66 research outputs found

    Pollinator monitoring in agroecosystems – general methods for evaluations in field studies

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    Extensive knowledge of the occurrence, condition and population changes of wild bee communities in agroecosystems is important. The knowledge is needed to understand the complexity of potential exposure routes to plant protection products in specific crops and agricultural scenarios or to evaluate possible impacts of treatments at a landscape scale taking into account other influencing parameters like the cultivation system or management practices.Extensive knowledge of the occurrence, condition and population changes of wild bee communities in agroecosystems is important. The knowledge is needed to understand the complexity of potential exposure routes to plant protection products in specific crops and agricultural scenarios or to evaluate possible impacts of treatments at a landscape scale taking into account other influencing parameters like the cultivation system or management practices

    Dual-Site Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease

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    Abnormal oscillatory activity in the subthalamic nucleus (STN) may be relevant for motor symptoms in Parkinson's disease (PD). Apart from deep brain stimulation, transcranial magnetic stimulation (TMS) may be suitable for altering these oscillations. We speculated that TMS to different cortical areas (primary motor cortex, M1, and dorsal premotor cortex, PMd) may activate neuronal subpopulations within the STN via corticofugal neurons projecting directly to the nucleus. We hypothesized that PD symptoms can be ameliorated by a lasting decoupling of STN neurons by associative dual-site repetitive TMS (rTMS). Associative dual-site rTMS (1 Hz) directed to PMd and M1 (“ADS-rTMS”) was employed in 20 PD patients treated in a blinded, placebo-controlled cross-over design. Results: No adverse events were noted. We found no significant improvement in clinical outcome parameters (videography of MDS-UPDRS-III, finger tapping, spectral tremor power). Variation of the premotor stimulation site did not induce beneficial effects either. A single session of ADS-rTMS was tolerated well, but did not produce a clinically meaningful benefit on Parkinsonian motor symptoms. Successful treatment using TMS targeting subcortical nuclei may require an intervention over several days or more detailed physiological information about the individual brain state and stimulation-induced subcortical effects

    A Single-Chain-Based Hexavalent CD27 Agonist Enhances T Cell Activation and Induces Anti-Tumor Immunity

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    Tumor necrosis factor receptor superfamily member 7 (TNFRSF7, CD27), expressed primarily by T cells, and its ligand CD27L (TNFSF7, CD70) provide co-stimulatory signals that boost T cell activation, differentiation, and survival. Agonistic stimulation of CD27 is therefore a promising therapeutic concept in immuno-oncology intended to boost and sustain T cell driven anti-tumor responses. Endogenous TNFSF/TNFRSF-based signal transmission is a structurally well-defined event that takes place during cell-to-cell-based contacts. It is well-established that the trimeric-trivalent TNFSF-receptor binding domain (TNFSF-RBD) exposed by the conducting cell and the resulting multi-trimer-based receptor clustering on the receiving cell are essential for agonistic signaling. Therefore, we have developed HERA-CD27L, a novel hexavalent TNF receptor agonist (HERA) targeting CD27 and mimicking the natural signaling concept. HERA-CD27L is composed of a trivalent but single-chain CD27L-receptor-binding-domain (scCD27L-RBD) fused to an IgG1 derived silenced Fc-domain serving as dimerization scaffold. The hexavalent agonist significantly boosted antigen-specific T cell responses while having no effect on non-specific T cells and was superior over stabilized recombinant trivalent CD27L. In addition, HERA-CD27L demonstrated potent single-agent anti-tumor efficacy in two different syngeneic tumor models, MC38-CEA and CT26wt. Furthermore, the combination of HERA-CD27L and an anti-PD-1 antibody showed additive anti-tumor effects highlighting the importance of both T cell activation and checkpoint inhibition in anti-tumor immunity. In this manuscript, we describe the development of HERA-CD27L, a true CD27 agonist with a clearly defined forward-signaling mechanism of action

    A systematic map of studies testing the relationship between temperature and animal reproduction

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    Funding: This work was funded by the European Society for Evolution (which funds a Special Topic Network on Evolutionary Ecology of Thermal Fertility Limits to CF, AB, RRS and TARP), the Natural Environment Research Council (NE/P002692/1 to TARP, AB and RRS, NE/X011550/1 to LRD and TARP), the Biotechnology and \Biological Sciences Research Council (BB/W016753/1 to AB, TARP and RRS) and a Heisenberg fellowship from the German Research Foundation (FR 2973/11-1 to CF).1. Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. 2. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). 3. Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. 4. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. 5. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.Publisher PDFPeer reviewe

    The interplay of family history of depression and early trauma: associations with lifetime and current depression in the German national cohort (NAKO)

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    INTRODUCTION: Family history of depression and childhood maltreatment are established risk factors for depression. However, how these factors are interrelated and jointly influence depression risk is not well understood. The present study investigated (i) if childhood maltreatment is associated with a family history of depression (ii) if family history and childhood maltreatment are associated with increased lifetime and current depression, and whether both factors interact beyond their main effects, and (iii) if family history affects lifetime and current depression via childhood maltreatment. METHODS: Analyses were based on a subgroup of the first 100,000 participants of the German National Cohort (NAKO), with complete information (58,703 participants, mean age = 51.2 years, 53% female). Parental family history of depression was assessed via self-report, childhood maltreatment with the Childhood Trauma Screener (CTS), lifetime depression with self-reported physician's diagnosis and the Mini-International Neuropsychiatric Interview (MINI), and current depressive symptoms with the depression scale of the Patient Health Questionnaire (PHQ-9). Generalized linear models were used to test main and interaction effects. Mediation was tested using causal mediation analyses. RESULTS: Higher frequencies of the childhood maltreatment measures were found in subjects reporting a positive family history of depression. Family history and childhood maltreatment were independently associated with increased depression. No statistical interactions of family history and childhood maltreatment were found for the lifetime depression measures. For current depressive symptoms (PHQ-9 sum score), an interaction was found, with stronger associations of childhood maltreatment and depression in subjects with a positive family history. Childhood maltreatment was estimated to mediate 7%–12% of the effect of family history on depression, with higher mediated proportions in subjects whose parents had a depression onset below 40 years. Abuse showed stronger associations with family history and depression, and higher mediated proportions of family history effects on depression than neglect. DISCUSSION: The present study confirms the association of childhood maltreatment and family history with depression in a large population-based cohort. While analyses provide little evidence for the joint effects of both risk factors on depression beyond their individual effects, results are consistent with family history affecting depression via childhood maltreatment to a small extent

    OberflÀchenkomplexmodellierung und reaktive Stofftransportmodellierung: Batchsorptions- und SÀulenexperimente mit Ni sowie Quarz, K-Feldspat und Muskovit

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    Adsorption on mineral surfaces is one important process controlling the migration of metal ions in the subsurface. In long-term safety assessments relating to the final disposal of radioactive waste, (ad)sorption has been usually described by the empirical linear distribution coefficient Kd. Alternatively, surface complexation models (SCM) provide the advantage to consider the impact of varying geochemical conditions on adsorption. Geochemical conditions are expected to change over the large time frames and spatial dimensions to be considered for geological radioactive waste repositories. The activation products Ni-63 and particularly long-living Ni-59 are relevant for long-term safety analyses. There has only been little research that focused on the fate of Ni in the underground as a function of variable geochemical boundary conditions. Even ubiquitously present minerals such as quartz, feldspar, and mica have been rarely studied with respect to Ni retardation and sorption processes in the past. The main objective of this work is the quantitative description of adsorption and migration of Ni interacting with quartz, K-feldspar, and muscovite surfaces via SCMs. Batch experiments were carried out to quantify the uptake of Ni in equilibrium with the minerals. The migration behavior of Ni was investigated via column experiments. Batch and column experimental results showed plausible sorption and retardation trends of Ni as a function of varied geochemical boundary conditions comprising the pH, ionic strength, initial Ni concentrations, solid-to-liquid ratios, and sulfate as complexing ligand. Batch sorption data was used for inverse surface complexation modeling to determine surface complexation parameters (SCP). In contrast to most studies, all sorption data covering a broad range of geochemical boundary conditions were used simultaneously to determine a single set of SCPs for each mineral. SCPs determined from batch experiments were used for forward reactive transport modeling (simulation) of Ni migration data from column experiments. Geochemical adsorption dependencies were satisfactorily modeled for quartz and K-feldspar. There were strong indications for the influence of Al competing with Ni for sorption sites for both minerals. For quartz a basic stern model approach with charge distribution and in terms of K-feldspar a diffuse double layer model yielded best model fits. Experimental data of muscovite could not be modeled because a reliable mineral specific acid-base parameterization and cation exchange coefficients have not been available. The application of SCPs in forward reactive transport modeling of K-feldspar, quartz, and a mixture of both minerals indicated a substantial system understanding and can enhance the reliability of long-term safety analyses compared to the use of e.g. the linear distribution coefficient Kd in solute transport codes. Finally, provided SCPs from this study are recommended for further use, and hence, contribute to close data gaps of thermodynamic databases for SCMs. Nevertheless, more research is needed for an in-depth mechanistic understanding and modeling e.g. in terms of the underlying acid-base parameterization, spectroscopic evidence of Ni surface complexes, potential surface precipitation, and competing sorption of Al and Ni.Die Adsorption an MineraloberflĂ€chen ist ein zentraler RĂŒckhaltemechanismus, der die MobilitĂ€t von Metallionen auf Grundwasserfließwegen wesentlich einschrĂ€nken kann. In Langzeitsicherheitsanalysen hinsichtlich der Endlagerung radioaktiver AbfĂ€lle wurde die (Ad)sorption bisher in der Regel durch den empirischen, linearen Verteilungskoeffizienten Kd erfasst. Alternativ dazu bieten OberflĂ€chenkomplexmodelle (SCM) den Vorteil, dass die Auswirkungen variierender geochemischer Randbedingungen auf die Adsorption berĂŒcksichtigt werden kann. Es ist zu erwarten, dass sich die geochemischen Bedingungen in den langen ZeitrĂ€umen und rĂ€umlichen Dimensionen, die fĂŒr geologische Endlager fĂŒr radioaktive AbfĂ€lle zu berĂŒcksichtigen sind, Ă€ndern. Die Aktivierungsprodukte Ni-63 und insbesondere das langlebige Ni-59 sind fĂŒr Langzeitsicherheitsanalysen relevant. Die Datenlage zum Sorptions- und Migrationsverhalten von Ni im Untergrund in AbhĂ€ngigkeit variabler geochemischer Randbedingungen ist gering. Selbst ubiquitĂ€re Minerale wie Quarz, Glimmer und FeldspĂ€te wurden mit Bezug zur Sorption und Retardation von Nickel kaum untersucht. Das wesentliche Ziel dieser Arbeit ist die quantitative Beschreibung der Adsorption und Migration von Ni in Wechselwirkung mit den MineraloberflĂ€chen von Quarz, K-Feldspat und Muskovit durch SCMs. Mittels Batchexperimenten wurde die Sorption von Ni im Gleichgewicht mit den Mineralien quantifiziert. Das Migrationsverhalten von Ni wurde in SĂ€ulenexperimenten untersucht. Die Ergebnisse der Batch- und SĂ€ulenexperimente zeigten plausible Sorptions- und Retardationstrends von Ni in AbhĂ€ngigkeit der gewĂ€hlten geochemischen Randbedingungen, die den pH-Wert, IonenstĂ€rke, initiale Ni-Konzentration, das Fest-FlĂŒssig-VerhĂ€ltnis und Sulfat als komplexierenden Liganden umfassten. Die Sorptionsdaten aus den Batchversuchen wurden fĂŒr die inverse Modellierung zur Bestimmung von OberflĂ€chenkomplexparametern (SCP) genutzt. Im Gegensatz zum Großteil publizierter Studien in diesem Forschungsfeld wurden sĂ€mtliche Sorptionsdaten als Funktion der geochemischen Randbedingungen im Modell simultan verwendet, um eine einzige Konstellation an SCPs fĂŒr das jeweilige Mineral zu erhalten. Diese Parameter wurden zur VorwĂ€rtsmodellierung des reaktiven Stofftransports der Ni-Migrationsdaten aus den SĂ€ulenversuchen eingesetzt. Die geochemischen AbhĂ€ngigkeiten der Adsorption konnten fĂŒr Quarz und K-Feldspat zufriedenstellend modelliert werden. Es gab deutliche Anhaltspunkte fĂŒr den Einfluss von Al, das mit Ni um SorptionsplĂ€tze beider Minerale konkurriert. FĂŒr Quarz erzielte ein Basic-Stern-Modell mit Ladungsverteilung und fĂŒr K-Feldspat ein diffuses Doppelschichtmodell die besten Modellergebnisse. Die experimentellen Daten von Muskovit konnten nicht modelliert werden, da eine belastbare mineralspezifische SĂ€ure-Base Parametrisierung sowie Kationenaustauschkoeffizienten nicht zur VerfĂŒgung standen. Hinsichtlich K-Feldspat, Quarz und einem Gemisch dieser beiden Minerale ließ die Anwendung der SCPs in der VorwĂ€rtsmodellierung des reaktiven Stofftransports auf ein substantielles SystemverstĂ€ndnis schließen. Somit könnte deren Anwendung gegenĂŒber der Verwendung des linearen Verteilungskoeffizienten Kd in Transportrechencodes zu einer Erhöhung der Aussagekraft in der Langzeitsicherheitsanalyse fĂŒhren. Die in dieser Arbeit ermittelten SCPs werden zur weiteren Verwendung empfohlen und tragen somit letztendlich zum Schließen von DatenlĂŒcken in thermodynamischen Datenbanken fĂŒr SCMs bei. Gleichwohl ist weitere Forschungsarbeit fĂŒr ein vertieftes mechanistisches VerstĂ€ndnis und der damit einhergehenden Modellierung z.B. hinsichtlich der zugrundliegenden SĂ€ure-Base Parametrisierungen, spektroskopischer Nachweise von Ni-OberflĂ€chenkomplexen, potentieller OberflĂ€chenausfĂ€llung sowie Sorptionskonkurrenz von Al und Ni erforderlich
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