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Objective. Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.
Measurements and Main Results. Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.
Conclusions. This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.
Die Flechte Cladonia stygia (Fr.) Ruoss wurde anlässlich einer Bestandsaufnahme der Rentierflechten 2009 erstmals aus Hessen gemeldet. Da die Unterscheidung von der ähnlichen C. rangiferina (L.) F. H. Wigg. anhand morphologischer Merkmale oft unsicher ist, wurden molekulargenetische Daten zur Identifizierung der hessischen Belege der Art herangezogen. Phylogenetische Stammbäume auf der Grundlage von sechs mitochondrialen und nuklearen Genloci untermauern die Abgrenzung beider Arten. Nur zwei von sieben gemeldeten hessischen Vorkommen gehören nach diesen Ergebnissen zu C. stygia, die übrigen zu C. rangiferina. Eine gezielte Suche nach C. stygia und eine durch molekulargenetische Daten untermauerte Bestimmung der Belege erscheint notwendig, um den Status der Art in Hessen zuverlässig beurteilen zu können.
Anlass für diese molekular-genetische Studie war der Verdacht, dass die seit 1986 bekannten und seitdem stark expandierten Populationen des Zwerg- Sonnenröschens (Fumana procumbens) im Naturschutzgebiet "Scheid bei Volkmarsen" in Nordhessen angesalbt wurden. Die Art war zuvor aus Nordhessen nicht gemeldet; lediglich in Südhessen waren isolierte Vorkommen auf kalkreichen Sanddünen bekannt. Eine Split-Netzwerk-Analyse basierend auf AFLP-Profilen von 69 Individuen an acht Lokalitäten konnte aufdecken, dass sich die südhessischen und französischen Populationen im Netzwerk jeweils klar als eigene Gruppen abgrenzen, während sich die nordhessischen Individuen mit den thüringischen, sachsen-anhaltinischen und gotländischen Aufsammlungen mischen. Die Frage nach der Ansalbung der Bestände lässt sich durch die Studie nicht beantworten. Wurde angesalbt, dann stammte das Ausgangsmaterial höchstwahrscheinlich aus den östlich sich anschließenden Populationen.
Za svojega kratkoga boravka u Petrogradu 1912. I. Milcetic; opisao je bogatu Bercicevu zbirku glagoljickih rukopisa i tiskanih knjiga iz Ruske nacionalne knjižnice, ali nije stigao podrobno prouciti svaki sastavni dio Berciceve grade. U Milceticevu opisu kodeksa br. 1 (Klimantovicev zbornik, 1514.) spominje se prolog Muke, ali se ne upozorava da se u nastavku toga prologa nalazi ulomak iz srednjovjekovnoga prikazanja sa scenom Judine izdaje Isusa. Ta je scena u srednjem vijeku ponajviše uznemiravala puk jer se tada od svega najviše mrzila laž, izdaja i prijetvornost. U radu se opisuju i prvi put objavljuju ulomci nepoznate redakcije Muke Isuhrstove iz petrogradske Berciceve zbirke (sign. Bc 1), koji predstavljaju za sada najstariji zapisani prolog i scenu hrvatskoga srednjovjekovnoga prikazanja pasionske tematike. Stihovi ulomaka usporeduju se s mladom ciklickom Mukom Spasitelja našega iz glagoljickoga Zbornika prikazanja (1556.), s kojom se u korpusu hrvatskoga srednjovjekovnoga pjesništva ti ulomci najviše podudaraju.
Reconstructions of the vegetation of Europe during the Last Glacial Maximum (LGM) are an enigma. Pollen-based analyses have suggested that Europe was largely covered by steppe and tundra, and forests persisted only in small refugia. Climate-vegetation model simulations on the other hand have consistently suggested that broad areas of Europe would have been suitable for forest, even in the depths of the last glaciation. Here we reconcile models with data by demonstrating that the highly mobile groups of hunter-gatherers that inhabited Europe at the LGM could have substantially reduced forest cover through the ignition of wildfires. Similar to hunter-gatherers of the more recent past, Upper Paleolithic humans were masters of the use of fire, and preferred inhabiting semi-open landscapes to facilitate foraging, hunting and travel. Incorporating human agency into a dynamic vegetation-fire model and simulating forest cover shows that even small increases in wildfire frequency over natural background levels resulted in large changes in the forested area of Europe, in part because trees were already stressed by low atmospheric CO2 concentrations and the cold, dry, and highly variable climate. Our results suggest that the impact of humans on the glacial landscape of Europe may be one of the earliest large-scale anthropogenic modifications of the earth system.
Im nordwestlichen Westfalen und der Grafschaft Bentheim wurde eine Bestandserhebung von Hypericum elodes durchgeführt. Mit Vorkommen an etwa 50 Gewässern dürfte diese Art innerhalb der Bundesrepublik Deutschland in der untersuchten Region ihren Verbreitungsschwerpunkt besitzen. Aspekte der Bestandsschwankungen und Gefährdung werden diskutiert.
In den Jahren 1986 bis 1990 wurde Ranunculus ololeucos (Reinweißer Hahnenfuß) im nordwestlichen Westfalen und südöstlichen Niedersachsen an 17 Gewässern beobachtet. Einen Verbreitungsschwerpunkt bildet der Naturraum "Gildehauser Venn". Ursache für viele Neu- und Wiederfunde dürfte der für Ranunculus ololeucos günstige Witterungsverlauf der letzten Jahre mit mehreren trockenen Sommerhalbjahren gewesen sein. Noch stärker als durch Eutrophierung erscheint die Art wie auch andere Littorelletea-Arten durch die zunehmende Versauerung der nährstoffarmen Stillgewässer gefährdet.
Vom Pillenfarn sind im Untersuchungsgebiet 22 aktuelle Fundorte bekannt; einen Verbreitungsschwerpunkt besitzt er im westfälisch-niedersächsischen Grenzgebiet, im Bereich des Gildehauser Venns und der Brechte. Der Pillenfarn besiedelt heute fast ausschließlich neu angelegte, meist nährstoffärmere, schwach saure bis neutrale, aber auch schwach basische Gewässer. Vorkommen an natürlichen Heideweihern (Witte Venn, Gildehauser Venn) sind heute erloschen. Wichtigste Ursache hierfür dürfte die Gewässerversauerung der letzten Jahrzehnte sein. Wasseranalysen ergaben bei einigen Faktoren recht uneinheitliche Werte. Insbesondere fielen bei einzelnen (z. T. belasteten) Gewässern erhöhte Stickstoff- und Calciumwerte auf. Unter optimalen Bedingungen bildet der Pillenfarn in dichten Rasen wachsend die Pillenfarn-Gesellschaft (Pilularietum globuliferae). Die Ausbildung von kennartenarmen und kennartenreichen Beständen dürfte vor allem auf die floristische Ausstattung des Standortes und seiner näheren Umgebung bei Anlage der Gewässer zurückzuführen sein. Die aus der Abb. 3 ersichtliche Vegetationszonierung kann als typisch für viele nährstoffärmere Pioniergewässer der nordwestdeutschen Sandgebiete angesehen werden.
Die im Gebiet des mittleren Teutoburger Waldes auftretenden Sedimentationsanomalien der turbiditischen "Rothenfelder Grünsande" und der "submarinen Großgleitung im Raum Halle" werden in das Ober-Turon gestellt und feinstratigraphisch neu gedeutet. Dabei können die "Rothenfelder Grünsande" erstmals mit einer Lage im Steinbruch Foerth, Halle/ Westf., nachgewiesen werden. Unbekannt war auch bisher das Vorkommen einer submarinen Gleitung im Steinbruch Anneliese, Bad Laer, in der ein weiterer Turbidit eingeschaltet ist. Die turbiditischen Rothenfelder Grünsande gehören lithostratigraphisch in die hohe "Untere Plänerkalk-Einheit (Iower limestone unit)" (ERNST& WOOD& RASEMANN 1984), biostratigraphisch in die untere Subprionocyclus normalis - Ammonitenzone und in die untere Inoceramus aff. frechi & Inoceramus cf. websteri - Inoceramen-Faunenzone. Eventstratigraphisch sind sie durch ihre Lage von einigen Metern über dem Tuff F und dem Micraster-Event gekennzeichnet. Die Untergrenzen der submarinen Gleitungen von HalielWestf. und vom Steinbruch Anneliese, Bad Laer, befinden sich lithostratigraphisch in der "Grauweißen Wechselfolge" (WOOD& ERNST& RASEMANN 1984). Im Steinbruch Foerth, HalLe/Westf., liegt die Basis der submarinen Gleitungen nur knapp über dem Beginn der Grauweißen Wechselfolge. In den verrutschten Gesteinsmassen läßt sich eine stratigraphische Abfolge vom hohen Ober-Turon bis in das Mittel-Coniac erkennen. Die Basis der submarinen Gleitung von Bad Laer liegt einige Meter höher als in HalielWestf. Ihre Mächtigkeit beträgt nur 5 m im Gegensatz zu der weit über 100 m mächtigen Rutschung von Halle/Westf.
Germany’s educational system has undergone a series of transformations during the last 40 years. In recent years, marked increases in enrolment have occurred. In response, admission requirements have been relaxed and new universities have been established. Academic distance education in the former Federal Republic of Germany (West Germany) was ushered in by the educational radio broadcasts around the end of the 1960s. Aside from the formation of the FernUniversität (Open University) in West Germany in 1975, there were significant developments in distance education occurring at the major universities in the German Democratic Republic (East Germany). After German reunification in 1990, the new unitary state launched programs to advance the development of distance education programs at conventional universities. Germany’s campus-based universities (Präsenzuniversitäten) created various entities, including central units and consortia of universities to design and market distance education programs. Hybridisation provides the necessary prerequisites for dual mode delivery, such as basic and continuing education programs, as well as for the combination of distance and campus-based education (Präsenzstudium). Hybridisation also has also opened the door for the creation of new programs. Following an initial phase in which distance education research is expected to centralize a trend towards decentralisation is likely to follow. The German Association for Distance Education (AG-F) offers a viable research network in distance education. Two dual mode case studies are also be surveyed: The Master of Arts degree, offered by the University of Koblenz-Landau, with Library Science as the second major, and the University of Kaiserslautern, where basic education will continue to be captured within the domain of the Präsenzstudium or campus-based education. The area in which distance education is flourishing most is within the field of academic continuing education, where external experts and authors are broadening the horizon of the campus. Multimedia networks will comprise the third generation of distance education.
RNA interference (RNAi) has emerged as a powerful tool to induce loss-of-function phenotypes by post-transcriptional silencing of gene expression. In this study we wondered whether inducible RNAi-cassettes integrated into cellular DNA possess the power to trigger neoplastic growth. For this purpose inducible RNAi vectors containing tetracycline (Tet)-responsive derivatives of the H1 promoter for the conditional expression of short hairpin RNA (shRNA) were used to target human polo-like kinase 1 (Plk1), which is overexpressed in a broad spectrum of human tumors. In the absence of doxycycline (Dox) HeLa clones expressing TetR, that carry the RNAi-cassette stably integrated, exhibited no significant alteration in Plk1 expression levels. In contrast, exposure to Dox led to marked downregulation of Plk1 mRNA to 3% and Plk1 protein to 14% in cell culture compared to mismatch shRNA/Plk1-expressing cells. As a result of Plk1 depletion cell proliferation decreased to 17%. Furthermore, for harnessing RNAi for silencing disease-related genes in vivo we transplanted inducible RNAi-HeLa cells onto nude mice. After administration of Dox knockdown of Plk1 expression was observed correlating to a significant inhibition of tumor growth. Taken together, our data revealed that genomically integrated RNAi-elements are suitable to hamper tumor growth by conditional expression of shRNA.
The interaction of fibroblast growth factors (FGFs) with their fibroblast growth factor receptors (FGFRs) are important in the signaling network of cell growth and development. SSR128129E (SSR),[1, 2] a ligand of small molecular weight with potential anti-cancer properties, acts allosterically on the extracellular domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain of FGFR remained elusive. This work reports the structural characterization of the interaction of SSR with one specific receptor, FGFR3, by NMR spectroscopy. This information provides a basis for rational drug design for allosteric FGFR inhibitors.
Music is an effective means of stress-reduction. However, to date there has been no systematic comparison between musical and language-based means of stress reduction in an ambulatory setting. Furthermore, although the aim for listening to music appears to play a role in its effect, this has not yet been investigated thoroughly. We compared musical means, language-based means like guided relaxation or self-enhancement exercises, and a combination of both with respect to their potential to reduce perceived stress. Furthermore, we investigated whether the aim one wants to achieve by listening to these means had an impact on their effect. We tested 64 participants (age: M = 40.09 years; 18 female) for 3–10 days during their everyday life using an app containing three means: musical means, language-based means, and a combination of both. For the music and the combination conditions participants were asked to select an aim: relaxation or activation. We measured perceived stress, relaxation, activation, and electrical skin resistance (ESR) as a marker of sympathetic nervous system (SNS) activity before and after using the app. Participants were instructed to use the app as often as desired. Overall, perceived stress was reduced after using the app, while perceived relaxation and activation were increased. There were no differences between the three means regarding their effect on perceived stress and relaxation, but music led to a greater increase in ESR and perceived activation compared to the other means. There was a decrease in ESR only for music. Moreover, perceived stress was reduced and perceived relaxation was increased to greater extent if the aim “relaxation” had been selected. Perceived activation, however, showed a larger increase if the aim had been “activation,” which was even more marked in the case of music listening. Our results indicate that all three means reduced perceived stress and promoted feelings of relaxation and activation. For enhancing feelings of activation music seems to be more effective than the other means, which was reflected in increased SNS activity as well. Furthermore, the choice of an aim plays an important role for the reduction of stress, and promotion of relaxation and activation.
The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.
1881 Viyana doğumlu olan Stefan Zweig, savaş ortamını bizzat yaşamış ve eserlerinde daima savaş karşıtı bir tutum sergilemiştir. Zweig'ın tek isteği, yaşanılan savaş sonrasında, insanların huzuru ve barışı yakalamasıdır. 1938-1942 yılları arasında Brezilya'da sürgündeyken kaleme aldığı "Satranç" adlı son eseri de göstermek istediği değerler açısından büyük bir öneme sahiptir. Zweig, insan ruhunun derinliklerine inerek, betimlemelerle ve benzetmelerle Nazizm'in/ Nazi Almanya'sının ülke ve insanlar üzerinde bıraktığı sosyal ve psikolojik etkileri yansıtmaya çalışır. Savaşın insanlığı getirdiği noktada, yazarın intiharından önce bıraktığı bir veda mektubu niteliği taşıyan bu eserde, Hitler iktidarının toplama kamplarının haricinde aydınlar için kullandığı başka bir yönteme dikkat çekilir. Zweig'e göre kullanılan bu yöntem, belki de toplama kamplarındaki insanların yaşadıklarından bile daha ağır bir zulümdür.
Alman Edebiyatı'nda önemli bir yere sahip olan Stefan Zweig, "Satranç" adlı eserinde, satranç oyunu üzerinden, yaşanılan tüm olumsuzluklara rağmen savaş döneminde bireylerin ayakta kalma/ var olmaya çalışma süreçlerini aktarır. Otobiyografik özellik gösteren eserde, savaş döneminde Naziler tarafından tutuklandıktan sonra yersiz-yurtsuzluğa mahkûm edilen bir karakterle, dünya satranç şampiyonu olan bir karakterin satranç mücadelesi ele alınır. 20. yüzyılın acımasızlığı gözler önüne serilirken, tarihsel olayların bıraktığı izlere ve o izlerle yaşamaya çalışmanın ne demek olduğuna yakından tanık olmak mümkündür. Bu çalışmada, eserden hareketle (metne bağlı/werkimmanent yaklaşımla) Nasyonal Sosyalizmin toplumda ve insanlar üzerinde bıraktığı izler, yarattığı yıkımlar ve Nasyonal Sosyalizm dönemi aktarılmaya çalışılmıştır.