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Ecological networks are more sensitive to plant than to animal extinction under climate change
(2016)
Impacts of climate change on individual species are increasingly well documented, but we lack understanding of how these effects propagate through ecological communities. Here we combine species distribution models with ecological network analyses to test potential impacts of climate change on >700 plant and animal species in pollination and seed-dispersal networks from central Europe. We discover that animal species that interact with a low diversity of plant species have narrow climatic niches and are most vulnerable to climate change. In contrast, biotic specialization of plants is not related to climatic niche breadth and vulnerability. A simulation model incorporating different scenarios of species coextinction and capacities for partner switches shows that projected plant extinctions under climate change are more likely to trigger animal coextinctions than vice versa. This result demonstrates that impacts of climate change on biodiversity can be amplified via extinction cascades from plants to animals in ecological networks.
Purpose: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy.
Methods: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected.
Results: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI.
Conclusion: A broad range of actionable alterations was targeted with available molecular therapeutics.
However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Im folgenden sollen an repräsentativen literarischen Werken Hauptaspekte der dichterischen Bedeutung des Teppichs aufgezeigt werden. Da Teppiche bei uns noch im 18. Jahrhundert mehr als Decken und Vorhänge denn als Bodenbelag verwendet wurden, ist die Terminologie auf diesem Gebiet fließend. Noch mehr gilt dies von der Antike." Die Auswahl der Texte ist nicht von der Verwendung oder der Herstellungstechnik, sondern von literarischen Gesichtspunkten bestimmt. Kultur- und Religionsgeschichte - so unentbehrlich sie für unseren Zusammenhang sind - bleiben Hintergrund, nicht Selbstzweck. Neben die Säkularisation sakraler Elemente tritt ebenbürtig die Verklärung des Realen. Die gewählte Gliederung nach Funktions- und Deutungstypen - Ehrenteppich, Bildteppich, Rasenteppich, Teppich als Trennendes, Lebensteppich, Teppich und Transfiguration des Raumes - läßt klarer als eine rein chronologische Gruppierung Grundmöglichkeiten poetischer Gestaltung und den individuellen Beitrag der Dichter hervortreten. Es versteht sich von selbst, daß bedeutende Texte unter mehreren Gesichtspunkten Beachtung heischen; Querverbindungen werden betont, Wiederholungen jedoch möglichst vermieden. Das Ziel unserer Fragestellung liegt einerseits in der Einzelinterpretation, zumal für die meisten unserer Texte die motivgeschichtliche Perspektive neu ist, andererseits in allgemeinen formalen und inhaltlichen Folgerungen.
Background: Risk stratification, detection of minimal residual disease (MRD), and implementation of novel therapeutic agents have improved outcome in acute lymphoblastic leukemia (ALL), but survival of adult patients with T-cell acute lymphoblastic leukemia (T-ALL) remains unsatisfactory. Thus, novel molecular insights and therapeutic approaches are urgently needed.
Methods: We studied the impact of B-cell CLL/lymphoma 11b (BCL11b), a key regulator in normal T-cell development, in T-ALL patients enrolled into the German Multicenter Acute Lymphoblastic Leukemia Study Group trials (GMALL; n = 169). The mutational status (exon 4) of BCL11b was analyzed by Sanger sequencing and mRNA expression levels were determined by quantitative real-time PCR. In addition gene expression profiles generated on the Human Genome U133 Plus 2.0 Array (affymetrix) were used to investigate BCL11b low and high expressing T-ALL patients.
Results: We demonstrate that BCL11b is aberrantly expressed in T-ALL and gene expression profiles reveal an association of low BCL11b expression with up-regulation of immature markers. T-ALL patients characterized by low BCL11b expression exhibit an adverse prognosis [5-year overall survival (OS): low 35% (n = 40) vs. high 53% (n = 129), P = 0.02]. Within the standard risk group of thymic T-ALL (n = 102), low BCL11b expression identified patients with an unexpected poor outcome compared to those with high expression (5-year OS: 20%, n = 18 versus 62%, n = 84, P < 0.01). In addition, sequencing of exon 4 revealed a high mutation rate (14%) of BCL11b.
Conclusions: In summary, our data of a large adult T-ALL patient cohort show that low BCL11b expression was associated with poor prognosis; particularly in the standard risk group of thymic T-ALL. These findings can be utilized for improved risk prediction in a significant proportion of adult T-ALL patients, which carry a high risk of standard therapy failure despite a favorable immunophenotype.
Ausgangspunkt ist die Beobachtung, dass sich empirisch eine inklusive Schule oftmals als eine differenzierte und differenzierende Schule darstellt. Dies bezieht sich etwa auf die Ausdifferenzierung der ‚heterogenen Lehrgruppe‘. Im zeitgemäßen inklusiven Unterricht sind allgemein- und sonderpädagogische Lehrkräfte ebenso wie Schulbegleitungen anwesend. Auch Sozialpädagog*innen und Therapeut*innen gehören vermehrt zum Schulalltag.
Vorliegende Studien dokumentieren, dass die Gestaltung inklusiver Schulen bzw. von inklusivem Unterricht von nicht intendierten Effekten und Widerständigkeiten der Akteur*innen begleitet ist. Im Beitrag werden – basierend auf der ProFiS-Studie – zwei Herausforderungen von inklusiven Schulen in den Mittelpunkt gerückt. Zum einen wird auf das Spannungsfeld von Professionalisierung und Deprofessionalisierung eingegangen. Zum anderen stellt das Verhältnis von Kategorisierung und Dekategorisierung eine Herausforderung dar. Beide Relationen sind als Spannungsverhältnisse untereinander und zueinander zu denken, die sich nicht ‚einfach‘ in eine Richtung auflösen lassen, sondern die in ihrer Widersprüchlichkeit gerade konstitutiv für die Praxis ‚inklusiver Schulen‘ wirken. Zentrale Frage des Beitrags ist, wie dieses komplexe Spannungsverhältnis der wechselseitigen Bezogenheit de/kategorisierender und de/professionalisierender Prozesse in professionellen Aktivitäten hervorgebracht wird.
Myocardial fibrosis and inflammation by CMR predict cardiovascular outcome in people living with HIV
(2021)
Objectives_: The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).
Background: PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.
Methods: This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).
Results: A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro–B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events.
Conclusions: Our findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).
We give a report of the fourth annual symposium of the Dry Grassland Working Group, which was organized in conjunction with the second workshop ‘Floristics and geobotany - Contributions to applied questions’, from 6 to 8 Sept. 2007 in Freising-Weihenstephan. The symposium was entitled ‘Restoration and spontaneous establishment of dry and semi-dry grasslands at traditional and urban-industrial sites’. Additionally, the aims of the Dry Grassland Working Group are shortly outlined and the next symposia of both groups are announced.
Joint Venture : International Max Planck Research School for comparative european legal history
(2002)
Gegenwärtigen Fusionspraktiken folgend, haben auch Rechtshistoriker sich verbündet, um international Synergien zu erzeugen. Das Max-Planck-Institut für europäische Rechtsgeschichte und das Institut für Rechtsgeschichte an der Johann Wolfgang Goethe-Universität haben – mit dem Segen und dem Geld ihrer "Mütter" – ein gemeinsames Forschungskolleg gegründet. ...
Species’ functional traits set the blueprint for pair-wise interactions in ecological networks. Yet, it is unknown to what extent the functional diversity of plant and animal communities controls network assembly along environmental gradients in real-world ecosystems. Here we address this question with a unique dataset of mutualistic bird–fruit, bird–flower and insect–flower interaction networks and associated functional traits of 200 plant and 282 animal species sampled along broad climate and land-use gradients on Mt. Kilimanjaro. We show that plant functional diversity is mainly limited by precipitation, while animal functional diversity is primarily limited by temperature. Furthermore, shifts in plant and animal functional diversity along the elevational gradient control the niche breadth and partitioning of the respective other trophic level. These findings reveal that climatic constraints on the functional diversity of either plants or animals determine the relative importance of bottom-up and top-down control in plant–animal interaction networks.