgonisten vor der Entstehung der Schizophrenie. Dieser Befund wurde durch neuste Studien von Zanardini et al. (2003) und Bocchio-Chiavetto et al. (2002), in denen die Träger des IL-1RN Allel 2 signifikant seltener bei den Schizophrenen vertreten waren, unterstützt

Galektin-3 in der Interaktion von T Zellen und Tumorzellen

Galektin-3 ist ein b-Galaktosid-bindendes Protein, das je nach Lokalisation unterschiedlichste Funktionen aufweist. Eine immunsuppressive Funktion von Galektin-3 wird im Kontext der Tumorimmunologie diskutiert. Im Rahmen dieser Arbeit wurde der Einfluss von Galektin-3 in der Interaktion von Tumorzellen mit T Zellen, insbesondere den für eine Immuntherapie interessanten gammadelta T Zellen, untersucht. Insgesamt deuten die Ergebnisse dieser Arbeit darauf hin, dass Galektin-3 in der Tumorumgebung eine immunsuppressive Funktion besitzt. Die Ergebnisse legen allerdings nahe, dass die immunsuppressive Wirkung von Galektin-3 durch einen adoptiven Transfer in vitro expandierter Vgamma9Vdelta2 gammadelta T Zellen allein oder in Kombination mit bispezifischen Antikörpern überkommen werden könnte

To What Extent Can Individualisation in Terms of Different Types of Mode Improve Learning Outcomes and Learner Satisfaction? A Pre-study

With the latest technological developments and associated new possibilities in teaching, the personalisation of learning is gaining more and more importance. It assumes that individual learning experiences and results could generally be improved when personal learning preferences are considered. To do justice to the complexity of the personalisation possibilities of teaching and learning processes, we illustrate the components of learning and teaching in the digital environment and their interdependencies in an initial model. Furthermore, in a pre-study, we investigate the relationships between the learner's ability to (digital) self-organise, the learner’s prior- knowledge learning in different variants of mode and learning outcomes as one part of this model. With this pre-study, we are taking the first step towards a holistic model of teaching and learning in digital environments

Relating vesicle shapes in pyroclasts to eruption styles

Vesicles in pyroclasts provide a direct record of conduit conditions during explosive volcanic eruptions. Although their numbers and sizes are used routinely to infer aspects of eruption dynamics, vesicle shape remains an underutilized parameter. We have quantified vesicle shapes in pyroclasts from fall deposits of seven explosive eruptions of different styles, using the dimensionless shape factor , a measure of the degree of complexity of the bounding surface of an object. For each of the seven eruptions, we have also estimated the capillary number, Ca, from the magma expansion velocity through coupled diffusive bubble growth and conduit flow modeling. We find that Ω is smaller for eruptions with Ca 1 than for eruptions with Ca 1. Consistent with previous studies, we interpret these results as an expression of the relative importance of structural changes during magma decompression and bubble growth, such as coalescence and shape relaxation of bubbles by capillary stresses. Among the samples analyzed, Strombolian and Hawaiian fire-fountain eruptions have Ca 1, in contrast to Vulcanian, Plinian, and ultraplinian eruptions. Interestingly, the basaltic Plinian eruptions of Tarawera volcano, New Zealand in 1886 and Mt. Etna, Italy in 122 BC, for which the cause of intense explosive activity has been controversial, are also characterized by Ca 1 and larger values of Ω than Strombolian and Hawaiian style (fire fountain) eruptions. We interpret this to be the consequence of syn-eruptive magma crystallization, resulting in high magma viscosity and reduced rates of bubble growth. Our model results indicate that during these basaltic Plinian eruptions, buildup of bubble overpressure resulted in brittle magma fragmentation.National Science Foundation EAR-1019872National Science Foundation EAR-081033

Rapid ascent and emplacement of basaltic lava during the 2005–06 eruption of the East Pacific Rise at ca. 9°51′N as inferred from CO2 contents

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth and Planetary Science Letters 453 (2016): 152-160, doi:10.1016/j.epsl.2016.08.007.Eruption rates at the mid–ocean ridges (MORs) are believed to strongly control the morphology and length of lava flows emplaced along the ridge axis, and thus the structure and porosity of the upper oceanic crust. Eruption rate also represents one of the few tools to gain insight into the driving pressures within sub-ridge magmatic systems. As eruption rate is inferred to vary systematically along the global mid-ocean ridge, understanding of how to assess eruption rate in submarine systems and how it maps to observable features of the ridge axis would provide a powerful tool to understand Earth's largest magmatic system. Eruption rates at MORs are poorly constrained, however, because of a lack of direct observations, preventing the duration of an eruption to be quantified. This study uses decompression experiments of MORB samples and numerical modeling of CO2 degassing to reconstruct the timescales for magma ascent and lava emplacement during the 2005–06 eruption of the East Pacific Rise at ca. 9°51’N. Samples collected from the lava flow are all supersaturated in dissolved CO2 contents, but CO2 decreases with distance from the vent, presumably as a consequence of progressive CO2 diffusion into growing bubbles. Samples collected at the vent contain ~105 vesicles per cm3. Pieces of these samples were experimentally heated to 1225°C at high pressure and then decompressed at controlled rates. Results, plus those from numerical modeling of diffusive bubble growth, indicate that magma rose from the axial magma chamber to the seafloor in ≤1 hour and at a rate of ≥2–3 km hr-1. Our modeling, as validated by experimental decompression of MORB samples with ~106 vesicles cm-3, also suggests that CO2 degassed from the melt within ~10–100 minutes as the vesicular lava traveled ~ 1.7 km along the seafloor, implying a volumetric flow rate on order of 103–4 m3 s-1. Given an ascent rate of ≥0.2 m s-1, the width of a rectangular dike feeding the lava would have been ~1–2 meters wide. MORB samples from the Pacific ridge are generally more supersaturated in dissolved CO2 than those from slower spreading Atlantic and Indian ridges. Our results suggest that Pacific MORBs ascend to the seafloor faster than Atlantic or Indian MORBsThis project was partially funded by a grant to J.E.G. from the U.S. National Science Foundation (OCE-1333882).2017-08-2

The fluid mechanics inside a volcano.

Abstract The style and evolution of volcanic eruptions are dictated by the fluid mechanics governing magma ascent. Decompression during ascent causes dissolved volatile species, such as water and carbon dioxide, to exsolve from the melt to form bubbles, thus providing a driving force for the eruption. Ascent is influenced not only by the nucleation and growth of gas bubbles, but also magma rheology and brittle deformation (fragmentation). In fact, all processes and magma properties within the conduit interact and are coupled. Ultimately, it is the ability of gas trapped within growing bubbles to expand or to be lost by permeable gas flow, which determines whether ascending magmas can erupt nonexplosively. We review and integrate models of the primary conduit processes to show when each process or property dominates and how these interact within a conduit. In particular, we illustrate how and why ascent rate may control eruptive behavior: slowly ascending magmas erupt effusively and rapidly ascending magmas erupt explosively

Characterizing trends in HIV infection among men who have sex with men in Australia by birth cohorts: results from a modified back-projection method

<p>Abstract</p> <p>Background</p> <p>We set out to estimate historical trends in HIV incidence in Australian men who have sex with men with respect to age at infection and birth cohort.</p> <p>Methods</p> <p>A modified back-projection technique is applied to data from the HIV/AIDS Surveillance System in Australia, including "<it>newly diagnosed HIV infections</it>", "<it>newly acquired HIV infections</it>" and "<it>AIDS diagnoses</it>", to estimate trends in HIV incidence over both calendar time and age at infection.</p> <p>Results</p> <p>Our results demonstrate that since 2000, there has been an increase in new HIV infections in Australian men who have sex with men across all age groups. The estimated mean age at infection increased from ~35 years in 2000 to ~37 years in 2007. When the epidemic peaked in the mid 1980s, the majority of the infections (56%) occurred among men aged 30 years and younger; 30% occurred in ages 31 to 40 years; and only ~14% of them were attributed to the group who were older than 40 years of age. In 2007, the proportion of infections occurring in persons 40 years or older doubled to 31% compared to the mid 1980s, while the proportion of infections attributed to the group younger than 30 years of age decreased to 36%.</p> <p>Conclusion</p> <p>The distribution of HIV incidence for birth cohorts by infection year suggests that the HIV epidemic continues to affect older homosexual men as much as, if not more than, younger men. The results are useful for evaluating the impact of the epidemic across successive birth cohorts and study trends among the age groups most at risk.</p

Magma decompression rates during explosive eruptions of Kīlauea volcano, Hawai'i, recorded by melt embayments

The decompression rate of magma as it ascends during volcanic eruptions is an important but poorly constrained parameter that controls many of the processes that influence eruptive behaviour. In this study we quantify decompression rates for basaltic magmas using volatile diffusion in olivine-hosted melt tubes (embayments) for three contrasting eruptions of Kīlauea volcano, Hawai'i. Incomplete exsolution of H₂O, CO₂ and S from the embayment melts during eruptive ascent creates diffusion profiles that can be measured using microanalytical techniques, and then modelled to infer the average decompression rate. We obtain average rates of ~0.05-0.45 MPa s-1 for eruptions ranging from Hawaiian style fountains to basaltic subplinian, with the more intense eruptions having higher rates. The ascent timescales for these magmas vary from around ~5 to ~36 minutes from depths of ~2 to ~4 km respectively. Decompression-exsolution models based on the embayment data also allow for an estimate of the mass fraction of pre-existing exsolved volatiles within the magma body. In the eruptions studied this varies from 0.1-3.2 wt%, but does not appear to be the key control on eruptive intensity. Our results do not support a direct link between the concentration of pre-eruptive volatiles and eruptive intensity; rather they suggest that for these eruptions decompression rates are proportional to independent estimates of mass discharge rate. Although the intensity of eruptions is defined by the discharge rate, based on the currently available dataset of embayment analyses it does not appear to scale linearly with average decompression rate. This study demonstrates the utility of the embayment method for providing quantitative constraints on magma ascent during explosive basaltic eruptions

NanoSIMS results from olivine-hosted melt embayments: Magma ascent rate during explosive basaltic eruptions

The explosivity of volcanic eruptions is governed in part by the rate at which magma ascends and degasses. Because the time scales of eruptive processes can be exceptionally fast relative to standard geochronometers, magma ascent rate remains difficult to quantify. Here we use as a chronometer concentration gradients of volatile species along open melt embayments within olivine crystals. Continuous degassing of the external melt during magma ascent results in diffusion of volatile species from embayment interiors to the bubble located at their outlets. The novel aspect of this study is the measurement of concentration gradients in five volatile elements (CO2, H2O, S, Cl, F) at fine-scale (5–10 μm) using the NanoSIMS. The wide range in diffusivity and solubility of these different volatiles provides multiple constraints on ascent timescales over a range of depths. We focus on four 100–200 μm, olivine-hosted embayments erupted on October 17, 1974 during the sub-Plinian eruption of Volcán de Fuego. H2O, CO2, and S all decrease toward the embayment outlet bubble, while F and Cl increase or remain roughly constant. Compared to an extensive melt inclusion suite from the same day of the eruption, the embayments have lost both H2O and CO2 throughout the entire length of the embayment. We fit the profiles with a 1-D numerical diffusion model that allows varying diffusivities and external melt concentrations as a function of pressure. Assuming a constant decompression rate from the magma storage region at approximately 220 MPa to the surface, H2O, CO2 and S profiles for all embayments can be fit with a relatively narrow range in decompression rates of 0.3–0.5 MPa/s, equivalent to 11–17 m/s ascent velocity and an 8 to 12 minute duration of magma ascent from ~ 10 km depth. A two stage decompression model takes advantage of the different depth ranges over which CO2 and H2O degas, and produces good fits given an initial stage of slow decompression (0.05–0.3 MPa/s) at high pressure (< 145 MPa), with similar decompression rates to the single-stage model for the shallower stage. The magma ascent rates reported here are among the first for explosive basaltic eruptions and demonstrate the potential of the embayment method for quantifying magmatic timescales associated with eruptions of different vigor