68034 research outputs found
Sort by
Die Verfügbarkeit des Unverfügbaren - Kommunikation mit Gott im lateinischen Christentum des europäischen Mittelalters
No full textDie Studie nimmt ein Phänomen in den Blick, welches zwar von zentraler Bedeutung für unser Verständnis der Geschichte Lateineuropas im Mittelalter ist, bisher jedoch noch nicht im Fokus geschichtswissenschaftlicher Forschung stand: die Kommunikation mit Gott. In zahlreichen zeitgenössischen Quellen – sei es in normativen Texten wie Gebetstraktaten, Liturgiekommentaren und Libri Oridnarii, oder sei es in erzählenden Quellen wie Historiographie und Hagiographie – wird Gott als Kommunikationspartner der Menschen beschrieben bzw. ins Bild gesetzt. Zwar muss sich die Geschichtswissenschaft der Frage enthalten, ob jene Kommunikation an sich möglich sei, jedoch kann (und sollte) sie zu einer Historisierung des fraglichen Phänomens beitragen. Denn obwohl die tradierten Formen von den religiösen Akteuren oftmals als etwas Gottgegebenes hingestellt werden, muss aus einer kulturwissenschaftlichen Perspektive die grundsätzliche Historizität der Gott-Mensch-Kommunikation konstatiert werden: Welche rituelle Praktik, welcher habituelle Gestus oder welche Gefühlslage jeweils als akzeptabel und angemessen gilt, um Gott zu adressieren, entscheidet sich an und verändert sich mit dem historischen Kontext – und ist damit historisch erklärungsbedürftig.
Zu dieser noch ausstehenden Historisierung des Phänomens leistet das Buch einen wesentlichen Beitrag, indem es der fraglichen Kommunikationsform aus einer problemorientierten sowie kommunikationstheoretisch reflektierten Perspektive nachspürt.
Zielgruppe(n) für dieses Buch
Historiker*innen, Religionswissenschaftler*innen, Mediävist*innen
Print-ISBN: 978311171214
Toward a Sustainable Future in Real Estate: Exploring the Synergy of Environmental Sustainability, Innovation, and Regulation
Full text linkThe dissertation consists of five individual contributions on the topics of environmental sustainability, innovation and regulation in the real estate industry
Characterization of chromatin remodeling enzymes in Plasmodium falciparum in vitro and in vivo and validation as putative drug targets
Full text linkThe complex life cycle of the malaria parasite Plasmodium falciparum (Pf) with its multifaceted morphological stages is accompanied by a high transcriptional variation. The orchestrated gene expression program is only explained in part by stage-specific transcription factors like the ApiAP2 family, as these factors are strongly under-represented in Pf. Global and local changes in chromatin structure during life cycle progression suggest the contribution of epigenetic mechanisms as a critical mechanism for fine-tuning gene regulation during malaria parasite development. The organization of genomic DNA in chromatin, which is relatively conserved across eukaryotes, exhibits remarkable differences in Pf, likely to accommodate the highly A/T-rich genome with > 90 % AT content in non-coding regions.
Chromatin remodeling enzymes (CREs) – responsible for re-positioning and eviction of nucleosomes at specific loci – are strongly reduced in number and highly divergent comparing Pf to other eukaryotes. We characterized the function of PfSnf2L (PF3D7_1104200), an ISWI-related CRE, by combining in vitro approaches, conditional knockout studies in vivo and specific drug targeting. We found PfSnf2L to be essential for parasite development in blood stages and to globally control just-in-time transcription regulation. Analyzing the enzymatic activity and its autoregulatory mechanism in vitro revealed qualitative and quantitative differences to known ISWI enzymes. In vivo mapping of the chromatin landscape showed that PfSnf2L shapes the promoter architecture of stage- specific genes through its nucleosome remodeling activity, thereby regulating the timing of gene activation and repression. The unique properties of the Plasmodium Snf2L allowed us to set up a customized drug screen specifically targeting the activity of the remodeling enzyme. The screen identified a potent inhibitor that specifically kills the parasite, phenocopies gene expression defects of PfSnf2L-KO, and inhibits the formation of sexual stages.
The findings of this study provide new insights in the complex epigenetic gene regulation of the parasite and highlight the crucial role of PfSnf2L - and CREs in general - in shaping and maintaining the unique nucleosomal landscape in Plasmodium falciparum. Furthermore, with their functional divergence, plasmodial CREs represent a potential target for new antimalarial drugs that will be required in view of emerging resistant parasite strains
Zustand des Zahnstatus von Patienten vor gefäßchirurgischer Prothesenimplantation
Full text linkDie pAVK und das Aneurysma gehören zu den weltweit häufigsten Gefäßerkrankungen, die beide von Arteriosklerose ausgehen. Die pAVK ist eine Erkrankung die vorzugsweise in den Extremitäten bzw. Beinen vorkommt und bei der durch Ablagerung von Cholesterin in die Gefäßwand eine Verengung der Arterien resultiert, die zum vollständigen Verschluss führen kann. Als Folge führt dies zu Symptomen wie Schmerzen beim Gehen und Kälte- sowie Schwächegefühl in den Beinen. Des Weiteren können Risikofaktoren wie Nikotinkonsum, Diabetes, Bluthochdruck und hohe Cholesterinwerte im Blut die Krankheit fördern oder im Fortschritt stärken. Daher muss bei einer Behandlung eine Änderung des Lebensstils in Kombination mit Medikamenten und gegebenenfalls auch ein chirurgischer Eingriff erfolgen, um den Blutfluss wiederherzustellen. Das Aneurysma ist eine Erweiterung der Arterienwand aufgrund von Schwäche oder Schädigung. Aneurysmen können an verschiedenen Orten im Körper auftreten. Sie sind häufig asymptomatisch, können bei einer Ruptur aber sofort lebensbedrohlich sein. Risikofaktoren sind Nikotinkonsum, Bluthochdruck und Arteriosklerose sowie eine genetische Veranlagung. Bei der Behandlung wird in Abhängigkeit vom Durchmesser und der Lage des Aneurysmas entschieden, ob medikamentös oder über endovaskuläre Verfahren sowie chirurgische Verfahren therapiert wird. Wenn man die Ergebnisse dieser Studie mit der V. Mundgesundheitsstudie für Deutschland (DMS V.) von 2014 vergleicht und sie dem Altersdurchschnitt von 70 Jahren gegenüberstellt, ist der Zahnstatus der hier untersuchten Patienten schlechter als der Durchschnitt. Zukünftig wäre es von wissenschaftlichem Interesse herauszufinden, ob eine gegenseitige Beeinflussung von Zahnstatus und Gefäßerkrankungen besteht. Es wären Maßnahmen zur Mundhygiene sinnvoll, die für die Patienten leicht und effektiv umzusetzen sind. Studien könnten durch mobile Einheiten vereinfacht werden, besonders wenn eine radiologische Untersuchung erfolgen soll, da die Patienten mit pAVK und fortgeschrittenen Fontaine-Stadien in dieser Studie zum großen Teil nicht mobil waren und Treppen ein Hindernis darstellen, vor allem wenn große Strecken in Anspruch genommen werden müssen. Eine Abfrage in der Anamnese, ob bei Patienten mit pAVK eine Parodontitis in der Vergangenheit diagnostiziert oder vermutet wurde wäre ebenfalls zu befürworten
The Woman Who Took the Initiative: A Look at Mark 5:25–34 from the Perspective of Power Dynamics
No full textThe paper takes a close look at the ‘hemorrhaging woman’ in Mark 5:25–34. The pericope is analyzed from the perspective of power dynamics. Utilizing tools of narratological analysis, both the woman and Jesus come into focus. By also taking concepts of social psychology into consideration, the question of power dynamics in the pericope is seen from a new perspective. Thus, the article differentiates what kind of power the woman and Jesus hold in Mark 5:25–34. The article argues that while Jesus is known by readers to hold both social and personal power, he does not actively exercise it in the pericope under consideration. The Woman who Took the Initiative on the other hand holds no social but a great deal of personal power which she not only holds but also applies to make sure she will receive the healing she has come for
Development of chemical methodologies for peptide and protein customization enabled by oxidative umpolung of cysteine thiol
No full textResidue-selective reactions on peptides and proteins allow such biomolecules to become druggable modalities through their precise customization by various functional units, thereby coming into the limelight in the area of drug discovery. Recently, some serendipitous discoveries on S-protected cysteine derivatives evoked our research focus on the S-chlorocysteine (S-Cl-Cys) derivative as a warhead for residue-selective reactions. Harsh reaction conditions required for the generation of the S-Cl-Cys from cysteine derivatives have prevented the S-Cl-Cys as a Umpolung Cys from being generally used in residue-selective reactions. In this context, I found mild reaction conditions that can generate S-Cl-Cys from S-protected cysteine derivatives and have shown their wide applicability to residue-selective modifications
DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders
No full textBCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting α helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and “specificity residues” impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins
Elevated plasma soluble lectin-like oxidised low-density lipoprotein receptor 1 as an independent prognostic biomarker in sepsis
Full text linkBackground
Soluble lectin-like oxidised low-density lipoprotein receptor 1 (sLOX-1) is overproduced during inflammation, with its expression and release triggered by C-reactive protein (CRP). As CRP levels are typically elevated in sepsis, this study aimed to investigate whether sLOX-1 levels increase in parallel.
Methods
Plasma sLOX-1 levels of 52 patients with systemic inflammatory response syndrome (SIRS), 45 patients with sepsis, 88 patients with septic shock and 37 controls were measured by ELISA. Associations with CRP, underlying diseases, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and bacterial infections were analysed.
Results
Plasma sLOX-1 levels were similarly elevated in patients with SIRS, sepsis, or septic shock compared to controls. Plasma sLOX-1 levels did not differ between male and female controls or patients. Plasma sLOX-1 levels were comparable in patients infected with SARS-CoV-2, Gram-negative bacteria, or Gram-positive bacteria. No association was observed between sLOX-1 levels and underlying liver cirrhosis or pancreatitis. Notably, plasma sLOX-1 levels correlated positively with leukocyte and basophil counts but showed no correlation with CRP or procalcitonin. Of clinical relevance, positive correlations were also found with aspartate aminotransferase (AST) and bilirubin levels. Among the 41 patients who did not survive, sLOX-1, AST, and bilirubin levels were significantly higher compared to those of survivors.
Conclusions
Plasma levels of sLOX-1 are elevated in patients with SIRS or sepsis and are significantly higher in non-survivors. Of note, they do not correlate with classical inflammatory markers, suggesting that sLOX-1 may function as an independent prognostic biomarker for predicting poor outcomes in patients with SIRS or sepsis
Controlling Coulomb correlations and fine structure of quasi-one-dimensional excitons by magnetic order
Full text linkMany surprising properties of quantum materials result from Coulomb correlations defining electronic quasiparticles and their interaction chains. In van der Waals layered crystals, enhanced correlations have been tailored in reduced dimensions, enabling excitons with giant binding energies and emergent phases including ferroelectric, ferromagnetic and multiferroic orders. Yet, correlation design has primarily relied on structural engineering. Here we present quantitative experiment–theory proof that excitonic correlations can be switched through magnetic order. By probing internal Rydberg-like transitions of excitons in the magnetic semiconductor CrSBr, we reveal their binding energy and a dramatic anisotropy of their quasi-one-dimensional orbitals manifesting in strong fine-structure splitting. We switch the internal structure from strongly bound, monolayer-localized states to weakly bound, interlayer-delocalized states by pushing the system from antiferromagnetic to paramagnetic phases. Our analysis connects this transition to the exciton’s spin-controlled effective quantum confinement, supported by the exciton’s dynamics. In future applications, excitons or even condensates may be interfaced with spintronics; extrinsically switchable Coulomb correlations could shape phase transitions on demand
Plasmodium blood stage development requires the chromatin remodeller Snf2L
Full text linkThe complex life cycle of the malaria parasite Plasmodium falciparum involves several major differentiation stages, each requiring strict control of gene expression. Fundamental changes in chromatin structure and epigenetic modifications during life cycle progression suggest a central role for these mechanisms in regulating the transcriptional program of malaria parasite development1,2,3,4,5,6. P. falciparum chromatin is distinct from other eukaryotes, with an extraordinarily high AT content (>80%)7 and highly divergent histones resulting in atypical DNA packaging properties8. Moreover, the chromatin remodellers that are critical for shaping chromatin structure are not conserved and are unexplored in P. falciparum. Here we identify P. falciparum Snf2L (PfSnf2L, encoded by PF3D7_1104200) as an ISWI-related ATPase that actively repositions P. falciparum nucleosomes in vitro. Our results demonstrate that PfSnf2L is essential, regulating both asexual development and sexual differentiation. PfSnf2L globally controls just-in-time transcription by spatiotemporally determining nucleosome positioning at the promoters of stage-specific genes. The unique sequence and functional properties of PfSnf2L led to the identification of an inhibitor that specifically kills P. falciparum and phenocopies the loss of correct gene expression timing. The inhibitor represents a new class of antimalarial transmission-blocking drugs, inhibiting gametocyte formation