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Die Rechtsgeschichte hat dem vormodernen Asyl lange Zeit einen bestenfalls marginalen Platz eingeräumt und es häufig als Hindernis auf dem Weg zum staatlichen Gewalt- und Justizmonopol bewertet oder den angeblichen "Missbrauch" des Asyls betont. Gleiches gilt cum grano salis für die allgemeine Geschichte, die wenige, eng begrenzte lokale Fallstudien beigesteuert hat, während umfassendere Darstellungen zur Geschichte der "Menschenrechte" oder zur historischen Kriminalitätsforschung das vormoderne Asylrecht weitgehend ignorieren. Erst in jüngster Zeit nahm die Zahl der Arbeiten zu, die sich intensiver mit der Geschichte des Asyls beschäftigen und neue Erkenntnisse sowie Forschungsperspektiven beitragen. ...
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment contribute to all stages of tumorigenesis and are usually considered to be tumor-promoting cells. CAFs show a remarkable degree of heterogeneity, which is attributed to developmental origin or to local environmental niches, resulting in distinct CAF subsets within individual tumors. While CAF heterogeneity is frequently investigated in late-stage tumors, data on longitudinal CAF development in tumors are lacking. To this end, we used the transgenic polyoma middle T oncogene-induced mouse mammary carcinoma model and performed whole transcriptome analysis in FACS-sorted fibroblasts from early- and late-stage tumors. We observed a shift in fibroblast populations over time towards a subset previously shown to negatively correlate with patient survival, which was confirmed by multispectral immunofluorescence analysis. Moreover, we identified a transcriptomic signature distinguishing CAFs from early- and late-stage tumors. Importantly, the signature of early-stage CAFs correlated well with tumor stage and survival in human mammary carcinoma patients. A random forest analysis suggested predictive value of the complete set of differentially expressed genes between early- and late-stage CAFs on bulk tumor patient samples, supporting the clinical relevance of our findings. In conclusion, our data show transcriptome alterations in CAFs during tumorigenesis in the mammary gland, which suggest that CAFs are educated by the tumor over time to promote tumor development. Moreover, we show that murine CAF gene signatures can harbor predictive value for human cancer.
Die vorliegende Münchner historische Dissertation untersucht am Beispiel der letzten Generation der Reichskammergerichtsassessoren die Wahrnehmung und Verarbeitung der Auflösung des Alten Reiches und die Bewältigung dieses epochalen Umbruchs durch die ehemaligen Richter bis in die Zeit des Deutschen Bundes hinein. Es geht folglich um Auflösung und Transfer eines Rechtssystems, das Mader am Beispiel der Bewältigungsstrategien der rund 20 Kammerrichter und ihrer Nachkarrieren detailliert rekonstruiert. Zwar fällt die Kritik des Verfassers an der "Untergangsorientierung" der Forschung zu einseitig und pauschal aus – denn diese hat das Funktionieren der Reichsverfassung auch in ihrer letzten Phase differenziert herausgearbeitet. Zutreffend ist jedoch, dass Fortwirkung, Kontinuität und Transfer des Alten Reiches, seines Rechts, seiner Institutionen und seiner Funktionsträger noch stärker erforscht werden sollten. ...
Allogeneic hematopoietic stem cell transplantation for congenital immune dysregulatory disorders
(2019)
Primary immunodeficiency disorders that predominantly affect immune regulation and mechanisms of self-tolerance have come into the limelight, because at least for a subgroup of monogenetic disorders, a targeted therapy has become available. Nevertheless, their management often involves the treatment of severely compromising, refractory, multi-organ autoimmunity, leading to further increased susceptibility to infections and complications of long-term immune suppressive treatment, including the risk of malignancy. While evidence for allogeneic hematopoietic stem cell transplantation (alloHSCT) as a curative treatment option for severely affected patients by this disease category accumulates, clear indications, and guidelines for alloHSCT are lacking. Predictive and stratification-relevant tools such as disease activity scores are largely missing and often there is not a consistent genotype-phenotype correlation within the same family to facilitate the decision whether to transplant or not. In this review, we provide a literature-based update on indications and outcomes of alloHSCT for congenital immune dysregulative inborn errors of immunity according to the IUIS classification 2017.
In seiner mit dem Otto-Hintze-Preis ausgezeichneten Habilitationsschrift bietet Markus Payk eine Entstehungsgeschichte des internationalen Rechtssystems, wie es in der Zwischenkriegszeit bestand. Demgemäß behandelt er die Pariser Vorortverträge – schwerpunktmäßig den Versailler Vertrag – von 1919/1920, mit denen ein neues zwischenstaatliches Regelungswerk erstellt wurde, das das gescheiterte System der Vorkriegszeit vor 1914 ablösen sollte. Der Autor will diese Verträge aus ihrem historischen und ideellen Kontext heraus erklären, um so deren wichtigste Charakteristika herauszuarbeiten und dabei verdeutlichen, dass ihnen "trotz aller Defizite […] [eine] einzigartige Stellung in der Geschichte der modernen Staatenbeziehungen" (S. 661) zukomme. ...
Collateral sprouting of surviving axons contributes to the synaptic reorganization after brain injury. To study this clinically relevant phenomenon, we used complex organotypic tissue cultures of mouse entorhinal cortex (EC) and hippocampus (H). Single EC-H cultures were generated to analyze associational sprouting, and double EC-H cultures were used to evaluate commissural sprouting of mossy cells in the dentate gyrus (DG) following entorhinal denervation. Entorhinal denervation (transection of the perforant path) was performed at 14 days in vitro (DIV) and associational/commissural sprouting was assessed at 28 DIV. First, associational sprouting was studied in genetically hybrid EC-H cultures of beta-actin-GFPtg and wild-type mice. Using calretinin as a marker, associational axons were found to re-innervate almost the entire entorhinal target zone. Denervation experiments performed with EC-H cultures of Thy1-YFPtg mice, in which mossy cells are YFP-positive, confirmed that the overwhelming majority of sprouting associational calretinin-positive axons are mossy cell axons. Second, we analyzed associational/commissural sprouting by combining wild-type EC-H cultures with calretinin-deficient EC-H cultures. In these cultures, only wild-type mossy cells contain calretinin, and associational and commissural mossy cell collaterals can be distinguished using calretinin as a marker. Nearly the entire DG entorhinal target zone was re-innervated by sprouting of associational and commissural mossy cell axons. Finally, viral labeling of newly formed associational/commissural axons revealed a rapid post-lesional sprouting response. These findings demonstrate extensive and rapid re-innervation of the denervated DG outer molecular layer by associational and commissural mossy cell axons, similar to what has been reported to occur in juvenile rodent DG in vivo.
Der vorliegende Band widmet sich für den Zeitraum von 1815 bis heute dem deutsch-französischen Verhältnis in 15 Einzelstudien, die entweder kulturwissenschaftlich ausgerichtet sind oder die dem Thema vor Ort in regionalen Fallbespielen nachgehen. Gemeinsame Klammer ist dabei der Rhein und dessen Anliegerregionen, womit die Herausgeber sich an neuere historische Forschungstrends anschließen. Anders als bisher wird der Rhein allerdings weder als deutschnationaler Fluss noch als natürliche französische Grenze wie vor 1945, aber auch nicht wie heute vielfach als europäisches Symbol verstanden, sondern als hybrider Raum, in dem verschiedene Akteure mit unterschiedlichen Interessen unter gegebenen Rahmenbedingungen aufeinandertrafen, was zu speziellen Prozessen und hybriden Strukturen in den jeweiligen Regionen führte. Das Ziel, die bisher dominierenden politisch motivierten Interpretationen in Frage zu stellen und die regionalen Besonderheiten und Widersprüche genauer wahrzunehmen, um die vorherrschenden nationalen und europäischen Interpretationen besser einzuordnen, erreicht der Band dabei vor allem durch die auf breiter Archivalienbasis erstellten Beiträge. ...
Background: Malaria is an increasing concern in Indonesia. Socio-demographic factors were found to strongly influence malaria prevalence. This research aimed to explore the associations between socio-demographic factors and malaria prevalence in Indonesia.
Methods: The study used a cross-sectional design and analysed relationships among the explanatory variables of malaria prevalence in five endemic provinces using multivariable logistic regression.
Results: The analysis of baseline socio-demographic data revealed the following independent risk variables related to malaria prevalence: gender, age, occupation, knowledge of the availability of healthcare services, measures taken to protect from mosquito bites, and housing condition of study participants. Multivariable analysis showed that participants who were unaware of the availability of health facilities were 4.2 times more likely to have malaria than those who were aware of the health facilities (adjusted odds ratio = 4.18; 95% CI 1.52–11.45; P = 0.005).
Conclusions: Factors that can be managed and would favour malaria elimination include a range of prevention behaviours at the individual level and using the networks at the community level of primary healthcare centres. This study suggests that improving the availability of a variety of health facilities in endemic areas, information about their services, and access to these is essential.
This paper focuses on the life and work of three of the most important men who arrived in the Philippines during the 16th century: the Augustinian Martín de Rada (1533–1578) studied at the universities of Paris and Salamanca. He was one of the best European scientists of his time in East Asia. The Dominican Domingo de Salazar (1512–1594), first bishop of Manila, studied the legitimacy of the conquest of the Philippines and wrote against the Spanish plan to conquest China. The Dominican Juan Cobo (? –1592) was the first Spanish to master the Chinese language and, through his book Shilu, the first European who introduced Christianity to the Chinese from a rational point of view and the first one to introduce European science into Chinese context. All of them were very influenced by the School of Salamanca and, from Manila, they always had their eyes on China. These three men of the late 16th century are paradigmatic examples of the influence of the University of Salamanca in the production of global knowledge in the early modernity.